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https://api.semanticscholar.org/CorpusID:10000013 | 10000013 | Protective Effect of <i>Camellia sinensis</i> on Methotrexate-Induced Small Intestinal Mucositis in Mice | 2,014 | Food and Nutrition Sciences | [
403616,
2292605
]
| [
"The intestinal epithelium forms a dynamic system of continuous proliferation, differentiation and cell death. In the crypt compartment, stem cells and proliferating cells produce new epithelial cells [1] . Collectively, the epithelial cells maintain a high barrier function. The use of cytostatic drugs like methotrexate in cancer treatment may severely impair intestinal epithelial function resulting in mucositis. This is clinically manifested by malabsorption, malnutrition, dehydration and diarrhea [1] . The gastrointestinal tract is particularly vulnerable to these effects, presumably because of high cell proliferation and turnover rates [2] . The mucosal damage is known to be induced initially as a consequence of loss of mitotic cells in the epithelium [3] leading to villi flattening and absorptive dysfunction [4] . The antimetabolite methotrexate is widely used in cancer chemotherapy, causing intestinal mucosal injury, by inhibition of dihydrofolate re-444 ductase, which is required for DNA synthesis and cell division [5] . The intestinal cells journey from the crypt to the villous tip is completed in 2 -5 days and terminates with the cell remotion by apoptosis and/or exfoliation [6, 7] . At highly metabolically and proliferative active tissue like the intestinal epithelium, Vitamin E protects membranes from damage by free radicals, and in mice is required to stem cell proliferation and oxide-reduction reactions [8, 9] . Others chemical compounds such as cathechins, present at green tea could counteract an oxidative event reducing inflammatory pattern. Methotrexateinduced enteropathy in rat small intestine, especially in jejunum, is characterized by diarrhea, villous atrophy and impaired digestive and absorptive function [10] , Additionally, MTX-induced injury has been exacerbated by malnutrition and of elemental diet consumption [11] . Thus, the aim of this study was to evaluate the effect of Camellia sinensis and vitamin E supplementation on the intestinal barrier function in this experimental model.\n\n Chemicals were obtained from the following manufacturers: Methotrexate (MTX; Immunex Corporation; Seatle, WA); Camellia sinensis (laboratório Brasmed, Brazil); Vitamins E (Laboratório Sundow). Diets included total nitrogen content around 10% -13%. All groups consumed commercial chow (Fri-Ribe-SP, Brazil).\n\n Animal experiments were performed with permission of the Experimental Ethical Committee of Federal University of Ceará-Brazil; and the protocol was complied with the Occupational Health and Safety in the Care and Use of Research Animal, National Research Council (National Academic Press, 1977). Male adults Swiss Mus musculus (n = 32, 35 -40 g) from Pharmacology and Physiology Department, Federal University of Ceará, were used throughout the experiments. Animals were housed in individual metabolic cages, maintained under a 12 hours light-dark cycle, and controlled access to a standard palletized diet and water. Mice were monitored daily, for signs of diarrhea, metabolic control and mortality. An experimental model of intestinal mucositis in rats as described previously [12] , was modified and adapted for mice.\n\n Control (PBS, phosphate buffer solution, via gavage), methotrexate (2.75 mg/kg/24 h sc) and Camellia sinensis decoction and vitamin E (10 IU/animal/24 h via gavage) groups (n = 8/group) were treated during three days. Tea decoction (20%) was prepared by soaking 20 g of green tea in 100 ml boiled water separately, soaked for 2 minutes and thereafter filtered. This filtrate was designated as \"green tea decoction\". The dose of this decoction orally administered to each mice was 0.1 ml/10g of body weight. Initial pilot study suggested that 20% of green tea preparation had given significant results, than 10% green tea. Therefore, we have decided to set forward our study with 20% green tea decoction. Since the maximum mucosal damage caused by MTX occurs after 72 hours after the MTX administration, and MTX+CS (methotrexate plus Camellia sininsis) or vitamin E (methotrexate plus vitamin E), all the mice were sacrificed (at 4 th day), under general anesthesia (50 mg/kg ketamine + 10 mg/kg xilazine im). Intestines of the mice were removed for histological examination just after they have been sacrificed, and put in formalin after being washed with iced isotonic saline solution. Histopathological changes in the intestinal cells were examined via qualitative blindly histological evaluation by a pathologist.",
"On the histological examination performed after the routine tissue processing, villus length and the crypt depth were morphometrically evaluated analyzing the tissue sections stained with hematoxylin eosin (H&E), measurements were done on 40 villi from 40 crypts per animal. To examine apoptotic events, sections were examined under light microscopy. Counts of apoptotic cells and apoptotic bodies were performed using 40× objective. Cells were scored as apoptotic if they exhibited cellular shrinkage with concurrent cytoplasmic eosinophilia, nuclear pyknosis, and fragmentation with associated apoptotic bodies. Areas of marked lymphocytic infiltration or necrosis were not used for counting.\n\n Statistical analysis was performed using GraphPad Prism 5.01 (GraphPad Software, San Diego, CA) and consisted of a two-way ANOVA with Bonferroni post hoc tests when appropriate. And groups were tested for homogeneous variance then used a Student's t test. Data are presented as mean ± standard error of the mean. For daily monitored parameters, repeated measures two-way ANOVA was performed. For all, p < 0.05 was considered significant.\n\n \n\n Mucositis condition was achieved at mice treated with methotrexate (2.75 mg/kg/day sc). \n\n Similarly, in this present study showed at Figure 1 (duodenum) and Figure 2 ( \n\n At green tea 20% decoction group, no mortality was achieved, similar to those results at ulceration ear mice experimental model induced by MTX. As expected, MTXinduced mucositis mice, presented (Figure 3 ) more intestinal cell death (9.30 ± 0.16 apoptotic bodies/field/ sample) when it compared to control (0.78 ± 0.02). Vitamin E supplementation do not alter apoptotic events (8.60 ± 0.07), however CS supplementation (2.40 ± 0.03 apoptotic bodies/field/sample) reduces intestinal cell death mainly at jejunum at inflammatory condition.\n\n Apart from fundamental basic research investigating \n\n \n\n 447 mechanisms by which the latter stages of cancer can be inhibited, there are no nutraceuticals that have advanced to the point of clinical trial testing. However, this is a promising area of basic research in cell lines and in animal models. At intestinal mucositis induced by methotrexate administration, the toxic effects are not considered to be a result of direct action on the gastrointestinal tract tissues but rather to be the consequence of an inhibition in dihydrofolate reductase synthesis. This enzyme is required to maintain the intracellular pool of tetrahydrofolate during purine and thymidine synthesis. The chemical and morphologic changes in the small intestine may be triggered by crypt cell damage [13] . To minimize the side effects in patients undergoing chemotherapy, it is important to reduce mucosal damage and stimulate tissue repair. Such intestinal damage is reported to be prevented by some kinds of nutrients and growth factors. Plant products are in use for a long time in Ayurvedic and folklore medicine for the cure of ailments with minimal side effects and comparable efficacy. Green tea term (Camellia sinensis) nominate a great variety of Thernaceae family plants, including 520 species, endemic in tropical and sub-tropical areas of Asia and South America. Green tea decoction has a medicinal use in these countries due to beneficial and potent antioxidants properties. As a medicinal beverage, it is recommended to nauseas, vomiting and at diarrhea condition. Antibacterial action had been used at infections and at wounds treatment [14] . Aside from the pluripotent effects of green tea polyphenols, exist an increasing list of molecular processes, including oxidative stress [15] . Cathechins, mainly (-)-epigallocatechin-3-gallate (EGCG), represent the largest group of flavonoids (flavan-3-ols) in the tea plant, in particular in fresh leaves and green tea. Injected and orally administered green tea cathechins, in vitro, significantly decreased bacterial LPS-induced alveolar bone desorption and IL-1 expression in the gingiva of BALB/c mice [15, 16] . Initially in mucositis development, direct DNA damage caused by the chemotherapy agents might lead to cellular death in the basal epithelium and submucosal cells, but clonal cell death occurs in only small part of the damaged cells. Vitamin E and CS protection occurred probably due a retardation of inflammatory process at progenitors intestinal crypt cells [17] [18] [19] . On the other hand, the methods used at present study are insufficient to explain completely the intensive damage at mucositis; but present results demonstrated clearly an amelioration of intestinal barrier morphology. Gastrointestinal impaired function could be positively modulated by Camellia sinensis [20] . At green tea 20% decoction group, no mortality was achieved, similar to those results at ulceration ear mice experimental model induced by MTX. These results agree with our finds at intestinal mucositis model. However, at this challenge, green tea treatment did not affect the main effect of methotrexate (arresting cell division in S-phase) [21] . Data suggest that an offer of CS or vitamin E supplementation could treat villous atrophy, cells crypt hyperplasia and increase of intestinal apoptosis, induced by MTX challenge.\n\n Marked intestinal barrier function disruption was caused by a methotrexate administration. In addition, a protecting effect of Camellia sinensis decoction at small intestine of mice with mucositis, was achieved similarly to antioxidant action of vitamin E. Probably, cathechins compounds of this green tea, initiate an antioxidant protection. However more pharmacological and biochemical assays are essential to elucidate protector mechanism, and potential active compounds."
]
| [
"Pharmacy & Pharmacology",
"Gastroenterology & Hepatology",
"Family Medicine & Primary Care"
]
|
https://api.semanticscholar.org/CorpusID:10000022 | 10000022 | Facial Plexiform Neurofibroma in a 13-year-old Girl with Neurofibromatosis-1 | 2,012 | Journal of Indian Academy of Oral Medicine and Radiology | [
1330040,
920090,
1219083
]
| [
"Neurofibromas may appear in every tissue, soft or hard, in the oral cavity.\n\n The most commonly affected site is the tongue. 4, 5, 9, 10, 12, 13 In the case here reported the neurofibroma was located in the gum, which is not a common location 4, 9 Shapiro et al state that gum involvement by neurofibroma in NF1 patients is 5%. 3 Localized oral neurofibromas usually appear as asymptomatic nodules covered by normally colored mucosa. 4, 7, 9, 12 However, when adjacent to cranial nerves, they can impair motor function of facial or hypoglossal nerves or the sensitivity of trigeminal nerve. 4, 7, 9 Gingival neurofibromas may cause dental malposition or impaction. 4, 12 NF1 patients may also show facial disfigurement due to hypoplasia or hyperplasia of maxilla, mandible, malar bone and TMJ. Facial PNs may also cause a facial asymmetry as seen in the present case.\n\n Exophthalmos may also be present due to a dysplasia of the sphenoid major wing. Radiological findings in oral neurofibromas include mandibular channel, mandibular foramen and mental foramen widening. 12 Neurofibromas may seldom be primarily intraosseous; in that case they usually appear as a unilocular, well-defined radiolucency. 9, 10 In the case here reported radiological manifestations, such as destruction of bone and sphenoid dysplasia were found. Most neurofibromas show low attenuation in CT scans, although some of them may show soft tissue density. Low density lesions contain a variable amount of Schwann cells, which are rich in lipids, cystic degeneration and xanthomatous alterations. 15 High density areas are thought to represent collagen rich or cellular areas. In magnetic resonance imaging (MRI), lesions show a low signal in T1 and a high signal in T2, with a variable highlighting with the contrast. 11 A high peripheral signal with a low central signal in T2 weighted images (bull's eye sign) is a typical sign of neurofibromas. 9, 11 A similar sign can be seen in CT; in this case there is a central high signal. 11 Histologically, neurofibromas are composed of a mixture of Schwann cells, perineural cells and endoneural fibroblasts, and they are not capsulated. 5, 8, 16 Schwann cells account for about 36 to 80% of lesional cells. These constitute the predominant cellular type and they usually have widened nuclei with an undulated shape and sharp corners. On electron microscopy Schwann cells can be seen embracing axons. These can be highlighted with silver or acetylcholinesterase staining or with immunohistochemical techniques when using the fluorescent microscope. It is estimated that between 0.7 and 31% of cells are perineural cells. In seldom cases this type of cells can predominate. 16 Neurofibromatous lesions usually evolve slowly, without pain, but during growth, puberty or pregnancy their evolution may be accelerated. 12 PN can be symptomatic at birth or become symptomatic through time. Early occurrence supports the idea that PN are congenital lesions, although there may be patients that develop PNs after 20 years of age. Total or partial resection of neurofibromatous lesions is the treatment of choice to solve esthetic or functional problems; it is advisable to wait for treatment until growth has been completed thus diminishing the risk of recurrence. 7, 9, 12, 13 Total resection with 1 cm margins whenever feasible is the treatment of choice for accessible and small tumors. 8 Friedrich et al suggest that early surgical interventions in small-sized PN in children can be advantageous, especially in the strategy to prevent their progression 17 Radiotherapy or chemotherapy are not recommended for treatment. 8, 12 Thalidomide has been used to treat pain in PNs. 7 Malignant transformation rate of neurofibromas in NF1 is 3 to 5 %. 4, 12, 13 NF1 patients must receive genetic counseling since this is an autosomal dominantly inherited disease and the likelihood of transmission to the children is 50% in both sexes. 4 Malignant transformation to neurofibrosarcoma bears a very bad prognosis and distant metastases are frequent, being the mean survival of 15% at 5 years. 18 Some authors state that recurrence may appear after surgical resection and that multiple recurrences increase the risk for malignant transformation.\n\n \n\n Emphasis must be made on the fact that while examining the oral cavity, dental surgeons should keep this disease under consideration when oral lesions characteristic of NF1 are present. These patients must be reviewed long-term because of eventual complications, especially that of malignant transformation.",
"Neurofibromatosis type 1 (NF1) was described in 1882 by Friedrich Daniel von Recklinghausen, who suggested the name neurofibroma for neural tissue tumors present in this disease and NF for the condition with multiple neurofibromas. Plexiform neurofibroma (PN), also called plexiform neuroma, pachydermatocele or neurofibromatous elephantiasis (elephantiasis neurofibromatosa), is classified as a benign peripheral nerve sheath tumor that surrounds multiple nervous fascicles. It is a nonmetastatic, highly vascularized, locally invasive tumor that has slow growth. PNs are one of the significant complications of NF1, which may occur during childhood and rarely develop after adolescence. PN can originate malignant peripheral nerve sheath tumor, which occurs in 2 to 5% of patients with PN.\n\n A 13-year-old female patient came to the hospital with the chief complaint of deformity on the left side of the face which was present since birth (Figs 1 and 2) .\n\n History reveals that the patient was born with facial deformity on the left side of the face. There was swelling of the left eye and at the age of 1 year she underwent surgery following which the left eye was removed. Three months\n\n after the surgery, she underwent radiation therapy for the deformity, but she did not complete the treatment. The facial skin in the deformed region turned brownish black in color after the radiation treatment. The deformity has not grown in size. She had again undergone surgery for the correction of the same facial deformity twice about a year back at government hospital. She gives history of a swelling present in the left side of the palate since birth. She also gives history of the presence of multiple brownish black pigmented spots all over her body.\n\n On examination, three swellings are seen on the left side of the face: 1. A single, localized swelling is seen in the left supraorbital region, ovoid in shape, brownish black in (Figs 3 to 8) .\n\n The shape of the mouth is irregular and there is diffuse swelling of the upper lip, drooping of the angle of the mouth on the left side. The mouth opening is normal. A freely movable firm mass can be felt on palpation of the labial sulcus in the anterior maxillary region. A single diffuse swelling is present on the left buccal mucosa. The swelling measures about 5 × 4 cm in size causing obliteration of the maxillary and mandibular buccal vestibule on the left side. The margins are ill defined, it is of the mucosal color, smooth surfaced and there are no secondary changes. On palpation the swelling is soft, nontender and there is no fluctuation or discharge from it. A single diffuse swelling is present on the hard palate on the left side measuring about 9 cm anterioposteriorly and 5 cm mediolaterally. The shape is irregular with ill defined margins. The surface is lobulated and there are folding present on the swelling. Focal areas of hyperpigmentation are also seen. The cusps of unerupted As history reveals the facial deformity is present right from the birth with accompanying brownish pigmentation in different parts of the body, it is a congenital swelling and can be provisionally diagnosed as PN with NF.\n\n The patient was subjected to radiographic investigations. Maxillary cross-sectional occlusal radiograph shows bone destruction in the left side with expansion of the buccal cortex on the left side, the nasal septum is deviated to the right, there is alveolar bone loss seen anteriorly and there is spacing between the anterior teeth (Fig. 10) . Posterioanterior view of the skull show opacification and obliteration of the left orbit and maxillary antrum, deviation of the nasal septum to the right side, the skull is enlarged on left parietal region and there is thinning of the mandible on the left side (Fig. 11) .\n\n Computed tomographic (CT) scan shows destruction of the left zygomatic bone with a hypodense space occupying lesion, the left orbit is not visualized. The maxillary antrum is obliterated on the left side with deviation of the nasal septum to the right side (Figs 12 and 13) . An incisional biopsy was done under local anesthesia. Two bits of tissue measuring 3 mm in diameter were taken from the swelling in the anterior palate and subjected to histopathological investigation.\n\n Section shows cells with elongated, bent nuclei separated by abundant, fine and sinuous collagen fibers. There is presence of nerve bundles, mild vascularity and areas of hemorrhage.",
"Overlying epithelium in orthokeratinized stratified squamous epithelium of normal thickness (Figs 14 and 15 ), van Gieson stain positive for collagen fibers (Fig. 16) and immunohistochemistry S-100 positivity is seen in few spindle cells and nerve bundles (Fig. 17 ) Histopathology is suggestive of neurofibroma.\n\n Correlating the history, clinical finding, radiological findings and histopathological findings the diagnosis of NF1 with facial PN was made. The patient was referred to a pediatric surgeon for further management.\n\n The characteristic feature of NF1 is the occurrence of peripheral nerve sheath tumors, neurofibromas, which are the most common cause of symptoms and disfigurement in NF1. 1 The term 'plexiform neurofibroma' is used to describe a network-like growth of tumor involving multiple fascicles of a nerve, leading to a diffuse mass of thickened nerve fibers surrounded by proteinaceous matrix. 1 PNs can be deep or superficial in location or a combination of the two. These tumors appear in utero or during early childhood in some patients and, therefore, they are present to interact with the skull, orbital structures and globe while they are still developing. The tumors affect nearby bone and invade almost all of the orbital structures, including the globe, extraocular muscles, optic nerve sheath and branches of the sensory nerves. Pigmented lesions are a common manifestation in NF1. These lesions usually appear during the first years of life or are present at birth, either as café au lait spots or as freckles. 4, 7, 8, 12, 13 Café au lait spots are hyperpigmented maculae that may vary in color from light brown to dark brown, their borders may be smooth or irregular. They may appear anywhere on the skin, but they are less common on the face. 4 Inguinal and axillary freckles (Crowe's sign) are frequently present. 4, 8 Multiple skin neurofibromas as well as angiomas are also characteristic in NF1. 4, 12, 13 There exist two main clinical forms of neurofibroma: Localized and PNs. Localized neurofibroma is the most frequent one in NF1. It develops along a peripheral nerve as a focal mass with well-defined margins. It is rarely present at birth but appears in late childhood or early adolescence. 4 The number of localized neurofibromas generally increases with age, and there is an increase in size and number of the lesions during pregnancy and puberty. 4, 8 Although skin is the predominantly affected organ, some others such as stomach, bowels, kidney, urine bladder, larynx or heart may become affected. In the head and neck, the most frequently affected sites are scalp, cheek, neck and oral cavity. 4 PN spreads along the peripheral nerve and may affect some nervous rami. 4, 14 This is a poorly circumscribed and locally invasive tumor. 14 About 21% of patients with NF1\n\n are affected with PNs. 13 Morbidity of PNs in NF1 is high since they tend to grow until reaching a great size and producing disfigurement. 6 Besides, the risk of malignization is between 2 and 5%. 4, 11 Due to its diffuse involvement/ appearance and soft consistency, palpation of neurofibroma is similar to that of lipoma, vascular malformation, lymphangioma or rhabdomyoma. 8 Bone involvement in NF1 may be due to both external resorption and internal osteolytic defects. External resorption may be due to the pressure applied on the bone by the neurofibroma, as it happens in the case here reported. 4, 8 It is well known that in NF1 bone malformations such as kyphoscoliosis or pseudoarthrosis may appear, and the temporomandibular joint (TMJ) may be involved. 8, 12, 17 Skeletal involvement is present in almost 40% of patients with NF1, being scoliosis the most common skeletal pathology. 11, 13, 17 Iris hamartoma, acoustic neuroma, central nervous system tumors (glioma, glioblastoma), macrocephaly and mental retardation (up to 40% of cases) can also be found. 12, 13 Oral cavity involvement appears in 66 to 72% of the cases of NF1. Lengthening of fungiform papillae happens in 50% of cases and is the most frequent finding. In 25% of NF patients oral neurofibromas can be seen. There is no racial, gender or age predilection for the development of oral neurofibromas in NF1."
