bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation to identify individual socioeconomic and health determinants of suicidal ideation using responses to a cross-sectional, community-based public health survey
Authors: Mulholland Helen , McIntyre Jason C , Haines-Delmont Alina , Whittington Richard , Comerford Terence , Corcoran Rhiannon 
Published: February 2021

ObjectivesTo address a gap in knowledge by simultaneously assessing a broad spectrum of individual socioeconomic and potential health determinants of suicidal ideation (SI) using validated measures in a large UK representative community sample.DesignIn this cross-sectional design, participants were recruited via random area probability sampling to participate in a comprehensive public health survey. The questionnaire examined demographic, health and socioeconomic factors. Logistic regression analysis was employed to identify predictors of SI.SettingCommunity setting from high (n=20) and low (n=8) deprivation neighbourhoods across the North West of England, UK.Participants4319 people were recruited between August 2015 and January 2016. There were 809 participants from low-deprivation neighbourhoods and 3510 from high-deprivation neighbourhoods. The sample comprised 1854 (43%) men and 2465 (57%) women.Primary outcome measuresSI was the dependent variable which was assessed using item 9 of the Patient Health Questionnaire-9 instrument.Results454 (11%) participants reported having SI within the last 2 weeks. Model 1 (excluding mental health variables) identified younger age, black and minority ethnic (BME) background, lower housing quality and current smoker status as key predictors of SI. Higher self-esteem, empathy and neighbourhood belonging, alcohol abstinence and having arthritis were protective against SI. Model 2 (including mental health variables) found depression and having cancer as key health predictors for SI, while identifying as lesbian, gay, bisexual, transgender or queer (LGBTQ) and BME were significant demographic predictors. Alcohol abstinence, having arthritis and higher empathy levels were protective against SI.ConclusionsThis study suggests that it could be useful to increase community support and sense of belonging using a public health approach for vulnerable groups (e.g. those with cancer) and peer support for people who identify as LGBTQ and/or BME. Also, interventions aimed at increasing empathic functioning may prove effective for reducing SI.
Novel approach to meta-analysis of tests and clinical prediction rules with three or more risk categories
Authors: Ebell Mark H , Walsh Mary E , Boland Fiona , McKay Brian , Fahey Tom 
Published: February 2021

ObjectiveMultichotomous tests have three or more outcome or risk categories, and can provide richer information and a better fit with clinical decision-making than dichotomous tests. Our objective is to present a fully developed approach to the meta-analysis of multichotomous clinical prediction rules (CPRs) and tests, including meta-analysis of stratum specific likelihood ratios.Study designWe have developed a novel approach to the meta-analysis of likelihood ratios for multichotomous tests that avoids the need to dichotomise outcome categories, and demonstrate its application to a sample CPR. We also review previously reported approaches to the meta-analysis of the area under the receiver operating characteristic curve (AUROCC) and meta-analysis of a measure of calibration (observed:expected) for multichotomous tests or CPRs.ResultsUsing data from 10 studies of the Cancer of the Prostate Risk Assessment (CAPRA) risk score for prostate cancer recurrence, we calculated summary estimates of the likelihood ratios for low, moderate and high risk groups of 0.40 (95% CI 0.32 to 0.49), 1.24 (95% CI 0.99 to 1.55) and 4.47 (95% CI 3.21 to 6.23), respectively. Applying the summary estimates of the likelihood ratios for each risk group to the overall prevalence of cancer recurrence in a population allows one to estimate the likelihood of recurrence for each risk group in that population.ConclusionAn approach to meta-analysis of multichotomous tests or CPRs is presented. A spreadsheet for data preparation and code for R and Stata are provided for other researchers to download and use. Combined with summary estimates of the AUROCC and calibration, this is a comprehensive strategy for meta-analysis of multichotomous tests and CPRs.
SOS! Summer of Smoke: a retrospective cohort study examining the cardiorespiratory impacts of a severe and prolonged wildfire season in Canada’s high subarctic
Authors: Howard Courtney , Rose Caren , Dodd Warren , Kohle Katherine , Scott Craig , Scott Patrick , Cunsolo Ashlee , Orbinski James 
Published: February 2021

