Costs of Summer Youth Employment to Prevent Violence: an Analysis and Implementer's Tool.

Gun homicide rates have risen 35% across the USA since the start of the COVID-19 pandemic. One promising intervention to prevent violent crime is summer youth employment programs (SYEPs), which provide youth with meaningful workplace experiences, prosocial engagements, and developmental opportunities during the summer months, when many otherwise lack structure. This paper presents a cost analysis of violence prevention-focused SYEPs to help implementers understand the costs generally and in their own community contexts-to advocate for adoption and secure funding of, effectively budget for, and successfully implement SYEPs. Researchers use an ingredient-based costing approach and provide a template for implementers to use and adapt for their context. SYEPs with the goal of reaching youth who are justice-involved or at risk of being victims or perpetrators of violence can cost $3331 per youth assisted, with 54% of this cost directly paid to youth through stipends. Cost per youth is driven by the intensity of the mentoring and support that community organizations provide to the program participants. Knowing the cost per youth assisted can inform further analysis, implementation, and expansion of SYEPs.

Nonfatal Firearm Injuries by Intent in the United States: 2016-2018 Hospital Discharge Records from the Healthcare Cost and Utilization Project.

INTRODUCTION: In addition to the nearly 40,000 firearm deaths each year, nonfatal firearm injuries represent a significant public health burden to communities in the United States. We aimed to describe the incidence and rates of nonfatal firearm injuries. METHODS: We calculated nonfatal firearm injury estimates using the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, including the Nationwide Emergency Department Samples and the National Inpatient Samples. We used the International Classification of Diseases, 10th Revision, Clinical Modification to identify firearm injury episodes. Deaths in the emergency department (ED) or as inpatients were excluded. RESULTS: In addition to the 118,171 persons shot and killed by firearms from 2016-2018, 228,380 people were shot (ratio 1.9:1) and treated at a hospital ED or admitted to hospital, a rate of 23.4 nonfatal firearm injury episodes per 100,000 population. The number of nonfatal injury episodes varied by year: 2018 had the lowest at 69,692, compared to 84,776 in 2017 and 73,912 in 2016. Unintentional injury episodes were the most frequent, accounting for 58.5% (n = 81,217) and 38.9% (n = 34,820) of total nonfatal firearm hospital discharges from the ED and inpatients, respectively. Assault episodes were the next most frequent, at 36.3% (n = 50,482) of ED and 49.5% (n = 44,290) of inpatient discharges. The highest rate of nonfatal firearm injury by five-year age group was for 20- to 24-year-olds. With an annual rate of 73.53 per 100,000 population, the rates for ages 20-24 were more than 10 times higher than the rates for patients younger than 15 or 60 years and older. More than half (53.4%, n = 121,884) of hospital-treated, nonfatal firearm injury episodes were patients living in ZIP codes with a median household income in the lowest quartile, compared to 7.5% (n = 17,102) for patients residing in the highest income quartile ZIP codes, a sevenfold difference. CONCLUSION: For every person shot and killed by a gun in the US, two more are wounded. Unlike firearm deaths, which are predominantly suicides, most nonfatal firearm injury episodes are unintentional or with an assault intent. Having a reliable source of nonfatal injury data is essential to understanding the incidence of firearm injuries.

Breast abnormalities in adolescents receiving antiretroviral therapy.

BACKGROUND: Antiretrovirals, particularly efavirenz (EFV), have been shown to cause breast abnormalities in adults. Little is known about the prevalence of these adverse effects among adolescents receiving antiretroviral therapy (ART). OBJECTIVES: The aim of this article was to examine the extent of breast abnormalities in adolescents receiving ART and determine any clinical associations. METHODS: A retrospective record review describing breast conditions in adolescents receiving ART at three facilities in Johannesburg was conducted. Patients aged 10-19 years, who presented from January to December 2014, were included in the study. Analyses were conducted to determine whether EFV was associated with increased breast conditions. RESULTS: Of the 631 patient records reviewed, 37 (6%) had an abnormal breast event documented; with 24/37 (65%) being male patients. Patients with abnormal breast conditions were 1.5 years older than patients with normal breast development (p < 0.0005). Forty-one abnormal breast events were observed in 37 patients, with 20 described as gynaecomastia or lipomastia (49%). Of the 37 patients, 44% (n = 19) had concurrent generalised lipodystrophy. Of those with an abnormal breast event, 71% of patients had CD4 counts > 500 cells/µL and were virologically suppressed (n = 29). Those on EFV had a significantly higher prevalence of breast abnormalities compared to other regimens (p = 0.016). CONCLUSION: Of the studied patients, 6% had an abnormal breast condition. The use of EFV and increased age were associated with breast abnormalities in this population. Further research is needed to better understand the implications of this potential side effect.

