Effect of a male-targeted digital decision support application aimed at increasing linkage to HIV care among men: Findings from the HITS cluster randomized clinical trial in rural South Africa.

Introduction: Linkage to HIV care remains suboptimal among men. We investigated the effectiveness of a male-targeted HIV-specific decision support app, Empowering People through Informed Choices for HIV (EPIC-HIV), on increasing linkage to HIV care among men in rural South Africa. Methods: Home-Based Intervention to Test and Start (HITS) was a multi-component cluster-randomized controlled trial among 45 communities in uMkhanyakude, KwaZulu-Natal. The development of EPIC-HIV was guided by self-determination theory and human-centered intervention design to increase intrinsic motivation to seek HIV testing and care among men. EPIC-HIV was offered in two stages: EPIC-HIV 1 at the time of home-based HIV counseling and testing (HBHCT), and EPIC-HIV 2 at 1 month after positive HIV diagnosis. Sixteen communities were randomly assigned to the arms to receive EPIC-HIV, and 29 communities to the arms without EPIC-HIV. Among all eligible men, we compared linkage to care (initiation or resumption of antiretroviral therapy after >3 months of care interruption) at local clinics within 1 year of a home visit, which was ascertained from individual clinical records. Intention-to-treat analysis was performed using modified Poisson regression with adjustment for receiving another intervention (i.e., financial incentives) and clustering at the community level. We also conducted a satisfaction survey for EPIC-HIV 2. Results: Among all 13,894 eligible men (i.e., ≥15 years and resident in the 45 communities), 20.7% received HBHCT, resulting in 122 HIV-positive tests. Among these, 54 men linked to care within 1 year after HBHCT. Additionally, of the 13,765 eligible participants who did not receive HBHCT or received HIV-negative results, 301 men linked to care within 1 year. Overall, only 13 men received EPIC-HIV 2. The proportion of linkage to care did not differ in the arms assigned to EPIC-HIV compared to those without EPIC-HIV (adjusted risk ratio=1.05; 95% CI:0.86-1.29). All 13 men who used EPIC-HIV 2 reported the app was acceptable, user-friendly, and useful for getting information on HIV testing and treatment. Conclusion: Reach was low although acceptability and usability of the app was very high among those who engaged with it. Enhanced digital support applications could form part of interventions to increase knowledge of HIV treatment for men. Clinical Trial Number: ClinicalTrials.gov # NCT03757104.

The impact of a conditional financial incentive on linkage to HIV care: Findings from the HITS cluster randomized clinical trial in rural South Africa.

Introduction: HIV elimination requires innovative approaches to ensure testing and immediate treatment provision. We investigated the effectiveness of conditional financial incentives on increasing linkage to HIV care in a 2×2 factorial cluster randomized controlled trial-Home-Based Intervention to Test and Start (HITS) - in rural South Africa. Methods: Of 45 communities in uMkhanyakude, KwaZulu-Natal, 16 communities were randomly assigned to the arms to receive financial incentives for home-based HIV counseling and testing (HBHCT) and linkage to care within 6 weeks (R50 [US$3] food voucher each) and 29 communities to the arms without financial incentives. We examined linkage to care (i.e., initiation or resumption of antiretroviral therapy after >3 months of care interruption) at local clinics within 6 weeks of a home visit, the eligibility period to receive the second financial incentive. Linkage to care was ascertained from individual clinical records. Intention-to-treat analysis (ITT) was performed using modified Poisson regression with adjustment for receiving another intervention (i.e., male-targeted HIV-specific decision support app) and clustering of standard errors at the community level. Results: Among 13,894 eligible men (i.e., ≥15 years and resident in the 45 communities), 20.7% received HBHCT, which resulted in 122 HIV-positive tests. Of these, 27 linked to care within 6 weeks of HBHCT. Additionally, of eligible men who did not receive HBHCT, 66 linked to care. In the ITT analysis, the proportion of linkage to care among men did not differ in the arms which received financial incentives and those without financial incentives (adjusted Risk Ratio [aRR]=0.78, 95% CI: 0.51-1.21). Among 19,884 eligible women, 29.1% received HBHCT, which resulted in 375 HIV-positive tests. Of these, 75 linked to care. Among eligible women who did not receive HBHCT, 121 linked to care within 6 weeks. Women in the financial incentive arms had a significantly higher probability of linkage to care, compared to those in the arms without financial incentives (aRR=1.50; 95% CI: 1.03-2.21). Conclusion: While a small once-off financial incentive did not increase linkage to care among men during the eligibility period of 6 weeks, it significantly improved linkage to care among women over the same period. Clinical Trial Number: ClinicalTrials.gov # NCT03757104.