]
| [
"Dental & Oral Medicine",
"Basic Medical Sciences",
"Medical Research & Methodology",
"General Surgery",
"Neurology",
"Radiology & Imaging"
]
|
https://api.semanticscholar.org/CorpusID:10000049 | 10000049 | H-Ras Isoform Mediates Protection Against Pressure Overload–Induced Cardiac Dysfunction in Part Through Activation of AKT | 2,017 | Circulation: Heart Failure | [
893772,
1663061
]
| [
"Sham operation was performed without aortic constriction.\n\n Hearts were analyzed for interstitial fibrosis using Masson's Trichrome, myocyte cross-sectional area (CSA) using wheat germ agglutinin, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).\n\n Homogenates were incubated with Raf-1 RBD agarose (Upstate, Millipore) for 40 minutes at 4°C to precipitate GTP-bound Ras according to manufacturer's instructions.\n\n All data are reported as mean±standard error of the mean. Student's t test was used to evaluate the difference in means between 2 groups. Multiple groups were analyzed using Levene's test to determine heterogeneity of variances, followed by Welch's analysis of variance. Post hoc multiple comparisons were performed using Tukey's test. Statistical analyses were performed using SPSS v24 and Graph Pad Prism 6.0. A P value <0.05 was considered significant.\n\n To determine the role of endogenous Ras isoforms on basal cardiac structure and function, we used H-and K-Ras loss-of-function mouse lines. Homozygous deletion of Kras is embryonic lethal 25 ; therefore, we used Kras +/− mice for this study. Kras +/− mice are viable and showed no obvious cardiac abnormalities in heart size, structure, and function compared with WT controls at baseline (10-12 weeks; Figure 1A through 1D) . Interestingly, homozygous disruption of Hras is tolerated, and mice are born at expected Mendelian ratios. 26 However, by 10 to 12 weeks of age, Hras −/− mice developed a mild but significant reduction in cardiac function, as determined by echocardiographic analysis (percent LV ejection fraction [%LVEF]; Figure 1E through 1H) . Hras −/− mice also had a modest but significant reduction in LV mass when compared with WT controls. In contrast, Hras +/− mice showed no difference in cardiac size or function compared with WT mice at baseline ( Figure 1E through 1H) .\n\n Mechanical stretch is known to activate Ras proteins in cardiomyocytes. 20 We, therefore, subjected WT mice to 1 and 7 days of pressure overload by transverse aortic constriction (TAC) and determined H-and K-Ras activation in the myocardium. We found that both isoforms were activated at 1 day post-TAC; however, only K-Ras activation was increased at 7 days post-TAC (Figure 2A and 2B) . To determine the role of these Ras isoforms in mediating pressure overload-induced cardiac hypertrophy and dysfunction, H-and K-Ras mutant mice were subjected to 4-week TAC. There was no significant difference in pressure gradients achieved in all TAC experiments ( Figure I in the Data Supplement). In response to pressure overload, Kras +/− mice showed a similar increase in cardiac hypertrophy, as determined by LV weight/tibia length, cardiomyocyte CSA, and fetal gene expression, when compared with WT littermates (Figure 2C through 2E; Figure II in the Data Supplement). However, we observed a trend toward reduced myocardial fibrosis and a significant reduction in TUNEL-positive cells in Kras +/− hearts after TAC compared with those of WT mice ( Figure 2F through 2H). Importantly, %LVEF was significantly greater in Kras +/− mice compared with that in WT mice after 4 weeks of TAC ( Figure 2I and Table 1 ). Furthermore, in Kras +/− mice, LV end-diastolic dimension was significantly smaller compared with that in WT controls after TAC (Table 1) , indicating attenuated chamber dilatation and improved systolic function. Taken together, these results indicate that reduced K-Ras expression does not alter the hypertrophic capability of the mouse heart but does attenuate cardiac maladaptation to pressure overload stress.\n\n H-Ras mutant mice were also subjected to pressure overload and assessed. Pressure overload-induced increases in LV weight/tibia length and cardiomyocyte CSA were not significantly different between Hras +/− mice and WT controls. However, Hras −/− mice had significantly attenuated LV weight/ \n\n +/− mice declined to a similar extent as in WT mice after 4 weeks of TAC. However, %LVEF was significantly further reduced in the Hras −/− mice after pressure overload ( Figure 3G and Table 2 ). Moreover, septal wall thickness was significantly smaller in Hras +/− and Hras −/− mice after TAC compared with that in WT mice.",
"T he Ras family of small GTPases consists of ubiquitously expressed signal transducers that relay extracellular cues inside the cell, thereby, regulating a host of signaling pathways and cellular responses. 1 Activation of Ras proteins is modulated through engagement of transmembrane receptors, both receptor tyrosine kinases and G-protein-coupled receptors, and through mechanical forces, that is, cell stretch/strain. These signals lead to guanine nucleotide exchange factor activation and Ras GTP loading. GTP-bound Ras is active and is able to bind to and signal through downstream effectors, the most established being Raf, 2-5 phosphoinositide 3-kinase (PI3K), 6 RalGDS, [7] [8] [9] PLCε, 10 and Tiam1. 11 Signal pathways elicited via Ras can modulate a variety of responses, including gene expression, growth, survival, proliferation, endocytosis, and cell motility.\n\n Ras proteins are highly relevant to human disease, and myriad studies have demonstrated Ras mutations in many types of cancers. 12 Human germ line mutations in Ras proteins, and known modulators of Ras signaling pathways, have been linked to the developmental disorders Neurofibromatosis type 1, cardio-facio-cutaneous, 13, 14 Noonan, [15] [16] [17] Costello, 18 and LEOPARD syndromes. Collectively referred to as RASopathies, these genetic disorders share dysregulation of Ras/mitogen-activated protein kinase (MAPK) signaling and phenotypic overlap, including craniofacial abnormalities, cardiac malformations, impaired cognitive ability, and increased cancer risk. Specifically, these patients present with cardiovascular abnormalities, including hypertrophic cardiomyopathy, atrial-septal defects, pulmonic stenosis, and tachycardia. Although the nature of these cardiac defects is heterogeneous and the cause of these differences remains unclear, these syndromes provide strong evidence of the importance of Ras proteins in human myocardial pathophysiology.\n\n To date, studies investigating the role of Ras signaling in a cardiac context have almost exclusively focused on the H-Ras isoform. Early work demonstrated that agonists and interventions that promote cardiomyocyte hypertrophy, characterized by increased cell size and activation of embryonic gene expression, also elicit activation of Ras. 19, 20 This growth response was demonstrated to require Ras activity, and later, the expression of activated H-Ras was shown to be sufficient to promote cardiomyocyte hypertrophy. 19, 21, 22 Myocardial expression of activated H-Ras12V driven by the myosin light chain 2v promoter was shown to cause increased left ventricular (LV) mass, hypertrophic gene expression, and functional decompensation H-Ras Mediates Cardioprotection via AKT in transgenic animals, 23 further supporting the hypothesis that H-Ras promotes cardiomyocyte hypertrophy, as well as suggesting a maladaptive response to increased cardiac H-Ras activity. Additional studies suggested that this response was reversible and may involve altered sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) function and calcium handling. 24 The objective of the current study was to determine the role of endogenous H-and K-Ras in pressure overloadinduced cardiac hypertrophy and heart failure. We used genetic loss-of-function mouse models and cultured neonatal rat cardiomyocytes (NRCMs) to interrogate each isoform in vivo and in vitro. Our findings indicate that H-Ras promotes cardiomyocyte hypertrophy and is cardioprotective during chronic pressure overload, whereas K-Ras does not promote growth and serves a deleterious function. We observed markedly less phosphorylated AKT and extracellular signal-regulated kinase (ERK) in pressure-overloaded Hras null hearts. Inhibition of AKT activation attenuated H-Ras-induced cardiomyocyte hypertrophy in vitro, and restoration of AKT signaling in vivo was able to rescue cardiac function in pressure-overloaded Hras null hearts. These results suggest that endogenous H-Ras mediates hemodynamic stress-induced cardiac hypertrophy and affords a cardioprotective function in the murine heart in part through activation of AKT.\n\n An expanded Methods section is available in the Data Supplement.\n\n \n\n +/− and Hras +/− mice have been described previously. 25, 26 All protocols concerning the use of animals were approved by the Institutional Animal Care and Use Committee at Rutgers, New Jersey Medical School.\n\n Mice were anesthetized and pressure overload induced by ligation of the transverse thoracic aorta."
]
| [
"Basic Medical Sciences",
"Medical Research & Methodology",
"Cardiology"
]
|
https://api.semanticscholar.org/CorpusID:10000061 | 10000061 | Cohort Profile: The Cebu Longitudinal Health and Nutrition Survey | 2,011 | International journal of epidemiology | [
1209618,
345821
]
| [
"The Cebu Longitudinal Health and Nutrition Survey (CLHNS) was originally conceptualized as an interdisciplinary study of infant-feeding patterns, particularly the overall sequencing of feeding events (milks and complementary foods), the factors affecting feeding decisions and how feeding patterns affect the infant, mother and household. The idea was to study these topics within as natural a setting as possible and to analyse how infant-feeding decisions interacted with social, economic and environmental factors to affect health, nutritional, demographic and economic outcomes. The study was subsequently expanded to cover a wide range of maternal and child health and demographic issues that could be well studied using a prospective, community-based sample.\n\n The study was initially the product of collaboration among researchers at the Carolina Population Center at the University of North Carolina at Chapel Hill (led by B.M.P. with J.S.A. and D.K.G.), The Office of Population Studies Foundation at the University of San Carlos in Cebu, Philippines (led by the late Director Wilhelm Fleiger) and the Nutrition Center of the Philippines (led by Florentino Solon). L.S.A. took the lead for follow-up surveys beginning in 1990. Later, the study team was expanded to include researchers presently at the Northwestern University (C.W.K. and T.M.D.) and Johns Hopkins University (M.J.H.). The study was initiated with cooperation and approval from the Cebu Department of Health. The CLHNS website includes a full list of investigators and their affiliations.\n\n The CLHNS was one of the first large-scale, population-based surveys designed with a conceptual framework in mind. The guiding framework was adapted from Mosley and Chen's health determinants model, 1 which posits that underlying community-, household-and individual-level variables affect a set of proximate health behaviours which, in turn, influence health outcomes such as growth and infectious disease morbidity and mortality. The study was designed by a highly interdisciplinary group of economists, sociologists, nutritionists, demographers and physicians.\n\n The CLHNS has been funded by a large number of government and non-government organizations (listed in the Funding section).\n\n The CLHNS covers a wide range of health-related topics specific to each stage of the life cycle. In the prenatal period, this included social, environmental, demographic, health services and nutritional factors that influence birth outcomes. In the first 2 years after birth, the focus was on infant feeding, morbidity and growth, and mothers' health and nutritional outcomes and birth spacing. During the 1991 follow-up, the focus was on childhood stunting, intellectual development and entry into school. As the cohort entered adulthood, emphasis was on early-life factors that predict schooling and academic achievement, and the development of obesity and cardiovascular disease (CVD) risk. Throughout, data were collected to enhance understanding of how changing community and household factors influence health outcomes. In parallel with the focus on following the original birth cohort, CLHNS mothers were followed to learn about their long-term patterns of health, birth spacing, family planning, diet, nutritional status, physical functioning, status, parent-child relationships and work patterns.\n\n Core questionnaire modules related to household socio-economic status (employment, education, income, assets, etc.), demographics and environment were retained to allow comparability over time. Additional items were added to modules to account for changing environments (e.g. the list of assets was expanded to include items such as cellular telephones and personal computers, which no household possessed at the time of the baseline survey). New modules were added over time to address age-appropriate and novel topics (e.g. the 1998 survey added an adolescent reproductive health module). Community surveys were related to health-care facilities, water sources, sanitation and food and commodity prices, and a wide array of other community infrastructure and service measures.\n\n In 1998, two subsamples of adolescents participated in additional studies. CLHNS adolescents with a birth weight of <2.6 kg, plus a random sample of those with birth weight of 52.6 kg, participated in a clinic study which collected fasting blood samples (n ¼ 619). In 100 of these adolescents, antibody response to a typhoid immunization was tracked. Qualitative research has also been conducted with subgroups of participants, related to women's status and decision making and family planning. In 2002 and 2005, a life-event history matrix was collected from the index young adults.\n\n In 2005, fasting blood samples were collected from all index young adults and their mothers, and saliva was collected for measurement of steroid hormones. The deoxyribose nucleic acid (DNA) was extracted from blood, and plasma was stored for subsequent laboratory analysis of selected biomarkers.\n\n As the original birth cohort has entered adulthood, several studies have focused on reproduction and reproductive biology.",
"In males, samples and data collected in 2005 were used to evaluate multiple sex steroids and measures of testicular function, which were related to parenting and fatherhood.\n\n A 2009-11 study is identifying new pregnancies and birth outcomes among index female young adults, thus making the CLHNS a three-generation study.\n\n Participants are residents of Metropolitan Cebu in the Philippines. With a population approaching 2 million, Metro Cebu is the country's second-largest metropolitan area. Located on the east coast of Cebu Island in the Visaya's region, it comprises four cities (Cebu City, Mandaue, Lapu-Lapu and Talisay) and seven municipalities in surrounding areas. Metro Cebu includes 270 administrative units (barangays), which are villages in the rural areas or neighbourhoods in urban areas. The urban core extends along the seacoast, and to the base of nearby mountains. The study area is ecologically diverse, with high-density urban neighbourhoods, less dense peri-urban areas, rural towns and more isolated mountain and island rural communities.\n\n In 1983, a single-stage cluster-sampling procedure was used to randomly select 17 urban and 16 rural barangays from among the 243 barangays of Metro Cebu identified in the 1980 census. The selected barangays, representing approximately 28 000 households, were surveyed to locate all pregnant women, who were asked, in person, to join the study. Fewer than 4% refused. Those who gave birth between 1 May 1983 and 30 April 1984 were included in the sample. A baseline interview was conducted among 3327 women during pregnancy. Of these, 3080 gave birth to a single live infant, 26 had multiple births, 42 had a stillbirth or miscarriage, 17 refused further participation after the baseline survey and 136 were out-migrants. The survey initially followed only the singleton index children and their mothers through the first 2 years of life. Demographic and socioeconomic differences between the 3080 mothers of singletons and those initially excluded from the sample were minimal, with younger age and lower parity being the only significant predictors of being in the excluded group. Twins and mothers whose infant died were later re-incorporated into the survey. The infants are a representative sample of births in Metro Cebu during a 1-year period. Their mothers are not representative of the Metro Cebu adult female population of childbearing age, owing to the fact that pregnancy was a requisite for entry into the study. Demographic characteristics of the women and infants are presented in Table 1 .\n\n How often have they been followed up?\n\n Surveys were conducted in the second to third trimester of pregnancy, immediately after birth and then every 2 months for 24 months. \n\n CLHNS individual and household data are collected during in-home interviews. The only exception is the 1998 biomarker sub-study, which was conducted in local health clinics. Community data are collected from key informants, who are typically the elected barangay leaders. \n\n Of the 3327 women included at baseline, 3080 remained in the study and had singleton live births during the 1-year period of eligibility. In the 2007-08 tracking survey, 63% of these 3080 mothers who were present at the birth information survey were located and interviewed, and 59% of the 3080 singletons were located and interviewed (Table 3) . Attrition was largely due to out-migration (e.g. 78% of the women not interviewed in 2007 have migrated outside sample area). Refusal rates at each survey ranged from 9 to 11% during the first year of data collection but substantially decreased over the years (5% in 2007) as rapport between participants and study team strengthened. To date, 232 of the 3080 index children, and 162 mothers of singletons are known to have died. The vast majority of child deaths occurred within the first 2 years of life. Compared with those lost to follow-up, women who participated in the 2007 survey were less educated, of higher parity and came disproportionately from rural, poorer households. Given that permanent migrants from the Metro Cebu area were not followed, the remaining sample is therefore selective of households with more residential stability. For example, 68% of the women in the 2007 survey have resided in the same barangay since baseline.\n\n More than 125 scholarly works based on the CLHNS and written by current collaborators have been published in demography, economics, epidemiology, biomedical, human biology, nutrition, public health and women's studies journals (a complete list of publications is available on the CLHNS web site)."
