Completion Date Research Articles

Job loss during pregnancy and the risk of miscarriage and stillbirth.

Does the exposure to job loss during pregnancy increase the risk of miscarriage or stillbirth? The experience of own or partner's job loss during the pregnancy is associated with an increased risk of miscarriageand stillbirth. Prior research on the psycho-social aspect of pregnancy loss has investigated the contextual and the individual-level stressors. At the contextual level, natural disasters, air pollution, and economic downturns are associated with higher risk of pregnancy loss. At the individual level, intense working schedules and financial strain are linked with increased risk of pregnancy loss both at early and later stages of the gestation. This work draws on high-quality individual data of 'Understanding Society', a longitudinal survey that has interviewed a representative sample of households living in the UK annually since 2009. Approximately 40000 households were recruited. The analyses use all the available survey waves (1-12, 2009-2022). The final sample consisted of 8142 pregnancy episodes that contain complete informationon pregnancy outcome and date of conception. Ongoing pregnancies at the time of the interview were excluded from the final sample. The outcome variable indicated whether a pregnancy resulted in a live birth or a pregnancy loss whereas the exposure variable identified the women's or their partner's job loss because of redundancy or a dismissal. Logistic regression models were employed to estimate the relation between job loss during pregnancy and pregnancy loss. The models were adjusted for an array of socio-demographic and economic characteristics following a stepwise approach. Several sensitivity analyses complemented the main findings. Baseline models controlling for women's demographic background and prior experience of miscarriage estimated an increased risk of pregnancy loss when women were exposed to their own or their partner's job loss during their pregnancy (odds ratio (OR) = 1.99, 95% CI: 1.32, 2.99). When the models were adjusted for all socio-economic and partnership-related covariates the association remained robust (OR = 1.81, 95% CI: 1.20, 2.73). First, the pregnancy outcome and the date of conception were self-reported and may besubjected to recall and social desirability bias. Second, although we adjusted for an array socio-demographic characteristics and self-reported health, other contextual factors might be correlated with both job loss and pregnancy loss. Third, owing to the limited sample size, we could not assess if the main finding holds across different socio-economic strata. By showing that exposure to a job loss during pregnancy increases the risk of miscarriage and stillbirth, we underline the relevance of pregnancy loss as a preventable public health matter. This result also calls for policy designthat enhances labour market protection and social security buffers for pregnant women and their partners. The authors received the following financial support for the research, authorship, and/or publication of this article: H2020 Excellent Science, H2020 European Research Council, Grant/Award Number: 694262 (project DisCont-Discontinuities in Household and Family Formation) and the Economic and Social Research Centre on Micro-Social Change (MiSoC). There are no conflicts of interest to declare.

Representation from India in multinational, interventional, phase 2 or 3 trials registered in Clinical Trials Registry-India: A cross-sectional study.

In multinational trials that have run in India, we wished to determine whether there was too much (60% or higher) recruitment from India. We downloaded all trial records from Clinical Trials Registry-India, CTRI, and stored them in a local SQLite database. We queried records registered in a recent 8-year period, ie 2013-2020 and evaluated the fraction of local participants in interventional Phase 2 or Phase 3 studies. 62 trials were completed, with completion dates available. Five trials (8%) had 60% or more planned recruitment from India. Four of the five (7% of 62) had a foreign sponsor, and therefore there was an unfair burden-benefit ratio on the Indian population. Seven trials (11%), of which six (10% of 62) had foreign sponsors, had 60% or more (of the total) actual recruitment from India, and for two trials (both with foreign sponsors), the data were meaningless. There were 362 studies that were listed as not completed, although, given their start date and estimated duration, some of them ought to have been. Twenty five cases (7% of 362) had 60% or more planned recruitment from India. Of these, 18 (5% of 362) had foreign sponsors and were potentially problematic. Even allowing for some delays in completion, 128 (35% of 362) studies ought to have been completed by the time of our study. As such, we identified several problematic trials for which the planned recruitment from India in multinational studies was 60% or more. We also identified trials in which the actual recruitment was significantly higher than the planned recruitment. Further, the records of several studies that were probably completed were not updated in CTRI in a timely manner. The Indian drug regulator needs to be particularly alert to the planned, or actual, over-recruitment of participants from India. Further, CTRI, alone or in collaboration with the regulator, needs to ensure that multinational trial records for the enrollment fields in particular are updated, in a timely manner.

Obstructive Sleep Apnea and a Comprehensive Remotely Supervised Rehabilitation Program: Protocol for a Randomized Controlled Trial.

