Recruitment Period Research Articles

How feasible is nutrition intervention research in eating disorders? Lessons learnt from a pilot parallel randomised controlled trial of tyrosine supplementation in adolescents with anorexia nervosa.

Eating disorders are complex illnesses with high morbidity and mortality. Yet, there is promising evidence to support the effects of nutrition on the brain and behaviour. One proposed example is the use of tyrosine as an adjunct treatment in anorexia nervosa (AN). However, recruitment and retention in eating disorder clinical trials has posed difficulties for researchers. The aim of this study was to pilot test a parallel randomised controlled trial (RCT) of tyrosine supplementation to explore the feasibility of recruitment and retention, intervention adherence and data collection methods from the perspective of participants and researchers. Feasibility was assessed using numbers participating, questionnaire completion in patients and parent/carers completing and declining participation, a researcher implementation record and clinical measures. Subjects included adolescents aged 12-17 years with AN. The study was conducted over a 12-week period, with the intervention group receiving 5mg of L-tyrosine supplement and the control group receiving a placebo. Recruitment targets were not met and recruitment to a full RCT based on the current study protocol and recruitment sites did not prove feasible. Of the 39 approached for RCT participation, seven were recruited to the RCT (18% response rate) despite extending recruitment periods, with 100% retained and analysed. Patients or parents/carers identified barriers to study participation including burden, the need to consume tyrosine as tablets, and the use of blood, urine and psychological testing. Blood tyrosine rose markedly for subjects in the intervention group. No side effects were reported or measured. This study offers a unique exploration of the feasibility of a tyrosine trial in anorexia nervosa and is of relevance to assist the success of future nutrition trials. Exploring the suitability of future study designs for nutrition intervention research is warranted.

Recruiting and retaining healthcare workers in Scotland to a longitudinal COVID-19 study: a descriptive analysis

BackgroundRapid timescales for the design and delivery of research were common during the COVID-19 pandemic. The recruitment and retention of healthcare workers (HCWs) as participants in research studies are notoriously challenging, but this was exacerbated during the pandemic by the unprecedented demand placed on the workforce. The SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN study) is a prospective multicentre cohort study following HCWs in the UK. This paper discusses the strategies and challenges associated with recruitment and retention of HCW participants in Scotland.MethodsThere were 44,546 HCWs recruited to the SIREN study, of whom 6,285 were recruited by research teams at ten different research sites in Scotland between October 2020 and March 2021. Information on target and actual sample size, availability of resource, recruitment rate, and recruitment and engagement strategies by site was collated from SIREN study documentation and discussions with local key SIREN site staff. Individual-level data from 6,153 HCW participants with ongoing consent for all data usage were also collated, including socio-demographic data and information on withdrawal (in first year) and opt-in to a study extension after one year. Factors associated with these outcomes were explored in logistic regression analyses.ResultsDifferent recruitment strategies were used in each site according to local agreements, protocol and staff capacity, with the recruitment period ranging from 13 to 160 days. The locally-agreed recruitment target was met in four sites. The proportion of participants who withdrew in the first year ranged from 3.1 to 24.8% by site, while subsequent opt-in to a 12-month study extension ranged from 28.6 to 74.8%. The sites with the highest proportions of withdrawals were the same four sites with lowest proportions of opt-in. On an individual level, there was a lower level of retention among younger participants, and those from lower socio-economic backgrounds and minority ethnic groups.ConclusionsSite-specific factors including research-readiness likely had a significant influence on recruitment and retention, more so than the specific recruitment or retention strategies employed. Independent of site factors, individual-level variables influenced recruitment and retention, suggesting targeted strategies may be needed to promote research engagement among particular socio-demographic groups.

Optimizing Sample Size Determinations for Phase 3 Clinical Trials in Type 2 Diabetes.

An informed estimate of subject-level variance is a key determinate for accurate estimation of the required sample size for clinical trials. Evaluating completed adult Type 2 diabetes studies submitted to the FDA for accuracy of the variance estimate at the planning stage provides insights to inform the sample size requirements for future studies. From the U.S. Food and Drug Administration (FDA) database of new drug applications containing 14,106 subjects from 26 phase 3 randomized studies submitted to the FDA in support of drug approvals in adult type 2 diabetes studies reviewed between 2013 and 2017, we obtained estimates of subject-level variance for the primary endpoint-change in glycated hemoglobin (HbA1c) from baseline to 6 months. In addition, we used nine additional studies to examine the impact of clinically meaningful covariates on residual standard deviation and sample size re-estimation. Our analyses show that reduced sample sizes can be used without interfering with the validity of efficacy results for adult type 2 diabetes drug trials. This finding has implications for future research involving the adult type 2 diabetes population, including the potential to reduce recruitment period length and improve the timeliness of results. Furthermore, our findings could be utilized in the design of future endocrinology clinical trials.

