Johns Hopkins Bloomberg School of Public Health

BACKGROUND: Cigarette smoking has been associated with incident heart failure (HF). However, the association between cigarette smoking and smoking cessation with HF subtypes has not been well elucidated, particularly among Black people. METHODS AND RESULTS: We investigated 4189 (never smoker n=2934, former smoker n=761, current smoker n=464) Black participants (mean age 54 years, 64% women) without a history of HF or coronary heart disease at baseline in the Jackson Heart Study. We examined the association of cigarette smoking with incident HF hospitalization and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction). After adjustment for confounding factors, current smoking was associated with incident HF (both subtypes) compared with never smoking. Smoking intensity among those who identified as currently smoking and smoking burden among those who ever smoked were associated with higher incidence of HF with preserved ejection fraction compared with never smoking. Lung function evaluated by spirometry at baseline did not significantly influence these associations. The risk of developing HF decreased with more years after smoking cessation, and more than 20 years of smoking cessation were required to reach a risk comparable to that of never smoking. CONCLUSIONS: Smoking cigarettes was associated with developing both subtypes of HF and it was independent from the influences on baseline lung function. Long-term smoking cessation is necessary to prevent the onset of HF in people who smoke cigarettes.

Synopsis This study investigates the association between forced displacement and the experience of menstrual shame, highlighting age and current displacement as influential factors of menstrual wellbeing amidst humanitarian crises.

Background The outcome of kidney transplant recipients with a history of complement-mediated thrombotic microangiopathy (cTMA) and those who develop post-transplant de novo TMA (dnTMA) is largely unknown. Methods We retrospectively studied all kidney transplant recipients with end-stage kidney disease secondary to cTMA and those who developed dnTMA, between Jan 2000 and Dec 2020 in our center. Results We identified 134 patients, 22 with cTMA and 112 had dnTMA. Patients with cTMA were younger at the time of TMA diagnosis (age at diagnosis, 28.9 ± 16.3. vs 46.5 ± 16.0 years; P < 0.001). T-cell mediated rejection, borderline rejection, and calcineurin inhibitor toxicity were more prevalent in the first kidney transplant biopsy (P < 0.05) in the dnTMA group, and antibody-mediated rejection was more prevalent in anytime-biopsy (P = 0.027). After adjusting for potential confounders, cTMA was associated with a sixfold increase in the hazard of transplant failure during the first-year post-transplant (adjusted hazard ratio (aHR): 6.37 [95%CI: 2.17 to18.68; P = 0.001]; the aHR decreased by 0.87 (95% CI: 0.76 to 0.99: P = 0.033) per year elapsed since transplantation. Long-term allograft survival was similar in both groups. Conclusion Post kidney transplant TMA is an important cause of poor allograft survival. More studies are needed to enhance our understanding and management of this disorder.

Background The migration of healthcare professionals from developing countries to more developed nations poses a significant challenge to healthcare systems in low- and middle-income countries. This study aimed to determine the proportion of doctors in Ghana who intend to migrate abroad and to identify the sociodemographic and "pull and push" factors that influence their intention. Methodology A cross-sectional survey was conducted among doctors in Ghana between March 1, 2024, and March 15, 2024, via an online-based semi-structured questionnaire. Doctors working in Ghana, regardless of nationality, were included. Descriptive statistics and logistic regression analyses were conducted to identify factors associated with the intention to emigrate. Statistical significance was set at a p-value of < 0.05. Results Almost all the doctors who responded to the questionnaire consented to participate (99.4%, 641/645). More than half (53.8%, n = 345) of the respondents were medical officers. Most respondents intended to migrate to practice abroad (71.8%, n = 460). The United States (59.7%), the United Kingdom (39.1%), and Canada (34.8%) were the most preferred destinations. After adjusting for covariates, young doctors between 20–29 years [(Adjusted Odd Ratios) AOR = 2.69, 95% CI = 1.13—6.39)], male doctors (AOR = 1.53, 95% CI = 1.04—2.25), doctors in lower professional ranks, and doctors in the field of diagnostics (AOR = 5.70, 95% CI = 1.16 – 28.03) had significantly higher odds of intending to migrate. In descending order of magnitude, the respondents strongly agreed that better remuneration (1.22 ± 0.63), better quality of life (1.22 ± 0.67), better working conditions (1.26 ± 0.69), and better postgraduate training (1.41 ± 0.80) were pull factors. The push factors were economic challenges (1.17 ± 0.49), a lack of a conducive working environment (1.56 ± 0.86), slow career progression (1.95 ± 1.07), excessive workload (2.07 ± 0.12), personal circumstances (2.26 ± 1.19), and poor postgraduate training (2.48 ± 1.22). Conclusion A substantial proportion of doctors in Ghana are considering emigration, driven by a combination of attractive opportunities abroad and challenging conditions in Ghana. Addressing these issues through improved remuneration, better working environments, and enhanced career development and training opportunities is crucial to retaining healthcare professionals.