Obstructive sleep apnea (OSA) is characterized by recurrent, intermittent partial or complete obstruction of the upper respiratory tract during sleep, which negatively affects the patient's daily quality of life (QoL). Middle-aged and older men who smoke and have obesity are most at risk. Even though the use of continuous positive airway pressure (CPAP) during sleep remains the gold standard treatment, various rehabilitation methods, such as exercise, respiratory therapy, myofunctional therapy, and nutritional lifestyle interventions, also appear to be effective. Moreover, it is increasingly recommended to use alternative or additional therapy options in combination with CPAP therapy. This study aims to evaluate if a comprehensive home-based, remotely supervised rehabilitation program (tele-RHB), in combination with standard therapy, can improve OSA severity by decreasing the apnea-hypopnea index (AHI); improve objective parameters of polysomnographic, spirometric, anthropometric, and body composition examinations; improve lipid profile, maximal mouth pressure, and functional capacity tests; and enhance the subjective perception of QoL, as well as daytime sleepiness in male participants with moderate to severe OSA. Our hypothesis is that a combination of the tele-RHB program and CPAP therapy will be more effective by improving OSA severity and the abovementioned parameters. This randomized controlled trial aims to recruit 50 male participants between the ages of 30 and 60 years with newly diagnosed moderate to severe OSA. Participants will be randomized 1:1, either to a 12-week tele-RHB program along with CPAP therapy or to CPAP therapy alone. After the completion of the intervention, the participants will be invited to complete a 1-year follow-up. The primary outcomes will be the polysomnographic value of AHI, Epworth Sleepiness Scale score, 36-Item Short Form Health Survey (SF-36) score, percentage of body fat, 6-minute walk test distance covered, as well as maximal inspiratory and expiratory mouth pressure values. Secondary outcomes will include polysomnographic values of oxygen desaturation index, supine AHI, total sleep time, average heart rate, mean oxygen saturation, and the percentage of time with oxygen saturation below 90%; anthropometric measurements of neck, waist, and hip circumference; BMI values; forced vital capacity; forced expiratory volume in 1 second; World Health Organization's tool to measure QoL (WHOQOL-BREF) score; and lipid profile values. Study recruitment began on October 25, 2021, and the estimated study completion date is December 2024. Analyses will be performed to examine whether the combination of the tele-RHB program and CPAP therapy will be more effective in the reduction of OSA severity and improvement of QoL, body composition and circumferences, exercise tolerance, lipid profile, as well as respiratory muscle and lung function, compared to CPAP therapy alone. The study will evaluate the effect of a comprehensive tele-RHB program on selected parameters mentioned above in male participants. The results of this intervention could help the further development of novel additional therapeutic home-based options for OSA. ClinicalTrials.gov NCT04759456; https://clinicaltrials.gov/ct2/show/NCT04759456. DERR1-10.2196/47460.

351 Snapshot of Transient Ischaemic Attack inpatient management at a model three Irish hospital

Abstract Background Transient Ischaemic Attack (TIA) is a common presentation to hospitals and portends a high risk for eventual stroke. The EXPRESS study suggested the benefit of urgent outpatient assessment of TIA, which was associated with a 80% risk reduction of early recurrent stroke when compared to usual care. The HSE model of care for stroke endorses that rapid access TIA clinics could reduce costs of hospital admissions. Average length of admission for TIA is 6.7 days in Ireland. This study aimed to examine TIA admission lengths and identify possible targets for improvement in a model three Irish hospital. Methods All patients with a HIPE coded diagnosis of ‘Transient Ischaemic Attack’ from 17/12/21 to 20/8/22 were included. All coded diagnoses of ‘Transient Ischaemic Attack’ had a normal MRI brain DWI—abnormal MRI DWI imaging is coded as stroke. Therefore the true number of TIAs was not captured. Hospital electronic databases were used to identify baseline demographics, date of inpatient investigation request and date of inpatient investigation completion. Results 64 cases were identified. The median age was 79 years (interquartile range 67 to 86 years). 45% were female. 52% were admitted under a stroke/geriatric team. Median length of admission was 4 days (IQR 3 to 7 days). CT was requested on median day 0. MRI, carotid doppler US and echocardiogram were requested on a median day 1. 94% underwent CT brain imaging on median day 1. 34 (53%) underwent MRI brain DWI, on median day 3. 13 (20%) underwent carotid doppler US, on median day 3. 20 (31%) underwent echocardiogram, on median day 4. Conclusion Length of hospital stay has improved compared to prior studies. Limited access to investigations may prolong hospital stay. Streamlining services with development of urgent outpatient TIA clinics, could improve outcomes, save clinician time, free up hospital beds and save hospital funding.

Tralokinumab Efficacy Over 1Year in Adults with Moderate-to-Severe Atopic Dermatitis: Pooled Data from Two Phase III Trials.

