Hyperbaric oxygen as a model of lens aging in the bovine lens: The effects on lens biochemistry, physiology and optics.

Age related nuclear (ARN) cataracts in humans take years to form and so experimental models have been developed to mimic the process in animals as a means of better understanding the etiology of nuclear cataracts in humans. A major limitation with these animal models is that many of the biochemical and physiological changes are not typical of that seen in human ARN cataract. In this review, we highlight the work of Frank Giblin and colleagues who established an in vivo animal model that replicates many of the changes observed in human ARN cataract. This model involves exposing aged guinea pigs to hyperbaric oxygen (HBO), which by causing the depletion of the antioxidant glutathione (GSH) specifically in the lens nucleus, produces oxidative changes to nuclear proteins, nuclear light scattering and a myopic shift in lens power that mimics the change that often precedes cataract development in humans. However, this model involves multiple HBO treatments per week, with sometimes up to a total of 100 treatments, spanning up to eight months, which is both costly and time consuming. To address these issues, Giblin developed an in vitro model that used rabbit lenses exposed to HBO for several hours which was subsequently shown to replicate many of the changes observed in human ARN cataract. These experiments suggest that HBO treatment of in vitro animal lenses may serve as a more economical and efficient model to study the development of cataract. Inspired by these experiments, we investigated whether exposure of young bovine lenses to HBO for 15 h could also serve as a suitable acute model of ARN cataract. We found that while this model is able to exhibit some of the biochemical and physiological changes associated with ARN cataract, the decrease in lens power we observed was more characteristic of the hyperopic shift in refraction associated with ageing. Future work will investigate whether HBO treatment to age the bovine lens in combination with an oxidative stressor such as UV light will induce refractive changes more closely associated with human ARN cataract. This will be important as developing an animal model that replicates the changes to lens biochemistry, physiology and optics observed in human ARN cataracts is urgently required to facilitate the identification and testing of anti-cataract therapies that are effective in humans.

The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology.

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.

Prediction of 30-day pediatric unplanned hospitalizations using the Johns Hopkins Adjusted Clinical Groups risk adjustment system.

BACKGROUND: The Johns Hopkins ACG System is widely used to predict patient healthcare service use and costs. Most applications have focused on adult populations. In this study, we evaluated the use of the ACG software to predict pediatric unplanned hospital admission in a given month, based on the past year's clinical information captured by electronic health records (EHRs). METHODS AND FINDINGS: EHR data from a multi-state pediatric integrated delivery system were obtained for 920,051 patients with at least one physician visit during January 2009 to December 2016. Over this interval an average of 0.36% of patients each month had an unplanned hospitalization. In a 70% training sample, we used the generalized linear mixed model (GLMM) to generate regression coefficients for demographic, clinical predictors derived from the ACG system, and prior year hospitalizations. Applying these coefficients to a 30% test sample to generate risk scores, we found that the area under the receiver operator characteristic curve (AUC) was 0.82. Omitting prior hospitalizations decreased the AUC from 0.82 to 0.80, and increased under-estimation of hospitalizations at the greater risk levels. Patients in the top 5% of risk scores accounted for 43% and the top 1% of risk scores accounted for 20% of all unplanned hospitalizations. CONCLUSIONS: A predictive model based on 12-months of demographic and clinical data using the ACG system has excellent predictive performance for 30-day pediatric unplanned hospitalization. This model may be useful in population health and care management applications targeting patients likely to be hospitalized. External validation at other institutions should be done to confirm our results.

Explaining patient delay in healthcare seeking and loss to diagnostic follow-up among patients with presumptive tuberculosis in Tanzania: a mixed-methods study.