Aims To assess the association of traditional risk factor burden and Life’s Simple 7 (LS7) score with incident atherosclerotic cardiovascular disease (ASCVD) across Lp(a) levels. Methods There were 6,676 participants without clinical ASCVD from the Multi-Ethnic Study of Atherosclerosis who underwent Lp(a) testing and were followed for incident ASCVD events (coronary heart disease and stroke). Low, intermediate, and elevated Lp(a) were defined as <30, 30-49, and >50 mg/dL, respectively. Cox proportional hazards regression assessed the association of traditional risk factors and LS7 score (poor: 0-8, average: 9-10, optimal: 11-14) with incident ASCVD across Lp(a) groups during a median follow-up of 17.7 years, adjusting for demographics and time-varying statin and aspirin therapy. Results The mean age was 62.1 years, 53% were women, and 61% were non-white. The median Lp(a) was 17 (IQR 8-41) mg/dL, 13% had Lp(a) 30-49 mg/dL, and 20% had Lp(a) >50 mg/dL. Individuals with Lp(a) >50 mg/dL had higher absolute event rates across all LS7 categories. There was no significant interaction between Lp(a) and LS7 score on incident ASCVD (p-interaction=0.60). Compared to a poor LS7 score, optimal LS7 conferred a lower risk for incident ASCVD among individuals with Lp(a) <30 (HR=0.45, 95% CI: 0.28-0.71), Lp(a) 30-49 (HR=0.12, 95% CI: 0.02-0.89), and Lp(a) >50 mg/dL (HR=0.35, 95% CI: 0.13-0.99). Conclusion Participants without clinical ASCVD who achieved an optimal LS7 score had ASCVD risk reduction regardless of Lp(a) level. These results emphasize the importance of a healthy lifestyle and ASCVD risk factor control among individuals with elevated Lp(a).

We studied cervicovaginal β-/γ-human papillomavirus (HPV) and their relationship to cervical precancer in women with HIV (WWH); having previously reported strong positive associations of β-/γ-HPV with incident head and neck cancer in the general population. Cases (N=124) had cervical intraepithelial neoplasia (CIN)-3 or CIN-2. Controls (N=247) were individually matched 2:1 to cases. Unexpectedly, multivariate analyses found strong inverse associations between β-/γ-HPV and CIN-2/CIN-3 (OR=0.19; 95% CI 0.04-0.86; P=0.03) with Ptrend<0.01. This is, to our knowledge, the first study of β-/γ-HPV and cervical precancer. If confirmed, a strong inverse (protective) association would be of potential clinical and biologic relevance.

