Costs analysis of a population level rabies control programme in Tamil Nadu, India

The study aimed to determine costs to the state government of implementing different interventions for controlling rabies among the entire human and animal populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadu’s efforts to control rabies. Anti-rabies vaccines were made available at all health facilities. Costs were estimated for five different combinations of animal and human interventions using an activity-based costing approach from the provider perspective. Disease and population data were sourced from the state surveillance data, human census and livestock census. Program costs were extrapolated from official documents. All capital costs were depreciated to estimate annualized costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted across all major cost centres to assess their relative impact on program costs. It was found that the annual costs of providing Anti-rabies vaccine alone and in combination with Immunoglobulins was \$0.7 million (Rs 36 million) and \$2.2 million (Rs 119 million), respectively. For animal sector interventions, the annualised costs of rolling out surgical sterilisation-immunization, injectable immunization and oral immunizations were estimated to be \$ 44 million (Rs 2,350 million), \$23 million (Rs 1,230 million) and \$ 11 million (Rs 590 million), respectively. Dog bite incidence, health systems coverage and cost of rabies biologicals were found to be important drivers of costs for human interventions. For the animal sector interventions, the size of dog catching team, dog population and vaccine costs were found to be driving the costs. Rabies control in Tamil Nadu seems a costly proposition the way it is currently structured. Policy makers in Tamil Nadu and other similar settings should consider the long-term financial sustainability before embarking upon a state or nation-wide rabies control programme

The Impact of Microclimate on Skin Health With Absorbent Incontinence Product Use An Integrative Review

This integrative review considers the role of skin occlusion and microclimate in incontinence-associated dermatitis (IAD), with a particular focus on disposable, body-worn, absorbent incontinence products. Although the mechanisms are not fully understood, the primary causes of IAD are well-established: occluded skin, in prolonged contact with urine and/or feces and exposed to abrasive forces, is more likely to be affected, and each of these factors can be influenced by wearing absorbent incontinence products. Studies comparing the effect of various absorbent products on skin health have been hindered by the many differences between compared products, making it difficult to clearly attribute any differences in performance to particular materials or design features. Nevertheless, the large and significant differences that have sometimes been found invite further work. Breathable back sheets can significantly reduce the temperature of occluded skin and the humidity of the adjacent air, and several treatments for nonwoven top sheet materials (used next to the skin) have been shown to impart antimicrobial properties in the laboratory, but an impact on IAD incidence or severity has yet to be demonstrated directly. Recent work to introduce sensing technology into absorbent incontinence products to reduce the exposure of skin to urine and feces, by encouraging prompt product changing, seems likely to yield measurable benefits in terms of reducing incidents of IAD as the technology develops. Published work to date suggests that there is considerable potential for products to be engineered to play a significant role in the reduction of IAD among users

Renal expression of vascular endothelial growth factor in lupus nephritis in the pediatric age group

Background: Vascular endothelial growth factor (VEGF) plays a crucial role in preservation of renal functions and may also serve as a useful biomarker in monitoring the progression of lupus nephritis (LN). Objective: We thought to correlate VEGF expression in the kidney with renal histopathology in lupus nephritis to unveil its possible relation to disease activity and severity.Methods: We consecutively enrolled 15 patients with lupus nephritis and ten renal biopsy specimens from patients with cystic renal diseases as controls. The study measurements included SLEDAI, SLICC/ ACR damage index and BILAG renal score. Paraffin sections from renal biopsies were subjected to routine haematoxylin and eosin staining and Immunohistochemical staining for VEGF. Results: Among SLE patients, 7 (46.7%) showed mild expression of VEGF, 5 (33.3%) showed moderate while 3 (20%) had strong expression of the marker. On the contrary, the control samples (100%) revealed strong marker expression. All subjects with class IV and V lupus nephritis had mild renal expression of VEGF. Renal expression of VEGF had a significant positive correlation with serum creatinine and complement C3 levels. The 24 hours’ excretion of urinary proteins had a significant negative correlation with the renal expression of the marker. On the other hand, the activity indices and therapeutic modalities did not correlate with VEGF expression. Conclusion: This pilot study among pediatric cases of SLE revealed mild to moderate VEGF expression in most cases of proliferative LN. Further longitudinal studies are needed to investigate the consequences of this finding on the prognosis of the disease.Keywords: VEGF, SLE, renal biopsy, lupus nephritis

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Global burden of disease due to smokeless tobacco consumption in adults : analysis of data from 113 countries

BACKGROUND: Smokeless tobacco is consumed in most countries in the world. In view of its widespread use and increasing awareness of the associated risks, there is a need for a detailed assessment of its impact on health. We present the first global estimates of the burden of disease due to consumption of smokeless tobacco by adults. METHODS: The burden attributable to smokeless tobacco use in adults was estimated as a proportion of the disability-adjusted life-years (DALYs) lost and deaths reported in the 2010 Global Burden of Disease study. We used the comparative risk assessment method, which evaluates changes in population health that result from modifying a population's exposure to a risk factor. Population exposure was extrapolated from country-specific prevalence of smokeless tobacco consumption, and changes in population health were estimated using disease-specific risk estimates (relative risks/odds ratios) associated with it. Country-specific prevalence estimates were obtained through systematically searching for all relevant studies. Disease-specific risks were estimated by conducting systematic reviews and meta-analyses based on epidemiological studies. RESULTS: We found adult smokeless tobacco consumption figures for 115 countries and estimated burden of disease figures for 113 of these countries. Our estimates indicate that in 2010, smokeless tobacco use led to 1.7 million DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus and, based on data from the benchmark 52 country INTERHEART study, 4.7 million DALYs lost and 204,309 deaths from ischaemic heart disease. Over 85 % of this burden was in South-East Asia. CONCLUSIONS: Smokeless tobacco results in considerable, potentially preventable, global morbidity and mortality from cancer; estimates in relation to ischaemic heart disease need to be interpreted with more caution, but nonetheless suggest that the likely burden of disease is also substantial. The World Health Organization needs to consider incorporating regulation of smokeless tobacco into its Framework Convention for Tobacco Control

