bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cataract-causing G91del mutant destabilised βA3 heteromers formation linking with structural stability and cellular viability
Authors: Wang Huaxia , Tian Qing , Xu Jingjie , Xu Wanyue , Yao Ke , Chen Xiangjun 
Published: September 2021

Background/aimsCongenital cataracts, which are genetically heterogeneous eye disorders, result in visual loss in childhood around the world. CRYBA1/BA3 serves as an abundant structural protein in the lens, and forms homomers and heteromers to maintain lens transparency. In previous study, we identified a common cataract-causing mutation, βA3-glycine at codon 91 (G91del) (c.271–273delGAG), which deleted a highly conserved G91del and led to perinuclear zonular cataract. In this study, we aimed to explore the underlying pathogenic mechanism of G91del mutation.MethodsProtein purification, size-exclusion chromatography, spectroscopy and molecular dynamics simulation assays were used to investigate the effects on the heteromers formation and the protein structural properties of βA3-crystallin caused by G91del mutation. Intracellular βA3-G91del overexpression, MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide) and cell apoptosis were used to investigate the cellular functions of βA3-G91del.ResultsβA3-crystallin and βB2-crystallin could form heteromers, which have much more stable structures than βA3 homomers. Interestingly, βA3/βB2 heteromers improved their resistance against the thermal stress and the guanidine hydrochloride treatment. However, the pathogenic mutation βA3-G91del destroyed the interaction with βB2, and thereby decreased its structural stability as well as the resistance of thermal or chemical stress. What’s more, the βA3-G91del mutation induced cell apoptosis and escaped from the protection of βB2-crystallin.ConclusionsβA3/βB2 heteromers play an indispensable role in maintaining lens transparency, while the βA3-G91del mutation destabilises heteromers formation with βB2-crystallin, impairs cellular viability and induces cellular apoptosis. These all might contribute to cataract development.
Diarrhoea and preadmission antibiotic exposure in COVID-19: a retrospective cohort study of 1153 hospitalised patients
Authors: Mateen Bilal Akhter , Samanta Sandip , Tullie Sebastian , O’Neill Sarah , Cargill Zillah , Kelly Gillian , Brennan Ewen , Patel Mehul , Al-Agil Mohammad , Galloway James , Teo James , Shawcross Debbie L , Kent Alexandra J , Hayee Bu'Hussain 
Published: September 2021

ObjectiveThe aims of this study were to describe community antibiotic prescribing patterns in individuals hospitalised with COVID-19, and to determine the association between experiencing diarrhoea, stratified by preadmission exposure to antibiotics, and mortality risk in this cohort.Design/methodsRetrospective study of the index presentations of 1153 adult patients with COVID-19, admitted between 1 March 2020 and 29 June 2020 in a South London NHS Trust. Data on patients’ medical history (presence of diarrhoea, antibiotic use in the previous 14 days, comorbidities); demographics (age, ethnicity, and body mass index); and blood test results were extracted. Time to event modelling was used to determine the risk of mortality for patients with diarrhoea and/or exposure to antibiotics.Results19.2% of the cohort reported diarrhoea on presentation; these patients tended to be younger, and were less likely to have recent exposure to antibiotics (unadjusted OR 0.64, 95% CI 0.42 to 0.97). 19.1% of the cohort had a course of antibiotics in the 2 weeks preceding admission; this was associated with dementia (unadjusted OR 2.92, 95% CI 1.14 to 7.49). After adjusting for confounders, neither diarrhoea nor recent antibiotic exposure was associated with increased mortality risk. However, the absence of diarrhoea in the presence of recent antibiotic exposure was associated with a 30% increased risk of mortality.ConclusionCommunity antibiotic use in patients with COVID-19, prior to hospitalisation, is relatively common, and absence of diarrhoea in antibiotic-exposed patients may be associated with increased risk of mortality. However, it is unclear whether this represents a causal physiological relationship or residual confounding.
Implementation of a non-emergent medical transportation programme at an integrated health system
Authors: Lyons Patrick G , Ramsey Brett A , Welker Michael , Guinn Megan , Ernest Janice K , Kosydor Ali , Maddox Thomas M 
Published: September 2021