Two phase III trials, ECZTRA 1 and 2, confirmed the efficacy and safety of tralokinumab versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To further explore the long-term efficacy of tralokinumab for AD, a pooled analysis of these trials was conducted. ECZTRA 1 and 2 patients (n = 1596 total) were randomized to tralokinumab 300mg or placebo every 2weeks (q2w) over 16weeks. Patients achieving Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 16, were re-randomized to tralokinumab q2w, every 4weeks (q4w), or placebo (tralokinumab withdrawal) for another 36weeks. Patients not achieving the response criteria at Week 16 received open-label tralokinumab q2w plus optional topical corticosteroids (TCS). A pooled, prespecified analysis assessed the proportions of Week 16 responders that maintained IGA 0/1 and/or EASI-75 at Week 52. Pooled data from all patients initiated with tralokinumab, regardless of the response at Week 16 or dosing regimen received thereafter, were analyzed post hoc. In patients who achieved the primary endpoints at Week 16, IGA 0/1 responses were maintained at Week 52 without rescue treatment (including TCS) by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, or placebo (tralokinumab withdrawal), respectively, while EASI-75 responses were maintained by 57.3%, 50.4%, and 26.4%, respectively (prespecified analysis). In a post hoc analysis of all patients initiated with tralokinumab, response rates improved over time with continued tralokinumab treatment beyond Week 16 to Week 52 for EASI-50 (63.1-82.7%), EASI-75 (37.6-61.8%), EASI-90 (20.4-37.3%), and IGA 0/1 (23.0-36.2%). Tralokinumab treatment provides progressive and sustained improvement over 1 year in the extent and severity of AD in patients with moderate-to-severe AD. NCT03131648 (ECZTRA 1); study start date: 30 May 2017; primary completion date: 7 August 2018; study completion date: 10 October 2019. NCT03160885 (ECZTRA 2); study start date: 12 June 2017; primary completion date: 4 September 2019; study completion date: 14 August 2019. INFOGRAPHIC.

Magnifying Gwendolyn Brooks: Creating a digital collection at the University of Illinois Library at Urbana-Champaign

The University of Illinois Urbana-Champaign Library is describing and digitising the Gwendolyn Brooks collection as part of the Saving America’s Treasures grant. This project began in the autumn of 2021, with the goal of making Brooks’s work visible and accessible. This paper discusses the first two stages of the project — the Red Album and the Black Scrapbook — objects that are full of mementos from Brooks’s personal and professional life. The paper focuses on the workflow and digitisation practices that the project team employed to create the first digital representations. It also reviews the team’s decisions, which would set the procedural policies and standards for all the remaining materials in the collection. The Red Album and the Black Scrapbook contain a variety of physical formats and materials, resulting in display issues for the digital collection. Collaboration between stakeholders from disparate units allowed for a streamlined approach from the initial description of the material through the hosting of digitised materials on the institution’s Digital Collections platform. This paper discusses challenges, the curatorial process, metadata, the process of description, digitisation, technical aspects and lessons learned from this project. Due to delays from the COVID-19 pandemic, the project’s expected completion date is summer 2023. This paper reflects on the processes and lessons learned throughout the project. It also discusses the most valuable lesson from this project, which is that the digitisation of large and complex collections must be adaptable in order to successfully meet the challenges that such materials offer.

Predictors of timeliness of vaccination among children of age 12–23 months in Boricha district, Sidama region Ethiopia, in 2019

BackgroundTraditional measurement of vaccine coverage can mask the magnitude of timely uptake of vaccine. Hence, the optimal measurement of timeliness is unclear due to variations in vaccine schedule among countries in the world. In Ethiopia, Oral Polio Virus (OPV), Pentavalent, Tetanus, H. influenza type B, Hepatitis B, and Pneumonia-Conjugate Vaccine (PCV) are basic vaccines which are taken at birth, six weeks, ten weeks, and fourteen weeks respectively. Despite its importance, information is scarce about on-time vaccination in the study area. Therefore, this study aimed to assess prevalence and factors associated with on-time vaccination among children of age 12–23 months in Boricha district, Sidama Ethiopia, in 2019.MethodsA community based survey was conducted in Boricha district, Sidama region Ethiopia from January 1–30 in 2019. Study participants were selected using stratified multistage sampling technique. Kebeles were stratified based on residence. First, Kebeles were selected using random sampling. Then, systematic random sampling was employed to reach each household. Data were collected using structured and interviewer administered questionnaire. Logistic regression analysis was employed to identify factors associated with timely vaccination. Then, independent variables with p-value < 0.25 in COR were fitted further into multivariate logistic regression analysis model to control the possible cofounders. AOR with 95% CI and p-value < 0.05 was computed and reported as the level of statistical significance.ResultsFrom a total of 614 study participants, only 609 study participants have responded to questions completely making a response rate of 99.2%. Prevalence of timeliness of vaccination was 26.8% (95% CI: 25, 28) in this study. Factors like children of women with formal education (AOR = 5.3, 95%CI,2.7, 10.4), absence of antenatal care visit (AOR = 4.2,95%CI, 1.8,9.8), home delivery (AOR = 6.2,95%CI,4.0,9.3), lack of postnatal care (AOR = 3.7,95%CI,1.1,13.3), and lack of information about when vaccines completion date (AOR = 2.0, 95% CI,1.13,3.8) were factors influences timely vaccination among children of age 12–23 months.ConclusionPrevalence of on-time vaccination among children of age 12–23 months is lower than national threshold. Therefore, sustained health education on vaccination schedule and reminder strategies should be designed and implemented. Furthermore, maternal and child health care services should be enhanced and coordinated to improve on-time uptake of vaccine.