Incidence, Clearance and Persistence of Penile High-Risk Human Papillomavirus among Rwandan Men who have Sex with Men.

BACKGROUND: Little is known about penile high-risk HPV among MSM in low-and-middle income countries. We aimed to determine the incidence, clearance and persistence of penile hrHPV among Rwandan MSM. METHODS: We enrolled 350 MSM (345 with valid HPV results), aged ≥18 years, at each visit (6-12 months apart), we collected penile PreservCyt specimens and blood for HPV and HIV testing, socio-demographic and behavioral variables. HPV testing was performed using the Ampfire assay. Penile hrHPV incidence and clearance/1,000 person-months of follow-up (PMF), prevalent- and incident-persistence were computed and compared by HIV status. RESULTS: The mean age was 27.7 ± 6.7 years and 19.4% were living with HIV. Penile hrHPV incidence was 34.8 (95% CI: 29.1, 41.8)/1,000 PMF. HPV16 (11.7, CI 9.26, 14.9) and HPV59 (6.1, CI 4.52, 8.39) had the highest incidence rates. Prevalent- and incident-persistence were 47.5% and 46.6%, respectively. HPV66 (33.3%), HPV52 (30.8%) and HPV16 (29.2%) had the highest prevalent-persistence and HPV33 (53.8%), HPV31 (46.7%) and HPV16 (42.6%) the highest incident-persistence. No differences were found by HIV status except for HPV45 (higher in MSM with HIV). CONCLUSION: We found high incidence and prevalent/incident-persistence of penile hrHPV among Rwandan MSM. This highlights the importance of preventive strategies for HPV-associated anogenital cancers.

Using stated preference methods to facilitate knowledge translation in implementation science.

Enhancing the arsenal of methods available to shape implementation strategies and bolster knowledge translation is imperative. Stated preference methods, including discrete choice experiments (DCE) and best-worst scaling (BWS), rooted in economics, emerge as robust, theory-driven tools for understanding and influencing the behaviors of both recipients and providers of innovation. This commentary outlines the wide-ranging application of stated preference methods across the implementation continuum, ushering in effective knowledge translation. The prospects for utilizing these methods within implementation science encompass (1) refining and tailoring intervention and implementation strategies, (2) exploring the relative importance of implementation determinants, (3) identifying critical outcomes for key decision-makers, and 4) informing policy prioritization. Operationalizing findings from stated preference research holds the potential to precisely align health products and services with the requisites of patients, providers, communities, and policymakers, thereby realizing equitable impact.

Interpretation of Complete Tumor Response on MRI Following Chemoradiotherapy of Rectal Cancer: Inter-Reader Agreement and Associated Factors in Multi-Center Clinical Practice.

OBJECTIVE: To measure inter-reader agreement and identify associated factors in interpreting complete response (CR) on magnetic resonance imaging (MRI) following chemoradiotherapy (CRT) for rectal cancer. MATERIALS AND METHODS: This retrospective study involved 10 readers from seven hospitals with experience of 80-10210 cases, and 149 patients who underwent surgery after CRT for rectal cancer. Using MRI-based tumor regression grading (mrTRG) and methods employed in daily practice, the readers independently assessed mrTRG, CR on T2-weighted images (T2WI) denoted as mrCRT2W, and CR on all images including diffusion-weighted images (DWI) denoted as mrCRoverall. The readers described their interpretation patterns and how they utilized DWI. Inter-reader agreement was measured using multi-rater kappa, and associated factors were analyzed using multivariable regression. Correlation between sensitivity and specificity of each reader was analyzed using Spearman coefficient. RESULTS: The mrCRT2W and mrCRoverall rates varied widely among the readers, ranging 18.8%-40.3% and 18.1%-34.9%, respectively. Nine readers used DWI as a supplement sequence, which modified interpretations on T2WI in 2.7% of cases (36/1341 [149 patients × 9 readers]) and mostly (33/36) changed mrCRT2W to non-mrCRoverall. The kappa values for mrTRG, mrCRT2W, and mrCRoverall were 0.56 (95% confidence interval: 0.49, 0.62), 0.55 (0.52, 0.57), and 0.54 (0.51, 0.57), respectively. No use of rectal gel, larger initial tumor size, and higher initial cT stage exhibited significant association with a higher inter-reader agreement for assessing mrCRoverall (P ≤ 0.042). Strong negative correlations were observed between the sensitivity and specificity of individual readers (coefficient, -0.718 to -0.963; P ≤ 0.019). CONCLUSION: Inter-reader agreement was moderate for assessing CR on post-CRT MRI. Readers' varying standards on MRI interpretation (i.e., threshold effect), along with the use of rectal gel, initial tumor size, and initial cT stage, were significant factors associated with inter-reader agreement.

