Effects of Low-Dose Glucocorticoid Prophylaxis on Chronic Graft-versus-Host Disease and Graft-versus-Host Disease–Free,Relapse-Free Survival after Haploidentical Transplantation: Long-Term Follow-Up of a Controlled,Randomized Open-Label Trial

This long-term follow-up study evaluated the effects of corticosteroid prophylaxis on graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low risk (n?=?83, group A) or high risk; patients at high risk were randomly assigned to receive (n?=?72, group B) or not receive (n?=?73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, nonrelapse mortality, leukemia-free survival, overall survival, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in all cases. Compared with the patients in group C, the cases in group B experienced a lower cumulative incidence of moderate to severe chronic GVHD (42% versus 20%; P = .010), herpes zoster infection (28% versus 12%; P = .010), pulmonary infections (42% versus 21%; P = .040), and osteonecrosis of the femoral head (ONFH; 16% versus 6%; P = .045) as well as better GRFS (59% versus 33%; P = .017). Factors associated with GRFS included total dose of corticosteroid used in the first 100days after transplantation (hazard ratio, 1.547; P?=?.015) and platelet recovery (hazard ratio, 1.456; P?=?.037). Our results suggest that low-dose glucocorticoid prophylaxis reduces GVHD and thus reduces the total dose of steroids, which might contribute to lower incidence of infections and ONFH and a superior GRFS, indicating that higher steroid doses are harmful. Reducing the total dose is of course beneficial. (ClinicalTrials.gov number, NCT01607580.)     

初始耐药肺结核调查分析

目的掌握信宜市肺结核病人初始耐药疫情,分析耐药的原因,制定预防对策。方法以胸片、痰涂片诊断为肺结核的初治患者为对象,进行结核菌培养,阳性者做链霉素（S）、异烟肼（I）、利福平（R）、乙胺丁醇（E）四种药敏试验。结果共检测188例,初始耐药62例,占32．98％。其中耐1种药物51例,占耐药总数的82．26％;耐2种以上药物11例,占耐药总数的17．74％。41—50岁为耐药最高峰,四种耐药次序为I〉R〉S〉E。结论信宜市耐药肺结核疫情相当严峻,应进一步分析耐药原因,探讨预防对策。     

Extended Risk Factors for Stroke Prevention

Stroke causes disability and high mortality, while it can be prevented by increasing public awareness of risk factors. The common known risk factors are hypertension, atrial fibrillation, heart failure, smoking, alcohol consumption, low physical activity, overweight and hypercholesterolemia. However, the deep understanding of risk factors is limited. Moreover, more risk factor emerges in recent years. To further increase the awareness of risk factors for stroke prevention, this review indicates the reasonable application of antihypertensive agents according to the age-dependent changes of hypertension, and some new risk factors including chronic kidney disease, obstructive sleep apnea, migraine with aura, working environment, genetic factors and air pollution. Therefore, internal risk factors (e.g. heredity, hypertension, hyperglycemia) and external risk factors (e.g. working environment, air pollution) are both important for stroke prevention. All of these are reviewed to provide more information for the pre-hospital prevention and management, and the future clinical studies.     

Ethnicity,length of residence,and prospective trends in body mass index in a national sample of Australian adults (2006–2014)

Purpose

Increasing global migration, high obesity in developed countries, and ethnic health inequalities are compelling reasons to monitor immigrant obesity trends. Longitudinal studies of ethnicity, length of residence, and adiposity in contexts outside of the United States are lacking.

Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in children in the HOME Study

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β = 4.6, 95% CI 0.5, 8.7) and BDE-153 (β = 4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.     

Nutrition et sclérose en plaques : le point de la littérature

Introduction and objectives

Nutritional data on multiple sclerosis are discordant and have a low accuracy. The objective of this article was to focus on the nutritional factors involved in multiple sclerosis, from the prevention of disease to the specific management of patients.

