bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preconception and periconception interventions to prevent low birth weight, small for gestational age and preterm birth: a systematic review and meta-analysis
Authors: Partap Uttara , Chowdhury Ranadip , Taneja Sunita , Bhandari Nita , De Costa Ayesha , Bahl Rajiv , Fawzi Wafaie 
Published: August 2022

BackgroundLow birth weight (LBW), including preterm birth (PTB) and small for gestational age (SGA), contributes a significant global health burden. We aimed to summarise current evidence on the effect of preconception and periconception interventions on LBW, SGA and PTB.MethodsIn this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library and WHO Global Index Medicus for randomised controlled trials and quasi-experimental studies published by 28 November 2020, which assessed interventions delivered in preconception and periconception or preconception and pregnancy. Primary outcomes were LBW, SGA and PTB. Studies were categorised by intervention type and delivery during preconception and periconception or during preconception and pregnancy. Estimates were pooled using fixed-effects or random-effects restricted maximum likelihood method meta-analyses. Quality of evidence for primary outcomes was assessed using the Grades of Recommendations, Assessment, Development and Evaluation approach.ResultsWe included 58 studies. Twenty-eight studies examined nutrition interventions (primarily micronutrient or food supplementation). Thirty studies (including one reporting a nutrition intervention) provided health interventions (general preconception health, early adverse pregnancy outcome prevention, non-communicable disease and infectious disease prevention and management). One study assessed a social intervention (reproductive planning). Studies varied in terms of specific interventions, including delivery across preconception or pregnancy, resulting in few studies for any single comparison. Overall, the evidence was generally very uncertain regarding the impact of any intervention on LBW, SGA and PTB. Additionally, preconception and periconception nutritional supplementation containing folic acid was associated with reduced risk of birth defects (10 studies, N=3 13 312, risk ratio: 0.37 (95% CI: 0.24 to 0.55), I2: 74.33%).ConclusionWe found a paucity of evidence regarding the impact of preconception and periconception interventions on LBW, SGA and PTB. Further research on a wider range of interventions is required to clearly ascertain their potential effectiveness.Trial registration numberThis review was prospectively registered with PROSPERO (CRD42020220915).
Prevalence and risk factors of lower extremity disease in high risk groups in Malawi: a stratified cross-sectional study
Authors: Kasenda Stephen , Crampin Amelia , Davies Justine , Malava Jullita Kenala , Manganizithe Stella , Kumambala Annie , Sandford Becky 
Published: August 2022

ObjectiveLow/middle-income countries face a disproportionate burden of cardiovascular diseases. However, among cardiovascular diseases, burden of and associations with lower extremity disease (LED) (peripheral arterial disease and/or neuropathy) is neglected. We investigated the prevalence and factors associated with LED among individuals known to have cardiovascular disease risk factors (CVDRFs) in Malawi, a low-income country with a significant prevalence of CVDRFs.DesignThis was a stratified cross-sectional study.SettingThis study was conducted in urban Lilongwe Area 25, and the rural Karonga Health and Demographic Surveillance Site.ParticipantsParticipants were at least 18 years old and had been identified to have two or more known CVDRFs.Main outcome measuresLED—determined by the presence of one of the following: neuropathy (as assessed by a 10 g monofilament), arterial disease (absent peripheral pulses, claudication as assessed by the Edinburgh claudication questionnaire or Ankle Brachial Pulse Index (ABPI) <0.9), previous amputation or ulceration of the lower limbs.ResultsThere were 806 individuals enrolled into the study. Mean age was 52.5 years; 53.5% of participants were men (n=431) and 56.7% (n=457) were from the rural site. Nearly a quarter (24.1%; 95% CI: 21.2 to 27.2) of the participants had at least one symptom or sign of LED. 12.8% had neuropathy, 6.7% had absent pulses, 10.0% had claudication, 1.9% had ABPI <0.9, 0.9% had an amputation and 1.1% had lower limb ulcers. LED had statistically significant association with increasing age, urban residence and use of indoor fires.ConclusionsThis study demonstrated that a quarter of individuals with two or more CVDRFs have evidence of LED and 2.4% have an amputation or signs of limb threatening ulceration or amputation. Further epidemiological and health systems research is warranted to prevent LED and limb loss.
Inequalities in the evolution of the COVID-19 pandemic: an ecological study of inequalities in mortality in the first wave and the effects of the first national lockdown in England
Authors: Welsh Claire , Albani Viviana , Matthews Fiona , Bambra Clare 
Published: August 2022