Risk of hematologic malignant neoplasms from head CT radiation in children and adolescents presenting with minor head trauma: a nationwide population-based cohort study.

OBJECTIVES: The carcinogenic risks of CT radiation in children and adolescents remain debated. We aimed to assess the carcinogenic risk of CTs performed in children and adolescents with minor head trauma. METHODS: In this nationwide population-based cohort study, we included 2,411,715 patients of age 0-19 with minor head trauma from 2009 to 2017. We excluded patients with elevated cancer risks or substantial past medical radiation exposure. Patients were categorized into CT-exposed or CT-unexposed group according to claim codes for head CT. The primary outcome was development of hematologic malignant neoplasms. Secondary outcomes included development of malignant solid neoplasms and benign neoplasms in the brain. We measured the incidence rate ratio (IRR) and incidence rate difference (IRD) using G-computation with Poisson regression adjusting for age, sex, hospital setting, and the type of head trauma. RESULTS: Hematologic malignant neoplasms developed in 100 of 216,826 patients during 1,303,680 person-years in the CT-exposed group and in 808 of 2,194,889 patients during 13,501,227 person-years in the CT-unexposed group. For hematologic malignant neoplasms, the IRR was 1.29 (95% CI, 1.03-1.60) and the IRD was 1.71 (95% CI, 0.04-3.37) per 100,000 person-years at risk. The majority of excess hematologic malignant neoplasms were leukemia (IRR, 1.40 [98.3% CI, 1.05-1.87]; IRD, 1.59 [98.3% CI, 0.02-3.16] per 100,000 person-years at risk). There were no between-group differences for secondary outcomes. CONCLUSIONS: Radiation exposure from head CTs in children and adolescents with minor head trauma was associated with an increased incidence of hematologic malignant neoplasms. CLINICAL RELEVANCE STATEMENT: Our study provides a quantitative grasp of the risk conferred by CT examinations in children and adolescents, thereby providing the basis for cost-benefit analyses and evidence-driven guidelines for patient triaging in head trauma. KEY POINTS: • This nationwide population-based cohort study showed that radiation exposure from head CTs in children and adolescents was associated with a higher incidence of hematologic malignant neoplasms. • The incidence rate of hematologic malignant neoplasms in the CT-exposed group was 29% higher than that in the CT-unexposed group (IRR, 1.29 [95% CI, 1.03-1.60]), and there were approximately 1.7 excess neoplasms per 100,000 person-years at risk in the CT-exposed group (IRD, 1.71 [0.04-3.37]). • Our study provides a quantified grasp of the risk conferred by CT examinations in children and adolescents, while controlling for biases observed in previous studies via specifying CT indication and excluding patients with predisposing conditions for cancer development.

Convergence of HIV and non-communicable disease epidemics: geospatial mapping of the unmet health needs in an HIV hyperendemic community in South Africa.

INTRODUCTION: As people living with HIV (PLHIV) are experiencing longer survival, the co-occurrence of HIV and non-communicable diseases has become a public health priority. In response to this emerging challenge, we aimed to characterise the spatial structure of convergence of chronic health conditions in an HIV hyperendemic community in KwaZulu-Natal, South Africa. METHODS: In this cross-sectional study, we used data from a comprehensive population-based disease survey conducted in KwaZulu-Natal, South Africa, which collected data on HIV, diabetes and hypertension. We implemented a novel health needs scale to categorise participants as: diagnosed and well-controlled (Needs Score 1), diagnosed and suboptimally controlled (Score 2), diagnosed but not engaged in care (Score 3) or undiagnosed and uncontrolled (Score 4). Scores 2-4 were indicative of unmet health needs. We explored the geospatial structure of unmet health needs using different spatial clustering methods. RESULTS: The analytical sample comprised 18 041 individuals. We observed a similar spatial structure for HIV among those with combined needs Score 2-3 (diagnosed but uncontrolled) and Score 4 (undiagnosed and uncontrolled), with most PLHIV with unmet needs clustered in the southern urban and peri-urban areas. Conversely, a high prevalence of need Scores 2 and 3 for diabetes and hypertension was mostly distributed in the more rural central and northern part of the surveillance area. A high prevalence of need Score 4 for diabetes and hypertension was mostly distributed in the rural southern part of the surveillance area. Multivariate clustering analysis revealed a significant overlap of all three diseases in individuals with undiagnosed and uncontrolled diseases (unmet needs Score 4) in the southern part of the catchment area. CONCLUSIONS: In an HIV hyperendemic community in South Africa, areas with the highest needs for PLHIV with undiagnosed and uncontrolled disease are also areas with the highest burden of unmet needs for other chronic health conditions, such as diabetes and hypertension. Our study has revealed remarkable differences in the distribution of health needs across the rural to urban continuum even within this relatively small study site. The identification and prioritisation of geographically clustered vulnerable communities with unmet health needs for both HIV and non-communicable diseases provide a basis for policy and implementation strategies to target communities with the highest health needs.