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https://api.semanticscholar.org/CorpusID:10000093 | 10000093 | Does Telecare Improve Interorganisational Collaboration? | 2,016 | International journal of integrated care | [
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"Health care systems in developed countries struggle with fragmentation of care, lack of coordination, and interorganisational collaboration [1] [2] [3] . Various political strategies have been developed and research undertaken to find solutions to each of these problems, yet fragmentation continues [2] . One attempt to address such problems has been through the innovation and implementation of digital tools that allow for fast and easy sharing of patient data [4, 5] . For example, experimentation with new initiatives such as telecare is growing at a rapid pace throughout the majority of the world [6] . Telecare is a new health service that involves the use of technology within patients' homes, such as home monitoring, safety monitoring, and information service technologies [7] . Certain of these technologies are already in broad use [8] , though home monitoring has yet to be institutionalised within the conventional treatment of persons with chronic diseases (for an exception, see [9] ). Various pilot studies of telecare show promising results, including enhancement of efficiency, improved quality of care, and better integration of care via the effective coordination of activities and collaboration between different health care providers [10] [11] [12] [13] .\n\n As telecare services have yet to become fully mainstream, the majority of research in the field is based on pilot projects [4] and has focused on economical and clinical effects [13] . Few studies have investigated how telecare may contribute to integrate activities and collaboration between different health providers (e.g., [10, 14] ). Thus, the following research question was asked: How does telecare affect interorganisational collaboration within a network of health care professionals from different organisations and political levels? Contrary to prior studies, this study examines a large-scale, cross-sector Danish telecare programme involving more than 1,200 patients with chronic obstructive pulmonary disease (COPD) who receive remote home monitoring from an interorganisational telecare network of eleven municipalities, four hospitals, and 225 general practitioners (GPs). The study offers two substantial contributions. First, it deepens our empirical knowledge of telecare in a complex, large-scale setting with multiple health care organisations. Second, it provides a nuanced understanding of how telecare reconfigures interorganisational networks in terms of interorganisational collaboration, dependency, and power structures.\n\n The Danish health care system is a mainly public system based on general taxation. The system is characterised by rather strong regulation from the state, and is managed politically at the state, regional, and municipality levels. The health care system is organised into primary and secondary health sectors. Primary health care services are mainly provided by two separate actors: self-employed GPs (family doctors) and municipalities (the local political level). GPs act as gatekeepers to the health care system, as the majority of access to hospital treatment (except for emergency visits) and municipal health services requires referrals from GPs. Municipalities provide preventive care, home care, and rehabilitation. Secondary health care services are provided by hospitals, which are led by regions (the regional political level). Hospitals perform specialised treatment, both during hospitalisations and as a part of outpatient clinic services [15] . Even though the Danish health care system is perceived to be one of the most integrated systems in Europe, it nonetheless struggles with fragmentation challenges [3] . Such fragmentation creates extensive demand for the integration of activities between the three main health providers (municipalities, hospitals, and GPs), especially concerning patients with chronic conditions [10] .\n\n The paper is based on a qualitative case study of TeleCare North [16] , the largest Danish telecare programme. This programme is rather distinct both in Denmark and internationally because it involves interorganisational collaboration between health care actors in the primary and secondary health sectors. Figure 1 depicts the actors in the telecare network of the programme.\n\n The aim of the programme is to improve collaboration between different health care providers, for example, by providing shared access to the same monitoring database. Furthermore, savings in terms of hospital (re)admissions and improved quality of life are expected outcomes of the programme [16] .\n\n TeleCare North focuses on the home monitoring of patients with COPD who live in the northern part of Denmark. These COPD patients self-measure oxygen level, blood pressure, pulse, and weight, and answer questions about their symptoms. This data is then sent to a shared monitoring database that allows not only GPs to access and monitor patients' data, but also health professionals from municipal health centres, municipal district nurse units, hospital wards, and hospital outpatient clinics. Conventionally, various groups of health care providers use their own electronic documentation systems that are not accessible to others outside their organisation.",
"So, our collaboration with the GPs can be characterised as non-existent.\"\n\n No interdependencies between hospital nurses and GPs were acknowledged by all interviewees. Similarly, the lung physicians, for example, did not express any dependency on the GPs or the increased need for collaboration. In line with this statement from the hospital nursenearly every GP was surprised to hear that the hospitals were a part of this programme even though it had been implemented for nearly six months at the time they were first interviewed. This clearly exemplified the non-existent collaboration between the hospitals and GPs. Similar to the hospital staff, none of the GPs expressed a need for greater or extended collaboration.\n\n At the municipalities, the need for interorganisational collaboration with the hospitals was more pronounced. The municipal nurses expected better information flow and knowledge exchange with hospital staff to be one of the goals of telecare. However, these expectations were not met, as one of the municipal nurses explained: \"We had one patient who was hospitalised. During his hospitalisation they changed his medicine and oxygen treatment. However, we were not notified at all, even though the hospital staff and his GP knew he was part of this telecare programme [and that we monitor his data, ed.] (. . .) Afterwards, we talked to the patient, and he assumed we knew about the changed medication and oxygen treatment, but we didn't.\"\n\n This lack of integration in terms of knowledge and activities between municipalities and hospitals created fragmented care for patients in two ways. First, missing information related to hospitalisation meant that municipal nurses lost a degree of their authority in terms of knowledge and were not able to build a treatment alliance with the hospital staff. Instead, communication across the sectors appeared incoherent. Therefore, telecare did not mediate a shared understanding or better information flow between the different health care providers from the municipalities and hospitals. Second, hospital actors did not integrate municipal nurses' or GPs' knowledge about the COPD patients into their work activities. For example, regular check-ups at the outpatient clinic were held as usual without the integration of telecare data or observations from the municipal nurses. The frequency of the check-ups was not changed regardless of whether or not the municipal nurses deemed patients to be on a stable COPD course without exacerbations, which reflected the limited collaborative efforts between the municipalities and hospitals. Hence, the integration of knowledge in the patients' courses and changes in behaviour was limited when relying solely on the voluntary behaviours and good-will of the collaborators.\n\n One episode, however, within a municipal nursing district unit, serves as an example of successful collaboration, as the following sequence from the study's observation notes illustrates: \"The municipal nurse calls a patient because his oxygen level is very low. They talk about his latest hospitalisation and how the physician at the lung ward recommends oxygen treatment. The municipal nurse supports this recommendation and the patient seems more convinced.\"\n\n This example illustrates how the two actors successfully collaborated across the primary and secondary sectors in an alliance so as to convince a patient about starting oxygen treatment. As a result, the information and recommendations from the two sectors were coherent and integrated for the patient. In this case, telecare created an opportunity to collaborate and mediate a shared understanding of the patient's treatment.\n\n Even though collaboration in most cases was close to non-existent, conflicts between municipal and hospital nurses were nonetheless identified in the study's interviews and observations. These conflicts concerned distrust of each other between the nurses. Certain patients were monitored at different times by both the municipalities and the hospitals. The majority of the nurses, regardless of their organisational affiliation, checked up on their patients when they were monitored by the other party, even though they were not supposed to, which led to suspicions concerning how the other party was reacting to patient data. One of the municipal nurses expressed this issue in the following way:\n\n \"Collaboration with the hospital has not been very successful. We have a patient who is currently being monitored by the hospital. I am curious, so I still check his data. I discovered that the hospital doesn't really react to bad vital signs from him. So I don't think the collaboration actually works.\"\n\n This nurse was not able to access the hospital's electronic medical record so as to see how the hospital nurses were reacting to the patient's measurements, but could only see the patient's basic data. Similar situations were observed in the hospitals. In the study's observations, it was evident that the counterpart (either the municipal or hospital nurses) did in fact react and offer treatment based on poor measurements, but this was not noted in the monitoring database in the telecare programme. As the health professionals only documented their actions and decision-making processes in the medical records of their own organisations, the sharing of knowledge was highly restricted.",
"The TeleCare North programme is managed by a steering group with representatives from municipalities, hospitals, GPs, and other relevant actors (e.g., patient unions and the National Agency for Digitisation), with a composition that reflects the interorganisational setup of the programme. At the administrative level, the programme's steering group facilitates interorganisational collaboration [17] . At the operational level, formal agreements between the municipalities, hospitals, and GPs assign roles and tasks to different municipalities, hospitals, and GPs. Municipalities are responsible for monitoring patients in a stable COPD course (which characterises the majority of patients in the programme), while hospitals are responsible for monitoring the most severe COPD patients. GPs are responsible for referring patients to the programme, and have an on-going responsibility to adjust each patient's measurements, such as concerning acceptable levels of oxygen in the blood. GPs serve much like a form of medical consultant to municipal nurses.\n\n To understand how telecare can integrate care across the different health care providers, it is necessary to understand how integration can be obtained. According to Axelsson and Axelsson (2006) , integration can be divided into vertical integration and horizontal integration. Vertical integration denotes integration between organisations or organisational units at different hierarchical levels, whereas horizontal integration denotes integration at the same hierarchical level. Collaboration involves a high degree of horizontal integration and a low degree of vertical integration. Collaboration can be difficult to achieve, as it often relies on voluntary agreements and mutual adjustments between organisations in the absence of a common hierarchical structure [17, 18] . Alternatively, cooperation involves both a high degree of vertical integration and a high degree of horizontal integration. Cooperation combines hierarchical control mechanisms with greater voluntary network collaboration in a complex matrix organisation [19] , requiring a kind of common hierarchical system or formal agreements in interorganisational contexts.\n\n Collaborative processes and interorganisational relations often take place within a network structure. Interorganisational networks emerge through the repeated interactions of organisational actors from different organisations, and are the result of different kinds of interdependencies between network organisations in terms of solving tasks or achieving certain goals [17, 20, 21] . By entering or forming networks, organisations gain access to new resources, such as information, competencies, knowledge, and money, which make it possible to solve tasks that they could not otherwise have handled by themselves [2, 17, [20] [21] [22] .\n\n Numerous kinds of network types exists (e.g. joint ventures, strategic alliances etc.) [23] but a certain type is of interest to this study because it denotes relations between different kind of organisations that collaborate to reach a shared goal: a systemic network. Such networks consist of different organisations with complementary competencies, services, or products that collaborate to solve a shared task in an interorganisational context. Completing shared goals requires the functional differentiation of roles, responsibilities, and tasks, as well as horizontal processes of collaboration and the integration of activities in a network [10, 17] . Thus, organisations are highly dependent on each other to solve shared tasks. Due to such dependency, tensions and conflicts may arise between the organisations, especially when one actor is more dependent on another. According to resource dependency theory, dependent actors have a weaker position in a network and may attempt to countervail asymmetrical dependency structures by forming coalitions or searching for alternative collaborators [20] . However, such attempts do not often go unnoticed by the more powerful actors in a network, who typically counteract to remain in a powerful position [24, 25] .\n\n Interorganisational relations and collaboration processes are thus dynamic, loaded with moves and countermoves to achieve the most advantageous position within a network. Furthermore, negotiations and power struggles concerning specific domains and the division of labour serve to (re)define, and sometimes blur, the boundaries between professionals and organisations within a network. This is especially evident in health care systems that include professional bureaucracies which rely on highly trained professionals (e.g. doctors), and are characterized by a high degree of functional specialization and decentralized decision-making structure [26] [27] [28] . According to Abbott (1988) the implementation of new tasks and technologies can create disturbances in existing power relations between professions and within systems of professions. Within systemic networks that consist of professional bureaucracies, tensions and power struggles should therefore be anticipated.\n\n Based on this conceptual framework, this study investigates the horizontal collaboration processes and dependency structures at the operational level among various health care professionals across different municipalities, hospitals, and GPs within a systemic network where tasks are predominantly mandated through formal agreements.",
"Consequently, the inability to gain insight into other institutions decision-making processes was a barrier to interorganisational collaboration.\n\n As demonstrated, telecare predominantly affected collaboration in the primary sector between municipalities and GPs. However, networks are unstable entities that fluctuate and change according to different network dynamics [31] , which was found to be the case in terms of horizontal collaboration processes in a year follow-up examination. Two main changes were identified. The first concerned collaboration between GPs and municipal nurses. Between the first and the second interview round, collaboration was found to have decreased. One hypothesis for this was that the need for collaboration simply decreased after initial challenges with telecare and adjustment of the programme were overcome. However, this was not altogether true. In certain cases, decreased collaboration was a result of telecare being utilised mainly as a mono-organisational service, with municipal nurses solving telecare tasks independently of GPs or hospitals. Interorganisational collaboration was thus in these cases almost non-existent. GPs were detached from the telecare services and no longer had any interactions with them. In other cases, the positive dynamic between the municipal nurses and GPs found in the study's first interview round was enforced, namely, with regard to the quality and professionalism of the municipal nurses' inquiries to GPs. One GP explained this on-going positive dynamic as follows:\n\n \"Collaboration with the municipal nurses is much better. It is more relevant; the questions from the nurses, who have all of this information from the patients' self-monitoring, have become much more relevant compared to the beginning of the programme.\"\n\n In these cases, there seemed to be greater mutual acknowledgement of interdependency and complementarity between the GPs and the nurses since the first interviews, with dependency relations appearing less asymmetrical, even though the nurses were still more dependent on the GPs than vice versa. The second change was related to the patients' role, as they had gained a more active role in their treatment and were more empowered to start treatment themselves according to their self-treatment plans. As a result, collaboration between municipal nurses and GPs became more indirect and mediated through the patients themselves. A municipal nurse explained this change of empowerment as follows: \"In the beginning of the project, the patients disclaimed responsibility for their disease. They expected me to contact their GP when they felt bad. Now, however, most of them have taken responsibility for their disease; they are in charge now.\"\n\n One GP elaborated on the indirect collaboration created by patients, who serve as links between different health providers:\n\n \"The patients are the link between the municipal nurses and me. They contact me because their municipal nurse told them to.\" Several GPs, however, stated that patients still perceive them as the medical authorities, and that the latter informs them each time they start self-treatment, even though the GPs do not require this information. Thus, it appears that the GPs' role as the medical authority remains intact despite the new central role of municipal nurses in patient courses. Despite these continuing changes, the amount of collaboration between the primary and secondary health sectors remained unchanged and almost non-existent.\n\n One of the main objectives with TeleCare North was to improve collaboration by developing and implementing an interorganisational telecare service among the three main health providers in Denmark (municipalities, GPs, and hospitals). The findings of this study reveal that telecare affected interorganisational collaboration to varying degrees, and that these degrees further changed over time. The analysed dyadic relations between municipalities and GPs in the primary sector and between the primary and secondary sectors, however, cannot be understood without taking into account other relations and dynamics in the network. Thus, the findings related to the dyadic relations at the broader network level will here be discussed.\n\n One of the basic aspects of systemic networks is that organisations are mutually dependent on each other to solve a joint task [17] . Interorganisational relations are interconnected in a complex web, with changes to certain relations affecting other relations in the network. Therefore, when collaboration between GPs and municipal nurses is enforced, it both affects and is affected by the interorganisational relations between GPs and hospitals and hospitals and municipalities. Interconnectedness was witnessed in the network in the following ways. Strong ties between GPs and municipal nurses were often associated with weak or non-existing collaboration with hospitals in the telecare network. Stronger collaboration and enhanced competencies in the primary sector appeared to supplement demand for hospital services and expertise when delivering daily telecare services. As a result, the hospitals' role and functions in the telecare network were nearly invisible to the other actors within it, which the following quote from a hospital nurse illustrates:\n\n \"It is my impression that the municipal nurses are skilled when handling the COPD patients. They don't need our expertise.",
