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    The potential impact of Brexit and immigration policies on the GP workforce in England: a cross-sectional observational study of GP qualification region and the characteristics of the areas and population they served in September 2016.
    BMC Med 2017 Nov 16;15(1):191. Epub 2017 Nov 16.
    NIHR School for Primary Care Research, University of Manchester, Manchester, UK.
    Background: The UK is dependent on international doctors, with a greater proportion of non-UK qualified doctors working in its universal health care system than in any other European country, except Ireland and Norway. The terms of the UK exit from the European Union can reduce the ability of European Economic Area (EEA) qualified doctors to work in the UK, while new visa requirements will significantly restrict the influx of non-EEA doctors. We aimed to explore the implications of policy restrictions on immigration, by regionally and spatially describing the characteristics of general practitioners (GPs) by region of medical qualification and the characteristics of the populations they serve. Read More

    DIET@NET: Best Practice Guidelines for dietary assessment in health research.
    BMC Med 2017 Nov 15;15(1):202. Epub 2017 Nov 15.
    MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO16 6YD, UK.
    Background: Dietary assessment is complex, and strategies to select the most appropriate dietary assessment tool (DAT) in epidemiological research are needed. The DIETary Assessment Tool NETwork (DIET@NET) aimed to establish expert consensus on Best Practice Guidelines (BPGs) for dietary assessment using self-report.

    Methods: The BPGs were developed using the Delphi technique. Read More

    An exploration of mortality risk factors in non-severe pneumonia in children using clinical data from Kenya.
    BMC Med 2017 Nov 13;15(1):201. Epub 2017 Nov 13.
    KEMRI - Wellcome Trust Research Programme, Nairobi, Kenya.
    Background: Childhood pneumonia is the leading infectious cause of mortality in children younger than 5 years old. Recent updates to World Health Organization pneumonia guidelines recommend outpatient care for a population of children previously classified as high risk. This revision has been challenged by policymakers in Africa, where mortality related to pneumonia is higher than in other regions and often complicated by comorbidities. Read More

    Advances and challenges in cirrhosis and portal hypertension.
    BMC Med 2017 Nov 10;15(1):200. Epub 2017 Nov 10.
    Swiss Liver Center, Hepatology, University Clinic for Visceral Surgery and Medicine (UVCM), Inselspital, University of Bern, MEM F807, Murtenstrasse 35, CH, 3010, Berne, Switzerland.
    Background: Liver cirrhosis is the fourth cause of death in adults in Western countries, with complications of portal hypertension being responsible for most casualties. In order to reduce mortality, development of accurate diagnostic methods for early diagnosis, effective etiologic treatment, improved pharmacological therapy for portal hypertension, and effective therapies for end-stage liver failure are required.

    Discussion: Early detection of cirrhosis and portal hypertension is now possible using simple non-invasive methods, leading to the advancement of individualized risk stratification in clinical practice. Read More

    Fluctuations in the incidence of type 1 diabetes in the United States from 2001 to 2015: a longitudinal study.
    BMC Med 2017 Nov 8;15(1):199. Epub 2017 Nov 8.
    Institute of Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan, USA.
    Background: While the United States has the largest number of children with type 1 diabetes mellitus, less is known regarding adult-onset disease. The present study utilizes nationwide data to compare the incidence of type 1 diabetes in youth (0-19 years) to that of adults (20-64 years).