Comparison of Empirically Derived and Model-Based Estimates of Key Population HIV Incidence and the Distribution of New Infections by Population Group in Sub-Saharan Africa.

BACKGROUND: The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates. METHODS: We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios. RESULTS: Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15-39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15-29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%-11.7%), both much lower than the 25% reported by UNAIDS. CONCLUSION: Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.

Measuring HIV Acquisitions Among Partners of Key Populations: Estimates From HIV Transmission Dynamic Models.

BACKGROUND: Key populations (KPs), including female sex workers (FSWs), gay men and other men who have sex with men (MSM), people who inject drugs (PWID), and transgender women (TGW) experience disproportionate risks of HIV acquisition. The UNAIDS Global AIDS 2022 Update reported that one-quarter of all new HIV infections occurred among their non-KP sexual partners. However, this fraction relied on heuristics regarding the ratio of new infections that KPs transmitted to their non-KP partners to the new infections acquired among KPs (herein referred to as "infection ratios"). We recalculated these ratios using dynamic transmission models. SETTING: One hundred seventy-eight settings (106 countries). METHODS: Infection ratios for FSW, MSM, PWID, TGW, and clients of FSW were estimated from 12 models for 2020. RESULTS: Median model estimates of infection ratios were 0.7 (interquartile range: 0.5-1.0; n = 172 estimates) and 1.2 (0.8-1.8; n = 127) for acquisitions from FSW clients and transmissions from FSW to all their non-KP partners, respectively, which were comparable with the previous UNAIDS assumptions (0.2-1.5 across regions). Model estimates for female partners of MSM were 0.5 (0.2-0.8; n = 20) and 0.3 (0.2-0.4; n = 10) for partners of PWID across settings in Eastern and Southern Africa, lower than the corresponding UNAIDS assumptions (0.9 and 0.8, respectively). The few available model estimates for TGW were higher [5.1 (1.2-7.0; n = 8)] than the UNAIDS assumptions (0.1-0.3). Model estimates for non-FSW partners of FSW clients in Western and Central Africa were high (1.7; 1.0-2.3; n = 29). CONCLUSIONS: Ratios of new infections among non-KP partners relative to KP were high, confirming the importance of better addressing prevention and treatment needs among KP as central to reducing overall HIV incidence.

Improving radiomics reproducibility using deep learning-based image conversion of CT reconstruction algorithms in hepatocellular carcinoma patients.

OBJECTIVES: CT reconstruction algorithms affect radiomics reproducibility. In this study, we evaluate the effect of deep learning-based image conversion on CT reconstruction algorithms. METHODS: This study included 78 hepatocellular carcinoma (HCC) patients who underwent four-phase liver CTs comprising non-contrast, late arterial (LAP), portal venous (PVP), and delayed phase (DP), reconstructed using both filtered back projection (FBP) and advanced modeled iterative reconstruction (ADMIRE). PVP images were used to train a convolutional neural network (CNN) model to convert images from FBP to ADMIRE and vice versa. LAP, PVP, and DP images were used for validation and testing. Radiomic features were extracted for each patient with a semi-automatic segmentation tool. We used concordance correlation coefficients (CCCs) to evaluate the radiomics reproducibility for original FBP (oFBP) vs. original ADMIRE (oADMIRE), oFBP vs. converted FBP (cFBP), and oADMIRE vs. converted ADMIRE (cADMIRE). RESULTS: In the test group including 30 patients, the CCC and proportion of reproducible features (CCC ≥ 0.85) for oFBP vs. oADMIRE were 0.65 and 32.9% (524/1595) for LAP, 0.65 and 35.9% (573/1595) for PVP, and 0.69 and 43.8% (699/1595) for DP. For oFBP vs. cFBP, the values increased to 0.92 and 83.9% (1339/1595) for LAP, 0.89 and 71.0% (1133/1595) for PVP, and 0.90 and 79.7% (1271/1595) for DP. Similarly, for oADMIRE vs. cADMIRE, the values increased to 0.87 and 68.1% (1086/1595) for LAP, 0.91 and 82.1% (1309/1595) for PVP, and 0.89 and 76.2% (1216/1595) for DP. CONCLUSIONS: CNN-based image conversion between CT reconstruction algorithms improved the radiomics reproducibility of HCCs. CLINICAL RELEVANCE STATEMENT: This study demonstrates that using a CNN-based image conversion technique significantly improves the reproducibility of radiomic features in HCCs, highlighting its potential for enhancing radiomics research in HCC patients. KEY POINTS: Radiomics reproducibility of HCC was improved via CNN-based image conversion between two different CT reconstruction algorithms. This is the first clinical study to demonstrate improvements across a range of radiomic features in HCC patients. This study promotes the reproducibility and generalizability of different CT reconstruction algorithms in radiomics research.