ObjectivesTo implement a unified non-emergency medical transportation (NEMT) service across a large integrated healthcare delivery network.MethodsWe assessed needs among key organisational stakeholders, then reviewed proposals. We selected a single NEMT vendor best aligned with organisational priorities and implemented this solution system-wide.ResultsOur vendor’s hybrid approach combined rideshares with contracted vehicles able to serve patients with equipment and other needs. After 6195 rides in the first year, we observed shorter wait times and lower costs compared with our prior state.DiscussionEssential lessons included (1) understanding user and patient needs, (2) obtaining complete, accurate and comprehensive baseline data and (3) adapting existing workflows—rather than designing de novo—whenever possible.ConclusionsOur implementation of a single-vendor NEMT solution validates the need for NEMT at large healthcare organisations, geographical challenges to establishing NEMT organisation-wide, and the importance of baseline data and stakeholder engagement.
Association between serum phosphate and mortality in critically ill patients: a large retrospective cohort study
Authors: Chen Yang , Luo Mengdi , Xu Huange , Zhao Weiwei , He Qing 
Published: September 2021

ObjectivesThis research aims to explore the impact of serum phosphate on the mortality of critically ill patients.DesignA retrospective large cohort study.SettingOur data were extracted from a publicly accessible database named ‘Multiparameter Intelligent Monitoring in Intensive Care Database III’.Participants27 131 patients were included by clear definitions of selection and exclusion criteria.InterventionsWe used initial phosphate at admission as a design variable. Patients were divided into six groups with different serum phosphate levels and five groups at different intensive care unit (ICU) departments.Primary and secondary outcomes28-day and 90-day mortality were primary outcomes. All-cause mortality and length of stay ICU were secondary outcomes.ResultsPatients with very-high-normal serum phosphate, hypophosphataemia and hyperphosphataemia had worse outcomes. And the relationship between serum phosphate and the probability of 28-day or 90-day mortality had a linear relationship. After adjustment for potential confounders, hypophosphataemia and hyperphosphataemia were not significantly associated with 28-day or 90-day mortality. Nevertheless, at the medical ICU, hyperphosphataemia was associated with increased 28-day or 90-day mortality (HR=0.64, 95% CI 0.48 to 0.84, p=0.0017; HR=0.72, 95% CI 0.57 to 0.91, p=0.0067, respectively), using group 2 (≥2.5 mg/dL and <3.0 mg/dL) as the reference group.ConclusionsPatients with very-high-normal serum phosphate also had worse outcomes, it might be necessary to re-evaluate the definitions of the normal reference range for serum phosphate. Hypophosphataemia and hyperphosphataemia are not the independent risk factors of 28-day or 90-day ICU mortality, which leads us to consider whether phosphate monitoring is not a necessary measure in critically ill patients. But hyperphosphataemia was associated with increased 28-day or 90-day mortality at the medical ICU, which emphasises the potential importance of early diagnosis and treatment of hyperphosphataemia for the patients who were admitted to the medical ICU.
Insight into the process of postpartum care utilisation and in-home support among vulnerable women in the Netherlands: an in-depth qualitative exploration
Authors: Laureij Lyzette T , van der Hulst Marije , Lagendijk Jacqueline , Been Jasper V , Ernst-Smelt Hiske E , Franx Arie , Lugtenberg Marjolein 
Published: September 2021

