Concordance and Discordance Between Patient-reported Remission, Patient-reported Outcomes, and Physician Global Assessment.

BACKGROUND: Although validated patient-reported outcome (PRO) measurements can categorize patients with inflammatory bowel disease (IBD) into clinical remission or active disease, patients may have different definitions of remission. The purpose of this study was to compare patient-defined remission to remission based on PRO measures and physician global assessment (PGA) and to understand the clinical and demographic factors associated with disagreements. METHODS: We retrospectively analyzed 3257 de-identified surveys from 2004 IBD patients who consented to participate in the Crohn's and Colitis Foundation's IBD Qorus Learning Health System between September 2019 and February 2021. We used logistic regression models with generalized estimating equations to analyze the clinical and demographic factors (eg, age, disease duration, health confidence) associated with discordance between patient-defined remission (yes/no) and PRO-defined remission for ulcerative colitis (UC; PRO2: stool frequency, rectal bleeding) and Crohn's disease (CD; PRO-3: average number of liquid stools, abdominal pain, well-being). RESULTS: Among patients with UC, overall concordance was 79% between patient self-report and PRO2-defined remission and 49% between patient self-report and PGA-defined remission. Among patients with CD, overall concordance was 69% between patient self-report and PRO3-defined remission and 54% between patient self-report and PGA-defined remission. Patients in PRO-defined remission were more likely to report active disease if they had IBD <5 years and low health confidence. Patients with PRO-defined active disease were more likely to report remission if they were not using prednisone and had high health confidence. CONCLUSION: Discordance exists between how remission is defined by patients, PRO measures, and PGA.

Discordance between patients' self-reported remission and remission defined based on patient-reported outcomes was observed in 31% of Crohn's disease visits and 21% of ulcerative colitis visits. Disease duration and health confidence were associated with discordance.

Age-specific burden of cervical cancer associated with HIV: A global analysis with a focus on sub-Saharan Africa.

HIV substantially worsens human papillomavirus (HPV) carcinogenicity and contributes to an important population excess of cervical cancer, particularly in sub-Saharan Africa (SSA). We estimated HIV- and age-stratified cervical cancer burden at a country, regional and global level in 2020. Proportions of cervical cancer (a) diagnosed in women living with HIV (WLHIV), and (b) attributable to HIV, were calculated using age-specific estimates of HIV prevalence (UNAIDS) and relative risk. These proportions were validated against empirical data and applied to age-specific cervical cancer incidence (GLOBOCAN 2020). HIV was most important in SSA, where 24.9% of cervical cancers were diagnosed in WLHIV, and 20.4% were attributable to HIV (vs 1.3% and 1.1%, respectively, in the rest of the world). In all world regions, contribution of HIV to cervical cancer was far higher in younger women (as seen also in empirical series). For example, in Southern Africa, where more than half of cervical cancers were diagnosed in WLHIV, the HIV-attributable fraction decreased from 86% in women ≤34 years to only 12% in women ≥55 years. The absolute burden of HIV-attributable cervical cancer (approximately 28 000 cases globally) also shifted toward younger women: in Southern Africa, 63% of 5341 HIV-attributable cervical cancer occurred in women <45 years old, compared to only 17% of 6901 non-HIV-attributable cervical cancer. Improved quantification of cervical cancer burden by age and HIV status can inform cervical cancer prevention efforts in SSA, including prediction of the impact of WLHIV-targeted vs general population approaches to cervical screening, and impact of HIV prevention.

The association between three key social determinants of health and life dissatisfaction: A 2017 behavioral risk factor surveillance system analysis.