    Methods: In this longitudinal study, the Clinformatics® Data Mart Database was used, which contains information from 61 million commercially insured Americans (years 2001-2015). Read More

    Group-based developmental BMI trajectories, polycystic ovary syndrome, and gestational diabetes: a community-based longitudinal study.
    BMC Med 2017 Nov 6;15(1):195. Epub 2017 Nov 6.
    Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, 3168, Australia.
    Background: Obesity is common in young women, increasing insulin resistance (IR) and worsening pregnancy complications, including gestational diabetes (GDM). Women with polycystic ovary syndrome (PCOS) are commonly obese, which aggravates the severity of PCOS clinical expression. Relationships between these common insulin-resistant conditions, however, remain unclear. Read More

    Prediction of uncomplicated pregnancies in obese women: a prospective multicentre study.
    BMC Med 2017 Nov 3;15(1):194. Epub 2017 Nov 3.
    Department of Women and Children's Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, SE1 7EH, UK.
    Background: All obese pregnant women are considered at equal high risk with respect to complications in pregnancy and birth, and are commonly managed through resource-intensive care pathways. However, the identification of maternal characteristics associated with normal pregnancy outcomes could assist in the management of these pregnancies. The present study aims to identify the factors associated with uncomplicated pregnancy and birth in obese women, and to assess their predictive performance. Read More

    Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area.
    BMC Med 2017 Nov 1;15(1):188. Epub 2017 Nov 1.
    School of Biological and Health Systems Engineering, Virginia G. Piper Biodesign Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, 85287, USA.
    Background: HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. We therefore assessed the diagnostic performance of a novel assay that directly quantitates serum levels of the Mycobacterium tuberculosis (Mtb) virulence factor 10-kDa culture filtrate protein (CFP-10) to overcome limitations associated with detecting Mtb bacilli in sputum or tissue biopsies.

    Methods: This study analyzed HIV-positive adults enrolled in a large, population-based TB screening and surveillance project, the Houston Tuberculosis Initiative, between October 1995 and September 2004, and assigned case designations using standardized criteria. Read More

    Comparative efficacy and safety of second-line treatments for advanced non-small cell lung cancer with wild-type or unknown status for epidermal growth factor receptor: a systematic review and network meta-analysis.
    BMC Med 2017 Oct 30;15(1):193. Epub 2017 Oct 30.
    Centre de Recherche Epidémiologie et Statistique Paris Sorbonne Cité, INSERM U1153, Paris, France.
    Background: Docetaxel, pemetrexed, erlotinib, and gefitinib are recommended as second-line treatment for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR). However, the number of published randomized clinical trials (RCTs) on this topic is increasing. Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis. Read More

    Spot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosis.
    BMC Med 2017 Oct 27;15(1):192. Epub 2017 Oct 27.
    School of Medicine, Medical and Biological Sciences, University of St Andrews, North Haugh, St Andrews, KY16 9TF, UK.
    Background: The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. Read More

    Is it them or is it us? Unravelling ethnic disparities in undergraduate clinical performance.
    BMC Med 2017 Oct 25;15(1):190. Epub 2017 Oct 25.
    Institute of Medical Education Research Rotterdam, Erasmus MC, University Medical Centre Rotterdam, Room AE-241, PO Box 2040, 3000 CA, Rotterdam, Netherlands.
    Given our increasingly diverse societies, there is an urgent need for research into the causes of persistent ethnic disparities in undergraduate clinical performance. It is argued that causes for underperformance can be identified from two perspectives, namely that of the students ('them') and that of the academic environment ('us'). Taking the 'us' perspective, Yeates et al. Read More

    A randomised trial of the influence of racial stereotype bias on examiners' scores, feedback and recollections in undergraduate clinical exams.
    BMC Med 2017 Oct 25;15(1):179. Epub 2017 Oct 25.
    Centre for Health Education Scholarship, Faculty of Health, University of British Columbia, Vancouver, Canada.
    Background: Asian medical students and doctors receive lower scores on average than their white counterparts in examinations in the UK and internationally (a phenomenon known as "differential attainment"). This could be due to examiner bias or to social, psychological or cultural influences on learning or performance. We investigated whether students' scores or feedback show influence of ethnicity-related bias; whether examiners unconsciously bring to mind (activate) stereotypes when judging Asian students' performance; whether activation depends on the stereotypicality of students' performances; and whether stereotypes influence examiner memories of performances. Read More

    Faecal immunochemical tests (FIT) can help to rule out colorectal cancer in patients presenting in primary care with lower abdominal symptoms: a systematic review conducted to inform new NICE DG30 diagnostic guidance.
    BMC Med 2017 Oct 24;15(1):189. Epub 2017 Oct 24.
    University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
    Background: This study has attempted to assess the effectiveness of quantitative faecal immunochemical tests (FIT) for triage of people presenting with lower abdominal symptoms, where a referral to secondary care for investigation of suspected colorectal cancer (CRC) is being considered, particularly when the 2-week criteria are not met.