ObjectivesTo determine healthcare service utilisation for cardiorespiratory presentations and outpatient salbutamol dispensation associated with 2.5 months of severe, unabating wildfire smoke in Canada’s high subarctic.DesignA retrospective cohort study using hospital, clinic, pharmacy and environmental data analysed using Poisson regression.SettingTerritorial referral hospital and clinics in Yellowknife, Northwest Territories, Canada.ParticipantsIndividuals from Yellowknife and surrounding communities presenting for care between 2012 and 2015.Main outcome measuresEmergency room (ER) presentations, hospital admissions and clinic visits for cardiorespiratory events, and outpatient salbutamol prescriptionsResultsThe median 24-hour mean particulate matter (PM2.5) was fivefold higher in the summer of 2014 compared with 2012, 2013 and 2015 (median=30.8 µg/m3), with the mean peaking at 320.3 µg/m3. A 10 µg/m3 increase in PM2.5 was associated with an increase in asthma-related (incidence rate ratio (IRR) (95% CI): 1.11 (1.07, 1.14)) and pneumonia-related ER visits (IRR (95% CI): 1.06 (1.02, 1.10)), as well as an increase in chronic obstructive pulmonary disease hospitalisations (IRR (95% CI): 1.11 (1.02, 1.20). Compared with 2012 and 2013, salbutamol dispensations in 2014 increased by 48%; clinic visits for asthma, pneumonia and cough increased; ER visits for asthma doubled, with the highest rate in females, in adults aged ≥40 years and in Dene people, while pneumonia increased by 57%, with higher rates in males, in individualsaged <40 years and in Inuit people. Cardiac variables were unchanged.ConclusionsSevere wildfires in 2014 resulted in extended poor air quality associated with increases in health resource utilization; some impacts were seen disproportionately among vulnerable populations, such as children and Indigenous individuals. Public health advisories asking people to stay inside were inadequately protective, with compliance possibly impacted by the prolonged exposure. Future research should investigate use of at-home air filtration systems, clean-air shelters and public health messaging which addresses mental health and supports physical activity.
Cost analysis of a mobile medical unit programme in Andhra Pradesh: a microcosting study protocol
Authors: Raikwar Aakash Ashok , Dogra Vishal , Giri Ashish , Rathnam Nitin , Hegde Shailendra Kumar 
Published: February 2021

IntroductionOffering primary healthcare through mobile medical units is an innovative way to reach the rural and the vulnerable population. With 292 mobile medical units, the Andhra Pradesh mobile medical unit (APMMU) programme is one of the largest health outreach programmes in rural India. However, India lacks reliable cost estimates for the health services delivered through mobile medical platforms. This study aims to estimate the unit cost of providing primary care services through mobile medical units in rural and tribal areas of Andhra Pradesh.Method and analysisCost analysis of 12 mobile medical units will be undertaken. We will use the activity-based microcosting technique from the providers’ perspective. A bottom-up approach will be used for cost estimation. Standardised tools will be used to collect data on activities and resources, and on the costs. Capital investments and recurrent costs will be measured and evaluated. Average unit costs, along with 95% CIs, will be reported. Sensitivity analysis will assess the cost estimate uncertainties and other cost assumptions.Ethics and disseminationPiramal Swasthya Management Research Institute’s ethics committee approved the study. The findings of the study will be disseminated through conference presentations, publications in peer-reviewed journals and advocacy with the national and state governments. This study will provide first-hand comprehensive cost estimates of provisioning primary healthcare services using mobile medical units in India.
Association among age, gender, menopausal status and small dense low-density lipoprotein cholesterol: a cross-sectional study
Authors: Izumida Toshihide , Nakamura Yosikazu , Sato Yukihiro , Ishikawa Shizukiyo 
Published: February 2021