Safety and efficacy of Placida® (fixed dose combination of flupentixol 0.5 mg and melitracen 10 mg) in comparison to escitalopram 10 mg and clonazepam 0.5 mg in patients with comorbid anxiety and depression: a randomized, double blind, double dummy, parallel group clinical trial

Background: Individuals with major depressive disorder (MDD) commonly present with comorbid anxiety and have greater depressive illness severity and chronicity, more suicide attempts, and completions. This randomized, double blind, double dummy, parallel-group clinical phase IV trial (CTRI/2022/11/047050) is aimed to compare the safety and efficacy of Placida® (FDC of flupentixol 0.5 mg + melitracen 10 mg) versus escitalopram + clonazepam in patients with comorbid anxiety and depression. Methods: This is a randomized, controlled, double blind, double dummy, parallel-group, phase IV trial. A total of 440 patients was enrolled across 11 sites in India who fulfilled the inclusion and exclusion criteria. All the subjects will be followed up for 2, 4, 6, 8, 10, 12, 16, 20, and 24 weeks with a buffer period of 1 week in each visit. The patient will be checked for severity of adverse events (AEs) and serious adverse events (SAEs). Efficacy will be assessed using the Hamilton depression rating scale (HAM-D), Hamilton anxiety rating scale (HAM-A) at baseline, weeks 4, 8 and 16, 24 score-reduction rate from baseline to end of treatment and extrapyramidal symptom rating scale (ESRS) at week 16 and end of the study. The first enrolment was done on 26 November 2022 and presently the subjects are under follow-up stage. The anticipated completion date for the study is March 2024. Conclusions: Outcomes of this trial will provide valuable information on safety and efficacy of Placida® as compared to escitalopram and clonazepam in treating patients with comorbid anxiety and depression. Trial Registration: The trial is registered with clinical trial registry India (CTRI/2022/11/047050) prospectively.

Posting of clinical trial results and other critical information from completed medicines trials on ClinicalTrials.gov.

Clinical trials transparency requires trial registration and the posting of results on a public register. US regulations also require the posting of protocols and statistical analysis plans (SAPs). For US Federal agency funded trials to be started on or after 21January2019, informed consent forms (ICFs) must also be posted. Posting these documents is not mandatory in other countries. We aimed to assess compliance with US regulations of trials conducted in the US or in other countries with respect to ICFs, protocols, SAPs, and results. This cross-sectional analysis (27April2023) comprised completed medicines trials to be started on or after 21January2019 registered on ClinicalTrials.gov. Trial data were registered by funder type (i.e., 'US federal agencies', industry, and 'all others') and development phase. Of 5,584 trials, 40% were conducted solely in the US. 47% and 12% of US and non-US trials had posted results. Some 40% of US trials had posted protocols and SAPs as did 9% of trials conducted in other countries. Only 10% (US) and 2% (other countries) of trials had posted ICFs. When the margin of the last 2 and 12 months after primary completion date were considered in the analysis, ICF posting rate did not change, but posting results increased to 64% for US trials. 'US Federal agencies' funded trials were significantly more likely to post ICFs than industry [OR 23.9 (12.5-45.7; <.001)] or 'all others' [OR 3.16 (1.79-5.56; <.001)]. Future interventions should be considered to encourage timely posting of trial results and information.

Correlates of child mental health and substance use related emergency department visits in Ontario: A linked population survey and administrative health data study.