Sex-specific models to predict 5-year mortality after ST-elevation myocardial infarction using machine learning: insight from FAST-MI registry

Abstract Background Most prognostic stratification tools in acute myocardial infarction (AMI) have been derived from populations including both women and men and including only a small proportion of women. Purpose Using supervised machine learning (ML), we examined the performance of 2 models assessing 5-year mortality after AMI, one derived from a population of women only and one from a population of men only, to determine whether sex-specific models improved outcome prediction. Methods This cohort study used the French registry on acute ST-elevation and non-ST-elevation myocardial infarction (FAST-MI) 2010 and 2015 surveys. This multicentric registry led in more than 200 French hospitals, enrolled all consecutive patients with acute myocardial infarction during a 1-month recruitment period. Our analysis included all men and women presenting STEMI who underwent invasive coronary angiography (ICA). To build and validate the models, the data set were split with a 70%/30% ratio into training and testing sets. The primary outcome was 5-year all-cause mortality. Then, 52 clinical, laboratory, ECG, echocardiographic, and ICA parameters were evaluated for feature selection using Boruta algorithm. Different supervised machine learning algorithms, including random forest (RF), were assessed for model building, and their performance were compared in women and men. To compare prediction accuracy according to sex, we evaluate the performance of the women-based ML model in men from the same cohort. Results 1,189 consecutive women and 3,685 men with STEMI (mean age 61±13 and 69±15 years, respectively) were recruited; 12% of men and 20% of women experienced 5-year all-cause mortality. Using Boruta algorithm, the 10 most important variables for prediction were selected (Figure 1). For women-based ML model building, the RF algorithm exhibited the best performance to predict mortality with an area under the receiver-operating characteristic curve (ROC-AUC) of 0.82 (95% CI: 0.77 – 0.88), an area under the precision-recall curve (PR-AUC) of 0.59 (95% CI: 0.54 – 0.64); and a F1-score of 0.58. The women-based ML model exhibited lower performance in men (ROC-AUC: 0.78; PR-AUC: 0.43; Figure 2). Conversely, the men-based model exhibited better accuracy in men than in women. Conclusion In a large multicentric cohort of STEMI patients, a women-based ML-model exhibited a good accuracy to predict 5-year all-cause mortality in women, but a drop of accuracy when applied to men. In mirror, the accuracy of the men-based model was lower in women. This suggests that sex-specific models might be superior to general models to predict mortality after AMI.Features selection and ML model buildingML model performance according to sex

Silent cerebral microvascular disease and longitudinal risk of cognitive decline in atrial fibrillation

Abstract Background A relationship between silent stroke and cognitive disorder has recently been suggested in patients with nonvalvular atrial fibrillation (NVAF). This research is an exploratory research study to investigate the occurrence of asymptomatic cerebrovascular disorders with NVAF. Methods The SKAF (Silent cerebral microvascular disease and longitudinal risK of cognitive decline in Atrial Fibrillation) study is a prospective, investigator-initiated, multicenter, observational study of Japanese patients with NVAF aged 60 years or older. We had planned to enroll two hundred NVAF patients with no history of symptomatic stroke or dementia, and an anticoagulant therapy with edoxaban is being performed or an anticoagulant therapy is not being performed, and one hundred patients with sinus rhythm, for comparison. We collected patient characteristics, clinical course, the data of head MRI test and cognitive function test (Montreal Cognitive Assessment (MoCA)) at the baseline and the 24 months follow-up. The primary endpoint was the composite of silent ischemic stroke and micro-bleeding over a 24-month follow-up period. The secondary endpoint was cognitive decline over a 24-month follow-up period. Results The study was started in October 2016, with a planned 2-year recruitment period. As of January 31, 2018, a total of 326 patients were enrolled. Of those, 99 patients with sinus rhythm (SR group) and 214 patients with NVAF (NVAF group) were analyzed (male, 193 (62%) patients; age, 72.2±6.5 years). 156 of 195 (80%) patients with NVAF received the anticoagulant therapy with edoxaban. There was no significant difference of the primary composite for the endpoints between two groups (17.4% versus 17.4%; p=1.00). The incidences of silent ischemic stroke and micro-bleeding in SR and NVAF groups over a 24-month follow-up period were 9.3% and 10.8% (p= 0.833), and 8.1% and 9.2% (p=1.00), respectively. The NVAF group exhibited a significantly larger decline in cognition changes in MoCA score than SR group (-0.830 versus 0,000; p=0.0131). Notably, NVAF was found to be associated with cognitive decline. Conclusion The SKAF registry provided an equivalent risk of silent cerebral microvascular disease in patients with SR and NVAF. Clinically, NVAF had an impact on cognitive decline.