ObjectivesSmall dense low-density lipoprotein cholesterol (sdLDL-C) might be a better cardiovascular disease (CVD) indicator than low-density lipoprotein cholesterol (LDL-C); however, details regarding its epidemiology remain elusive. The present study aimed at evaluating the association between the demographic factors, such as age, gender and menopausal status, and sdLDL-C levels and sdLDL-C/LDL-C ratio in the Japanese population.DesignThis was a cross-sectional study.Setting13 rural districts in Japan, 2010–2017.ParticipantsThis study included 5208 participants (2397 men and 2811 women), who underwent the health mass screening that was conducted in accordance with the medical care system for the elderly and obtained informed consent for this study.ResultsIn total, 517 premenopausal women (mean age ±SD, 45.1±4.2 years), 2294 postmenopausal women (66.5±8.8 years) and 2397 men (64.1±11.2 years) were analysed. In men, the sdLDL-C levels and sdLDL-C/LDL-C ratio increased during younger adulthood, peaked (36.4 mg/dL, 0.35) at 50–54 years, and then decreased. In women, relatively regular increasing trends of sdLDL-C level and sdLDL-C/LDL-C ratio until approximately 65 years (32.7 mg/dL, 0.28), followed by a downward or pleated trend. Given the beta value of age, body mass index, fasting glucose and smoking and drinking status by multiple linear regression analysis, standardised sdLDL-C levels and sdLDL-C/LDL-C ratio in 50-year-old men, premenopausal women and postmenopausal women were 26.6, 22.7 and 27.4 mg/dL and 0.24, 0.15 and 0.23, respectively. The differences between premenopausal and postmenopausal women were significant (p<0.001).ConclusionsSdLDL-C and sdLDL-C/LDL-C ratios showed different distributions by age, gender and menopausal status. A subgroup-specific approach would be necessary to implement sdLDL-C for CVD prevention strategies, fully considering age-related trends, gender differences and menopausal status.
Country-level determinants of the severity of the first global wave of the COVID-19 pandemic: an ecological study
Authors: Pana Tiberiu A , Bhattacharya Sohinee , Gamble David T , Pasdar Zahra , Szlachetka Weronika A , Perdomo-Lampignano Jesus A , Ewers Kai D , McLernon David J , Myint Phyo K 
Published: February 2021

ObjectiveWe aimed to identify the country-level determinants of the severity of the first wave of the COVID-19 pandemic.DesignEcological study of publicly available data. Countries reporting >25 COVID-19 related deaths until 8 June 2020 were included. The outcome was log mean mortality rate from COVID-19, an estimate of the country-level daily increase in reported deaths during the ascending phase of the epidemic curve. Potential determinants assessed were most recently published demographic parameters (population and population density, percentage population living in urban areas, population >65 years, average body mass index and smoking prevalence); economic parameters (gross domestic product per capita); environmental parameters (pollution levels and mean temperature (January–May); comorbidities (prevalence of diabetes, hypertension and cancer); health system parameters (WHO Health Index and hospital beds per 10 000 population); international arrivals; the stringency index, as a measure of country-level response to COVID-19; BCG vaccination coverage; UV radiation exposure; and testing capacity. Multivariable linear regression was used to analyse the data.Primary outcomeCountry-level mean mortality rate: the mean slope of the COVID-19 mortality curve during its ascending phase.ParticipantsThirty-seven countries were included: Algeria, Argentina, Austria, Belgium, Brazil, Canada, Chile, Colombia, the Dominican Republic, Ecuador, Egypt, Finland, France, Germany, Hungary, India, Indonesia, Ireland, Italy, Japan, Mexico, the Netherlands, Peru, the Philippines, Poland, Portugal, Romania, the Russian Federation, Saudi Arabia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the UK and the USA.ResultsOf all country-level determinants included in the multivariable model, total number of international arrivals (beta 0.033 (95% CI 0.012 to 0.054)) and BCG vaccination coverage (−0.018 (95% CI −0.034 to –0.002)), were significantly associated with the natural logarithm of the mean death rate.ConclusionsInternational travel was directly associated with the mortality slope and thus potentially the spread of COVID-19. Very early restrictions on international travel should be considered to control COVID-19 outbreaks and prevent related deaths.
Neonatal mortality and leading causes of deaths: a descriptive study in China, 2014–2018
Authors: Liu Yuxi , Kang Leni , He Chunhua , Miao Lei , Qiu Xiaoqiong , Xia Weipeng , Zhu Jun , Liang Juan , Li Qi , Wang Yanping , Liu Hanmin 
Published: February 2021

