Johns Hopkins Bloomberg School of Public Health

When competing events occur, there are two main options for handling them analytically that invoke different assumptions: 1) censor person-time after a competing event (which is akin to assuming they could be prevented) to calculate a conditional risk; or 2) do not censor them (allow them to occur) to calculate an unconditional risk. The choice of estimand has implications when weighing the relative frequency of a beneficial outcome and an adverse outcome in a risk–benefit analysis. We review the assumptions and interpretations underlying the two main approaches to analyzing competing risks. Using a popular metric in risk–benefit analyses, the Benefit-Risk Ratio, and a toy dataset, we demonstrated that conclusions about whether a treatment was more beneficial or more harmful can depend on whether one uses conditional or unconditional risks. We argue that unconditional risks are more relevant to decision-making about exposures with competing outcomes than conditional risks.

Menstruation touches all spheres of human society, including psychology, education, business, policy, race, and religion. This narrative review aims to describe the relationship menstruation holds with these spaces. First, menstruation plays many roles in psychology — premenstrual syndrome affects psychological well-being, and in turn, psychological stress impacts menstruation. Functional hypothalamic amenorrhea can result when stress hormones inhibit the hypothalamus-pituitary-ovarian axis. Furthermore, menstruation has many implications for all aged individuals, especially adolescents and those who are menopausal. These implications underscore the importance of proper education surrounding menstruation, which can be achieved via social media, school systems, family, and clinicians. However, menstrual health education is highly variable depending on the state and family that someone is raised in. Additionally, menstruation can pose a financial burden as menstrual products can be expensive and access to these products is limited for those who are homeless, incarcerated, and low-income. Recent public policy measures in various states have aimed to achieve “menstrual equity,” by requiring public schools to supply free menstrual products in bathrooms. Furthermore, racial disparities exist with menstrual disorders. Uterine fibroids occur more frequently in Black menstruators compared to White menstruators, and Black women experience worse outcomes overall with fibroids and endometriosis management. Finally, analysis of religion and its relationship to menstruation underscores the immense stigma and “impurity” associated with menstruation. Overall, this review highlights the universality of menstruation in society. As a “fifth vital sign,” there is significant room for improvement in terms of education, research, and cultural acceptance of menstruation. Future research should explore interventions to reduce these gaps.

Background Femoral fragility fractures in older adults can result in devastating loss of physical function and independence. Skeletal muscle atrophy likely contributes to disability. The purpose of this study was to characterize the change in skeletal muscle mass, investigate the relationship with malnutrition and physical function, and identify risk factors for skeletal muscle loss. Methods Adults ≥65 years of age who were treated with operative fixation of an isolated femoral fragility fracture were enrolled in this multicenter, prospective observational study. Skeletal muscle mass was assessed within 72 hours of admission using multifrequency bioelectrical impedance analysis, which was repeated at 6 weeks, 3 months, and 6 months. Sarcopenia was defined by sex-specific cutoffs for the appendicular skeletal muscle mass index. The Mini Nutritional Assessment was used to measure nutritional status at the time of injury. Physical function was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function domain. Linear mixed models were used to evaluate changes in skeletal muscle mass and PROMIS Physical Function scores over time and to evaluate factors associated with skeletal muscle mass changes. Results Ninety participants (74% female) with a mean age of 77.6 ± 9.0 years were enrolled. At the time of injury, 30 (33%) were sarcopenic and 44 (49%) were at risk for malnutrition or had malnutrition. Older age was associated with lower skeletal muscle mass (age of ≥75 versus <75 years: least squares mean [and standard error], −3.3 ± 1.6 kg; p = 0.042). From the time of injury to 6 weeks, participants lost an average of 2.4 kg (9%) of skeletal muscle mass (95% confidence interval [CI] = ‒3.0 to ‒1.8 kg; p < 0.001). This early loss did not recover by 6 months (1.8 kg persistent loss compared with baseline [95% CI = ‒2.5 to ‒1.1 kg]; p < 0.001). Participants with normal nutritional status lost more skeletal muscle mass from baseline to 6 weeks after injury compared with those with malnutrition (1.3 kg more loss [standard error, 0.6 kg]; p = 0.036). A 1-kg decrease in skeletal muscle mass was associated with an 8-point decrease in the PROMIS Physical Function (model parameter estimate, 0.12 [standard error, 0.04]; p = 0.002). Conclusions We found that older adults with femoral fragility fractures lost substantial skeletal muscle mass and physical function. Participants with adequate baseline nutrition actually lost more muscle mass than those who were malnourished, indicating that future investigations of interventions to prevent muscle loss should focus on older adults regardless of nutritional status. Level of Evidence Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

