Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants).

Home parenteral nutrition and employment in patients with intestinal failure: Factors associated with return to employment.

Background & Aims: Home parenteral nutrition (HPN) is provided to patients with intestinal failure (IF). HPN can however affect the patients' quality of life and ability to remain in employment. The aim of this study was to determine the effect of HPN on employment and factors associated with the likelihood of maintaining or returning to employment while on HPN.

Completeness in clerking: The surgical admissions proforma.

Background: The accessibility of surgical patient data is a key safety concern, and relies on efficient clerking and handovers. This project assessed whether the introduction of a surgical clerking proforma improved the recording of patient information in the surgical admissions unit (SAU) at Northwick Park Hospital.

Materials And Methods: Existing patient notes were assessed on content and ease of access, using two independent surveys conducted over a 5-day period.

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication.

Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study.

Background: Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain.

Objectives: Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF).

Methods: This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy.

Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study.

Background: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians.

Methods: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score--GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure.

Mild Cognitive Impairment in Rural Tanzania: Prevalence, Profile, and Outcomes at 4-Year Follow-up.

Objective: Mild cognitive impairment (MCI) is recognized as a high-risk condition for conversion to dementia, although data on outcomes of MCI in sub-Saharan Africa are scarce. We investigated outcomes of MCI over a 4-year period in Tanzania and considered risk factors for conversion to dementia.

Methods: In a longitudinal cohort study in the Hai district, Tanzania, patients with MCI were identified during a two-phase prevalence study carried out in 2010.

Frequency and determinants of intracranial atherosclerotic stroke in urban Pakistan.

Background: Intracranial atherosclerosis (ICAD) is a frequent underlying mechanism of ischemic stroke. There is little direct evidence on its frequency and determinants from regions of high prevalence. This study explores the conventional and socioeconomic risk factors of ICAD in a South Asian population.

Palliative care in people with idiopathic Parkinson's disease who die in hospital.

Background: The UK National Institute for Health and Clinical Excellence guidelines state that palliative care options for people with Parkinson's disease (PD) should be discussed.

Aims: To investigate whether palliative care guidelines are adhered to for people with PD who die in hospital.

Setting/participants: The medical notes of all people with a diagnosis of idiopathic PD who were living in two adjacent areas of northeast England and who died over a 3-year period were examined.

Hypercalcemia in a male-to-female transgender patient after body contouring injections: a case report.

Introduction: Body contouring injections by non-licensed providers are frequently sought out by a subset of the male-to-female transgender community. Although short-term side effects such as pulmonary embolism and injection site infection are well known, long-term consequences of such practices are less well studied.

Case Presentation: Here we describe the case of a 40-year-old African American male-to-female transgender patient who presented to our institution with hypercalcemia and acute renal failure secondary to body contouring injections with industrial strength silicone by non-licensed providers, a decade prior to her visit.

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci.

Stroke radiology and distinguishing characteristics of intracranial atherosclerotic disease in native South Asian Pakistanis.

Background: There are no descriptions of stroke mechanisms from intracranial atherosclerotic disease in native South Asian Pakistanis.

Methods: Men and women aged ≥ 18 years with acute stroke presenting to four tertiary care hospitals in Karachi, Pakistan were screened using magnetic resonance angiography/transcranial Doppler scans. Trial of ORG 10172 in Acute Stroke Treatment criteria were applied to identify strokes from intracranial atherosclerotic disease.

Russell body duodenitis: a histopathological and molecular approach to a rare clinical entity.

Russell bodies are pink eosinophilic accumulations within plasma cells. To date, two hypotheses have attempted to elucidate the biological events behind the formation of these bodies. One theory sustains that such bodies constitute cytoplasmic accumulation of immunoglobulin derivatives contained in the perinuclear cistern of the smooth endoplasmic reticulum because of an increased synthesis or altered secretion.

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry.

Genetic determinants of major blood lipids in Pakistanis compared with Europeans.

Background: Evidence is sparse about the genetic determinants of major lipids in Pakistanis.

Methods And Results: Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans.

Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans.

Objective: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry.

Methods And Results: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans.

The Karachi intracranial stenosis study (KISS) Protocol: an urban multicenter case-control investigation reporting the clinical, radiologic and biochemical associations of intracranial stenosis in Pakistan.

Background: Intracranial stenosis is the most common cause of stroke among Asians. It has a poor prognosis with a high rate of recurrence. No effective medical or surgical treatment modality has been developed for the treatment of stroke due to intracranial stenosis.

The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia.

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30-80 years.