Geospatial assessment of the convergence of communicable and non-communicable diseases in South Africa.

Introduction: Several low-and middle-income countries are undergoing rapid epidemiological transition with a rising burden of non-communicable diseases (NCDs). South Africa (SA) is a country with one of the largest HIV epidemics worldwide and a growing burden of NCDs where the collision of these epidemics poses a major public health challenge. Methods: Using data from a large nationally representative survey, the South Africa Demographic and Health Survey (SADHS 2016), we conducted a geospatial analysis of several diseases including HIV, tuberculosis (TB), cardiovascular, respiratory, and metabolic diseases to identify areas with a high burden of co-morbidity within the country. We explored the spatial structure of each disease and associations between diseases using different spatial and visual data methodologies. We also assessed the individual level co-occurrence of HIV and the other diseases included in the analysis. Results: The spatial distribution for HIV prevalence showed that this epidemic is most intense in the eastern region of the country, mostly within the Gauteng, Mpumalanga, and Kwazulu-Natal provinces. In contrast, chronic diseases had their highest prevalence rates the southern region of the country, particularly in the Eastern and Western Cape provinces. Individual-level analyses were consistent with the spatial correlations and found no statistically significant associations between HIV infection and the presence of any NCDs. Conclusions: We found no evidence of geospatial overlap between the HIV epidemic and NCDs in SA. These results evidence the complex epidemiological landscape of the country, characterized by geographically distinct areas exhibiting different health burdens. The detailed description of the heterogenous prevalence of HIV and NCDs in SA reported in this study could be a useful tool to inform and direct policies to enhance targeted health service delivery according to the local health needs of each community.

Distribution of small bowel involvement and its association with clinical outcomes in patients with Crohn's disease.

We aimed to evaluate the distribution of small-bowel involvement in Crohn's disease (CD) and its association with clinical outcomes. This study included CD patients who underwent computed tomography (CT) at initial diagnosis from June 2006 to April 2021. Two abdominal radiologists reviewed the CT images, and independently rated the presence of "bowel wall thickening," "stricture," and "fistula or abscess" in the small bowel segments of jejunum, distal jejunum/proximal ileum, distal ileum, and terminal ileum, respectively. Based on findings of the image review, each patient's "disease-extent imaging score" and "behavior-weighted imaging score" (a higher score indicative of more structuring or penetrating disease) were calculated. Major clinical outcomes (emergency department [ED] visit, operation, and use of corticosteroids or biologics) were compared according to the 2 scores and L4 involvement by the Montreal classification. The proportions of involvement in the jejunum, distal jejunum/proximal ileum, distal ileum, and terminal ileum were 2.0%, 30.3%, 82.2%, and 71.7%, respectively, identifying 30.3% of patients as having L4 disease and 69.7% of patients as having involvement of multiple segments. Clinical outcomes were not significantly associated with the disease-extent imaging score or L4 involvement. However, significant differences were noted for the ED visits and the use of biologics, according to the behavior-weighted imaging score. Moreover, in multivariable analysis, disease behavior was the only factor associated with all clinical outcomes (ED visit, hazard ratio [HR] 2.127 [1.356-3.337], P = .001; operation, HR 8.216 [2.629-25.683], P < .001; use of corticosteroid, HR 1.816 [1.249-2.642], P = .002; and use of biologics, HR 2.352 [1.492-3.708], P < .001). Initial disease behavior seems to be a more critical factor for clinical outcomes of CD than the extent or distribution of small-bowel involvement on CT.

Methyl lucidone inhibits airway inflammatory response by reducing TAK1 activity in human bronchial epithelial NCI-H292 cells.

