Factorial Trial Research Articles

A mixed methods process evaluation: understanding the implementation and delivery of HIV prevention services integrated within sexual reproductive health (SRH) with or without peer support amongst adolescents and young adults in rural KwaZulu-Natal, South Africa

BackgroundCombination prevention interventions, when integrated with community-based support, have been shown to be particularly beneficial to adolescent and young peoples’ sexual and reproductive health. Between 2020 and 2022, the Africa Health Research Institute in rural South Africa conducted a 2 × 2 randomised factorial trial among young people aged 16–29 years old (Isisekelo Sempilo) to evaluate whether integrated HIV and sexual and reproductive health (HIV/SRH) with or without peer support will optimise delivery of HIV prevention and care. Using mixed methods, we conducted a process evaluation to provide insights to and describe the implementation of a community-based peer-led HIV care and prevention intervention targeting adolescents and young people.MethodsThe process evaluation was conducted in accordance with the Medical Research Council guidelines using quantitative and qualitative approaches. Self-completed surveys and clinic and programmatic data were used to quantify the uptake of each component of the intervention and to understand intervention fidelity and reach. In-depth individual interviews were used to understand intervention experiences. Baseline sociodemographic factors were summarised for each trial arm, and proportions of participants who accepted and actively engaged in various components of the intervention as well as those who successfully linked to care were calculated. Qualitative data were thematically analysed.ResultsThe intervention was feasible and acceptable to young people and intervention implementing teams. In particular, the STI testing and SRH components of the intervention were popular. The main challenges with the peer support implementation were due to fidelity, mainly because of the COVID-19 pandemic. The study found that it was important to incorporate familial support into interventions for young people’s sexual health. Moreover, it was found that psychological and social support was an essential component to combination HIV prevention packages for young people.ConclusionThe results demonstrated that peer-led community-based care that integrates SRH services with HIV is a versatile model to decentralise health and social care. The family could be a platform to target restrictive gender and sexual norms, by challenging not only attitudes and behaviours related to gender among young people but also the gendered structures that surround them.

Individual Placement and Support and Participatory Workplace Intervention on the Work Participation of People with Disabilities: A Randomised Controlled Trial.

This study assessed the effectiveness of Individual Placement and Support (IPS), Participatory Workplace Intervention (PWI), and IPS + PWI on work participation and health of people with work disabilities. A randomised controlled 2 × 2 factorial trial with 120 clients and an 18-month follow-up was performed. Differences between IPS and no-IPS and between PWI and no-PWI were assessed using log-rank tests and Cox proportional hazards models. In the IPS group, restricted mean survival time (RMST) for sustainable paid employment was 352days, compared to 394 in the no-IPS group (HR = 1.47, 95% CI = 0.81-2.63). In the PWI group the RMST was 378days, compared to 367 in the no-PWI group (HR = 0.89, 95% CI = 0.48-1.64). For the secondary outcome 'starting any paid employment, a trial placement, or education' RMST was significantly lower for the IPS group (222days) than for the no-IPS group (335days; HR = 1.85, 95% CI = 1.01-3.42). Mental health was significantly lower (worse) in the PWI group (difference -4.07, 95% CI = -7.93 to -0.22) than in the no-PWI group. For all other secondary outcomes, no statistically significant differences were found. No statistically significant differences were observed in the duration until starting sustainable employment between IPS and no-IPS, and between PWI and no-PWI. The duration until starting any paid employment, a trial placement, or education was shorter in the IPS group than in the no-IPS group, but further research should explore whether this also increases sustainable employment in the longer term.

Improving medication adherence among persons with cardiovascular disease through m-health and community health worker-led interventions in Kerala; protocol for a type II effectiveness-implementation research-(SHRADDHA-ENDIRA)