The impact of adverse events on health-related quality of life among patients receiving treatment for drug-resistant tuberculosis in Johannesburg, South Africa.

BACKGROUND: Adverse events (AEs) are common during treatment of drug-resistant tuberculosis (DR-TB). Little is known about the health-related quality of life (HRQoL) of patients receiving treatment for DR-TB or the effect of AEs on HRQoL. METHODS: We conducted a cross-sectional study among adult patients with laboratory-confirmed rifampicin resistant tuberculosis (TB) on DR-TB treatment at a public-sector outpatient DR-TB clinic in Johannesburg, South Africa between 02/2015-01/2018. Data on HRQoL using the Medical Outcomes Short Form-36 (SF-36) questionnaire and self-reported AEs were collected by trained interviewers through face-to-face interviews. We report averages for the eight major domains and mental (MCS) and physical health (PCS) component summary scores, stratified by whether AEs were reported in the last four weeks. For comparative purposes, we enrolled two other patient groups and included data on a separate group of healthy adults. RESULTS: We enrolled 149 DR-TB patients (median age 36 years IQR 29-43, 55% male, 77.9% HIV-positive, 81% on ART, 61.8% on a standard long-course regimen and 44.3% on DR-TB treatment for less than 6 months). 58/149 (38.9%) patients reported a total of 122 AEs in the preceding 4 weeks, of these the most common were joint pain (n = 22), peripheral neuropathy (n = 16), hearing loss (n = 15), nausea and vomiting (n = 12) and dizziness or vertigo (n = 11). SF-36 domains and summary scores (MCS and PCS) were lower in those who reported an AE compared to those who did not, and both were lower than healthy adults. Compared to those who did not report an AE, patients who reported AEs were more likely to have a low MCS (aRR 2.24 95% CI 1.53-3.27) and PCS (aRR 1.52 95% CI 1.07-2.18) summary score. HRQoL was lower among those on DR-TB treatment for 6 months or less. CONCLUSION: Results show that DR-TB had a substantial impact on patients' quality of life, but that AEs during the early months on treatment may be responsible for reducing HRQoL even further. Our findings highlight the negative effects of injectable agents on HRQoL. Patients require an integrative patient-centered approach to deal with DR-TB and HIV and the potential overlapping toxicities which may be worsened by concurrent treatment.

Unraveling the South African Breast Cancer Story: The Relationship of Patients, Delay to Diagnosis, and Tumor Biology With Stage at Presentation in an Urban Setting.

BACKGROUND: Adverse outcomes from breast cancer disproportionately affect women in sub-Saharan Africa, with delay the most studied contribution to advanced stage at presentation. However, tumor molecular biology and its contribution to advanced stage are yet to be explored. MATERIALS AND METHODS: Patients newly diagnosed with breast cancer in a South African tertiary breast center completed a questionnaire and file review concerning socioeconomics, delay to care, stage at presentation, and molecular characteristics. Logistic regression was done to determine the relative risk of advanced stage presentation. RESULTS: Advanced stage was present in 70.1% (n = 162) of the 231 participants, with 55.8% stage III (n = 129) and 32% (n = 72) having a T4 tumor. The median age was 56 y with 21.6% (n = 47) aged <45 y. Most common subtype was luminal B (57.7%, n = 128) followed by luminal A (21.6%, n = 48), triple negative (13.9%, n = 31), and HER2 positive (6.7%, n = 15). Lobular cancer (incidence risk ratio [IRR], 1.29; 95% confidence interval [CI], 1.03-1.62), high grade and intermediate grade tumors (IRR, 1.90; 95% CI, 1.15-3.13 and IRR, 1.95; 95% CI, 1.18-3.22, respectively), high Ki67 proliferation index (IRR, 1.30; 95% CI, 1.02-1.66), and HER2 overexpression (IRR, 1.32; 95% CI, 1.12-1.55) were more likely to present with advanced disease, as were luminal B (HER2+) cancers (adjusted IRR [aIRR], 1.46; 95% CI, 1.10-1.95). Although on univariate analysis Black and young participants were both more likely to have advanced stage (IRR, 1.23; 95% CI, 1.01-1.49 and IRR, 1.25; 95% CI, 1.04-1.51, respectively), in multivariate analysis controlling for tumor biology and delay, these were no longer significant (aIRR, 1.12; 95% CI, 0.91-1.37 and aIRR, 1.17; 95% CI, 0.94-1.48, respectively). CONCLUSIONS: Tumor biology has a compelling role in the etiology of advanced-stage disease irrespective of socioeconomic factors. Accurate pathologic assessment is important in planning breast cancer care in Africa.

Impact of Xpert MTB/RIF and decentralized care on linkage to care and drug-resistant tuberculosis treatment outcomes in Johannesburg, South Africa.