21 Exploring the clinical presentation and health service utilization in autistic children and adolescents diagnosed with avoidant / restrictive food intake disorder: A descriptive study

Abstract Background Avoidant/restrictive food intake disorder (ARFID) is an eating disorder with much clinical variability, negatively impacting growth, nutrition, psychosocial functioning and overall well-being. ARFID is more frequently reported in neurotypical populations than in neurodivergent populations. Little is known about the clinical presentation and healthcare utilization of autistic individuals with ARFID. Objectives The purpose of this study was to understand the clinical presentation, laboratory abnormalities and health system utilization amongst autistic individuals diagnosed with ARFID within the community. Design/Methods We completed a comprehensive multidisciplinary assessment on autistic individuals less than18 years of age who were diagnosed with ARFID by their community physician. Recruitment period: June 2020-June 2021. Results Nineteen autistic individuals completed a comprehensive multidisciplinary assessment; of these, 42.1% (8/19) met criteria for Autism Spectrum Disorder (ASD) severity level 1. The onset of restrictive eating manifested at M(SD)= 2.5 (0.7) years, and the age of ASD diagnosis was 4.2 (3.8) years. Of these, 78.9% (15/19) had the onset of feeding difficulties either prior to or at the time of their ASD diagnosis (Figure 1). Dependence on enteral feeding or nutritional supplements (74%), psychosocial impairment (68%), and nutritional deficiencies (42%) were the criteria commonly met for ARFID. Sensory-based avoidance (100%) and lack of interest in food (89%) were the two most reported potential drivers for the dysfunctional feeding behaviour based on the Pica , ARFID, and Rumination Disorder Interview-AR-Q. Neurodevelopment disorder comorbidities included ADHD (26.3%), Anxiety (21.1%), and Intellectual Developmental Disability (15.8%). Constipation (68.4%) and nutritional deficits (63.15%) were the most common medical comorbidities recorded. Nutritional profile revealed Vitamin D deficit in 50% (8/16), Anaemia 21% (4/19), Vitamin B1 deficit 20% (2/10). Additionally, three participants (17.7%, 3/17) had deficits in Vitamin B12, Zinc, Vitamin C and low ferritin levels. Four autistic individuals (21.1%, 4/19) were hospitalized because of their restrictive eating. 68.4% (13/19) autistic individuals had involvement of at least one allied health professional (OT or SLP or BT). No participants had a prior multidisciplinary feeding assessment or intervention to address restrictive eating. Conclusion ARFID is an eating disorder observed within autistic individuals. Evidence suggests food related sensory sensitivities and lack of interest in food are potential drivers of ARFID in the context of ASD. A comprehensive multidisciplinary assessment is needed to elucidate factors driving restrictive eating to inform targeted evidence-based interventions.

Tranexamic Acid for reduction of intra- and postoperative TRansfusion requirements in elective Abdominal surgery (TATRA): study protocol for an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized superiority trial with two parallel groups

BackgroundIntra- and postoperative hemorrhage is a relevant problem in major abdominal surgery, leading to acute anemia and necessitating transfusion of packed red blood cells. It is estimated that in 30% of abdominal surgeries, intra- or postoperative transfusion is required. Transfusion potentially has detrimental health effects and poses a considerable socioeconomic burden. Tranexamic acid, a lysine analog inhibiting plasminogen activation and providing clot stability, has been used to reduce hemorrhage. While there is ample evidence in other surgical disciplines, it is almost completely lacking in abdominal surgery.MethodsThis multicenter double-blind parallel group randomized superiority trial will compare tranexamic acid (loading dose 1000 mg over 10 min prior to skin incision, maintenance dose 125 mg/h continuously until skin closure or until 1000 mg have been administered) to placebo in patients ≥ 18 years undergoing elective esophagectomy, gastrectomy, colectomy, rectal resection, pancreatic resection, or hepatectomy. The primary efficacy endpoint is the intra- or postoperative transfusion of at least one unit of packed red blood cells. Key secondary endpoints are the number of transfused units per patient, estimated intraoperative blood loss, postoperative complications/mortality, length of hospital stay, operation/anesthesia time, D-dimer levels, and quality of life. Sample size calculation is based on the assumption that in the control group, 30% of patients require transfusion while the intervention achieves a risk reduction of 33%, reducing the probability to 20%. With a type one error of 5% and a power of 90%, using a two-sided χ2 test, this results in 412 patients per group. Accounting for non-compliance, 425 patients are to be randomized per group. The total trial duration will be 30 months with a recruitment period of 18 months.DiscussionIf the proposed trial yielded positive results, the routine use of tranexamic acid in major abdominal surgery would be supported. This would avoid acute anemia with detrimental effects such as tissue hypoxia and organ injury, as well as the negative immediate and delayed effects of transfusions.Trial registrationEU CT Nr: 2023–509970-43–01, NCT06414031. Registered on 10 May 2024.