Cryptococcus is a genus of saprophytic fungi with global distribution. Two species complexes, Cryptococcus neoformans and Cryptococcus gattii , pose health risks to humans and animals. Cryptococcal infections result from inhalation of aerosolized spores and/or desiccated yeasts from terrestrial reservoirs such as soil and trees. More recently, C. gattii has been implicated in infections in marine mammals, suggesting that inhalation of cells from the air-water interface is also an important, yet understudied, mode of respiratory exposure. Based on historical records and epidemiological factors, water transport has been hypothesized to play a role in the spread of C. gattii from tropical to temperate environments. However, the dynamics of fungal persistence and transport in water have not been fully studied. The size of the cryptococcal capsule was previously shown to reduce cell density and increase buoyancy. Here, we demonstrate that cell buoyancy is also impacted by the salinity of the solution in which cells are suspended, with the formation of a halocline significantly slowing the rate of settling and resulting in persistence of C. neoformans within 1 cm of the water surface for over 60 min and C. gattii for 4–6 h. During the culture of three strains of C. gattii in yeast peptone dextrose media, we also identified aggregates of extracellular polysaccharide with complex structures, which we hypothesize from rafts that entrap cells and augment buoyancy. These findings illustrate new mechanisms by which cryptococcal cells may persist in aquatic environments, with important implications for aqueous transport and pathogen exposure. IMPORTANCE Cryptococcosis is a major fungal disease leading to morbidity and mortality worldwide. Cryptococcus neoformans is a major fungal species of public health concern, causing opportunistic systemic infections in immunocompromised patients. Cryptococcus gattii was traditionally a pathogenic fungus confined primarily to tropical regions, but in the 1990s, it emerged in the temperate climates of British Columbia, Canada and the Pacific Northwest of the United States. Outbreaks in these areas also led to the first host record of cryptococcosis in free-ranging cetaceans. C. gattii is particularly concerning as an emerging fungal pathogen due to its capacity to cause clinical disease in immunocompetent patients, its recent spread to a new ecological niche, and its higher resistance to antifungal therapies. Our research defines fungal characteristics that influence the transport of cryptococci through water and persistence of fungal cells near the water surface, improving our understanding of potential mechanisms for cryptococcal environmental transport.

This study aimed to understand facilitators and barriers to returning to in-person learning for youth, caregivers, and school staff from three communities in the Navajo Nation and the White Mountain Apache Tribe following the 2020 COVID-19-driven school closures. A safe and rapid return to school through effective and acceptable COVID-19 mitigation strategies was vital for students’ social and scholastic development and the resilience of staff and families. We interviewed school staff (n = 36), caregivers of youth ages 4 to 16 (n = 28), and youth ages 11 to 16 (n = 25 from the four communities regarding COVID-19 safety measures, school reopening, and return to in-person learning. Interviews were done by research staff from the same communities and guided by the Theoretical Domains Framework (TDF). A team of local research staff with faculty support from afar, coded interview transcripts using codes based on the TDF and through consensus development of additional emergent codes. Participants found regular COVID-19 testing a suitable alternative to contact tracing and social distancing. While, participants generally acknowledged the safety of testing and vaccinations, they also emphasized the importance of self-determination in adopting these strategies. Protection of family and community were strong motivators for adherence to COVID-19-related safety protocols including engagement in testing or vaccination. All participants were generally motivated to return to in-person learning as virtual learning led to challenges with curricular retention, the provision of academic and non-academic supports, and maintaining social engagement. Virtual learning had effects on caregivers and staff as they took on additional roles amidst virtual learning and pandemic-related demands. Findings from this study are relevant to future pandemic planning and while the findings in the study are highly contextualized, the findings may generalize to other NA communities or other groups who have faced historical maltreatment and ongoing injustices. Maintaining in-person learning is a high priority for stakeholders, and study participants were motivated to participate in additional COVID-19 risk mitigation strategies to return while also protecting more vulnerable people in the community. In many Native American communities, future planning should account for the importance of keeping schools open, while motivating stakeholders to adopt mitigation strategies by emphasizing the greater collective good.

