Methodological Standards for the Design, Implementation, and Analysis of Randomized Trials in Cardiac Surgery: A Scientific Statement From the American Heart Association

Cardiac surgery presents specific methodological challenges in the design, implementation, and analysis of randomized controlled trials. The purposes of this scientific statement are to review key standards in cardiac surgery randomized trial design and implementation, and to provide recommendations for conducting and interpreting cardiac surgery trials. Recommendations include a careful evaluation of the suitability of the research question for a clinical trial, assessment of clinical equipoise, feasibility of enrolling a representative patient cohort, impact of practice variations on the safety and efficacy of the study intervention, likelihood and impact of crossover, and duration of follow-up. Trial interventions and study end points should be predefined, and appropriate strategies must be used to ensure adequate deliverability of the trial interventions. Every effort must be made to ensure a high completeness of follow-up; trial design and analytic techniques must be tailored to the specific research question and trial setting.

Effect of Foot Reflexology Protocol on Premenstrual Syndrome Symptoms in Nursing Students: a Pre–Post Pilot Study

Background: Premenstrual syndrome is a highly prevalent cyclical disorder among women of childbearing age which interferes with daily activities, mood, and quality of life. Purpose: To evaluate the effects of a foot reflexology protocol on relieving pre-menstrual syndrome symptoms in nurs-ing students. Setting: Nursing School, São Paulo Uni-versity, Brazil. Participants: A convenience sample of 17 nursing students, diagnosed with moderate-to-severe premenstrual syn-drome as assessed by the Premenstrual Symptoms Screening Tool (PSST). Research design: A pre–post pilot inter-vention study. Intervention: The intervention consist-ed of eight reflexology sessions lasting 30 minutes for eight weeks. Main Outcome Measure: Evaluation of the participants by the PSST applied at the beginning and at the end of the study. Results: The participants had an average age of 21.7 (±2.6) years, ranging from 19 to 28 years; all were single, and most were in the third year of the course (58.8%); 75.6% lived with their family; 82.4% do not use contraceptives; 64.7% reported regular menstrual flow with an average duration of 5.1 (±1.1) days, and an average menstrual cycle interval of 29.3 (±4.9) days. The intervention significantly reduced the premenstrual symptoms assessed by the PSST (p<.017) with a pre–post difference of 10.2 points in the overall score, and the items score decreased between 1.2 to 3.4 for difficulty concentrating, insomnia, hy-persomnia, feeling overwhelmed, muscle/joint pain, bloating, weight gain; and be-tween 3.5 to 5.2 to anger/irritability, anxiety/tension, tearful, depressed mood, de-creased interest in daily activities, fatigue, overeating, and breast tenderness. There was a significant decrease regarding the functional impact of premenstrual symp-toms domain in the overall score with a pre–post difference of 10.7, and between 1.7 and 3.0 for all of the items (p<.04), except for the item “your home responsibilities”. Conclusion: Foot reflexology has shown promising results in reducing premen-strual syndrome symptoms.

Expansion Points Intervention in Young Children with Speech Sound Disorders: A Multiple Baseline Design

The purpose of this investigation was to evaluate the efficacy of expansion points (EXP) intervention with a modified criterion for preschool children with speech sound disorders (SSD). Three preschool-aged children were enrolled in a single-subject multiple baseline intervention study. Intervention took place over 16 sessions. Pre- and post-intervention data are provided. Three outcome measures (generalization to probe words and gains in percent consonants correct, PCC, in words and in conversation) were evaluated to measure the effectiveness of the EXP intervention. All three of the participants demonstrated gains by the end of the intervention phase when measuring PCC in single words. Two of the three participants demonstrated gains in PCC in conversational speech. Progress on individual phonemes was variable across participants. Utilizing the EXP approach, two of the three children showed gains in all three outcome measures. One child showed variable performance in one outcome measure, improvement in one, and a decrease in one. Findings suggest that EXP should be further explored to evaluate intervention efficacy.