Knowledge of the sociodemographic, behavioural, and clinical characteristics of children visiting emergency departments (EDs) for mental health or substance use concerns in Ontario, Canada is lacking. Using data from a population-based survey linked at the individual level to administrative health data, this study leverages a provincially representative sample and quasi-experimental design to strengthen inferences regarding the extent to which children's sociodemographic, behavioural, and clinical characteristics are associated with the risk of a mental health or substance use related ED visit. 9,301 children aged 4-17 years participating in the 2014 Ontario Child Health Study were linked retrospectively (6 months) and prospectively (12 months) with administrative health data on ED visits from the National Ambulatory Care Reporting System. Modified Poisson regression was used to examine correlates of mental health and substance use related ED visits among children aged 4-17 years over a 12-month period following their survey completion date, adjusting for ED visits in the 6 months prior to their survey completion date. Subgroup analyses of youths aged 14-17 years who independently completed survey content related to peer victimisation, substance use, and suicidality were also conducted. Among children aged 4-17 years, older age, parental immigrant status, internalising problems, and perceived need for professional help were statistically significant correlates that increased the risk of a mental health or substance use related ED visit; low-income and suicidal ideation with attempt were statistically significant only among youths aged 14-17 years. Knowledge of the sociodemographic, behavioural, and clinical characteristics of children visiting EDs for mental health and substance use related concerns is required to better understand patient needs to coordinate effective emergency mental health care that optimises child outcomes, and to inform the development and targeting of upstream interventions that have the potential to prevent avoidable ED visits. Growing rates of child mental health and substance use related ED visits have been observed internationally.A population-based survey linked at the individual level to administrative health data was used to examine the extent to which children's sociodemographic, behavioural, and clinical characteristics are associated with the risk of a mental health or substance use related ED visit in Ontario, Canada.Older age, low-income, parental immigrant status, perceived need for professional help, internalising problems, and suicidality increase the risk of an ED visit.Knowledge of the characteristics of children visiting EDs can be used to coordinate effective emergency mental health care that optimises child outcomes, and to inform the development and targeting of upstream interventions that have the potential to prevent avoidable ED visits.

TIPS-05 ADJUVANT TEMOZOLOMIDE CHEMOTHERAPY FOLLOWING RADIOTHERAPY IN NEWLY DIAGNOSED LOW-GRADE GLIOMA PATIENT WITH RESIDUE TUMORS: A MULTICENTER, OPEN LABEL, RANDOMIZED TRIAL

Abstract Low-grade glioma (LGG) with infiltrative nature and frequent growth in eloquent area in brain often makes total resection impossible. Although post-radiation adjuvant temozolomide (TMZ) is the standard of care for high-grade gliomas, and radiotherapy and/or TMZ are recommended for the treatment of residue low-grade gliomas, the efficacy of combined radiotherapy with adjuvant TMZ for residue LGG remains to be defined. We have initiated a randomized clinical trial in 2012 to test whether radiotherapy with subsequent TMZ chemotherapy will improve survival of patients with residue LGG compared to radiotherapy alone. This study was approved by the Ethics Committee of the Sun Yat-sen University Cancer Center, Guangzhou, China (approval No. 5010-2012-03) and was registered with ClinicalTrials.gov (NCT01649830). Inclusion Criteria: Patients age of 18 years to 60 years, with incompletely resected supratentorial WHO grade 2 astrocytoma, oligodendroglioma or oligodendroastrocytoma. Enrolled patients were randomized into: radiation therapy alone (RT) or radiotherapy with subsequent TMZ chemotherapy (RC) group. Start Date: July 2012, Estimated Primary Completion Date:August 2025. Radiation therapy will start within 8 weeks after neurosurgical procedures, with a total dose of 54.0 Gy in 27 - 30 fractions over 6 - 7 weeks. Four weeks after radiotherapy, patients in RC group will receive 6 cycle of TMZ dosed at 200 mg/m2 daily for 5 consecutive days, repeated every 28 days. We have completed enrollment on December 2018 with valid cases of 248 patients. Up to last follow-up date of Feb. 2023, 204 cases were analyzed (see table). There is no significant difference between RT group and RC group on both PFS and OS (5-year PFS 68.9% vs 75.2%, p=0.680; 5-year OS 92.0% vs 86.0%, p=0.400). Longer follow-up and molecular subgroup analysis are currently on the way, which could show benefit in special molecular subgroup.

A Corpus of Illuminated Qurʾāns from Coastal East Africa

Abstract This article examines a little-known corpus of illuminated Qurʾān manuscripts that were produced between ca. 1750–ca. 1850 in the Swahili city-states of Pate, Siyu, and Faza on Pate Island in the Lamu archipelago (Kenya). Now dispersed in collections in Kenya, Tanzania, Oman, the UK, and the USA, the manuscripts have many distinctive features: decorative frontispieces, sūra titles, basmalas, and division and prostration markers; locally developed Arabic script styles; colophons containing names of copyists and completion dates; endowment dedications; northern Italian-made paper; and, blind-stamped, leather covers. The list of known manuscripts presented in the appendix is aimed at encouraging the identification, digitization, and study of other manuscripts in the corpus. The study of their content, materiality, and contexts of production can advance scholarship on the histories of Islamic manuscript production in coastal East Africa and provide comparative material for manuscript studies in other regions of Eastern Africa and the Indian Ocean.