ObjectivesTo examine how ecological inequalities in COVID-19 mortality rates evolved in England, and whether the first national lockdown impacted them. This analysis aimed to provide evidence for important lessons to inform public health planning to reduce inequalities in any future pandemics.DesignLongitudinal ecological study.Setting307 lower-tier local authorities in England.Primary outcome measureAge-standardised COVID-19 mortality rates by local authority, regressed on Index of Multiple Deprivation (IMD) and relevant epidemic dynamics.ResultsLocal authorities that started recording COVID-19 deaths earlier were more deprived, and more deprived authorities saw faster increases in their death rates. By 6 April 2020 (week 15, the earliest time that the 23 March lockdown could have begun affecting death rates) the cumulative death rate in local authorities in the two most deprived deciles of IMD was 54% higher than the rate in the two least deprived deciles. By 4 July 2020 (week 27), this gap had narrowed to 29%. Thus, inequalities in mortality rates by decile of deprivation persisted throughout the first wave, but reduced during the lockdown.ConclusionsThis study found significant differences in the dynamics of COVID-19 mortality at the local authority level, resulting in inequalities in cumulative mortality rates during the first wave of the pandemic. The first lockdown in England was fairly strict—and the study found that it particularly benefited those living in more deprived local authorities. Care should be taken to implement lockdowns early enough, in the right places—and at a sufficiently strict level—to maximally benefit all communities, and reduce inequalities.
Estimation of smoking-related mortality and its contribution to educational inequalities in life expectancy in Spain: an observational study, 2016–2019
Authors: Piñeiro Bárbara , Trias-Llimós Sergi , Spijker Jeroen J A , Blanes Llorens Amand , Permanyer Iñaki 
Published: August 2022

ObjectiveTo estimate smoking-related mortality and its contribution to educational inequalities in life expectancy in Spain.DesignNationwide, observational study from 2016 to 2019. Population-attributable fractions were used to estimate age, sex and education-specific cause-of-death smoking-attributable mortality. Life table techniques and decomposition methods were used to estimate potential gains in life expectancy at age 35 and the cause-specific contributions of smoking-related mortality to life expectancy differences across educational groups.SettingSpain.ParticipantsWe use cause-specific mortality data from population registers and smoking prevalence from the National and the European Health Survey for Spain from 2017 and 2019/2020, respectively.ResultsWe estimated 219 086 smoking-related deaths during 2016–2019, equalling 13% of all deaths, 83.7% of those in men. In the absence of smoking, potential gains in male life expectancy were higher among the low-educated than the high-educated (3.1 vs 2.1 years). For women, educational differences were less and also in the opposite direction (0.6 vs 0.9 years). The contribution of smoking to life expectancy differences between high-educated and low-educated groups accounted for 1.5 years among men, and −0.2 years among women. For men, the contribution of smoking to these differences was mostly driven by cancer in middle age, cardiometabolic diseases at younger ages and respiratory diseases at older ages. For women, the contribution to this gap, although negligible, was driven by cancer at older ages among the higher educated.ConclusionsSmoking remains a relevant preventable risk factor of premature mortality in Spain, disproportionately affecting life expectancy of low-educated men.
COCOS trial: COrticosteroids for COVID-19-induced loss of Smell–protocol for a single-centred, double-blind, randomised, placebo-controlled trial
Authors: Schepens Emma J A , Boek Wilbert M , Boesveldt Sanne , Stegeman Inge , Stokroos Robert J , Kamalski Digna M A 
Published: August 2022