Poor health outcomes disproportionately impact certain populations in the United States owing to the inequitable distribution of social determinants of health (SDOH). Using the 2017 Behavioral Risk Factor Surveillance System (BRFSS), we estimated the association of three adverse SDOH (housing insecurity, food insecurity, and financial instability) with life dissatisfaction. Participants were from Wisconsin, Minnesota, and Ohio, the only states that included the SDOH and Emotional Support and Life Satisfaction modules (n = 25,850). Six percent of respondents reported life dissatisfaction. Those who reported housing insecurity (Prevalence difference (PD) = 14.2 per 100, 95% CI [7.6, 20.7]), food insecurity (PD = 10.9 [7.1, 14.7]), and financial instability (PD = 5.6 [4.9, 6.3]) had higher prevalence of life dissatisfaction. The differences in prevalence of life dissatisfaction, comparing those with and without an adverse SDOH, decreased with increased emotional support (for housing insecurity, food insecurity, and financial instability, respectively: low support, PD = 30.2 [11.6, 48.8], 22.1 [11.6, 32.6], 16.4 [12.0, 20.8]; high support, PD = 4.8 [-2.9, 12.6], 4.8 [0.0, 9.7], 1.7 [1.1, 2.3]). Participants with frequent mental distress (FMD) had greater prevalence differences than those without FMD (for housing insecurity, food insecurity, and financial instability, respectively: with FMD, PD = 15.4 [7.5, 23.3], 10.7 [4.7, 16.7], 14.4 [9.6, 19.3]; without FMD, PD = 6.1 [-0.5, 12.5], 5.3 [1.6, 9.0], 2.5 [2.0, 3.0]). Social determinants may not only influence physical health but also have an impact on psychological well-being. This impact may be altered by levels of emotional support and FMD.

Early Child Development Assessments and Their Associations with Long-Term Academic and Economic Outcomes: A Systematic Review.

Developmental screening instruments were designed as diagnostic tools, but there is growing interest in understanding whether select tools can also be used systematically in research to examine intervention impacts on long-term outcomes. As such, this systematic review aims to examine associations between child development assessment tools and educational attainment, academic achievement, or wealth. We included studies identified in PubMed, PsycINFO, and Educational Resources Information Center if they reported an association between at least one tool from a pre-established list and one outcome of interest after age 10. Of 597 studies identified, 11 met inclusion criteria; three examined educational attainment as the outcome of interest, six examined academic achievement, one wealth, and one both educational attainment and wealth. Intelligence tests were utilized in five of the included studies, neuropsychological/executive function or behavior tools were used in five, and one study used tools across the domains. High-quality studies were identified across all three of the domains, but educational attainment and wealth had the greatest proportion of high-quality studies, as compared to academic achievement. Our review demonstrates the potential for certain child development assessment tools to adequately assess long-term outcomes of interest, but additional prospective studies using validated, culturally appropriate tools are needed. PROSPERO registration number: CRD42018092292.

Assessment of the Feasibility and Acceptability of Using Water Pasteurization Indicators to Increase Access to Safe Drinking Water in the Peruvian Amazon.

Approximately two billion people lack access to microbiologically safe drinking water globally. Boiling is the most popular household water treatment method and significantly reduces diarrheal disease, but is often practiced inconsistently or ineffectively. The use of low-cost technologies to improve boiling is one approach with potential for increasing access to safe drinking water. We conducted household trials to evaluate the feasibility and acceptability of water pasteurization indicators (WAPIs) in the Peruvian Amazon in 2015. A total of 28 randomly selected households were enrolled from a rural and a peri-urban community. All households trialed two WAPI designs, each for a 2-week period. Ninety-six percent of participants demonstrated the correct use of the WAPIs at the end of each trial, and 88% expressed satisfaction with both WAPI models. Ease of use, short treatment time, knowledge of the association between WAPI use and improved health, and the taste of treated water were among the key factors that influenced acceptability. Ease of use was the key factor that influenced design preference. Participants in both communities preferred a WAPI with a plastic box that floated on the water's surface compared with a WAPI with a wire that was dipped into the pot of drinking water while it was heating (77% versus 15%, P < 0.001); we selected the box design for a subsequent randomized trial of this intervention. The high feasibility and acceptability of the WAPIs in this study suggest that these interventions have potential to increase access to safe water in resource-limited settings.

Perspectives on the Future of Epidemiology: A Framework for Training.