Preferences for health economics presentations among vaccine policymakers and researchers

PurposeMeasure the preferences of decision makers and researchers associated with the Advisory Committee on Immunization Practices (ACIP) regarding the recommended format for presenting health economics studies to the ACIP.MethodsWe conducted key informant interviews and an online survey of current ACIP work group members, and current and previous ACIP voting members, liaison representatives, and ex-officio members to understand preferences for health economics presentations. These preferences included the presentation of results and sensitivity analyses, the role of health economics studies in decision making, and strategies to improve guidelines for presenting health economics studies. Best-worst scaling was used to measure the relative value of seven attributes of health economics presentations in vaccine decision making.ResultsThe best-worst scaling survey had a response rate of 51% (n = 93). Results showed that summary results were the most important attribute for decision making (mean importance score: 0.69) and intermediate outcomes and disaggregated results were least important (mean importance score: −0.71). Respondents without previous health economics experience assigned sensitivity analysis lower importance and relationship of the results to other studies higher importance than the experienced group (sensitivity analysis scores: −0.15 vs. 0.15 respectively; relationship of the results: 0.13 vs. −0.12 respectively). Key informant interviews identified areas for improvement to include additional information on the quality of the analysis and increased role for liaisons familiar with health economics.ConclusionAdditional specificity in health economics presentations could allow for more effective presentations of evidence for vaccine decision making.     

Analysis of relationships between polymorphisms in the genes encoding the pentameric complex and neutralization of clinical cytomegalovirus isolates

IntroductionAs congenital cytomegalovirus (CMV) infection is one of the major causes of birth defects and developmental abnormalities, it is essential to develop vaccines and therapeutic antibodies against CMV. Clinical trials demonstrated that the subunit vaccine based on glycoprotein B, which had been believed to be the major target for neutralization, did not induce sufficient protective immunity. On the other hand, it has been reported that the immunization of animals with the Pentamer, the pentameric complex of gH/gL/UL128/UL130/UL131A, induced strong neutralizing antibodies. Here, we sought to clarify whether any polymorphic alterations present in the Pentamer of clinical isolates affect neutralization by anti-Pentamer antibodies.MethodsSequences of the genes encoding the Pentamer components of 25 Japanese clinical isolates were determined. Neutralization of infection by two seropositive sera and by anti-Pentamer serum was measured using a CMV reporter cell line based on ARPE-19.ResultsPolymorphisms of the amino acid sequence of UL128, UL130, and UL131A ORFs were limited and clustered into two major groups. The identified alterations, except UL128 I140T, were mapped outside of the reported regions recognized by neutralizing antibodies. Anti-Pentamer serum neutralized infection with all isolates to a similar degree and had no correlation with the polymorphic groups.ConclusionsOur findings indicate that Pentamer antigens prepared from Merlin Fix strain induce antibodies that neutralize infection with all isolates to a similar level and that anti-Pentamer antibodies neutralize CMV infection better than do human sera, suggesting that vaccines and therapeutic antibodies based on Pentamer as an antigen have some promise.     

The impact of immunization programs on 10 vaccine preventable diseases in Italy: 1900–2015

BackgroundVaccination has determined a dramatic decline in morbidity and mortality from infectious diseases over the last century. However, low perceived risk of the infectious threat and increased concern about vaccines’ safety led to a reduction in vaccine coverage, with increased risk of disease outbreaks.MethodsAnnual surveillance data of nationally communicable infectious diseases in Italy between 1900 and 2015 were used to derive trends in morbidity and mortality rates before and after vaccine introduction, focusing particularly on the effect of vaccination programs. Autoregressive integrated moving average models were applied to ten vaccine-preventable diseases: diphtheria, tetanus, poliomyelitis, hepatitis B, pertussis, measles, mumps, rubella, chickenpox, and invasive meningococcal disease. Results of these models referring to data before the immunization programs were projected on the vaccination period to estimate expected cases. The difference between observed and projected cases provided estimates of cases avoided by vaccination.ResultsThe temporal trend for each disease started with high incidence rates, followed by a period of persisting reduction. After vaccine introduction, and particularly after the recommendation for universal use among children, the current rates were much lower than those forecasted without vaccination, both in the whole population and among the 0-to-4 year olds, which is, generally, the most susceptible age class. Assuming that the difference between incidence rates before and after vaccination programs was attributable only to vaccine, more than 4 million cases were prevented, and nearly 35% of them among children in the early years of life. Diphtheria was the disease with the highest number of prevented cases, followed by mumps, chickenpox and measles.ConclusionsUniversal vaccination programs represent the most effective prevention tool against infectious diseases, having a major impact on human health. Health authorities should make any effort to strengthen public confidence in vaccines, highlighting scientific evidence of vaccination benefits.