bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability of Spatiotemporal Gait Kinematics During Treadmill Walking: Is There a Hawthorne Effect?
Authors: Farhan Saaniya , Avalos Marco A. , Rosenblatt Noah J. 
Published: April 2023

Spatiotemporal gait kinematics and their variability are commonly assessed in clinical and laboratory settings to quantify fall risk. Although the Hawthorne effect, or modifications in participant behavior due to knowledge of being observed, has the potential to impact such assessments, it has received minimal attention in the study of gait—particularly gait variability. The purpose of this study was to quantify the Hawthorne effect on variability and central tendency measures of fall-related spatiotemporal gait parameters. Seventeen healthy young adults walked on a treadmill at a self-selected velocity for 2 minutes under covert evaluation (ie, without awareness of being evaluated) and 2 minutes under overt evaluation. The movement was recorded using motion capture technology, from which we calculated mean value and step-to-step variability (using standard deviation and mean absolute deviation) of step length, step width, percent double support, percent stance phase, and stride time. Although central tendencies were unaffected by evaluation type, four-of-five measures of variability were significantly lower during overt evaluation for at least one-of-two metrics. Our results suggest a Hawthorne effect on locomotor control. Researchers should be aware of this phenomenon when designing research studies and interpreting gait assessments.
Moving Beyond the Characterization of Activity Intensity Bouts as Square Waves Signals
Authors: O’Brien Myles W. , Petterson Jennifer L. , Pellerine Liam P. , Shivgulam Madeline E. , Kimmerly Derek S. , Frayne Ryan J. , Hettiarachchi Pasan , Johansson Peter J. 
Published: April 2023

Wearable activity monitors provide objective estimates of time in different physical activity intensities. Each continuous stepping period is described by its length and a corresponding single intensity (in metabolic equivalents of task [METs]), creating square wave–shaped signals. We argue that physiological responses do not resemble square waves, with the purpose of this technical report to challenge this idea and use experimental data as a proof of concept and direct potential solutions to better characterize activity intensity. Healthy adults (n = 43, 19♀; 23 ± 5 years) completed 6-min treadmill stages (five walking and five jogging/running) where oxygen consumption (3.5 ml O2·kg−1·min−1 = 1 MET) was recorded throughout and following the cessation of stepping. The time to steady state was ∼1–1.5 min, and time back to baseline following exercise was ∼1–2 min, with faster stepping stages generally exhibiting longer durations. Instead of square waves, the duration intensity signal reflected a trapezoid shape for each stage. The METs per minute during the rise to steady state (upstroke slopes; average: 1.7–6.3 METs/min for slow walking to running) may be used to better characterize activity intensity for shorter activity bouts where steady state is not achieved (within ∼90 s). While treating each activity bout as a single intensity is a much simpler analytical procedure, characterizing each bout in a continuous manner may better reflect the true physiological responses to movement. The information provided herein may be used to improve the characterization of activity intensity, definition of bout breaks, and act as a starting point for researchers and software developers interested in using wearables to measure activity intensity.
Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine
Authors: Che Ye , Gribenko Alexey V. , Song Xi , Handke Luke D. , Efferen Kari S. , Tompkins Kristin , Kodali Srinivas , Nunez Lorna , Prasad A. Krishna , Phelan Lynn M. , Ammirati Mark , Yu Xiaodi , Lees Joshua A. , Chen Wei , Martinez Lyndsey , Roopchand Vidia , Han Seungil , Qiu Xiayang , DeVincenzo John P. , Jansen Kathrin U. , Dormitzer Philip R. , Swanson Kena A. 
Published: April 2023