Over the past century, the field of epidemiology has evolved and adapted to changing public health needs. Challenges include newly emerging public health concerns across broad and diverse content areas, new methods, and vast data sources. We recognize the need to engage and educate the next generation of epidemiologists and prepare them to tackle these issues of the 21st century. In this commentary, we suggest a skeleton framework upon which departments of epidemiology should build their curriculum. We propose domains that include applied epidemiology, biological and social determinants of health, communication, creativity and ability to collaborate and lead, statistical methods, and study design. We believe all students should gain skills across these domains to tackle the challenges posed to us. The aim is to train smart thinkers, not technicians, to embrace challenges and move the expanding field of epidemiology forward.

Projected impact and cost-effectiveness of community-based versus targeted azithromycin administration strategies for reducing child mortality in sub-Saharan Africa.

BACKGROUND: Trials of mass drug administration (MDA) of azithromycin (AZM) report reductions in child mortality in sub-Saharan Africa (SSA). AZM targeted to high-risk children may preserve benefit while minimizing antibiotic exposure. We modeled the cost-effectiveness of MDA to children 1-59 months of age, MDA to children 1-5 months of age, AZM administered at hospital discharge, and the combination of MDA and post-discharge AZM. METHODS AND FINDINGS: Models employed a payer perspective with a 1-year time horizon. Cost-effectiveness was presented as cost per DALY averted and death averted, with probabilistic sensitivity analyses. The model included parameters for macrolide resistance, adverse events, hospitalization, and mortality sourced from published data. Assuming a base-case 1.64% mortality risk among children 1-59 months old, 3.1% among children 1-5 months old, 4.4% mortality risk post-discharge, and 13.5% mortality reduction per trial data, post-discharge AZM would avert ~45,000 deaths, at a cost of $2.84/DALY (95% uncertainty interval [UI]: 1.71-5.57) averted. MDA to only children 1-5 months old would avert ~186,000 deaths at a cost of $4.89/DALY averted (95% UI: 2.88-11.42), MDA to all under-5 children would avert ~267,000 deaths a cost of $14.26/DALY averted (95% UI: 8.72-27.08). Cost-effectiveness decreased with presumed diminished efficacy due to macrolide resistance. CONCLUSIONS: Targeting AZM to children at highest risk of death may be an antibiotic-sparing and cost-effective, or even cost-saving, strategy to reduce child mortality. However, targeted AZM averts fewer absolute deaths and may not reach all children who would benefit. Any AZM administration decision must consider implications for antibiotic resistance.

Prevalence, predictors, and management of advanced HIV disease among individuals initiating ART in Senegal, West Africa.

BACKGROUND: The WHO guidelines for the management of advanced HIV disease recommend a package of care consisting of rapid initiation of antiretroviral therapy (ART), enhanced screening and diagnosis of tuberculosis (TB) and cryptococcal meningitis, co-trimoxazole prophylaxis, isoniazid preventive therapy (IPT), fluconazole pre-emptive therapy, and adherence support. The goals of this study were to determine the prevalence of advanced HIV disease among individuals initiating ART in Senegal, to identify predictors of advanced disease, and to evaluate adherence to the WHO guidelines. METHODS: This study was conducted among HIV-positive individuals initiating ART in Dakar and Ziguinchor, Senegal. Clinical evaluations, laboratory analyses, questionnaires and chart review were conducted. Logistic regression was used to identify predictors of advanced disease. RESULTS: A total of 198 subjects were enrolled; 70% were female. The majority of subjects (71%) had advanced HIV disease, defined by the WHO as a CD4 count < 200 cells/mm3 or clinical stage 3 or 4. The median CD4 count was 185 cells/mm3. The strongest predictors of advanced disease were age ≥ 35 (OR 5.80, 95%CI 2.35-14.30) and having sought care from a traditional healer (OR 3.86, 95%CI 1.17-12.78). Approximately one third of subjects initiated ART within 7 days of diagnosis. Co-trimoxazole prophylaxis was provided to 65% of subjects with CD4 counts ≤350 cells/mm3 or stage 3 or 4 disease. TB symptom screening was available for 166 subjects; 54% reported TB symptoms. Among those with TB symptoms, 39% underwent diagnostic evaluation. Among those eligible for IPT, one subject received isoniazid. No subjects underwent CrAg screening or received fluconazole to prevent cryptococcal meningitis. CONCLUSIONS: This is the first study to report an association between seeking care from a traditional healer and presentation with WHO defined advanced disease in sub-Saharan Africa. Given the widespread use of traditional healers in sub-Saharan Africa, future studies to further explore this finding are indicated. Although the majority of individuals in this study presented with advanced disease and warranted management according to WHO guidelines, there were numerous missed opportunities to prevent HIV-associated morbidity and mortality. Programmatic evaluation is needed to identify barriers to implementation of the WHO guidelines and enhanced funding for operational research is indicated.