In this article, we introduce a new command, clan, that conducts a cluster-level analysis of cluster randomized trials. The command simplifies adjusting for individual- and cluster-level covariates and can also account for a stratified design. It can be used to analyze a continuous, binary, or rate outcome.

Background Non-Hispanic Black and Hispanic patients with symptomatic PAD may receive different treatments than White patients with symptomatic PAD. The delivery of guideline-directed medical treatment may be a modifiable upstream driver of race and ethnicity-related disparities in outcomes such as limb amputation. The purpose of our study was to investigate the prescription of preoperative antiplatelets and statins in producing disparities in the risk of amputation following revascularization for symptomatic peripheral artery disease (PAD). Methods We used data from the Vascular Quality Initiative, a vascular procedure-based registry in the United States (2011–2018). We estimated the probability of preoperative antiplatelet and statin prescriptions and 1-year incidence of amputation. We then estimated the amputation risk difference between race/ethnicity groups that could be eliminated under a hypothetical intervention. Results Across 100,579 revascularizations, the 1-year amputation risk was 2.5% (2.4%, 2.6%) in White patients, 5.3% (4.9%, 5.6%) in Black patients, and 5.3% (4.7%, 5.9%) in Hispanic patients. Black (57.5%) and Hispanic patients (58.7%) were only slightly less likely than White patients (60.9%) to receive antiplatelet and statin therapy. However, the effect of antiplatelets and statins was greater in Black and Hispanic patients such that, had all patients received these medications, the estimated risk difference comparing Black to White patients would have reduced by 8.9% (–2.9%, 21.9%) and the risk difference comparing Hispanic to White patients would have been reduced by 17.6% (–0.7%, 38.6%). Conclusion Even though guideline-directed care appeared evenly distributed by race/ethnicity, increasing access to such care may decrease health care disparities in major limb amputation.

Introduction Overdose prevention sites (OPS) are evidence-based interventions to improve public health, yet implementation has been limited in the USA due to a variety of legal impediments. Studies in various US settings have shown a high willingness to use OPS among urban and rural people who inject drugs, but data among people who use drugs (PWUD) via non-injection routes of administration in suburban areas are lacking. Methods We utilized cross-sectional data from a sample of suburban PWUD who have not injected drugs in the past 3 months (N = 126) in Anne Arundel County, Maryland. We assessed PWUDs’ likelihood of using a hypothetical OPS and perceived potential barriers to accessing OPS. We tested for associations between sociodemographic characteristics, drug use, service access, and overdose experiences with willingness to utilize OPS. Findings Participants’ median age was 42, and the majority were men (67%) and non-Hispanic Black (79%). Sixty-six percent reported willingness to use an OPS. Concerns about confidentiality (29%), arrest (20%), and transportation costs (22%) were the most anticipated barriers to using OPS. Men (75% vs 55%, p = 0.015), participants who used heroin (53% vs 32%, p = 0.017), and participants who used multiple overdose prevention behaviors (e.g., using fentanyl test strips) (36% vs 19%, p = 0.006) were more likely to report willingness to use OPS. Conclusion Most suburban non-injecting PWUD in the sample were willing to use an OPS. OPS implementation strategies in suburban settings should be tailored to reach PWUD via non-injection routes of administration while meeting the unique needs of suburban contexts.