    Methods: We conducted a systematic review following published guidelines for systematic reviews of diagnostic tests. Twenty-one resources were searched up until March 2016. Read More

    Voluntary stopping of eating and drinking: is medical support ethically justified?
    BMC Med 2017 Oct 20;15(1):186. Epub 2017 Oct 20.
    Palliative Care Service, Technical University Munich, Munich, Germany.
    Background: Physician-assisted dying has been the subject of extensive discussion and legislative activity both in Europe and North America. In this context, dying by voluntary stopping of eating and drinking (VSED) is often proposed, and practiced, as an alternative method of self-determined dying, with medical support for VSED being regarded as ethically and legally justified.

    Argument: In our opinion, this view is flawed. Read More

    State of inequality in malaria intervention coverage in sub-Saharan African countries.
    BMC Med 2017 Oct 18;15(1):185. Epub 2017 Oct 18.
    Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051, Basel, Switzerland.
    Background: Scale-up of malaria interventions over the last decade have yielded a significant reduction in malaria transmission and disease burden in sub-Saharan Africa. We estimated economic gradients in the distribution of these efforts and of their impacts within and across endemic countries.

    Methods: Using Demographic and Health Surveys we computed equity metrics to characterize the distribution of malaria interventions in 30 endemic countries proxying economic position with an asset-wealth index. Read More

    Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease.
    BMC Med 2017 Oct 16;15(1):184. Epub 2017 Oct 16.
    Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan, People's Republic of China.
    Background: One-third of inflammatory bowel disease (IBD) patients show no response to infliximab (IFX) induction therapy, and approximately half of patients responding become unresponsive over time. Thus, identification of potential treatment response biomarkers are of great clinical significance. This study employs spectroscopy-based metabolic profiling of serum from patients with IBD treated with IFX and healthy subjects (1) to substantiate the use of spectroscopy as a semi-invasive diagnostic tool, (2) to identify potential biomarkers of treatment response and (3) to characterise the metabolic changes during management of patients with tumour necrosis factor-α inhibitors. Read More

    Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria.
    BMC Med 2017 Oct 13;15(1):183. Epub 2017 Oct 13.
    Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University, 1044 W Walnut St R4 402D, Indianapolis, Indiana, USA.
    Background: Expression of group A and the A-like subset of group B Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying the role of distinct PfEMP1 variants on malaria disease severity challenging. The application of retinopathy in the recent years has provided a further method to clinically evaluate children with cerebral malaria (CM). Read More

    Spatial model for risk prediction and sub-national prioritization to aid poliovirus eradication in Pakistan.
    BMC Med 2017 Oct 11;15(1):180. Epub 2017 Oct 11.
    Institute for Disease Modeling, 3150 138th Ave SE, Bellevue, WA, 98005, USA.
    Background: Pakistan is one of only three countries where poliovirus circulation remains endemic. For the Pakistan Polio Eradication Program, identifying high risk districts is essential to target interventions and allocate limited resources.