BACKGROUND: Delay in healthcare seeking and loss to diagnostic follow-up (LDFU) contribute to substantial increase in tuberculosis (TB) morbidity and mortality. We examined factors, including perceived causes and prior help seeking, contributing to delay and LDFU during referral to a TB clinic among patients with presumptive TB initially seeking help at the pharmacies in Dar es Salaam Tanzania. METHODS: In a TB clinic, a semi-structured interview based on the explanatory model interview catalogue (EMIC) framework for cultural epidemiology was administered to presumptive TB patients enrolled at pharmacies during an intervention study. We assessed delay in seeking care at any medical care provider for a period of ≥3 weeks after the onset of symptoms, LDFU during referral (not reaching the TB clinic), and LDFU for three required TB clinic visits among the presumptive and confirmed TB patients. Logistic regression models were used to assess factors associated with delay and LDFU. RESULTS: Among 136 interviewed patients, 86 (63.2%) were LDFU from pharmacies and TB clinic while 50 (36.8%) were non-LDFU. Out of 136 patients 88 (64.7%) delayed seeking care, of whom 59 (67%) were females. Among the 86 (63.2%) patients in LDFU group, 62 (72.1%) delayed seeking care, while among the 50 (36.8%) non-LDFU, 26 (52.0%) had also delayed seeking care. Prior consultation with a traditional healer (aOR 2.84, 95% CI 1.08-7.40), perceived causes as ingestion (water and food) (aOR 0.38 CI 0.16-0.89), and substance use (smoking and alcohol) (aOR 1.45 CI 0.98-2.14) were all associated with patient delay. Female gender was associated with LDFU (aOR 3.80, 95% CI 1.62-8.87) but not with delay. Other conditions as prior illness and heredity were also associated with LDFU but not delay (aOR 1.48 CI 1.01-2.17). CONCLUSION: Delay and LDFU after referral from the pharmacies were substantial. Notable effects of diagnosis and female gender indicate a need for more attention to women's health to promote timely and sustained TB treatment. Public awareness to counter misconceptions about the causes of TB is needed.

Periarticular Liposomal Bupivacaine Injection Versus Intra-Articular Bupivacaine Infusion Catheter for Analgesia After Total Knee Arthroplasty: A Double-Blinded, Randomized Controlled Trial.

BACKGROUND: Intra-articular bupivacaine hydrochloride (HCl) infusion catheters and periarticular injections of liposomal bupivacaine are often used as postoperative local anesthetics. The purpose of this study was to compare the efficacies of these local anesthetics following total knee arthroplasty. METHODS: This study was a superiority trial with a randomized, controlled, double-blinded design. Patients were randomly assigned to either delivery of bupivacaine HCl by the ON-Q* Pain Relief System pump (n = 96) or by an injection of Exparel (liposomal bupivacaine) (n = 104). The primary outcome of this study was cumulative narcotic consumption on postoperative days 0 through 3. Narcotic consumption data were collected retrospectively from in-hospital records while patients were in the hospital. Following discharge, narcotic consumption data were gathered from patient surveys, as were secondary outcomes measures. RESULTS: We did not identify greater narcotic use in the ON-Q* group compared with the Exparel group (p = 0.641). The mean difference between the groups was 0.5 morphine equivalent (95% confidence interval [CI] = -1.7 to +2.8), with the ON-Q* group consuming an average 10.4 morphine equivalents (95% CI = 8.7 to 12.0) compared with 10.9 (95% CI = 9.3 to 12.5) in the Exparel group. There were no significant differences between groups with regard to any of the secondary measures of pain with the exception of pain while walking and pain with physical therapy (p = 0.019 and p = 0.010, respectively), both of which showed an approximately 1-point difference in favor of the ON-Q* group on a visual analog scale (VAS). There were also no differences in the postoperative side effects, including nausea, constipation, or vomiting, or in the rates of study-related complications, patient satisfaction, or length of hospital stay. CONCLUSIONS: Exparel did not have superior efficacy compared with the ON-Q* Pain Relief System as reflected by narcotic consumption, our primary outcome. There were small significant differences, in favor of the ON-Q* group, in 2 secondary measures of pain during activity, but these approximately 1-point VAS differences are unlikely to be clinically relevant. The choice of a local anesthetic modality should be based on a combination of safety, convenience, and cost considerations. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Cancer, ageing, multimorbidity and primary care.