"Before [the telecare programme, ed.] we perceived our self as the experts, and of course we are still the experts in some aspects, but when it comes to COPD, we are quite equal with the municipal nurses, who assess the patients' data.\"\n\n Despite their near invisibility to the other players in the network, no counteractions were taken by the hospitals to re-establish the dependency structures that favoured their powerful position as COPD experts.\n\n In other cases where collaboration between municipal nurses and GPs was weak or non-existent, more informal, ad hoc collaboration between municipal nurses and hospital staff emerged, with GPs distanced within the telecare network. Traditionally, collaboration between municipal nurses and hospitals was mediated by GPs, who referred patients to hospitals or municipal health services. However, when the GPs refused to collaborate and mediate the link between the hospitals and municipalities the municipal nurses found alternative strategies to collaborate directly with hospitals when GPs refused to participate and serve as mediators. A municipal nurse commented on this issue as follows:\n\n \"We asked the GP about a self-treatment plan, but he refused to take it, so instead we contacted the lung physician at the hospital, who made a more comprehensive treatment plan (. . .). So, we find our loopholes [when the GPs refuse to collaborate, ed.].\"\n\n The above comment reflects the asymmetrical dependency structures of the telecare network and how they force municipal nurses to initiate and maintain collaboration with various medical experts (GPs, hospital nurses, or doctors). Such unequal dependency structures speak to how more dependent organisations (in this case, the municipalities) are left in a vulnerable position in terms of support and ability to react properly on poor measurements. However, as has been shown in this study, it is nonetheless possible for dependent organisations to work their way around certain obstacles in a network and build interorganisational relations to fulfil their needs.\n\n Based on the findings of this study, it is important it is to take into account power and dependency structures when studying networks. These structures have often been omitted in studies on networks, as mutual dependency has been assumed to equalise power asymmetries [32] . Indeed, such power and dependency structures are not stable, but fluctuate and change according to network dynamics and changes in network organisations and broader contexts [24, 31, 33] . Fluctuation and changes in power and dependency structures was evident in the telecare network when municipal nurses became less dependent on medical expertise as they became accustomed to telecare tasks and gained more specialised knowledge concerning COPD and their patients. Consequently, the dependency and power structures in the telecare network changed, and the three health providers could act more independently in solving telecare tasks. However, with this came the risk of losing the incentive to collaborate.\n\n Each of the actors in the network was not able to reach the shared network goals alone. For example, the network set the goal of reducing ordinary check-ups at the hospitals and among GPs. To fulfil this goal, both hospitals and GPs were dependent on municipal nurses and their assessments of patients' conditions. However, the hospital staff and GPs continued to work independently of the municipal nurses, and thus the network goal was not reached. To achieve this goal, a greater balance between autonomy and dependency in the network was required, which should be developed and maintained through the effective management of horizontal network processes [17, 34] . The findings of this study further suggest that the integration of activities in the telecare network must be achieved beyond mere collaboration. For example, it may be beneficial to focus on vertical integration through hierarchical mechanisms. That is, cooperation [18] -which involves a high degree of hierarchical control mechanisms, voluntary agreements, and mutual adjustments between organisations -may be a more useful method for developing complex health services that cross organisational boundaries.\n\n This study followed a qualitative case study design. Throughout the study, rich descriptions of the organisational settings and contexts allow the findings of the study to be transferred to similar settings, as well as be generalised for further analyses. The internal validity and credibility of the results were gained through the presentation to and validation of the findings by practitioners in the telecare programme. Even though the results were controversial (as they revealed that network goals were not achieved), the different practitioners confirmed the findings within their own organisations. Moreover, the researcher's insight into the field enhanced the credibility of the findings [35] .\n\n The analytical choice to divide the network into dyadic relations may be perceived as a limitation of the study. The decision was made to decrease the complexity and comprehensiveness of full network analysis. Though, dividing the network into dyadic relations does not offer a full analysis at the network level [22] . Analysing networks at the network level, however, was beyond the scope of this study. Consequently, a full explanation of the network's dynamics is not offered in this study. Instead, the dyadic relationships and their interconnectedness are investigated and discussed in relation to network goals and dynamics.\n\n The implementation of telecare was found to affect interorganisational collaboration between municipalities, hospitals, and GPs to varying degrees. The changes identified in this study with regard to interorganisational relations were related to structural properties, power, and dependency structures in the telecare network. The telecare network was centralised, with the municipalities serving as its central organisations. This central position gave the former power, and thus the municipal nurses had increased influence on COPD treatment, which challenged the medical authority of GPs, as well as generated intra-professional conflicts between the hospital and municipal nurses. The municipalities were put in a vulnerable position, as they were significantly more dependent on the medical expertise of GPs or hospital staff than the other way around. This dependency initially instigated intensified collaboration among municipal nurses and GPs. When collaboration with the GPs was impossible or difficult to establish, the municipal nurses found alternative strategies for receiving medical expertise from hospital staff. Otherwise, the hospitals were nearly invisible to the other actors in the telecare network. The dependency structures, however, changed during the period that the telecare network was studied. The municipalities became less dependent on medical expertise as their experiences and knowledge about monitoring COPD patients grew. Accordingly, municipal nurses' collaboration with the GPs was less intense. However, both the GPs and municipal nurses characterised their collaboration as more professional and relevant as a result of telecare use, and that such professionalization had in certain cases been reinforced over time. At the same time, the telecare programme also led to interprofessional power struggles, as the municipal nurses challenged the GPs autonomy and positions as medical authorities. This study illustrates how networks fluctuate and change according to internal network dynamics and external dynamics. To improve or change interorganisational relations, continual effort and attention must be given to the power and dependency structures of networks and their interrelated dynamics.\n\n Carl Erik Moe, Professor, Department of Information Systems/Centre for e-Health and Care Technologies, University of Agder, Norway.",
"The second section offers findings concerning the collaboration between primary health sector (GPs and municipalities) figures and hospitals in the secondary health sector. The third section identifies changes of interorganisational collaboration within the telecare network between the two data collections. Based on these results, the findings concerning the broader telecare network and implications for interorganisational collaboration among the three different health providers in the network are given.\n\n The analysis of each organisational part of the telecare network revealed that only municipal nurses experienced significant changes in their work after the implementation of telecare, which in turn affected their collaboration with GPs. Traditionally, municipal nurses are generalists that lack training within a specialised field. In the telecare network, the majority of smaller municipalities had only generalist nurses, whereas the larger municipalities had specialised nurses. Half of the interviewed municipal nurses did not have specialised COPD competencies. The study's observations revealed that municipal nurses were struggling when assessing patient data, as this new task required specialised, indepth knowledge about COPD. Telecare was found to have forced the municipal nurses into specialist roles formerly belonging to hospital nurses.\n\n The new requirements of these specialist roles affected the nurses' collaboration with GPs, as they required increased support from GPs for the legitimacy of their data assessment. The result was more intense collaboration between municipal nurses and GPs due to the significant increase of queries from municipal nurses. Moreover, collaboration itself became more professional because, through the use of telecare, the inquiries of the municipal nurses were more precisely formulated and supported by comprehensive knowledge and information regarding patients' conditions. One GP expressed how collaboration was professionalized as a result of telecare of the collaboration as follows:\n\n \"The municipal nurses can now deliver certain interesting observations of patients which I find useful. So, yes, telecare supports our collaboration.\"\n\n The positive perception of collaboration after the implementation of telecare also resonated in the municipalities, as explained by a municipal nurse:\n\n \"Now I communicate more and better with the GPs because our communication has more substance than before. I get more professional inputs, which I would not have gotten from another nurse. So, yeah, I really appreciate it.\"\n\n In several cases, intensified collaboration was recognised as a way of increasing quality of treatment for the involved COPD patients.\n\n Collaborative efforts in relation to telecare were initiated solely by the municipal nurses, who were highly dependent on the GPs' medical expertise. From the GPs' perspective, they could solve tasks independently of the nurses, and furthermore, felt no obligation to collaborate with the nurses. This asymmetrical dependency left the municipal nurses in a vulnerable position, leading to frustrations with GPs that were unwilling to collaborate. Despite the seemingly subordinate position of the municipal nurses, however, they were able to challenge the GPs' position and authority in the decision-making process due to their newly gained knowledge about COPD and the patients' conditions which was gained through telecare.\n\n Both the nurses and the GPs articulated underlying issues of interprofessional tension in the interviews and observations. The GPs expressed that the municipal nurses were controlling their work and questioning their decisions about the treatment of the COPD patients. Consequently, they felt that the municipal nurses were infringing upon their professional domain. As for the municipal nurses, they expressed a similar sentiment, though in a slightly different way. Some of the nurses had experiences with GPs that suddenly became hostile and very protective of their status as clinical decision-makers. One of the nurses explained this hostility: \"I suggested another self-treatment plan to one of the GPs and this annoyed the GP. She wouldn't comply with my suggestion because, she said, 'I have the clinical knowledge and expertise in this field. I'm in charge and I decide how this patient is treated'. It was like she wanted to put me in my place.\"\n\n The majority of the municipal nurses also spoke about how their new knowledge gave them greater influence in relation to the GPs in terms of treatment and in the clinical decision-making process. Regardless of these underlying issues and asymmetrical dependency relations, however, telecare supported the interorganisational collaboration between municipal nurses and GPs within the primary health sector by making the collaboration more professional.\n\n In general, collaboration facilitated by telecare services among health care professionals from hospitals in the secondary health sector and the municipalities and GPs of the primary health sector was very restricted. The interviewed health care professionals from each of these areas characterised cross-sector collaboration as weak or non-existent. One hospital nurse discussed the weak ties between her and the GPs: \"I haven't been collaborating with the GPs at all in relation to telecare. (. . .) Actually, I don't find it necessary to collaborate more extensively with them. If they refer a patient to hospital treatment, well, then the referral is enough communication for us. What else do we need to collaborate about?"
]
| [
"Geriatrics",
"Public Health & Epidemiology",
"Healthcare Administration & Management"
]
|
https://api.semanticscholar.org/CorpusID:10000101 | 10000101 | Successful angioplasty for radial artery chronic total occlusion in a patient with digital gangrene | 2,013 | Postępy w Kardiologii Interwencyjnej = Advances in Interventional Cardiology | [
1143740
]
| [
"In contrast to lower limb, the upper limb critical ischemia is an uncommon clinical entity. Diabetes mellitus (DM) and chronic renal insufficiency (CRI) are the concomitant conditions for most of these patients [1, 2] . Patients with critical hand ischemia (CHI) generally experience pain, discoloration, ulcerations, tissue necrosis, and/or gangrene of the fingers which require urgent revascularization. As a result of excessive calcification and extensive disease, these patients are not appropriate for surgical treatment. We presented a case of upper extremity ischemia and digital gangrene treated successfully with percutaneous transluminal angioplasty (PTA).\n\n A 59-year-old woman with DM and CHI being treated with hemodialysis referred to Department of Cardiology, Bezmialem Foundation University Hospital with digital ulceration of the left hand fourth finger. Despite appropriate antiischemic and antibiotherapy, an unhealing necrotic lesion with soft tissue infection of the distal part of the fourth finger persisted (Figure 1 ). Preliminary arteriography, via right transfemoral approach (6F Judkins right 4.0 catheter, Medtronic Inc, Minneapolis, MN, USA) performed and confirmed a patent brachial artery with a proximal total occlusion of the radial artery and functionally occluded ulnar artery in the mid portion ( Figure 2 ). We planned to perform PTA.\n\n The brachial artery was engaged with a 6F Judkins right 4.0 (Medtronic Inc, Minneapolis, MN, USA) guiding catheter. A hi-torque Pilot® 50 (Abbott Laboratories, Abbott Park, IL, USA) guidewire was gently advanced through the radial artery until the deep palmar arch was reached. A Corsair microcatheter (CM, Asahi Intecc Co. Japan) was used to crossing through the total occlusion. By using 2.0 mm × 80 mm × 150 mm and 2.5 mm × 100 mm × 150 mm peripheral balloons (Fox SV, Abbott Laboratories, Abbott Park, IL, USA ), the lesions were dilated at high pressure (15 bar) for 5 min (Figu re 3). A good final angiographic result was obtained with immediate pain relief (Figure 4) . The patient was discharged with dual antiplatelet therapy on the day after the procedure. She was asymptomatic and the finger was almost healed at 2 month follow up ( Figure 5 ).\n\n We performed successful balloon angioplasty due to diffuse and severe calcific total occlusion of the radial artery. Hand healing and limb salvage were provided at 2 months after the procedure.\n\n Critical hand ischemia (CHI) caused by chronic occlusive arterial disease is an uncommon condition [1, 3] . Occlusive disease of the infrabrachial arteries is most frequently caused by thromboembolic disease, arterial injury and arthritis [4] . DM and CRI are the concomitant conditions in most of these patients [1, 2] . Patients with CHI generally experience ulcerations, tissue necrosis, and/or gangrene of the fingers which require urgent revascularization. Percutaneous intervention is preferred as a first-line therapy for arterial occlusive disease of the upper extremity [5] . Severe calcification and diffuse disease especially in patients with CRI undergoing hemodialysis are important factors affecting the success of the process. In such lesions, especially with the use of previous short balloons, the development of dissection is inevitable which affect the success of the process. However, new generation long and high-pressure-resistant peripheral balloons significantly reduced the formation of dissection and significantly increased the success of the [6] . The patient underwent percutaneous balloon angioplasty for radial arterial occlusion and hand salvage was provided except infected fourth finger.\n\n Conventional PTA is limited by high rates of vascular recoil, dissection, and restenosis [7] . However, dissection is significantly reduced with the use of long-and pressureresistant balloons. Although it develops recoil, the flow limitation may not occur. In our case, we performed balloon angioplasty for the diffuse and severe calcified total occlusion of the radial artery. We used long and high pressure resistant balloons and remained inflated for 5 min. Our result suggested that this approach is quite effective in relieving symptoms of critical ischemia and improving finger pressures, so as to allow the lesions of the finger to completely heal. Two months after the procedure, the finger was almost healed.\n\n In conclusion, PTA with long-and pressure-resistant balloons could be considered as an effective option for the treatment of CHI. A successful procedure could avoid amputation.\n\n R Re ef fe er re en nc ce es s"
]
| [
"Vascular Surgery"
]
|
https://api.semanticscholar.org/CorpusID:10000114 | 10000114 | Severe Acute Respiratory Syndrome: SARS: One Toronto Hospital Experience | 2,003 | Awhonn Lifelines | [
2244848,
736929
]
| [
"In late March 2003, health care workers in the greater Toronto area, in Ontario, embarked upon a new era in health care. Severe acute respiratory syndrome (SARS) had been identified as a trend in several hospitals.\n\n To deal with the increasing crisis, a Code Orange was declared by the Ministry of Health. A Provincial Operations Centre (POC) was established to centralize management of the SARS outbreak province-wide.\n\n It was not long before the inadequacies of current hospital emergency measures manuals became apparent. The manuals were developed to assist hospital personnel in dealing with \"one time\" sentinel types of events. There was an immediate need to develop and implement procedures and guidelines specifically relevant to SARS. All the new guidelines were focused on containment of the disease and protection of all patients, health care workers and visitors. The great challenge was to manage a disease about which very little was known, and about which knowledge would be constantly emerging.\n\n Door screening was implemented for everyone entering the hospital. Specific entrances were identified for use and all others were sealed off, thus securing the perimeter and ensuring that no one entered who did not pass through screening. All nonurgent procedures and clinics were cancelled, and visiting restrictions were implemented.\n\n Volunteers, salespersons and delivery personnel weren't permitted to enter the hospital. screeners' role involved promoting public relations, communicating policies, de-escalating resistance, and offering solutions or options. Isolation rooms and units were identified and prepared for patient use. The Women and Children's Health Program prepared protocols to manage care of SARS patients in the Maternal Newborn areas, as well as in Pediatrics. Since the programs consist of services at two sites, it was decided that the higher risk unit would become the triage and isolation unit for birthing patients. When other local hospitals had to close their services due to SARS, women were redirected to this unit to receive care. The nurses assumed the added workload with caring and stamina.\n\n Planning for the care of a woman with SARS requiring a cesarean birth and/or care of ill newborns presented additional challenges, as minimal patient movement and contact with others was desirable. The plan of care for women who have been contacts of SARS patients, and who remain asymptomatic, includes providing LDRP care in a birthing room using respiratory isolation precautions. If a mother and her newborn are stable, they are discharged 24 hours postpartum to complete their quarantine period at home with Public Health follow-up. A woman requiring cesarean birth will remain with her healthy newborn in the birthing isolation room, where she will receive all needed nursing care, to decrease the potential for exposure in other areas of the hospital. Women who require isolation would be managed in the birthing unit and then transferred to a designated SARS Alliance hospital. Transfer protocols for women and newborns requiring tertiary-level care and retro-transfer procedures were developed at the provincial level and implemented locally.\n\n Neonatal and pediatric patients are transferred and treated at the Hospital for Sick Children. The Toronto area hospitals with maternal, newborn, and pediatric services are members of a local, collaborative network, which proved to be an enabler and an advantage when the network took a lead role in providing scientific and practical guidelines for managing services for women and children during the outbreak.\n\n Strict infection control principles were adhered to based on the current understanding that transmission is primarily through droplet infection. Disposable equipment and protective coverings for nondisposable items were obtained. Carts containing disposable patient care supplies were filled and placed outside the door of the isolation rooms. The rooms were blocked from use by other patients to ensure immediate availability. The nursing staff were provided with frequent education updates as information became available.\n\n Staffing presented another unpredictable challenge. Many nurses and other health care personnel work at more than one hospital in the Toronto area. When hospitals were closed and the staff sent home for a 10-day quarantine period, those staff members were not able to go to work at other locations, leaving gaps in schedules and units short-staffed. Nursing agencies were also affected, which further limited the availability of nurses.\n\n Initially, directives from the POC were being received frequently throughout the day, seven days per week. The administration team, including the infection control practitioners and educators, provided 24-hour coverage onsite and by pager. The need to communicate changes frequently and effectively requires significant teamwork, as the directives must be put into a user-friendly format for staff and then communicated to all. There have been frequent modifications made to procedures and guidelines to ensure their consistency with the most recent directives. It became apparent quickly that every document had to include the date and time of generation to ensure that staff were always working from the most recent information. Yellow paper was used to distinguish SARS-related information.\n\n Protective wear for nurses includes N95 masks, goggles or face shields and gowns and gloves.",
"While providing protection, the garb has also presented some challenges, including:\n\n • patients having difficulty understanding the nurse when she or he was speaking through the mask • skin reactions among the staff related to wearing the masks and the frequent use of alcohol-based hand sanitizer\n\n • respiratory difficulties, such as shortness of breath • headaches and discomfort from being hot while in the protective clothing\n\n Family-centered care has been a consideration through the SARS experience. Birthing women have been permitted to have one support person with them throughout their hospital stay. This was increased to two support persons when the restrictions were relaxed. Babies in the NICU and pediatric patients may have two parents with them (plus two significant others). Asymptomatic women have been encouraged to breastfeed in the absence of evidence to the contrary. The lessons learned from this experience have included an increased appreciation for the level of integration that exits within the health care system as evidenced by the impact on all hospitals when one or two hospitals are closed and their staff are placed on quarantine. The present system for emergency codes doesn't address a situation such as SARS; a code for a nonsentinel event such as \"infectious disease\" would be useful.\n\n It's essential to place the date and time on every piece of paper generated during an ongoing crisis, as there are frequent updates and changes made as more information becomes available. The value and contribution of families and significant others of health care workers must not be underestimated or taken for granted. Staff burnout is a risk factor with any ongoing crisis.\n\n The mother-baby nurses have found that new mothers seem to have more teachable moments and are more attentive to the teaching that is provided during these times. They reported observing improved breastfeeding outcomes and attribute those observations to the lack of visitors and other distractions.\n\n The impact of SARS on a hospital community is multifaceted. Families of health care workers have been affected by quarantine, longer than usual hours and stress and illnesses related to wearing the protective apparel. The Public Health units have been stretched to the limit, and access to health care usually associated with a hospital (e.g., prenatal, postpartum and lactation clinics) has been more challenging. Misinformation has created public reactions that require time and energy to address.\n\n Health care delivery in Toronto has been changed forever by SARS. Organizations are reviewing once liberal visiting policies, ongoing screening at entrances, alternatives for off-site provision of out-patient services and numerous other strategies that will support the ability of the hospital to continue to provide inpatient acute care and emergency services when the next crisis occurs.\n\n Throughout this experience, the nurses have demonstrated understanding when new information did not always seem to make sense, caring when in great personal discomfort, commitment when the hours of crisis became days, weeks and then months, and a sense of humor to help everyone cope with a new, complex infectious disease."