"Improved" But Not Necessarily Safe: An Assessment of Fecal Contamination of Household Drinking Water in Rural Peru.

The indicator used to measure progress toward the Millennium Development Goal (MDG) for water is access to an improved water supply. However, improved supplies are frequently fecally contaminated in developing countries. We examined factors associated with Escherichia coli contamination of improved water supplies in rural Pisco province, Peru. A random sample of 207 households with at least one child less than 5 years old was surveyed, and water samples from the source and storage container were tested for E. coli contamination. Although over 90% of households used an improved water source, 47% of source and 43% of stored water samples were contaminated with E. coli. Pouring or using a spigot to obtain water from the storage container instead of dipping a hand or object was associated with decreased risk of contamination of stored water (adjusted prevalence ratio [aPR] = 0.58, 95% confidence interval [CI] = 0.42, 0.80). Container cleanliness (aPR = 0.67, 95% CI = 0.45, 1.00) and correct handwashing technique (aPR = 0.62, 95% CI = 0.42, 0.90) were also associated with decreased contamination risk. These findings highlighted the limitations of improved water supplies as an indicator of safe water access. To ensure water safety in the home, household water treatment and improved hygiene, water handling, and storage practices should be promoted.

Analysis of liquid bead microarray antibody assay data for epidemiologic studies of pathogen-cancer associations.

BACKGROUND: Liquid bead microarray antibody (LBMA) assays are used to assess pathogen-cancer associations. However, studies analyze LBMA data differently, limiting comparability. METHODS: We generated 10,000 Monte Carlo-type simulations of log-normal antibody distributions (exposure) with 200 cases and 200 controls (outcome). We estimated type I error rates, statistical power, and bias associated with t-tests, logistic regression with a linear exposure and with the exposure dichotomized at 200 units, 400 units, the mean among controls plus two standard deviations, and the value corresponding to the optimal sensitivity and specificity. We also applied these models, and data visualizations (kernel density plots, receiver operating characteristic (ROC) curves, predicted probability plots, and Q-Q plots), to two empirical datasets to assess the consistency of the exposure-outcome relationship. RESULTS: All strategies had acceptable type I error rates (0.03 ≤ P ≤ 0.048), except for the dichotomization according to optimal sensitivity and specificity, which had a type I error rate of 0.27. Among the remaining methods, logistic regression with a linear predictor (Power=1.00) and t-tests (Power=1.00) had the highest power to detect a mean difference of 1.0 MFI (median fluorescence intensity) on the log scale and were unbiased. Dichotomization methods upwardly biased the risk estimates. CONCLUSION: These results indicate that logistic regression with linear predictors and unpaired t-tests are superior to logistic regression with dichotomized predictors for assessing disease associations with LBMA data. Logistic regression with continuous linear predictors and t-tests are preferable to commonly used LBMA dichotomization methods.

Care-seeking and appropriate treatment for childhood acute respiratory illness: an analysis of Demographic and Health Survey and Multiple Indicators Cluster Survey datasets for high-mortality countries.