IntroductionHyposmia and anosmia are common in COVID-19. Most patients regain normal smell within 4 weeks, but severe loss of smell persists roughly in 20% after 2 months and may last up to a year or longer. These persistent smell disorders greatly influence daily life. It is hypothesised that COVID-19 induces inflammation around the olfactory nerve and in the olfactory pathway, leading to smell disorders. Corticosteroids might reduce this local inflammatory response and improve smell.Methods and analysisWe will conduct a single-centre, randomised, placebo-controlled trial to determine the efficacy of a short high-dose treatment of oral prednisolone for persistent loss of smell after COVID-19 in the early phase. We will include 116 patients with persistent (>4 weeks) loss of smell within 12 weeks of COVID-19 diagnosis, based on a positive PCR/antigen test. One group receives 40 mg of prednisolone for 10 days and the other group receives matching placebo treatment. In addition, all patients will perform smell training for 12 weeks. The primary outcome is objective olfactory function measured by means of sniffin’ sticks test. Secondary outcomes are objective gustatory function by means of taste strips test and subjective taste and smell ability, trigeminal sensations, quality of life and nasal symptoms, measured by three questionnaires. These outcomes will be measured at inclusion before treatment and 12 weeks later.Ethics and disseminationThe Institutional Review Board of the University Medical Center Utrecht approved the research protocol (21-635/G-D, October 2021). The trial results will be shared in peer-reviewed medical journals and scientific conferences.Trial registration numberNL9635. EUCTR2021-004021-71-NL.
rTMS for poststroke pusher syndrome: study protocol for a randomised, patient-blinded controlled clinical trial
Authors: Meng Lijiao , Tsang Raymond C C , Ge Yanlei , Guo Qifan , Gao Qiang 
Published: August 2022

IntroductionPoststroke pusher syndrome (PS) prevalence is high. Patients with PS require longer rehabilitation with prolonged length of stay. Effective treatment of PS remains a challenge for rehabilitation professionals. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is effective and recommended in the clinical guidelines of stroke rehabilitation. However, the role of rTMS for PS has not been examined. The study is to assess the efficacy of a specific rTMS programme for patients with PS in reducing pushing behaviour, enhancing motor recovery and improving mobility, as well as testing the safety of rTMS for patients with PS.Methods and analysisA randomised, patient and assessor blinded sham-controlled trial with two parallel groups will be conducted. Thirty-four eligible patients with PS will be randomly allocated to receive either rTMS or sham rTMS for 3 weeks. The primary assessment outcome is the pushing behaviour measured by the Burke Lateropulsion Scale and Scale for Contraversive Pushing. The secondary outcomes are the motor functions and mobility measured by the Fugl-Meyer Assessment Scale (motor domain) and Modified Rivermead Mobility Index, and any adverse events. Assessment will be performed at baseline and 1 week, 2 weeks and 3 weeks after intervention. Repeated-measures analysis of variance will be used for data analysis with the level of significance level set at 0.05.Ethics and disseminationThe protocol has been approved by the Biomedical Ethics Committee of West China Hospital, Sichuan University on 23 March 2022 (2022-133). The trial findings will be published in peer-reviewed journals.Trial registration numberChinese Clinical Trial Registry (ChiCTR2200058015).
Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis
Authors: Yin Xuejun , Rodgers Anthony , Perkovic Adam , Huang Liping , Li Ka-Chun , Yu Jie , Wu Yangfeng , Wu J H Y , Marklund Matti , Huffman Mark D , Miranda J Jaime , Di Tanna Gian Luca , Labarthe Darwin , Elliott Paul , Tian Maoyi , Neal Bruce 
Published: August 2022