BACKGROUND: In 2011, South Africa improved its ability to test for rifampicin-resistant TB (RR-TB) by introducing GeneXpert MTB/RIF. At the same time, the South African National TB program adopted a policy decentralized, outpatient treatment for drug resistant (DR-) TB. We aim to analyze the impact of these changes on linkage to care and DR-TB treatment outcomes. METHODS: We retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 (early cohort) and 07/2013-06/2014 (late cohort) with records of patients initiating DR-TB treatment at one of the city's four public sector treatment sites. We determine the proportion of persons diagnosed with RR-TB who initiated DR-TB treatment and report time to treatment initiation (TTI) before and after the implementation of Xpert MTB/RIF roll-out in Johannesburg, South Africa. We conducted a sub-analysis among those who initiated DR-TB treatment at the decentralized outpatient DR-TB centers to determine if delays in treatment initiation have a subsequent impact on treatment outcomes. RESULTS: Five hundred ninety four patients were enrolled in the early cohort versus 713 in the late cohort. 53.8 and 36.8% of patients were diagnosed with multi-drug resistant TB in the early and late cohorts, respectively. The proportion of RR-TB confirmed cases diagnosed by Xpert MTB/RIF increased from 43.4 to 60.5% between the early and late cohorts, respectively. The proportion who initiated treatment increased from 43.1% (n = 256) to 60.3% (n = 430) in the late cohort. Pre-treatment mortality during the early and the late cohort reduced significantly from 17.5 to 5.8% while lost to follow-up remained high. Although TTI reduced by a median of 19 days, from 33 days (IQR 12-52) in the early cohort to 14 days (IQR 7-31) in the late cohort, this did not translate to improved treatment outcomes and we found no difference in terms of treatment success or on-treatment mortality for those that initiated without delay vs. those that deferred initiation. CONCLUSION: Pre-treatment mortality reduced significantly during late Xpert MTB/RIF coverage but there was no significant difference after treatment was initiated. Despite improvements there is still a significant diagnosis and treatment gap for patients diagnosed with RR-TB and improving treatment outcomes remains critical.

High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen.

South African patients with rifampicin-resistant tuberculosis (TB) and resistance to fluoroquinolones and/or injectable drugs (extensively drug-resistant (XDR) and preXDR-TB) were granted access to bedaquiline through a clinical access programme with strict inclusion and exclusion criteria.PreXDR-TB and XDR-TB patients were treated with 24 weeks of bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed. 200 patients were enrolled: 87 (43.9%) had XDR-TB, 99 (49.3%) were female and the median age was 34 years (interquartile range (IQR) 27-42). 134 (67.0%) were living with HIV; the median CD4+ count was 281 cells·µL-1 (IQR 130-467) and all were on antiretroviral therapy.16 out of 200 patients (8.0%) did not complete 6 months of bedaquiline: eight were lost to follow-up, six died, one stopped owing to side effects and one was diagnosed with drug-sensitive TB. 146 out of 200 patients (73.0%) had favourable outcomes: 139 (69.5%) were cured and seven (3.5%) completed treatment. 25 patients (12.5%) died, 20 (10.0%) were lost from treatment and nine (4.5%) had treatment failure. 22 adverse events were attributed to bedaquiline, including a QT interval corrected using the Fridericia formula (QTcF) >500 ms (n=5), QTcF increase >50 ms from baseline (n=11) and paroxysmal atrial flutter (n=1).Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this preXDR-TB and XDR-TB cohort.

Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study.