MEF2C-MYOCD and Leiomodin1 Suppression by miRNA-214 Promotes Smooth Muscle Cell Phenotype Switching in Pulmonary Arterial Hypertension.

BACKGROUND: Vascular hyperproliferative disorders are characterized by excessive smooth muscle cell (SMC) proliferation leading to vessel remodeling and occlusion. In pulmonary arterial hypertension (PAH), SMC phenotype switching from a terminally differentiated contractile to synthetic state is gaining traction as our understanding of the disease progression improves. While maintenance of SMC contractile phenotype is reportedly orchestrated by a MEF2C-myocardin (MYOCD) interplay, little is known regarding molecular control at this nexus. Moreover, the burgeoning interest in microRNAs (miRs) provides the basis for exploring their modulation of MEF2C-MYOCD signaling, and in turn, a pro-proliferative, synthetic SMC phenotype. We hypothesized that suppression of SMC contractile phenotype in pulmonary hypertension is mediated by miR-214 via repression of the MEF2C-MYOCD-leiomodin1 (LMOD1) signaling axis. METHODS AND RESULTS: In SMCs isolated from a PAH patient cohort and commercially obtained hPASMCs exposed to hypoxia, miR-214 expression was monitored by qRT-PCR. miR-214 was upregulated in PAH- vs. control subject hPASMCs as well as in commercially obtained hPASMCs exposed to hypoxia. These increases in miR-214 were paralleled by MEF2C, MYOCD and SMC contractile protein downregulation. Of these, LMOD1 and MEF2C were directly targeted by the miR. Mir-214 overexpression mimicked the PAH profile, downregulating MEF2C and LMOD1. AntagomiR-214 abrogated hypoxia-induced suppression of the contractile phenotype and its attendant proliferation. Anti-miR-214 also restored PAH-PASMCs to a contractile phenotype seen during vascular homeostasis. CONCLUSIONS: Our findings illustrate a key role for miR-214 in modulation of MEF2C-MYOCD-LMOD1 signaling and suggest that an antagonist of miR-214 could mitigate SMC phenotype changes and proliferation in vascular hyperproliferative disorders including PAH

Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases

Age-associated neurodegenerative disorders such as Alzheimer’s disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential

Ulnar dimelia variant: a case report

We report a case of ulnar dimelia, commonly called mirror hand, in a 2-month-old female child who had restriction of elbow flexion and forearm rotation. There was no facial or other internal organ malformation. Radiographs revealed seven triphalangeal digits with double ulnae (one following the other) and absent radius. To the best of the authors’ knowledge, this is the first report of this mirror hand deformity in which fingers are symmetrical while duplicated ulnae are not

Hepatic artery aneurysm repair: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hepatic artery aneurysms remain a clinically significant entity. Their incidence continues to rise slowly and mortality from spontaneous rupture is high. Repair is recommended in those aneurysms greater than 2 cm in diameter. It is not surprising that vascular comorbidities, such as ischaemic heart disease, are common in surgical patients, particularly those with arterial aneurysms such as these. The decision of when to operate on patients who require urgent surgery despite having recently suffered an acute coronary syndrome remains somewhat of a grey and controversial area. We discuss the role of delayed surgery and postoperative followup of this vascular problem.</p> <p>Case presentation</p> <p>A 58-year-old man was admitted with a 5.5 cm hepatic artery aneurysm. The aneurysm was asymptomatic and was an incidental finding as a result of an abdominal computed tomography scan to investigate an episode of haemoptysis (Figure <figr fid="F1">1</figr>). Three weeks prior to admission, the patient had suffered a large inferior myocardial infarction and was treated by thrombolysis and primary coronary angioplasty. Angiographic assessment revealed a large aneurysm of the common hepatic artery involving the origins of the hepatic, gastroduodenal, left and right gastric arteries and the splenic artery (Figures <figr fid="F2">2</figr> and <figr fid="F3">3</figr>). Endovascular treatment was not considered feasible and immediate surgery was too high-risk in the early post-infarction period. Therefore, surgery was delayed for 3 months when aneurysm repair with reconstruction of the hepatic artery was successfully performed. Graft patency was confirmed with the aid of an abdominal arterial duplex. Plasma levels of conventional liver function enzymes and of alpha-glutathione-<it>S</it>-transferase were within normal limits. This was used to assess the extent of any hepatocellular damage perioperatively. The patient made a good recovery and was well at his routine outpatient check-ups.</p> <p>Conclusion</p> <p>There is no significant difference in cardiac risk in patients who have undergone vascular surgery within 6 months of a myocardial infarction compared with those who have had the operation in the 6 to12 month time frame. Use of alpha-glutathione-<it>S</it>-transferase gives an indication of the immediate state of hepatic function and should be used in addition to traditional liver function tests to monitor hepatic function postoperatively.</p

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112