    Methods: Using a hierarchical Bayesian framework we developed a spatial Poisson hurdle model to jointly model the probability of one or more paralytic polio cases, and the number of cases that would be detected in the event of an outbreak. Read More

    A randomised, double-blind clinical phase II trial of the efficacy, safety, tolerability and pharmacokinetics of a single dose combination treatment with artefenomel and piperaquine in adults and children with uncomplicated Plasmodium falciparum malaria.
    BMC Med 2017 Oct 9;15(1):181. Epub 2017 Oct 9.
    Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
    Background: The clinical development of a single encounter treatment for uncomplicated malaria has the potential to significantly improve the effectiveness of antimalarials. Exploratory data suggested that the combination of artefenomel and piperaquine phosphate (PQP) has the potential to achieve satisfactory cure rates as a single dose therapy. The primary objective of the study was to determine whether a single dose of artefenomel (800 mg) plus PQP in ascending doses is an efficacious treatment for uncomplicated Plasmodium falciparum malaria in the 'target' population of children ≤ 5 years of age in Africa as well as Asian patients of all ages. Read More

    The cost determinants of routine infant immunization services: a meta-regression analysis of six country studies.
    BMC Med 2017 Oct 6;15(1):178. Epub 2017 Oct 6.
    Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
    Background: Evidence on immunization costs is a critical input for cost-effectiveness analysis and budgeting, and can describe variation in site-level efficiency. The Expanded Program on Immunization Costing and Financing (EPIC) Project represents the largest investigation of immunization delivery costs, collecting empirical data on routine infant immunization in Benin, Ghana, Honduras, Moldova, Uganda, and Zambia.

    Methods: We developed a pooled dataset from individual EPIC country studies (316 sites). Read More

    The risk of type 2 oral polio vaccine use in post-cessation outbreak response.
    BMC Med 2017 Oct 4;15(1):175. Epub 2017 Oct 4.
    Institute for Disease Modeling, Bellevue, WA, USA.
    Background: Wild type 2 poliovirus was last observed in 1999. The Sabin-strain oral polio vaccine type 2 (OPV2) was critical to eradication, but it is known to revert to a neurovirulent phenotype, causing vaccine-associated paralytic poliomyelitis. OPV2 is also transmissible and can establish circulating lineages, called circulating vaccine-derived polioviruses (cVDPVs), which can also cause paralytic outbreaks. Read More

    Can learning health systems help organisations deliver personalised care?
    BMC Med 2017 Oct 2;15(1):177. Epub 2017 Oct 2.
    Krefting Research Centre, Department of Internal Medicine, University of Gothenburg, Gothenburg, Sweden.
    There is increasing international policy and clinical interest in developing learning health systems and delivering precision medicine, which it is hoped will help reduce variation in the quality and safety of care, improve efficiency, and lead to increasing the personalisation of healthcare. Although reliant on similar policies, informatics tools, and data science and implementation research capabilities, these two major initiatives have thus far largely progressed in parallel. In this opinion piece, we argue that they should be considered as complementary, synergistic initiatives whereby the creation of learning health systems infrastructure can support and catalyse the delivery of precision medicine that maximises the benefits and minimises the risks associated with treatments for individual patients. Read More

    Towards new recommendations to reduce the burden of alcohol-induced hypertension in the European Union.
    BMC Med 2017 Sep 28;15(1):173. Epub 2017 Sep 28.
    Drugs Intervention Group, semFYC, Ibiza Primary Health Care Center, Madrid, Spain.
    Background: Hazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets. Read More

    Continental-scale, data-driven predictive assessment of eliminating the vector-borne disease, lymphatic filariasis, in sub-Saharan Africa by 2020.
    BMC Med 2017 Sep 27;15(1):176. Epub 2017 Sep 27.
    Center for Research Computing, University of Notre Dame, Notre Dame, IN, 46556, USA.
    Background: There are growing demands for predicting the prospects of achieving the global elimination of neglected tropical diseases as a result of the institution of large-scale nation-wide intervention programs by the WHO-set target year of 2020. Such predictions will be uncertain due to the impacts that spatial heterogeneity and scaling effects will have on parasite transmission processes, which will introduce significant aggregation errors into any attempt aiming to predict the outcomes of interventions at the broader spatial levels relevant to policy making. We describe a modeling platform that addresses this problem of upscaling from local settings to facilitate predictions at regional levels by the discovery and use of locality-specific transmission models, and we illustrate the utility of using this approach to evaluate the prospects for eliminating the vector-borne disease, lymphatic filariasis (LF), in sub-Saharan Africa by the WHO target year of 2020 using currently applied or newly proposed intervention strategies. Read More

    Is Graves' disease a primary immunodeficiency? New immunological perspectives on an endocrine disease.
    BMC Med 2017 Sep 25;15(1):174. Epub 2017 Sep 25.
    Medical University Department, Clinic for Endocrinology, Diabetes & Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
    Background: Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research.