In focus: Engaging Black and African American women in oncology supportive care interventions.

54 Background: For individuals navigating cancer, unaddressed psychosocial needs can adversely impact quality of life, treatment adherence, and healthcare expenditures. It is recognized that African American cancer survivors are more likely to experience distress, yet they are underrepresented in studies that evaluate interventions. Mind Over Matter (MOM) is a five-week psychoeducational program aimed at bolstering emotional coping skills. A previous study among predominantly White female-identifying breast cancer survivors revealed improvements from pre to post-MOM for anxiety, depression, and physical symptom severity and interference; no data exists for women who identify as Black and/or African American. This presentation will illustrate the strategies and processes implemented to recruit, consent, and retain Black and African American cancer survivors to test the feasibility and acceptability of MOM. Methods: In forming the research team, the diversity in institutions, experience, racial and cultural identities, and professional perspectives were prioritized. As a result of this process, team members were social workers and psychologists, one was at an HBCU institution, and another was a patient advocate from the Black community who was hired and trained enabling full participation in the research process. To improve access all aspects of the study were available online and the intervention was offered virtually in the evening to support participants' availability. Efforts were made to build relationships with non-profit organizations, then disseminating the study through emails, healthcare systems, and social media. Results: During the 3-month recruitment period, 79 individuals expressed interest in the study via email and the study website. Of these, 40 participants (50.6%) enrolled in the study, surpassing the goal of 27. Half of the enrolled survivors learned about the study through community, medical, and academic organizations, while 20% and 10% were referred via the home health system and social media, respectively. 17.5% were referred from unspecified sources. Conclusions: Through robust team development, strategic community partnerships, using a study design that addressed common barriers (e.g., program hours and delivery method, tech orientation, incentives) and a high touch approach, this study successfully enrolled half of the Black and African American female-identified cancer survivors who expressed interest in this mixed-methods study. Clinical trial information: NCT06168825 .

National implementation trial of BeUpstanding™: an online initiative for workers to sit less and move more.

The online BeUpstanding™ program is an eight-week workplace-delivered intervention for desk-based workers to raise awareness of the benefits of sitting less and moving more and build a supportive culture for change. A workplace representative (the "champion") delivers the program, which includes a workshop where teams collectively choose their sit less/move more strategies. A toolkit provides the champion with a step-by-step guide and associated resources to support program uptake, delivery, and evaluation. Here we report on the main findings from the Australian national implementation trial of BeUpstanding. Recruitment (12/06/2019 to 30/09/2021) was supported by five policy and practice partners, with desk-based work teams from across Australia targeted. Effectiveness was measured via a single arm, repeated-measures trial. Data were collected via online surveys, toolkit analytics, and telephone calls with champions. The RE-AIM framework guided evaluation, with adoption/reach (number and characteristics); effectiveness (primary: self-reported workplace sitting time); implementation (completion of core components; costs); and, maintenance intentions reported here. Linear mixed models, correcting for cluster, were used for effectiveness, with reach, adoption, implementation, and maintenance outcomes described. Of the 1640 website users who signed-up to BeUpstanding during the recruitment period, 233 were eligible, 198 (85%) provided preliminary consent, and 118 (50.6%) champions consented and started the trial, with 94% (n = 111 champions) completing. Trial participation was from across Australia and across industries, and reached 2,761 staff, with 2,248 participating in the staff survey(s): 65% female; 64% university educated; 17% from a non-English speaking background. The program effectively changed workplace sitting (-38.5 [95%CI -46.0 to -28.7] minutes/8-hour workday) and all outcomes targeted by BeUpstanding (behaviours and culture), with small-to-moderate statistically-significant effects observed. All participating teams (n = 94) completed at least 5/7 core steps; 72.4% completed all seven. Most champions spent $0 (72%) or >$0-$5 (10%) per team member; most (67/70 96%) intended to continue or repeat the program. BeUpstanding can be adopted and successfully implemented by a range of workplaces, reach a diversity of staff, and be effective at creating a supportive culture for teams of desk-based workers to sit less and move more. Learnings will inform optimisation of the program for longer-term sustainability. ACTRN12617000682347.