ObjectiveTo gain insight into the process of postpartum care utilisation and in-home support among vulnerable women.Design, method, participants and settingA qualitative interview study was conducted among 23 pregnant and postpartum vulnerable women in the Netherlands, following a grounded theory approach. Women were determined as vulnerable by their healthcare providers. Theoretical sampling of participants was applied and was alternated by data analysis to include information-rich cases until saturation was achieved.ResultsA conceptual framework of postpartum care utilisation was generated consisting of three phases: pregnancy, early postpartum period and late postpartum period. Within these phases, information provision, parenting self-efficacy and social network were identified as overarching themes. Perceived inadequate information on content of postpartum care posed a major barrier to forming realistic expectations during pregnancy and hindered its utilisation. Low self-efficacy facilitated postpartum care utilisation. All women experienced increased self-efficacy during and after postpartum care. Support from a social network influenced expectations regarding the added value of postpartum care during pregnancy, and lowered actual utilisation during the postpartum period. The costs of postpartum care and the role of the maternity care assistant acted as general barriers or facilitators influencing the three overarching themes and therefore postpartum care utilisation indirectly.ConclusionsOur findings suggest that postpartum care utilisation among vulnerable women may be improved by considering the particular phase and relevant themes applying to individual women, and adapt care accordingly. We recommend to provide comprehensive, understandable information and to emphasise the gains of postpartum care in improving self-efficacy for vulnerable women. Moreover, involving a woman’s social network in postpartum care may add value to this care for this population.
Lag times in the publication of network meta-analyses: a survey
Authors: Tonin Fernanda S , Araujo Ariane G , Fachi Mariana M , Ferreira Vinicius L , Pontarolo Roberto , Fernandez-Llimos Fernando 
Published: September 2021

ObjectiveWe assessed the extent of lag times in the publication and indexing of network meta-analyses (NMAs).Study designThis was a survey of published NMAs on drug interventions.SettingNMAs indexed in PubMed (searches updated in May 2020).Primary and secondary outcome measuresLag times were measured as the time between the last systematic search and the article submission, acceptance, online publication, indexing and Medical Subject Headings (MeSH) allocation dates. Time-to-event analyses were performed considering independent variables (geographical origin, Journal Impact Factor, Scopus CiteScore, open access status) (SPSS V.24, R/RStudio).ResultsWe included 1245 NMAs. The median time from last search to article submission was 6.8 months (204 days (IQR 95–381)), and to publication was 11.6 months. Only 5% of authors updated their search after first submission. There is a very slightly decreasing historical trend of acceptance (rho=−0.087; p=0.010), online publication (rho=−0.080; p=0.008) and indexing (rho=−0.080; p=0.007) lag times. Journal Impact Factor influenced the MeSH allocation process, but not the other lag times. The comparison between open access versus subscription journals confirmed meaningless differences in acceptance, online publication and indexing lag times.ConclusionEfforts by authors to update their search before submission are needed to reduce evidence production time. Peer reviewers and editors should ensure authors’ compliance with NMA standards. The accuracy of these findings depends on the accuracy of the metadata used; as we evaluated only NMA on drug interventions, results may not be generalisable to all types of studies.
Patterns of sexual violence against adults and children during the COVID-19 pandemic in Kenya: a prospective cross-sectional study
Authors: Rockowitz Sarah , Stevens Laura M , Rockey James C , Smith Lisa L , Ritchie Jessica , Colloff Melissa F , Kanja Wangu , Cotton Jessica , Njoroge Dorothy , Kamau Catherine , Flowe Heather D 
Published: September 2021

ObjectivesThis study examined patterns of sexual violence against adults and children in Kenya during the COVID-19 pandemic to inform sexual violence prevention, protection, and response efforts.DesignA prospective cross-sectional research design was used with data collected from March to August 2020.SettingKenya.Participants317 adults, 224 children.Main measuresPerpetrator and survivor demographic data, characteristics of the assault.ResultsBivariate analyses found that children were more likely than adults to be attacked during daytime (59% vs 44%, p<0.001) by a single perpetrator rather than multiple perpetrators (31% vs 13%, p<0.001) in a private as opposed to a public location (66% vs 45%, p<0.001) and by someone known to the child (76% vs 58%, p<0.001). Children were violated most often by neighbours (29%) and family members (20%), whereas adults were equally likely to be attacked by strangers (41%) and persons known to them (59%). These variables were entered as predictors into a logistic regression model that significantly predicted the age group of the survivor, χ2(5, n=541)=53.3, p<0.001.ConclusionsPatterns of sexual violence against adult and child survivors during the COVID-19 pandemic are different, suggesting age-related measures are needed in national emergency plans to adequately address sexual violence during the pandemic and for future humanitarian crises.
Implementation of patient-centred care: which system-level determinants matter from a decision maker’s perspective? Results from a qualitative interview study across various health and social care organisations
Authors: Leidner Carmen , Vennedey Vera , Hillen Hendrik , Ansmann Lena , Stock Stephanie , Kuntz Ludwig , Pfaff Holger , Hower Kira Isabel 
Published: September 2021