Invasion of human erythrocytes by Plasmodium falciparum (Pf) merozoites relies on the interaction between two parasite proteins: apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2). While antibodies to AMA1 provide limited protection against Pf in non-human primate malaria models, clinical trials using recombinant AMA1 alone (apoAMA1) yielded no protection due to insufficient functional antibodies. Immunization with AMA1 bound to RON2L, a 49-amino acid peptide from its ligand RON2, has shown superior protection by increasing the proportion of neutralizing antibodies. However, this approach relies on the formation of a complex in solution between the two vaccine components. To advance vaccine development, here we engineered chimeric antigens by replacing the AMA1 DII loop, displaced upon ligand binding, with RON2L. Structural analysis confirmed that the fusion chimera (Fusion-FD12) closely mimics the binary AMA1-RON2L complex. Immunization studies in female rats demonstrated that Fusion-FD12 immune sera, but not purified IgG, neutralized vaccine-type parasites more efficiently compared to apoAMA1, despite lower overall anti-AMA1 titers. Interestingly, Fusion-FD12 immunization enhanced antibodies targeting conserved epitopes on AMA1, leading to increased neutralization of non-vaccine type parasites. Identifying these cross-neutralizing antibody epitopes holds promise for developing an effective, strain-transcending malaria vaccine.

Objective To estimate the associations between gestational weight gain (GWG) during pregnancy and neonatal outcomes in low and middle income countries. Design Individual participant data meta-analysis. Setting Prospective pregnancy studies from 24 low and middle income countries. Main outcome measures Nine neonatal outcomes related to timing (preterm birth) and anthropometry (weight, length, and head circumference) at birth, stillbirths, and neonatal death. Analysis methods A systematic search was conducted in PubMed, Embase, and Web of Science which identified 53 prospective pregnancy studies published after the year 2000 with data on GWG, timing and anthropometry at birth, and neonatal mortality. GWG adequacy was defined as the ratio of the observed maternal weight gain over the recommended weight gain based on the Institute of Medicine body mass index specific guidelines, which are derived from data in high income settings, and the INTERGROWTH-21st GWG standards. Study specific estimates, adjusted for confounders, were generated and then pooled using random effects meta-analysis models. Maternal age and body mass index before pregnancy were examined as potential modifiers of the associations between GWG adequacy and neonatal outcomes. Results Overall, 55% of participants had severely inadequate (<70%) or moderately inadequate (70% to <90%) GWG, 22% had adequate GWG (90-125%), and 23% had excessive GWG (≥125%). Severely inadequate GWG was associated with a higher risk of low birthweight (adjusted relative risk 1.62, 95% confidence interval 1.51 to 1.72; 48 studies, 93 337 participants; τ ² =0.006), small for gestational age (1.44, 1.36 to 1.54; 51 studies, 93 191 participants; τ ² =0.016), short for gestational age (1.47, 1.29 to 1.69; 40 studies, 83 827 participants; τ ² =0.074), and microcephaly (1.57, 1.31 to 1.88; 31 studies, 80 046 participants; τ ² =0.145) compared with adequate GWG. Excessive GWG was associated with a higher risk of preterm birth (1.22, 1.13 to 1.31; 48 studies, 103 762 participants; τ ² =0.008), large for gestational age (1.44, 1.33 to 1.57; 47 studies, 90 044 participants; τ ² =0.009), and macrosomia (1.52, 1.33 to 1.73; 29 studies, 68 138 participants; τ ² =0) compared with adequate GWG. The direction and magnitude of the associations between GWG adequacy and several neonatal outcomes were modified by maternal age and body mass index before pregnancy. Conclusions Inadequate and excessive GWG are associated with a higher risk of adverse neonatal outcomes across settings. Interventions to promote optimal GWG during pregnancy are likely to reduce the burden of adverse neonatal outcomes, however further research is needed to assess optimal ranges of GWG based on data from low and middle income countries.

The growing number of people living with dementia (PLWD) requires a coordinated clinical response to deliver pragmatic, evidence‐based interventions in frontline care settings. However, infrastructure to support such a response is lacking. Moreover, there are too few researchers conducting rigorous embedded pragmatic clinical trials (ePCTs) to make the vision of high quality, widely accessible dementia care a reality. National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's disease and Related Dementias Clinical Trials (IMPACT) Collaboratory seeks to improve the pipeline of early career researchers qualified to lead ePCTs by funding career development awards. Even with support from the Collaboratory, awardees face practical and methodological challenges to success, recently exacerbated by the COVID‐19 pandemic. We first describe the training opportunities and support network for the IMPACT CDA recipients. This report then describes the unique career development challenges faced by early‐career researchers involved in ePCTs for dementia care. Topics addressed include challenges in establishing a laboratory, academic promotion, mentoring and professional development, and work‐life balance. Concrete suggestions to address these challenges are offered for early‐career investigators, their mentors, and their supporting institutions. While some of these challenges are faced by researchers in other fields, this report seeks to provide a roadmap for expanding the work of the IMPACT Collaboratory and initiating future efforts to recruit, train, and retain talented early‐career researchers involved in ePCTs for dementia care.