]
| [
"Public Health & Epidemiology",
"Infectious Disease",
"General Pediatrics",
"Occupational & Environmental Health"
]
|
https://api.semanticscholar.org/CorpusID:10000133 | 10000133 | Population-based Study of Chronic Lung Disease in Very Low Birth Weight Infants in North Carolina in 1994 With Comparisons With 1984 | 1,999 | Pediatrics | [
950818,
1766572,
750542
]
| [
"This increase in CLD was coincident with decreased postneonatal mortality at 3 and 6 months in 1994, compared with 1984 within all birth weight groups except for infants with birth weights of 1001 to 1250 g. For all infants and within each birth weight category, significantly fewer infants in 1994 were receiving ventilator therapy at 30 days of age compared with 1984. Conversely, the rates of supplemental oxygen therapy at 30 days and 3 months increased significantly for each birth weight category, as well as for all infants. Comparisons \n\n From 1984 to 1994, the rate of VLBW births in North Carolina rose at nearly twice the rate of rise of the overall birth rate. The increase was highest among infants with birth weights from 500 to 750 g. In part, this increase may reflect reporting differences. Although the definition of a live birth has remained constant over this period, 6 in 1994 extremely small infants might have been reported more often as live births. It is probable that in 1984 some live-born infants of extremely low birth weight were judged to be nonviable and considered fetal deaths. Moreover, the fetal death rate decreased by 10% from 1984 to 1994. More aggressive perinatal care of fetuses at the margin of viability also may have caused the noted reduction in fetal mortality. The relative increase in the rate of VLBW births may be a response to changing prenatal conditions resulting in preterm delivery. As the use of techniques to augment fertility has increased, the rate of multiple births has risen. However, this increase is seen primarily in the 1501 to 2500 g birth weight group. 7 In addition, it is possible that the population has changed to become one with an increased risk for preterm labor. Finally, the increase in VLBW births may reflect not only an increase in the number of preterm infants but also an increase in the proportion of infants with intrauterine growth restriction.\n\n In 1994, among VLBW infants in North Carolina, the incidence of CLD, defined as treatment with either supplemental oxygen or ventilation, was 44% at 30 days' postnatal age and 25% at 36 weeks' PMA. Both of these rates suggest that CLD continues to be a common morbidity among preterm infants. However, the latter definition may have greater significance. Oxygen supplementation at early postnatal ages may be required because of lung immaturity rather than a pathologic process. 8 Observations at later time points may have greater prognostic value. Shennan et al 9 found that a supplemental oxygen requirement at 36 weeks' PMA had nearly twice the predictive value for abnormal pulmonary outcomes during infancy compared with oxygen dependency at 28 days of age. This was supported by deRegnier et al, 10 who found that an increased risk of neurodevelopmental, sensory, and growth impairments, in addition to an increased rate of hospital readmission had a higher association with oxygen dependency at 36 weeks' PMA, compared with oxygen dependency at 28 days' postnatal age. Palta et al 11 reported recently that oxygen therapy at 36 weeks' PMA had both strong positive and negative predictive values for hospital readmission, asthma, and use of pulmonary medications, although radiographic evidence of CLD at 30 days provided the best predictive value. Thus, supplemental oxygen dependency at 36 weeks' PMA serves as an improved predictive measure of outcome for the VLBW infant.\n\n Our study also confirmed that ventilator therapy for Ͼ48 hours identifies an at-risk group of infants for development of CLD. It is possible that this group is characterized by a poor response to exogenous surfactant therapy 12 or that any use of mechanical ventilator therapy leads to CLD. 13, 14 We confirmed the strong inverse relationship among birth weight and both mortality and CLD. Of infants with birth weight 500 to 1000 g, 48% developed CLD compared with 12% of infants with birth weight from 1001 to 1500 g. The data emphasize the fact that CLD continues to be a significant public health concern that is linked to the improved survival of extremely premature infants.\n\n The 1994 North Carolina CLD rate at 36 weeks' PMA is similar to the rate reported recently by the large multicenter Neonatal Research Network in the United States (25% vs 19%). 4 However, North Carolina had significantly higher rates of CLD compared with a contemporary population-based study from outside the United States. Fenton et al 15 investigated the incidence of CLD in two regions in Canada and England in 1990.",
"T he incidence of very low birth weight (VLBW) births remains an important public health concern in the United States. In 1994, 1.3% of all infants born in the United States weighed Ͻ1500 g at birth. 1 Collectively, disorders relating to short gestation represent the second leading cause of infant mortality, accounting for 13% of all infant deaths in the United States in 1994 and 1995. 1 VLBW infants often require complex, lengthy, and costly medical management. In addition, these infants experience multiple morbidities, the most common being infantile chronic lung disease (CLD). Kraybill et al 2 reported the incidence of CLD in 1984 from a population-based study of VLBW infants in North Carolina. This study defined an at-risk population as those who received assisted ventilation for Ͼ48 hours and who had survived 30 days. The CLD rate for these at-risk VLBW infants at 30 days of age was 54%. Recent studies in the postsurfactant era have reported 30-day CLD rates of 27%, 3 31%, 4 and 6%. 5 These multicenter studies reported outcomes for all VLBW infants admitted to participating neonatal intensive care units (NICUs) rather than for a defined at-risk population. The data of Palta et al 3 suggested an increase in CLD from the presurfactant to postsurfactant period, but survival without CLD morbidity did not change.\n\n We performed a population-based study of VLBW infants in North Carolina to determine survival and rates of CLD. To identify the impact of perinatal and neonatal therapies introduced in the past decade, changes in outcomes were investigated by comparing these results with the study conducted by Kraybill et al. 2 \n\n The 13 NICUs in North Carolina that routinely manage VLBW infants participated in the study. The outcomes of VLBW infants with birth weights between 500 and 1500 g born during the period beginning January 1, 1994, and ending December 31, 1994, who survived Ͼ48 hours were investigated. The outcomes of infants with birth weights Ͻ500 g were not investigated, because they are not provided intensive care routinely and they rarely survive. Both inborn and outborn infants cared for at a participating center were included in the study. In this report, the term VLBW refers to infants with birth weights 500 to 1500 g.\n\n The total number of live births in North Carolina in 1994 and the birth weight distribution of all VLBW infants were obtained from the North Carolina State Center for Health Statistics. State vital statistics data were also used to identify the number and birth weight distribution of all neonatal deaths at Ͻ48 hours of age as well as the number of multiple births and fetal deaths.\n\n Study data were collected prospectively through a questionnaire distributed to collaborators at each center. The questionnaire was constructed to obtain basic demographics, survival data, and pulmonary outcome for each infant. When necessary, retrospective chart reviews were performed to obtain missing data. Completed data sheets were sent to a central site and entered into a commercial database (EpiInfo, Centers for Disease Control and Prevention, Atlanta, GA).\n\n Gestational age was calculated based on obstetric expected due dates if the mother's dates were consistent with obstetric examinations during pregnancy. Alternatively, for inconsistent dates, the Ballard examination was used.\n\n The rate of CLD in 1994 was calculated using the definition of treatment with supplemental oxygen or ventilator therapy at 36 weeks' postmenstrual age (PMA).\n\n For the purpose of comparison with the 1984 North Carolina cohort, 2 the group of infants believed to be at risk for CLD was defined as those infants who received mechanical ventilation for Ն48 hours and who survived to Ն30 days of age. Similarly, for this at-risk group, supplemental oxygen and ventilator therapy were noted at 30 days, 3 months, and 6 months of postnatal age, and CLD rates at each time point were calculated using the number of at-risk infants as the denominator. Infants discharged from the NICU without supplemental oxygen therapy before 3 months of age were considered to be independent of the need for supplemental oxygen at 3 and 6 months. For infants who were receiving supplemental oxygen when discharged from a participating center to home or to a community hospital, follow-up data were obtained from the infant's local care provider. Survival was defined as being alive at discharge to home or at 6 months of age if still hospitalized (also referred to as in-hospital survival).\n\n Population differences were tested using the 2 analysis and Fisher's exact test. Probability levels Ͻ.05 were considered significant.",
"Relative risks (RRs) and 95% CIs were calculated using EpiInfo software.\n\n \n\n In 1994, there were 1570 live births to North Carolina residents with birth weights between 500 and 1500 g. A total of 30 infants were delivered out-ofstate. Of the remaining 1540 infants cared for in North Carolina nurseries, there were 60 for whom only the birth weight was known. For 67 infants, survival outcome, but not pulmonary outcome, was known, therefore survival data were available for 1480 infants (96% of in-state VLBW births), and complete data were available for 1413 infants (92% of in-state VLBW births). Table 1 depicts the birth weight distribution of the births and the number of infants for whom data were missing or incomplete. The mean gestational age of the study infants was 28.7 weeks (SD: 2.6), and the median gestational age was 29 weeks (range: 22-37 weeks).\n\n The 1994 survival and pulmonary outcomes by birth weight category are shown in Table 1 . In 1994, 78% of the study population survived to 36 weeks' PMA. Survival rates were related inversely to birth weight; 94% of infants with birth weights from 1001 to 1500 g survived compared with 58% of infants with birth weights from 500 to 1000 g (P Ͻ .0001; RR: 0.64; 95% CI: 0.60 -0.68).\n\n Among the survivors in 1994, 25% met our definition of CLD with 4% receiving ventilator support and 21% receiving supplemental oxygen at 36 weeks' PMA. The rate of CLD was related inversely to birth weight. Among infants with birth weights from 500 to 1000 g, the incidence of CLD was 46% compared with 13% for infants with birth weights from 1000 to 1500 g (P Ͻ .0001; RR: 3.5; 95% CI: 2.8 -4.3). Table 1 also presents the outcomes at 30 days of age.\n\n Ventilator therapy for Ͼ48 hours remained a significant risk factor for CLD in 1994 and accounted for 89% of infants with CLD at 36 weeks' PMA ( Table 2 ). The effect of ventilator therapy duration was modified by birth weight; the RR of CLD for infants 751 to 1000 g birth weight was 3.3 (95% CI: 1.6 -6.7), whereas the RR for CLD in infants 1251 to 1500 g birth weight was 14.8 (5.3-41.7).\n\n In 1994, there were 101 396 total live births in North Carolina compared with 85 986 in 1984, an increase of 18%. The number of VLBW births increased 34% from 1147 in 1984 to 1540 in 1994. The VLBW rate also increased 15%, from 1.3% to 1.5% of all live births. In 1994, the number of infants with birth weights from 500 to 750 g increased twofold and made up 23% of VLBW infants compared with 15% in 1984. A small increase in VLBW multiple births accounted for Ͻ1% of VLBW births. The fetal death rate decreased by 10% from 8.8 to 7.9 per 1000 live births. 6 In 1994, 79% of the VLBW infants survived to discharge or to 6 months of age if still hospitalized (Table 3) . Compared with 1984, there was a significant increase in survival across all birth weight categories. The greatest difference occurred in the 500 to 750 g birth weight group with 54% more of these infants surviving in 1994 compared with 1984. The 1994 pulmonary outcomes with comparisons to 1984 are shown in Table 4 . In 1994, 633 VLBW infants (43%) were at risk compared with 41% of VLBW infants in 1984. In 1994, among at-risk infants, 68% had CLD at 30 days of age, compared with 54% in 1984 (RR: 1.27; 95% CI: 1.15-1.40). Significant increases in 1994 CLD rates among at-risk infants also were observed at 3 and 6 months."