Assessing willingness to pay for children's COVID-19 vaccination among healthcare providers and users using a theory-based discrete choice experiment

Improving vaccine coverage among children is crucial to prevent the long-term consequences of COVID-19 infections and the emergence of resistant COVID-19 variants, especially in resource-scarce settings. This study determined factors influencing the willingness to take and pay for COVID-19 vaccine for children among Vietnamese healthcare professionals and the public. A Theory-Based discrete-choice experiment was focused on a different topic related to vaccines, including the COVID-19 vaccine for children, Monkeypox, the adult COVID-19 booster, the HIV vaccine, and a potential future pandemic. The recruitment period was from April to August 2022, and a total of 5700 Vietnamese individuals aged 16 and above from various regions of the country participated in the study. The data for the sub-study on the COVID-19 vaccination for children was completed by 891 of these participants. Most participants agreed on vaccination for all children. Among healthcare professionals it was 76.2% and 69.3% for the general population. Healthcare professionals were the main source of vaccine information (70.7%). Payment options of 50%, 100%, and full subsidy were the most popular. Concerns about vaccine characteristics were associated with lower acceptance among healthcare professionals and the general public. The burden of historical medical expenses negatively correlated with willingness to pay for vaccination, while service satisfaction positively correlated with willingness to pay. To develop an effective vaccination program among children in Vietnam, providing accurate information and satisfying vaccine services, primarily through knowledgeable and professional healthcare providers, can improve the willingness to vaccinate and pay for the COVID-19 vaccine.

Effect of impaired kidney function on outcomes and treatment effects of oral anticoagulant regimes in patients with atrial fibrillation in a real-world registry.

The impact of impaired kidney function on outcomes and treatment benefits of vitamin-K antagonists (VKA) versus direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) has insufficiently been investigated in randomized controlled studies (RCTs). Most studies and registries are either biased due to incomplete enrolment of consecutive patients in large pharma industry sponsored registries, or due to short recruitment periods or incomplete assessment of important variables in national registries. This study uses data from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB), a retrospective single-center registry of 10,222 consecutive patients with AF presenting to the emergency department of University Hospital of Heidelberg from June 2009 until March 2020. Rates of all-cause mortality, stroke, major bleeding and myocardial infarction (MI) were related to the presence and severity of impaired presenting kidney function, as well as to assigned treatment with VKA vs. DOAC. The risks for all-cause mortality (HR: 3.26, p<0.001), stroke (HR: 1.58, p<0.001), major bleeding (HR: 2.28, p<0.001) and MI (HR: 2.48, p<0.001) were significantly higher in patients with an eGFR<60 ml/min at admission and increased with decreasing eGFR. After adjustment for variables of CHA2DS2VASc-score, presence of eGFR <60 ml/min remained as an independent predictor for all-cause mortality, major bleeding and MI. The hazard ratio (HR) for all-cause mortality, major bleedings and MI was significantly lower in patients receiving DOAC compared to VKA. Findings from our large real-life registry confirm the data from RCTs and extend our knowledge on the effectiveness and safety of DOACs to subjects that were underrepresented in RCTs.

Challenges in Conducting Exercise Recovery Studies in Older Adults and Considerations for Future Research: Findings from a Nutritional Intervention Study.

Maximising the potential benefit of resistance exercise (RE) programs by ensuring optimal recovery is an important aim of exercise prescription. Despite this, research surrounding recovery from RE in older adults is limited and inconsistent. The following randomised controlled trial was designed to investigate the efficacy of milk consumption for improving recovery from RE in older adults. However, the study encountered various challenges that may be applicable to similar studies. These include recruitment issues, a lack of measurable perturbations in muscle function following RE, and potential learning effects amongst participants. Various considerations for exercise research have arisen from the data which could inform the design of future studies in this area. These include (i) recruitment-consider ways in which the study design could be altered to aid recruitment or allow a longer recruitment period; (ii) learning effects and familiarisation-consider potential learning effects of outcome measures and adjust familiarisation accordingly; (iii) identify, validate and optimise protocols for outcome measures that are applicable for the specific population; (iv) adjust the exercise protocol according to the specific aims of the study (e.g., are you replicating a usual exercise bout or is the intent to cause large amounts of muscle damage?).