ObjectiveThe present study estimated the national and urban–rural levels and causes of neonatal deaths in China annually between 2014 and 2018 to provide data support for the further end of preventable neonatal deaths for China and other low-income and middle-income countries.MethodsThe study was based on data from the National Maternal and Child Health Surveillance System. All neonates of surveillance districts (gestational week: ≥28 weeks) who died after delivery have been involved in the study. The mortality rate and the leading causes of death for neonates were analysed.ResultsThe neonatal mortality rate (NMR) of China has steadily decreased from 5.9 deaths per 1000 live births in 2014 to 3.9 deaths per 1000 live births in 2018. The NMR in 2018 of urban and rural areas was 2.2 deaths per 1000 live births and 4.7 deaths per 1000 live births, respectively. The leading preventable causes of neonatal deaths are the same in the urban and rural areas were same, which were preterm birth, intrapartum complications and pneumonia. Mortality rates of these three causes fell significantly between 2014 and 2018 but contributed to a higher proportion of deaths in rural areas than urban areas. The proportion of preventable deaths accounted for 74.6% in 2018.ConclusionsThe NMR of China has decreased steadily from 2014 to 2018. However, the inequality between urban and rural areas still exists. The goal of government interventions should be to reduce the health inequality of neonates and further take targeted measures to eliminate preventable neonatal death.
Clinical and cost-effectiveness of an online-delivered group-based pain management programme in improving pain-related disability for people with persistent pain—protocol for a non-inferiority randomised controlled trial (iSelf-help trial)
Authors: Hale Leigh , Devan Hemakumar , Davies Cheryl , Dean Sarah Gerard , Dowell Anthony , Grainger Rebecca , Gray Andrew R , Hempel Dagmar , Ingham Tristram , Jones Bernadette , Leung William , Mills Jessica , Saipe Barbara , Shipton Edward , Perry Meredith 
Published: February 2021

IntroductionPersistent non-cancer pain affects one in five adults and is more common in Māori—the Indigenous population of New Zealand (NZ), adults over 65 years, and people living in areas of high deprivation. Despite the evidence supporting multidisciplinary pain management programmes (PMPs), access to PMPs is poor due to long waiting lists. Although online-delivered PMPs enhance access, none have been codesigned with patients or compared with group-based, in-person PMPs. This non-inferiority trial aims to evaluate the clinical and cost-effectiveness of a cocreated, culturally appropriate, online-delivered PMP (iSelf-help) compared with in-person PMP in reducing pain-related disability.Methods and analysisMixed-methods, using a modified participatory action research (PAR) framework, involving three phases. Phase I involved cocreation and cultural appropriateness of iSelf-help by PAR team members. Phase II: The proposed iSelf-help trial is a pragmatic, multicentred, assessor-blinded, two-arm, parallel group, non-inferiority randomised controlled trial. Adults (n=180, age ≥18 years) with persistent non-cancer pain eligible for a PMP will be recruited and block randomised (with equal probabilities) to intervention (iSelf-help) and control groups (in-person PMP). The iSelf-help participants will participate in two 60-minute video-conferencing sessions weekly for 12 weeks with access to cocreated resources via smartphone application and a password-protected website. The control participants will receive group-based, in-person delivered PMP. Primary outcome is pain-related disability assessed via modified Roland Morris Disability Questionnaire at 6 months post intervention. Secondary outcomes include anxiety, depression, stress, pain severity, quality of life, acceptance, self-efficacy, catastrophising and fear avoidance. Data will be collected at baseline, after the 12-week intervention, and at 3 and 6 months post intervention. We will conduct economic analyses and mixed-method process evaluations (Phase IIA).Ethics and disseminationThe Health and Disability Ethics Committee approved the study protocol (HDEC18/CEN/162). Phase III involves dissemination of findings guided by the PAR team as outcomes become apparent.Trial registration numberACTRN 12619000771156.
Closing schools for SARS-CoV-2: a pragmatic rapid recommendation
Authors: Bekkering Geertruida , Delvaux Nicolas , Vankrunkelsven Patrik , Toelen Jaan , Aertgeerts Sigrid , Crommen Sofie , Bruyckere Pedro De , Devisch Ignaas , Lernout Tinne , Masschalck Katrien , Milissen Nore , Molenberghs Geert , Pascal Annelies , Plomteux Oscar , Raes Marc , Rans Lise , Seghers Alexandra , Sweldens Lode , Vandenbussche Jeroen , Vanham Guido , Wollants Elke , Aertgeerts Bert 
Published: February 2021