]
| [
"Public Health & Epidemiology",
"General Pediatrics"
]
|
https://api.semanticscholar.org/CorpusID:10000161 | 10000161 | Uncommon T12 Burst Fracture after an Epileptic Crisis | 2,011 | Case Reports in Orthopedics | [
1644693
]
| [
"Patients suffering from epilepsy have an increased risk of fractures. This can be associated with the trauma induced directly by the seizure itself or resulting from a fall due to the seizure. If posterior shoulder dislocation seems to be the most common clinical entity associated to epileptic crisis, vertebral fractures are commonly overlooked, because these fractures tend to be asymptomatic [1, 2] . We describe here a case of a \"diabolo\" burst fracture of T12 body, which occurred during a single incidence of grand mal seizure and was diagnosed only two days after the seizure episode due to the appearance of back pain.\n\n A-thirty-five year old female was admitted to our emergency unit with the main complaint of low back pain that appeared one day ago without any history of trauma. She only reported that two days ago she was admitted to another hospital after an epileptic crisis where she was treated and observed for 24 hours.\n\n Anamnestically she has a history of intractable epilepsy diagnosed in her early 20 years.\n\n She admits an irregular consumption of her medications. Otherwise she is in good health.\n\n On inspection, no signs of trauma or bruises were found on her back or buttocks. Percussion of her spinal column revealed pain in the midlumbar area accompanied by an important contracture of the paraspinal muscles. Neurological examination did not reveal any alteration in sensitivity of the upper extremities, lower extremities, or in the presacral area.\n\n Deep tendon reflexes were normal. On rectal examination, the sphincteric tone was normal.\n\n The patient was able to stand and walk. Urinalysis tests were normal as well as blood chemistry values.\n\n Because of her symptomatology, thoracolumbar spine radiography was obtained. It showed a burst fracture of T12 with a local kyphosis of 35\n\n • ( Figure 1 ). Investigations were completed by a CT-Scan of the lesion that confirmed the diagnosis of a \"Diablo\" burst fracture of T12 or Denis B type fracture, with disruption of the posterior wall but with no neurological compromise ( Figure 2) .\n\n The patient was then admitted to the hospital where she underwent a 2-stage posteroanterior stabilisation and fixation of her column from T11 till L1. Postoperatively, she had no neurological lesions and resumed walking with crutches for the first 4 weeks (Figures 3 and 4) .\n\n Epileptic seizures affect approximately 0.2-0.5% of the general population. Up to 3% of epileptic patients are injured by either direct or accidental consequence of epileptic seizures 2 Case Reports in Orthopedics [ [1] [2] [3] [4] . Seizure-related fracture varies in terms of location. While the spine is the most common epilepsy related fracture site, other potential locations include facial bones, glenohumeral joint, humerus, distal radius, and proximal humerus [1] [2] [3] 5] . Bilateral posterior dislocation or fracture dislocation of the shoulders is highly suggestive of seizurerelated injuries [1, 4] . The incidence of symptomatic spinal fracture from a seizure is rare and is estimated to occur in 1% of epileptic patients, whereas asymptomatic spinal fracture may be as high as 15-16%. The most common fracture location in the vertebral column is the upper to midthoracic region (T3-T8), in contrast to thoracolumbar junction or the cervical spine fractures frequently found in patients with external trauma [6, 7] . Usually this distinctive distribution occurs because compressive forces during contraction of the muscles are concentrated along the anterior and middle columns of the midthoracic kyphosis curves [6, 7] . A burst fracture is a descriptive term for an injury to the spine in which the vertebral body is severely compressed. The term burst implies that the margins of the vertebral body spread out in all directions. This is a much more severe injury than a compression fracture for two reasons. With the bony margins spreading out in all directions the spinal cord is liable to be injured. The bony fragment that is spread out toward the spinal cord can bruise the spinal cord causing paralysis or partial neurological injury. Spinal burst fracture often occur at the thoracolumbar junction and accounts for about 15% of spinal injuries [8] . Denis classified burst fractures into five categories on the basis of radiographic appearance [9] . Type B is the most common and involves the superior end plate and retropulsion of the superoposterior cortex. Type C is rare and involves fracture of the inferior end plate only. Type A includes fracture of both end plates. Type D is a burst rotation injury while type D is a lateral flexion burst injury.\n\n Neurological injury has been reported to occur in 30% ± 60% of the patients with thoracolumbar burst fractures [8, 9] .\n\n Limb et al. [10] suggest that the static image of the canal obtained by the computerized tomography scans hours or days after the injury does not necessarily reflect the displacement at the time of injury, which is what determines the initial neurological insult. The degree of spinal canal narrowing reflects the canal resting position of the vertebral body fragments after the trauma. This would explain why the present study failed to show any association between the extent of canal compromise and the extent of neurological deficit. In burst fractures of the thoracolumbar and lumbar spine, there is no correlation between the neurological deficit and the recovery pattern with the extent of canal compromise.\n\n Burst fracture of vertebral bodies after a grand mal seizure is not common. T12 burst fracture as a direct consequence of an epileptic crisis, to best of our knowledge, has not been related in the literature. Probably this is attributed to the fact that the seizure trauma resulting from axial skeletal contraction force is usually not sufficient to cause burst fracture.\n\n Antiepileptic drugs are known to increase the risk of fracture in epileptic patients through the reduction of the bone mineral density [11] [12] [13] . But so far, no evidence exists to suggest that spinal precautions are necessary in all seizure patients, and the routine use of spinal precautions in uncomplicated seizure patient's has been questioned [14, 15] .\n\n In conclusion, forceful contraction during a convulsive seizure can result in vertebral burst fracture, although this is not very common.\n\n The absence of external trauma and the postictal consciousness disturbance usually delay the early diagnosis.\n\n A complaint of back pain should be looked for in epileptic patients after a grand mal seizure, and if it is positive, it should raise a strong suspicion of vertebral fracture and thus should be evaluated radiographically."
]
| [
"Public Health & Epidemiology",
"Orthopedic Surgery"
]
|
https://api.semanticscholar.org/CorpusID:10000176 | 10000176 | Severe Spastic Contractures and Diabetes Mellitus Independently Predict Subsequent Minimal Trauma Fractures Among Long-Term Care Residents. | 2,016 | Journal of the American Medical Directors Association | [
201616,
3479
]
| [
"When bilateral involvements of the same joint were counted, the percentage ranged from 4% in the finger joints to 53.7% in the shoulder joints.\n\n As shown in Table 3 , almost all patients (90.9%) had at least 1 severe contracture, with 59.4% having severe contractures involving more than 2 extremities, and 40.5% having severe contractures involving all 4 extremities. The prevalence of contractures in the upper extremities (85.4%) was similar to that of contractures in the lower extremities (75%).\n\n The presence of severe spastic contractures, defined as a decrease of 50% or more of the normal PROM of the joint with coexisting severe spasticity with an MAS score higher than 3, was also found in a small proportion of the study population ( Table 2 ). The prevalence of severe spastic contractures ranged from 3.7% in the finger joints to 15.7% in hip joints when involvement of 1 side was counted. When bilateral involvements of the same joint were counted, the percentage ranged from 0.8% in the elbow joints to 11.7% in the hip joints.\n\n Twelve MTFs and no traumatic fractures occurred during the study period (Table 4) ; therefore, the incidence rate of MTF in our cohort is 1.1 per 100 persons per year. The most common site of fracture was the femur (67%), followed by the humerus (17%). One resident had a fracture in the right foot, and another resident had a fracture in the left superior pubic ramus of the pelvic bone. Among these 12 residents, only 2 (17%) received orthopedic surgery for the fractures, and the remainder were treated conservatively.\n\n Seven out of 12 residents (58%) died during the follow-up period; the mean survival after the MTF event for these 7 residents was 18 months (SD ¼ 12.6). For the other 5 surviving residents with MTF, Presence of both severe contracture and severe spasticity in a joint. the mean follow-up time from the fracture event until the end of the study was 27 months (SD ¼ 17.6).\n\n We found that the following factors were predictive of subsequent MTF in the univariate Cox regression (Table 5 ): (1) the presence of bilateral severe knee contractures [P ¼ .025, hazard ratio (HR) ¼ 3.93] and (2) diabetes mellitus (P ¼ .019, HR ¼ 3.92). When spasticity was combined to bilateral severe knee contracture, the resulting factor (bilateral severe spastic knee contractures) became the strongest predictor for subsequent MTF (P < .0001, HR ¼ 14.73). Other factors including age, sex, nutritional status, cognitive status, mobility, incontinence, enteral feeding, other coexisting medical diseases, or previous bone fractures did not predict subsequent MTF.\n\n Multivariate Cox regression analysis revealed 2 independent predictors of subsequent MTF (Table 6 ): (1) bilateral severe spastic knee contractures (P < .0001, HR ¼ 16.50) and (2) diabetes mellitus (P ¼ .018, HR ¼ 4.03).\n\n This study is the first long-term cohort study to demonstrate that severe spastic contractures and diabetes mellitus could independently predict subsequent MTF. Although many previous studies have examined the predictors of fall-related bone fractures among nursing home residents, 18e21 MTFs are caused by a different mechanism, and occur in the subgroup of long-term care residents who are more dependent and immobile. 1, 2, 7, 8 It is considered that in addition to a dramatic decrease in bone mass and bone quality, torsion torques during care-related maneuvers may also contribute to the occurrence of MTF in long-term care residents. 2, 4 Our study showed that bilateral severe knee contractures independently predicted (P ¼ .005, HR ¼ 6.19) subsequent MTF. This may be explained by the fact that daily care procedures such as positioning, transferring, turning, grooming, and change of incontinence pads are more difficult for the very frail and debilitated residents with bilateral severe knee contractures, which may lead to added torque during these routine care procedures. This finding is consistent with a previous study that found that joint contractures may act like a point of leverage to exert any external force to the nearby fragile bone and thereby cause fractures.",
"Minimal trauma fractures (MTFs) or spontaneous bone fractures occur mostly in debilitated and dependent long-term care residents, without the degree of trauma that usually causes a bone break. 1e8 They are also called \"care-related fractures,\" as these incidents occur mostly during basic care procedures. The prevalence of MTF according to 3 prospective cohort studies ranges from 0.4 to 0.84 per 100 persons per year. 1, 4, 7 MTF are devastating events in long-care residents, causing pain and suffering, and increasing morbidity and mortality. 2e4 Moreover, there may be medico-legal issues raised after a MTF for the possibility of mistreatment and inadequate care procedures. 1, 2 Despite their impact, reports on MTF are scarce, and currently there has been only 1 prospective cohort study that explored the predictors of MTF. 1 Kane et al 1 followed 1903 residents in 11 skilled nursing care facilities for 1 year, and 16 MTFs occurred. They found no predictive factors of MTF other than severely impaired mobility. However, their study did not examine the contribution by spasticity and contractures or other medical comorbidities. On the other hand, the authors of a review article proposed several risk factors for MTF according to 3 previous studies, 1, 3, 4 and these factors were age older than 80 years, female sex, prolonged period of immobility (2 years or more), neurologic disease including advanced dementia, and prior fracture history. 2 Nevertheless, except for the study by Kane et al 1 as mentioned before, the other 2 studies were either case series of patients with MTF 3 or follow-up study on the outcomes of only patients with MTF 4 ; these study designs were not able to identify the independent predictors of MTF. Spasticity and hypertonic contractures are also recognized as major causes of morbidity and sufferings (pain, pressure ulcers, skin infections, functional disability) among long-term care residents, 9e11 and are considered to be a potential cause of MTF. 7 Previous studies showed that the prevalence of contractures with or without hypertonia in nursing home residents ranged from 22% to 61%. 9e11 However, the relationship between limb spasticity or contractures and subsequent MTF has not yet been established. Takamoto et al 7 reported in their observational study that joint contractures were found adjacent to the fracture sites in 18 patients with reported MTFs; hence, the authors proposed that joint contractures might be one of the risk factors leading to MTF, 7 but no formal statistical analysis was presented.\n\n We conducted this long-term cohort study to examine the epidemiology of spasticity and hypertonic contractures and their relationship with MTF among the most debilitated and dependent long-term care residents, and to determine the incidence and independent predictors of MTF in this vulnerable population.\n\n In Hong Kong, long-term care residents who are in need of continuous medical and nursing care for their activities of daily living (such as bathing, toileting, feeding, grooming, and transfer) are placed on the central infirmary waiting list and admitted to special care units both in the public and private institutions. 12 The estimated total number of this population is over 57,000. 13 Cheshire Home (Shatin) is a 300-bed long-term care hospital that receives residents from the central infirmary waiting list. As such, its patient population provides a representative sample of the most debilitated and dependent longterm care residents in Hong Kong. We analyzed the clinical data of all consecutive long-term care residents who were in the central infirmary waiting list in Hong Kong and were under care in the Cheshire Home (Shatin) from March 2007 to March 2016.\n\n Upon admission to the Cheshire Home (Shatin), all residents received a baseline comprehensive multidisciplinary assessment. The medical team assessed the residents' medical comorbidities, medications list, history of previous fractures, and any recent acute hospitalizations. Blood tests, including serum albumin, hemoglobin, and renal and liver function tests, were routinely taken. The nursing team assessed the demographic data and nutritional status, including the body mass index, mobility, mental status, type of restraints used (if any), communication abilities, baseline skin integrity and pain assessment, urinary continence, and bowel habits. The occupational therapists assessed the cognitive function using the Rancho Los Amigos ScaleRevised, 14 activities of daily living using the Barthel index, limb power and function, any contractures or limb spasticity, and seating assessment."
