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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Department of Counseling and School Psychology, University of Massachusetts Boston, Boston, Massachusetts, USA.
Background: Recently, health screening recommendations have gone beyond screening for early-stage, asymptomatic disease to include "screening" for presently experienced health problems and symptoms using self-report questionnaires. We examined recommendations from three major national guideline organizations to determine the consistency of recommendations, identify sources of divergent recommendations, and determine if guideline organizations have identified any direct randomized controlled trial (RCT) evidence for the effectiveness of questionnaire-based screening.
Methods: We reviewed recommendation statements listed by the Canadian Task Force on Preventive Health Care (CTFPHC), the United Kingdom National Screening Committee (UKNSC), and the United States Preventive Services Task Force (USPSTF) as of 5 September 2016. Read More
Background: Pregnancy and pregnancy loss may be linked to cardiovascular disease (CVD). However, the evidence is still inconsistent, especially in East Asians, whose reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy, miscarriage, induced abortion, and stillbirth with CVD incidence among Chinese women. Read More
Hughes Hall, University of Cambridge, Cambridge, CB1 2EW, UK.
Mehdizah and colleagues recently described the prevalence of General Medical Council regulatory performance assessments by doctors' country of primary medical qualification. This article has caused anger within the UK-international medical community because it identifies graduates of certain countries with significantly raised prevalence.The present article comments on evidence from published Royal College of General Practitioners' data that support these conclusions. Read More
Background: The use of the point-of-care lateral flow lipoarabinomannan (LF-LAM) test may expedite tuberculosis (TB) diagnosis in HIV-positive patients. However, the test's clinical utility is poorly defined outside sub-Saharan Africa.
Methods: The study enrolled consecutive HIV-positive adults at a tertiary referral hospital in Yangon, Myanmar. Read More
Background: The criteria for defining severe malaria have evolved over the last 20 years. We aimed to assess the strength of association of death with features currently characterizing severe malaria through a systematic review and meta-analysis.
Method: Electronic databases (Medline, Embase, Cochrane Database of Systematic Reviews, Thomson Reuters Web of Knowledge) were searched to identify publications including African children with severe malaria. Read More
Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London, 6th Floor, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK.
Background: Clinicians are inaccurate at predicting survival. The 'Surprise Question' (SQ) is a screening tool that aims to identify people nearing the end of life. Potentially, its routine use could help identify patients who might benefit from palliative care services. Read More
Depression remains a debilitating condition with an uncertain aetiology. Recently, attention has been given to the renin-angiotensin system. In the central nervous system, angiotensin II may be important in multiple pathways related to neurodevelopment and regulation of the stress response. Read More
Background: There is evidence that social anxiety disorder (SAD) is a prevalent and disabling disorder. However, most of the available data on the epidemiology of this condition originate from high income countries in the West. The World Mental Health (WMH) Survey Initiative provides an opportunity to investigate the prevalence, course, impairment, socio-demographic correlates, comorbidity, and treatment of this condition across a range of high, middle, and low income countries in different geographic regions of the world, and to address the question of whether differences in SAD merely reflect differences in threshold for diagnosis. Read More
Background: Dementia and diabetes mellitus are common long-term conditions and co-exist in a large number of older people. People living with dementia (PLWD) may be less able to manage their diabetes, putting them at increased risk of complications such as hypoglycaemia. The aim of this review was to identify key mechanisms within different interventions that are likely to improve diabetes outcomes in PLWD. Read More
Background: Cognitive impairment of various kinds is common in older people admitted to hospital, but previous research has usually focused on single conditions in highly-selected groups and has rarely examined associations with outcomes. This study examined prevalence and outcomes of cognitive impairment in a large unselected cohort of people aged 65+ with an emergency medical admission.
Methods: Between January 1, 2012, and June 30, 2013, admissions to a single general hospital acute medical unit aged 65+ underwent a structured specialist nurse assessment (n = 10,014). Read More
Background: Antibiotic resistance is threatening to make gonorrhoea untreatable. Point-of-care (POC) tests that detect resistance promise individually tailored treatment, but might lead to more treatment and higher levels of resistance. We investigate the impact of POC tests on antibiotic-resistant gonorrhoea. Read More
Background: Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages. Read More
Background: Postoperative ischemia is a frequent phenomenon in patients with brain tumors and is associated with postoperative neurological deficits and impaired overall survival. Particularly in the field of cardiac and vascular surgery, the application of a brief ischemic stimulus not only in the target organ but also in remote tissues can prevent subsequent ischemic damage. We hypothesized that remote ischemic preconditioning (rIPC) in patients with brain tumors undergoing elective surgical resection reduces the incidence of postoperative ischemic tissue damage and its consequences. Read More
Background: Compassionate use is the use of unapproved drugs outside of clinical trials. So far, compassionate use regulations have been introduced in the US, Canada, many European countries, Australia and Brazil, and treatment on a compassionate use basis may be performed in Japan and China. However, there are important differences between relevant regulations in individual countries, particularly that approval by a research ethics committee (institutional review board) is a requirement for compassionate use in some countries (e. Read More
Division of Hematology Oncology, Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Background: Surrogate outcomes are not intrinsically beneficial to patients, but are designed to be easier and faster to measure than clinically meaningful outcomes. The use of surrogates as an endpoint in clinical trials and basis for regulatory approval is common, and frequently exceeds the guidance given by regulatory bodies.
