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Supplemental Digital Content is Available in the Text., Introduction: Recent studies project thousands of additional AIDS-related deaths because of COVID-19–related disruptions in HIV care. However, the extent to which disruptions in care have materialized since the start of the pandemic is not well understood. Methods: We use electronic health records to investigate how the pandemic has affected clinic visits, patients' antiretroviral therapy (ART) supply, and viral suppression for a cohort of 14,632 HIV clients from a large HIV clinic in Kampala, Uganda. We complement this with an analysis of electronically measured longitudinal ART adherence data from a subcohort of 324 clients. Results: Clinic visits decreased by more than 50% after a national lockdown started. The risk of patients running out of ART on a given day increased from 5% before the lockdown to 25% 3 months later (Relative Risk Ratio of 5.11, 95% confidence interval: 4.99 to 5.24) and remained higher than prelockdown 6 months later at 13% (Relative Risk Ratio of 2.60; 95% confidence interval: 2.52 to 2.70). There was no statistically significant change in electronically measured adherence or viral suppression. Conclusion: We document substantial gaps in HIV care after the start of the COVID-19 pandemic in Uganda. This suggests that measures to improve access should be explored as the pandemic persists. However, ART adherence was unaffected for the subcohort for whom we measured electronic adherence. This suggests that some clients may have stockpiles of ART tablets from previous prescriptions that allowed them to keep taking their medication even when they could not visit the clinic for ART refills.

Background: Well-validated risk prediction models help to identify individuals at high risk of diseases and suggest preventive measures. A recent systematic review reported lack of validated prediction models for low back pain (LBP). We aimed to develop prediction models to estimate the 8-year risk of developing LBP and its recurrence. Methods: A population based prospective cohort study using data from 435,968 participants in the National Health Insurance Service-National Sample Cohort enrolled from 2002 to 2010. We used Cox proportional hazards models. Results: During median follow-up period of 8.4 years, there were 143,396 (32.9%) first onset LBP cases. The prediction model of first onset consisted of age, sex, income grade, alcohol consumption, physical exercise, body mass index (BMI), total cholesterol, blood pressure, and medical history of diseases. The model of 5-year recurrence risk was comprised of age, sex, income grade, BMI, length of prescription, and medical history of diseases. The Harrell’s C-statistic was 0.812 (95% confidence interval [CI], 0.804-0.820) and 0.916 (95% CI, 0.907-0.924) in validation cohorts of LBP onset and recurrence models, respectively. Age, disc degeneration, and sex conferred the highest risk points for onset, whereas age, spondylolisthesis, and disc degeneration conferred the highest risk for recurrence. Conclusions: LBP risk prediction models and simplified risk scores have been developed and validated using data from general medical practice. This study also offers an opportunity for external validation and updating of the models by incorporating other risk predictors in other settings, especially in this era of precision medicine.

Background Germinoma preferentially occurs in pediatric and young adult age groups. Although they are responsive to treatment with chemotherapy and radiation, the treatment may cause long-term sequelae in their later lives. Here, we searched for clinical and histopathological features to predict the prognosis of germinoma and affect treatment response. Methods A total of 114 germinoma cases were included in the analysis. We investigated the association between clinical factors, tumor cell content, and progression-free survival (PFS). Results The tumor cell content was widely distributed from Conclusions We found that tumor cell content significantly affected the prognosis of germinomas. Although validation of these results using an independent and larger cohort is necessary, this potentially opens the possibility of leveraging this pathological factor in future clinical trials when stratifying the treatment intensity.