    Main Text: Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. Read More

    Lifestyle precision medicine: the next generation in type 2 diabetes prevention?
    BMC Med 2017 Sep 22;15(1):171. Epub 2017 Sep 22.
    Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital, SE-205 02, Malmö, Sweden.
    The driving force behind the current global type 2 diabetes epidemic is insulin resistance in overweight and obese individuals. Dietary factors, physical inactivity, and sedentary behaviors are the major modifiable risk factors for obesity. Nevertheless, many overweight/obese people do not develop diabetes and lifestyle interventions focused on weight loss and diabetes prevention are often ineffective. Read More

    A 25-gene classifier predicts overall survival in resectable pancreatic cancer.
    BMC Med 2017 Sep 20;15(1):170. Epub 2017 Sep 20.
    Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm UMR1068, CNRS UMR725, Aix-Marseille Université, Marseille, France.
    Background: Pancreatic carcinoma is one of the most lethal human cancers. In patients with resectable tumors, surgery followed by adjuvant chemotherapy is the only curative treatment. However, the 5-year survival is 20%. Read More

    Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis.
    BMC Med 2017 Sep 18;15(1):172. Epub 2017 Sep 18.
    4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 1 Rimini Street, 124 62, Athens, Greece.
    Background: A subanalysis of a randomized clinical trial indicated sepsis survival benefit from interleukin (IL)-1 blockade in patients with features of the macrophage activation-like syndrome (MALS). This study aimed to investigate the frequency of MALS and to develop a biomarker of diagnosis and prognosis.

    Methods: Patients with infections and systemic inflammatory response syndrome were assigned to one test cohort (n = 3417) and a validation cohort (n = 1704). Read More

    Borrelia infection and risk of celiac disease.
    BMC Med 2017 Sep 15;15(1):169. Epub 2017 Sep 15.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Background: Environmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease. Read More

    Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial.
    BMC Med 2017 Sep 13;15(1):168. Epub 2017 Sep 13.
    Department of Medical Microbiology, Radboud University Medical Center, Geert Grooteplein 28, Microbiology 268, 6500 HB, Nijmegen, The Netherlands.
    Background: A highly efficacious vaccine is needed for malaria control and eradication. Immunization with Plasmodium falciparum NF54 parasites under chemoprophylaxis (chemoprophylaxis and sporozoite (CPS)-immunization) induces the most efficient long-lasting protection against a homologous parasite. However, parasite genetic diversity is a major hurdle for protection against heterologous strains. Read More

    Core competencies for scientific editors of biomedical journals: consensus statement.
    BMC Med 2017 Sep 11;15(1):167. Epub 2017 Sep 11.
    Chinese Medical Journal, Beijing, China.
    Background: Scientific editors are responsible for deciding which articles to publish in their journals. However, we have not found documentation of their required knowledge, skills, and characteristics, or the existence of any formal core competencies for this role.