PURPOSE Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during adjuvant ET will enhance symptom detection, symptom management, and persistence. METHODS Eligible patients were initiating ET for stage 0-III breast cancer. Participants completed ePRO surveys via smartphone at baseline and 1, 3, 6, and 12 months. Measures included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Fatigue, and Vaginal Discomfort; plus Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items assessing joint pain, hot flashes, vaginal dryness, concentration problems, and memory problems. Scores surpassing prespecified thresholds triggered alerts, and recommended symptom management pathways were provided to clinicians. The primary objective was to evaluate feasibility, assessed by survey completion rates, with targets of >65% for the baseline survey and ≥1 follow-up survey during the first 6 months. Secondary objectives included 12-month ET discontinuation rate (target: ≤15%), describing symptoms and evaluating pathway implementation. RESULTS Among 250 participants, 73.2% completed the baseline survey and 69.6% completed ≥1 follow-up survey during the first 6 months. Thirty-one percent of participants had ≥1 symptom alert at baseline and 74% had ≥1 symptom alert during follow-up. The proportions of participants for whom pathway-concordant symptom management was documented at each time point ranged from 12.8% to 36.6%. Twenty-eight participants (11.2%) discontinued ET by 12 months. CONCLUSION Symptom monitoring with ePROs during adjuvant ET is feasible. Despite infrequent documentation of pathway-concordant symptom management after symptom alerts, ePROs were associated with favorable short-term ET persistence.

Benefits of breastfeeding for both the mother and the child are well established, but a comprehensive and robust study to investigate the protective effect of breastfeeding and attenuated time effect stratified by cause of morbidity are lacking. This study is based on the nationwide birth cohort in Korea that includes data on all infants born from 2009 to 2015. Of 1,608,540 children, the median follow-up period was 8.41 years (interquartile range, 6.76-10.06). When compared to children with fully formula feeding, the hospital admission rate was 12% lower in those with partially breastfeeding and 15% lower in those with exclusive breastfeeding. The apparent protective effect of breastfeeding was reduced with increasing age. Our study provides potential evidence of the beneficial association of breastfeeding on subsequent hospital admissions. The protective effect declined over time as the children grew older. Encouraging any breastfeeding for at least the first 6 months among infants is an important public health strategy to improve overall child health.

Transgender women who sell sex (TWSS) experience high rates of HIV acquisition. Antiretrovirals for pre-exposure prophylaxis (PrEP) represent an efficacious HIV prevention strategy. The social and structural factors affecting PrEP delivery amongst TWSS are underexplored in the literature. We conducted ethnographic research to examine how multilevel social and structural factors manifest in TWSS’s lived experiences and affect PrEP delivery and use. Twenty-four transgender women were recruited from the SAPPHIRE cohort and completed interviews focused on barriers and facilitators to PrEP engagement in the context of street-based sex work. Stakeholder interviews (N = 7) were also conducted. Our findings suggest there are unique features of the risk environment that can collectively impede PrEP use among TWSS.

Background Overuse of preoperative cardiac testing contributes to high healthcare costs and delayed surgeries. A large body of research has evaluated factors associated with variation in preoperative cardiac testing. However, patient, provider, and system‐level factors associated with variation in testing have not been systematically studied. Objective To conduct a systematic review to better delineate the patient, provider, and system‐level factors associated with variation in preoperative cardiac testing. Methods We included studies of an adult US population evaluating a patient, provider, or system‐level factor associated with variation in preoperative cardiac testing for noncardiac surgery since 2012. Our search strategy used terms related to preoperative testing, diagnostic cardiac tests, and care variation with Ovid MEDLINE and Embase from inception through January 2023. We extracted study characteristics and factors associated with variation and qualitatively analyzed them. We assessed risk of bias using the Newcastle–Ottawa Scale and Evidence Project Risk of Bias tool. Results Twenty‐eight articles met inclusion criteria. Older age and higher comorbidity were strongly associated with higher‐intensity testing. The evidence for provider and system‐level covariates was weaker. However, there was strong evidence that a focus on primary care and away from preoperative clinic and cardiac consultations was associated with less testing and that interventions to reduce low‐value testing can be successful. Conclusions There is significant interprovider and interhospital variation in preoperative cardiac testing, the correlates of which are not well‐defined. Further work should aim to better understand these factors.