Background To illustrate the public health potential of linking individual bedside data with community-based household data in a poor rural setting, we estimated excess pediatric mortality risk after discharge from St Francis Designated District Hospital in Ifakara, Tanzania. Methods Linked data from demographic and clinical surveillance were used to describe post-discharge mortality and survival probability in children aged Results Between March 2003 and March 2007, demographic surveillance included 28,910 children aged 0 to 5 years and among them 831 (3%) were admitted at least once to the district hospital. From all the children under the demographic surveillance 57,880 person years and 1381 deaths were observed in 24 months of follow up. Survivors of hospital discharge aged 0–5 years were almost two times more likely to die than children of the same age in the community who had not been admitted (RR = 1.9, P Conclusion This study illustrates the potential of linking health related data from facility and household levels. Our results suggest that families may need additional support post hospitalization.

BackgroundYouth living with HIV (YLHIV) in Sub-Saharan African (SSA) are less likely to adhere to antiretroviral therapy (ART) and other health-related regimens. As a consequence, YLHIV are not only at risk for health problems and mental health comorbidities, but are also at risk for cognitive deficits, including in areas of memory and executive functioning. The Suubi+Adherence study followed 702 adolescents (10-16 years of age) receiving bolstered standard of care and a family economic empowerment intervention comprising an incentivized youth financial savings account (YSA) augmented with financial literacy training (FLT) and peer mentorship. The study findings pointed to superior short-term viral suppression and positive adolescent health and mental health functioning among participants receiving the intervention. The original group of adolescents who received Suubi+Adherence are now transitioning into young adulthood. This paper presents a protocol for the follow-up phase titled Suubi+Adherence Round 2.MethodsThe original cohort in Suubi+Adherence will be tracked for an additional five years (2020-2025). Specifically, the long term follow-up will allow to: 1) ascertain the extent to which the short term outcomes identified in the first 6 years of the intervention are maintained as the same group transitions through young adulthood; and 2) address new scientific questions regarding ART adherence; HIV care engagement; protective health behaviors; and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. Additionally, the team examines the potential mechanisms through which the observed long-term outcomes happen. Moreover, the Suubi+Adherence-Round 2 adds a qualitative component and extends the cost effectiveness component.DiscussionGuided by asset and human development theories, Suubi+Adherence-R2 will build on the recently concluded Suubi+Adherence study to conduct one of the largest and longest running studies of YLHIV in SSA as they transition into young adulthood. The study will address new scientific questions regarding long-term ART adherence, HIV care engagement, protective health behaviors, and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. The findings may inform efforts to improve HIV care among Uganda’s YLHIV, with potential replicability in other low-resource countries.Trial registrationClinicalTrials.gov, ID:NCT01790373

BackgroundThere is plenitude of information on HIV infection among pregnant mothers attending antenatal care (ANC) in sub-Saharan Africa. However, the epidemiology of HBV–HIV co-infections in the same cohort is not clear despite the common route of transmission of both viruses. The aim of our study was to synthesize data on the prevalence of HBV–HIV co-infection among pregnant women attending ANC in Sub-Saharan Africa to assist in the design of public health interventions to mitigate the challenge.MethodsThe study was done in tandem with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards and the Cochran’s Q test, I2statistics for heterogeneity and the prevalence were calculated using commercially available software called MedCalcs (https://www.medcalc.org). A random effect model was used to pool the prevalence since all the heterogeneities were high (≥ 78%) and Phet P ResultsThe overall pooled prevalence of HBV–HIV co-infection among pregnant mothers in sub-Saharan Africa was low 3.302% (95%CI = 2.285 to 4.4498%) with heterogeneities (I2) of 97.59% (P > 0.0001). Within regional sub group meta-analyses, West Africa had significantly higher prevalence of 5.155% (95% = 2.671 to 8.392%) with heterogeneity (I2) of 92.25% (P P 2) 91.15% (P P 2)94.90% (P P 2 > 89%,P 2) = 78.4% (P = 0.0314). Age, marital status and employment were independent factors significantly associated with risk of HBV–HIV co-infection (P P > 0.05). After meta-regression for year of publication and sample size for HBsAg positivity, the results were not significantly associated with HBV pooled prevalence for sample size (P = 0.146) and year of publication (P = 0.560). Following sensitivity analysis, the HBsAg pooled prevalence slightly increased to 3.429% (95% CI = 2.459 to 4.554%) with heterogeneity I2 = 96.59% (95% CI = 95.93 to 97.14%), P ConclusionThere is an urgent need for routine HBV screening among HIV positive pregnant mothers attending antenatal care in sub-Saharan Africa to establish the extent of HBV–HIV co-infection in this cohort. Future studies need to investigate the putative risk factors for HBV–HIV co-infection and prioritize plausible control strategies.