BACKGROUND: Acute lower respiratory illness (ALRI) is a major global cause of morbidity and mortality among children under 5. Antibiotic treatment for ALRI is inexpensive and decreases case fatality, but care-seeking patterns and appropriate treatment vary widely across countries. This study sought to examine patterns of appropriate treatment and estimate the burden of cases of untreated ALRI in high mortality countries. METHODS: This study used cross-sectional survey data from the Phase 5/Phase 6 DHS and MIC3/MICS4 for 39 countries. We analyzed care-seeking patterns and antibiotic treatment based on country-level trends, and estimated the burden of untreated cases using country-level predictors in a general linear model. RESULTS: According to this analysis, over 66 million children were not treated with antibiotics for ALRI in 2010. Overall, African countries had a lower proportion of mothers who sought care for a recent episode of ALRI (41% to 86%) relative to Asian countries (75% to 87%). Seeking any care for ALRI was inversely related to seeking public sector care. Treatment with antibiotics ranged from 8% in Nepal to 87% in Jordan, and was significantly associated with urban residence. CONCLUSIONS: Untreated ALRI remains a substantial problem in high mortality countries. In Asia, the large population numbers lead to a high burden of children with untreated ALRI. In Africa, care-seeking behaviors and access to care issues may lead to missed opportunities to treat children with antibiotics.

Sexually explicit online media and sexual risk among men who have sex with men in the United States.

This study aimed to describe sexually explicit online media (SEOM) consumption among men who have sex with men (MSM) in the United States and examine associations between exposure to unprotected anal intercourse (UAI) in SEOM and engagement in both UAI and serodiscordant UAI. MSM in the U.S. who accessed a men-seeking-men website in the past year (N = 1,170) were recruited online for a cross-sectional, Internet-based survey of sexual risk and SEOM consumption. In the 3 months prior to interview, more than half (57 %) of the men reported viewing SEOM one or more times per day and almost half (45 %) reported that at least half of the SEOM they viewed portrayed UAI. Compared to participants who reported that 0-24 % of the SEOM they viewed showed UAI, participants who reported that 25-49, 50-74, or 75-100 % of the SEOM they viewed portrayed UAI had progressively increasing odds of engaging in UAI and serodiscordant UAI in the past 3 months. As SEOM has become more ubiquitous and accessible, research should examine causal relations between SEOM consumption and sexual risk-taking among MSM as well as ways to use SEOM for HIV prevention.

HIV shedding in the oral cavity: an assessment of HIV type, immunovirologic, demographic and oral factors.

OBJECTIVE: To quantify the prevalence and burden of HIV type 2 (HIV-2) and HIV-1 RNA in the oral cavity of antiretroviral therapy-naive HIV-infected Senegalese individuals and to identify correlates of oral HIV viral loads. DESIGN: A cross-sectional study of 163 HIV-1 and 27 HIV-2-infected antiretroviral therapy-naive Senegalese adults. METHODS: Participants received clinical and oral exams and provided blood and oral wash samples for viral load and plasma CD4 count ascertainment. Logistic and interval regression models were used to identify univariate and multivariable associations between presence and level of oral HIV RNA and various immunovirologic, local and demographic factors. RESULTS: Presence of detectable oral HIV RNA was less common in HIV-2-infected compared with HIV-1-infected study participants (33% vs 67%, OR 0.25, 95% CI 0.11 to 0.59). HIV type was no longer associated with oral shedding of HIV when plasma viral load was considered. Detection of oral HIV RNA was associated with increased plasma viral load in both HIV-1-infected and HIV-2-infected individuals (HIV-1, OR 1.89, 95% CI 1.24 to 2.61; HIV-2, OR 1.93, 95% CI 1.1 to 3.39). Oral HIV-1 detection was also associated with periodontal disease (OR 3.02, 95% CI 1.16 to 7.87). CONCLUSIONS: Oral shedding of HIV-2 RNA is less common than HIV-1 RNA, a likely consequence of lower overall viral burden. Both systemic and local factors may contribute to shedding of HIV in the oral cavity.

Stochastic models to demonstrate the effect of motivated testing on HIV incidence estimates using the serological testing algorithm for recent HIV seroconversion (STARHS).

