An observational study of patient characteristics associated with the mode of admission to acute stroke services in North East, England

Objective Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services. Study design and setting A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases. Results Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis. Conclusion Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations

Nutritional Status Has Marginal Influence on the Metabolism of Inorganic Arsenic in Pregnant Bangladeshi Women

BACKGROUND: The interindividual variation in metabolism of inorganic arsenic (iAs), involving methylation via one-carbon metabolism, has been well documented, but the reasons remain unclear. OBJECTIVES: In this population-based study we aimed to elucidate the effect of nutrition on As methylation among women in Matlab, Bangladesh, where people are chronically exposed to iAs via drinking water. METHODS: We studied effects of macronutrient status using body mass index (BMI) among 442 women in early pregnancy (gestational week 8), and effects of micronutrient status (plasma folate, vitamin B12, zinc, ferritin, and selenium) among 753 women at gestational week 14. Arsenic metabolites in urine were measured by HPLC combined with hydride generation inductively coupled plasma mass spectrometry. RESULTS: The median concentration of As in urine was 97 microg/L (range, 5-1,216 microg/L, adjusted by specific gravity). The average proportions of iAs, monomethylarsonic acid, and dimethylarsinic acid in urine in gestational week 8 were 15%, 11%, and 74%, respectively. Thus, the women had efficient As methylation in spite of being poorly nourished (one-third had BMIs < 18.5 kg/m2) and having elevated As exposure, both of which are known to decrease As methylation. The metabolism of iAs was only marginally influenced by micronutrient status, probably because women, especially in pregnancy and with low folate intake, have an efficient betaine-mediated remethylation of homocysteine, which is essential for an efficient As methylation. CONCLUSIONS: In spite of the high As exposure and prevalent malnutrition, overall As methylation in women in early pregnancy was remarkably efficient. The As exposure level had the greatest impact on As methylation among the studied factors

Enhanced Case Detection and Improved Diagnosis of PKDL in a Kala-azar-Endemic Area of Bangladesh

PKDL is a skin disorder which usually develops in 10–20% and about 60% of patients with visceral leishmaniasis (VL) after treatment respectively in the Indian subcontinent and Sudan. However, cases among people without prior VL have also been reported. Except skin lesion, PKDL patients are healthy and usually do not feel sick. However, persistence of a few PKDL cases is sufficient to initiate a new epidemic of anthroponotic VL. Thus, identifying and treating people with PKDL is a key strategy for the elimination of kala-azar. Diagnosis of PKDL relies upon clinical criteria and a serological test which is not specific for PKDL. The use of the existing laboratory diagnostic tools for confirmation of PKDL among PKDL suspects is unknown. In the Indian subcontinent, PKDL is not self-limited and needs to be treated with sodium stibogluconate injections for 4–6 months. No data are available relating to treatment compliance by patients, particularly in Bangladesh. The results of the present study showed that trained village volunteers were useful for identifying PKDL suspects, and diagnostic confirmation improved with the use of PCR. However, patients' adherence to prescribed treatment was poor