ObjectivesThe healthcare system is characterised by a high degree of complexity and involves various actors at different institutional levels and in different care contexts. To implement patient-centred care (PCC) successfully, a multidimensional consideration of influencing factors is required. Our qualitative study aims to identify system-level determinants of PCC implementation from the perspective of different health and social care organisations (HSCOs).DesignA qualitative study using n=20 semistructured face-to-face interviews with n=24 participants was carried out between August 2017 and May 2018. Interview data were analysed based on concepts of qualitative content analysis using an inductive and deductive approach.Setting and participantsInterviews were conducted with clinical and managerial decision makers from multiple HSCOs in the model region of Cologne, Germany. Participants were recruited via networks of practice partners and cold calling.ResultsThis study identified various determinants on the system level that are associated with PCC implementation. Decision makers described external regulations as generating an economically controlled alignment of the healthcare system. The availability and qualification of staff resources and patient-related incentives of financial resources were identified as an eminent requirement for providers to deliver PCC. Participants considered the strict separation of financing and delivery of healthcare into inpatient and outpatient sectors to be a barrier to PCC. Interorganisational collaboration and information exchange were identified as facilitators of PCC, as they enable continuous patient care cycles.ConclusionThe results showed the necessity of enforcing paradigm changes at the system level from disease-centredness to patient-centredness while aligning policy and reimbursement decisions directly with patient needs and values. A systematic, long-term planned strategy that extends across all organisations is lacking, rather each organisation seeks its own possibilities to implement PCC activities under external restrictions.Trial registration numberDRKS00011925
Comprehensive review of statistical methods for analysing patient-reported outcomes (PROs) used as primary outcomes in randomised controlled trials (RCTs) published by the UK’sHealth Technology Assessment(HTA) journal (1997–2020)
Authors: Qian Yirui , Walters Stephen J , Jacques Richard , Flight Laura 
Published: September 2021

ObjectivesTo identify how frequently patient-reported outcomes (PROs) are used as primary and/or secondary outcomes in randomised controlled trials (RCTs) and to summarise what statistical methods are used for the analysis of PROs.DesignComprehensive review.SettingRCTs funded and published by the United Kingdom’s (UK) National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme.Data sources and eligibilityHTA reports of RCTs published between January 1997 and December 2020 were reviewed.Data extractionInformation relating to PRO use and analysis methods was extracted.Primary and secondary outcome measuresThe frequency of using PROs as primary and/or secondary outcomes; statistical methods that were used for the analysis of PROs as primary outcomes.ResultsIn this review, 37.6% (114/303) of trials used PROs as primary outcomes, and 82.8% (251/303) of trials used PROs as secondary outcomes from 303 NIHR HTA reports of RCTs. In the 114 RCTs where the PRO was the primary outcome, the most used PRO was the Short-Form 36 (8/114); the most popular methods for multivariable analysis were linear mixed model (45/114), linear regression (29/114) and analysis of covariance (13/114); logistic regression was applied for binary and ordinal outcomes in 14/114 trials; and the repeated measures analysis was used in 39/114 trials.ConclusionThe majority of trials used PROs as primary and/or secondary outcomes. Conventional methods such as linear regression are widely used, despite the potential violation of their assumptions. In recent years, there is an increasing trend of using complex models (eg, with mixed effects). Statistical methods developed to address these violations when analysing PROs, such as beta-binomial regression, are not routinely used in practice. Future research will focus on evaluating available statistical methods for the analysis of PROs.
Treatment of early-stage breast cancer with percutaneous thermal ablation, an open-label randomised phase 2 screening trial: rationale and design of the THERMAC trial
Authors: van de Voort Elles M F , Struik Gerson M , Koppert Linetta B , Moelker Adriaan , Debets Reno , Yo Glenn , Macco Maura J P V , Sinke Renata H J A , Franckena Martine , Birnie Erwin , Verhoef Cornelis , Klem Taco M A L 
Published: September 2021