Smoking and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study

Objective. To investigate the association between smoking-related traits and subfertility. Design. Prospective study. Setting. Nationwide cohort in Norway. Patients. 28,606 women (average age 30) and 27,096 men (average age 33) with questionnaire and genotype information from the Norwegian Mother, Father and Child Cohort Study. Intervention. Self-reported information on smoking (having ever smoked [both sexes], age at smoking initiation [women only], smoking cessation [women only], and cigarettes smoked per week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting the mentioned traits were estimated for Mendelian randomization (MR) analyses. Main outcome measure. Subfertility, defined as time-to-pregnancy >=12 months. Results. A total of 10% of couples were subfertile. In multivariable regression accounting for age, years of education, body mass index, and number of previous pregnancies, having ever smoked was not linked to subfertility in women or men. A higher intensity of tobacco use in women who were current smokers was related to greater odds of subfertility (+ 1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR] 1.12, 95% confidence interval [CI] 1.03 to 1.21), also after adjusting for the partner's tobacco use. Later smoking initiation (+ 1 SD [3.2 years]: OR 0.89, 95% CI 0.84 to 0.95) and smoking cessation (relative to not quitting: OR 0.83, 95% CI 0.75 to 0.93) were linked to decreased subfertility in women who had ever smoked. Nevertheless, MR results were not directionally consistent for smoking intensity and cessation and were imprecisely estimated in two-sample MR, with wide confidence intervals that overlapped with the multivariable regression results. In men, greater smoking intensity was marginally linked to greater odds of subfertility in multivariable analyses, but this association was attenuated when adjusting for the partner's smoking intensity (+ 1 SD [54 cigarettes/week]: OR 1.05, 95% CI 0.96 to 1.15). MR estimates were directionally consistent but again imprecisely estimated. Conclusions. We did not find robust evidence of an effect of smoking on subfertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding. The relevant limitations across all methods highlights the need for larger studies with information on subfertility.

Does improved interpreter uptake reduce self-discharge rates in hospitalised patients? A successful hospital intervention explained

Background Aboriginal language interpreters are under-utilised in healthcare in northern Australia. Self-discharge from hospital is an adverse outcome occurring at high rates among Aboriginal people, with poor communication thought to be a contributor. We previously reported increased Aboriginal interpreter uptake and decreased rates of self-discharge during implementation of a 12-month hospital-based intervention. Interrupted time-series analysis showed sudden increase and up-trending improvement in interpreter use, and a corresponding decrease in self-discharge rates, during a 12-month intervention period (April 2018—March 2019) compared with a 24-month baseline period (April 2016 –March 2018). This paper aims to investigate reasons for these outcomes and explore a potential causal association between study activities and outcomes. Methods The study was implemented at the tertiary referral hospital in northern Australia. We used the Template for Intervention Description and Replication (TIDieR) as a framework to describe intervention components according to what, how, where, when, how much, tailoring, modifications and reach. Components of the study intervention were: employment of an Aboriginal Interpreter Coordinator, ‘Working with Interpreters’ training for healthcare providers, and championing of interpreter use by doctors. We evaluated the relative importance of intervention components according to TIDieR descriptors in relation to outcomes. Activities independent of the study that may have affected study findings were reviewed. The relationship between proportion of hospital separations among Aboriginal people ending in self-discharge and numbers of Aboriginal interpreter bookings made during April 2016-March 2019 was tested using linear regression. ‘Working with Interpreters’ training sessions were undertaken at a regional hospital as well as the tertiary hospital. Training evaluation comprised an anonymous online survey before the training, immediately after and then at six to eight months. Survey data from the sites were pooled for analysis. Results Employment of the Aboriginal Interpreter Coordinator was deemed the most important component of the intervention, based on reach compared to the other components, and timing of the changes in outcomes in relation to the employment period of the coordinator. There was an inverse association between interpreter bookings and self-discharge rate among Aboriginal inpatients throughout the baseline and intervention period (p = 0.02). This association, the timing of changes and assessment of intercurrent activities at the hospital indicated that the study intervention was likely to be casually related to the measured outcomes. Conclusions Communication in healthcare can be improved through targeted strategies, with associated improvements in patient outcomes. Health services with high interpreter needs would benefit from employing an interpreter coordinator.

Gut Microbiome Signatures Linked to HIV-1 Reservoir Size and Viremia Control

BackgroundThe potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial.ResultsViremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways, including methanogenesis and carbohydrate biosynthesis, were significantly decreased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size.ConclusionsThis proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption.