Cancer care is complex, and made more so by multimorbidity and ageing. Multimorbidity affects all stages of cancer care from prevention and early detection through to end of life care. The effectiveness of cancer treatments in multimorbid patients may not be understood, as many conditions common in older people may be exclusion criteria in oncology clinical trials. The interaction between pre-existing physical capacity, multiple medical conditions and ageing can delay diagnosis, impact on treatments, complicate survivor care, and impact on decisions about starting and ceasing treatments. General Practitioners (GPs) manages multimorbidity routinely, yet the GP role in comprehensive cancer care is limited. Integration of GP management of multimorbidity in conjunction with oncology services should improve patient outcomes. Integration of care for these patients can educate patients on the minimisation of multimorbidity, develop personalised screening plans and contribute to the wholistic management of people in the surveillance period. GPs should have a major role in end of life care. Integration of general practice and oncology should benefit patient care.

Sociocultural determinants of anticipated acceptance of pandemic influenza vaccine in Pune, India: a community survey using mixed-methods.

OBJECTIVES: To investigate community priority and determinants of pandemic influenza vaccine acceptance in Pune, India. Community willingness to accept vaccines is often neglected in pandemic preparedness. Despite an acknowledged need, few such studies have been done in lower income countries. METHODS: A cross-sectional, mixed-methods study used semi-structured explanatory model interviews to assess anticipated acceptance of nasal and injectable vaccines at different prices among 436 urban and rural residents. Logistic regression models identified sociocultural determinants of vaccine acceptance. RESULTS: Over 93 % anticipated acceptance at no-cost; 87.8 % for INR 150 nasal vaccine; 74.1 % for INR 500 and 61.7 % for INR 1000 injectable vaccines. Some respondents preferred low-cost over free vaccines. Illness-related concerns about social isolation, contaminants identified as perceived causes, private-hospital or traditional-healer help seeking, and income were positively associated with anticipated acceptance. Humoral imbalances as perceived cause, home remedies for help-seeking and age were negatively associated. CONCLUSIONS: High acceptability of pandemic influenza vaccines indicates good prospects for mass vaccination. It appeared that confidence was higher in the vaccines than in the health systems delivering them. Vaccination programmes should consider sociocultural determinants influencing vaccine acceptance.

Characterization of the Effects of Hyperbaric Oxygen on the Biochemical and Optical Properties of the Bovine Lens.

PURPOSE: To assess the morphologic, biochemical, and optical properties of bovine lenses treated with hyperbaric oxygen. METHODS: Lenses were exposed to hyperbaric nitrogen (HBN) or hyperbaric oxygen (HBO) for 5 or 15 hours, lens transparency was assessed using bright field microscopy and lens morphology was visualized using confocal microscopy. Lenses were dissected into the outer cortex, inner cortex, and core, and glutathione (GSH) and malondialdehyde (MDA) measured. Gel electrophoresis and Western blotting were used to detect high molecular weight aggregates (HMW) and glutathione mixed protein disulfides (PSSG). T2-weighted MRI was used to measure lens geometry and map the water/protein ratio to allow gradient refractive index (GRIN) profiles to be calculated. Optical modeling software calculated the change in lens optical power, and an anatomically correct model of the light pathway of the bovine eye was used to determine the effects of HBN and HBO on focal length and overall image quality. RESULTS: Lenses were transparent and lens morphology similar between HBN- and HBO-treated lenses. At 5- and 15-hour HBO exposure, GSH and GSSG were depleted and MDA increased in the core. Glutathione mixed protein disulfides were detected in the outer and inner cortex only with no appearance of HMW. Optical changes were detectable only with 15-hour HBO treatment with a decrease in the refractive index of the core, slightly reduced lens thickness, and an increase in optimal focal length, consistent with a hyperopic shift. CONCLUSIONS: This system may serve as a model to study changes that occur with advanced aging rather than nuclear cataract formation per se.

Evaluation of Gallium Citrate Formulations against a Multidrug-Resistant Strain of Klebsiella pneumoniae in a Murine Wound Model of Infection.