Integrated viral and immune monitoring in a prospective COVID-19 cohort from India.

In this study, we report on longitudinal kinetics of cellular immune subsets following SARS-CoV-2 infection in a cohort of hospitalized individuals and evaluate the interplay of these profiles with infecting viral variants, humoral immunity including neutralizing responses, vaccination history and clinical outcomes. A cohort of 121 SARS-CoV-2 infected individuals exhibiting varying disease states were prospectively evaluated for lymphopenic profiles, anti-viral humoral responses and infecting viral variants for a period of up to 90 days spanning the period, February 2021-January 2022 (2nd and 3rd waves of infection). A total of 51 participants received at least one vaccine dose of indigenous vaccines (Covishield or Covaxin) prior to recruitment. When stratified in terms of mortality, B and NK cells, in contrast to the T cell compartment, did not recover from nadir levels in non-survivors who were largely unvaccinated. No discriminatory signature was identified for non-survivors in terms of anti-NC or anti-S1-RBD IgG CLIA profiles including GenScript S1-RBD assays. Evaluation of sVCAM and sMAdCAM revealed opposing dynamics that correlated with disease severity and convalescence respectively. Viral variant analysis revealed delta and omicron variants to comprise majority of the infections which reflected national transmission kinetics during the period of recruitment. Our results demonstrate the importance of monitoring circulating biomarkers for convalescence as well as mortality in COVID-19 progression. Delta variants of SARS-CoV-2 clearly demonstrated increased pathogenicity and warrants sustained viral surveillance for re-emergence of these strains. Our findings with respect to vaccination advocate for continued vaccine development and administration of COVID-19 vaccines.

Early Intervention after Rape to prevent post-traumatic stress symptoms (the EIR-study): an internal pilot study of a randomized controlled trial

BackgroundRape is one of the trauma incidents with the highest risk of subsequent post-traumatic stress disorder. Early interventions, such as prolonged exposure therapy (PE), have shown promise in preventing PTSD following a sexual assault. The primary objective of this internal pilot trial was to examine the feasibility of the EIR study protocol, which used modified prolonged exposure therapy (mPE) as a preventive intervention after rape.MethodsThis parallel two-arm clinical pilot study involved three sexual assault centers (SACs) in Trondheim, Oslo, and Vestfold, with data collected between June 2022 and March 2023. Women seeking assistance at one of these three SACs within 72 h after rape or attempted rape received acute medical treatment and forensic examinations. Women who wanted further psychosocial treatment were, if eligible and consenting, recruited to complete baseline assessments and a clinical interview before being randomized to one of two study arms. The intervention group prescribed up to five sessions of modified PE (mPE) in addition to treatment as usual (TAU), starting within the first 14 days after the rape incident, followed by weekly sessions. The other group received TAU.The present pilot evaluation is based on 22 participants, i.e., nine mPE + TAU and 13 TAU alone. Primary outcomes were predefined progression criteria regarding recruitment, retention, intervention implementation, a harm reporting system, and applying biological measurements and actigraphy.ResultsDuring the 6-month recruitment period, 235 women visited the three SACs. After eligibility screening and consent, 22 (9.4%) women were randomized. Three months later, 14 (63.6%) participants completed the final assessments. Intervention implementation was successful using trained SAC personnel to deliver mPE. The harm reporting system was used according to the study’s plan, and adverse and serious adverse events were detected during the trial. The biological measurements and actigraphy had substantial missing data but were still considered usable for statistical analyses.ConclusionIt may be feasible to conduct a full-scale RCT of early intervention after rape by comparing mPE + TAU to TAU alone. Minor design refinements were made to the protocol to enhance the main study outcome.Trial registrationClinicalTrials.gov Identifier: NCT05489133. Registered on 15 July 2022, retrospectively.

PFAS Levels, Early Life Factors, and Mammographic Breast Density in Premenopausal Women.