Background: Uganda has successfully reduced pediatric HIV infections through prevention of mother-to-child transmission of HIV (PMTCT) programs, yet little is known about adherence to infant-specific components of interventions. We hypothesized that infants born to mothers receiving the WiseMama (WM) electronic drug monitoring (EDM)-based adherence intervention would have increased uptake of six-week post-natal nevirapine (NVP) infant prophylaxis and better adherence to six-week early infant diagnosis (EID) HIV testing. Methods: At two sites in Uganda, the Wise Infant Study (WIN) prospectively followed an infant cohort. Infants were born to women enrolled in an RCT testing the effect of real-time reminders delivered via EDM on maternal adherence to antiretroviral therapy. We assessed intrapartum and discharge receipt of NVP prophylaxis using pharmacy and infant HIV DNA testing laboratory data. Results: Of 121 women eligible for WIN, 97 (80%) consented and enrolled; 46 had been randomized to control and 51 to intervention. There were no differences in receipt of a six-week NVP supply (control 87%, intervention 82%, p = 0.53). Receipt of any NVP prophylaxis did not vary by delivery location (p = 0.35), and although 12% of infants were delivered at non-study health facilities, they were not less likely to receive NVP at discharge (p = 0.37). Among infants with a completed HIV test, there was no difference in mean time to first test (control 52 days (SD 18), intervention 51 days (SD 15), p = 0.86). Only one infant, in the control group, tested positive for HIV. Conclusion and Global Health Implications: We found no significant differences in adherence to infant PMTCT practices between intervention and control infants with relatively high rates of NVP receipt albeit with suboptimal adherence to six-week EID testing. Further work is needed to ensure improved access, uptake, and follow-up of HIV-exposed infants in the Option B+ era. Key words: • Prevention of maternal to child transmission of HIV • HIV • Nevirapine • Antiretroviral therapy prophylaxis • Early infant diagnosis • HIV-exposed infants Copyright © 2020 Murillo et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in this journal, is properly cited.

To assess the effect of a savings-led economic empowerment intervention on viral suppression among adolescents living with HIV. Using data from Suubi + Adherence, a longitudinal, cluster randomized trial in southern Uganda (2012–2017), we examine the effect of the intervention on HIV RNA viral load, dichotomized between undetectable (< 40 copies/ml) and detectable (≥ 40 copies/ml). Cluster-adjusted comparisons of means and proportions were used to descriptively analyze changes in viral load between study arms while multi-level modelling was used to estimate treatment efficacy after adjusting for fixed and random effects. At 24-months post intervention initiation, the proportion of virally suppressed participants in the intervention cohort increased tenfold (ΔT2–T0 = + 10.0, p = 0.001) relative to the control group (ΔT2–T0 = + 1.1, p = 0.733). In adjusted mixed models, simple main effects tests identified significantly lower odds of intervention adolescents having a detectable viral load at both 12- and 24-months. Interventions addressing economic insecurity have the potential to bolster health outcomes, such as HIV viral suppression, by improving ART adherence among vulnerable adolescents living in low-resource environments. Further research and policy dialogue on the intersections of financial security and HIV treatment are warranted.