Background Cross-sectional surveys using the Standardized Monitoring and Assessment of Relief and Transitions methodology have been conducted annually in Chad since 2015 to evaluate population-level nutritional status. Objective This analysis characterizes national and subnational trends in child wasting and women’s thinness from 2015 to 2021 in Chad and identifies risk factors during the COVID-19 pandemic. Methods Annual survey data with 12,000 to 15,000 households were included. Wasting was estimated for children 6 to 59 months using the WHO child growth standards, and among women 15 to 49 years, thinness was defined as mid-upper arm circumference <23 cm. Trends were stratified by agroecological zone, and chi-square tests used to assess statistical significance. Simple and multivariate logistic regression models were conducted for 2020 and 2021 to identify risk factors of wasting and thinness. Results About 11,958 to 17,897 children and 9883 to 15,535 women contributed values each year. National wasting and thinness rates did not significantly decrease over the 7-year period (wasting: 14.1% to 12.1%, P = .43; thinness: 15.2% to 13.4%, P = .51) and wasting rose from 2020 to 2021. The Saharan and Sahelian zones had consistently higher rates compared to the Sudanian zone. Younger age, male sex, inadequate infant and young child feeding practices, and poorer household socio-economic factors were associated with greater odds of child wasting. For women, younger age, lack of nutrition knowledge, and poorer household socio-economic factors increased the odds of thinness. Conclusions Undernutrition in Chad has not improved since 2015, and the COVID-19 pandemic likely exacerbated the crisis among children nationally and among women subnationally. Multisectoral approaches and regional targeting of interventions are recommended.

Background: Cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) are altered many years before the onset of clinical symptoms of mild cognitive impairment (MCI). Incorporating clinical symptom onset time into biomarker modeling may enhance our understanding of changes preceding MCI. Objective: Using a new analytical approach, we examined patterns of biomarker change prior to MCI symptom onset among individuals who progressed from normal cognition to MCI, stratified based on the age of symptom onset. We also analyzed biomarker patterns of change among participants who remained cognitively normal, and examined potential modifiers of biomarker trajectories, including demographics and apolipoprotein E (APOE) status. Methods: Analyses included 93 participants who progressed from normal cognition to MCI and 186 participants who remained cognitively normal, over an average follow-up period of 16.2 years. CSF biomarkers, including Aβ 42, Aβ 40, total tau (t-tau), and phosphorylated tau181 (p-tau181), were measured using the fully automated Lumipulse assays. Results: Among participants who progressed to MCI, Aβ 42/Aβ40 decreased, and t-tau and p-tau181 increased. For participants who did not progress to MCI, CSF biomarkers showed relatively stable patterns. In both progressors and non-progressors, APOE4 carriers showed lower Aβ 42/Aβ40 levels (compared to non-carriers) at each point of the mean curves. Among non-progressors, APOE4 carriers had higher levels of p-tau181, p-tau181/(Aβ 42/Aβ40), and t-tau/(Aβ 42/Aβ 40). Additionally, among those who did not progress, female sex was associated with higher levels of t-tau, p-tau181, t-tau/(Aβ 42/Aβ 40), and p-tau181/(Aβ 42/Aβ 40). Conclusions: These findings suggest that this analytic approach may provide additional insights into biomarker changes during early phases of AD.