BackgroundCardiovascular disease (CVD) is the leading cause of mortality worldwide, and at present, India has the highest burden of acute coronary syndrome and ST-elevation myocardial infarction (MI). A key reason for poor outcomes is non-adherence to medication.MethodsThe intervention is a 2 × 2 factorial design trial applying two interventions individually and in combination with 1:1 allocation ratio: (i) ASHA-led medication adherence initiative comprising of home visits and (ii) m-health intervention using reminders and self-reporting of medication use. This design will lead to four potential experimental conditions: (i) ASHA-led intervention, (ii) m-health intervention, (iii) ASHA and m-health intervention combination, (iv) standard of care. The cluster randomized trial has been chosen as it randomizes communities instead of individuals, avoiding contamination between participants. Subcenters are a natural subset of the health system, and they will be considered as the cluster/unit. The factorial cluster randomized controlled trial (cRCT) will also incorporate a nested health economic evaluation to assess the cost-effectiveness and return on investment (ROI) of the interventions on medication adherence among patients with CVDs. The sample size has been calculated to be 393 individuals per arm with 4–5 subcenters in each arm. A process evaluation to understand the effect of the intervention in terms of acceptability, adoption (uptake), appropriateness, costs, feasibility, fidelity, penetration (integration of a practice within a specific setting), and sustainability will be done.DiscussionThe effect of different types of intervention alone and in combination will be assessed using a cluster randomized design involving 18 subcenter areas. The trial will explore local knowledge and perceptions and empower people by shifting the onus onto themselves for their medication adherence. The proposal is aligned to the WHO-NCD aims of improving the availability of the affordable basic technologies and essential medicines, training the health workforce and strengthening the capacity of at the primary care level, to address the control of NCDs. The proposal also helps expand the use of digital technologies to increase health service access and efficacy for NCD treatment and may help reduce cost of treatment.Trial registrationThe trial has been registered with the Clinical Trial Registry of India (CTRI), reference number CTRI/2023/10/059095.

Zinc phytotoxicity and cationic micronutrients contents in quinoa as influenced by high Zn levels and soil amendments

Contamination of soils with heavy metals (HMs) is a serious concern due to the non-biodegradability and accumulation of these metals in living organism. The aim of this study was to evaluate the effectiveness of fish scale powder, chitin, and chitosan in reducing zinc (Zn) accumulation of quinoa grown on Zn-polluted soil. A 3*4 factorial greenhouse trial was conducted with three levels of Zn contamination (0, 100, and 200 mg kg−1) and four types of amendment (control, and 0.15% of each fish scale powder, chitin, and chitosan). The quinoa seeds were sown in soil treated with Zn contamination and amendments. Results showed that application of amendments especially chitosan increased shoot and root dry weight and greenness index of quinoa leaf. While high soil Zn levels decreased cationic micronutrients uptake in quinoa shoot, chitosan addition desirably enhanced cationic micronutrients uptake in quinoa shoot. Overall, amendment addition significantly decreased Zn concentration and uptake in plant; the highest decrease was observed following the application of chitosan. Although the application of high Zn levels significantly increased the values of phytoextraction efficiency, application of chitin and chitosan significantly decreased it. The value of translocation factor was lower than one, demonstrating that a large amount of Zn was stabilized in the root tissues, while a small amount of this metal was transferred to aboveground parts of quinoa. Results of this study revealed that fish scales derivatives were effective in preventing Zn toxicity and at the same time increasing cationic micronutrients contents of quinoa grown on HMs-polluted soil.

Effectiveness of integrating HIV prevention within sexual reproductive health services with or without peer support among adolescents and young adults in rural KwaZulu-Natal, South Africa (Isisekelo Sempilo): 2 × 2 factorial, open-label, randomised controlled trial

