Seroprevalence of Subclinical HEV Infection in Healthy Pregnant Urban Dwellers of Bangladesh: Identification of Possible Risk Factors

Background: Hepatitis caused by hepatitis E Virus (HEV) is not uncommon in developing countries. It is usually a self-limiting conferring immunity against subsequent infection. However, HEV infection during pregnancy results in varying degree of morbidity, often fatal. The present study was designed to find out the seroprevalence of subclinical HEV infection during pregnancy at different trimesters without history of hepatitis. Materials and Methods: A total 255 asymptomatic healthy pregnant women of three trimesters (85×3=255) with no history of jaundice were included in this cross-sectional study. The subjects were sub-grouped according to socioeconomic status and education level. HEV IgG antibody in serum was determined by enzyme linked immunosorbent assay (ELISA). Results were expressed as number (percent). Chi-square, Odds Ratio and 95% CI were calculated as applicable. Data analyses were carried out using statistical package for social science for Windows Version 15.0. A p<0.05 was taken as level of significance. Results: Seropositivity for HEV IgG was 38% (96/255) in pregnant women; the higher percentages were recorded in the 2nd and 3rd trimesters − 41% and 46% respectively. The seropositivity of HEV IgG was significantly high in pregnant women with low education level ((p=0.001; OR=2.70, 95% CI=1.602−4.575) and low socioeconomic status (OR=7.54, 95% CI=4.118−13.029) having monthly income below 27,000 taka (p=0.001). Conclusion: Data concluded that seroprevalence of anti-HEV IgG is higher at third trimester in pregnant women in Bangladesh where low socio-economic status and less education level were identified as possible risk factors. Appropriate measures may diminish the possible exposure to infection and reduce maternal mortality

Maternal Micronutrient Supplementation and Long Term Health Impact in Children in Rural Bangladesh

BackgroundLimited data is available on the role of prenatal nutritional status on the health of school-age children. We aimed to determine the impact of maternal micronutrient supplementation on the health status of Bangladeshi children.MethodsChildren (8.6–9.6 years; n = 540) were enrolled from a longitudinal mother-child cohort, where mothers were supplemented daily with either 30mg iron and 400μg folic acid (Fe30F), or 60mg iron and 400μg folic acid (Fe60F), or Fe30F including 15 micronutrients (MM), in rural Matlab. Blood was collected from children to determine the concentration of hemoglobin (Hb) and several micronutrients. Anthropometric and Hb data from these children were also available at 4.5 years of age and mothers at gestational week (GW) 14 and 30.ResultsMM supplementation significantly improved (p≤0.05) body mass index-for-age z-score (BAZ), but not Hb levels, in 9 years old children compared to the Fe30F group. MM supplementation also reduced markers of inflammation (p≤0.05). About 28%, 35% and 23% of the women were found to be anemic at GW14, GW30 and both time points, respectively. The prevalence of anemia was 5% and 15% in 4.5 and 9 years old children, respectively. The adjusted odds of having anemia in 9 year old children was 3-fold higher if their mothers were anemic at both GW14 and GW30 [Odds Ratio (OR) = 3.05; 95% Confidence Interval (CI) 1.42, 6.14, P = 0.002] or even higher if they were also anemic at 4.5 years of age [OR = 5.92; 95% CI 2.64, 13.25; P<0.001].ConclusionMaternal micronutrient supplementation imparted beneficial effects on child health. Anemia during pregnancy and early childhood are important risk factors for the occurrence of anemia in school-age children

Defects in ER–endosome contacts impact lysosome function in hereditary spastic paraplegia