Respiratory syncytial virus (RSV) is the leading, global cause of serious respiratory disease in infants and is an important cause of respiratory illness in older adults. No RSV vaccine is currently available. The RSV fusion (F) glycoprotein is a key antigen for vaccine development, and its prefusion conformation is the target of the most potent neutralizing antibodies. Here, we describe a computational and experimental strategy for designing immunogens that enhance the conformational stability and immunogenicity of RSV prefusion F. We obtained an optimized vaccine antigen after screening nearly 400 engineered F constructs. Through in vitro and in vivo characterization studies, we identified F constructs that are more stable in the prefusion conformation and elicit ~10-fold higher serum-neutralizing titers in cotton rats than DS-Cav1. The stabilizing mutations of the lead construct (847) were introduced onto F glycoprotein backbones of strains representing the dominant circulating genotypes of the two major RSV subgroups, A and B. Immunization of cotton rats with a bivalent vaccine formulation of these antigens conferred complete protection against RSV challenge, with no evidence of disease enhancement. The resulting bivalent RSV prefusion F investigational vaccine has recently been shown to be efficacious against RSV disease in two pivotal phase 3 efficacy trials, one for passive protection of infants by immunization of pregnant women and the second for active protection of older adults by direct immunization.
Dietary sugar consumption and health: umbrella review
Authors: Huang Yin , Chen Zeyu , Chen Bo , Li Jinze , Yuan Xiang , Li Jin , Wang Wen , Dai Tingting , Chen Hongying , Wang Yan , Wang Ruyi , Wang Puze , Guo Jianbing , Dong Qiang , Liu Chengfei , Wei Qiang , Cao Dehong , Liu Liangren 
Published: April 2023

Abstract

Objective
To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary sugar consumption and health outcomes.

Design
Umbrella review of existing meta-analyses.

Data sources
PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and hand searching of reference lists.

Inclusion criteria
Systematic reviews and meta-analyses of randomised controlled trials, cohort studies, case-control studies, or cross sectional studies that evaluated the effect of dietary sugar consumption on any health outcomes in humans free from acute or chronic diseases.

Results
The search identified 73 meta-analyses and 83 health outcomes from 8601 unique articles, including 74 unique outcomes in meta-analyses of observational studies and nine unique outcomes in meta-analyses of randomised controlled trials. Significant harmful associations between dietary sugar consumption and 18 endocrine/metabolic outcomes, 10 cardiovascular outcomes, seven cancer outcomes, and 10 other outcomes (neuropsychiatric, dental, hepatic, osteal, and allergic) were detected. Moderate quality evidence suggested that the highest versus lowest dietary sugar consumption was associated with increased body weight (sugar sweetened beverages) (class IV evidence) and ectopic fatty accumulation (added sugars) (class IV evidence). Low quality evidence indicated that each serving/week increment of sugar sweetened beverage consumption was associated with a 4% higher risk of gout (class III evidence) and each 250 mL/day increment of sugar sweetened beverage consumption was associated with a 17% and 4% higher risk of coronary heart disease (class II evidence) and all cause mortality (class III evidence), respectively. In addition, low quality evidence suggested that every 25 g/day increment of fructose consumption was associated with a 22% higher risk of pancreatic cancer (class III evidence).

Conclusions
High dietary sugar consumption is generally more harmful than beneficial for health, especially in cardiometabolic disease. Reducing the consumption of free sugars or added sugars to below 25 g/day (approximately 6 teaspoons/day) and limiting the consumption of sugar sweetened beverages to less than one serving/week (approximately 200-355 mL/week) are recommended to reduce the adverse effect of sugars on health.

Systematic review registration
PROSPERO CRD42022300982.
Association of hemoglobin A1c stability with mortality and diabetes complications in older adults with diabetes
Authors: Conlin Paul R , Zhang Libin , Li Donglin , Nelson Richard E , Prentice Julia C , Mohr David C 
Published: April 2023