Approximately 200 000 South Africans acquired HIV in 2021 despite the availability of universal HIV test and treat and pre-exposure prophylaxis (PrEP). The aim of this study was to test the effectiveness of sexual and reproductive health services or peer support, or both, on the uptake of serostatus neutral HIV services or reduction of sexually transmissible HIV. We did an open-label, 2 × 2 randomised factorial trial among young people in a mostly rural area of KwaZulu-Natal, South Africa. Inclusion criteria included being aged 16-29 years, living in the mapped geographical areas that were accessible to the area-based peer navigators, being willing and able to provide informed consent, and being willing to provide a dried blood spot for anonymous HIV testing and HIV viral load measurement at 12 months. Participants were randomly allocated by computer-generated algorithm to one of four groups: those in the standard-of-care group were referred to youth-friendly services for differentiated HIV prevention (condoms, universal HIV test and treat with antiretroviral therapy, and PrEP if eligible); those in the sexual and reproductive health services group received baseline self-collected specimens for sexually transmitted infection (STI) testing and referral to integrated sexual and reproductive health and HIV prevention services; those in the peer support group were referred to peer navigators for health promotion, condom provision, and facilitation of attendance for differentiated HIV prevention services; and those in the final group received a combination of sexual and reproductive health services and peer support. Coprimary outcomes were linkage to clinical services within 60 days of enrolment, proportion of participants who had sexually transmissible HIV at 12 months after enrolment, and proportion of sampled individuals who consented to participation and gave a dried blood spot for HIV testing at 12 months. Logistic regression was used for analyses, and adjusted for age, sex, and rural or peri-urban area of residence. This study is registered with ClinicalTrials.gov (NCT04532307) and is closed. Between March 2, 2020, and July 7, 2022, 1743 (75·7%) of 2301 eligible individuals were enrolled and followed up. 12-month dried blood spots were collected from 1168 participants (67·0%). The median age of the participants was 21 years (IQR 18-25), 51·4% were female, and 51·1% had secondary level education. Baseline characteristics and 12-month outcome ascertainment were similar between groups. 755 (43·3%) linked to services by 60 days. 430 (49·8%) of 863 who were in the sexual reproductive health services group were linked to care compared with 325 (36·9%) of 880 who were not in the sexual and reproductive health services group (adjusted odds ratio [aOR] 1·68; 95% CI 1·39-2·04); peer support had no effect: 385 (43·5%) of 858 compared with 370 (43·1%) of 885 (1·02, 0·84-1·23). At 12 months, 227 (19%) tested ELISA-positive for HIV, of whom 41 (18%) had viral loads of 400 copies per mL; overall prevalence of transmissible HIV was 3·5%. 22 (3·7%) of 578 participants in the sexual and reproductive health services group had transmissible HIV compared with 19 (3·3%) of 590 not in the sexual and reproductive health services group (aOR 1·12; 95% CI 0·60-2·11). The findings were also non-significant for peer support: 21 (3·3%) of 565 compared with 20 (3·3%) of 603 (aOR 1·03; 95% CI 0·55-1·94). There were no serious adverse events or deaths during the study. This study provides evidence that STI testing and sexual and reproductive health services create demand for serostatus neutral HIV prevention in adolescents and young adults in Africa. STI testing and integration of HIV and sexual health has the potential to reach those at risk and tackle unmet sexual health needs. US National Institute of Health, Bill & Melinda Gates Foundation, and 3ie.

Effects of Price Subsidy and Health Education on Sales of Reduced-Sodium Potassium-Enriched Salt: A Cluster Factorial Trial

Effects of Price Subsidy and Health Education on Sales of Reduced-Sodium Potassium-Enriched Salt: A Cluster Factorial Trial

Anaerobic Treatment of N-(Phosphonometyl) Glycine Using Mixed Culture in Batch Reactor

Pesticides have been used in the fight against various pests to increase crop growth in our country and the world. In recent years, high concentrations of toxic and detection of carcinogenic pesticides indicates that these substances are transported to groundwater and pollute water resources. N- (phosphonomethyl) glycine are also used in large quantities. In this study, the optimization of anaerobic treatment of N- (phosphonomethyl) glycine was investigated by applying a statistical-based experimental design. Full factorial trials different initial pesticide concentrations and cosubstrate type were established, making up 9 different experimental setups. Trials were performed in 2 replicates. The experiments were carried out in Oxitop C bottles with stirring at a working volume of 200 mL. The pH was adjusted to 7 ± 0.2. Trials were performed at 35oC for 30 days. At the end of the process, the removal of the trials according to the input and output COD and pesticide values were examined. As a result, the most efficient COD removal was achieved 98,96 % when pesticide concentration of 5 mg L-1 and glucose as cosubstrate were used. The highest pesticide removal was found to be 74,83% when pesticide concentration of 25 mg L-1 and glucose was used as cosubstrate.

Virtual parental presence with coaching for reducing preoperative anxiety in children: a feasibility and pilot randomized controlled trial