ObjectivesThe Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results.MethodsWe searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups.ResultsThere were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was −4.61 mm Hg (95% CI −6.07 to −3.14) and of diastolic blood pressure (DBP) was −1.61 mm Hg (95% CI −2.42 to −0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a −1.53 mm Hg (95% CI −3.02 to −0.03, p=0.045) greater reduction in SBP and a −0.95 mm Hg (95% CI −1.78 to −0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94).ConclusionsThe beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide.Trial registration numberCRD42020161077.
Shift work with and without night shifts and breast cancer risk in a cohort study from Finland
Authors: Härmä Mikko , Ojajärvi Anneli , Koskinen Aki , Lie Jenny-Anne , Hansen Johnni 
Published: August 2022

ObjectivesTo examine the association of shift work with and without night work with breast cancer among women in the public sector.MethodsUsing the Finnish Public Sector cohort study (N=33 359, mean age of 40.6 years at baseline), we investigated the associations of shift work and potential confounders with incident breast cancer. Exposure to permanent day work or shift work was defined from first two consecutive surveys from 2000, 2004, 2008 or 2012 and past information on exposure in a subcohort (n=20 786). Incident cases of breast cancer (n=1129) were retrieved from the National Cancer Register and the cohort members were followed to the end of 2016. HR and 95% CI from Cox proportional hazard regression models were calculated.ResultsShift work with and without night shifts was not overall associated with breast cancer. When stratified according to age, both shift work without nights (HR 2.01, 95% CI 1.12 to 3.60) and shift work with nights (OR 2.05, 95% CI 1.04 to 4.01) were associated with an increased risk after a period of 10 years or more follow-up among women aged 50 years or older, when adjusted for age, socioeconomic status, children, smoking, alcohol and body mass index. In a subgroup with past information on exposure to shift work, the increased risk by longer exposure to shift work was not significant.ConclusionsThis study provides support for an increased risk of breast cancer among elderly shift workers. However, insufficient information on exposure and intensity of night work may attenuate the risk estimates.
Performance status and survival in cancer patients undergoing palliative care: retrospective study
Authors: Allende-Pérez Silvia , Rodríguez-Mayoral Oscar , Peña-Nieves Adriana , Bruera Eduardo 
Published: August 2022

ObjectiveAccurate forecasting the life expectancy of patients with cancer is adamantly needed for adequate decision-making in the Palliative Care Services (PCS) context. Nonetheless, physician forecast is often inaccurate, hindering end of life (EOL) decisions. In this study, we determined the prognostic value of two oncology performance status (PS) scales at first referral to PCS.MethodsRetrospective analysis of 6310 patients consecutively admitted to PCS at the Instituto Nacional de Cancerología (2012–2018). Demographic and PS (as per Karnofsky (KPS) and Eastern Cooperative Oncology Group (ECOG) scales) information was retrieved and the overall survival of patients calculated according to PS. Concordance of each scale was assessed in the overall population and according to age.ResultsOverall survival was significantly associated with ECOG and KPS (p<0.05). A total of 2278 (36.1%) and 2296 (36.4%) patients were referred to PCS in their last month of life and most had a poor PS (ECOG 3–4, 59.1%; KPS <50, 54.4%). Both PS scales had high concordance in the overall population (K=0.6189 (KPS); K=0.6058 (ECOG)), but a higher value was observed among the subgroup of patients aged ≥65 (K=0.6339 (KPS); 0.6252 (ECOG)). Concordance was lowest among younger (≤39) patients.ConclusionsPS as assessed by the most widely known tools is strongly associated with overall survival of patients with cancer attending PCS. No large differences were observed among the scales, though results slightly favour the use of KPS. Early referral to PCS and accurate survival prediction can aid in relevant decision-making for patients approaching EOL.
Oscillatory positive expiratory pressure therapy in COPD (O-COPD): a randomised controlled trial
Authors: Alghamdi Saeed M , Alsulayyim Abdullah S , Alasmari Ali M , Philip Keir E J , Buttery Sara C , Banya Winston A S , Polkey Michael I , Birring Surinder S , Hopkinson Nicholas S 
Published: August 2022