IntroductionHemoglobin A1c (A1c) treatment goals in older adults should be individualized to balance risks and benefits. It is unclear if A1c stability over time within unique target ranges also affects adverse outcomes.Research design and methodsWe conducted a retrospective observational cohort study from 2004 to 2016 of veterans with diabetes and at least four A1c tests during a 3-year baseline. We generated four distinct categories based on the percentage of time that baseline A1c levels were within patient-specific target ranges: ≥60% time in range (TIR), ≥60% time below range (TBR), ≥60% time above range (TAR), and a mixed group with all times <60%. We assessed associations of these categories with mortality, macrovascular, and microvascular complications.ResultsWe studied 397 634 patients (mean age 76.9 years, SD 5.7) with an average of 5.5 years of follow-up. In comparison to ≥60% A1c TIR, mortality was increased with ≥60% TBR, ≥60% TAR, and the mixed group, with HRs of 1.12 (95% CI 1.11 to 1.14), 1.10 (95% CI 1.08 to 1.12), and 1.06 (95% CI 1.04 to 1.07), respectively. Macrovascular complications were increased with ≥60% TBR and ≥60% TAR, with estimates of 1.04 (95% CI 1.01 to 1.06) and 1.06 (95% CI 1.03 to 1.09). Microvascular complications were lower with ≥60% TBR (HR 0.97, 95% CI 0.95 to 1.00) and higher with ≥60% TAR (HR 1.11, 95% CI 1.08 to 1.14). Results were similar with higher TIR thresholds, shorter follow-up, and competing risk of mortality.ConclusionsIn older adults with diabetes, mortality and macrovascular complications are associated with increased time above and below individualized A1c target ranges. Higher A1c TIR may identify patients with lower risk of adverse outcomes.
Prevalence estimates of major depressive disorder in 27 European countries from the European Health Interview Survey: accounting for imperfect diagnostic accuracy of the PHQ-8
Authors: Fischer Felix , Zocholl Dario , Rauch Geraldine , Levis Brooke , Benedetti Andrea , Thombs Brett , Rose Matthias , Kostoulas Polychronis 
Published: April 2023

BackgroundCut-offs on self-report depression screening tools are designed to identify many more people than those who meet criteria for major depressive disorder. In a recent analysis of the European Health Interview Survey (EHIS), the percentage of participants with Patient Health Questionnaire-8 (PHQ-8) scores ≥10 was reported as major depression prevalence.ObjectiveWe used a Bayesian framework to re-analyse EHIS PHQ-8 data, accounting for the imperfect diagnostic accuracy of the PHQ-8.MethodsThe EHIS is a cross-sectional, population-based survey in 27 countries across Europe with 258 888 participants from the general population. We incorporated evidence from a comprehensive individual participant data meta-analysis on the accuracy of the PHQ-8 cut-off of ≥10. We evaluated the joint posterior distribution to estimate the major depression prevalence, prevalence differences between countries and compared with previous EHIS results.FindingsOverall, major depression prevalence was 2.1% (95% credible interval (CrI) 1.0% to 3.8%). Mean posterior prevalence estimates ranged from 0.6% (0.0% to 1.9%) in the Czech Republic to 4.2% (0.2% to 11.3%) in Iceland. Accounting for the imperfect diagnostic accuracy resulted in insufficient power to establish prevalence differences. 76.4% (38.0% to 96.0%) of observed positive tests were estimated to be false positives. Prevalence was lower than the 6.4% (95% CI 6.2% to 6.5%) estimated previously.ConclusionsPrevalence estimation needs to account for imperfect diagnostic accuracy.Clinical implicationsMajor depression prevalence in European countries is likely lower than previously reported on the basis of the EHIS survey.
Burden experienced by informal caregivers of children with sickle cell disease (SCD): a qualitative exploratory study at Tamale Teaching Hospital, Ghana
Authors: Mumuni Najart Deborah , Osman Wahab , Alhassan Basour Adam , Alhassan Afizu 
Published: April 2023

ObjectiveThis study sought to explore the burden experienced by informal caregivers in caring for their children with sickle cell disease (SCD).DesignA qualitative exploratory design was employed in the study using in-depth interviews.SettingThe study was conducted at the sickle cell clinic of the Tamale Teaching Hospital, Ghana.ParticipantsData were gathered from 15 purposively selected informal caregivers, whose children with SCD received care at the sickle cell clinic of the Tamale Teaching Hospital, using a semistructured in-depth interview guide in May–June 2021. Their responses were audio-taped, transcribed and analysed using the reflexive thematic analysis approach.ResultsFive major themes emerged from data analysis. These were: the burden of children’s ill-health; financial burden; employment challenges; psychosocial burden and determinants of caregivers’ burden. These burdens destabilised the personal lives, financial standing, social relationships, and employment of caregivers in general and that of other immediate family members, thus, impacting family processes and health.ConclusionsHealth professionals must devise strategies for counselling, early diagnosis and effective management of children with SCD across Ghana. The Ministry of Health must subsidise medications and laboratory services for children with SCD to help minimise the financial burden on caregivers. Further, counselling and psychological support services must be established in hospitals to assist caregivers to cope effectively.
Codesigning a social prescribing pathway to address the social determinant of health concerns of children with cerebral palsy and their families in Australia: a protocol for a mixed-methods formative research study
Authors: Ostojic Katarina , Paget Simon , Martin Tanya , Dee-Price Betty-Jean , McIntyre Sarah , Smithers Sheedy Hayley , Mimmo Laurel , Burnett Heather , Scott Timothy , Berg Alison , Masi Anne , Scarcella Michele , Calderan Jack , Azmatullah Sheikh , Mohamed Masyitah , Woodbury Mackenzie , Wilkinson Alunya , Zwi Karen , Dale Russell , Eapen Valsamma , Lingam Raghu , Strnadová Iva , Woolfenden Susan 
Published: April 2023

IntroductionSocial determinants of health (SDH) are contributors to health inequities experienced by some children with cerebral palsy and pose barriers to families engaging with complex and fragmented healthcare systems. There is emerging evidence to support ‘social prescribing’ interventions that systematically identify SDH concerns and refer patients to non-medical social care support and services to address their needs. To date, social prescribing has not been trialled specifically for children with neurodevelopmental disabilities, including cerebral palsy, in Australia. This study aims to codesign a social prescribing programme to address SDH concerns of children with cerebral palsy and their families who attend one of the three tertiary paediatric rehabilitation services in New South Wales, Australia.Methods and analysisThis is a qualitative multi-site study conducted at the three NSW paediatric hospitals’ rehabilitation departments using a codesign approach. Children aged 12–18 years with cerebral palsy, parents/caregivers of children (aged 0–18 years) with cerebral palsy, and clinicians will be involved in all stages to codesign the social prescribing programme. The study will consist of three components: (1) ‘what we need’, (2) ‘creating the pathways’ and (3) ‘finalising and sign off’. This project is overseen by two advisory groups: one group of young adults with cerebral palsy and one group of parents of young people with cerebral palsy. The study will be guided by the biopsychosocial ecological framework, and analysis will follow Braun and Clark’s thematic approach.Ethics and disseminationThe study protocol was approved by the human research ethics committee of the Sydney Children’s Hospitals Network. This codesign study will inform a future pilot study of feasibility and acceptability, then if indicated, a pilot clinical trial of efficacy. We will collaborate with all project stakeholders to disseminate findings and undertake further research to build sustainable and scalable models of care.Trial registration numberACTRN12622001459718.
Study protocol of a phase 2, randomised, placebo-controlled, double-blind, adaptive, parallel group clinical study to evaluate the efficacy and safety of recombinant alpha-1-microglobulin in subjects at high risk for acute kidney injury following open-chest cardiac surgery (AKITA trial)
Authors: Mazer C David , Siadati-Fini Niloufar , Boehm Johannes , Wirth Felix , Myjavec Andrej , Brown Craig D , Koyner Jay L , Boening Andreas , Engelman Daniel T , Larsson Tobias E , Renfurm Ronny , de Varennes Benoit , Noiseux Nicolas , Thielmann Matthias , Lamy Andre , Laflamme Maxime , von Groote Thilo , Ronco Claudio , Zarbock Alexander 
Published: April 2023

IntroductionAcute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies.Methods and analysisThis is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites.Ethics and disseminationThe trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code ‘2021-778 f-A’) and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal.Trial registration numberNCT05126303.
Hospitalisation profile in England and Wales, 1999 to 2019: an ecological study
Authors: Naser Abdallah Y 
Published: April 2023