    Methods: We describe the development of a minimum set of core competencies for scientific editors of biomedical journals. Read More

    Cost-effectiveness analysis of quadrivalent seasonal influenza vaccines in England.
    BMC Med 2017 Sep 8;15(1):166. Epub 2017 Sep 8.
    Respiratory Diseases Department, Public Health England, 61 Colindale Avenue, London, NW9 5EQ, UK.
    Background: As part of the national seasonal influenza vaccination programme in England and Wales, children receive a quadrivalent vaccine offering protection against two influenza A strains and two influenza B strains. Healthy children receive a quadrivalent live attenuated influenza vaccine (QLAIV), whilst children with contraindications receive the quadrivalent inactivated influenza vaccine (QIIV). Individuals aged younger than 65 years in the clinical risk populations and elderly individuals aged 65+ years receive either a trivalent inactivated influenza vaccine (TIIV) offering protection from two A strains and one B strain or the QIIV at the choice of their general practitioner. Read More

    A 13-gene expression-based radioresistance score highlights the heterogeneity in the response to radiation therapy across HPV-negative HNSCC molecular subtypes.
    BMC Med 2017 Sep 1;15(1):165. Epub 2017 Sep 1.
    Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, Lyon, F-69008, France.
    Background: Radiotherapy for head and neck squamous cell carcinomas (HNSCC) is associated with a substantial morbidity and inconsistent efficacy. Human papillomavirus (HPV)-positive status is recognized as a marker of increased radiosensitivity. Our goal was to identify molecular markers associated with benefit to radiotherapy in patients with HPV-negative disease. Read More

    Reduced growth velocity across the third trimester is associated with placental insufficiency in fetuses born at a normal birthweight: a prospective cohort study.
    BMC Med 2017 Aug 31;15(1):164. Epub 2017 Aug 31.
    Mercy Perinatal, Mercy Hospital for Women, Melbourne, Australia.
    Background: While being small-for-gestational-age due to placental insufficiency is a major risk factor for stillbirth, 50% of stillbirths occur in appropriate-for-gestational-age (AGA, > 10th centile) fetuses. AGA fetuses are plausibly also at risk of stillbirth if placental insufficiency is present. Such fetuses may be expected to demonstrate declining growth trajectory across pregnancy, although they do not fall below the 10th centile before birth. Read More

    A pragmatic lifestyle modification programme reduces the incidence of predictors of cardio-metabolic disease and dysglycaemia in a young healthy urban South Asian population: a randomised controlled trial.
    BMC Med 2017 Aug 30;15(1):146. Epub 2017 Aug 30.
    Cardiovascular Division, Faculty of Life Science & Medicine, King's College London, London, UK.
    Background: There is an increasing incidence of type 2 diabetes mellitus (T2DM) in young urban South-Asians. We tested the effect of a pragmatic trimonthly lifestyle modification (LSM) programme (P-LSM) versus a less-intensive 12-monthly control LSM (C-LSM) intervention on a primary composite endpoint of predictors of cardio-metabolic disease (new onset T2DM, hypertension, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and markers of cardio-renal disease) in participants aged 5-40 years with risk factors for T2DM.

    Methods: This was a randomised controlled trial performed at the National Diabetes Centre, Sri-Lanka. Read More

    Gestational diabetes mellitus-right person, right treatment, right time?
    BMC Med 2017 Aug 28;15(1):163. Epub 2017 Aug 28.
    School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK.
    Background: Personalised treatment that is uniquely tailored to an individual's phenotype has become a key goal of clinical and pharmaceutical development across many, particularly chronic, diseases. For type 2 diabetes, the importance of the underlying clinical heterogeneity of the condition is emphasised and a range of treatments are now available, with personalised approaches being developed. While a close connection between risk factors for type 2 diabetes and gestational diabetes has long been acknowledged, stratification of screening, treatment and obstetric intervention remains in its infancy. Read More

    Trade-off between benefits, harms and economic efficiency of low-dose CT lung cancer screening: a microsimulation analysis of nodule management strategies in a population-based setting.
    BMC Med 2017 Aug 25;15(1):162. Epub 2017 Aug 25.
    Center for Health Economics Research Hannover (CHERH), Leibniz University of Hannover, Otto-Brenner-Str.1, 30159, Hannover, Germany.
    Background: In lung cancer screening, a nodule management protocol describes nodule assessment and thresholds for nodule size and growth rate to identify patients who require immediate diagnostic evaluation or additional imaging exams. The Netherlands-Leuvens Screening Trial and the National Lung Screening Trial used different selection criteria and nodule management protocols. Several modelling studies have reported variations in screening outcomes and cost-effectiveness across selection criteria and screening intervals; however, the effect of variations in the nodule management protocol remains uncertain. Read More