BackgroundPreoperative anxiety in children causes negative postoperative outcomes. Parental presence at induction is a non-pharmacological strategy for relieving anxiety; nevertheless, it is not always possible or effective, namely when parents are overly anxious. Parental presence via video has been demonstrated to be useful in other contexts (divorce, criminal court). This study reports the feasibility of a randomized controlled trial to investigate the effect of video parental presence and parental coaching at induction on preoperative anxiety. MethodsThe study was a randomized, 2 × 2 factorial design trial examining parental presence (virtual vs. physical) and coaching (provided vs. not provided). Feasibility was assessed by enrollment rate, attrition rate, compliance, and staff satisfaction with virtual method with the NASA-Task Load Index (NASA-TLX) and System Usability Scale (SUS). For the children's anxiety and postoperative outcomes, the modified Yale Preoperative Anxiety Scale (mYPAS) and Post-Hospitalization Behavioral Questionnaire (PHBQ) were used. Parental anxiety was evaluated with the State-Trait Anxiety Inventory (STAI) questionnaire. ResultsA total of 41 parent/patient dyads were recruited. The enrollment rate was 32.2%, the attrition rate 25.5%. Compliance was 87.8% for parents and 85% for staff. The SUS was 67.5/100 and 63.5/100 and NASA-TLX was 29.2 (21.5–36.8) and 27.6 (8.2–3.7) for the anesthesiologists and induction nurses, respectively. No statistically significant difference was found in mYPAS, PHBQ and STAI. ConclusionA randomized controlled trial to explore virtual parental presence effect on preoperative anxiety is feasible. Further studies are needed to investigate its role and the role of parent coaching in reducing preoperative anxiety.

Study Protocol for Pain Self-Management and Patient-Oriented Buprenorphine Dosing for Pain and Retention in Office-Based Opioid Treatment: A Hybrid Type 1, 2 × 2 Factorial Randomized Controlled Trial.

Chronic pain is a significant factor for patients with opioid use disorder (OUD) contributing to suboptimal retention in buprenorphine treatment, which is a crucial predictor of long-term health outcomes. This study aims to address the critical need for effective interventions targeting chronic pain management within office-based opioid treatment (OBOT) programs. We are conducting a multisite, hybrid type 1, 2 × 2 factorial randomized clinical trial to determine the effectiveness of 2 novel interventions, pain self-management (PSM) and patient-oriented buprenorphine dosing (POD), to decrease pain interference and improve retention in buprenorphine treatment. PSM, a manualized and customizable approach delivered through individual and peer-led group sessions, aims to decrease pain-related symptoms and quality of life. POD involves split dosing of buprenorphine to extend the duration of analgesia to better match its duration of efficacy at managing OUD symptoms, leading to improved retention in buprenorphine treatment. Eligible participants will be randomized into 1 of 4 groups: (1) PSM + POD, (2) PSM + Standard Buprenorphine Dosing, (3) Usual Care + POD, or (4) Usual Care + Standard Buprenorphine Dosing. Usual Care refers to usual care for chronic pain and Standard Buprenorphine Dosing refers to the participant's current dosing regimen. Secondary objectives encompass overall pain reduction, decreased opioid use, improved pain symptom management, and exploration of implementation strategies. The supplemental approved protocol provides comprehensive insights into the procedures and variables being investigated. As part of the HEAL Initiative®-funded Integrative Management of Chronic Pain and OUD for Whole Recovery (IMPOWR) network, this study aims to fill gaps in behavioral and medication treatments for individuals with co-occurring chronic pain and OUDs, improving pain management and retention in care. Successful outcomes from this trial may inform future larger trials, offering essential evidence for implementation considerations and reimbursement decisions.

Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial.

Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. This hypothesis-generating analysis used biospecimens collected from a multi-centre 2×2 factorial randomized design of 116 patients with stage I-III breast and colorectal cancer who were randomized to 12weeks of (1) aerobic exercise (moderate intensity titrated to 220min/week); (2) metformin (850mg daily for 2weeks and then titrated to 850mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log-transformed, and main effects analyses were conducted using linear mixed-effects regression models. The type I error rate was controlled with the Holm sequential testing procedure. Randomization to exercise increased leukaemia inhibitory factor (1.26pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P=0.001) and interleukin-15 (2.23pg/mL, 95% CI: 0.87, 3.60; adjusted P=0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (-2.69pg/mL, 95% CI: -4.31, -1.07; adjusted P=0.014) and interleukin-15 (-1.74pg/mL, 95% CI: -2.79, -0.69; adjusted P=0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons. This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis-generating observation warrants further basic, translational and clinical investigation and replication.