Background Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Purpose Well-validated risk prediction models help to stratify individuals on the basis of their disease risks and to guide health care professionals in decision-making. The incidence of nephrolithiasis has been increasing in Korea. Racial differences in the distribution of and risk for nephrolithiasis have been reported in Asia but no population-specific nephrolithiasis models have been developed. We aimed to develop a simplified nephrolithiasis prediction model for the Korean population by using data from general medical practice. Materials and methods This was a prospective, population-based cohort study in Korea. A total of 497,701 participants from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) were enrolled from 2002 to 2010. A Cox proportional hazards model was used. Results During a median follow-up time of 8.5 years (range, 2.0-8.9 years) and among 497,701 participants, there were 15,783 cases (3.2%) of nephrolithiasis. The parsimonious model included age, sex, income grade, alcohol consumption, body mass index, total cholesterol, fasting blood glucose, and medical history of diseases. The Harrell's C-statistic was 0.806 (95% confidence interval [CI], 0.790-0.821) and 0.805 (95% CI, 0.782-0.827) in the derivation and validation cohorts, respectively. Conclusions The results of the present study imply that nephrolithiasis risk can be predicted by use of data from general medical practice and based on predictors that clinicians and individuals from the general population are likely to know. This model comprises modifiable risk factors and can be used to identify those at higher risk who can modify their lifestyle to lower their risk for nephrolithiasis. This study also offers an opportunity for external validation or updating of the model through the incorporation of other risk predictors in other settings.

To report the prevalence of hypertension and projected 10-year absolute risk of acute cardiovascular disease in a large prospectively followed cohort of HIV-positive youth and adults beginning antiretroviral therapy in sub-Saharan Africa.HIV-positive individuals seeking HIV treatment, ages 13 years and older, were assessed for repeated blood pressure measurements over the first year following initiation of antiretroviral therapy, including serum total cholesterol, high-density lipoprotein, CD4 cell count and related clinical and laboratory measurements. Outcomes include hypertension, defined according to the 7th Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure categories, and Framingham Risk Score based 10-year cardiovascular disease risk estimates.Five thousand, five hundred and sixty-three patients had at least two blood pressure measurements on at least two separate occasions during the first year of antiretroviral therapy [median age of therapy initiation 34, first and third quartile (Q1-Q3) 28-40 years, 1841 (33.1%) men, baseline CD4 cell count 161 cells/μl (Q1-Q3 72-231 cells/μl]. Hypertension was diagnosed in 1551 patients [27.9%, 95% confidence interval (CI) 26.7- 29.1] including 786 (14.1%, 95% CI 13.2-15.1) who met criteria for stage 2 hypertension. The age-standardized prevalence for Ugandans aged 13 or more was 24.8% (95% CI 23.8-26.1). Among those with complete laboratory studies (n=1102), nearly all women were in the 10% or less 10-year Framingham Risk Score category, but 20% of men were at at least 10% or more long-term risk of acute cardiovascular disease.Efforts to combine HIV treatment with vascular disease risk factor prevention and management are urgently needed to address noncommunicable disease multimorbidity in HIV-positive persons in sub-Saharan Africa, particularly in men.

BACKGROUND: Retaining patients in clinical care is necessary to ensure successful antiretroviral treatment (ART) outcomes. Among patients who discontinue care, some reenter care at a later stage, whereas others are or will be lost from follow-up. We examined risk factors for health care interruptions and loss to follow-up within a cohort receiving ART in Uganda. METHODS: Using a large hospital cohort providing free universal ART and HIV clinical care, we assessed characteristics and risk factors for treatment interruptions, defined as a 12-month absence from care at Mildmay, and loss to follow-up, defined as absence from care greater than 12 months without reengagement in care at Mildmay. We included patients aged 14 years and above. We assessed these outcomes over time using Kaplan-Meier analysis and multivariable regression. RESULTS: Of 6970 eligible patients, 784 (11.2%) had a health care interruption of at least 12 months and 217 (3.1%) were lost to follow-up. Patients experiencing health care interruptions had higher baseline CD4 T-cell counts at ART initiation, defined as ≥ 250 cells per cubic millimeter [odds ratio (OR): 1.29, 95% confidence intervals (CI): 1.11 to 1.50], and lower levels of education (OR: 1.32, 95% CI: 1.09 to 1.61). Adolescents were much more likely to be lost to follow-up (OR: 3.11, 95% CI: 2.23 to 4.34). In contrast, having a partner (OR: 0.22, 95% CI: 0.16 to 0.31) or being sexually active at baseline (OR: 0.40, 95% CI: 0.28 to 0.55) was protective of loss to follow-up. CONCLUSIONS: Within this cohort, long periods of unsupervised health care interruptions were common.

The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients’ treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P

Background: The severity and outcome of malaria is influenced by host immunity in which chemokines such as Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) play an important role. Previous studies show that variations in the RANTES gene affect RANTES protein production, hence altering host immunity. In this study, the relationship between presence of mutations in RANTES and incidence of malaria in a cohort of children living in a malaria-endemic area of Uganda was determined. Methods: This was a longitudinal study comprising of 423 children aged between 6 months and 9 years, who were actively followed up for 1 year. Malaria episodes occurring in the cohort children were detected and the affected children treated with national policy drug regimen. Mutations in the RANTES gene were determined by PCR-RFLP method and their frequencies were calculated. A multivariate negative binomial regression model was used to estimate the impact of RANTES mutations on malaria incidence. In all statistical tests, a P-value of

We conducted a prospective cohort study of 306 HIV-1-infected women, followed from seroconversion for median 6.4 years in Uganda (UG) and Zimbabwe (ZM) to describe the incidence of major clinical outcomes (MCOs), defined as World Health Organization stage 4 conditions and any tuberculosis (TB). In Uganda, 19 MCOs occurred in 13 participants at median 4.6 years and a median CD4 count of 213 cells/mm3. In Zimbabwe, 29 MCOs occurred in 27 participants at median 4.0 years ( P < 0.001 versus UG) and median CD4 count of 219 cells/mm3 ( P = 0.83 versus UG). MCO incidence was not statistically different (UG: 2.82 cases/100 person-years versus ZM: 2.45; P = 0.64) except for TB (UG: 0.59 versus ZM: 2.02 cases/100 person-years; P = 0.02). This significant difference in TB incidence is primarily due to a TB screening and isoniazid prevention therapy programme that was implemented in Uganda, but not in Zimbabwe, highlighting the importance of integrated TB screening and treatment within HIV programmes.

The purpose of this study was to evaluate the frequency of multifocal osteonecrosis in patients with sickle cell disease. Between 1980 and 1989, 200 patients with sickle cell disease were treated in our institution for osteonecrosis. The patient population consisted of 102 males and 88 females with a mean age of twenty-six years at the time of presentation (range, eighteen to thirty-five years) and was followed until the year 2005. This cohort of patients was follow-up during average 15 years (until the year 2005). Multifocal osteonecrosis was defined as a disease of 3 or more anatomic sites. At the time of presentation, 49 patients were identified as having multifocal osteonecrosis. At the most recent follow-up, 87 patients had multifocal osteonecrosis. So at the last follow up among these eighty-seven patients, the occurrence of osteonecrosis was 158 lesions of the proximal femur associated with 151 proximal humerus osteonecroses, thirty-three lateral femoral condyle osteonecroses, twenty-eight distal femoral metaphysis osteonecroses, twenty-seven medial femoral condyle osteonecroses, twenty-three tibial plateau osteonecroses, twenty-one upper tibial metaphysis osteonecroses and forteen ankle osteonecroses. The total number of osteonecrosis was 455 in these 87 patients. The epiphyseal lesions were more frequent than the metadiaphyseal lesions excepted in the proximal tibia (Table 3). In conclusion, in patients with sickle cell disease, the risk of multifocal osteonecrosis is very high. In patients with hip osteonecrosis, the other joints should be evaluated with radiograph and MRI if the joint is symptomatic. In patients with osteonecrosis of the knee, shoulder or ankle, the patients’ hip should be evaluated by radiographs or MRI, regardless of whether the hip is symptomatic.