A Brief, Mobile Intervention to Decrease Depression and Loneliness and Improve Relationship Quality During the Covid-19 Pandemic

Introduction: Effective, scalable interventions to address depression and loneliness and improve the quality of social relationships are needed for public health in pandemic and non-pandemic contexts. Towards this end, a randomized, controlled trial tested a mobile-based intervention, derived from social psychological and relationship science, for improving relational well-being and decreasing depression and loneliness. Methods: Participants were randomly assigned to either intervention (n = 719) or assessment only (n = 701) conditions and completed daily diary surveys for 28 days in the midst of the first wave of the Covid-19 pandemic. In the middle 14 days of the study, intervention participants received daily text-message suggestions for improving relational and mental well-being. Results: Results indicated that the intervention decreased depression and loneliness and improved relationships during the intervention period but these changes were not sustained when the intervention ceased. Discussion: Results are encouraging in that evidence-based suggestions can be scaled effectively but additional efforts are required to sustain improvements over time.

Nutrition integrated agricultural extension—a case study in Western Kenya

Summary Integrating nutrition communication in agricultural intervention programs aimed at increased food availability and accessibility in resource-poor areas is crucial. To enhance the sustainability and scalability of nutrition communication, the present study piloted the approach of ‘nutrition integrated agricultural extension’ and tested nutrition-related outcomes with two types of nutrition messages (specific vs. sensitive) and two delivery channels (public sector vs. private sector). The study intervention comprised (i) vegetable seed kit distribution, (ii) ongoing agricultural extension activities by public or private sectors and (iii) nutrition communication with two different messages. The intervention was tested with three treatment arms and reached 454 farmers (&gt;65% female) in rural Kakamega County, Western Kenya. Pre-/post-surveys measured outcome variables focused on farmers’ nutrition-related knowledge, attitudes and practices in vegetable production and consumption, and household dietary diversity score. Results showed that all treatments increased nutrition knowledge (p &lt; 0.05). Nutrition-specific communication was more effective than nutrition-sensitive communication. Nutrition communication through either the public or the private agricultural sector was both effective. Before the study intervention, many participants believed that vegetable consumption was beneficial and wanted to increase intake. After the intervention, the number of participants who felt eating more vegetables was challenging decreased slightly. Nutrition communication was found to be especially important in conveying recommended food amounts and promoting increased vegetable consumption. Seasonality affected on-farm crop diversity and vegetable consumption results in this study.

Design and Implementation of a Real-time Monitoring Platform for Optimal Sepsis Care in an Emergency Department: Observational Cohort Study

Background Sepsis is the leading cause of death in US hospitals. Compliance with bundled care, specifically serial lactates, blood cultures, and antibiotics, improves outcomes but is often delayed or missed altogether in a busy practice environment. Objective This study aims to design, implement, and validate a novel monitoring and alerting platform that provides real-time feedback to frontline emergency department (ED) providers regarding adherence to bundled care. Methods This single-center, prospective, observational study was conducted in three phases: the design and technical development phase to build an initial version of the platform; the pilot phase to test and refine the platform in the clinical setting; and the postpilot rollout phase to fully implement the study intervention. Results During the design and technical development, study team members and stakeholders identified the criteria for patient inclusion, selected bundle measures from the Center for Medicare and Medicaid Sepsis Core Measure for alerting, and defined alert thresholds, message content, delivery mechanisms, and recipients. Additional refinements were made based on 70 provider survey results during the pilot phase, including removing alerts for vasopressor initiation and modifying text in the pages to facilitate patient identification. During the 48 days of the postpilot rollout phase, 15,770 ED encounters were tracked and 711 patient encounters were included in the active monitoring cohort. In total, 634 pages were sent at a rate of 0.98 per attending physician shift. Overall, 38.3% (272/711) patients had at least one page. The missing bundle elements that triggered alerts included: antibiotics 41.6% (136/327), repeat lactate 32.4% (106/327), blood cultures 20.8% (68/327), and initial lactate 5.2% (17/327). Of the missing Sepsis Core Measures elements for which a page was sent, 38.2% (125/327) were successfully completed on time. Conclusions A real-time sepsis care monitoring and alerting platform was created for the ED environment. The high proportion of patients with at least one alert suggested the significant potential for such a platform to improve care, whereas the overall number of alerts per clinician suggested a low risk of alarm fatigue. The study intervention warrants a more rigorous evaluation to ensure that the added alerts lead to better outcomes for patients with sepsis.