]
| [
"Geriatrics"
]
|
https://api.semanticscholar.org/CorpusID:10000179 | 10000179 | Integrated Disease Management: A Critical Review of Foreign and Portuguese Experience | 2,014 | Acta medica portuguesa | [
636851,
1788333,
1087750,
352223
]
| [
"− Health Care Organization -changes at the larger organizational level, from structure, goals to values improved by a strong leadership.\n\n Interventions described in the reviewed articles were also classified according to the Cochrane Effective Practice and Organization of Care (EPOC) taxonomy 10 (Appendix 1), considering whether they were organizational, professional, regulatory or financial interventions. The item 'patient interventions' was also included in the present study to encompass interventions related with the following: distribution of educational materials, education sessions, reminders, etc.\n\n Patient outcomes and other results were classified using the approach proposed by Zwar et al 11 : professional adherence to guidelines; patient adherence to treatment; patient health service use; patient physiological measure of disease; patient risk behavior; patient quality of life; patient health status; patient functional status; patient satisfaction. Two additional itens were added: 'patient education' and 'costs'.\n\n In 2011, a literature search in both Medline and Cochrane databases was undertaken to identify documents published on IDM, between January 2006 to end of June 2011.\n\n We used keywords and Medical Subject Headings (MeSH) descriptors ( Inclusion criteria were: 1) publications in English, French, Spanish or Portuguese; 2) about diseases in human beings; 3) covering populations aged over 19 with one or more of the above-mentioned diseases.\n\n Articles were classified according to the three areas of coverage considered in the integration level category: 'macro', 'meso' or 'micro'. The review focused on evidence of lessons useful to informing policy at national level, and therefore, only the full text studies under the 'macro' dimension were included in the analysis.\n\n We excluded documents consisting a study of one or two patients or which did not describe specific interventions. Fig.1 details the steps in the identification of the articles and the number excluded at each stage.\n\n Data was extracted and introduced directly into an 'Excel' database by a researcher and reviewed by a second one. All disagreements were resolved through discussion and consensus within the research team.\n\n All articles retrieved (N = 61) were grouped according to the CCM main focus using Wagner et al's definition. 2 Interventions were classified according to the EPOC taxonomy 10 and results were classified using the approach proposed by Zwar et al.\n\n Overall results were discussed considering the Portuguese experience as a benchmark. rEsULts The initial search identified 1 251 articles, of which 621 were retained after an initial screening. After the exclusion of duplicates, this number fell to 337 articles. Articles on the 'Macro' dimension (N = 88) were extracted by one investigator and checked by a second one. Only the 61 full text studies under the 'macro' dimension were selected for analysis.\n\n Data was first characterized according to the main bibliometric components. Programmes were then characterized according to their integration level, CCM elements, IDM intervention using the EPOC taxonomy and finally according to their outcomes and effectiveness.\n\n Supplementary material is available for more detailed information about the results (Synthesis of Results in Appendix 2).\n\n 72% of total articles (n = 44) were identified in Medline (PubMed), 10% (n = 6) in Cochrane Database of Systematic Reviews and 18% (n = 11) were found in both of databases. All articles were in English; 51% had diabetes mellitus as the key disease-focus, followed by asthma and coronary disease ( Table 2 ). 52% of the articles (n = 32) presented studies were conducted in the USA; other studies were from the Netherlands, the United Kingdom, Germany and Australia; none referred Portugal.\n\n Classification identified 15 studies as 'research support', 12 as 'randomized controlled trials', nine as 'evaluation studies', eight as comparative studies and 17 were classified in ca-tegories such as 'review' (n = 3), 'controlled clinical trial' (n = 3), 'cohort study' (n = 3), 'quasi-experimental design' (n = 2), 'case study' (n = 2), 'multicenter study' (n = 1) and 'meta-analysis' (n = 1).\n\n 'Population Health Management' published six articles, 'The American Journal of Managed Care' four, 'BMC Health Services Research', 'Diabetes care' and 'Medical Care' three each.\n\n Of the 61 articles classified as 'macro' interventions, 25 were implemented by managed care organizations (19 in USA and 2 in Germany), 22 by organized groups of family doctors, e.g.",
"28 IDM programmes that incorporate provider education, feedback and reminders, are associated with improvements in disease control. 5 The production, distribution and impact of guidelines vary among countries, for instance, in England, for instance, the Health Department NICE produces evidence-based guidelines and tools, 25 and in the USA, most activities in CDM are found in health plans, such as those implemented by the National Committee for Quality Assurance, Kaiser Permanente and similar organizations. 25 Portugal, like other European countries, has a tradition of regulating health care at central level, through guidelines, clinical auditing and inspections and believe that under the IDM model, health professionals become more involved in cost-effective guidance and in clinical governance.\n\n The CCM provides a useful conceptual framework for understanding some of the elements considered essential for the management of chronic disease and the interplay between its elements.\n\n 11 But when it comes to their effectiveness show that interventions applied to diabetes and coronary disease tend to concentrate the highest number of statistically significant improvements. 21 While the literature and the findings of the present study identified some evidence of improvements in patient outcomes, an objective evaluation requires to consider the health care context, whether it is of public or private provision, and the beliefs and attitudes of the patients.\n\n \n\n Quantitative data about 'physiological measure of disease', 'service use', 'health status' and 'risk behavior', were more frequently used than qualitative outcomes like 'satisfaction', 'adherence to treatment' and 'quality of life'.\n\n There is evidence that clinical outcomes are easier to measure through standard tests and procedures, e.g. annual retinal examination or screening of diabetic nephropathy, which explains their frequent use. 16, 21, 29 Service utilization is commonly measured by calculating inpatient admission rate and emergency room attendance. 16, 21, 29 A review of literature in 2006 concluded that there is some evidence that disease management programmes can reduce unplanned admissions. 5 A survey conducted in ten European countries in 2010 shows that clinical parameters, hospital admissions and life-style changes are the most commonly used progress indicators in terms of implementation of disease programmes. 4 We identified only one programme, the Netherlands, that monitors changes on patient satisfaction, even though, this is widely recognized, as an important dimension of health care. 4, 9 In Portugal all patients included in the national IDM programme periodically report their satisfaction level.\n\n Different countries are at different stages in the implementation and development IDM programmes. Countries also use different types of intervention, monitor results with different follow up periods and even use diverse concepts and models to refer to their approach to manage chronic diseases. 5 As a result, good practices are not easily replicated and different measures of performance and impact evaluation are not standardized.\n\n The present article provides insights on the response of different countries' to the challenges of CDM, by analyzing different interventions of IDM programmes implemented at the political, management and health care levels.\n\n In the case of Portugal, IDM programmes incorporate all the CCM elements, each at different stages of development. Like other European countries, 8 Portugal also developed incentives to manage chronic diseases and hence reduce the fragmentation of care and improve cost control and quality. 6, 7 This review highlights the CCM elements and EPOC interventions related with self-management support and patient interventions, which are the less developed components in Portugal. The Portuguese experience is more focused in professional interventions, such as monitorization of standards, guidelines adoption, quality audit, financial interventions (payment for performance) and organisational interventions (formal integration of services with the identification of a chronic disease reference network). In the near future more attention should be given to the patient/community empowerment.\n\n There is little robust evidence of what works or not at IDM, particularly in the CCM, 20 and how health care systems should be organized. This appears to be country and context specific: countries have their own institutional arrangements, economic conditions, level of political commitment, planning tradition, as well as capacity and dynamics in the relationship among the numerous stakeholders, 1, 19, 21 no standard indicators are used to measure outcomes, 5, 11, 16 and there is no monitoring culture. 30, 31 In Portugal the most frequently used mechanisms to measure outcomes are 'physiological measures' and 'service use'. The Portuguese programme is one of the few that's applies initiatives to measure 'patient satisfaction' systematically but others parameters could also be incorporated such as 'health status' and 'risk behaviour'.\n\n It remains a challenge to draw overall conclusions, because of the heterogeneity of disease management interventions 29 and of the population selection criteria to evaluate chronic care management programmes. 16 Conclusions of the present literature search must be treated with caution, avoiding generalizations and judgements based on the analysis of interventions in a single field or in a single country. 19 To better understand whether policy reforms in the management of chronic diseases deliver the promising results, more attention should be paid to monitoring the design, implementation and outcomes of each intervention. [30] [31] [32] \n\n Anabela Coelho is employed by the Directorate-General of Health and was involved in the implementation of the IDM Project. There were no conflicts of interest declared by the authors.\n\n Involvement of Anabela Coelho in the implementation of the IDM Project was free of financial incentives. No funding sources were declared by the remaining authors.",
"13, 14 The chronic diseases, which were included in this search (diabetes mellitus, asthma, coronary disease, etc.) reflect the 'burden of disease' of countries with the highest income and the most commonly managed at primary health care level. 15 We were able to identify several types of studies, using different methods and levels of rigour. The three most common types of evaluation designs applied to IDM program evaluation: were experimental designs, quasi-experimental designs, e.g. pre-post intervention studies with comparison group, and pre-experimental designs, e.g. pre-post studies without comparison group.\n\n \n\n In general, findings show that countries developed their IDM strategies as part of a national or regional policy 17 in order to improve patient outcomes and reduce wastefulness. 5 A collaborative intervention between primary and secondary care was found only in four articles, which evidences that the interface between primary and secondary care still presents challenges in most countries. 17 It also shows that IDM programmes, as discussed by other authors, 15 have their main focus on primary health care rather than on secondary health care as IDM programmes were mainly found to be developed within the context of managed care organizations or organized general or family practices.\n\n The highest number of IDM programmes was reported in the USA. 15 In 2005 UK established the National Health Service and Social Care Model, which based on the 'pyramid of care' adapted from Kaiser Permanente, helped introducing teams in primary care and creating a network of community providers. 17 Other European countries such as Spain, Italy, Ireland and Portugal, progressively moved towards the same approach.\n\n More than half of studies reported two or more components from CCM and no country had all six components been implemented. 19 Better outcomes are associated with the presence and implementation of multiple CCM elements. 20 Portugal is one of the few countries where the IDM program includes all six components at different levels of development.\n\n 6 'Delivery System Design' separates the acute from the programmed care by offering an effective patient care through treatment units and reference centres; 'Decision Support' and 'Selfmanagement Support' it integrate evidence-based clinical guidelines into professional practice and patients day life through a web base decision support system namely platform 'Dados de Saúde'.\n\n Programmes with 'self-management support', 'clinical information system', 'delivery system design' and 'decision support' 21 as predominant CCM elements, were considered effective. The Portuguese IDM program for the End Stage Renal Disease was evaluated as an efficient initiative of coordination [22] [23] [24] in which the empowerment of patients, the use of evidence-based clinical practices, the prospective payment and the involvement of all the stakeholders contributed to control health spending without compromising quality of care.\n\n In general, the methodology for implementing disease management and for measuring its effects, in the perspective of the CDM, is still in its infancy. 16, 25 The lack of quality data represents a major challenge for informed planning, health policies development, implementation and evaluation, and programmes and community-based intervention oriented to patients with chronic diseases. 1, 21 The difficulty in assessing the effect of this model through experimental studies probably explains why such studies are rare 21 and that no stronger evidence is available.\n\n Even though most of studies reported improvements with statistical significance, evidence on the cost-effectiveness of the CCM is still scarce, and more research is needed to understand the implications for practices, payers, and patients. 20 There is also little quantitative evidence documenting the relative importance 1 and effectiveness 25 of each component separately. Further research is also required to explore the most effective combinations of CCM elements and the different implementation processes in order to increase the likelihood of improvements. 20, 26 Despite the scarcity of evidence regarding the effectiveness of IDM intervention in general, there is a growing body of studies showing that when compared to standard health care, self-management approaches provide benefits to participants, particularly in terms of knowledge, impact of self-management behaviours and health status. 27 The Care Continuum Alliance defends that the successful selfmanagement of a chronic disease can slow down disease progression, improve quality of life and save money.\n\n Other authors 4 conclude that most disease management programmes give more emphasis to the compliance with medical prescriptions than to other self-management components, such as the involvement of the family and community, limiting self-management interventions in favour of self-monitoring of some clinical parameters and lifestyle changes.\n\n Educational sessions and distribution of educational material seem to be highly valued interventions by patients and professionals. The empowerment of patients and the increase of their knowledge are sine qua non conditions in all disease management programmes; but to have patients better informed, proactive and more involved in decisionmaking processes, the personalization of education sessions and materials is needed, as well as continuing access to relevant information. 4 In Portugal as in other European countries, the development of a patient portal is under implementation and some services that improved CDM and continuity of care, are already offered.",
"This article reviews findings from empirical evaluations of integrated disease management (IDM) programmes. The aim was to describe the integration levels, identify the most frequent interventions and outcomes and to synthesise knowledge about their implementation and performance. The article focuses on discussing the documented good practices in the international literature that could improve the IDM Portuguese model implemented in 2008.\n\n The article starts with a brief description of the most recent developments and the context of IDM programmes; then the results of the literature search conducted in 2011 are presented; and finally, the evidence is synthesised in order to identify lessons that can be learned from international experiences.\n\n context Chronic Disease Management (CDM) initiatives were originally developed in the United States (USA) in line with the recommendation of Centers for Disease Control and Prevention, which state that the health care system should target diseases where effective public health preventive strategies exist, or are the subject of promising research.\n\n CDM programmes aim to enable health care systems to be more supportive to patient-provider interactions, 2 to improve overall health status and to reduce healthcare costs generated by chronic conditions.\n\n In 2012, the European Commission encouraged the replication of CDM models through an integrated care methodology known to improve the quality and accessibility of care to patients with a chronic condition (Opening speech on the European Year for Active Ageing and Solidarity between Generations, January 18, 2012 by Dalli J). In order to reduce deficiencies such as inadequate care transitions, inefficient information flow between different levels of care and low patient engagement, 3 several European countries have, also, moved in that direction. 4 In the case of Portugal, a national CDM project named Integrated Disease Management (IDM) was launched in 2008, endorsed by the Ministry of Health. The introduction of the concept of integration was proposed as an alternative to fragmentation, duplication and inefficient use of resources in chronic disease management. 5 The development of an IDM model became the main chronic disease strategy and decision-making tool in clinical management. It was perceived as a quality-driven approach to lead the reorganization of the Portuguese healthcare delivery structure 6 and to rationalize service provision to improve productivity, quality and price control. 7, 8 In the context of great economic restraint this initiative increased the responsibility of patients (as self managers), providers (as clinical managers) and policy makers (as regulatory managers) involved in all phases of chronic diseases. 6 The Ministry of Health regulates health care delivery through a national online data base of patient's records, included in all IMD programmes, together with a set of clinical guidelines and auditing practices. This online system is an important tool for the follow-up of patients, the monitoring of quality of care, as well as the motoring of the epidemiological evolution of the disease.\n\n One of the key and most innovative components of this program was the introduction of a funding model, similar to 'pay for performance', in which providers receive a lump sum per patient if they achieve some performance targets. Expected results are risk sharing with providers, patientcentred care practices, coordination of care, population risk stratification and the implementation of a direct relationship between funding and quality and safety clinical parameters. \n\n In many countries the coordination and integration of care remains a major challenges. 3 In the literature there is no formal or consensual definition of integration of care. In non English-speaking countries the different concepts to describe integrated care are even more diverse. 9 For the purpose of this review, Curry and Ham´s 5 definition and classification was used: \"integration is concerned with the processes of bringing organizations and professionals together, with the aim of improving outcomes for patients and service users through the delivery of integrated care\".\n\n Several countries have adapted IDM programmes to their own health care systems. 4 However, for the purpose of the present study, programmes were classified through the Chronic Care Model (CCM) conceptual framework. The six essential and interrelated elements of the CCM 2 are: − Delivery System Design -A clear division of multiprofessional labour, separating the acute from the programmed care, in order to support process and structures through an effective patient care. − Self-management Support -Collaborative strategies from education to support services based on self--management principles, in a variety of formats that help patients and their families to acquire the skills to manage their condition. − Decision Support -Integration of evidence based clinical guidelines into practice, reminder systems, continuing medical education and inter-provider communications. − Clinical Information Systems -Availability and comprehensiveness of clinical data during patient visits with reminder system to improve compliance with guidelines, performance measures and planning of care. − Community Resources -Link with community based resources (hospitals, home care agencies, self help groups and senior homes)."
]
| [
"Public Health & Epidemiology",
"Healthcare Administration & Management"
]
|
https://api.semanticscholar.org/CorpusID:10000185 | 10000185 | REPRINT: Good Laboratory Practice: Preventing Introduction of Bias at the Bench | 2,009 | International Journal of Stroke | [
949907,
884660
]
| [
"Nearly 10 years after the first Stroke Therapy Academic Industry Roundtable (STAIR) participants established guidelines intended to support the translation of neuroprotective efficacy from bench to bedside (1) , there is still no clinically effective neuroprotective drug for stroke. One interpretation of this observation is that measures outlined in STAIR I have failed to deliver the promised improvements in drug development. However, a dispassionate analysis of data presented over the last 10 years suggests that the 'STAIR hypothesis' -that improvements in animal experimental design will lead to improvements in translational efficiency -is yet to be adequately tested. Adhering to the standards of conducting and reporting of experiments, in order to reduce the confounding effects of bias and ensure adequate statistical power as outlined below, will increase the confidence with which we can assess new data and maximize our chances of developing effective therapies.\n\n The original STAIR proposal was that by paying due attention to experimental bias, to the breadth of physiological variables known to influence stroke outcome in patients and by testing therapies in a range of model systems that might more faithfully reproduce the key facets of stroke pathophysiology, we would be able to translate what appeared to be clear evidence of neuroprotective efficacy in animals to the more heterogeneous circumstances of human stroke. While we believe strongly that failure to adequately consider variables such as age, comorbidity, physiological status and timing of drug administration contribute to the disparity between the results of animal models and clinical trials, they have been reviewed elsewhere (1, 2) and are not the subject of this article.\n\n Analyses of data supporting the efficacy of various neuroprotective strategies (3) (4) (5) have revealed that while many researchers adhere closely to the ethos of these guidelines, as a community we do not. A simple checklist derived from the STAIR guidelines to provide an overview of the range of data available for 1026 candidate therapies (4) revealed that only a handful came close to meeting the STAIR guidelines. A higher score against this checklist was accompanied by a marked reduction in effect size. This later trend could be seen clearly even within the data for individual drugs (6) . Moreover, studies that reported measures to avoid bias such as random allocation to treatment group, blinded induction of ischemia or the blinded assessment of outcome (7, 8) , gave a markedly lower estimate of efficacy. Despite this, there has been some evidence of improvement in study quality, and the performance of animal stroke studies is substantially better than that for most other models of neurological disease (5) . And yet, the majority of investigators still do not report whether or not they took measures to avoid bias. Systematic reviews and meta-analyses of data from animal stroke studies suggest that these studies may be substantially distorted by experimental bias. Taken together, publications supporting the efficacy of NXY-059 include randomized data with allocation concealment and blinded outcome assessment, but most individual publications do not report these measures. Analyses of those data suggest that at least half of the reported 44% improvement in outcome could be attributed to experimental bias, specifically a failure to randomize the allocation to experimental group, a failure to conceal treatment group allocation from the surgeon or a failure to blind the assessment of outcome (8) . Similar observations have been made of the hypothermia literature, where nonrandomized studies and studies without blinded outcome assessment appear to give a relative overestimation of efficacy of 27% and 19%, respectively (7) . Despite the widely recognized importance of these aspects of study design, analyses conducted by the CAMARADES group suggest that only 36% of studies reported random allocation to treatment group, only 11% reported allocation concealment and only 29% reported the blinded assessment of outcome (5) .\n\n A related issue is the number of animals used in experiments. The probability of detecting a difference of a given size between groups is related to the number of animals in each group, the size of the difference and the variability in the outcome measure used. However, only 3% of studies identified in systematic reviews reported using a sample size calculation (5) . Importantly, if sample size calculations are based on falsely large estimates of effect size, studies will not be powered to detect real differences between treatment and control groups. Indeed, post hoc analysis suggests that most experimental stroke studies have only a one in three chance of detecting a 20% difference in outcome.\n\n These problems are not unique to the preclinical study of stroke. Clinical stroke trials have had problems with inadequate sample size (9) and have also failed to report whether they took measures to avoid bias (10) .",
"Indeed, Cochrane's observation that 'when humans have to make observations there is always the possibility of bias' (11) was a lynchpin of the CONSORT (Consolidated Standards of Reporting Trials) initiative to improve the reporting, design, conduct, analysis and interpretation of randomized-controlled trials to inform decision making in health care (11, 12) . This initiative led to substantial improvements in the reporting and the conduct of clinical trials (13) .\n\n On the basis of the available evidence, it would now seem reasonable to suggest that preclinical testing in animal models of stroke, and indeed other models of disease, should adopt similar standards to ensure that decision making is based on high-quality unbiased data (5, 14) . Adoption of such standards would have the added benefit of reducing wasteful utilization of financial and animal resources.\n\n In general, studies should only be considered for publication if their Methods section includes a description of how they have addressed the standards below, or if authors make a cogent argument for why these standards are not relevant to their work. For these components of a paper, citation of methods described in previous publications is not considered sufficient. These requirements should not preclude publication of important observational, pilot or hypothesis-generating data, but the conclusions of such studies should reflect their preliminary nature. 1. Animals: The precise species, strain, substrain and source of animals used should be stated. Where applicable (for instance, in studies with genetically modified animals), the generation should also be given, as well as the details of the wild-type control group (for instance littermate, back cross, etc.).\n\n The manuscript should describe how the size of the experiment was planned. If a sample size calculation was performed this should be reported in detail, including the expected difference between groups, the expected variance, the planned analysis method, the desired statistical power and the sample size thus calculated. For parametric data, variance should be reported as 95% confidence limits or standard deviations rather than as the standard error of the mean. 3. Inclusion and exclusion criteria: Where the severity of ischemia has to reach a certain threshold for inclusion (for instance a prespecified drop in perfusion detected with laserDoppler flowmetry, or the development of neurological impairment of a given severity), this should be stated clearly. Usually, these criteria should be applied before the allocation to experimental groups. If a prespecified lesion size is required for inclusion this, as well as the corresponding exclusion criteria should be detailed. 4. Randomization: The manuscript should describe the method by which animals were allocated to experimental groups. If this allocation was by randomization, the method of randomization (coin toss, computer-generated randomization schedules) should be stated. Picking animals 'at random' from a cage is unlikely to provide adequate randomization. For comparisons between groups of genetically modified animals (transgenic, knockout), the method of allocation to for instance sham operation or focal ischemia should be described.\n\n The method of allocation concealment should be described. Allocation is concealed if the investigator responsible for the induction, maintenance and reversal of ischemia and for decisions regarding the care of (including the early sacrifice of) experimental animals has no knowledge of the experimental group to which an animal belongs. Allocation concealment might be achieved by having the experimental intervention administered by an independent investigator, or by having an independent investigator prepare a drug individually and label it for each animal according to the randomization schedule as outlined above. These considerations also apply to comparisons between groups of genetically modified animals, and if phenotypic differences (e.g. coat coloring) prevent allocation concealment this should be stated. 6. Reporting of animals excluded from analysis: All randomized animals (both overall and by treatment group) should be accounted for in the data presented. Some animals may, for very good reasons, be excluded from analysis, but the circum-stances under which this exclusion will occur should be determined in advance, and any exclusion should occur without knowledge of the experimental group to which the animal belongs. The criteria for exclusion and the number of animals excluded should be reported. 7. Blinded assessment of outcome: The assessment of outcome is blinded if the investigator responsible for measuring infarct volume, for scoring neurobehavioral outcome or for determining any other outcome measures has no knowledge of the experimental group to which an animal belongs. The method of blinding the assessment of outcome should be described. Where phenotypic differences prevent the blinded assessment of for instance neurobehavioral outcome, this should be stated. 8. Reporting potential conflicts of interest and study funding: Any relationship that could be perceived to introduce a potential conflict of interest, or the absence of such a relationship, should be disclosed in an acknowledgments section, along with information on study funding and for instance supply of drugs or of equipment.\n\n We consider that these measures are of central importance to Good Laboratory Practice in the modeling of cerebral ischemia. Many groups already perform experiments to these high standards, and we hope that they will now report this in full, and that others follow their lead. Finally, we do not consider these requirements to represent a final or a complete list of appropriate measures necessary to avoid bias. Future additions may be required as further evidence emerges and as the experience of authors and reviewers evolves."