Decision Analysis of Offshore Channel Maintenance Dredging in PT. PQR

The offshore channel maintenance dredging completion date, which was performed by PT. ABC (PT. PQR’s contractor) using crane barge XYZ, was delayed to 19 May 2023 (43.4 days delayed). Two main problem were identified using Kepner Tregoe Situation Analysis (KT-SA) based on the company data processing and one most main contributing problem (lack of daily sediment production; the initial plan was 1500 m3/day) then be analyzed using Kepner Tregoe Problem Analysis (KT-PA) and the root cause was constructed using cause-map with brainstorming method included in the process between author and some of PT. ABC dredging crew in crane barge XYZ. Substitute, Combine, Adapt, Modify, Put on another use, Eliminate, Rearrange (SCAMPER) technique then be brought in the brainstorming session with PT. ABC dredging crew on crane barge ABC to bring alternative solutions for the root cause of the problem. Furthermore, the SCAMPER result be brought to brainstorming with PT. PQR dredging operation assistant manager, as the problem holder and matter expert, and filtered to three most possible alternative solutions. These three most possible solutions then examined using Simple Multiple Attribute Rating Technique (SMART) method with eight stages were performed. The criteria used in this method are offshore channel dredging project cost, offshore channel dredging project schedule, coordination with other entity, and permit to work (PTW) &amp; derogation. The objectives of this research are knowing what factors affecting the dredging project in PT. PQR offshore channel case and the alternative solution to be brought in the next offshore channel maintenance dredging.

The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma.

The influence of genetic factors on survival following a diagnosis of hepatocellular carcinoma (HCC) remains unclear. To assess whether genetic polymorphisms influencing the susceptibility to develop HCC are also associated with HCC prognosis. We included United Kingdom Biobank (UKB) participants diagnosed with HCC after study enrolment. The primary outcome was all-cause mortality. Patients were followed from the date of HCC diagnosis to death or the registry completion date. Five HCC susceptibility loci were investigated: rs738409 (PNPLA3), rs58542926 (TM6SF2); rs72613567 (HSD17B13); rs2242652 (TERT) and rs708113 (WNT3A). The associations between these genetic variants and HCC mortality risk were assessed using Cox regression, adjusted for age, sex, ethnicity, aetiology, severity of the underlying liver disease and receipt of curative HCC treatment. The final sample included 439 patients; 74% had either non-alcoholic fatty liver disease or alcohol-related liver disease. There were 321 deaths during a mean follow-up of 1.9 years per participant. Kaplan-Meier survival estimates at 1, 3 and 5 years were 53.2%, 31.2% and 22.6% respectively. In multivariate analysis, rs72613567:TA (HSD17B13) was the only genetic susceptibility variant significantly associated with all-cause mortality risk (aHR: 0.74; 95% CI: 0.61-0.90; p = 0.003). Other associated factors were Baveno stage 3-4 (aHR: 1.65; 95% CI: 1.05-2.59; p = 0.03) and HCC treatment with curative intent (aHR: 0.25; 95% CI: 0.17-0.37; p < 0.001). The rs72613567:TA polymorphism in HSD17B13 is not only associated with a reduction in the risk of developing HCC but with a survival benefit in HCC once established. Therapeutic inhibition of HSD17B13 may augment survival in individuals with HCC.

Scholarly activity following National Institutes of Health Women’s Reproductive Health Research K12 training—a cohort study

National Institutes of Health funding to address basic reproductive health for common female conditions remains disproportionately low, in part because of low success rates of grant applications by obstetrician-gynecologists. This study aimed to evaluate the scholarly productivity of individuals supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Women's Reproductive Health Research K12 career development award, created to advance careers of obstetrician-gynecologist physician-scientists. We performed a cohort study of individuals who completed at least 2 years of Women's Reproductive Health Research training by June 30, 2015, and had at least 5-year follow-up. Earliest training start date was December 1, 1998. Primary outcomes from public data sources (National Institutes of Health RePORTER, PubMed, iCite) were (1) number of total and R01 National Institutes of Health grants as principal investigator; (2) numbers of total and first and last author publications; and (3) median and highest publication impact factor measured by the relative citation ratio. Secondary outcomes from an email survey subcohort were total number of research grants, federally funded grants, and number of National Institutes of Health grants as coinvestigator; institutional promotions and academic appointments, national and National Institutes of Health leadership roles; and career and mentorship satisfaction. Outcomes were recorded at 5, 10, and 15 years postgraduation, and aggregate anonymized data were divided into 3 groups using Women's Reproductive Health Research completion dates: June 30 of 2005, 2010, and 2015. Temporal trends were assessed. Results were stratified by gender, number of awarded grant cycles (1-2 vs 3-4), and specialty type. Analyses used Fisher exact or Pearson chi-square tests, and Mantel-Haenszel tests of trend. The distribution of the cohort (N=178) by graduation completion date was: on or before June 30, 2005 (57 [32%]); July 1, 2005 to June 30, 2010 (60 [34%]); and July 1, 2010 to June 30, 2015 (61 [34%]). Most participants were female (112 [64%]) and maternal-fetal medicine trained (53 [30%]), followed by no fellowship (50 [28%]). Of the 178 participants, 72 (40%) received additional National Institutes of Health funding as a principal investigator, 45 (25%) received at least 1 R01, and 23 (13%) received 2 to 5 R01s. There were 52 (31%) scholars with >10 first author publications, 66 (39%) with >10 last author publications, and 108 (63%) with ≥25 publications. The highest relative citation ratio was a median of 8.07 (interquartile range, 4.20-15.16). There were 121 (71%) scholars with relative citation ratio ≥5, indicating >5-fold greater publication impact than that of other National Institutes of Health-funded scientists in similar areas of research. No differences by gender, institution, or temporal trends were observed. Of the full cohort, 69 (45.7%) responded to the survey; most self-identified as women (50 [73%]) and White (51 [74%]). Our findings suggest that the infrastructure provided by an institutional K award is an advantageous career development award mechanism for obstetrician-gynecologists, a group of predominantly women surgeons. It may serve as a corrective for the known inequities in National Institutes of Health funding by gender.