Human papillomavirus (HPV) is a common sexually transmitted pathogen and the infectious cause of HPV-related oropharyngeal carcinoma (HPV-OPC). HPV-OPC is distinct in its pathophysiology, epidemiology, and clinical course from HPV-negative head and neck squamous cell carcinoma (HNSCC). The incidence of HPV-OPC has steadily grown over the past several decades. This rise has been attributed to sexual behaviors that increase exposure to HPV. While intensive investigation is clarifying the risk factors and treatment strategies for HPV-OPC, the natural history of carcinogenic HPV infection in HNSCC and whether HPV-OPC can be prevented remain incompletely understood. This chapter provides an overview of carcinogenic HPV infection, the epidemiology of oral HPV infection, and ongoing efforts to devise early detection and prevention strategies for HPV-OPC.

Introduction Tuberculosis (TB) preventive treatment (TPT) is recommended for people living with HIV (PLHIV) in high TB burden settings. While 6 months of daily isoniazid remains widely used, shorter regimens are now available. However, little is known about preferences of PLHIV for key features of TPT regimens. Methods From July to November 2022, we conducted a discrete choice experiment among adult PLHIV engaged in care at an urban HIV clinic in Kampala, Uganda. Participants chose between two hypothetical TPT regimens with five different features (pills per dose, frequency, duration, need for adjusted antiretroviral therapy [ART] dosage and side effects), organized across nine random choice tasks. We analysed preferences using hierarchical Bayesian estimation, latent class analysis and willingness‐to‐trade simulations. Results Of 400 PLHIV, 392 (median age 44, 72% female, 91% TPT‐experienced) had high‐quality choice task responses. Pills per dose was the most important attribute (relative importance 32.4%, 95% confidence interval [CI] 31.6–33.2), followed by frequency (20.5% [95% CI 19.7–21.3]), duration (19.5% [95% CI 18.6–20.5]) and need for ART dosage adjustment (18.2% [95% CI 17.2–19.2]). Latent class analysis identified three preference groups: one prioritized less frequent, weekly dosing (N = 222; 57%); another was averse to ART dosage adjustment (N = 107; 27%); and the last prioritized short regimens with fewer side effects (N = 63; 16%). All groups highly valued fewer pills per dose. Overall, participants were willing to accept a regimen of 2.8 months’ additional duration [95% CI: 2.4–3.2] to reduce pills per dose from five to one, 3.6 [95% CI 2.4–4.8] months for weekly rather than daily dosing and 2.2 [95% CI 1.3–3.0] months to avoid ART dosage adjustment. Conclusions To align with preferences of PLHIV in Uganda, decision‐makers should prioritize the development and implementation of TPT regimens with fewer pills, less frequent dosing and no need for ART dosage adjustment, rather than focus primarily on duration of treatment.

Background The utilization of Annual Wellness Visits (AWVs), preventive healthcare visits covered by Medicare Part B, has grown steadily since their inception in 2011. However, longitudinal patterns and variations in use across enrollees, providers, and clinics remain poorly understood. Objective This study aimed to analyze AWV usage trends from 2018 to 2022 among a sizable cohort of Medicare beneficiaries, employing electronic health record (EHR) data. The goal was to assess AWV frequency and explore variations across enrollees, providers, and clinics. Design This retrospective observational study utilized EHR data from Medicare beneficiaries aged 66 and above, receiving continuous primary care from 2018 to 2022 ( N = 24,549). Enrollees were classified into three categories based on their AWV utilization over a 5‐year period: low users (0–1 AWVs), moderate users (2–3 AWVs), and regular users (4–5 AWVs). AWV usage patterns were examined across individual demographics and provider/clinic characteristics using multilevel regression models. Key Results Over the 2018–2022 period, 58.6% were regular AWV users, 27.7% were moderate users, and 13.7% were low users. Differences in primary care providers and clinics accounted for 56.4% (95% CI, 45.3%–66.9%) of the variation between low and regular users. Among enrollees who visited the same providers and clinics, individuals were less likely to be regular users of AWVs if they were 85 and older, Hispanic, from socioeconomically disadvantaged areas, or had multiple comorbidities. Conclusions The majority of Medicare beneficiaries in the study engaged with AWVs, with 86% having two or more over the 5‐year period. These findings underscore the broad acceptance of AWVs among beneficiaries but also show that clinic and provider factors influence usage, especially among older, minoritized, and socioeconomically disadvantaged populations. Interventions at the provider and clinic levels are necessary to further improve AWV uptake, particularly for vulnerable groups.