Background: Methyl lucidone (ML), a methyl derivative of lucidone, has anti-inflammatory properties. However, the molecular mechanisms that reduce the inflammatory effect of ML in human lung epithelial cells remain unkown. This study aimed to elucidate the molecular mechanisms underlying the anti-inflammatory effect of ML. Methods: Four compounds (ML, methyl linderone, kanakugiol, and linderone) from Lindera erythrocarpa Makino were evaluated for their ability to reduce MUC5AC secretion levels in phorbol-12-myristate-13-acetate (PMA)-stimulated NCI-H292 cells using ELISA. The expression and secretion levels of inflammatory response-related proteins were analyzed using quantitative reverse transcription-PCR, ELISA, and western blotting. To determine whether ML directly regulates TGF-ß-activated kinase 1 (TAK1), we performed an in vitro kinase assay. Results: ML treatment effectively reduced the levels of inflammatory cytokines, including interleukin-1ß and TNF-α, increased by stimulation. Furthermore, ML downregulated the pathway cascade of both IκB kinase (IKK)/NF-κB and p38 mitogen-activated protein (MAP) kinase/CREB by inhibiting the upstream kinase TAK1. An in vitro kinase analysis confirmed that ML treatment significantly reduced the kinase activity of TAK1. Conclusion: ML pretreatment repressed the PMA-stimulated inflammation reaction by reducing the TAK1-mediated IKK/NF-κB and p38 MAP kinase/CREB signaling. These findings suggest that ML may improve respiratory health and can be used as a dietary supplement or functional food to prevent inflammatory lung diseases.

Impact of family networks on uptake of health interventions: evidence from a community-randomized control trial aimed at increasing HIV testing in South Africa.

INTRODUCTION: While it is widely acknowledged that family relationships can influence health outcomes, their impact on the uptake of individual health interventions is unclear. In this study, we quantified how the efficacy of a randomized health intervention is shaped by its pattern of distribution in the family network. METHODS: The "Home-Based Intervention to Test and Start" (HITS) was a 2×2 factorial community-randomized controlled trial in Umkhanyakude, KwaZulu-Natal, South Africa, embedded in the Africa Health Research Institute's population-based demographic and HIV surveillance platform (ClinicalTrials.gov # NCT03757104). The study investigated the impact of two interventions: a financial micro-incentive and a male-targeted HIV-specific decision support programme. The surveillance area was divided into 45 community clusters. Individuals aged ≥15 years in 16 randomly selected communities were offered a micro-incentive (R50 [$3] food voucher) for rapid HIV testing (intervention arm). Those living in the remaining 29 communities were offered testing only (control arm). Study data were collected between February and November 2018. Using routinely collected data on parents, conjugal partners, and co-residents, a socio-centric family network was constructed among HITS-eligible individuals. Nodes in this network represent individuals and ties represent family relationships. We estimated the effect of offering the incentive to people with and without family members who also received the offer on the uptake of HIV testing. We fitted a linear probability model with robust standard errors, accounting for clustering at the community level. RESULTS: Overall, 15,675 people participated in the HITS trial. Among those with no family members who received the offer, the incentive's efficacy was a 6.5 percentage point increase (95% CI: 5.3-7.7). The efficacy was higher among those with at least one family member who received the offer (21.1 percentage point increase (95% CI: 19.9-22.3). The difference in efficacy was statistically significant (21.1-6.5 = 14.6%; 95% CI: 9.3-19.9). CONCLUSIONS: Micro-incentives appear to have synergistic effects when distributed within family networks. These effects support family network-based approaches for the design of health interventions.

The met and unmet health needs for HIV, hypertension, and diabetes in rural KwaZulu-Natal, South Africa: analysis of a cross-sectional multimorbidity survey.