Unpublished completed obstetric randomized clinical trials registered at ClinicalTrials.gov: how big is this issue?

A portion of obstetrical randomized clinical trials (RCTs) registered at ClinicalTrials.gov are not published in peer-reviewed journals. To compare the characteristics of completed published versus unpublished randomized clinical trials in obstetrics registered on ClinicalTrials.gov, and to identify barriers to publication. This cross-sectional study queried ClinicalTrials.gov for all completed obstetrical randomized clinical trials registered between January 1, 2009, and December 31, 2018. For each completed obstetrical RCT, we abstracted the following registration fields from ClinicalTrials.gov: ClinicalTrials.gov identifier; recruitment status; trial start and completion dates; study results; type of intervention; study phase; enrollment size; funder type; location; and facilities. Calculated variables included time to completion. In May 2021, we used PubMed and Google Scholar to identify the publication status of completed trials, and we compared the characteristics of published vs. unpublished RCTs. The corresponding authors' email addresses for the unpublished studies were collected from ClinicalTrials.gov and departmental websites. Between September 2021- March 2022, authors of these completed but unpublished obstetrical RCTs were contacted and invited to respond to a survey examining perceptions of barriers to publication, responses of which were collected and presented as counts and percentages. Of the 647 obstetrical randomized clinical trials marked as completed on ClinicalTrials.gov, 378 (58%) were published, and 269 (42%) were unpublished. Unpublished trials were more likely to have an enrollment size of <50 participants (14.5% published, 25.3% unpublished; P < 0.001), and less likely to be conducted at multiple sites (25.4% vs. 17.5%; p < 0.02). The main barriers to publication reported in the survey by authors whose trials were not published included: lack of time (30%), change in employment or completion of training (25%), and results that were not of statistical significance (15%). Among the obstetrical randomized clinical trials registered and marked as completed on ClinicalTrials.gov, over 40% were unpublished. Unpublished trials were more likely to be smaller studies, conducted by researchers who reported experiencing a lack of time as the most common barrier to study publication.

Quality of life of transgender people under the lens of social determinants of health: a scoping review protocol

IntroductionThere is an urgent need for knowledge about the transgender population to inform the development of clinical protocols and training of health professionals on the unique issues affecting this population....

Multi-Criteria Decision-Making in Public Procurement: An Empirical Study of Contractor Selection for Landslide Rehabilitation

When carrying out construction work, identifying the best contractor is a critical component of the project life cycle in the construction industry. The investor must use effective and efficient strategies to create a competitive bidding environment in public projects. The research presented in this paper was conducted to demonstrate the competitive nature of public procurements, where contractors compete to present the best bid and win the contract. To award the contract, the best offer must be selected. Based on different strategies and multi-criteria decision-making approaches this study proposes a method for identifying the most suitable strategy out of eight bidding strategies on four different lots, resulting in the most suitable one for landslide rehabilitation in the Brčko district. The results reveal the optimal approach to follow to minimize time and financial losses in the case of landslide rehabilitation during periods of market instability. Such research findings validate the efficiency of the bidding strategies-based decision-making support. The proposed method allows for compromise on both the completion date and the lowest bid made by the winning contractor.

Assessing safe and personalised maternity and neonatal care through a pandemic: a case study of outcomes and experiences in two trusts in England using the ASPIRE COVID-19 framework

BackgroundThe COVID-19 pandemic has resulted in profound and far-reaching impacts on maternal and newborn care and outcomes. As part of the ASPIRE COVID-19 project, we describe processes and outcome measures relating to safe and personalised maternity care in England which we map against a pre-developed ASPIRE framework to establish the potential impact of the COVID-19 pandemic for two UK trusts.MethodsWe undertook a mixed-methods system-wide case study using quantitative routinely collected data and qualitative data from two Trusts and their service users from 2019 to 2021 (start and completion dates varied by available data). We mapped findings to our prior ASPIRE conceptual framework that explains pathways for the impact of COVID-19 on safe and personalised care.ResultsThe ASPIRE framework enabled us to develop a comprehensive, systems-level understanding of the impact of the pandemic on service delivery, user experience and staff wellbeing, and place it within the context of pre-existing challenges.Maternity services experienced some impacts on core service coverage, though not on Trust level clinical health outcomes (with the possible exception of readmissions in one Trust). Both users and staff found some pandemic-driven changes challenging such as remote or reduced antenatal and community postnatal contacts, and restrictions on companionship. Other key changes included an increased need for mental health support, changes in the availability and uptake of home birth services and changes in induction procedures. Many emergency adaptations persisted at the end of data collection. Differences between the trusts indicate complex change pathways. Staff reported some removal of bureaucracy, which allowed greater flexibility.During the first wave of COVID-19 staffing numbers increased, resolving some pre-pandemic shortages: however, by October 2021 they declined markedly. Trying to maintain the quality and availability of services had marked negative consequences for personnel. Timely routine clinical and staffing data were not always available and personalised care and user and staff experiences were poorly captured.ConclusionsThe COVID-19 crisis magnified pre-pandemic problems and in particular, poor staffing levels. Maintaining services took a significant toll on staff wellbeing. There is some evidence that these pressures are continuing. There was marked variation in Trust responses. Lack of accessible and timely data at Trust and national levels hampered rapid insights. The ASPIRE COVID-19 framework could be useful for modelling the impact of future crises on routine care.

Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials.

Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144). The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials. The safety of secukinumab was evaluated in subgroups of pediatric patients defined by age (6 to <12 and 12 to <18 years) and bodyweight (<25 kg, 25 to <50 kg, and ≥50 kg) in the pooled population. Patients received secukinumab low dose (LD; 75/75/150 mg), secukinumab high dose (HD; 75/150/300 mg), placebo, or etanercept (0.8 mg/kg). For safety analyses, data were pooled from the pediatric studies NCT03668613 and NCT02471144, and presented alongside the pooled data from four adult pivotal studies (NCT01365455, NCT01636687, NCT01358578, NCT01555125). A total of 198 pediatric patients (overall exposure: 184.6 patient-years [PY]) and 1989 adult patients (1749.5 PY) receiving secukinumab up to week 52 were included in this analysis. At week 52, the incidence of adverse events (AEs) was lower in the lower age and bodyweight subgroups. The AEs reported within these subgroups were consistent with the overall AEs reported in this analysis. Overall, exposure-adjusted incidence rates for treatment-emergent AEs were lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with the etanercept (266.3/100 PY) and adult pools (256.1/100 PY). Up to 52 weeks, the incidence rates of the AEs in the secukinumab-treated patients in the 6 to <12 years subgroup and 12 to <18 years subgroup were 167.7/100 PY and 214.7/100 PY, respectively. Similarly, incidence rates of the AEs in the secukinumab-treated patients in the <25 kg, 25 kg to <50 kg, and ≥50 kg subgroups were 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY, respectively. Nasopharyngitis was the most frequently reported AE in secukinumab-treated pediatric patients across age (<12 years: 11.8/100 PY; ≥12 years: 42.4/100 PY) and bodyweight (<25 kg: 22.8/100 PY; 25 kg to <50 kg: 19.0/100 PY; ≥50 kg: 43.0/100 PY). Of the 198 secukinumab-treated pediatric patients, one reported nail Candida, one reported skin Candida, and two reported vulvovaginal Candida. Transient and mostly mild events of neutropenia were observed with secukinumab, none leading to study treatment discontinuation. No incidence of treatment-emergent anti-drug antibodies was reported in pediatric patients treated with secukinumab. Secukinumab was well tolerated in pediatric patients with moderate to severe and severe plaque psoriasis across age and bodyweight subgroups. The overall safety profile of secukinumab in pediatric patients was consistent with that of adult patients. NCT03668613 (Novartis Study Code CAIN457A2311, referred to as A2311), actual study start date: August 29, 2018; actual primary completion date: September 19, 2019; estimated study completion date: September 14, 2023. NCT02471144 (Novartis Study Code CAIN457A2310, referred to as A2310), study start date: September 29, 2015; primary completion date: December 13, 2018; estimated study completion date: March 31, 2023.