Skin and soft tissue infections (SSTIs) are a common occurrence in health care facilities with a heightened risk for immunocompromised patients. Klebsiella pneumoniae has been increasingly implicated as the bacterial agent responsible for SSTIs, and treatment can be challenging as more strains become multidrug resistant (MDR). Therefore, new treatments are needed to counter this bacterial pathogen. Gallium complexes exhibit antimicrobial activity and are currently being evaluated as potential treatment for bacterial infections. In this study, we tested a topical formulation containing gallium citrate (GaCi) for the treatment of wounds infected with K. pneumoniae. First, the MIC against K. pneumoniae ranged from 0.125 to 2.0 µg/ml GaCi. After this in vitro efficacy was established, two topical formulations with GaCi (0.1% [wt/vol] and 0.3% [wt/vol]) were tested in a murine wound model of MDR K. pneumoniae infection. Gross pathology and histopathology revealed K. pneumoniae-infected wounds appeared to close faster with GaCi treatment and were accompanied by reduced inflammation compared to those of untreated controls. Similarly, quantitative indications of infection remediation, such as reduced weight loss and wound area, suggested that treatment improved outcomes compared to those of untreated controls. Bacterial burdens were measured 1 and 3 days following inoculation, and a 0.5 to 1.5 log reduction of CFU was observed. Lastly, upon scanning electron microscopy analysis, GaCi treatment appeared to prevent biofilm formation on dressings compared to those of untreated controls. These results suggest that with more preclinical testing, a topical application of GaCi may be a promising alternative treatment strategy for K. pneumoniae SSTI.

Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer.

BACKGROUND: Fresh patient specimens of castrate-resistant prostate cancer (CRPC) are invaluable for studying tumor heterogeneity and responses to current treatments. They can be used for primary patient-derived xenografts (PDXs) or serially transplantable PDXs, but only a small proportion of samples grow successfully. To improve the efficiency and quality of PDXs, we investigated the factors that determine the initial engraftment of patient tissues derived from TURP specimens. METHODS: Fresh tissue was collected from castrate patients who required a TURP for urinary symptoms. Tissue was grafted under the renal capsule of immune-compromised mice for up to 14 weeks. The abundance of cancer in ungrafted and grafted specimens was compared using histopathology. Mice were castrated or implanted with testosterone pellets to determine the androgen-responsiveness of CRPC PDXs from TURP tissue. RESULTS: Primary PDXs were successfully established from 7 of 10 patients that underwent grafting. Of the 112 grafts generated from these 10 patients, 21% contained cancer at harvest. Grafts were most successful when the original patient specimens contained high amounts of viable cancer, defined as samples with (i) at least 50% cancer cells, (ii) no physical damage, and (iii) detectable Ki67 expression. PDX grafts survived in castrated hosts and proliferated in response to testosterone, confirming that they were castrate resistant but androgen-responsive. CONCLUSIONS: Primary PDXs of CRPC can be established from TURP specimens with modest success. The take rate can be increased if the original tissues contain sufficient numbers of actively proliferating cancer cells. Selecting specimens with abundant viable cancer will maximize the rate of engraftment and increase the efficiency of establishing PDXs that can be serially transplanted.

Predictors of perioperative blood loss in total joint arthroplasty.