Radiographic knee osteoarthritis in ex-elite table tennis players

<p>Abstract</p> <p>Background</p> <p>Table tennis involves adoption of the semi-flexed knee and asymmetrical torsional trunk movements creating rotational torques on the knee joint which may predispose players to osteoarthritis (OA) of the knee. This study aims to compare radiographic signs of knee OA and associated functional levels in ex-elite male table tennis players and control subjects.</p> <p>Methods</p> <p>Study participants were 22 ex-elite male table tennis players (mean age 56.64 ± 5.17 years) with 10 years of involvement at the professional level and 22 non-athletic males (mean age 55.63 ± 4.08 years) recruited from the general population. A set of three radiographs taken from each knee were evaluated by an experienced radiologist using the Kellgren and Lawrence (KL) scale (0-4) to determine radiographic levels of OA severity. The intercondylar distance was taken as a measure of lower limb angulation. Participants also completed the pain, stiffness, and physical function categories of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) 3.1 questionnaire.</p> <p>Results</p> <p>The results showed 78.3% of the ex-elite table tennis players and 36.3% of controls had varying signs of radiographic knee OA with a significant difference in the prevalence levels of definite radiographic OA (KL scale > 2) found between the two groups (<it>P </it>≤ 0.001). Based on the WOMAC scores, 68.2% of the ex-elite table tennis players reported symptoms of knee pain compared with 27.3% of the controls (<it>p </it>= 0.02) though no significant differences were identified in the mean physical function or stiffness scores between the two groups. In terms of knee alignment, 73.7% of the ex-elite athletes and 32% of the control group had signs of altered lower limb alignment (genu varum) (<it>p </it>= 0.01). Statistical differences were found in subjects categorized as having radiographic signs of OA and altered lower limb alignment (<it>p </it>= 0.03).</p> <p>Conclusions</p> <p>Ex-elite table tennis players were found to have increased levels of radiological signs of OA in the knee joint though this did not transpire through to altered levels of physical disability or knee stiffness in these players when compared with subjects from the general population suggesting that function in these players is not severely impacted upon.</p

Comparison of care and outcomes for myocardial infarction by heart failure status between United Kingdom and Japan

Aims: Prognosis for ST-segment elevation myocardial infarction (STEMI) is worse when heart failure is present on admission. Understanding clinical practice in different health systems can identify areas for quality improvement initiatives to improve outcomes. In the absence of international comparison studies, we aimed to compare treatments and in-hospital outcomes of patients admitted with ST elevation myocardial infarction (STEMI) by heart failure status in two healthcare-wide cohorts. Methods and results: We used two nationwide databases to capture admissions with STEMI in the United Kingdom (Myocardial ischemia National Audit Project, MINAP) and Japan (Japanese Registry of All Cardiac and Vascular Diseases-Diagnostic Procedure Combination, JROAD-DPC) between 2012 and 2017. Participants were stratified using the HF Killip classification into three groups; Killip 1: no congestive heart failure, Killip 2–3: congestive heart failure, Killip 4: cardiogenic shock. We calculated crude rate and case mix standardized risk ratios (CSRR) for use of treatments and in-hospital death. Patients were younger in the United Kingdom (65.4 [13.6] vs. 69.1 [13.0] years) and more likely to have co-morbidities in the United Kingdom except for diabetes and hypertension. Japan had a higher percentage of heart failure and cardiogenic shock patients among STEMI during admission than that in the United Kingdom. Primary percutaneous coronary intervention (pPCI) rates were lower in the United Kingdom compared with Japan, especially for patients presenting with Killip 2–3 class heart failure (pPCI use in patients with Killip 1, 2–3, 4: Japan, 86.2%, 81.7%, 78.7%; United Kingdom, 79.6%, 58.2% and 79.9%). In contrast, beta-blocker use was consistently lower in Japan than in the United Kingdom (61.4% vs. 90.2%) across Killip classifications and length of hospital stay longer (17.0 [9.7] vs. 5.0 [7.4] days). The crude rate of in-hospital mortality increased with increasing Killip class group. Both the crude rate and CSRR was higher in the United Kingdom compared with Japan for Killip 2–3 (15.8% vs. 6.4%, CSRR 1.80 95% CI 1.73–1.87, P < 0.001), and similar for Killip 4 (36.9% vs. 36.3%, CSRR 1.11 95% CI 1.08–1.13, P < 0.001). Conclusions: Important differences in the care and outcomes for STEMI with heart failure exist between the United Kingdom and Japan. Specifically, in the United Kingdom, there was a lower rate of pPCI, and in Japan, fewer patients were prescribed beta blockers and hospital length of stay was longer. This international comparison can inform targeted quality improvement programmes to narrow the outcome gap between health systems

Dramatic Increases in Obesity and Overweight Prevalence and Body Mass Index Among Ethnic-Immigrant and Social Class Groups in the United States, 1976–2008

