bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of clinical and methodological characteristics of early COVID-19 treatment clinical trials: so much work, so many lost opportunities
Authors: Mainoli Beatrice , Machado Tiago , Duarte Gonçalo S. , Prada Luísa , Gonçalves Nilza , Ferreira Joaquim J. , Costa João 
Published: February 2021

Abstract
Background
The COVID-19 pandemic continues to rage on, and clinical research has been promoted worldwide. We aimed to assess the clinical and methodological characteristics of treatment clinical trials that have been set forth as an early response to the COVID-19 pandemic.

Methods
First, we reviewed all registered clinical trials on COVID-19. The World Health Organization International Trials Registry Platform and national trial registries were searched for COVID-19 trials through April 19th, 2020. For each record, independent researchers extracted interventions, participants, and methodological characteristics.
Second, on September 14th, 2020 we evaluated the recruitment status and availability of the results of COVID-19 treatment trials previously identified.

Results
In April 2020, a total of 580 trials evaluating COVID-19 treatment were registered. Reporting quality was poor (core participant information was missing in 24.1 to 92.7%). Between 54.0 and 93.8% of the trials did not plan to include older people or those with a higher baseline risk. Most studies were randomised (67.9%), single-centre (58.3%), non-industry-funded (81.1%), to be conducted in China (47.6%), with a median duration of 184 days and a median sample size of 100 participants. Core endpoints (mortality, clinical status, and hospitalization length) were planned to be assessed in 5.2 to 13.1% of the trials. Five months later, 66 trials (11.4%) were reported as “Completed”, and only 46 (7.9%) had public results available. One hundred forty-four of 580 trials (24.8%) either had the status “Not yet recruiting” or “Suspended”, and 18 (3.1%) trials were prematurely stopped (“Terminated” or “Withdrawn”) The number of completed trials and trials with results are much lower than anticipated, considering the planned follow-up.

Conclusions
Our results raise concerns about the success of the initial global research effort on COVID-19 treatment. The clinical and methodological characteristics of early COVID-19 treatment trials limit their capability to produce clear answers to critical questions in the shortest possible time.
Perinatal outcome after vacuum assisted delivery with digital feedback on traction force; a randomised controlled study
Authors: Romero Stefhanie , Pettersson Kristina , Yousaf Khurram , Westgren Magnus , Ajne Gunilla 
Published: February 2021

Abstract
Background
Low and mid station vacuum assisted deliveries (VAD) are delicate manual procedures that entail a high degree of subjectivity from the operator and are associated with adverse neonatal outcome. Little has been done to improve the procedure, including the technical development, traction force and the possibility of objective documentation. We aimed to explore if a digital handle with instant haptic feedback on traction force would reduce the neonatal risk during low or mid station VAD.

Methods
A two centre, randomised superiority trial at Karolinska University Hospital, Sweden, 2016–2018. Cases were randomised bedside to either a conventional or a digital handle attached to a Bird metal cup (50 mm, 80 kPa). The digital handle measured applied force including an instant notification by vibration when high levels of traction force were predicted according to a predefined algorithm. Primary outcome was a composite of hypoxic ischaemic encephalopathy, intracranial haemorrhage, seizures, death and/or subgaleal hematoma. Three hundred eighty low and mid VAD in each group were estimated to decrease primary outcome from six to 2 %.

Results
After 2 years, an interim analyse was undertaken. Meeting the inclusion criteria, 567 vacuum extractions were randomized to the use of a digital handle (n = 296) or a conventional handle (n = 271). Primary outcome did not differ between the two groups: (2.7% digital handle vs 2.6% conventional handle). The incidence of primary outcome differed significantly between the two delivery wards (4% vs 0.9%, p < 0.05). A recalculation of power revealed that 800 cases would be needed in each group to show a decrease in primary outcome from three to 1 %. This was not feasible, and the study therefore closed.

Conclusions
The incidence of primary outcome was lower than estimated and the study was underpowered. However, the difference between the two delivery wards might reflect varying degree of experience of the technical equipment. An objective documentation of the extraction procedure is an attractive alternative in respect to safety and clinical training. To demonstrate improved safety, a multicentre study is required to reach an adequate cohort. This was beyond the scope of the study.

Trial registration
ClinicalTrials.gov NCT03071783, March 1, 2017, retrospectively registered.
Neurobehavioural and cognitive effects of prenatal exposure to organochlorine compounds in three year old children
Authors: Vermeir Griet , Covaci Adrian , Van Larebeke Nik , Schoeters Greet , Nelen Vera , Koppen Gudrun , Viaene Mineke 
Published: February 2021

Abstract
Background
We report data of a Belgian observational prospective cohort study regarding cognitive and behavioural development until the age of 36 months in relation to internal exposure to organochlorine pollutants [sum of polychlorinated biphenyls (sum PCB), dioxin-like activity, PCB118, PCB170, hexachlorobenzene (HCB) and p,p’-dichlorodiphenyldichloroethylene (DDE)] measured in cord blood.

Methods
Participants were recruited as part of an Flemish Environmental Health Survey (2002–2006). Two hundred and six mother-child pairs were recruited. Hundred twenty five toddlers [Reynell Taal Ontwikkelings Schalen (language development, RTOS), Snijders-Oomen Niet-verbale intelligentietest (non-verbal intelligence, SON), Bayley Scales, milestones, Infant Behaviour Questionnaire (IBQ), gender specific play behaviour, Neurobehavioral Evaluation System (NES)-attentional task] and their mothers [Home Observation Measurement of the Environment (HOME), Wechsler Abbreviated Scale of Intelligence (WASI), State-Trait Anxiety Inventory (STAI), general questionnaires] were tested. Statistical analysis was performed with the SPSS program. Much attention was paid to confounding factors.

Results
In the first years of development, higher organochlorine pollutants were associated with less active children (delayed crawling: sum PCB*HCB (p < 0.05), sumPCB*DDE (p < 0.1); delayed first steps alone: sum PCB (p < 0.5), PCB118 (p < 0.01), PCB170 (p < 0.01), HCB (p < 0.01); less switching between toys: sum PCB (p < 0.01); less switching between toys in boys: PCB118 (p < 0.01), sum PCB(p < 0.01)). At 12 months children with higher dioxin-like activity tended to show less fear responses(p < 0.1) (IBQ 12 months). At 36 months, a slower development of language comprehension (RTOS) was related to all organochlorine exposure parameters(p < 0.1 or p < 0.05) except DDE. Lower nonverbal IQ scores (SON) were related to PCB118 in boys only(p < 0.05 or p < 0.01). Less masculine and more non-gender specific play behaviour was associated with sum PCB in boys and girls at 36 months(p < 0.1). Moreover, PCB118 (p < 0.05), PCB170 (p < 0.1), HCB(p < 0.05) and DDE(p < 0.05) were associated with diminished masculine play behaviour in boys.

Conclusion
Our data confirm the observations that neurobehavioral development of young children is adversely influenced by environmental concentrations of PCBs, especially in boys. In this context, observation of play behaviour seems to be a reliable, easy to perform and sensitive test to detect neurotoxic effects of chemicals like PCB’s and dioxin-like compounds in very young children. On the basis of our results, we hypothesize that an underarrousal pattern may play a role in the spectrum of effects measured in toddlers prenatally exposed to PCBs and dioxin-like compounds.
Study protocol: baby-OSCAR trial: Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial
Authors: Gupta Samir , Juszczak Edmund , Hardy Pollyanna , Subhedar Nimish , Wyllie Jonathan , Kelsall Wilf , Sinha Sunil , Johnson Sam , Roberts Tracy , Hutchison Elisabeth , Pepperell Justine , Linsell Louise , Bell Jennifer L. , Stanbury Kayleigh , Laube Marketa , Edwards Clare , Field David ,   on behalf of the ‘The Baby-OSCAR Collaborative Group’
Published: February 2021

Abstract
Background
The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks’ gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age. Untreated PDA can be associated with several serious and life-threatening short and long-term complications. Reliable data to support clinical decisions about PDA treatment are needed to prevent serious complications in high risk babies, while minimising undue exposure of infants. With the availability of routine bedside echocardiography, babies with a large PDA can be diagnosed before they become symptomatic.

Methods
This is a multicentre, masked, randomised, placebo-controlled parallel group trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies (23+ 0–28+ 6 weeks’ gestation) improves short and long-term health and economic outcomes. With parental informed consent, extremely preterm babies (born between 23+ 0–28+ 6 weeks’ gestation) admitted to tertiary neonatal units are screened using echocardiography. Babies with a large PDA on echocardiography, defined by diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern, are randomly allocated to either ibuprofen or placebo within 72 h of birth. The primary endpoint is the composite outcome of death by 36 weeks’ postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age.

Discussion
Prophylactic pharmacological treatment of all preterm babies unnecessarily exposes them to potentially serious side effects of drug treatment, when their PDA may have closed spontaneously. However, delaying treatment until babies become symptomatic could result in loss of treatment benefit as irreversible damage may have already been done.
Targeted, early pharmacological treatment of PDA in asymptomatic babies has the potential to overcome the disadvantages of both prophylactic (overtreatment) and symptomatic approaches (potentially too late). This could result in improvements in the clinically important short-term clinical (mortality and moderate or severe BPD at 36 weeks’ postmenstrual age) and long-term health outcomes (moderate or severe neurodevelopment disability and respiratory morbidity) measured at 2 years corrected age.

Trial registration
ISRCTN84264977. Date assigned: 15/09/2010.
How does the sexual, physical and mental health of young adults not in education, employment or training (NEET) compare to workers and students?
Authors: Tanton Clare , McDonagh Lorraine , Cabecinha Melissa , Clifton Soazig , Geary Rebecca , Rait Greta , Saunders John , Cassell Jackie , Bonell Chris , Mitchell Kirstin R. , Mercer Catherine H. 
Published: February 2021

Abstract
Background
Syndemic theory highlights the potential for health problems to interact synergistically, compounding impact. Young adults not in education, employment or training (NEET) are more likely to experience disadvantage and poorer general health outcomes. However, there is little research on their sexual health, or the extent to which this clusters with mental and physical health outcomes.

Methods
Analysis of data from 16 to 24 year olds (1729 men, 2140 women) interviewed 2010–12 for Britain’s third National Survey of Sexual Attitudes and Lifestyles. Natsal-3 is a national probability sample survey using computer-assisted personal interviewing with computer-assisted self-interviewing. Participants were classified as workers, students or NEET. We used multivariable logistic regression to examine associations between being NEET (relative to worker or student) and risk behaviours and outcomes in physical, sexual and mental health domains. We then examined how risk behaviours and poor health outcomes cluster within and across domains.

Results
15% men and 20% women were NEET; 36% men and 32% women were workers; and 49% men and 48% women were students. Young people who were NEET were more likely to report smoking and drug use (men) than other young people. There were few differences in sexual health, although NEETs were more likely to report condomless sex, and NEET women, unplanned pregnancy (past year). Risk behaviours clustered more within and across domains for NEET men. Among NEET women, poor health outcomes clustered across mental, physical and sexual health domains.

Conclusions
Harmful health behaviours (men) and poor health outcomes (women) clustered more in those who are NEET. This points to a possible syndemic effect of NEET status on general ill health, especially for women. Our paper is novel in highlighting that elevated risk pertains to sexual as well as mental and physical health.
How did governmental interventions affect the spread of COVID-19 in European countries?
Authors: Post Richard A. J. , Regis Marta , Zhan Zhuozhao , van den Heuvel Edwin R. 
Published: February 2021

Abstract
Background
To reduce the transmission of the severe acute respiratory syndrome coronavirus 2 in its first wave, European governments have implemented successive measures to encourage social distancing. However, it remained unclear how effectively measures reduced the spread of the virus. We examined how the effective-contact rate (ECR), the mean number of daily contacts for an infectious individual to transmit the virus, among European citizens evolved during this wave over the period with implemented measures, disregarding a priori information on governmental measures.

Methods
We developed a data-oriented approach that is based on an extended Susceptible-Exposed-Infectious-Removed (SEIR) model. Using the available data on the confirmed numbers of infections and hospitalizations, we first estimated the daily total number of infectious-, exposed- and susceptible individuals and subsequently estimated the ECR with an iterative Poisson regression model. We then compared change points in the daily ECRs to the moments of the governmental measures.

Results
The change points in the daily ECRs were found to align with the implementation of governmental interventions. At the end of the considered time-window, we found similar ECRs for Italy (0.29), Spain (0.24), and Germany (0.27), while the ECR in the Netherlands (0.34), Belgium (0.35) and the UK (0.37) were somewhat higher. The highest ECR was found for Sweden (0.45).

Conclusions
There seemed to be an immediate effect of banning events and closing schools, typically among the first measures taken by the governments. The effect of additionally closing bars and restaurants seemed limited. For most countries a somewhat delayed effect of the full lockdown was observed, and the ECR after a full lockdown was not necessarily lower than an ECR after (only) a gathering ban.
Burden of cancers attributable to modifiable risk factors in Malaysia
Authors: Teh H. S. , Woon Y. L. 
Published: February 2021

Abstract
Background
This is a systematic assessment of the burden of cancers in Malaysia in 2018 using epidemiologic approach. The purpose of this study was to identify the proportion of cancers in Malaysia that were attributable to the modifiable risk factors of excess weight, alcohol intake, physical inactivity, tobacco smoking and to estimate the number of cancer cases that could be prevented if the exposure to the modifiable risk factor was reduced.

Methods
We estimated the Population Attributable Fraction (PAF) of the modifiable risk factors to cancers incidences in Malaysia. The two parameters used for the estimation were exposure prevalence from national representative surveys and the relative risk of getting the cancers from worldwide literature review.

Results
Among 38,426 cancer incidences in 2018 from Globocan data, we estimated that 22.2% (95% confidence interval (CI):14.9 to 29.6%) of the cancer incidences included in this study were attributable to the investigated modifiable risk factors. 39.1% (95% CI:27.2 to 49.7%) and 10.5% (95% CI:5.8 to 15.7%) of cancers in male and female respectively, were attributable to the studied modifiable risk factors. The top main cancers attributed by the risk factors were lung cancer (65.1%; 95% CI:56.4 to 72.9%), laryngeal cancer (63.6%; 95% CI:39.9 to 80.5%), and oesophageal cancer (51.5%; 95% CI:39.9 to 62.0%). For each risk factor studied across genders, tobacco smoking contributed the most (14.3%; 95% CI:9.9 to 17.3%), followed by excess weight (7.0%; 95% CI:4.1 to 10.2%), physical inactivity (1.0%; 95% CI:0.4 to 1.7%) and alcohol intake (0.6%; 95% CI:0.2 to 1.0%).

Conclusion
Findings from this study suggests that tobacco smoking and excess weight are the two predominant factors out of the four studied risk factors for cancer cases in Malaysia. Nationwide public health prevention campaigns tailored to these risk factors are recommended. However, the other risk factors such as physical inactivity and alcohol intake shall not be neglected. PAFs are estimated based on the best available data that we have currently. Regular collection of other risk factor exposure prevalence data is vital for future analyses.
Fragility fracture identifies patients at imminent risk for subsequent fracture: real-world retrospective database study in Ontario, Canada
Authors: Adachi Jonathan D. , Brown Jacques P. , Schemitsch Emil , Tarride Jean-Eric , Brown Vivien , Bell Alan D. , Reiner Maureen , Packalen Millicent , Motsepe-Ditshego Ponda , Burke Natasha , Slatkovska Lubomira 
Published: February 2021

Abstract
Background
The secondary fracture prevention gap in the osteoporosis field has been previously described as a ‘crisis’. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1–2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures.

Methods
This retrospective observational study used de-identified health services data from the publicly funded healthcare system in Ontario, the largest province of Canada. Patients aged > 65 with an index fragility fracture occurring between 2011 and 2015 were identified from the ICES Data Repository using International Classification of Diseases (ICD)-10 codes. We examined median time to subsequent fragility fractures for osteoporotic fracture sites until the end of follow-up (2017). BMD assessment and use of osteoporosis therapies following index fracture were also characterized.