UNLABELLED: UPDATE The print version of this article has errors that have been corrected in the online version of this article. In the Materials and Methods section, the sentence that reads as "During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with a hemoglobin level of no less than 11 mg/dL or a hematocrit level of at least 33%." in the print version now reads as "During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with a hemoglobin level of no less than 11 g/dL or a hematocrit level of at least 33%." in the online version. In Table III, the footnote that reads as "The values are given as the estimate and the standard error in milligrams per deciliter." in the print version now reads as "The values are given as the estimate and the standard error in grams per deciliter." in the online version. BACKGROUND: Despite advances in surgical and anesthetic techniques, lower-extremity total joint arthroplasty is associated with considerable perioperative blood loss. As predictors of perioperative blood loss and allogenic blood transfusion have not yet been well defined, the purpose of this study was to identify clinical predictors for perioperative blood loss and allogenic blood transfusion in patients undergoing total joint arthroplasty. METHODS: From 2000 to 2008, all patients undergoing unilateral primary total hip or knee arthroplasty who met the inclusion criteria were enrolled in the study. Perioperative blood loss was calculated with use of a previously validated formula. The predictors of perioperative blood loss and allogenic blood transfusion were identified in a multivariate analysis. RESULTS: Eleven thousand three hundred and seventy-three patients who underwent total joint arthroplasty, including 4769 patients who underwent total knee arthroplasty and 6604 patients who underwent total hip arthroplasty, were evaluated. Multivariate analysis indicated that an increase in blood loss was associated with being male (263.59 mL in male patients who had undergone total hip arthroplasty and 233.60 mL in male patients who had undergone total knee arthroplasty), a Charlson Comorbidity Index of >3 (293.99 mL in patients who had undergone total hip arthroplasty and 167.96 mL in patients who had undergone total knee arthroplasty), and preoperative autologous blood donation (593.51 mL in patients who had undergone total hip arthroplasty and 592.30 mL in patients who had undergone total knee arthroplasty). In patients who underwent total hip arthroplasty, regional anesthesia compared with general anesthesia reduced the amount of blood loss. The risk of allogenic blood transfusion increased with the amount of blood loss in the patients who underwent total hip arthroplasty (odds ratio, 1.43 [95% confidence interval, 1.40 to 1.46]) and the patients who underwent total knee arthroplasty (odds ratio, 1.47 [95% confidence interval, 1.42 to 1.51]), but the risk of blood transfusion increased with the Charlson Comorbidity Index only in patients who underwent total knee arthroplasty (odds ratio, 3.2 [95% confidence interval, 1.99 to 5.15]). The risk of allogenic blood transfusion decreased with preoperative autologous blood donation in patients who underwent total hip arthroplasty (odds ratio, 0.01 [95% confidence interval, 0.01 to 0.02]) and patients who underwent total knee arthroplasty (odds ratio, 0.02 [95% confidence interval, 0.01 to 0.03]). CONCLUSIONS: This study identified some clinical predictors for blood loss in patients undergoing total joint arthroplasty that we believe can be used for implementing more effective blood conservation strategies. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

A preclinical xenograft model of prostate cancer using human tumors.

Most cases of prostate cancer are now diagnosed as moderate-grade localized disease. These tumor specimens are important tools in the discovery and translation of prostate cancer research; however, unlike more advanced tumors, they are notoriously difficult to grow in the laboratory. We developed a system for efficiently xenografting localized human prostate cancer tissue, and we adapted this protocol to study the interactions between the specific subsets of epithelial and stromal cells. Fresh prostate tissues or isolated epithelial cells are recombined with mouse seminal vesicle mesenchyme (SVM) and grafted under the renal capsule of immunodeficient mice for optimum growth and survival. Alternatively, mouse mesenchyme can be replaced with human prostate fibroblasts in order to determine their contribution to tumor progression. Grafts can be grown for several months to determine the effectiveness of novel therapeutic compounds when administered to host mice, thereby paving the way for personalizing the treatment of individual prostate cancers.

Acceptability--a neglected dimension of access to health care: findings from a study on childhood convulsions in rural Tanzania.