]
| [
"Basic Medical Sciences",
"Public Health & Epidemiology"
]
|
https://api.semanticscholar.org/CorpusID:10000198 | 10000198 | Dynamic radionuclide imaging with 99mTc-sucralfate in the detection of oesophageal ulceration. | 1,989 | Gut | [
1302563,
1631111
]
| [
"The time-activity curves for this patient are given in Figure 4 and similarly show persistent activity in the In all patients who were imaged in the erect position immediately after the supine dynamic sucralfate study, no oesophageal uptake could be found, even when the transit study had shown prolonged activity on the condensed dynamic image and time-activity curves.\n\n The results are summarised in a 2x2 table, given in the Table. Using oesophagoscopy as the gold standard for determining the presence of oesophageal ulceration, the labelled dynamic sucralfate imaging has a positive predictive value of 92% for ulceration present, and 86% for ulceration absent, correlating with oesophagitis grades 1-3.\n\n Multiple sucralfate studies have been done in a small number of patients to assess whether the technique can be used to show the response to therapy of patients with oesophageal ulceration. The images shown in Figure 5 are from one such patient and clearly show a gradual lessening of the abnormally prolonged oesophageal activity during the course of therapy. will show an 'afterglow' compared with the colloid swallow.\n\n As most ulceration in the oesophagus is superficial, our experience suggests that sucralfate tends to adhere only in the immediate period after swallowing. This makes the transit study more likely to produce a positive result than delayed static imaging.\n\n In the erect position the swallowing of fluids is not a simple peristaltic activity and not all the mucosa comes into contact with the bolus. Erect swallowing studies with labelled sucralfate would therefore have a reduced probability of producing a positive result, and thus have little clinical value. We have shown the supine transit study to be a sensitive indicator of oesophageal mucosal damage. One particular example of this can be seen in Figure 5 , where the patient had little endoscopic evidence of any remaining ulceration at the time of the third study, but nevertheless produced a slightly abnormal sucralfate study. This may be the result of incomplete healing at the mucosal level, causing the sucralfate to remain positive in an oesophagus which is visually normal at endoscopy.\n\n Endoscopy does of course provide more precise Discussion Work published by Goff\"l using delayed static imaging at 30 minutes post administration or later showed labelled sucralfate to be a poor indicator of oesophageal ulceration, giving positive results only in cases of deep penetrating ulcers within the gullet. Patient positioning is important, however, as supine transit is a peristaltic phenomenon and when the study is done in this position all the mucosa comes into contact with the swallowed bolus. If ulceration is present the sucralfate will come into contact with exposed protein and binding may occur, the rest of the bolus passing through the oesophagus and into the stomach. Thus the dynamic sucralfate study Having shown a 92% positive predictive value for dynamic sucralfate imaging of oesophageal ulceration, we now limit endoscopy to initial evaluation and to acquire histology for the exclusion of a malignant process. Subsequent follow up is by dynamic sucralfate imaging.\n\n It is important that all oesophageal ulcers are biopsied to exclude malignant disease. In this study, however, the use of endoscopy did not add any information with regard to oesophageal disease when the labelled sucralfate study was normal. The 99mTc-sucralfate dynamic transit study is rapid, non-invasive and has a low radiation dose. These properties, combined with a high probability of a correct result, suggest that the sucralfate study has real value: (i) as a screening test in deciding who should be endoscoped and (ii) a test suitable for following the progress of a patient undergoing therapy for oesophageal ulceration without resort to further endoscopy.\n\n Further studies are warranted to assess the full potential of the dynamic sucralfate study.",
"results for the detection of ulceration throughout the gastrointestinal tract.' Previous work has tended to concentrate on the applications of labelled sucralfate in the stomach, small, and large bowel, although its use has been documented in the oesophagus,\" with mainly negative results from static imaging techniques. We describe here the use of 99mTc-labelled sucralfate in the investigation of oesophageal mucosal ulceration using a dynamic transit study. We have compared this with the barium swallow, using endoscopy as the gold standard for the detection of oesophageal ulceration.\n\n \n\n Initial swallows were made with 99mTc-labelled albumin colloid (microlite, Du Pont) as a suitable non-absorbable tracer. The kits were prepared according to the manufacturer's instructions. In preparing the labelled sucralfate, a similar method to that of Dawson7 was utiised, although in this study we have used 500 mg sucralfate powder, labelled with 30 MBq of 99mTc-HSA (Medi-Physics) radiopharma-Dynamic radionaiclide imaging with 99nm F(--slicralftate in the detection ofoesophageal ulceration1 ceutical per patient. The 99mTc-HSA was prepared by reconstituting a kit with 0-5 ml water for injection. 60 MBq of 99mTc pertechnetate was added in a volume of 1-3 ml, the vial shaken and allowed to stand for 20 minutes. The sucralfate was then suspended in 5 ml of HCI (pH 4) and shaken vigorously.\n\n Half the contents of the 99mTc-HSA vial was then added to the sucralfate and shaken. After centrifugation at 1400 g for 10 minutes, the supernatant was removed and resuspended in 5 ml water. Measurement of supernatant activity not bound to sucralfate was less than 0-5 MBq. Radiochemical purity measurements using paper chromatography were in agreement with those obtained by Dawson. 99mTc-col[LOID SWAL ILOW All patients made two separate swallows each, using 1( MBq 99mTc-colloid in 10 ml. The studies were performed supine with a computer acquisiton of 100 frames for each swallow at 0-5 s/frame, with a 32 x32 matrix. Having swallowed the radioactive bolus the patients were instructed not to swallow again for a period of 30 s, after which time a dry swallow was permitted. The data were processed to give timeactivity curves over the proximal, middle, and distal thirds of the oesophagus, whole oesophagus and stomach. Mean transit times were calculated from these curves. Condensed dynamic images were also obtained, based on the method of Svedberg.' 99mTc-suCRALFA EI[ SWALL OW After the colloid swallows, one swallow was performed supine on each patient using 30 MBq 99mTc-sucralfate. The method of acquisition was the same as for the colloid swallow, with 100 frames at 0(5 s/ frame. The data so obtained were processed in an identical manner, with time-activity curves, mean transit times and condensed dynamic images.\n\n S U BJ EC [S Sixty two consecutive patients were studied prospectively, 24 men with a mean age of 55 years (range 18-80 years). These patients presented to a specialist thoracic surgical outpatient department over a 10 month period. They represent general practitioner referrals and referrals from other consultants. Length of history was recorded at presentation an the symptoms assessed on the deMeester scale. This information is part of a larger clinical database and was not used in this particular study.\n\n All patients had endoscopy with fibreoptic or rigid instruments, and were classified for oesophageal ulceration on a scale of 0-3: (=no apparent oesophagitis; 1=linear ulceration; 2=discrete ulceration; and 3=confluent ulceraton with or without a fibrous stricture. Figure 1 , with the vertical axes marked to indicate the relative the relative positions of the mouth and stomach. The timeactivity curves for this patient are shown in Figure 2 . The typical pattern in a patient with oesophageal ulceration shows the condensed dynamic image having a persistent area of activity on the sucrailfate which is not present on the colloid swallow (Fig. 3) ."
]
| [
"Radiology & Imaging",
"Gastroenterology & Hepatology"
]
|
https://api.semanticscholar.org/CorpusID:10000204 | 10000204 | Rate of Family Refusal of Organ Donation in Dead-Brain Donors: the Iranian Tissue Bank Experience | 2,013 | International Journal of Organ Transplantation Medicine | [
1896438,
1052239
]
| [
"Of these, 412 (47%) were excluded from the study for unsuitability for donation according to the medical protocols (n=205; 23.4%), not fulfilling the brain death criteria (n=66; 7.5%), they were found death before interviewing with their relatives (n=39; 4.4%), lack of facility management and logistics in the hospital of origin (n=12; 1.3%), lack of suitable recipients (n=7; 0.8%), absence of patients' relatives (n=19; 2.2%), and for legal or suspicious issues re-\n\n The families of the remaining cases (n=462) had been interviewed and 343 (74.2%) gave consent to donate their patients' organs. During the process of supervision by our OPU, another 130 cases failed to donate (Fig 1) the main reasons of which were disagreement with the diagnosis of death and waiting for a miracle to happen.\n\n The demographic data of 213 remaining cases are summarized in Table 1 . The mean±SD age of the patients was 29.8±13.2 years; the male/ female ratio was almost 2 (141/72). The most common cause of brain death was head trauma due to traffic collisions (n=120; 56.3%) and cerebrovascular accidents (n=40; 18.8%). The refusal rate from 2007 to 2011 has decreased respectively, from 30.4% to 20% in Tehran, and from 57.1% to 51.6% in other cities (Fig 2) . The overall refusal rate was 25.8%. The number of donors with organ retrieval increased from 20 in 2007 to 74 in 2011. The mean number of organs retrieved was 3.6.\n\n One of the main concerns of all transplantation teams is understanding of relatives of a potential dead-brain donor of the nature of the brain death and the opportunity arisen to save other patients' lives by their appropriate actions and timely decision. Refusal to give consent for organ donation for this problem is still common in many countries including Iran [8] [9] [10] . In another OPU in Tehran, the refusal rate was 74% in 2009 [6] . What is important is the improvement in the rate of giving consent for solid organ donation. Saviozzi, et al, reported a reduction in refusal rate from 46.4% in 2001 to 19.5% in 2009 and concluded that the presence of experienced, committed health care personnel is mandatory to increase the available organ donor pool. Our study confirmed such a decrease and the role of experienced staff in OPU too [11] . On the other hand, general public education is necessary to persuade them to understand their responsibility for meeting the transplantation needs of the community, as it has already met for blood donation; also they should be informed of the meaning of brain death as clear as possible. Arjmand, et al, in their case-control study on 178 donor cardholders and the same number of a control participants showed that inadequate knowledge about donation and transplantation was the main reason for refusal to donate organ and tissue [12] . We need programs to sensitize the general population aiming at better acceptance of BDD process. This was confirmed by fluctuations in the refusal to consent rate in cities other than Tehran, despite the absolute rise in the number of donors (Fig 2) ; the nadir of graph was when some cities, without any background, were added to our OPU system. However, continuous support of an experienced team and the perseverance in repeated visits of all potential donors by the team members have increased the number of donation in spite of high refusal rates in cities other than Tehran. Another striking finding was the high percentage of donor pool from traffic collisions victims who had a mean age of 30 years. This was comparable to other studies from Iran and other developing countries; this emphasizes the necessity for a quick response of the team and widespread education [6, 7, 13] . Furthermore, the decrease in time between the patient admission to ICU and making the primary diagnosis of brain death by the first EEG taken by the coordinator team, is a promising finding which supports the positive impact of training and expertise plus quick response of the personnel for future planning.\n\n Identification of potential donors by the ICU staff, which took place in this study, and reporting them to our organ procurement organization (OPU) resulted in taking consent from 53% of suitable donors. This rate was 80% in the study by Khoddami Vishteh, et al [6] . One of the main reasons for the difference observed between these two studies may be due to the centers recently joined to our center; the new centers did not have any background on the subject and if we could have had more training courses and case studies, the rate would be increased.\n\n In conclusion, like other studies, we found that public belief has an important role in their refusal rate; presence of experienced coordinators would be very important in getting the consent from families; they can provide understandable answers to family members' questions; their help is paramount even in areas without previous background in BDD. Family Refusal of Organ Donation in Dead-Brain Donors",
"T he growing gap between organ supply and demand remains a worldwide serious problem for patients with endstage organ failure. Each country has tried various models to tackle this issue [1, 2] . The United States achieved an increase in deceased transplants by extended use of older donors (23 pmp in 2000 compared to 25.6 pmp in 2010), as the motor vehicle crash deaths decreased significantly by enforcing the comprehensive road safety laws [3, 4] . It is reported that over 90% of the world's fatalities on the roads take place in low-and middle-income countries (21.5 and 19.5 per 100,000 population, respectively). This rate in Iran is 32.7 per 100,000 population, annually [5] . It seems that if the donor coordinator team could act quickly and approach correctly the family of one whose life is not salvageable, other lives might be saved through transplantation of the patient's organs.\n\n After the legislation of \"organ transplantation and brain death act\" ratified in 2000 and allocation of a large amount of budget to organ procurement units (OPU) and hospitals by the Ministry of Health and Medical Education, the brain death donation (BDD) program has been supported and deceased donation has increased from 0.2 pmp in 2000 to 4.1 pmp in 2010 [3] . However, the program is still in its infancy and we need more than 3-fold this rate to save patients' lives.\n\n One of the reasons for losing such organs is not to recognizing potential donors by ICU staff, announcing death of patient before official declaration of brain death and a high refusal rate of deceased donors' families to donate organs [4, 6] .\n\n In Iran, the BDD network consists of 13 OPUs. There are also five brain death identification units in cities without any transplantation centers that refer cases to the OPUs. Donor transfer occurs by the coordinating team and donor's medical condition is managed until harvesting [1, 7] . Regions without OPU are covered by nearby OPUs.\n\n We conducted this study to determine the trend of dead-brain patients' relatives refusal to donate patients' organs since 2007 to 2011.\n\n This study was a retrospective review of all patients who had been introduced as brain death to the OPU of Iranian Tissue Bank between April 2007 and April 2012, according to a preliminary neurological exam performed in the hospital of origin. The refusal rate of deadbrain patients' families to donate the patients' organs and their reasons were evaluated.\n\n According to the Iranian national routines, being informed of a potential dead-brain donor, the brain death identification unit staff goes to the hospital, approaches the family; if the family members agree to donate the patient's organ, the management process to save organs and maintain their suitability and preliminary tests, verbal consultation with specialists starts and after a satisfactory electroencephalogram (EEG), the identified deadbrain donor is transferred to the center ICU. After admission, parallel with medical supervision and monitoring to confirm brain death to declare it officially, the family gives their written approval.\n\n The obtained data of patients from transplant coordinator team consisted of age, sex, cause of death, duration of ICU admission to the first positive neurological examination indicating brain death, the duration from diagnosis to transfer to OPU and confirmatory tests for the declaration of brain death, the number of harvested organs, the reasons why patient's relatives refused to donate organs, and the number and specialty of the independent medical specialists who reviewed the case. Because of the observational and retrospective nature of the study, the University Research Deputy did not ask for the approval of the Ethics Committee.\n\n During the last two years, we have established new Brain Death Identification Units (BDIU) in cities without previous background and trained their team of ICU nurses and coordinators. Therefore, our main activity in Tehran has moved to other OPUs. This made it possible to collect data from other centers too.\n\n A total of 874 ICU admitted patients with severe brain injury (Glasgow coma score <7) in the hospital of origin had been introduced to our center and visited by the coordinator team from April 2007 to April 2012."
]
| [
"Public Health & Epidemiology"
]
|
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