OBJECTIVES: To produce valid seroincidence estimates, the serological testing algorithm for recent HIV seroconversion (STARHS) assumes independence between infection and testing, which may be absent in clinical data. STARHS estimates are generally greater than cohort-based estimates of incidence from observable person-time and diagnosis dates. The authors constructed a series of partial stochastic models to examine whether testing motivated by suspicion of infection could bias STARHS. METHODS: One thousand Monte Carlo simulations of 10,000 men who have sex with men were generated using parameters for HIV incidence and testing frequency from data from a clinical testing population in Seattle. In one set of simulations, infection and testing dates were independent. In another set, some intertest intervals were abbreviated to reflect the distribution of intervals between suspected HIV exposure and testing in a group of Seattle men who have sex with men recently diagnosed as having HIV. Both estimation methods were applied to the simulated datasets. Both cohort-based and STARHS incidence estimates were calculated using the simulated data and compared with previously calculated, empirical cohort-based and STARHS seroincidence estimates from the clinical testing population. RESULTS: Under simulated independence between infection and testing, cohort-based and STARHS incidence estimates resembled cohort estimates from the clinical dataset. Under simulated motivated testing, cohort-based estimates remained unchanged, but STARHS estimates were inflated similar to empirical STARHS estimates. Varying motivation parameters appreciably affected STARHS incidence estimates, but not cohort-based estimates. CONCLUSIONS: Cohort-based incidence estimates are robust against dependence between testing and acquisition of infection, whereas STARHS incidence estimates are not.

Lower levels of HIV-2 than HIV-1 in the female genital tract: correlates and longitudinal assessment of viral shedding.

BACKGROUND: The differing magnitude of the HIV-1 and HIV-2 epidemics is likely a consequence of differing transmission rates between the two viruses. Similar to other sexually transmitted pathogens, risk of HIV-1 and HIV-2 transmission is likely associated with the presence and amount of HIV in the genital tract. Thus, understanding patterns of, and risk factors for HIV genital tract shedding is critical to effective control of HIV transmission. METHODS: We evaluated HIV DNA and RNA detection in cervicovaginal specimens among 168 HIV-1 and 50 HIV-2-infected women in Senegal, West Africa. In a subset of 31 women (20 with HIV-1, 11 with HIV-2), we conducted a prospective study in which cervicovaginal specimens were taken at 3-day intervals over a 6-week period. RESULTS: We found significantly lower rates and levels of HIV-2 RNA (58% shedding; 13% with >1000 copies/ml) in the female genital tract than HIV-1 RNA (78% shedding; 40% with >1000 copies/ml) (P = 0.005 and 0.005, respectively), and shedding correlated with plasma viral load irrespective of virus type (odds ratio = 1.9, 95% confidence interval = 1.3-2.8 for each log10 increase in HIV viral RNA). Plasma viral load, not HIV type, was the strongest predictor of genital viral load. Over 80% of closely monitored women, regardless of HIV type, had at least intermittent HIV RNA detection during every 3-day sampling over a 6-week time period. CONCLUSION: These data help in explaining the different transmission rates between HIV-1 and HIV-2 and may provide new insights regarding prevention.

Longitudinal assessment of infecting serovars of Chlamydia trachomatis in Seattle public health clinics: 1988-1996.

BACKGROUND: There have been few longitudinal studies of fluctuations in the prevalence of Chlamydia trachomatis serovars in a given community; such studies could improve our understanding of the epidemiology and transmission of C trachomatis. STUDY DESIGN: This was a longitudinal study of 7110 female patients (62%) and 4344 male patients (38%) presenting with first-time infections to health department clinics between 1988 and 1996. GOAL: The goal was to ascertain trends in the proportion of infecting serovars over the 9-year study period and determine independent relationships between serovar and age, gender, race, and year of infection. RESULTS: Serovar E was the most prevalent (32%), followed by F (18%) and D (13%). Being female, African American, and infected with serovar B was associated with young age (P < 0.001, P < 0.001, and P = 0.09, respectively). Class C serovars were found in older patients (P < 0.001). Over the 9-year period, the percentage of infections with serovar types F and G increased (P = 0.007, P = 0.009), those with I and K decreased (P < 0.001, P = 0.008), and those with B, D, D-, E, H, Ia, and J remained stable. The age of those with positive Chlamydia cultures decreased (P < 0.001). CONCLUSION: In this population, while the major serovars appeared stable over 9 years, significant changes in the distribution of minor serovars, especially G, were observed over time.