BACKGROUND: Acceptability is a poorly conceptualized dimension of access to health care. Using a study on childhood convulsion in rural Tanzania, we examined social acceptability from a user perspective. The study design is based on the premise that a match between health providers' and clients' understanding of disease is an important dimension of social acceptability, especially in trans-cultural communication, for example if childhood convulsions are not linked with malaria and local treatment practices are mostly preferred. The study was linked to health interventions with the objective of bridging the gap between local and biomedical understanding of convulsions. METHODS: The study combined classical ethnography with the cultural epidemiology approach using EMIC (Explanatory Model Interview Catalogue) tool. EMIC interviews were conducted in a 2007/08 convulsion study (n = 88) and results were compared with those of an earlier 2004/06 convulsion study (n = 135). Earlier studies on convulsion in the area were also examined to explore longer-term changes in treatment practices. RESULTS: The match between local and biomedical understanding of convulsions was already high in the 2004/06 study. Specific improvements were noted in form of (1) 46% point increase among those who reported use of mosquito nets to prevent convulsion (2) 13% point decrease among caregivers who associated convulsion with 'evil eye and sorcery', 3) 14% point increase in prompt use of health facility and 4)16% point decrease among those who did not use health facility at all. Such changes can be partly attributed to interventions which explicitly aimed at increasing the match between local and biomedical understanding of malaria. Caregivers, mostly mothers, did not seek advice on where to take an ill child. This indicates that treatment at health facility has become socially acceptable for severe febrile with convulsion. CONCLUSION: As an important dimension of access to health care 'social acceptability' seems relevant in studying illnesses that are perceived not to belong to the biomedical field, specifically in trans-cultural societies. Understanding the match between local and biomedical understanding of disease is fundamental to ensure acceptability of health care services, successful control and management of health problems. Our study noted some positive changes in community knowledge and management of convulsion episodes, changes which might be accredited to extensive health education campaigns in the study area. On the other hand it is difficult to make inference out of the findings as a result of small sample size involved. In return, it is clear that well ingrained traditional beliefs can be modified with communication campaigns, provided that this change resonates with the beneficiaries.

Illness meanings and experiences for pre-ulcer and ulcer conditions of Buruli ulcer in the Ga-West and Ga-South Municipalities of Ghana.

BACKGROUND: Ghana is a Buruli ulcer (BU) endemic country yet there is paucity of socio-cultural research on BU. Examining distinctive experiences and meanings for pre-ulcers and ulcers of BU may clarify the disease burden, illness experience and local perceptions of causes and spread, and environmental features of BU, which are useful to guide public health programmes and future research. This study aimed to explain local meanings and experiences of BU for persons with pre-ulcers and ulcers in the Ga-West and Ga-South municipalities in Accra. METHODS: Semi-structured interviews based on the Explanatory Model Interview Catalogue framework were administered to 181 respondents comprising 15 respondents with pre-ulcers and 166 respondents with ulcers. The Wilcoxon rank-sum test was used to compare categories of illness experiences (PD) and perceived causes (PC) among respondents with pre-ulcer and ulcer conditions. The Fisher's exact test was used to compare the most troubling PD and the most important PC variables. Qualitative phenomenological analysis of respondents' narratives clarified illness experiences and meanings with reference to PC and PD variables. RESULTS: Families of respondents with pre-ulcers and the respondents themselves were often anxious about disease progression, while families of respondents with ulcers, who had to give care, worried about income loss and disruption of school attendance. Respondents with pre-ulcers frequently reported swimming in ponds and rivers as a perceived cause and considered it as the most important PC (53.3%). Respondents with ulcers frequently attributed their BU illness to witchcraft (64.5%) and respondents who claimed they had no water contact, questioned the credibility of health messages CONCLUSIONS: Affected persons with pre-ulcers are likely to delay treatment because of social and financial constraints and the absence of pain. Scepticism on the role of water in disease contagion and prolonged healing is perceived to make ideas of witchcraft as a PC more credible, among respondents with ulcers. Health messages should address issues of locally perceived risk and vulnerability. Guided by study findings, further research on the role of environmental, socio-cultural and genetic factors in BU contagion, is also needed to clarify and formulate health messages and strengthen public health initiatives.

Help-seeking for pre-ulcer and ulcer conditions of Mycobacterium ulcerans disease (Buruli ulcer) in Ghana.

This study examined sociocultural features of help-seeking for Buruli ulcer-affected persons with pre-ulcers and ulcers in a disease-endemic area in Ghana. A sample of 181 respondents were purposively selected. Fisher's exact test was used to compare help-seeking variables for pre-ulcers and ulcers. Qualitative phenomenologic analysis of narratives clarified the meaning and content of selected quantitative help-seeking variables. For pre-ulcers, herbal dressings were used to expose necrotic tissues and subsequently applied as dressings for ulcers. Analgesics and left-over antibiotics were used to ease pain and reduce inflammation. Choices for outside-help were influenced by the perceived effectiveness of the treatment, the closeness of the provider to residences, and family and friends. Health education is required to emphasize the risk of self-medication with antibiotics and the importance of medical treatment for pre-ulcers, and to caution against the use of herbs to expose necrotic tissues, which could lead to co-infections.