Contacts between endosomes and the endoplasmic reticulum (ER) promote endosomal tubule fission, but the mechanisms involved and consequences of tubule fission failure are incompletely understood. We found that interaction between the microtubule-severing enzyme spastin and the ESCRT protein IST1 at ER–endosome contacts drives endosomal tubule fission. Failure of fission caused defective sorting of mannose 6-phosphate receptor, with consequently disrupted lysosomal enzyme trafficking and abnormal lysosomal morphology, including in mouse primary neurons and human stem cell–derived neurons. Consistent with a role for ER-mediated endosomal tubule fission in lysosome function, similar lysosomal abnormalities were seen in cellular models lacking the WASH complex component strumpellin or the ER morphogen REEP1. Mutations in spastin, strumpellin, or REEP1 cause hereditary spastic paraplegia (HSP), a disease characterized by axonal degeneration. Our results implicate failure of the ER–endosome contact process in axonopathy and suggest that coupling of ER-mediated endosomal tubule fission to lysosome function links different classes of HSP proteins, previously considered functionally distinct, into a unifying pathway for axonal degeneration.This work was supported by grants to E. Reid: UK Medical Research Council Project Grant (MR/M00046X/1), Wellcome Trust Senior Research Fellowship in Clinical Science (082381), Project Grant from United States Spastic Paraplegia Foundation, Project Grant from Tom Wahlig Stiftung, and Project Grant form UK HSP Family Group. J.R. Edgar is supported by the Wellcome Trust (grant 086598). T. Newton and G. Pearson are supported by the Medical Research Council PhD studentships (G0800117 and MR/K50127X/1). F. Berner was supported by the National Institute for Health Research Biomedical Research Centre at Addenbrooke's Hospital. B. Winner is supported by the Tom Wahlig Advanced Fellowship, the German Federal Ministry of Education and Research (01GQ113), the Bavarian Ministry of Education and Culture, Sciences and Arts in the framework of the Bavarian Molecular Biosystems Research Network and ForIPS, and the Interdisciplinary Centre for Clinical Research (University Hospital of Erlangen, N3 and F3). Cambridge Institute for Medical Research is supported by a Wellcome Trust Strategic Award (100140) and Equipment Grant (093026)

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Maternal Micronutrient Supplementation and Long Term Health Impact in Children in Rural Bangladesh.

Limited data is available on the role of prenatal nutritional status on the health of school-age children. We aimed to determine the impact of maternal micronutrient supplementation on the health status of Bangladeshi children.Children (8.6-9.6 years; n = 540) were enrolled from a longitudinal mother-child cohort, where mothers were supplemented daily with either 30mg iron and 400μg folic acid (Fe30F), or 60mg iron and 400μg folic acid (Fe60F), or Fe30F including 15 micronutrients (MM), in rural Matlab. Blood was collected from children to determine the concentration of hemoglobin (Hb) and several micronutrients. Anthropometric and Hb data from these children were also available at 4.5 years of age and mothers at gestational week (GW) 14 and 30.MM supplementation significantly improved (p≤0.05) body mass index-for-age z-score (BAZ), but not Hb levels, in 9 years old children compared to the Fe30F group. MM supplementation also reduced markers of inflammation (p≤0.05). About 28%, 35% and 23% of the women were found to be anemic at GW14, GW30 and both time points, respectively. The prevalence of anemia was 5% and 15% in 4.5 and 9 years old children, respectively. The adjusted odds of having anemia in 9 year old children was 3-fold higher if their mothers were anemic at both GW14 and GW30 [Odds Ratio (OR) = 3.05; 95% Confidence Interval (CI) 1.42, 6.14, P = 0.002] or even higher if they were also anemic at 4.5 years of age [OR = 5.92; 95% CI 2.64, 13.25; P<0.001].Maternal micronutrient supplementation imparted beneficial effects on child health. Anemia during pregnancy and early childhood are important risk factors for the occurrence of anemia in school-age children

The odds of having anemia at 9 years of age if the mother were anemic at GW-14 or GW-30 or if the children were anemic at 4.5 years of age.

<p>Abbreviation: Fe30F, 30mg iron and 400μg folic acid; Fe60F, 60mg iron and 400μg folic acid; MM, Fe30F including 15 micronutrients, GW, Gestational week.</p