Background Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure. Methods We developed an agent-based, household-structured TB and MDR/RR-TB transmission model, calibrated to an illustrative setting in India. We simulated contact investigation in households of patients with MDR/RR-TB, comparing an MDR/RR-TPT regimen (assuming 6-month duration, 70% efficacy) and associated active case finding against alternatives of contact investigation without TPT or no household intervention. We simulated the TB and MDR/RR-TB incidence averted relative to placebo over two years, as measurable by a typical trial, as well as the incidence averted over a longer time horizon, in the broader population, and relative to no contact investigation. Results Observing TPT and placebo recipients for two years as in a typical trial, MDR/RR-TPT was measured to prevent 72% [Interquartile range: 45–100%] of incident MDR/RR-TB among recipients; median number-needed-to-treat to prevent one MDR/RR-TB case was 73, compared to placebo. This number-needed-to-treat decreased to 54 with 13-18 years of observation, to 27 when downstream transmission effects were also considered, and to 12 when the effects of active TB screening were included by comparing to a no-household-contact-intervention scenario. Conclusions If forthcoming trial results demonstrate efficacy, the long-term population impact of TPT for MDR/RR-TB – including the large effect of increased active TB detection among MDR/RR-TB contacts – could be much greater than suggested by trial outcomes alone.

Intersecting forms of stigma including both HIV and sex work stigma have been known to impede HIV prevention and optimal treatment outcomes among FSW. Recent research has indicated that intersectional stigma can be resisted at the community and individual level. We assessed pathways between HIV stigma, sex work stigma, social cohesion and viral suppression among a cohort of 210 FSW living with HIV in the Dominican Republic. Through Poisson regression we explored the relationship between HIV outcomes and internalized, anticipated and enacted HIV and sex work stigma, and resisted sex work stigma. We employed structural equation modeling to explore the direct effect of various forms of stigma on HIV outcomes, and the mediating effects of multi-level stigma resistance including social cohesion at the community level and occupational dignity at the individual level. 76.2% of FSW were virally suppressed and 28.1% had stopped ART at least once in the last 6 months. ART interruption had a significant negative direct effect on viral suppression (OR = 0.26, p < 0.001, 95% CI: 0.13–0.51). Social cohesion had a significant positive direct effect on viral suppression (OR = 2.07, p = 0.046, 95% CI: 1.01–4.25). Anticipated HIV stigma had a significant negative effect on viral suppression (OR = 0.34, p = 0.055, 95% CI: 0.11–1.02). This effect was mediated by the interaction between cohesion and dignity which rendered the impact of HIV stigma on viral suppression not significant. Findings demonstrate that while HIV stigma has a negative impact on viral suppression among FSW, it can be resisted through individual and collective means. Results reinforce the importance of community-driven, multi-level interventions.

Positive psychological interventions (PPIs) are activities that target positive variables (e.g., gratitude or kindness) to elicit a positive response in a population, such as improving adaptive functioning, promoting well-being, reducing depression, or enhancing quality of life. Despite several decades of evidence, a meta-analysis by White et al. (2019) concluded that the effect sizes of PPIs may be smaller than previously recorded and that their effects on depression may be generally nonsignificant. In the current study, we created a new PPI, called the Best-Self PPI (BS-PPI), to provide a proof-of-concept of two relatively unexplored properties of PPIs that may enhance effect sizes, which are: (1) combining PPI domains (i.e., multiple targeted positive variables) into a single intervention and (2) designing PPIs to target cognitive mechanisms of change. Using a double-masked procedure, we randomly assigned undergraduate students (n = 133) between the ages of 18 and 32 (Mage = 19.97, SD = 1.66; women; n = 85, 63.9%; White: n = 87, 65.41%) to complete either the BS-PPI – containing elements of meaning, character strengths, and optimism – or a control condition before completing measures of depression, psychological well-being, and affect. One day later, the participants completed a measure of affect and the Self-Referential Encoding Task, a behavioral measure of self-referential processing bias, which is the strength and the valance of the words one uses to describe oneself, to test the potential of targeting a cognitive mechanism of change. One week later, participants completed measures of depression, psychological well-being, and affect. The results suggest the BS-PPI did not affect depression, well-being, or affect compared to the control group despite the consistency of this study with many other PPI studies (e.g., sample size, design, and population), which aligns with the White et al. (2019) meta-analysis. We discuss the implications of this failed proof-of-concept for PPI research and recommendations for moving forward with these relatively unexplored properties.