Cultural epidemiology of neurasthenia spectrum disorders in four general hospital outpatient clinics of urban Pune, India.

Disorders emphasizing symptoms of fatigue and/or weakness, collectively termed Neurasthenia Spectrum Disorders (NSDs), typically emphasize a biological basis in the West and social origins in East Asia. In India, explanatory concepts are diverse. To clarify, 352 outpatients in Psychiatry, Medicine, Dermatology, and Ayurved clinics of an urban hospital were interviewed with a version of the Explanatory Model Interview Catalogue. Comparisons of categories and narratives of illness experience and meaning across clinics indicated both shared and distinctive features. Explanatory models of NSDs highlighted social distress, ''tensions,'' and both general and clinic-specific physical, psychological, and cultural ideas. Findings indicate the importance of social contexts and cultural meaning in explanatory models of neurasthenia, as well as the potential clinical relevance of the construct of Neurasthenia Spectrum Disorder.

Explaining suicide in an urban slum of Mumbai, India: a sociocultural autopsy.

BACKGROUND: Health demographic mortality studies use verbal autopsies to identify suicide as a cause of death. Psychological autopsies focus almost exclusively on associated high-risk psychiatric disorders. New approaches considering contextual factors are needed for preventing suicide and promoting mental health. AIMS: This study examined explanations of suicide reported by surviving family members or close friends with reference to social, cultural, and environmental conditions as well as the challenges of life in the Malavani slum of Mumbai. METHODS: An EMIC (Explanatory Model Interview Catalog) interview based on a cultural epidemiological framework considered underlying problems, perceived causes, and sociocultural contexts. It was administered to survivors of 76 people who had died by suicide (56.6% women). RESULTS: Accounts of underlying problems typically referred to various aspects of tension (73.7%). Perceived causes often identified multiple factors. The sociocultural contexts of suicide included the victimization of women, the personal and social impact of problem drinking, marital problems, physical health problems, mental tension, possession and sorcery. Women were particularly vulnerable to the impact of problem drinking by a spouse or father. CONCLUSIONS: This study demonstrates the value of an approach to sociocultural autopsy examining local contexts and explanations of suicide. Findings highlight needs for both mental health services and culturally sensitive social interventions.

Socio-cultural factors explaining timely and appropriate use of health facilities for degedege in south-eastern Tanzania.

BACKGROUND: Convulsions is one of the key signs of severe malaria among children under five years of age, potentially leading to serious complications or death. Several studies of care-seeking behaviour have revealed that local illness concepts linked to convulsions (referred to as degedege in Tanzanian Kiswahili) called for traditional treatment practices while modern treatment was preferred for common fevers. However, recent studies found that even children with convulsions were first brought to health facilities. This study integrated ethnographic and public health approaches in order to investigate this seemingly contradictory evidence. Carefully drawn random samples were used to maximize the representativity of the results. METHODS: The study used a cultural epidemiology approach and applied a locally adapted version of the Explanatory Model Interview Catalogue (EMIC), which ensures a comprehensive investigation of disease perception and treatment patterns. The tool was applied in three studies; i) the 2004 random sample cross-sectional community fever survey (N = 80), ii) the 2004-2006 longitudinal degedege study (N = 129), and iii) the 2005 cohort study on fever during the main farming season (N = 29). RESULTS: 71.1% of all convulsion cases were brought to a health facility in time, i.e. within 24 hours after onset of first symptoms. This compares very favourably with a figure of 45.6% for mild fever cases in children. The patterns of distress associated with less timely health facility use and receipt of anti-malarials among children with degedege were generalized symptoms, rather than the typical symptoms of convulsions. Traditional and moral causes were associated with less timely health facility use and receipt of anti-malarials. However, the high rate of appropriate action indicates that these ideas were not so influential any more as in the past. Reasons given by caretakers who administered anti-malarials to children without attending a health facility were either that facilities were out of stock, that they lacked money to pay for treatment, or that facilities did not provide diagnosis. CONCLUSION: The findings from this sample from a highly malaria-endemic area give support to the more recent studies showing that children with convulsions are more likely to use health facilities than traditional practices. This study has identified health system and livelihood factors, rather than local understandings of symptoms and causes relating to degedege as limiting health-seeking behaviours. Improvements on the supply side and the demand side are necessary to ensure people's timely and appropriate treatment: Quality of care at health facilities needs to be improved by making diagnosis and provider compliance with treatment guidelines more accurate and therapies including drugs more available and affordable to communities. Treatment seeking needs to be facilitated by strengthening livelihoods including economic capabilities.