IntroductionBreast cancer is the most frequently diagnosed malignancy worldwide but almost half of the patients have an excellent prognosis with a 5-year survival rate of 98%–99%. These patients could potentially be treated with thermal ablation to avoid surgical excision, reduce treatment-related morbidity and increase patients’ quality of life without jeopardising treatment effectiveness. Previous studies showed highest complete ablation rates for radiofrequency, microwave and cryoablation. However, due to heterogeneity among studies, it is unknown which of these three techniques should be selected for a phase 3 comparative study.Methods and analysisThe aim of this phase 2 screening trial is to determine the efficacy rate of radiofrequency, microwave and cryoablation with the intention to select one treatment for further testing in a phase 3 trial. Additionally, exploratory data are obtained for the phase 3 trial. The design is a multicentre open-label randomised phase 2 screening trial. Patients with unifocal, invasive breast cancer with a maximum diameter of 2 cm without lymph node or distant metastases are included. Triple negative, Bloom-Richardson grade 3 tumours and patients with an indication for neoadjuvant chemotherapy will be excluded. Included patients will be allocated to receive one of the three thermal ablation techniques. Three months later surgical excision will be performed to determine the efficacy of thermal ablation. Treatment efficacy in terms of complete ablation rate will be assessed with CK 8/18 and H&E staining. Secondary outcomes include feasibility of the techniques in an outpatient setting, accuracy of MRI for complete ablation, patient satisfaction, adverse events, side effects, cosmetic outcome, system usability and immune response.Ethics and disseminationThis study protocol was approved by Medical Research Ethics Committee of the Erasmus Medical Center, Rotterdam, the Netherlands. Study results will be submitted for publication in peer-reviewed journals.Trial registration numberNL9205 (www.trialregister.nl); Pre-results.
Relationship between food insecurity and smoking status among women living with and at risk for HIV in the USA: a cohort study
Authors: Sheira Lila A , Frongillo Edward A , Hahn Judith , Palar Kartika , Riley Elise D , Wilson Tracey E , Adedimeji Adebola , Merenstein Daniel , Cohen Mardge , Wentz Eryka L , Adimora Adaora A , Ofotokun Ighovwerha , Metsch Lisa , Turan Janet M , Tien Phyllis C , Weiser Sheri D 
Published: September 2021

ObjectivesPeople living with HIV (PLHIV) in the USA, particularly women, have a higher prevalence of food insecurity than the general population. Cigarette smoking among PLHIV is common (42%), and PLHIV are 6–13 times more likely to die from lung cancer than AIDS-related causes. This study sought to investigate the associations between food security status and smoking status and severity among a cohort of predominantly low-income women of colour living with and without HIV in the USA.DesignWomen enrolled in an ongoing longitudinal cohort study from 2013 to 2015.SettingNine participating sites across the USA.Participants2553 participants enrolled in the Food Insecurity Sub-Study of the Women’s Interagency HIV Study, a multisite cohort study of US women living with HIV and demographically similar HIV-seronegative women.OutcomesCurrent cigarette smoking status and intensity were self-reported. We used cross-sectional and longitudinal logistic and Tobit regressions to assess associations of food security status and changes in food security status with smoking status and intensity.ResultsThe median age was 48. Most respondents were African-American/black (72%) and living with HIV (71%). Over half had annual incomes ≤US$12 000 (52%). Food insecurity (44%) and cigarette smoking (42%) were prevalent. In analyses adjusting for common sociodemographic characteristics, all categories of food insecurity were associated with greater odds of current smoking compared with food-secure women. Changes in food insecurity were also associated with increased odds of smoking. Any food insecurity was associated with higher smoking intensity.ConclusionsFood insecurity over time was associated with smoking in this cohort of predominantly low-income women of colour living with or at risk of HIV. Integrating alleviation of food insecurity into smoking cessation programmes may be an effective method to reduce the smoking prevalence and disproportionate lung cancer mortality rate particularly among PLHIV.