Results
Among 115,776 patients with an index fragility fracture, 17.8% incurred a second fragility fracture. Median time between index and second fracture occurring at any site was 555 days (interquartile range: 236–955). For each index fracture site examined, median time from index to second fracture was < 2 years. The proportion of patients with BMD assessment was 10.3% ≤1 year prior to and 16.4% ≤1 year post index fracture. The proportion of patients receiving osteoporosis therapy was 29.8% ≤1 year prior, 34.6% ≤1 year post, and 25.9% > 3 years post index fracture.

Conclusions
This cohort of Canadian patients aged > 65 years who experienced a fragility fracture at any site are at imminent risk of experiencing subsequent fracture within the next 2 years and should be proactively assessed and treated.
Prevalence of musculoskeletal disorders among perioperative nurses: a systematic review and META-analysis
Authors: Clari Marco , Godono Alessandro , Garzaro Giacomo , Voglino Gianluca , Gualano Maria Rosaria , Migliaretti Giuseppe , Gullino Attilia , Ciocan Catalina , Dimonte Valerio 
Published: February 2021

Abstract
Background
To evaluate the prevalence of work-related musculoskeletal disorders (WRMSDs) in perioperative nurses and to explore their association with personal characteristics.

Methods
Medline, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Cochrane Library and Joanna Briggs Institute Database were systematically searched. A meta-analysis calculating event rates, and relative 95% Confidence Intervals (CI) was performed for each musculoskeletal body region. The contribution of perioperative nurses’ sex, age, and BMI was assessed through a meta-regression.

Results
Twenty-two studies, considering 3590 perioperative nurses, were included in the systematic review. The highest prevalence of WRMSDs was found for the lower-back (62%; 95% CI 0.54–0.70), followed by knee (47%; 95% CI 0.36–0.59), shoulder (44%; 95% CI 0.37–0.51), waist (42%; 95% CI 0.31–0.53), neck (39%; 95% CI 0.29–0.51), ankle-feet (35%; 95% CI 0.22–0.51), upper-back (34%; 95% CI 0.25–0.44), hand-wrist (29%; 95% CI 0.20–0.40), and elbow (18%; 95% CI 0.12–0.26). Meta-regression showed that sex, age, and BMI were not significant predictors of low-back disorders (p = 0.69; R2 = 0).

Conclusions
WRMSDs represent a high prevalence issue among perioperative nurses. Perioperative nurses, in general, are steadily exposed to both physical and temporal risk factors. Further studies should be addressed to identify specific interventions aimed at reducing the burden of WRMSDs including ergonomic education and physical rehabilitation. Our data could be used in future studies as a reference to assess the risk of WRMSDs in other health-care professionals’ population.
Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned
Authors: Bianco Federico , Salomone Fabrizio , Milesi Ilaria , Murgia Xabier , Bonelli Sauro , Pasini Elena , Dellacà Raffaele , Ventura Maria Luisa , Pillow Jane 
Published: February 2021

AbstractDelivery of medications to preterm neonates receiving non-invasive ventilation (NIV) represents one of the most challenging scenarios for aerosol medicine. This challenge is highlighted by the undersized anatomy and the complex (patho)physiological characteristics of the lungs in such infants. Key physiological restraints include low lung volumes, low compliance, and irregular respiratory rates, which significantly reduce lung deposition. Such factors are inherent to premature birth and thus can be regarded to as theintrinsic factorsthat affect lung deposition. However, there are a number ofextrinsic factorsthat also impact lung deposition: such factors include the choice of aerosol generator and its configuration within the ventilation circuit, the drug formulation, the aerosol particle size distribution, the choice of NIV type, and the patient interface between the delivery system and the patient. Together, these extrinsic factors provide an opportunity to optimize the lung deposition of therapeutic aerosols and, ultimately, the efficacy of the therapy.In this review, we first provide a comprehensive characterization of both the intrinsic and extrinsic factors affecting lung deposition in premature infants, followed by a revision of the clinical attempts to deliver therapeutic aerosols to premature neonates during NIV, which are almost exclusively related to the non-invasive delivery of surfactant aerosols. In this review, we provide clues to the interpretation of existing experimental and clinical data on neonatal aerosol delivery and we also describe a frame of measurable variables and available tools, including in vitro and in vivo models, that should be considered when developing a drug for inhalation in this important but under-served patient population.