ObjectiveHospital-related indicators are used to prioritise, benchmark and monitor certain healthcare components to improve quality. This study aimed to determine the hospital admissions profile in England and Wales between 1999 and 2019.DesignEcological study.SettingA population-based study of hospitalised patients in England and Wales.ParticipantsAll patients of all ages and genders who were hospitalised in National Health Service (NHS) hospitals and NHS-funded independent sector hospitals.Outcome measureHospital admission rates in England and Wales related to various diseases/causes, which were identified using the diagnostic codes (A00-Z99).ResultsThere was a 48.5% rise in hospital admission rates from 246 366.7 (95% CI 246 249.8 to 246 483.7) in 1999 to 365 858.7 (95% CI 365 736.3 to 365 981.2) in 2019 per million persons (p<0.05). The most common causes of hospital admissions were diseases of the digestive system; symptoms, signs, and abnormal clinical and laboratory findings; and neoplasms, which accounted for 11.5%, 11.4% and 10.5%, respectively. The age range of 15–59 years accounted for 43.4% of all hospital admissions. Around 56.0% of all hospital admissions were by female patients. In comparison to 1999, the hospital admission rate for males grew by 53.7%, from 218 363.7 (95% CI 218 203.2 to 218 524.3) to 335 618.9 (95% CI 335 448.1 to 335 789.6) per million persons in 2019. When compared with 1999, the hospital admission rate for females increased by 44.7%, rising from 273 032.5 (95% CI 272 863.5 to 273 201.5) to 395 154.6 (95% CI 394 979.9 to 395 329.4) per million persons.ConclusionA notable increase was observed in the rate of hospital admissions for all causes in England and Wales. Elderly age and female gender were significant factors that influenced the rate of hospital admissions. Future research is required to identify preventable risk factors for hospital admission.
Addressing food insecurity and chronic conditions in community health centres: protocol of a quasi-experimental evaluation of Recipe4Health
Authors: Rosas Lisa G , Chen Steven , Xiao Lan , Emmert-Aronson Benjamin O , Chen Wei-ting , Ng Elliot , Martinez Erica , Baiocchi Mike , Thompson-Lastad Ariana , Markle Elizabeth A , Tester June 
Published: April 2023

IntroductionChronic conditions, such as diabetes, obesity, heart disease and depression, are highly prevalent and frequently co-occur with food insecurity in communities served by community health centres in the USA. Community health centres are increasingly implementing ‘Food as Medicine’ programmes to address the dual challenge of chronic conditions and food insecurity, yet they have been infrequently evaluated.Methods and analysisThe goal of this quasi-experimental study was to evaluate the effectiveness of Recipe4Health, a ‘Food as Medicine’ programme. Recipe4Health includes two components: (1) a ‘Food Farmacy’ that includes 16 weekly deliveries of produce and (2) a ‘Behavioural Pharmacy’ which is a group medical visit. We will use mixed models to compare pre/post changes among participants who receive the Food Farmacy alone (n=250) and those who receive the Food Farmacy and Behavioural Pharmacy (n=140). The primary outcome, fruit and vegetable consumption, and secondary outcomes (eg, food security status, physical activity, depressive symptoms) will be collected via survey. We will also use electronic health record (EHR) data on laboratory values, prescriptions and healthcare usage. Propensity score matching will be used to compare Recipe4Health participants to a control group of patients in clinics where Recipe4Health has not been implemented for EHR-derived outcomes. Data from surveys, EHR, group visit attendance and produce delivery is linked with a common identifier (medical record number) and then deidentified for analysis with use of an assigned unique study ID. This study will provide important preliminary evidence on the effectiveness of primary care-based strategies to address food insecurity and chronic conditions.Ethics and disseminationThis study was approved by the Stanford University Institutional Review Board (reference protocol ID 57239). Appropriate study result dissemination will be determined in partnership with the Community Advisory Board.