Discussion: In this article, we demonstrate that the use of surrogates in oncology is widespread and increasing. Read More
Boston Children's Hospital, Boston, Massachusetts, USA.
Background: Adverse psychosocial exposures in early life, namely experiences such as child maltreatment, caregiver stress or depression, and domestic or community violence, have been associated in epidemiological studies with increased lifetime risk of adverse outcomes, including diabetes, heart disease, cancers, and psychiatric illnesses. Additional work has shed light on the potential molecular mechanisms by which early adversity becomes "biologically embedded" in altered physiology across body systems. This review surveys evidence on such mechanisms and calls on researchers, clinicians, policymakers, and other practitioners to act upon evidence. Read More
Background: Environmental and lifestyle changes, in addition to the ageing of populations, are generally believed to account for the rapid global increase in type 2 diabetes prevalence and incidence in recent decades.
Discussion: In this review, we present a comprehensive overview of factors contributing to diabetes risk, including aspects of diet quality and quantity, little physical activity, increased monitor viewing time or sitting in general, exposure to noise or fine dust, short or disturbed sleep, smoking, stress and depression, and a low socioeconomic status. In general, these factors promote an increase in body mass index. Read More
Background: The advent of rapid and inexpensive sequencing technology allows scientists to decipher heterogeneity within primary tumours, between primary and metastatic sites, and between metastases. Charting the evolutionary history of individual tumours has revealed drivers of tumour heterogeneity and highlighted its impact on therapeutic outcomes.
Discussion: Scientists are using improved sequencing technologies to characterise and address the challenge of tumour heterogeneity, which is a major cause of resistance to therapy and relapse. Read More
Background: Resistance and tolerance to Plasmodium falciparum can determine the progression of malaria disease. However, quantitative evidence of tolerance is still limited. We investigated variations in the adverse impact of P. Read More
Background: In patients with stage II colorectal cancer (CRC) the number of surgically retrieved lymph nodes (LNs) is associated with prognosis, resulting in a minimum of 10-12 retrieved LNs being recommended for this stage. Current guidelines do not provide a recommendation regarding LN yield in T1 CRC. Studies evaluating LN yield in T1 CRC suggest that such high LN yields are not feasible in this early stage, and a lower LN yield might be appropriate. Read More
Background: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Methods: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Read More
The damage to health caused by intimate partner violence demands effective responses from healthcare providers and healthcare systems worldwide. To date, most evidence for the few existing, effective interventions in use comes from high-income countries. Gupta et al. Read More
Background: Rigorous evaluations of health sector interventions addressing intimate partner violence (IPV) in low- and middle-income countries are lacking. We aimed to assess whether an enhanced nurse-delivered intervention would reduce IPV and improve levels of safety planning behaviors, use of community resources, reproductive coercion, and mental quality of life.
Methods: We randomized 42 public health clinics in Mexico City to treatment or control arms. Read More
Background: The United Nation's Sustainable Development Goals for 2030 include reducing premature mortality from non-communicable diseases (NCDs) by one third. To assess the feasibility of this goal in China, we projected premature mortality in 2030 of NCDs under different risk factor reduction scenarios.
Methods: We used China results from the Global Burden of Disease Study 2013 as empirical data for projections. Read More
Current trends in population ageing show that, in the near future, while more people will live longer, more will also die at any one time. Health systems, as well as individual practitioners, are only just becoming aware of the extent of this problem. Health systems will have to rapidly change practice to manage the number of people dying in the coming years, many with complex multimorbid conditions. Read More
Background: The World Health Organisation (WHO) recommends parasitological diagnosis of malaria before treatment, but use of malaria rapid diagnostic tests (mRDTs) by community health workers (CHWs) has not been fully tested within health services in south and central Asia. mRDTs could allow CHWs to diagnose malaria accurately, improving treatment of febrile illness.
Methods: A cluster randomised trial in community health services was undertaken in Afghanistan. Read More
Background: Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer.
Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Read More
Gout, the most prevalent inflammatory arthritis worldwide, is associated with cardiovascular and renal diseases, and is an independent predictor of premature death. The frequencies of obesity, chronic kidney disease (CKD), hypertension, type 2 diabetes, dyslipidaemias, cardiac diseases (including coronary heart disease, heart failure and atrial fibrillation), stroke and peripheral arterial disease have been repeatedly shown to be increased in gout. Therefore, the screening and care of these comorbidities as well as of cardiovascular risk factors are of outmost importance in patients with gout. Read More