Vaginal progesterone, oral progesterone, 17-OHPC, cerclage, and pessary for preventing preterm birth in at-risk singleton pregnancies: an updated systematic review and network meta-analysis.

BACKGROUND: Recent progesterone trials call for an update of previous syntheses of interventions to prevent preterm birth. OBJECTIVES: To compare the relative effects of different types and routes of administration of progesterone, cerclage, and pessary at preventing preterm birth in at-risk women overall and in specific populations. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL, and Web of Science up to 1 January 2018. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing preterm birth in at-risk singleton pregnancies. DATA COLLECTION AND ANALYSIS: We used a piloted data extraction form and performed Bayesian random-effects network meta-analyses with 95% credibility intervals (CrI), as well as pairwise meta-analyses, rating the quality of the evidence using GRADE. MAIN RESULTS: We included 40 trials (11 311 women). In at-risk women overall, vaginal progesterone reduced preterm birth <34 (OR 0.43, 95% CrI 0.20-0.81) and <37 weeks (OR 0.51, 95% CrI 0.34-0.74), and neonatal death (OR 0.41, 95% CrI 0.20-0.83). In women with a previous preterm birth, vaginal progesterone reduced preterm birth <34 (OR 0.29, 95% CI 0.12-0.68) and <37 weeks (OR 0.43, 95% CrI 0.23-0.74), and 17α-hydroxyprogesterone caproate reduced preterm birth <37 weeks (OR 0.53, 95% CrI 0.27-0.95) and neonatal death (OR 0.39, 95% CI 0.16-0.95). In women with a short cervix (≤25 mm), vaginal progesterone reduced preterm birth <34 weeks (OR 0.45, 95% CI 0.24-0.84). CONCLUSIONS: Vaginal progesterone was the only intervention with consistent effectiveness for preventing preterm birth in singleton at-risk pregnancies overall and in those with a previous preterm birth. TWEETABLE ABSTRACT: In updated NMA, vaginal progesterone consistently reduced PTB in overall at-risk pregnancies and in women with previous PTB.

Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

BACKGROUND: Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it. OBJECTIVES: To compare progesterone, cerclage and pessary, determine their relative effects and rank them. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study. DATA COLLECTION AND ANALYSIS: We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT). MAIN RESULTS: We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks. CONCLUSIONS: Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae. TWEETABLE ABSTRACT: Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.

Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.

BACKGROUND: About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. OBJECTIVES: To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. SELECTION CRITERIA: Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. MAIN RESULTS: We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I2  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I2  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I2  22%). CONCLUSION: In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. TWEETABLE ABSTRACT: Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.

Malnutrition in Pre-school Children across Different Geographic Areas and Socio-Demographic Groups in Ghana.

Objective Malnutrition in children pervades all aspects of their health, growth, cognitive and social development and can lead to irreversible and lifelong effects. We examine the prevalence and determinants of malnutrition in children under 5 in the Ghanaian population. Methods Using data from the latest available Ghana Demographic and Health Survey (GDHS), we estimated and compared prevalence of malnutrition in children among the different subgroups of the population. We used multivariable logistic regression to identify potential factors associated with childhood malnutrition in Ghana. Results Overall, 35.6 % (95 % CI: 33.6, 37.6) of Ghanaian children under 5 years of age suffer from some form of malnutrition. Specifically, 27.5 % (95 % CI: 25.1, 28.7), 13.8 % (95 % CI: 12.5, 15.3), 8.9 % (95 % CI: 7.8, 10.2) were stunted, underweight and wasted, respectively. Results from the logistic regression indicate that gender and age of the child, educational and nutritional status of the mother, and financial status of the household are risk factors associated with childhood malnutrition in Ghana. Conclusions for Practice In view of the observed high rate of malnutrition among Ghanaian children despite the interventions that have been in place since the 1990s, there is a need for increased awareness and improved targeted interventions as well as knowledge translation tools including extensive education on infant and young child feeding practices.

Survival Analysis in the Presence of Competing Risks: The Example of Waitlisted Kidney Transplant Candidates.

Competing events (or risks) preclude the observation of an event of interest or alter the probability of the event's occurrence and are commonly encountered in transplant outcomes research. Transplantation, for example, is a competing event for death on the waiting list because receiving a transplant may significantly decrease the risk of long-term mortality. In a typical analysis of time-to-event data, competing events may be censored or incorporated into composite end points; however, the presence of competing events violates the assumption of "independent censoring," which is the basis of standard survival analysis techniques. The use of composite end points disregards the possibility that competing events may be related to the exposure in a way that is different from the other components of the composite. Using data from the Scientific Registry of Transplant Recipients, this paper reviews the principles of competing risks analysis; outlines approaches for analyzing data with competing events (cause-specific and subdistribution hazards models); compares the estimates obtained from standard survival analysis, which handle competing events as censoring events; discusses the appropriate settings in which each of the two approaches could be used; and contrasts their interpretation.

Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy.

Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3-87.0%) and 98.9% (96.3-100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1-99.4%) and 100.0% (99.9-100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4-95.5%) and 92.6% (86.5-96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6-97.5%) and 99.2% (98.4-99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.37.

Does non-pharmacological therapy for antenatal depression reduce risks for the infant?

Depression during pregnancy has been associated with an increased risk of adverse outcomes for the infant such as preterm birth. These risks are not reduced with pharmacological treatment, but the effect of non-pharmacological therapies is unknown. We performed a systematic review to assess the risk of adverse perinatal outcomes in non-pharmacologically treated depressed women compared to non-depressed women. We found no studies that met our inclusion criteria, highlighting a critical need for research on this topic.

HLA-DR and -DQ eplet mismatches and transplant glomerulopathy: a nested case-control study.

We conducted a nested case-control study from a cohort of adult kidney transplant recipients to assess the risk of transplant glomerulopathy (TG) as a function of donor and recipient HLA-DR and -DQ incompatibility at the eplet level. Cases (n = 52) were defined as patients diagnosed with transplant glomerulopathy based on biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n = 104) with a similar follow-up from transplantation were randomly selected from the remaining cohort. HLAMatchmaker was used to ascertain the number of DRB1/3/4/5, DQA1 and DQB1 related eplet mismatches (eplet load). Multivariable conditional logistic regression models demonstrated an increase in the odds of TG (odds ratios [OR] of 2.84 [95% confidence interval (CI): 1.03, 7.84] and 4.62 [95% CI: 1.51, 14.14]) in the presence of 27-43 and >43 HLA-DR + DQ related eplet mismatches versus <27 eplet mismatches, respectively. When the eplet load was modeled as a continuous variable, the OR for TG was 1.25 (95% CI: 1.04, 1.50) for every 10 additional HLA-DR + DQ eplet mismatches. Our study suggests that minimization of HLA-DR + DQ eplet mismatches may decrease the incidence of transplant glomerulopathy diagnosed by indication biopsies. The role of eplet immunogenicity/antigenicity as determinants of allograft outcomes requires further study.

Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.

BACKGROUND: Objectives were to describe the reliability and validity of a new paediatric-specific mucositis scale, the Children's International Mucositis Evaluation Scale (ChIMES). METHODS: In a multi-centre prospective study, children aged 0 to ≤18 years were eligible if they were receiving any of the following: myeloablative stem cell transplantation (SCT), ≥60 mg m(-2) course(-1) doxorubicin or ≥12 g m(-2) methotrexate. Multiple measures of mucositis were included along with ChIMES. Respondents were parent proxy report for children aged <12 years, and child self-report for children aged 12-18 years and 8 to <12 years. Mucositis diaries were completed at baseline and on Days 7-17 following chemotherapy/conditioning. On Day 14, the respondent reported presence of mucositis and change since the previous day. RESULTS: The 185 respondents included parents (N=98), children aged 12-18 years (N=66) and children aged 8 to <12 years (N=21). Test-retest reliability was excellent for ChIMES Total Score and ChIMES Percentage Score with r>0.8 for all respondent types. Criteria for construct validation were met across all measures. ChIMES also demonstrated responsiveness with significant differences between baseline and Day 14. CONCLUSION: ChIMES is a paediatric-specific measure of mucositis with favourable psychometric properties. It exhibits reliability, construct validity and responsiveness. ChIMES should be incorporated into clinical trials of mucositis prevention and treatment in paediatric cancer and SCT.

Invasive fungal infections in paediatric acute myeloid leukaemia.

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in paediatric acute myeloid leukaemia (AML). This study describes risk factors for IFI and IFI-related sepsis in this population. We conducted a population-based, retrospective cohort study of children with AML in Canada. IFIs during chemotherapy and prior to haematopoietic stem cell transplantation, relapse, persistent disease or death were identified. Risk factors for proven or probable IFI were examined. Among courses complicated by IFI, risk factors for sepsis were also evaluated. There were 341 children with AML included of which 41 (12.0%) experienced 46 different episodes of IFI. Candida species accounted for 23 (50.0%) of IFIs and Aspergillus spp. accounted for 14 (30.4%). Days of broad-spectrum antibiotics, days of corticosteroids and neutropenia at start of the course were independently associated with IFI. Only days of fever were independently associated with IFI-related sepsis. Invasive fungal infections occurred in 12.0% of paediatric AML patients. Risk factors for IFI and IFI-related sepsis were identified. This knowledge may help to consider targeted strategies.

Mould-active compared with fluconazole prophylaxis to prevent invasive fungal diseases in cancer patients receiving chemotherapy or haematopoietic stem-cell transplantation: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Objectives were to compare systemic mould-active vs fluconazole prophylaxis in cancer patients receiving chemotherapy or haematopoietic stem cell transplantation (HSCT). METHODS: We searched OVID MEDLINE and the Cochrane Central Register of Controlled Trials (1948-August 2011) and EMBASE (1980-August 2011). Randomised controlled trials of mould-active vs fluconazole prophylaxis in cancer or HSCT patients were included. Primary outcome was proven/probable invasive fungal infections (IFI). Analysis was completed by computing relative risks (RRs) using a random-effects model and Mantel-Haenszel method. RESULTS: From 984 reviewed articles, 20 were included in this review. Mould-active compared with fluconazole prophylaxis significantly reduced the number of proven/probable IFI (RR 0.71, 95% CI 0.52 to 0.98; P=0.03). Mould-active prophylaxis also decreased the risk of invasive aspergillosis (IA; RR 0.53, 95% confidence interval (CI) 0.37-0.75; P=0.0004) and IFI-related mortality (RR 0.67, 95% CI 0.47-0.96; P=0.03) but is also associated with an increased risk of adverse events (AEs) leading to antifungal discontinuation (RR 1.95, 95% CI 1.24-3.07; P=0.004). There was no decrease in overall mortality (RR 1.0; 95% CI 0.88-1.13; P=0.96). CONCLUSION: Mould-active compared with fluconazole prophylaxis significantly reduces proven/probable IFI, IA, and IFI-related mortality in cancer patients receiving chemotherapy or HSCT, but increases AE and does not affect overall mortality. (PROSPERO Registration: CRD420111174).

The effect of exercise on pQCT parameters of bone structure and strength in postmenopausal women--a systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Inconsistent study findings of exercise on areal bone density highlight the need to include parameters of bone geometry and volumetric bone density measurements. Using a systematic review and meta-analysis, we found a decrease in bone loss through the maintenance of cortical and trabecular volumetric bone mineral density (BMD). Studies with longer exercise durations and larger sample sizes are needed. INTRODUCTION: Exercise has long been recommended to prevent age-related loss of bone mass in postmenopausal women. However, inconsistent study findings on the effect of exercise on BMD preservation have highlighted the importance of extending the evaluation of bone to include the parameters of bone geometry. We conducted both a systematic review and meta-analysis of the effects of exercise on bone geometry and volumetric BMD in postmenopausal women. METHODS: We searched MEDLINE, PubMed, and EMBASE from 1950 to April 2009 and included prospective, randomized controlled trials of healthy postmenopausal women where the intervention involved exercise or sport and outcomes included quantitative or peripheral quantitative computed tomography bone parameters. Outcome variables included: total volumetric BMD, cortical volumetric BMD (CvBMD), trabecular volumetric BMD (TrvBMD), total bone mineral content, cortical BMC, total bone area, cortical area, polar stress-strain index, and bone strength index. RESULTS: Six studies satisfied our inclusion and exclusion criteria. Lower extremity exercises resulted in small (∼0.9%) but significant improvements in TrvBMD of the distal tibia (p = 0.0006) and in CvBMD of the tibial shaft (p = 0.0007). Studies with longer durations of exercise (12 months) and those in early postmenopausal women showed significant changes in CvBMD at the tibial shaft. CONCLUSIONS: We conclude that exercise in postmenopausal women may decrease bone loss by maintaining cortical and trabecular volumetric BMD. To better understand the effect of exercise on bone geometric structure and strength, more studies of longer duration and larger sample sizes are needed.

Outpatient and oral antibiotic management of low-risk febrile neutropenia are effective in children--a systematic review of prospective trials.

BACKGROUND: There is no consensus on whether therapeutic intensity can be reduced safely in children with low-risk febrile neutropenia (FN). Our primary objective was to determine whether there is a difference in efficacy between outpatient and inpatient management of children with low-risk FN. Our secondary objective was to compare oral and parenteral antibiotic therapy in this population. METHODS: We performed electronic searches of Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials, and limited studies to prospective pediatric trials in low-risk FN. Percentages were used as the effect measure. RESULTS: From 7,281 reviewed articles, 16 were included in the meta-analysis. Treatment failure, including antibiotic modification, was less likely to occur in the outpatient setting compared with the inpatient setting (15 % versus 28 %, P = 0.04) but was not significantly different between oral and parenteral antibiotic regimens (20 % versus 22 %, P = 0.68). Of the 953 episodes treated in the outpatient setting and 676 episodes treated with oral antibiotics, none were associated with infection-related mortality. CONCLUSION: Based on the combination of results from all prospective studies to date, outpatient and oral antibiotic management of low-risk FN are effective in children and should be incorporated into clinical care where feasible.

Genetic analysis of inherited bone marrow failure syndromes from one prospective, comprehensive and population-based cohort and identification of novel mutations.

INTRODUCTION: Inherited bone marrow failure syndromes (IBMFSs) often have substantial phenotypic overlap, thus genotyping is often critical for establishing a diagnosis. OBJECTIVES AND METHODS: To determine the genetic characteristics and mutation profiles of IBMFSs, a comprehensive population-based study that prospectively enrols all typical and atypical cases without bias is required. The Canadian Inherited Marrow Failure Study is such a study, and was used to extract clinical and genetic information for patients enrolled up to May 2010. RESULTS: Among the 259 primary patients with IBMFS enrolled in the study, the most prevalent categories were Diamond-Blackfan anaemia (44 patients), Fanconi anaemia (39) and Shwachman-Diamond syndrome (35). The estimated incidence of the primary IBMFSs was 64.5 per 10(6) births, with Fanconi anaemia having the highest incidence (11.4 cases per 10(6) births). A large number of patients (70) had haematological and non-haematological features that did not fulfil the diagnostic criteria of any specific IBMFS category. Disease-causing mutations were identified in 53.5% of the 142 patients tested, and in 16 different genes. Ten novel mutations in SBDS, RPL5, FANCA, FANCG, MPL and G6PT were identified. The most common mutations were nonsense (31 alleles) and splice site (28). Genetic heterogeneity of most IBMFSs was evident; however, the most commonly mutated gene was SBDS, followed by FANCA and RPS19. CONCLUSION: From this the largest published comprehensive cohort of IBMFSs, it can be concluded that recent advances have led to successful genotyping of about half of the patients. Establishing a genetic diagnosis is still challenging and there is a critical need to develop novel diagnostic tools.

Cost effectiveness of outpatient treatment for febrile neutropaenia in adult cancer patients.

BACKGROUND: There is uncertainty whether low-risk episodes of febrile neutropaenia (FN) in adult cancer patients are best managed in the in- or outpatient setting. METHODS: A Monte Carlo cost-utility model was created to compare four treatment strategies for low-risk FN: (1) treatment in hospital with intravenous antibiotics (HospIV); (2) early discharge after 48 h in-patient observation, followed by oral outpatient treatment (EarlyDC); (3) outpatient management with IV antibiotics (HomeIV); and (4) outpatient management with oral antibiotics (HomePO). The model used a health-care payer perspective and a time horizon of one FN episode. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollars) and incremental cost-effectiveness ratios (ICER). Parameter uncertainty was assessed with probabilistic sensitivity analyses. RESULTS: HomePO was cost saving ($3470 vs $4183), but less effective (0.65 QAFNE vs 0.72 QAFNE) than HomeIV. The corresponding ICER was $10,186 per QAFNE. Both EarlyDC ($6115; 0.66 QAFNE) and HospIV ($13,557; 0.62 QAFNE) were dominated strategies. At a willingness-to-pay (WTP) threshold of $4,000 per QAFNE, HomePO and HomeIV were cost effective in 54 and 38% of simulations, respectively. INTERPRETATION: For adult cancer patients with an episode of low-risk FN, treatment in hospital is more expensive and less effective than outpatient strategies.

Outpatient management of cancer patients with febrile neutropenia: a systematic review and meta-analysis.

BACKGROUND: In some centers, outpatient management for cancer patients with low-risk febrile neutropenia (FN) has been implemented into routine clinical practice. Our objective was to evaluate the current level of evidence before supporting widespread adoption of outpatient management for this population. METHODS: We systematically reviewed randomized controlled trials evaluating efficacy and safety of outpatient management of FN. RESULTS: From 1448 reviewed articles, 14 studies were included for meta-analysis. (i) Inpatient versus outpatient setting (6 studies) was not significantly associated with treatment failure [risk ratio 0.81; 95% confidence interval (CI) 0.55-1.19; P = 0.28]. Death occurred in 13 of 742 FN episodes with no difference between the two groups (risk ratio 1.11; 95% CI 0.41-3.05; P = 0.83). (ii) Outpatient oral versus outpatient parenteral antibiotics (8 studies) were similarly efficacious with no association between route of drug administration and treatment failure (risk ratio 0.93; 95% CI 0.65-1.32; P = 0.67). No death occurred in 857 FN episodes. CONCLUSION: Based on the current literature, outpatient treatment of FN is a safe and efficacious alternative to inpatient management. Variation between studies in terms of time to discharge, choice of antibiotic class, and age of study population may limit the interpretation of the data.

Comparative analysis of Shwachman-Diamond syndrome to other inherited bone marrow failure syndromes and genotype-phenotype correlation.

Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman-Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population-based study. Thirty-four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS-negative SDS patients may have more severe hematological failure and milder pancreatic disease.

Fruit and vegetable intake and bone health in women aged 45 years and over: a systematic review.

UNLABELLED: High fruit and vegetable intake may be associated with improved bone status among women aged ≥ 45 years. This is the first systematic review that specifically assessed this association and identified research gaps. The benefits of fruit and vegetables (F&V) on bone health remain unclear. Further studies are needed. INTRODUCTION: F&V have several components that are beneficial to bones. Some studies report that high F&V intake is associated with improved bone status in middle aged and aged women; however, findings are inconsistent. The objective was to systematically review observational and interventional studies that investigated the effects of F&V intake on incidence of osteoporotic fractures, bone mineral density (BMD), and bone turnover markers (BTM) in women aged ≥ 45 years and to identify potential research gaps. METHODS: Electronic databases were searched, and peer-reviewed manuscripts published in English, with F&V intake as a main dietary exposure, were included. Data selection, extraction, and evaluation of risk of bias were performed independently by two reviewers. RESULTS: Eight studies were included. One cohort study reported cross-sectional as well as longitudinal data. There was significant between-study heterogeneity in design, definition, and amount of F&V intake, outcomes, analyses, and reporting of results. Two studies had low, two had moderate, and four had high risk of bias. Among reports with low or moderate risk of bias, two cross-sectional analyses reported positive associations between F&V intake and BMD of the forearm, lumbar spine, or total hip, whereas one randomized controlled trial and two prospective cohort analyses reported no effects. One trial reported no associations between F&V and BTM. CONCLUSIONS: Based on limited evidence, the benefits of F&V on bone health remain unclear for women aged ≥ 45 years. Further studies with low risk of bias are needed.

Effect of whole-body vibration on BMD: a systematic review and meta-analysis.

SUMMARY: Our systematic review and meta-analysis of randomized controlled trials (RCTs) examining whole-body vibration (WBV) effect on bone mineral density (BMD) found significant but small improvements in hip areal BMD (aBMD) in postmenopausal women and in tibia and spine volumetric BMD in children/adolescents, but not in other BMD measurements in postmenopausal women and young adults. INTRODUCTION: Animal experiments report anabolic bone changes in response to WBV, but data in humans are limited. Our objective is to conduct a systematic review and meta-analysis of RCTs examining WBV effect on BMD. METHODS: Eligible RCTs included randomized or quasi-randomized trials, with follow-up of ≥ 6 months, examining WBV effects on BMD in ambulatory individuals without secondary causes of osteoporosis. The weighted mean differences between WBV and control groups in absolute pre-post change in spine and hip aBMD, and in spine and tibia trabecular volumetric BMD (vBMD) were calculated. RESULTS: eight RCTs in postmenopausal women (five RCTs), young adults (one RCT), and children and adolescents (two RCTs) were included. The regimens were heterogeneous, study durations were relatively short, and available data was mostly per-protocol. In postmenopausal women, WBV was found to significantly increase hip aBMD (0.015 g cm(-2); 95% confidence interval (CI), 0.008-0.022; n = 131) versus controls, but not spine aBMD (n = 181) or tibia trabecular vBMD (n = 29). In young adults, WBV did not increase spine or hip bone mineral content, or tibia trabecular vBMD (n = 53). In children and adolescents, WBV significantly increased spine (6.2 mg cm(-3); 95% CI, 2.5-10.0; n = 65) and tibia (14.2 mg cm(-3); 95% CI, 5.2-23.2; n = 17) trabecular vBMD. CONCLUSIONS: We found significant but small improvements in BMD in postmenopausal women and children and adolescents, but not in young adults. WBV is a promising new modality, but before recommendations can be made for clinical practice, large-scale long-term studies are needed to determine optimal magnitude, frequency, and duration.

TNF-alpha-308 G/A polymorphism and responsiveness to TNF-alpha blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis.

Although tumor necrosis factor-alpha (TNF-alpha) blockade is a very effective therapy for rheumatoid arthritis (RA), not all patients achieve a favorable outcome. The objective of this study was to determine if the common TNF-alpha variant -308(A) predicts poor response to TNF-alpha inhibitors in RA patients using meta-analysis. Studies were identified using MEDLINE and EMBASE. Data were extracted based on DAS28 or achieving at least American College of Rheumatology 20 response. A total of nine studies met the inclusion criteria representing a total of 692 RA patients. There was no significant heterogeneity among study effect sizes (P=0.36). The frequency of the A allele was 22% (119/531) in responders and 37% (60/161) in non-responders. The odds of having the A allele was lower in responders versus non-responders (odds ratio (OR)=0.43, 95% confidence intervals (CI): 0.28-0.68, P=0.000245), irrespective of the TNF-alpha inhibitor prescribed, indicating that the -308(A) variant predicts poor response to TNF-alpha inhibitors. The clinical utility of prospectively genotyping for this variant when initiating anti-TNF-alpha therapy for RA should now be formally assessed.