BackgroundOscillatory positive expiratory pressure (OPEP) devices are intended to facilitate sputum clearance and reduce cough, but there is limited evidence for their effectiveness in COPD, or to guide patient selection. We aimed to assess the impact of OPEP therapy on quality of life and objective measures of cough and sleep disturbance in patients with COPD with regular sputum production.MethodsWe enrolled stable patients with COPD, who reported sputum production every day or most days, into an assessor-blind, parallel-group, randomised controlled trial comparing 3 months of using an Acapella device against usual care (including use of the active cycle of breathing technique). The primary outcome was cough-related quality of life measured using the Leicester Cough Questionnaire (LCQ). Secondary outcomes included fatigue (Functional Assessment of Chronic Illness Therapy, FACIT score) and generic quality of life (EuroQol-5 Dimensions, EQ-5D). In a substudy (n=45), objective monitoring of cough and disturbance/movement during sleep were also available.Results122 participants (61/61 OPEP/control) were recruited, 40% female, 17% smokers, FEV1 38 (25–56)% predicted, and age 62±10 years. 103 completed the study (55/48 OPEP/control). Use of OPEP was associated with an improvement in LCQ compared with controls; MD (95% CI) 1.03 (0.71 to 2.10); (p=0.03), FACIT score 4.68 (1.34 to 8.02); (p<0.001) and EQ-5D 4.00 (0.49 to 19.75); (p=0.04). There was also an improvement in cough frequency −60 (−43 to −95) coughs/24 hours (p<0.001), but no statistically significant effect on sleep disturbance was identified.ConclusionsRegular use of an Acapella device improves symptoms and quality of life in people with COPD who produce sputum daily or most days.Trial registration numberISRCTN44651852.
Mesenchymal stromal cells-derived extracellular vesicles reprogramme macrophages in ARDS models through the miR-181a-5p-PTEN-pSTAT5-SOCS1 axis
Authors: Su Yue , Silva Johnatas Dutra , Doherty Declan , Simpson David A , Weiss Daniel J , Rolandsson-Enes Sara , McAuley Daniel F , O'Kane Cecilia M , Brazil Derek P , Krasnodembskaya Anna D 
Published: August 2022

RationaleA better understanding of the mechanism of action of mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) is needed to support their use as novel therapies for acute respiratory distress syndrome (ARDS). Macrophages are important mediators of ARDS inflammatory response. Suppressor of cytokine signalling (SOCS) proteins are key regulators of the macrophage phenotype switch. We therefore investigated whether SOCS proteins are involved in mediation of the MSC effect on human macrophage reprogramming.MethodsHuman monocyte-derived macrophages (MDMs) were stimulated with lipopolysaccharide (LPS) or plasma samples from patients with ARDS (these samples were previously classified into hypo-inflammatory and hyper-inflammatory phenotype) and treated with MSC conditioned medium (CM) or EVs. Protein expression was measured by Western blot. EV micro RNA (miRNA) content was determined by miRNA sequencing. In vivo: LPS-injured C57BL/6 mice were given EVs isolated from MSCs in which miR-181a had been silenced by miRNA inhibitor or overexpressed using miRNA mimic.ResultsEVs were the key component of MSC CM responsible for anti-inflammatory modulation of human macrophages. EVs significantly reduced secretion of tumour necrosis factor-α and interleukin-8 by LPS-stimulated or ARDS plasma-stimulated MDMs and this was dependent on SOCS1. Transfer of miR-181a in EVs downregulated phosphatase and tensin homolog (PTEN) and subsequently activated phosphorylated signal transducer and activator of transcription 5 (pSTAT5) leading to upregulation of SOCS1 in macrophages. In vivo, EVs alleviated lung injury and upregulated pSTAT5 and SOCS1 expression in alveolar macrophages in a miR181-dependent manner. Overexpression of miR-181a in MSCs significantly enhanced therapeutic efficacy of EVs in this model.ConclusionmiR-181a-PTEN-pSTAT5-SOCS1 axis is a novel pathway responsible for immunomodulatory effect of MSC EVs in ARDS.