Mammographic breast density (MBD) is a strong risk factor and an intermediate phenotype for breast cancer, yet there are limited studies on how environmental pollutants are associated with MBD. We investigated associations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) levels with measures of MBD and evaluated if early life factors modified any associations. Metabolon performed metabolomics analysis using ultrahigh-performance liquid chromatography/tandem accurate mass spectrometry in fasting blood from 705 premenopausal women completing their annual screening mammogram in St. Louis, Missouri. We calculated least square means (LSM) of mammographic volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV) by quartiles (Q) of PFOS, PFOA, and PFHxS from multivariable linear regression modeling overall and stratified by recruitment period, race, age at menarche, and body shape at age 10. Models were adjusted for age, age at menarche, body fat percentage, race, family history of breast cancer, oral contraceptive use, alcohol consumption, parity/age at first birth, and body shape at age 10. PFOS, PFOA, and PFHxS were not significantly associated with VPD or NDV. PFHxS was significantly positively associated with DV (, , , ; ). PFOS was positively associated with DV (, , , ; ) with DV being 8.1%, 12%, and 12.3% higher in Q2, Q3, and Q4 compared to Q1. Among women who were underweight/normal weight at age 10, PFOS was positively associated with VPD (, , , ; ) while there was an inverse association among women who were overweight/obese at age 10 (, , , ; ) (). We report novel associations of PFHxS and PFOS with DV in premenopausal women. PFOS, PFOA, and PFHxS were not associated with VPD and NDV. In addition, body shape at age 10 may modify the associations of PFOS with MBD. Further studies are needed to validate our findings and to evaluate the associations of other per- and polyfluoroalkyl substances (PFAS), as well as mixtures of PFAS, with MBD. https://doi.org/10.1289/EHP14065.

Abstract P225: Persistent Vascular Dysfunction and Blood Pressure Elevation Over 12 Months After COVID-19 Recovery in Non-Hypertensive Adults – LOCHINVAR Study

Background: The potential long-term vascular consequences of COVID-19, particularly in relation to future hypertension risk, remain poorly understood. This study aims to elucidate the longitudinal blood pressure trajectories in individuals who have recovered from COVID-19 but were not hypertensive prior to their infection, over a 12-month observational period. Methods: This study enrolled participants who had recovered from a hospital-admitted COVID-19 infection at least 12 weeks prior and had no history of hypertension. A control group was established from individuals with no prior SARS-CoV-2 infection, confirmed by a negative antibody test. All participants underwent ambulatory blood pressure monitoring (ABPM), flow-mediated dilation (FMD), and 6-minute walk test (6MWT) both at baseline and after 12 months. RAAS phenotyping was conducted at baseline. Paired t-tests and multivariable adjusted regression models were employed in the analyses of the full-dataset and per-protocol subset (because of variation in participant characteristics due to changing COVID-19 landscape during the recruitment period). Results: The full dataset had 97 participants (SARS-CoV-2 Negative:Positive 60:37) and per protocol data set had 66 participants (SARS-CoV-2 Negative:Positive 51:15). The median age was 50 (IQR:42-54) years with majority females. Per-protocol analysis revealed the positive group showed an increase in systolic and diastolic blood pressure (SBP/DBP) by 4.6/4.5 mmHg, a decrease in FMD by 3.2%, and an improvement in the 6MWT distance by 145.6 meters over 12 months, compared to the negative group (Figure 1). Baseline RAAS phenotyping showed no significant differences between groups. Conclusions: Our study demonstrates a significant increase in diastolic blood pressure 12 months following COVID-19 recovery in previously non-hypertensive individuals, accompanied by a decline in FMD. These findings suggest a possible vascular basis for the development of hypertension post-COVID-19 recovery.

Clinical trials involving rare gynaecological cancers

Clinical trials that investigate therapies for rare gynaecological cancers (RGC) are essential to provide evidence-based data towards new effective and safe treatments, however, they present unique challenges. The main objective of this narrative review is to summarize completed phase III clinical trials investigating therapies for RGC and to discuss the outcomes of these trials. PRISMA guidelines were used to report the steps of the review. We searched the WHO´s International Clinical Trials Registry Platform, clinicaltrials.gov and PubMed / Medline for publications reporting results from clinical trials on RGC including at least one medication. From 31 identified phase III clinical trials, 13 were still ongoing, four were terminated and just eight (25.8 %) had posted results and/or publications. The latter completed trials were mostly multi-center and located in at least two continents, participants were mainly adults, and the recruitment period varied from about 2.5 to 10.5 years. Allocation was randomized with parallel assignment in 7 out of 8 trials, while only one trial had double masking. The most common primary outcome measure was progression-free survival (PFS), followed by overall survival (OS). Patient-reported outcomes were secondary outcome measures in four completed trials, assessing quality of life by various questionnaires. Most of the trials did not meet their primary endpoints. By highlighting the scarcity of clinical trials on RGC, our findings further emphasize the need for designing, conducting and sustaining phase III clinical trials to investigate innovative therapies for these conditions and report meaningful outcome measures.