    The contribution of risk factors to socioeconomic inequalities in multimorbidity across the lifecourse: a longitudinal analysis of the Twenty-07 cohort.
    BMC Med 2017 Aug 24;15(1):152. Epub 2017 Aug 24.
    Department of General Practice & Primary Care, University of Glasgow, 1 Horselethill Road, Glasgow, G12 8UX, Scotland.
    Background: Multimorbidity is a major challenge to health systems globally and disproportionately affects socioeconomically disadvantaged populations. We examined socioeconomic inequalities in developing multimorbidity across the lifecourse and investigated the contribution of five behaviour-related risk factors.

    Methods: The Twenty-07 study recruited participants aged approximately 15, 35, and 55 years in 1987 and followed them up over 20 years. Read More

    Association of bariatric surgery with risk of acute care use for hypertension-related disease in obese adults: population-based self-controlled case series study.
    BMC Med 2017 Aug 23;15(1):161. Epub 2017 Aug 23.
    Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
    Background: Hypertension carries a large societal burden. Obesity is known as a risk factor for hypertension. However, little is known as to whether weight loss interventions reduce the risk of hypertension-related adverse events, such as acute care use (emergency department [ED] visit and/or unplanned hospitalization). Read More

    Highlights in soft tissue sarcomas and gastrointestinal stromal tumours (GIST) trials reported at ASCO 2017 Annual Meeting.
    BMC Med 2017 Aug 22;15(1):160. Epub 2017 Aug 22.
    Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy.
    Herein, we summarise the results of the most relevant studies presented at the 2017 ASCO Annual Meeting in the field of soft tissue sarcomas (STSs) and gastrointestinal stromal tumours (GISTs). Innovations on the management of localised disease, highlights from the different experiences in the metastatic setting and large studies on rare histologies will be included. Special attention will be paid to results on immunotherapy, antiangiogenics use in histology with limited sensitivity to standard chemotherapy and new compounds. Read More

    The impact of repeated vaccination on influenza vaccine effectiveness: a systematic review and meta-analysis.
    BMC Med 2017 Aug 21;15(1):159. Epub 2017 Aug 21.
    Public Health Ontario, 480 University Avenue Suite 300, Toronto, Ontario, M5G 1V2, Canada.
    Background: Conflicting results regarding the impact of repeated vaccination on influenza vaccine effectiveness (VE) may cause confusion regarding the benefits of receiving the current season's vaccine.

    Methods: We systematically searched MEDLINE, Embase, PubMed, and Cumulative Index to Nursing and Allied Health Literature from database inception to August 17, 2016, for observational studies published in English that reported VE against laboratory-confirmed influenza for four vaccination groups, namely current season only, prior season only, both seasons, and neither season. We pooled differences in VE (∆VE) between vaccination groups by influenza season and type/subtype using a random effects model. Read More

    What makes gouty inflammation so variable?
    BMC Med 2017 Aug 18;15(1):158. Epub 2017 Aug 18.
    VA San Diego Healthcare System, 111K, 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.
    Acute gout arthritis flares contribute dominantly to gout-specific impaired health-related quality of life, representing a progressively increasing public health problem. Flares can be complex and expensive to treat, partly due to the frequent comorbidities. Unmet needs in gout management are more pressing given the markedly increasing gout flare hospital admission rates. Read More

    Circulating tumor DNA for personalized lung cancer monitoring.
    BMC Med 2017 Aug 17;15(1):157. Epub 2017 Aug 17.
    Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 60 Murray St. Box 32, Floor 6, Rm L6-201, Toronto, ON, MST 3L9, Canada.
    Advances in deep sequencing technology have led to developments in personalized medicine. Here, we describe the implications of a recent investigation that sequenced ctDNA from the plasma of non-small cell lung cancer patients to develop personalized ctDNA tests. These 'liquid biopsies' have shown promise in monitoring tumor growth and response to treatment, providing a timely overview of mutations present in the tumor. Read More