BACKGROUND: The convergence of infectious diseases and non-communicable diseases in South Africa is challenging to health systems. In this analysis, we assessed the multimorbidity health needs of individuals and communities in rural KwaZulu-Natal and established a framework to quantify met and unmet health needs for individuals living with infectious and non-communicable diseases. METHODS: We analysed data collected between May 25, 2018, and March 13, 2020, from participants of a large, community-based, cross-sectional multimorbidity survey (Vukuzazi) that offered community-based HIV, hypertension, and diabetes screening to all residents aged 15 years or older in a surveillance area in the uMkhanyakude district in KwaZulu-Natal, South Africa. Data from the Vukuzazi survey were linked with data from demographic and health surveillance surveys with a unique identifier common to both studies. Questionnaires were used to assess the diagnosed health conditions, treatment history, general health, and sociodemographic characteristics of an individual. For each condition (ie, HIV, hypertension, and diabetes), individuals were defined as having no health needs (absence of condition), met health needs (condition that is well controlled), or one or more unmet health needs (including diagnosis, engagement in care, or treatment optimisation). We analysed met and unmet health needs for individual and combined conditions and investigated their geospatial distribution. FINDINGS: Of 18 041 participants who completed the survey (12 229 [67·8%] were female and 5812 [32·2%] were male), 9898 (54·9%) had at least one of the three chronic diseases measured. 4942 (49·9%) of these 9898 individuals had at least one unmet health need (1802 [18·2%] of 9898 needed treatment optimisation, 1282 [13·0%] needed engagement in care, and 1858 [18·8%] needed a diagnosis). Unmet health needs varied by disease; 1617 (93·1%) of 1737 people who screened positive for diabetes, 2681 (58·2%) of 4603 people who screened positive for hypertension, and 1321 (21·7%) of 6096 people who screened positive for HIV had unmet health needs. Geospatially, met health needs for HIV were widely distributed and unmet health needs for all three conditions had specific sites of concentration; all three conditions had an overlapping geographical pattern for the need for diagnosis. INTERPRETATION: Although people living with HIV predominantly have a well controlled condition, there is a high burden of unmet health needs for people living with hypertension and diabetes. In South Africa, adapting current, widely available HIV care services to integrate non-communicable disease care is of high priority. FUNDING: Fogarty International Center and the National Institutes of Health, the Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, the South African Medical Research Council, the South African Population Research Infrastructure Network, and the Wellcome Trust. TRANSLATION: For the isiZulu translation of the abstract see Supplementary Materials section.

Optimizing the pipeline of multipurpose prevention technologies: opportunities across women's reproductive lifespans.

HIV/AIDS and maternal mortality are the two leading causes of death among women of reproductive age in sub-Saharan Africa. A growing body of research investigates opportunities for multipurpose prevention technologies (MPTs) that prevent unintended pregnancy, HIV, and/or other sexually transmitted infections (STIs) with a single product. More than two dozen MPTs are currently in development, most of them combining contraception with HIV pre-exposure prophylaxis, with or without protection from other STIs. If successful, such MPTs could offer women benefits at multiple levels: greater motivation for effective use; lower product administration burden; accelerated integration of HIV, STI, and reproductive health services; and opportunities to circumvent stigma by using contraception as a "fig leaf" for HIV and/or STI prevention. However, even if women find respite from product burden, lack of motivation, and/or stigma in contraceptive-containing MPTs, their use of MPTs will be interrupted, often multiple times, over the reproductive lifecourse due to desire for pregnancy, pregnancy and breastfeeding, menopause, and changes in risk. Interruptions to the benefits of MPTs could be avoided by combining HIV/STI prevention with other life-stage-appropriate reproductive health products. New product concepts could include combining prenatal supplements with HIV and STI prevention, emergency contraception with HIV post-exposure prophylaxis, or hormone replacement therapies for menopause with HIV and STI prevention. Research is needed to optimize the MPT pipeline based on the populations underserved by available options and the capacity of resource-constrained health systems to deliver novel preventative healthcare products.

Cost-effectiveness of the dual prevention pill for contraception and HIV pre-exposure prophylaxis.

Introduction: Women in sub-Saharan Africa (SSA) experience the world's highest rates of both HIV infection and unintended pregnancy. The Dual Prevention Pill (DPP) is a novel multipurpose prevention technology (MPT) that co-formulates HIV pre-exposure prophylaxis (PrEP) and combined hormonal oral contraception into a single daily pill. As a dual indication product, the DPP may be preferred by women facing these overlapping health risks. However, most SSA countries face severe healthcare resource constraints. Research is needed to assess whether, in what populations, and in what use cases the DPP would be cost-effective. Methods: We augmented an agent-based SSA HIV model with maternal health parameters including unintended pregnancy, abortion, and maternal mortality. Based on a previous market analysis, we assumed a primary DPP user population of current oral contraceptive users ages 25-49, and alternative user populations in different risk groups (age 15-24, sex workers, HIV-serodiscordant couples) and baseline product use profiles (unmet need for contraception, oral PrEP use, condom use). In three geographies (western Kenya, Zimbabwe, South Africa), we estimated HIV infections averted, pregnancies averted, disability-adjusted life-years (DALYs) averted, and the incremental cost-effectiveness ratio (ICER) over a 30-year time horizon, assuming equivalent adherence to the DPP as to oral contraceptives, higher adherence, or lower adherence. Results: The DPP is likely to be a cost-effective alternative to oral PrEP among users in need of contraception. Among women not already using PrEP, the DPP is likely to be cost-saving in sex workers and serodiscordant couples. The DPP is unlikely to be cost-effective in oral contraceptive users in the general population. Switching from oral contraception to the DPP could be net harmful in some settings and populations if it were to substantially reduces adherence to oral contraception. Results were robust to a range of time horizons or discount rates. Conclusion: The DPP has the potential to be cost-effective and cost-saving in populations at substantial HIV risk. Outcomes are sensitive to adherence, implying that effective counseling and decision-making tools for users considering the DPP will be essential. More research is needed to understand real-life adherence patterns and ensure health benefits achieved from contraception alone are not lost.