10-year outcome trajectories of people with mental illness and their families who receive services from multidisciplinary case management and outreach teams: protocol of a multisite longitudinal study

IntroductionIndividuals with mental illness and their families often undergo their recovery process in their communities. This study explored the long-term outcome trajectories of individuals and families who received case management...

Growth Restriction in the Offspring of Mothers With Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, characterized by subfertility, increased risk of metabolic diseases, and pregnancy complications. Previous studies diverge regarding the association between maternal PCOS and newborn anthropometrics. To explore the association between maternal PCOS and newborn anthropometrics and the modifying effects of maternal body mass index, PCOS phenotype, and gestational diabetes. This cohort study followed up women from the first half of pregnancy to birth and combined data from 3 clinical trials of pregnant women with PCOS and a reference population consisting of participants in the Norwegian Mother, Father, and Child Cohort (MoBa) Study, with data from the Medical Birth Registry of Norway. The recruitment period for the clinical trials was between October 1, 2000, and August 31, 2017, and for MoBa, between July 1, 1999, and December 31, 2008. Participants included women with singleton pregnancies and live-born children. Data were analyzed from January 1 to June 15, 2023. Maternal PCOS status. Newborn birth weight, birth length, and head circumference as continuous variables and z scores, and ponderal index (calculated as the birth weight in grams × 100 divided by the birth length in centimeters cubed), placenta weight, and ratio of birth weight to placenta weight (BWPW). The cohort included 390 pregnant women with PCOS (mean [SD] age, 29.6 [4.2] years) and 68 708 women in the reference group (mean [SD] age, 30.4 [4.5] years). Offspring in the PCOS group had lower birth weight, birth length, and head circumference than in the reference group offspring. The estimated mean differences in z scores were -0.26 (95% CI, -0.38 to -0.14) for birth weight, -0.19 (95% CI, -0.33 to -0.05) for birth length, and -0.13 (95% CI, -0.26 to -0.01) for head circumference. The PCOS group also had a lower ponderal index (-0.04 [95% CI, -0.07 to -0.004] g × 100/cm3) and placenta weight (-24 [95% CI, -43 to -5)] g), and higher BWPW ratio (0.4 [95% CI, 0.3 to 0.5]). The association between growth restriction and PCOS was more apparent when additionally adjusting for body mass index. Neither PCOS phenotype nor gestational diabetes diagnosis was associated with neonatal anthropometry in women with PCOS. In this cohort of mother-infant pairs, maternal PCOS status was associated with lower birth weight, shorter birth length, and smaller head circumference in the offspring. This growth restriction was more pronounced when adjusting for BMI, providing insight into the association between PCOS and body mass index. The study contributed to the understanding of how PCOS affects the offspring.

Colombian surgical outcomes study insights on perioperative mortality rate, a main indicator of the lancet commission on global surgery – a prospective cohort study

Surgical care holds significant importance in healthcare, especially in low and middle-income countries, as at least 50% of the 4.2 million deaths within the initial 30 days following surgery take place in these countries. The Lancet Commission on Global Surgery proposed six indicators to enhance surgical care. In Colombia, studies have been made using secondary data. However, strategies to reduce perioperative mortality have not been implemented. This study aims to describe the fourth indicator, perioperative mortality rate (POMR), with primary data in Colombia. A multicentre prospective cohort study was conducted across 54 centres (hospitals) in Colombia. Each centre selected a 7-day recruitment period between 05/2022 and 01/2023. Inclusion criteria involved patients over 18 years of age undergoing surgical procedures in operating rooms. Data quality was ensured through a verification guideline and statistical analysis using mixed-effects multilevel modelling with a case mix analysis of mortality by procedure-related, patient-related, and hospital-related conditions. 3807 patients were included with a median age of 48 (IQR 32-64), 80.3% were classified as ASA I or II, and 27% of the procedures had a low-surgical complexity. Leading procedures were Orthopedics (19.2%) and Gynaecology/Obstetrics (17.7%). According to the Clavien-Dindo scale, postoperative complications were distributed in major complications (11.7%, 10.68-12.76) and any complication (31.6%, 30.09-33.07). POMR stood at 1.9% (1.48-2.37), with elective and emergency surgery mortalities at 0.7% (0.40-1.23) and 3% (2.3-3.89) respectively. The POMR was higher than the ratio reported in previous national studies, even when patients had a low-risk profile and low-complexity procedures. The present research represents significant public health progress with valuable insights for national decision-makers to improve the quality of surgical care. This work was supported by Universidad del Rosario and Fundación Cardioinfantil-Instituto de Cardiología grant number CTO-057-2021, project-ID IV-FGV017.