Maternal iodine status in a multi-ethnic UK birth cohort: associations with autism spectrum disorder.

BACKGROUND: Maternal iodine requirements increase during pregnancy to supply thyroid hormones essential for fetal brain development. Maternal iodine deficiency can lead to hypothyroxinemia, a reduced fetal supply of thyroid hormones which, in the first trimester, has been linked to an increased risk of autism spectrum disorder (ASD) in the child. No study to date has explored the direct link between maternal iodine deficiency and diagnosis of ASD in offspring. METHODS: Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6955 mothers at 26-28 weeks gestation participating in the Born in Bradford (BiB) cohort. Maternal iodine status was examined in relation to the probability of a Read (CTV3) code for autism being present in a child's primary care records through a series of logistic regression models with restricted cubic splines. RESULTS: Median (inter-quartile range) UIC was 76 µg/L (46, 120) and I:Cr was 83 µg/g (59, 121) indicating a deficient population according to WHO guidelines. Ninety two children (1·3%) in our cohort had received a diagnosis of ASD by the census date. Overall, there was no evidence to support an association between I:Cr or UIC and ASD risk in children aged 8-12 years (p = 0·3). CONCLUSIONS: There was no evidence of an increased clinical ASD risk in children born to mothers with mild-to-moderate iodine deficiency at 26 weeks gestation. Alternative functional biomarkers of exposure and a wider range of conditions may provide further insight.

Maternal iodine status, intrauterine growth, birth outcomes and congenital anomalies in a UK birth cohort.

BACKGROUND: Severe iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outcomes, finding inconsistent evidence for specific outcomes. METHODS: Maternal iodine status was estimated from spot urine samples collected at 26-28 weeks' gestation from 6971 mothers in the Born in Bradford birth cohort. Associations with outcomes were examined for both urinary iodine concentration (UIC) and iodine-to-creatinine ratio (I:Cr). Outcomes assessed included customised birthweight (primary outcome), birthweight, small for gestational age (SGA), low birthweight, head circumference and APGAR score. RESULTS: There was a small positive association between I:Cr and birthweight in adjusted analyses. For a typical participant, the predicted birthweight centile at the 25th percentile of I:Cr (59 µg/g) was 2.7 percentage points lower than that at the 75th percentile of I:Cr (121 µg/g) (99% confidence interval (CI) 0.8 to 4.6), birthweight was predicted to be 41 g lower (99% CI 13 to 69) and the predicted probability of SGA was 1.9 percentage points higher (99% CI 0.0 to 3.7). There was no evidence of associations using UIC or other birth outcomes, including stillbirth, preterm birth, ultrasound growth measures or congenital anomalies. CONCLUSION: Lower maternal iodine status was associated with lower birthweight and greater probability of SGA. Whilst small, the effect size for lower iodine on birthweight is comparable to environmental tobacco smoke exposure. Iodine insufficiency is avoidable, and strategies to avoid deficiency in women of reproductive age should be considered. TRIAL REGISTRATION: ClinicalTrials.gov NCT03552341. Registered on June 11, 2018.

Care Toward the End of Life in Older Populations and Its Implementation Facilitators and Barriers: A Scoping Review.

PURPOSE: To inform health system improvements for care of elderly populations approaching the end of life (EOL) by identifying important elements of care and implementation barriers and facilitators. DESIGN: A scoping review was carried out to identify key themes in EOL care. Articles were identified from MEDLINE, the Cochrane Library, organizational websites, and internet searches. Eligible publications included reviews, reports, and policy documents published between 2005 and 2016. Initially, eligible documents included reviews or reports concerning effective or important models or components of EOL care in older populations, and evidence was thematically synthesized. Later, other documents were identified to contextualize implementation issues. RESULTS: Thematic synthesis using 35 reports identified key features in EOL care: (1) enabling policies and environments; (2) care pathways and models; (3) assessment and prognostication; (4) advance care planning and advance directives; (5) palliative and hospice care; (6) integrated and multidisciplinary care; (7) effective communication; (8) staff training and experience; (9) emotional and spiritual support; (10) personalized care; and (11) resources. Barriers in implementing EOL care include fragmented services, poor communication, difficult prognostication, difficulty in accepting prognosis, and the curative focus in medical care. CONCLUSIONS: Quality EOL care for older populations requires many core components but the local context and implementation issues may ultimately determine if these elements can be incorporated into the system to improve care. Changes at the macro-level (system/national), meso-level (organizational), and micro-level (individual) will be required to successfully implement service changes to provide holistic and person-centered EOL care for elderly populations.

Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis.

OBJECTIVE: To determine the most efficacious treatment for eradication of Helicobacter pylori with the lowest likelihood of some common adverse events among pre-recommended and newer treatment regimens. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Cochrane Library, PubMed, and Embase without language or date restrictions. STUDY SELECTION: Full text reports of randomised controlled trials that compared different eradication treatments for H pylori among adults. RESULTS: Of the 15,565 studies identified, 143 were eligible and included. Data on 14 kinds of treatments were available. Of 91 possible comparisons for the efficacy outcome, 34 were compared directly and the following treatments performed better: seven days of concomitant treatment (proton pump inhibitor and three kinds of antibiotics administered together), 10 or 14 days of concomitant treatment, 10 or 14 days of probiotic supplemented triple treatment (standard triple treatment which is probiotic supplemented), 10 or 14 days of levofloxacin based triple treatment (proton pump inhibitor, levofloxacin, and antibiotic administered together), 14 days of hybrid treatment (proton pump inhibitor and amoxicillin used for seven days, followed by a proton pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days), and 10 or 14 days of sequential treatment (five or seven days of a proton pump inhibitor plus amoxicillin, followed by five or seven additional days of a proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin). In terms of tolerance, all treatments were considered tolerable, but seven days of probiotic supplemented triple treatment and seven days of levofloxacin based triple treatment ranked best in terms of the proportion of adverse events reported. CONCLUSION: Comparison of different eradication treatments for H pylori showed that concomitant treatments, 10 or 14 days of probiotic supplemented triple treatment, 10 or 14 days of levofloxacin based triple treatment, 14 days of hybrid treatment, and 10 or 14 days of sequential treatment might be better alternatives for the eradication of H pylori.

Fruit intake and cardiovascular disease mortality in the UK Women's Cohort Study.

In observational studies, fruit intake is associated with a reduced risk of cardiovascular disease (CVD), though fruit type has been less frequently explored. The aim of the current study was to explore the association between total fruit and fruit subgroup intake according to polyphenol content and CVD mortality in the UK Women's Cohort Study. Total fruit intake (g/day) derived from a 217-item food frequency questionnaire was obtained from 30,458 women (aged 35-69 years) at baseline from 1995-1998. Fruit intakes were sub-categorised according to similarities in polyphenol profile from Phenol Explorer, including berries, citrus, drupes, pomes and tropical fruits. Mortality events were derived from the NHS Central Register. During the mean follow-up period of 16.7 years, 286 fatal CVD deaths [138 coronary heart disease (CHD), 148 stroke] were observed. Survival analysis was conducted using participants free from history of CVD at baseline. Total fruit intake was associated with lower risk of CVD and CHD mortality, with a 6-7 % reduction in risk for each 80 g/day portion consumed (99 % CI 0.89, 1.00 and 0.85, 1.01 respectively). Concerning particular fruit types, the direction of the associations tended to be inverse, but point estimates and tests for trend were not generally statistically significant. However, women in the highest intake group of grapes and citrus experienced a significant reduction in risk of CVD and stroke respectively compared with non-consumers [HR 0.56 (99 % CI 0.32, 0.98) and 0.34 (0.14, 0.82) respectively]. These findings support promoted guidelines encouraging fruit consumption for health in women, but do not provide strong evidence to suggest that fruit type is as important.

The method quality of cross-over studies involved in Cochrane Systematic Reviews.

BACKGROUND: It is possible that cross-over studies included in current systematic reviews are being inadequately assessed, because the current risk of bias tools do not consider possible biases specific to cross-over design. We performed this study to evaluate whether this was being done in cross-over studies included in Cochrane Systematic Reviews (CSRs). METHODS: We searched the Cochrane Library (up to 2013 issue 5) for CSRs that included at least one cross-over trial. Two authors independently undertook the study selection and data extraction. A random sample of the CSRs was selected and we evaluated whether the cross-over trials in these CSRs were assessed according to criteria suggested by the Cochrane handbook. In addition we reassessed the risk of bias of these cross-over trials by a checklist developed form the Cochrane handbook. RESULTS: We identified 688 CSRs that included one or more cross-over studies. We chose a random sample of 60 CSRs and these included 139 cross-over studies. None of these CSRs undertook a risk of bias assessment specific for cross-over studies. In fact items specific for cross-over studies were seldom considered anywhere in quality assessment of these CSRs. When we reassessed the risk of bias, including the 3 items specific to cross-over trials, of these 139 studies, a low risk of bias was judged for appropriate cross-over design in 110(79%), carry-over effects in 48(34%) and for reporting data in all stages of the trial in 114(82%).Assessment of biases in cross-over trials could affect the GRADE assessment of a review's findings. CONCLUSION: The current Cochrane risk of bias tool is not adequate to assess cross-over studies. Items specific to cross-over trials leading to potential risk of bias are generally neglected in CSRs. A proposed check list for the evaluation of cross-over trials is provided.

Concordant analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression between primary colorectal cancer and matched metastases.

Current data on the concordance of KRAS, BRAF, PIK3CA mutation status or PTEN expression status between primary tumors and metastases in colorectal cancer (CRC) are conflicting. We conducted a systematic review and meta-analysis to examine concordance and discordance of the status of these four biomarkers between primary tumors and corresponding metastases in CRC patients. The biomarker status in primary tumors was used as the reference standard. Concordance data for KRAS, BRAF, PIK3CA and PTEN were provided by 43, 16, 9 and 7 studies, respectively. The pooled concordance rate was 92.0% (95% CI: 89.7%-93.9%) for KRAS, 96.8% (95% CI: 94.8%-98.0%) for BRAF, 93.9% (95% CI: 89.7%-96.5%) for PIK3CA and 71.7% (95% CI: 57.6%-82.5%) for PTEN. The pooled false positive and false negative rates for KRAS were 9.0% (95% CI: 6.5%-12.4%) and 11.3% (95% CI: 8.0%-15.8%), respectively. KRAS, BRAF and PIK3CA mutations are highly concordant between primary tumors and corresponding metastases in CRC, but PTEN loss is not. Nine percent of patients with wild-type KRAS in primary tumors who received anti-EGFR treatment had mutant KRAS in metastases, while 11.3% patients with mutant KRAS primary tumors had wild-type KRAS in the metastases. These 11.3% patients currently do not receive potentially beneficial anti-EGFR treatment.