Comparison of AmpFire and MY09/11 assays for HPV genotyping in anogenital specimen of Rwandan men who have sex with men.

Introduction: The AmpFire HPV genotyping Assay (Atila Biosystems, Mountain View, CA, USA) is a new test for which there are few data regarding its analytic performance and reliability. Using anal and penile swab specimens from a cohort study of men who have sex with men (MSM) in Rwanda, we compared high-risk HPV (hrHPV) detection by AmpFire done at two laboratories, one at University of California San Francisco (UCSF) and the other Rwanda Military Hospital, and well-validated MY09/11-based assay done at UCSF. Methods: Anal and penile specimens collected from 338 MSM from March 2016 to September 2016 were tested for high-risk HPV genotypes (hrHPV) by MY09/11, AmpFire UCSF and AmpFire RMH. Cohen's kappa coefficient was used to test for reproducibility. Results: The hrHPV positivity by MY09/11 and AmpFire UCSF was 13% and 20.7% (k = 0.73) for anal specimens and was 26.3% and 32.6% (k = 0.67) for penile specimens. Specifically, good reproducibility was for types 16 and 18 (k = 0.69 and k = 0.71) for anal specimens and (k = 0.50 and k = 0.72) for penile specimens. The hrHPV positivity by AmpFire at UCSF and RMH was 20.7% for both laboratories (k = 0.87) for anal specimens and was 34.9% and 31.9% (k = 0.89) for penile specimens. Specifically, excellent reproducibility was for types 16 and 18 for anal specimens (k = 0.80 and k = 1.00) and penile specimens (k = 0.85 and k = 0.91). Conclusion: Results show that MY09/11 and AmpFire assays have good reproducibility while the AmpFire UCSF and RMH assays have excellent reproducibility. These results show that AmpFire is a promising HPV genotyping test.

Radiology Residents' Independent Diagnosis of Appendicitis Using 2-mSv Computed Tomography: A Secondary Analysis of a Large Pragmatic Randomized Trial.

OBJECTIVE: To compare the diagnostic performance and clinical outcomes of 2-mSv computed tomography (CT) and conventional-dose CT (CDCT), following radiology residents' interpretation of CT examinations for suspected appendicitis. MATERIALS AND METHODS: Altogether, 3074 patients with suspected appendicitis aged 15-44 years (28 ± 9 years, 1672 females) from 20 hospitals were randomly assigned to the 2-mSv CT (n = 1535) or CDCT (n = 1539) groups in a pragmatic trial from December 2013 and August 2016. Overall, 107 radiology residents participated in the trial as readers in the form of daily practice after online training for 2-mSv CT. They made preliminary CT reports, which were later finalized by attending radiologists via addendum reports, for 640 and 657 patients in the 2-mSv CT and CDCT groups, respectively. We compared the diagnostic performance of the residents, discrepancies between preliminary and addendum reports, and clinical outcomes between the two groups. RESULTS: Patient characteristics were similar between the 640 and 657 patients. Residents' diagnostic performance was not significantly different between the 2-mSv CT and CDCT groups, with a sensitivity of 96.0% and 97.1%, respectively (difference [95% confidence interval {CI}], -1.1% [-4.9%, 2.6%]; P = 0.69) and specificity of 93.2% and 93.1%, respectively (0.1% [-3.6%, 3.7%]; P > 0.99). The 2-mSv CT and CDCT groups did not significantly differ in discrepancies between the preliminary and addendum reports regarding the presence of appendicitis (3.3% vs. 5.2%; -1.9% [-4.2%, 0.4%]; P = 0.12) and alternative diagnosis (5.5% vs. 6.4%; -0.9% [-3.6%, 1.8%]; P = 0.56). The rates of perforated appendicitis (12.0% vs. 12.6%; -0.6% [-4.3%, 3.1%]; P = 0.81) and negative appendectomies (1.9% vs. 1.1%; 0.8% [-0.7%, 2.3%]; P = 0.33) were not significantly different between the two groups. CONCLUSION: Diagnostic performance and clinical outcomes were not significantly different between the 2-mSv CT and CDCT groups following radiology residents' CT readings for suspected appendicitis.