Background Dexamethasone is a steroid used in the treatment of hospitalized patients with severe COVID-19. However, the effect of dexamethasone in patients with SCD remains unclear given that steroids may precipitate vaso-occlusive crisis (VOC) in patients with SCD. Methods and findings We performed a retrospective analysis of patients with SCD who were hospitalized at Johns Hopkins Health System between June 1, 2020 and June 26, 2022. We reviewed individual charts to assess severity of illness and eligibility for dexamethasone treatment. The exposure of interest was treatment with dexamethasone. Outcomes of interest included incident VTE, length of hospital stay, ICU admission, follow up-VOC and mortality. We identified 30 patients with SCD and COVID-19 who were eligible for dexamethasone treatment, 13 of whom received dexamethasone. Dexamethasone was associated with an increased risk of incident VTE (risk difference = 36%; 95% CI 8%, 66%) after adjustment for high-risk genotypes, >3 hospitalizations, and receipt of anticoagulation. There was an increase in the risk difference of ICU admission and an increased length of stay in crude and adjusted analyses however these associations were not statistically significant. Conclusions We analyzed outcomes among patients with SCD who were hospitalized for COVID-19 and eligible for dexamethasone. Our study suggests that in this population, treatment with dexamethasone increases the risk of incident VTE. There was a suggestion of an increased risk of ICU admission as well as increased length of hospitalization; larger studies are needed to confirm these findings.

Background Critically ill hospitalized patients with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized. Methods In a cohort study of 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and more than 20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms. Results Predictive models reveal that IgG binding and ACE2 binding inhibition responses at 1 MPE are positively and anti-Spike antibody-mediated complement activation at enrollment is negatively associated with an increased probability of intubation or death from COVID-19 within 3 MPE. Conclusions At enrollment, serological antibody measures are more predictive than demographic variables of subsequent intubation or death among hospitalized COVID-19 patients.

Objective To estimate the effect of antidepressant initiation on viral non-suppression among people with HIV (PWH) with clinically recognized, untreated depression. Design Retrospective, observational cohort study. Methods We included clinical diagnoses of depression from January 2012-June 2022 among PWH in the Johns Hopkins HIV Clinical Cohort without another serious psychiatric illness who had initiated antiretroviral therapy. We excluded diagnoses less than 90 days from a prior diagnosis, antidepressant prescription, or >1 mental health visits. We estimated the association between initiating an antidepressant within 1 month of the index depression diagnosis and viral load non-suppression (>200 copies/mL) on the first viral load 3–12 months subsequent. We adjusted for a comprehensive set of demographic and clinical confounders. Results We included 2,346 depression diagnoses among 946 patients; patients initiated an antidepressant following 16%. The risk of viral non-suppression in the absence of antidepressant treatment was 15.6% (95% confidence interval [CI]: 13.1, 18.4). Antidepressant initiation was not associated with viral non-suppression (risk difference: 0.5%; 95% CI: -3.7, 4.8) or secondary outcomes: improvement or resolution of depressive symptoms or adherence to scheduled clinic visits. Conclusions In this sample of patients with as-yet-untreated depression, in a setting with co-located, low-barrier psychiatric services, antidepressant treatment was not associated with improved viral suppression. Pharmacologic management of depression has documented benefits in other studies. However, there may be a subset of PWH with depression who have been previously unsuccessfully treated with antidepressants who are less likely to respond to approved pharmacologic options and who require different interventions to improve their viral suppression.