Clinical and economic impact of falsely decreased calcium values caused by gadoversetamide interference.

OBJECTIVE: Gadolinium is administered as a contrast agent in MRI procedures. Two gadolinium-based contrast agents, gadodiamide and gadoversetamide, interfere with colorimetric total serum calcium methods. The purpose of this prospective observational study was to examine the incidence of calcium interference after gadoversetamide procedures, associated clinical outcomes, and costs 20 months after implementation of quality assurance and physician education programs. MATERIALS AND METHODS: Records of patients who received gadoversetamide from June 24, 2006, to October 7, 2006, were reviewed to determine if a routine calcium test had been performed after the injection. Calcium values were repeated with an alternate method that is less susceptible to gadoversetamide interference. If the difference was > or = 2.0 mg/dL or if the initial test value was < or = 7.0 mg/dL, patient charts were reviewed for any related treatment. Costs associated with this algorithm were tracked. RESULTS: The initial calcium test was performed after gadoversetamide in 766 of 3,439 instances. The alternate test was performed in 633 of 766. One hundred twenty-five of 633 (20%) showed a difference in calcium values that was > or = 0.7 mg/dL, with 16 showing differences of > or = 1.6 mg/dL. Chart review for 56 instances revealed that calcium supplements were administered in 22 of 56 around the time of gadoversetamide injection. However, none appeared to be related to the spurious hypocalcemia. The total additional cost (reagent and technologist) for following this algorithm for just over 3 months was $6,807. CONCLUSION: Approximately 20% of patients receiving gadoversetamide exhibited spurious hypocalcemia. No patients were identified who received inappropriate calcium because of this interference. This may be attributable to the quality assurance and physician education programs.

Prevalence of clinically significant functional fatigue or weakness in specialty outpatient clinics of Pune, India.

Disorders of fatigue are important in clinical practice but inadequately studied in developing countries. Questions about their consistency and variation across cultures also require attention. The standard professional diagnostic formulations of these disorders, namely, chronic fatigue syndrome and neurasthenia, are not used widely in India, perhaps due to lack of research and poor appreciation of their clinical significance. Recognising patients with clinically significant functional fatigue or weakness often seek help from various care-givers, prevalence of this condition was studied in four specialty clinics of Sassoon Hospital, Pune. An operationally defined set of criteria was used to create a screening instrument. Trained research assistants surveyed 1,874 consecutive patients from psychiatry, medicine, dermatology, and ayurved clinics. Data were entered and analysed to compute the rates of this condition, compare them across clinics and between sexes, and to compute rates adjusted for age, sex, and the clinic attended. Overall prevalence was 5.02% with higher rates in the dermatology and ayurved clinics than in psychiatry and medicine clinics. The female preponderance (63.83%) was notable (p < 0.001). Mean age of patients with this condition was similar across clinics. Logistic regression showed female sex (OR 2.19, 95% CI 1.41 to 3.40) and dermatology clinic (OR 1.70, 1.02 to 2.85) to be significant predictors of CS-FoW. Female preponderance indicates the need for studies with gender focus. Clinical and cultural epidemiological studies informing psychiatrists as well as other physicians are necessary. Need for counselling for majority of these patients calls for appropriate changes in healthcare delivery.