(054) OPTIMIZING INTERNET-BASED PSYCHOSOCIAL INTERVENTION FOR BREAST CANCER-RELATED SEXUAL MORBIDITY: PROTOCOL FOR A FACTORIAL TRIAL

Abstract Introduction Although 3 in 4 breast cancer survivors report significant sexual concerns following treatment, few receive support for these concerns. Delivering sexual health care to breast cancer survivors via the Internet could overcome many of the barriers to in-person interactions, including limited availability of resources and stigma. Prior research on telehealth interventions for breast cancer survivors’ sexual health has limitations. First, survivors continue to endorse time burden as a leading reason for declining telehealth sexual health interventions. Second, prior trial designs have not been able to determine which intervention components work best for which survivors. This knowledge is crucial to refine and personalize sexual health care for survivors. Objective Use the Multiphase Optimization Strategy (MOST) methodological framework to achieve the following aims: (1) develop an Internet intervention for breast cancer-related sexual health that is optimized for greatest impact; and (2) determine how intervention components work (i.e., mediators) and for whom they work best (i.e., moderators). Methods 320 partnered, post-treatment female breast cancer survivors who endorse at least one bothersome sexual symptom (i.e., pain with sex, vaginal dryness, low sexual desire, difficulty with orgasm) related to their breast cancer treatment will be enrolled. Recruitment will be conducted via a US-national community oncology research program representing more than 1,000 individual practice locations. In this factorial trial, participants will be randomized to receive a combination of 4 intervention components: psychoeducation about cancer-related sexual morbidity, training for communication with their health care team, training for communication with their partners, and intimacy promotion skills training. These components were selected as they are supported by our intervention research, are consistent with survivorship guidelines, and align with survivors’ preferences found in our qualitative research. Components will be implemented using a robust Internet intervention platform with tailoring and highly-engaging elements like animation, video, and automated email prompts. Survivors will complete assessments at baseline (pre-randomization) and 3- and 6-month post-assessments. First, the impact of intervention components on survivors’ sexual distress (Female Sexual Distress Scale-Desire, Arousal, Orgasm) and sexual functioning (Female Sexual Function Inventory) will be tested. Next, a select set of mediators (i.e., sexual functioning knowledge, sexual communication self-efficacy with clinicians and partner, emotional intimacy with partner) and moderators (i.e., menopausal status, adjuvant endocrine therapy use, psychological distress, relationship duration and satisfaction) will be evaluated. Results Institutional review board approvals are in progress, with clinical trial registration to follow. Data collection is anticipated to begin in Spring 2024 and be completed in 2027. Conclusions Findings from this trial will accelerate the development of more effective sexual health interventions for breast cancer survivors by determining how intervention components work and for whom various components work best. By identifying the combination of intervention components likely to provide breast cancer survivors the greatest sexual health benefit for the least burden, this study will result in the first Internet intervention optimized for maximum impact for the undertreated, prevalent, and distressing problem of breast cancer-related sexual morbidity. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: AHC: grants from Janssen, Relmada Therapeutics, Inc., and Sage Therapeutics; personal fees from Acadia, Alkermes, Allergan, AMAG Pharmaceuticals, Inc., Fabre-Kramer, Ovoca Bio plc, Pure Tech Health, Sage Therapeutics, Takeda/Lundbeck, WCG MedAvante-ProPhase, Ballantine Books/Random House, Changes in Sexual Functioning Questionnaire, Guilford Publications; personal fees and other from S1 Biopharma; and other from Euthymics and Mediflix LLC. GL: consultant or research affiliation with Agios Pharmaceuticals, Inc; Denovo Biopharma; IN8bio; Incyte Corporation; Novocure Inc.; oblato; ONO Pharma; Sumitomo Dainippon Pharma Co., Ltd. LR: financial and/or business interest in BeHealth Solutions and is a consultant to Mahana Therapeutics.

Spermidine mitigates salt stress in grapevine with alterations in physicochemical properties and nutrient composition

AbstractBackgroundPolyamines are plant growth regulators that exert a pivotal role in salt tolerance.AimsThis research focused on investigating the effect of spermidine on morphological and physicochemical characteristics and ion accumulation of two grapevine cultivars under NaCl stress.MethodsA greenhouse experiment was conducted with three factors, including two grapevine cultivars (Vitis vinifera L. cv. Bidaneh‐Sefid and cv. Siah‐Sardasht), four levels of NaCl (together with the nutrient solution, including 0 [control], 20, 40, and 80 mM), and four spermidine levels ([foliar spray], 0 [control], 0.25, 0.5, and 1 mM). The experiment was performed in a factorial trial in accordance with a randomized complete design with three replicates.ResultsVegetative growth indices, including leaf number, fresh and dry weight of shoot, and root, were decreased by NaCl treatments. The application of spermidine positively reduced the effects of NaCl on morphological characteristics. Moreover, NaCl and/or spermidine significantly (p ≤ 0.05) improved antioxidant enzyme activities associated with rising total protein accumulation. NaCl stress significantly decreased ion percentage (calcium, magnesium, phosphate, potassium, iron, and zinc) in the leaves of both cultivars. Based on the results, increasing salinity levels significantly boosted plant Na+ and Cl− percentage, along with increased membrane permeability and malondialdehyde (MDA) concentration. Interestingly, cv. Bidaneh‐Sefid leaves accumulated less Na+ and Cl− compared to the other cultivar. On the other hand, applying spermidine reduced the levels of Na+ and Cl− in both cultivars, and this reduction was associated with a decrease in membrane permeability and MDA concentration.ConclusionsThe findings confirmed the role of spermidine in reducing the negative effects of NaCl, although more investigations with different grapevine cultivars under NaCl stress are required.

Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n–3 fatty acid eicosapentaenoic acid: a secondary analysis of the seAFOod polyp prevention trial

BackgroundA fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences the expression of FADS1, which controls the synthesis of n–6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n–3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for proinflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n–3 HUFAs. ObjectivesWe tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2×2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 mo (ISRCTN05926847). MethodsParticipant Indel genotype was determined by polymerase chain reaction (PCR) blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention with its placebo. Presence of ≥1 Indel I allele and an interaction term (I allele × active intervention) were covariates. ResultsIn 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR]: 0.92; 95% confidence interval: 0.74, 1.16), mirroring original seAFOod trial analysis. However, the presence of ≥1 I allele identified EPA users with a significant reduction in colorectal polyp number (IRR: 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR. ConclusionsThe FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n–3 HUFAs in other populations and healthcare settings is warranted.The seAFOod polyp prevention trial and STOP-ADENOMA study were registered at International Standard Randomised Controlled Trial Number registry as ISRCTN05926847.

Engagement in mHealth-Prompted Self-Measured Blood Pressure Monitoring Among Participants Recruited From a Safety-Net Emergency Department: Secondary Analysis of the Reach Out Trial.

Hypertension, a key modifiable risk factor for cardiovascular disease, is more prevalent among Black and low-income individuals. To address this health disparity, leveraging safety-net emergency departments for scalable mobile health (mHealth) interventions, specifically using text messaging for self-measured blood pressure (SMBP) monitoring, presents a promising strategy. This study investigates patterns of engagement, associated factors, and the impact of engagement on lowering blood pressure (BP) in an underserved population. We aimed to identify patterns of engagement with prompted SMBP monitoring with feedback, factors associated with engagement, and the association of engagement with lowered BP. This is a secondary analysis of data from Reach Out, an mHealth, factorial trial among 488 hypertensive patients recruited from a safety-net emergency department in Flint, Michigan. Reach Out participants were randomized to weekly or daily text message prompts to measure their BP and text in their responses. Engagement was defined as a BP response to the prompt. The k-means clustering algorithm and visualization were used to determine the pattern of SMBP engagement by SMBP prompt frequency-weekly or daily. BP was remotely measured at 12 months. For each prompt frequency group, logistic regression models were used to assess the univariate association of demographics, access to care, and comorbidities with high engagement. We then used linear mixed-effects models to explore the association between engagement and systolic BP at 12 months, estimated using average marginal effects. For both SMBP prompt groups, the optimal number of engagement clusters was 2, which we defined as high and low engagement. Of the 241 weekly participants, 189 (78.4%) were low (response rate: mean 20%, SD 23.4) engagers, and 52 (21.6%) were high (response rate: mean 86%, SD 14.7) engagers. Of the 247 daily participants, 221 (89.5%) were low engagers (response rate: mean 9%, SD 12.2), and 26 (10.5%) were high (response rate: mean 67%, SD 8.7) engagers. Among weekly participants, those who were older (>65 years of age), attended some college (vs no college), married or lived with someone, had Medicare (vs Medicaid), were under the care of a primary care doctor, and took antihypertensive medication in the last 6 months had higher odds of high engagement. Participants who lacked transportation to appointments had lower odds of high engagement. In both prompt frequency groups, participants who were high engagers had a greater decline in BP compared to low engagers. Participants randomized to weekly SMBP monitoring prompts responded more frequently overall and were more likely to be classed as high engagers compared to participants who received daily prompts. High engagement was associated with a larger decrease in BP. New strategies to encourage engagement are needed for participants with lower access to care.

Mailed feedback to primary care physicians on antibiotic prescribing for patients aged 65 years and older: pragmatic, factorial randomised controlled trial

ObjectivesTo evaluate whether providing family physicians with feedback on their antibiotic prescribing compared with that of their peers reduces antibiotic prescriptions. To also identify effects on antibiotic prescribing from case-mix...

Evaluation of the pharmacodynamic interaction effect of augmentation agents with clozapine in patients with treatment-resistant schizophrenia: A simulation study of clinical data

IntroductionThe aim of the study was to evaluate interaction effect of various augmentation strategies with clozapine in patients with Treatment-resistant schizophrenia. MethodsData was extracted for change in positive and negative syndrome scale (PANSS) or brief psychiatric rating scale (BPRS) scores for monotherapy with various antipsychotic agents alone and their combination with clozapine. Individual patient data was generated using simulation of data (factorial trial framework) from published clinical trials for sample sizes from eight to 400 to evaluate interaction effect through linear modeling. Dose equivalents were calculated, and best fit models were determined for simulated data. ResultsThe polynomial model was found to be the best fit for the simulated data to determine interaction effect of combination. The clozapine augmentation with risperidone and ziprasidone was found to be antagonistic, whereas it was additive for haloperidol, aripiprazole, and quetiapine. A synergistic effect was observed for ECT combined with clozapine (Interaction effect: -7.62; p <0.001). A sample size of 250-300 may be sufficient to demonstrate a clinically significant interaction in future trials. ConclusionClozapine may be augmented with electroconvulsive therapy, leading to the enhancement of antipsychotic effect. Though some antipsychotics like aripiprazole demonstrate additive effects, they may also add to the adverse effects.

Electroacupuncture and carbamazepine for patients with trigeminal neuralgia: a randomized, controlled, 2 × 2 factorial trial

BackgroundTrigeminal neuralgia (TN) is difficult to treat due to its severe pain intensity and recurring episodes, which significantly impact quality of life.ObjectivesWe aimed to assess the effectiveness of electroacupuncture (EA) in alleviating the pain intensity in TN, and to determine whether EA combined with low-dosage carbamazepine (CBZ) has a synergistic effect.MethodsA multi-centre, randomized, 2 × 2 factorial trial was conducted. Participants who met the inclusion criteria received active EA or sham EA for 60 min, three times a week for four weeks; CBZ (300 mg per day) or placebo for four weeks. The primary outcome was the change in visual analog scale (VAS) score from baseline to weeks 2, 4, 16, and 28. Secondary outcomes included quality of life and adverse events.ResultsA total of 120 participants (75 females and 45 males; mean (SD) age, 58.5 (15.3) years) were included. The main effects of EA and CBZ were significant (P < 0.001), and there was a significant interaction was identified between the interventions (P = 0.041). Participants who received EA (mean difference [MD], −0.3 [95% CI, −0.40 to −0.20] at week 2; −1.6 [−1.70 to −1.50] at week 4; −1.1 [−1.31 to −0.89] at week 16; −0.8 [−1.01 to −0.59] at week 28), CBZ (MD, −0.6 [95% CI, −0.70 to −0.50] at week 2; −0.9 [−1.03 to −0.77] at week 4, −0.2 [−0.41 to 0.01] at week 16, 0.2 [−0.01 to 0.41] at week 28), and the combination of both (MD, −1.8 [95% CI, −1.90 to −1.70] at week 2; −3.7 [−3.83 to −3.57] at week 4, −3.4 [−3.61 to −3.19] at week 16, −2.9 [−3.11 to −2.69] at week 28) had a greater reduction in VAS score over the treatment phase than their respective control groups (sham EA, placebo, and sham EA plus placebo). EA-related adverse events (6/59, 10.17%) were lower than that of CBZ (15/59, 25.42%) during the whole phases.ConclusionsEA or CBZ alone are effective treatments for TN, while the combination of EA and low-dosage CBZ exerts a greater benefit. These findings in this trial demonstrate that the combination of EA and low-dosage CBZ may be clinically effective under certain circumstances.Trial registrationNCT03580317.

Salicylic acid foliar application meliorates Portulaca oleraceae L. growth responses under Pb and Ni over-availability while keeping reliable phytoremediation potential

The efficacy of SA foliar use on Pb and Ni-induced stress tolerance and phytoremediation potential by Portulaca oleraceae L. were assayed as a factorial trial based on a completely randomized design with four repetitions. The factors included; SA foliar application (0 and 100 µM) and HMs application of Pb [0, 150, and 225 mg kg−1 soil Lead (II) nitrate] and Ni [0, 220, and 330 mg kg−1 soil Nickel (II) nitrate]. Plant height, stem diameter, shoot and root fresh and dry weight, photosynthetic pigments, total soluble proteins, palmitic acid, stearic acid, arachidic acid, and some macro- and micro-elements contents were reduced facing the HMs stress, but SA foliar application ameliorated these traits. HMs stress increased malondialdehyde content, total antioxidant activity, total flavonoids, phenolics, and linolenic acid content, while SA foliar application declined the mentioned parameters. Moreover, shoot and root Pb and Ni content enhanced in the purslane plants supplemented by SA under the HMs stress. The results propose SA foliar application as a reliable methodology to recover purslane growth characters and fatty acid profiles in the soil contaminated with the HMs. The idea is that SA would be potentially effective in alleviating HMs contamination while keeping reasonable phytoremediation potential.

Decision-making in the multiphase optimization strategy: Applying decision analysis for intervention value efficiency to optimize an information leaflet to promote key antecedents of medication adherence.

Advances in the multiphase optimization strategy (MOST) have suggested a new approach, decision analysis for intervention value efficiency (DAIVE), for selecting an optimized intervention based on the results of a factorial optimization trial. The new approach opens possibilities to select optimized interventions based on multiple valued outcomes. We applied DAIVE to identify an optimized information leaflet intended to support eventual adherence to adjuvant endocrine therapy for women with breast cancer. We used empirical performance data for five candidate leaflet components on three hypothesized antecedents of adherence: beliefs about the medication, objective knowledge about AET, and satisfaction with medication information. Using data from a 25 factorial trial (n = 1603), we applied the following steps: (i) We used Bayesian factorial analysis of variance to estimate main and interaction effects for the five factors on the three outcomes. (ii) We used posterior distributions for main and interaction effects to estimate expected outcomes for each leaflet version (32 total). (iii) We scaled and combined outcomes using a linear value function with predetermined weights indicating the relative importance of outcomes. (iv) We identified the leaflet that maximized the value function as the optimized leaflet, and we systematically varied outcome weights to explore robustness. The optimized leaflet included two candidate components, side-effects, and patient input, set to their higher levels. Selection was generally robust to weight variations consistent with the initial preferences for three outcomes. DAIVE enables selection of optimized interventions with the best-expected performance on multiple outcomes.

An Egg Intervention Improves Ponderal But Not Linear Growth Among Infants 6–12 mo of Age in Rural Bangladesh

BackgroundAnimal source foods are rich in multiple nutrients. Regular egg consumption may improve infant growth in low- and middle-income countries. ObjectivesTo assess the impact of daily egg consumption on linear growth among 6–12-mo olds in rural Bangladesh. MethodsWe conducted a 2 × 4 factorial cluster-randomized controlled trial allocating clusters (n = 566) to treatment for enteric pathogens or placebo and a daily egg, protein supplement, isocaloric supplement, or control. All arms received nutrition education. Here, we compare the effect of the egg intervention versus control on linear growth, a prespecified aim of the trial. Infants were enrolled at 3 mo. We measured length and weight at 6 and 12 mo and visited households weekly to distribute eggs and monitor compliance. We used linear regression models to compare 12-mo mean length, weight, and z-scores for length-for-age (LAZ), weight-for-length, and weight-for-age (WAZ), and log-binomial or robust Poisson regression to compare prevalence of stunting, wasting, and underweight between arms. We used generalized estimating equations to account for clustering and adjusted models for baseline measures of outcomes. ResultsWe enrolled 3051 infants (n = 283 clusters) across arms, with complete 6 and 12 mo anthropometry data from 1228 infants (n = 142 clusters) in the egg arm and 1109 infants (n = 141 clusters) in the control. At baseline, 18.5%, 6.0%, and 16.4% were stunted, wasted, and underweight, respectively. The intervention did not have a statistically significant effect on mean LAZ (β: 0.05, 95% confidence interval [CI]: −0.01, 0.10) or stunting prevalence (β: 0.98, 95% CI: 0.89, 1.13) at 12 mo. Mean weight (β: 0.07 kg, 95% CI: 0.02, 0.11) and WAZ (β: 0.06, 95% CI: 0.02, 0.11) were significantly higher in the egg compared with control arms. ConclusionsProvision of a daily egg for 6 mo to infants in rural Bangladesh improved ponderal but not linear growth. Trial registration numberNCT03683667, https://clinicaltrials.gov/ct2/show/NCT03683667.