Novel insights into the aetiology of granulomatosis with polyangiitis—a case–control study using the Clinical Practice Research Datalink

Objectives We aimed to provide insights into the aetiology of granulomatosis with polyangiitis (GPA), by conducting a large case–control study using a general population-based, prospectively collected database of healthcare records. Methods We compared all incident cases of GPA in the Clinical Practice Research Datalink 1990–2014, with up to 10 age-, sex- and general practice-matched controls. We identified potential risk factors, recorded numbers of cases and controls exposed to each, and calculated odds ratios (ORs) using conditional logistic regression. Our main analysis excluded data recorded during 1 year before diagnosis, to prevent early symptoms being mistaken for risk factors. Results We identified 757 people with GPA and matched 7546 controls. People with GPA were five times more likely to have a previous diagnosis of bronchiectasis (OR = 5.1, 95% CI: 2.7, 9.4; P 5 years prior to diagnosis. People with GPA were two to three times more likely than controls to have previous diagnoses of autoimmune diseases or chronic renal impairment, and these effects also remained stable >5 years prior to diagnosis. People with GPA were more likely to have a diagnosis of pulmonary fibrosis (OR = 5.7, 95% CI: 1.7, 19.5; P = 0.01) and sinus infections (OR = 2.7, 95% CI: 1.8, 4.2; P < 0.0001) recorded in the 3 years before diagnosis, but not before this. We also found former smoking, some medications and higher socio-economic status significantly, but less strongly, associated. Conclusion We found novel long-term associations between GPA and pre-existing bronchiectasis and autoimmune diseases

Abdominal obesity, an independent cardiovascular risk factor in Indian subcontinent: A clinico epidemiological evidence summary

Evidence is emerging that obesity-associated cardiovascular disorders (CVD) show variations across regions and ethnicities. However, it is unclear if there are distinctive patterns of abdominal obesity contributing to an increased CVD risk in South Asians. Also, potential underlying mechanistic pathways of such unique patterns are not comprehensively reported in South Asians. This review sets out to examine both. A comprehensive database search strategy was undertaken, namely, PubMed, Embase and Cochrane Library, applying specific search terms for potentially relevant published literature in English language. Grey literature, including scientific meeting abstracts, expert consultations, text books and government/non-government publications were also retrieved. South Asians have 3-5% higher body fat than whites, at any given body mass index. Additional distinctive features, such as South Asian phenotype, low adipokine production, lower lean body mass, ethno-specific socio-cultural and economic factors, were considered as potential contributors to an early age-onset of obesity-linked CVD risk in South Asians. Proven cost-effective anti-obesity strategies, including the development of ethno-specific clinical risk assessment tools, should be adopted early in the life-course to prevent premature CVD deaths and morbidity in South Asians

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

A Cost-Effectiveness Analysis Of A Potential Biosimilar As A Primary Prophylactic Therapy Against Chemotherapy Induced Febrile Neutropenia For Breast Cancer Patients

This presentation aims at constructing a decision analytic model with the help of TreeAge software package to estimate a cost-effective measure (ICER – Incremental cost effectiveness ratio) for a proposed biosimilar in the US against chemotherapy induced febrile neutropenia for breast cancer patients. This measure of cost-effectiveness will be compared to two currently marketed biologicals, Filgrastim and Pegfilgrastim. A sensitivity analysis along with a probabilistic sensitivity analysis will be performed to test for the robustness of the model. This research aims at estimating whether the biosimilar will be a cost saving drug, as a prophylactic therapy, when it comes into the American market compared to the two current biologicals. With the economic burden of chemotherapy induced neutropenia being quite significant, estimating how the cost-effectiveness equation changes with a new biosimilar in the market is the central theme of this research. The Affordable Care Act of 2010 and the recent presidential elections of 2012 have given a lot of impetus on containing healthcare costs and effective utilization of economic resources. Hence, this form of economic evaluation and decision analysis is a vital segment of research contributing to impacting outcomes research in a big way. Expected Results: Biosimilar Filgrastim is expected to show a superior savings compared to the original Filgrastim biological, while the ICER between the biosimilar and Pegfilgrastim will have to be estimated and published after the model is run. Keywords: biosimilar, cost-effectiveness, febrile neutropenia, ICER, Filgrastim, Pegfilgrasti

Visual Outcomes Following Optic Nerve Sheath Fenestration

"Idiopathic intracranial hypertension (or pseudotumor cerebri) is a condition of increased intracranial pressure in the absence of vascular lesion or intracranial mass1. Symptoms of IIH include headache, pulsatile tinnitus, transient visual obscurations, and diplopia. Untreated IIH can present with the long-term sequela of visual loss2. In approximately 10% of patients with untreated IIH, visual loss will progress to the point of meeting the legal criteria for blindness3. The objective of this study was to determine the safety of optic nerve sheath fenestration (ONSF) for the treatment of patients with intracranial hypertension in the immediate 6 month post-operative period and its efficacy in reducing optic disk edema.

Contrasting presentations of the same disease: A comparison of two cases of amyloidosis presenting with eyelid involvement

Purpose: Localized amyloidosis can affect numerous tissues throughout the body and can also affect a variety of peri-ocular tissues including the conjunctiva, extra-ocular muscles, peri-orbital soft tissue, and lacrimal gland. We report two cases of amyloidosis presenting with eyelid involvement. Observations: The first case represented a more subtle presentation of skin thickening with a pre-septal cellulitis, while the second case had a dramatic presentation of edema evolving into tissue dehiscence and spontaneous hemorrhage with ongoing angioedema and systemic coagulopathy. Conclusions and importance: The two cases of biopsy-proven orbital/peri-ocular amyloidosis demonstrate the different clinical presentations that may go from the subtle to dramatic, depending on which peri-ocular tissues are affected and to what degree. Standards for treatment of amyloidosis remain conservative initially with surgery or radiation recommended only for refractory cases, but additional therapies are under investigation. Clinicians should have high clinical suspicion for amyloidosis with findings such as skin thickening or significant periorbital edema and should always consider tissue biopsy and further workup for amyloidosis if the findings worsen or do not resolve with treatment of more common conditions such as cellulitis