BackgroundIn Belgium, schools closed during the first lockdown in March 2020, with a partial reopening in May. They fully reopened in September. During the summer, infections started to increase in the general population, speeding up in September. Some measures were taken to limit social contacts but those were insufficient to mitigate the exponential rise of infections in October. Children were still receiving all lessons at school at that time and it was questioned whether this position was tenable. We systematically compared the benefits and harms of closing primary and secondary schools and developed a recommendation.MethodsA multidisciplinary panel, including school pupils and teachers, educational experts, clinicians and researchers, produced this recommendation in compliance with the standards for trustworthy rapid guidelines. The recommendation is based on data collected through national surveillance or studies from Belgium, and supported by a rapid literature review.ResultsClosing schools during the first lockdown probably resulted in a large learning delay and possibly led to more cases of child abuse. We are uncertain about the effect on the infection rate, hospitalisations, transmission rates, mental health of children, teachers and parents. The panel concluded that the balance of benefits and harms of closing schools clearly shifts against closing schools. Detrimental effects are even worse for vulnerable children. This recommendation is affected by the local virus circulation.ConclusionThe guideline panel issues a strong recommendation against closing schools when the virus circulation is low to moderate, and a weak recommendation against closing schools when the virus circulation is high. It does not apply when the school system cannot function due to lack of teachers, too many children who are at home or a shortage of support services. As the results of international studies are consistent with Belgian study results, this recommendation may also be relevant internationally.
Optimized EGFR Blockade Strategies in EGFR Addicted Gastroesophageal Adenocarcinomas
Authors: Corso Simona , Pietrantonio Filippo , Apicella Maria , Migliore Cristina , Conticelli Daniela , Petrelli Annalisa , D'Errico Laura , Durando Stefania , Moya-Rull Daniel , Bellomo Sara E. , Ughetto Stefano , Degiuli Maurizio , Reddavid Rossella , Fumagalli Uberto , De Pascale Stefano , Sgroi Giovanni , Rausa Emanuele , Baiocchi Gian Luca , Molfino Sarah , De Manzoni Giovanni , Bencivenga Maria , Siena Salvatore , Sartore-Bianchi Andrea , Morano Federica , Corallo Salvatore , Prisciandaro Michele , Di Bartolomeo Maria , Gloghini Annunziata , Marsoni Silvia , Sottile Antonino , Sapino Anna , Marchiò Caterina , Dahle-Smith Asa , Miedzybrodzka Zosia , Lee Jessica , Ali Siraj M. , Ross Jeffrey S. , Alexander Brian M. , Miller Vincent A. , Petty Russell , Schrock Alexa B. , Giordano Silvia 
Published: February 2021

Abstract

Purpose:
Gastric and gastroesophageal adenocarcinomas represent the third leading cause of cancer mortality worldwide. Despite significant therapeutic improvement, the outcome of patients with advanced gastroesophageal adenocarcinoma is poor. Randomized clinical trials failed to show a significant survival benefit in molecularly unselected patients with advanced gastroesophageal adenocarcinoma treated with anti-EGFR agents.

Experimental Design:
We performed analyses on four cohorts: IRCC (570 patients), Foundation Medicine, Inc. (9,397 patients), COG (214 patients), and the Fondazione IRCCS Istituto Nazionale dei Tumori (206 patients). Preclinical trials were conducted in patient-derived xenografts (PDX).

Results:
The analysis of different gastroesophageal adenocarcinoma patient cohorts suggests that EGFR amplification drives aggressive behavior and poor prognosis. We also observed that EGFR inhibitors are active in patients with EGFR copy-number gain and that coamplification of other receptor tyrosine kinases or KRAS is associated with worse response. Preclinical trials performed on EGFR-amplified gastroesophageal adenocarcinoma PDX models revealed that the combination of an EGFR mAb and an EGFR tyrosine kinase inhibitor (TKI) was more effective than each monotherapy and resulted in a deeper and durable response. In a highly EGFR-amplified nonresponding PDX, where resistance to EGFR drugs was due to inactivation of the TSC2 tumor suppressor, cotreatment with the mTOR inhibitor everolimus restored sensitivity to EGFR inhibition.

Conclusions:
This study underscores EGFR as a potential therapeutic target in gastric cancer and identifies the combination of an EGFR TKI and a mAb as an effective therapeutic approach. Finally, it recognizes mTOR pathway activation as a novel mechanism of primary resistance that can be overcome by the combination of EGFR and mTOR inhibitors.
See related commentary by Openshaw et al., p. 2964