    Ibrutinib continues to influence the therapeutic landscape of chronic lymphocytic leukemia: new data presented at ASCO 2017.
    BMC Med 2017 Aug 16;15(1):156. Epub 2017 Aug 16.
    Department Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, Viale Pio X, 88100, Catanzaro, Italy.
    According to data presented at the 2017 American Society of Oncology (ASCO) Annual Meeting, with more than 4 years of follow-up, ibrutinib continues to provide clinical utility in chronic lymphocytic leukemia (CLL). However, treatment of CLL patients with high-risk cytogenetics features remains a challenge and the outcome of these hard-to-treat patients is dismal. At the 2017 ASCO Meeting, results of the GENUINE phase III trial showed that, by adding ublituximab, a glycoengineered, anti-CD20 type 1 monoclonal antibody, to ibrutinib, the overall response rate (ORR), complete response rate (CRR), and minimal residual disease (MRD) negativity may be improved in high-risk CLL patients. Read More

    Intervention Now to Eliminate Repeat Unintended Pregnancy in Teenagers (INTERUPT): a systematic review of intervention effectiveness and cost-effectiveness, and qualitative and realist synthesis of implementation factors and user engagement.
    BMC Med 2017 Aug 15;15(1):155. Epub 2017 Aug 15.
    Whitaker Research Ltd., Bangor, UK.
    Background: Unintended repeat conceptions can result in emotional, psychological and educational harm to young women, often with enduring implications for their life chances. This study aimed to identify which young women are at the greatest risk of repeat unintended pregnancies; which interventions are effective and cost-effective; and what are the barriers to and facilitators for the uptake of these interventions.

    Methods: We conducted a mixed-methods systematic review which included meta-analysis, framework synthesis and application of realist principles, with stakeholder input and service user feedback to address this. Read More

    Gestational hypertensive disorders and retinal microvasculature: the Generation R Study.
    BMC Med 2017 Aug 14;15(1):153. Epub 2017 Aug 14.
    Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
    Background: Changes in the microvasculature associated with pre-eclampsia and gestational hypertension have been proposed as a potential pathway in the development of cardiovascular disease. We examined whether gestational hypertensive disorders, such as pre-eclampsia and gestational hypertension, are related to the maternal retinal microvasculature status after pregnancy.

    Methods: This study is part of an ongoing population-based prospective cohort study. Read More

    Risk and predictors of psoriasis in patients with breast cancer: a Swedish population-based cohort study.
    BMC Med 2017 Aug 11;15(1):154. Epub 2017 Aug 11.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Väg 12A, 171 77, Stockholm, Sweden.
    Background: The risk of psoriasis in patients with breast cancer is largely unknown, as available evidence is limited to case findings. We systematically examined the incidence and risk factors of psoriasis in patients with breast cancer.

    Methods: A Swedish nationwide cohort of 56,235 breast cancer patients (2001-2012) was compared to 280,854 matched reference individuals from the general population to estimate the incidence and hazard ratio (HR) of new-onset psoriasis. Read More

    Characterizing measles transmission in India: a dynamic modeling study using verbal autopsy data.
    BMC Med 2017 Aug 10;15(1):151. Epub 2017 Aug 10.
    Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
    Background: Decreasing trends in measles mortality have been reported in recent years. However, such estimates of measles mortality have depended heavily on assumed regional measles case fatality risks (CFRs) and made little use of mortality data from low- and middle-income countries in general and India, the country with the highest measles burden globally, in particular.

    Methods: We constructed a dynamic model of measles transmission in India with parameters that were empirically inferred using spectral analysis from a time series of measles mortality extracted from the Million Death Study, an ongoing longitudinal study recording deaths across 2. Read More

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