This study examined trends in US obesity and overweight prevalence and body mass index (BMI) among 30 immigrant groups, stratified by race/ethnicity and length of immigration, and among detailed education, occupation, and income/poverty groups from 1976 to 2008. Using 1976–2008 National Health Interview Surveys, differentials in obesity, overweight, and BMI, based on self-reported height and weight, were analyzed by using disparity indices, logistic, and linear regression. The obesity prevalence for the US population aged ≥18 tripled from 8.7% in 1976 to 27.4% in 2008. Overweight prevalence increased from 36.9% in 1976 to 62.0% in 2008. During 1991–2008, obesity prevalence for US-born adults increased from 13.9 to 28.7%, while prevalence for immigrants increased from 9.5 to 20.7%. While immigrants in each ethnic group and time period had lower obesity and overweight prevalence and BMI than the US-born, immigrants’ risk of obesity and overweight increased with increasing duration of residence. In 2003–2008, obesity prevalence ranged from 2.3% for recent Chinese immigrants to 31–39% for American Indians, US-born blacks, Mexicans, and Puerto Ricans, and long-term Mexican and Puerto Rican immigrants. Between 1976 and 2008, the obesity prevalence more than quadrupled for those with a college education or sales occupation. Although higher prevalence was observed for lower education, income, and occupation levels in each period, socioeconomic gradients in obesity and overweight decreased over time because of more rapid increases in prevalence among higher socioeconomic groups. Continued immigrant and socioeconomic disparities in prevalence will likely have substantial impacts on future obesity trends in the US

Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) can contribute to variable degrees of fitness and/or disease predisposition. Recent studies show that at least 1% of any given genome is copy number variable when compared to the human reference sequence assembly. Homozygous deletions (or CNV nulls) that are found in the normal population are of particular interest because they may serve to define non-essential genes in human biology.</p> <p>Results</p> <p>In a genomic screen investigating CNV in Autism Spectrum Disorders (ASDs) we detected a heterozygous deletion on chromosome 10p12.1, spanning the Patched-domain containing 3 (<it>PTCHD3</it>) gene, at a frequency of ~1.4% (6/427). This finding seemed interesting, given recent discoveries on the role of another Patched-domain containing gene (<it>PTCHD1</it>) in ASD. Screening of another 177 ASD probands yielded two additional heterozygous deletions bringing the frequency to 1.3% (8/604). The deletion was found at a frequency of ~0.73% (27/3,695) in combined control population from North America and Northern Europe predominately of European ancestry. Screening of the human genome diversity panel (HGDP-CEPH) covering worldwide populations yielded deletions in 7/1,043 unrelated individuals and those detected were confined to individuals of European/Mediterranean/Middle Eastern ancestry. Breakpoint mapping yielded an identical 102,624 bp deletion in all cases and controls tested, suggesting a common ancestral event. Interestingly, this CNV occurs at a break of synteny between humans and mouse. Considering all data, however, no significant association of these rare <it>PTCHD3 </it>deletions with ASD was observed. Notwithstanding, our RNA expression studies detected <it>PTCHD3 </it>in several tissues, and a novel shorter isoform for <it>PTCHD3 </it>was characterized. Expression in transfected COS-7 cells showed <it>PTCHD3 </it>isoforms colocalize with calnexin in the endoplasmic reticulum. The presence of a patched (Ptc) domain suggested a role for <it>PTCHD3 </it>in various biological processes mediated through the Hedgehog (Hh) signaling pathway. However, further investigation yielded one individual harboring a homozygous deletion (<it>PTCHD3 </it>null) without ASD or any other overt abnormal phenotype. Exon sequencing of <it>PTCHD3 </it>in other individuals with deletions revealed compound point mutations also resulting in a null state.</p> <p>Conclusion</p> <p>Our data suggests that <it>PTCHD3 </it>may be a non-essential gene in some humans and characterization of this novel CNV at 10p12.1 will facilitate population and disease studies.</p

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact