Potential Public Health Impact Research Articles

The clinical and economic costs associated with regional disparities in varicella vaccine coverage in Italy over 50 years (2020–2070)

Italy implemented two-dose universal varicella vaccination (UVV) regionally from 2003 to 2013 and nationally from 2017 onwards. Our objective was to analyze regional disparities in varicella outcomes resulting from disparities in vaccine coverage rates (VCRs) projected over a 50-year time-horizon (2020–2070). A previously published dynamic transmission model was updated to quantify the potential public health impact of the UVV program in Italy at the national and regional levels. Four 2-dose vaccine strategies utilizing monovalent (V) and quadrivalent (MMRV) vaccines were evaluated for each region: (A) MMRV-MSD/MMRV-MSD, (B) MMRV-GSK/MMRV-GSK, (C) V-MSD/MMRV-MSD, and (D) V-GSK/MMRV-GSK. Costs were reported in 2022 Euros. Costs and quality-adjusted life-years (QALYs) were discounted 3% annually. Under strategy A, the three regions with the lowest first-dose VCR reported increased varicella cases (+ 34.3%), hospitalizations (+ 20.0%), QALYs lost (+ 5.9%), payer costs (+ 22.2%), and societal costs (+ 14.6%) over the 50-year time-horizon compared to the three regions with highest first-dose VCR. Regions with low first-dose VCR were more sensitive to changes in VCR than high first-dose VCR regions. Results with respect to second-dose VCR were qualitatively similar, although smaller in magnitude. Results were similar across all vaccine strategies.

Accelerating implementation of adolescent digital health prevention programs: analysis of insights from Australian stakeholders.

Chronic disease risk factors are increasing amongst adolescents, globally. Digital health prevention programs, which provide education and information to reduce chronic disease risk factors need to be equitable and accessible for all. For their success, multiple highly engaged stakeholders should be involved in development and implementation. This study aimed to evaluate stakeholders' support for, and perspectives on potential public health impact of digital health prevention programs for adolescents and potential pathways for future implementation. Qualitative semi-structured online interviews with stakeholders. Stakeholder mapping identified key individuals, groups and organizations across Australia that may influence the implementation of digital health prevention programs for adolescents. Recorded and transcribed interviews were analyzed within the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) Framework, using deductive content analysis. Nineteen interviews were conducted in 2023 with stakeholders from government, health, non-government organizations, youth services, education, community settings and others. Four overarching themes were identified: (i) existing digital health initiatives are not fit for purpose; (ii) the co-creation of digital health prevention programs is critical for successful implementation; (iii) digital health prevention programs must address equity and the unique challenges raised by technology and; (iv) system level factors must be addressed. Stakeholders broadly supported digital health prevention programs, yet raised unique insights to ensure that future programs create public health impact by improving chronic disease risk factors among adolescents. These insights can be applied in future development of digital health prevention programs for adolescents to strengthen widespread implementation.

Design and selection of drug properties to increase the public health impact of next-generation seasonal malaria chemoprevention: a modelling study.

Seasonal malaria chemoprevention (SMC) is recommended for disease control in settings with moderate to high Plasmodium falciparum transmission and currently depends on the administration of sulfadoxine-pyrimethamine plus amodiaquine. However, poor regimen adherence and the increased frequency of parasite mutations conferring sulfadoxine-pyrimethamine resistance might threaten the effectiveness of SMC. Guidance is needed to de-risk the development of drug compounds for malaria prevention. We aimed to provide guidance for the early prioritisation of new and alternative SMC drugs and their target product profiles. In this modelling study, we combined an individual-based malaria transmission model that has explicit parasite growth with drug pharmacokinetic and pharmacodynamic models. We modelled SMC drug attributes for several possible modes of action, linked to their potential public health impact. Global sensitivity analyses identified trade-offs between drug elimination half-life, maximum parasite killing effect, and SMC coverage, and optimisation identified minimum requirements to maximise malaria burden reductions. Model predictions show that preventing infection for the entire period between SMC cycles is more important than drug curative efficacy for clinical disease effectiveness outcomes, but similarly important for impact on prevalence. When children younger than 5 years receive four SMC cycles with high levels of coverage (ie, 69% of children receiving all cycles), drug candidates require a duration of protection half-life higher than 23 days (elimination half-life >10 days) to achieve reductions higher than 75% in clinical incidence and severe disease (measured over the intervention period in the target population, compared with no intervention across a range of modelled scenarios). High coverage is crucial to achieve these targets, requiring more than 60% of children to receive all SMC cycles and more than 90% of children to receive at least one cycle regardless of the protection duration of the drug. Although efficacy is crucial for malaria prevalence reductions, chemoprevention development should select drug candidates for their duration of protection to maximise burden reductions, with the duration half-life determining cycle timing. Explicitly designing or selecting drug properties to increase community uptake is paramount. Bill & Melinda Gates Foundation and the Swiss National Science Foundation.

The potential public health impact of the respiratory syncytial virus prefusion F protein vaccine in people aged ≥60 years in Japan: results of a Markov model analysis

ABSTRACT Background Respiratory syncytial virus (RSV), a common respiratory pathogen, can lead to severe symptoms, especially in older adults (OA). A recently developed RSV prefusion F protein (RSVPreF3 OA) vaccine confers high protection against RSV lower respiratory tract disease (LRTD) over two full RSV seasons. The aim of this study was to assess the potential public health impact of RSVPreF3 OA vaccination in the Japanese OA population. Research design and methods A static Markov model was used to estimate the number of symptomatic RSV cases, hospitalizations and deaths in the Japanese population aged ≥ 60 years over a 3-year time horizon. Japan-specific RSV epidemiology and healthcare resource use parameters were used; vaccine efficacy was derived from a phase 3 randomized study (AReSVi-006, NCT04886596). Vaccination coverage was set to 50%. Results Without vaccination, >5 million RSV acute respiratory illness (ARI) would occur (2.5 million LRTD and 2.8 million upper respiratory tract infections) leading to ~ 3.5 million outpatient visits, >534,000 hospitalizations and ~ 25,500 RSV-related deaths over 3 years. Vaccination could prevent > 1 million RSV-ARI cases, 728,000 outpatient visits, 143,000 hospitalizations and 6,840 RSV-related deaths. Conclusions RSVPreF3 OA vaccination is projected to have a substantial public health impact by reducing RSV-related morbidity and mortality in the OA population.

Cross-Species Transmission Potential of H4 Avian Influenza Viruses in China: Epidemiological and Evolutionary Study.

H4 avian influenza viruses (AIVs) have been widely detected in live poultry markets in China. However, the potential public health impact of H4 AIVs remains largely uncertain. Here, we fully analyzed the distribution and phylogenetic relationship of H4 AIVs in China. We obtained 31 isolates of H4 viruses in China during 2009-2022 through surveillance in poultry-associated environments, such as live poultry markets and poultry farms. Genomic sequence analysis together with publicly available data revealed that frequent reassortment and introduction of H4 AIV from wild birds to poultry may have occurred. We identified 62 genotypes among 127 whole genome sequences of H4 viruses in China, indicating that H4 AIVs had great genetic diversity in China. We also investigated molecular markers and found that drug resistance mutations frequently occurred in the M2 protein and a few mutations related to receptor binding and the host signature in H4 AIVs. Our study demonstrates the cross-species transmission potential of H4 AIVs in China and provides some reference significance for its risk assessment.

Sources of information on monkeypox virus infection. A systematic review with meta-analysis

BackgroundMonkeypox (Mpox) virus infection is a topic of growing interest today because of its potential public health impact and concern about possible outbreaks. Reliable and up-to-date sources of information that provide accurate data on its transmission, symptoms, prevention, and treatment are essential for understanding and effectively addressing this disease. Therefore, the aim of the present study is to determine the prevalence of sources of information on Mpox virus infection.MethodsAn exhaustive systematic review and meta-analysis was carried out using the information available in the PubMed, Scopus, Web of Science, Embase, and ScienceDirect databases up to August 3, 2023. The data were analyzed using R software version 4.2.3. The quality of the cross-sectional studies that formed part of this review was assessed using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) tool. In addition, a subgroup analysis was performed based on the study populations.ResultsThrough electronic searches of five databases, a total of 1833 studies were identified. Twenty-four cross-sectional articles were included, with a total sample of 35,959 participants from 34 countries. The pooled prevalence of each of the included information sources was: social networks reached 59% (95% CI: 50–68%; 29,146 participants; 22 studies; I2 = 100%; p < 0.01); the Internet was 61% (95% CI: 44–77%; 14,002 participants; 5 studies; I2 = 100%; p < 0.01), radio reached 10% (95% CI: 07–13%; 8917 participants; 4 studies; I2 = 93%; p < 0.01), television accounted for 24% (95% CI: 09–43%; 14,896 participants; 8 studies; I2 = 100%; p < 0.01), and the combination of radio and television accounted for 45% (95% CI: 31–60%; 4207 participants; 7 studies; I2 = 99%; p < 0.01); for newspapers, it was 15% (95% CI: 05–27%; 2841 participants; 6 studies; I2 = 99%; p < 0.01), friends and relatives accounted for 19% (95% CI: 12–28%; 28,470 participants; 19 studies; I2 = 100%; p < 0.01), the World Health Organization (WHO) accounted for 17% (95% CI: 07–29%; 1656 participants; 3 studies; I2 = 97%; p < 0.01), the Centers for Disease Control and Prevention (CDC) accounted for 10% (95% CI: 03–21%; 2378 participants; 3 studies; I2 = 98%; p < 0.01), and the combination of WHO and CDC websites accounted for 60% (95% CI: 48–72%; 1828 participants; 4 studies; I2 = 96%; p < 0.01), and finally, scientific articles and journals accounted for 24% (95% CI: 16–33%; 16,775 participants; 13 studies; I2 = 99%; p < 0.01).ConclusionThe study suggests that people access a variety of information sources to gain knowledge about Mpox virus infection, with a strong emphasis on online sources such as social networks and the Internet. However, it is important to note that the quality and accuracy of information available from these sources can vary, underscoring the need to promote access to reliable and up-to-date information about this disease to ensure public health.

Effects of probiotics on biogenic amines content in fermented milk during fermentation and storage

This study aimed to investigate the formation of biogenic amines (BAs) during fermentation and storage in fermented milk. The traditional culture was used as a control, and three different probiotics were added to the above culture as different experimental groups. Results revealed that the degree of protein hydrolysis in fermented milk increased during fermentation but decreased during storage, reaching a maximum value (14.8–17.3%) at the end of fermentation. The trends of total amino acid content and total BAs content were similar to those of the degree of hydrolysis. The total amino acid content reached a maximum value (2.83–3.22 mg/mL) after 24 h of post-ripening. Fermented milk had the highest tyramine content, but it was always below 10 mg/L. The total BAs content in fermented milk during fermentation and storage ranged from 9.04 to 15.2 mg/L and 6.37 to 14.0 mg/L, respectively. These levels consistently remained below the threshold considered harmful to humans. The pH reduction rate, the total bacterial cell number, the degree of hydrolysis, and the total amino acid content in fermented milk all affected the formation and content of BAs. This study provides a foundation for assessing the potential public health impact of BAs in fermented milk.

The WHO has Declared COVID-19 is No Longer a Pandemic-Level Threat: A Perspective Evaluating Potential Public Health Impacts.

The WHO has Declared COVID-19 is No Longer a Pandemic-Level Threat: A Perspective Evaluating Potential Public Health Impacts.

Modelling the Potential Public Health Impact of Different COVID-19 Vaccination Strategies with an Adapted Vaccine in Singapore

ABSTRACT Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has been a dynamically changing virus, requiring the development of adapted vaccines. This study estimated the potential public health impact alternative vaccination strategies for COVID-19 in Singapore. Research Design and Methods The outcomes of alternative vaccination strategies with a future adapted vaccine were estimated using a combined Markov decision tree model. The population was stratified by high- and standard-risk. Using age-specific inputs informed by local surveillance data and published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations. Results Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 278,614 cases 21,558 hospitalizations, 239 deaths, Singapore dollars (SGD) 277 million in direct medical costs, and SGD 684 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (3%), hospitalizations (29%), infections (145%), direct costs (90%), and indirect costs (192%) compared to the base case. Conclusions Broader vaccination strategies using an adapted booster vaccine could have substantial public health and economic impact in Singapore.

EPH102 Potential Public Health Impact of Bivalent Respiratory Syncytial Virus Prefusion F (RSVpreF) Maternal Vaccine for Prevention of Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Illness (LRTI) Among Canadian Infants

EPH102 Potential Public Health Impact of Bivalent Respiratory Syncytial Virus Prefusion F (RSVpreF) Maternal Vaccine for Prevention of Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Illness (LRTI) Among Canadian Infants

1942. Potential Public Health Impact of Bivalent Respiratory Syncytial Virus Prefusion F (RSVpreF) Maternal Vaccine for Prevention of RSV among US Infants

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract illness (LRTI) among young children. A bivalent stabilized prefusion F subunit vaccine (RSVpreF) for pregnant people to protect their infants against RSV-LRTI is currently under review by the US Food and Drug Administration. We evaluated the potential public health impact, measured as the reduction in clinical outcomes and economic costs, of maternal vaccination with RSVpreF for the prevention of RSV-LRTI among US infants. Methods A cohort model was employed to depict clinical outcomes and economic costs of RSV-LRTI from birth to age 1 year, lifetime consequences of premature death, and impact of maternal vaccination with RSVpreF among infants. Clinical outcomes were projected (monthly) based on infant age, gestational age in weeks (wGA) at birth, RSV disease and fatality rates, and mother’s vaccination status, and included cases of medically attended RSV-LRTI and RSV-LRTI deaths. Vaccine effectiveness was derived from interim trial analyses and was assumed to vary by clinical presentation (hospital vs. ambulatory), timing of vaccine administration relative to birth, and wGA at birth. Economic costs were generated based on cases and corresponding unit costs. The public health impact of RSVpreF was evaluated assuming year-round use and 100% uptake. Results Without use of maternal RSVpreF vaccine, 48,246 hospitalizations, 144,495 emergency department (ED) encounters, and 399,313 outpatient clinic (OC) visits are projected to occur annually among the US birth cohort of 3.7M infants aged &amp;lt; 12 months. Maternal vaccination with RSVpreF resulted in a reduction of 24,520 hospitalizations, 45,957 ED encounters, and 128,745 OC visits, corresponding with a decrease in direct medical costs equal to $691.8 million and indirect (non-medical) costs equal to $110.0 million (Table).Table.Clinical outcomes and economic costs among US infants aged &amp;lt;1 year with maternal use of RSVpreF vaccine versus no intervention Conclusion Results from this evaluation indicate that maternal vaccination with RSVpreF would substantially reduce the clinical and economic burden of RSV-LRTI in infants. These results may be conservative as we did not include potential for reductions in outcomes such as maternal RSV disease, household transmission, and long-term sequelae such as asthma. Disclosures Ahuva Hanau, BS, Pfizer Inc.: Grant/Research Support Kimberly M. Shea, Ph.D., M.P.H., Pfizer: Employment|Pfizer: Stocks/Bonds Derek Weycker, Ph.D., Pfizer Inc.: Grant/Research Support Mark Atwood, MS, Pfizer Inc.: Grant/Research Support Erin Quinn, BS, Eisai Inc.: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|GRAIL: Advisor/Consultant|Pfizer Inc.: Advisor/Consultant|Santen Pharmaceutical: Advisor/Consultant Emily Kutrieb, B.A., Pfizer Inc.: Advisor/Consultant Jessica E. Atwell, PhD, MPH, Pfizer: Stocks/Bonds Alejandro D. Cane, MD, PhD, Pfizer: Stocks/Bonds Bradford D. Gessner, M.D, M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Sarah J. Pugh, PhD, MPH, Pfizer Inc: Salary|Pfizer Inc: Stocks/Bonds Amy W. Law, PharmD, Pfizer: Employment|Pfizer: Stocks/Bonds

Mycobacteriosis in slaughter pigs from South Africa from 1991 to 2002: Mycobacterium spp. diversity and Mycobacterium avium complex genotypes.

Mycobacterium avium complex (MAC) bacteria are the most prominent etiological agents of lymphadenitis in pigs. M. avium subspecies hominissuis (MAH) is a member of MAC and has been reported in many parts of the world to be the most prevalent non-tuberculous mycobacteria (NTM) to cause mycobacteriosis in humans, mainly in children. Thus, the economic and zoonotic impact of MAC species are increasingly being recognized. In South Africa, little is known about the distribution of NTM and the molecular epidemiology of M. avium in pigs. In this study, lymph nodes including mandibular, mesenteric, submandibular, and retropharyngeal, with tuberculosis-like lesions were collected during routine meat inspection of slaughter pigs with no disease symptoms (n = 132), between 1991 and 2002. These pigs were slaughtered at 44 abattoirs distributed across seven of the nine South African provinces. Mycobacterial culture, polymerase chain reaction (PCR), and sequencing of the Mycobacterium specific 577 bp 16S rRNA gene fragment were performed for species and subspecies identification. The majority of the isolates (each per sample); 114 (86.4%) were identified as MAH, 8 (6%) as MAA/M. avium subsp. silvaticum, 4 (3%) were Mycobacterium tuberculosis, 2 (1.5%) as Mycobacterium intracellulare, and 1 (0.75%) as Mycobacterium bovis. The other isolates were identified as Mycobacterium lentiflavum (0.75%), Mycobacterium novocastrense (0.75%), and a Micrococcus spp. (0.75%). Using an eight-marker MLVA typing tool, we deciphered at least nine MIRU VNTR INMV types of MAH and MAA. Identification of known zoonotic mycobacteria, including MAH, MAA, M. intracellulare, M. bovis, and M. tuberculosis, from slaughter pigs has a potential public health impact and also strengthens recognition of the potential economic impact of MAC. This study has also for the first time in South Africa, revealed MAC MIRU VNTR INMV genotypes which will aid in the future epidemiological investigation of MAC in South Africa.

Abstract 16988: Conventional and Regionally Distinctive Risk Factors for First-Onset Myocardial Infarction in Bangladesh. The Bangladesh Risk of Acute Vascular Events (BRAVE) Study

Background: South Asians may be particularly susceptible to premature myocardial infarction (MI) owing both to classic cardiovascular risk factors and distinctive practices more common in South Asian populations. Hypothesis: Identifying modifiable risk factors for MI in South Asian populations should inform prevention strategies. Goal: To study conventional risk factors and several distinctive South Asian characteristics and practices in relation to the likelihood of first-ever MI in Bangladesh. Methods: In a case-control study involving 8,133 first MI cases and 8,122 controls, we calculated odds ratios (ORs) for MI (adjusted, when appropriate, for age, sex, smoking status, history of diabetes, history of hypertension, family history of MI, and LDL-cholesterol) and assessed their potential public health impact using population attributable fractions (PAFs). Results: The mean (SD) age of first MI was 53 (11) years. Adjusted ORs (95% CIs) were 2.75 (2.53-2.99) for cigarette smoking, 2.33 (2.08-2.60) for parental history of MI, 2.26 (2.07-2.48) for history of hypertension, 1.79 (1.61-1.98) for history of diabetes, and 1.61 (1.55-1.67) per 1-SD higher LDL-cholesterol. The highest PAFs (95% CIs) were for current cigarette smoking (48.9% [46.1%-51.6%]), higher LDL-cholesterol (32.4% [30.2%-34.4%]) and history of hypertension (14.7% [13.2%-16.1%]). As for regionally distinctive practices, ORs were 4.05 (3.15-5.21) with biri smoking, 2.04 (1.48-2.81) with chewing tobacco, and 1.26 (1.05-1.51) with parental history of first cousin marriage. Conclusion: In a large case-control study, we confirmed the relevance of several conventional risk factors to risk of first-onset MI in the Bangladesh population. We also identified significant associations with MI of practices distinctive to South Asian populations, including indigenous modes of tobacco consumption and parental first-cousin marriage, apparently independent of conventional risk factors. These findings should help identify opportunities for cardiovascular disease prevention in South Asia that embrace both conventional and regionally distinctive risk factors.

Effects of a Self-Guided Transdiagnostic Smartphone App on Patient Empowerment and Mental Health: Randomized Controlled Trial.

Mental disorders impact both individuals and health systems. Symptoms and syndromes often remain undetected and untreated, resulting in chronification. Besides limited health care resources, within-person barriers such as the lack of trust in professionals, the fear of stigmatization, or the desire to cope with problems without professional help contribute to the treatment gap. Self-guided mental health apps may support treatment seeking by reducing within-person barriers and facilitating mental health literacy. Digital mental health interventions may also improve mental health related self-management skills and contribute to symptom reduction and the improvement of quality of life. This study aims to investigate the effects of a self-guided transdiagnostic app for mental health on help seeking, reduced stigma, mental health literacy, self-management skills, mental health symptoms, and quality of life using a randomized controlled design. Overall, 1045 participants (recruited via open, blinded, and web-based recruitment) with mild to moderate depression or anxiety-, sleep-, eating-, or somatization-related psychopathology were randomized to receive either access to a self-guided transdiagnostic mental health app (MindDoc) in addition to care as usual or care as usual only. The core features of the app were regular self-monitoring, automated feedback, and psychological courses and exercises. The coprimary outcomes were mental health literacy, mental health-related patient empowerment and self-management skills (MHPSS), attitudes toward help seeking, and actual mental health service use. The secondary outcomes were psychopathological symptom burden and quality of life. Data were collected at baseline and 8 weeks and 6 months after randomization. Treatment effects were investigated using analyses of covariance, including baseline variables as predictors and applying multiple imputation. We found small but robust between-group effects for MHPSS (Cohen d=0.29), symptoms burden (Cohen d=0.28), and quality of life (Cohen d=0.19) 8 weeks after randomization. The effects on MHPSS were maintained at follow-up. Follow-up assessments also showed robust effects on mental health literacy and preliminary evidence for the improvement of help seeking. Predictors of attrition were lower age and higher personality dysfunction. Among the non-attritors, predictors for deterioration were less outpatient treatment and higher initial symptom severity. A self-guided transdiagnostic mental health app can contribute to lasting improvements in patient empowerment. Symptoms of common mental disorders and quality of life improved faster in the intervention group than in the control group. Therefore, such interventions may support individuals with symptoms of 1 or more internalizing disorders, develop health-centered coping skills, prevent chronification, and accelerate symptom improvement. Although the effects for individual users are small and predictors of attrition and deterioration need to be investigated further, the potential public health impact of a self-guided intervention can be large, given its high scalability. German Clinical Trials Register DRKS00022531; https://drks.de/search/de/trial/DRKS00022531.

Improving Mild to Moderate Depression With an App-Based Self-Guided Intervention: Protocol for a Randomized Controlled Trial.

Depression is one of the most prevalent mental disorders and frequently co-occurs with other mental disorders. Despite the high direct and indirect costs to both individuals and society, more than 80% of those diagnosed with depression remain with their primary care physician and do not receive specialized treatment. Self-guided digital interventions have been shown to improve depression and, due to their scalability, have a large potential public health impact. Current digital interventions often focus on specific disorders, while recent research suggests that transdiagnostic approaches are more suitable. This paper presents the protocol for a study that aims to assess the efficacy of a self-guided transdiagnostic app-based self-management intervention in patients with mild or moderate depression with and without comorbid mental disorders. Specifically, we are investigating the impact of the intervention on symptoms of depression, quality of life, anxiety symptoms, and mental health-related patient empowerment and self-management skills. The intervention under investigation, MindDoc with Prescription, is a self-guided digital intervention aimed at supporting individuals with mild to moderate mental disorders from the internalizing spectrum, including depression. The app can be used as a low-threshold psychosocial intervention. Up to 570 adult patients will be randomized to either receive the intervention in addition to care as usual or only care as usual. We are including adults with a permanent residency in Germany and mild or moderate depression according to International Classification of Diseases, 10th Revision, criteria (F32.0, F32.1, F33.0, and F33.1). Clinical interviews will be conducted to confirm the diagnosis. Data will be collected at baseline as well as 8 weeks and 6 months after randomization. The primary outcome will be depression symptom severity after 8 weeks. Secondary outcomes will be quality of life, anxiety symptom severity, and patient empowerment and self-management behaviors. Data will be analyzed using multiple imputations, using the intention-to-treat principle, while sensitivity analyses will be based on additional imputation strategies and a per-protocol analysis. Recruitment for the trial started on February 7, 2023, and the first participant was randomized on February 14, 2023. As of September 5, 2023, 275 participants have been included in the trial and 176 have provided the primary outcome. The rate of missing values in the primary outcome is approximately 20%. Data from this efficacy trial will be used to establish whether access to the intervention is associated with an improvement in depression symptoms in individuals diagnosed with mild or moderate depression. The study will contribute to expanding the evidence base on transdiagnostic digital interventions. German Registry of Clinical Trials DRKS00030852; https://drks.de/search/de/trial/DRKS00030852. DERR1-10.2196/46651.

Motivational Enhancement Interventions to Increase Pre-Exposure Prophylaxis Use in Sexual Minority Men Who Use Stimulants: Protocol for a Pilot Sequential Multiple Assignment Randomized Trial.

Although pre-exposure prophylaxis (PrEP) could substantially mitigate HIV risk, sexual minority men who use stimulants commonly experience difficulties with engaging in PrEP clinical services. Motivational interviewing (MI) and contingency management (CM) reduce substance use and condomless anal sex (CAS) in this population, but these motivational enhancement interventions require modifications to promote engagement along the PrEP care continuum. PrEP Readiness Interventions for Supporting Motivation (PRISM) is a pilot sequential multiple assignment randomized trial testing the feasibility, acceptability, and preliminary effectiveness of distinct combinations of telehealth MI and CM in 70 cisgender sexual minority men who use stimulants that are not currently taking PrEP. A national sample was recruited via social networking applications to complete a baseline assessment and mail-in HIV testing. Those with nonreactive HIV results were randomized to receive either (1) a 2-session MI intervention focusing on PrEP use (session 1) and concomitant stimulant use or CAS (session 2) or (2) a CM intervention with financial incentives for documented evidence of PrEP clinical evaluation by a medical provider (US $50) and filling a PrEP prescription (US $50). At the 3-month follow-up assessment, participants who reported they had not filled a prescription for PrEP were randomized a second time to either (1) switch to a second-stage intervention (ie, MI+CM or CM+MI) or (2) continue with assessments only. Outcomes for both responders and nonresponders were reassessed at a 6-month follow-up. The primary outcome is documented evidence of filling a PrEP prescription over 6 months. Self-reported secondary outcomes include PrEP clinical evaluation by a medical provider, stimulant use, and CAS. Qualitative exit interviews were conducted with a subgroup of responders and nonresponders to characterize their experiences with the MI and CM interventions. Implementation of PRISM underscores challenges in reaching sexual minority men who use stimulants to optimize HIV prevention efforts. Approximately 1 in 10 (104/1060) eligible participants have enrolled. Of the 104 who enrolled, 87 (84%) completed mail-in HIV testing. We delivered 5 preliminary HIV-positive results, including posttest counseling with referrals to confirmatory testing. Lessons learned from PRISM underscore the central importance of a flexible, participant-centered approach to support the engagement of sexual minority men who use stimulants. Leveraging telehealth platforms to deliver motivational enhancement interventions also expanded their reach and potential public health impact with this high-priority population. Further research is needed to determine the effectiveness of telehealth MI and CM for supporting PrEP use in sexual minority men who use stimulants. ClinicalTrials.gov NCT04205487; https://clinicaltrials.gov/study/NCT04205487. DERR1-10.2196/48459.

Applying an Implementation Framework to the Dissemination of a School-Based Child Sexual Abuse Prevention Program.

Since the 1980s, school-based child sexual abuse (CSA) prevention programs have been the prevailing prevention strategy in the United States. Despite demonstrated effectiveness, there is a lack of infrastructure and educational policy ensuring all students receive these programs. A pragmatic application of the RE-AIM implementation framework, this study provides an overview of a multi-county implementation effort of the school-based CSA prevention program, Safe Touches. Implementation efforts across five counties in a Mid-Atlantic state are described at three levels: organizational (school districts), child, and program facilitator. Children's CSA-related knowledge was measured at four time points: pre-workshop, immediately post-workshop, and then 6 and 12 months post-workshop. Facilitators completed an anonymous survey post-implementation. Over the course of one and a half academic years, Safe Touches was implemented in 718 public school districts, reaching in total 14,235 second-grade students. Students' significantly increased knowledge from pre- to post-workshop and gains were maintained at 6 and 12 months (ps <.001). A total of 29 disclosures of maltreatment were made by students to facilitators during or after the workshop. Facilitators generally adopted Safe Touches and attested to the feasibility and benefits of its large-scale implementation as well as the negligible negative impacts for children. When implemented systematically, school-based CSA prevention is able to reach a high number of students, effectively increase CSA-related knowledge, and facilitates disclosures. To maximize the potential public health impact, it is suggested that state funds be allocated to support the implementation of such programs as part of standard education costs.

Supporting Pharmacovigilance Signal Validation and Prioritization with Analyses of Routinely Collected Health Data: Lessons Learned from an EHDEN Network Study.

Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals. The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process. Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals. Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15-60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine healthdata. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development. Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost-benefit of integrating these analyses at this stage of signal management requires further research.

The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design

BackgroundHeart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF). MethodsThis clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO3) or a placebo capsule daily for 6 wk. Primary outcome measures are muscle power determined by isokinetic dynamometry and peak aerobic capacity (VO2peak) determined during an incremental treadmill exercise test. Endpoints include the acute effects of a single dose of KNO3 and longer-term effects of 6 wk of KNO3. The study is adequately powered to detect expected increases in these outcomes at P < 0.05 with 1-β>0.80. DiscussionThe iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future ‘pivotal’, phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant.

Modelling the potential public health impact of different vaccination strategies with an omicron-adapted bivalent vaccine in Thailand

ABSTRACTBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has continuously evolved, requiring the development of adapted vaccines. This study estimated the impact of the introduction and increased coverage of an Omicron-adapted bivalent booster vaccine in Thailand.Research Design and MethodsThe outcomes of booster vaccination with an Omicron-adapted bivalent vaccine versus no booster vaccination were estimated using a combined cohort Markov decision tree model. The population was stratified into high- and standard-risk subpopulations. Using age-specific inputs informed by published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations.ResultsBooster vaccination in only the elderly and high-risk subpopulation was estimated to avert 97,596 cases 36,578 hospitalizations, 903 deaths, THB 3,119 million in direct medical costs, and THB 10,589 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (95%), hospitalizations (512%), infections (782%), direct costs (550%), and indirect costs (687%) compared to the base case.ConclusionsBroader vaccination with an Omicron-adapted bivalent booster vaccine could have significant public health and economic benefits in Thailand.