BACKGROUND: Addition of bedaquiline to treatment for multidrug-resistant tuberculosis was associated with an increased risk of death in a phase 2b clinical trial, resulting in caution from WHO. Following a compassionate access programme and local regulatory approval, the South African National Tuberculosis Programme began widespread use of bedaquiline in March, 2015, especially among patients with extensively drug resistant tuberculosis for whom no other effective treatment options were available. We aimed to compare mortality in patients on standard regimens with that of patients on regimens including bedaquiline. METHODS: In this retrospective cohort study, we analysed patient data from the South African rifampicin-resistant tuberculosis case register (EDRweb), and identified additional mortality using the national vital statistics register. We excluded patients who started treatment before July 1, 2014, or after March 31, 2016; patients younger than 15 years or older than 75 years; patients without documented rifampicin resistance, and patients with pre-extensively drug-resistant tuberculosis (multidrug-resistant tuberculosis with further resistance to a second-line injectable or fluoroquinolone). We compared all-cause mortality between patients who received bedaquiline in treatment regimens and those who did not. Patients who did not receive bedaquiline had kanamycin or capreomycin and moxifloxacin as core medicines in their regimen. We estimated hazard ratios for mortality separately for multidrug-resistant or rifampicin-resistant tuberculosis and extensively drug-resistant tuberculosis and adjusted using propensity score quintile strata for the potential confounders of sex, age, HIV and antiretroviral therapy status, history of prior tuberculosis, valid identification number, and year and province of treatment. FINDINGS: 24 014 tuberculosis cases were registered in the EDRweb between July 1, 2014, and March 31, 2016. Of these, 19 617 patients initiated treatment and met our analysis eligibility criteria. A bedaquiline-containing regimen was given to 743 (4·0%) of 18 542 patients with multidrug-resistant or rifampicin-resistant tuberculosis and 273 (25·4%) of 1075 patients with extensively drug-resistant tuberculosis. Among 1016 patients who received bedaquiline, 128 deaths (12·6%) were reported, and there were 4612 deaths (24·8%) among 18 601 patients on the standard regimens. Bedaquiline was associated with a reduction in the risk of all-cause mortality for patients with multidrug-resistant or rifampicin-resistant tuberculosis (hazard ratio [HR] 0·35, 95% CI 0·28-0·46) and extensively drug-resistant tuberculosis (0·26, 0·18-0·38) compared with standard regimens. INTERPRETATION: Our retrospective cohort analysis of routinely reported data in the context of high HIV and extensively drug-resistant tuberculosis prevalence showed that bedaquiline-based treatment regimens were associated with a large reduction in mortality in patients with drug-resistant tuberculosis, compared with the standard regimen. FUNDING: None.

Age Differences by Sex in Antiretroviral-Naïve Participants: Pooled Analysis from Randomized Clinical Trials.

Age and sex effects on antiretroviral therapy (ART) response are not well elucidated. Our pooled analysis of 40 randomized clinical trials measured the association of age and sex on CD4+ T cell count changes and virologic suppression using multivariable regression modeling. The average increase in CD4+ T cell count from baseline to week 48 was 17.3 cells/mm3 lower and clinically insignificant (95% confidence interval -30.8 to -3.8) among women ages ≥ 50 years (n = 573), compared to women ≤ 35 years (n = 3,939). Results were similar for men. Virologic suppression odds were 60% and 21% times greater among participants ≥50 years compared to ≤35 years, in women and men, respectively. In both sexes, larger increases in CD4+ T cell count changes were observed in younger, compared to older, participants; however, virologic suppression was higher in older, compared to younger, participants suggesting a non-sex-specific age effect response to ART.

Incremental Cost Effectiveness of Bedaquiline for the Treatment of Rifampicin-Resistant Tuberculosis in South Africa: Model-Based Analysis.

BACKGROUND: Nearly 20,000 people were diagnosed with multi-drug and rifampicin-resistant tuberculosis (MDR/RR-TB) in South Africa in 2015, yet only one-half of the patients who start treatment are expected to have a successful outcome. There is increasing evidence of the effectiveness and safety of new drug regimens containing bedaquiline for MDR/RR-TB; however, whether they are affordable for high-burden, limited-resource settings is uncertain. OBJECTIVE: Our objective was to determine the incremental cost effectiveness of a bedaquiline-based regimen for MDR/RR-TB treatment in South Africa compared with the standard kanamycin-based regimen. METHODS: We established a Markov model for ambulatory treatment of MDR/RR-TB in a high-HIV prevalence setting, parameterized using clinical outcomes from the South African National TB Programme (SA NTP) before (2012-2014) and after (2015-2016) bedaquiline roll-out. The effectiveness of treatment was evaluated in disability-adjusted life-years (DALYs). Ingredient costs from the provider's perspective were collected in 2016 South African Rand and converted to $US, including bedaquiline at $US675.23 per 6-month treatment course. Culture conversion rates were derived from the phase IIb trial of bedaquiline, and disability adjustments were adapted from published literature. Costs and effectiveness were discounted at 3%. RESULTS: For non-bedaquiline regimens, the total expected cost over the 10-year time horizon for a patient with MDR/RR-TB was $US4439 with disability-adjusted survival of 5.1 years. Replacing capreomycin with bedaquiline in patients who failed MDR/RR-TB treatment and required treatment for extensively drug-resistant (XDR-TB) resulted in cost savings ($US4356; 1.8% less) and similar effectiveness (0.02 DALYs averted). As a result, the standard regimen (no bedaquiline) was dominated. Replacing kanamycin with bedaquiline to provide all patients with MDR/RR-TB access to bedaquiline cost $US4647 (4.3% more) and averted 0.17 DALYs compared with the no bedaquiline regimen. The incremental cost-effectiveness ratio was $US1242/DALY averted. CONCLUSION: Markov modelling indicates providing bedaquiline for all patients with MDR/RR-TB could increase the 24-month treatment success rate in South Africa from 56.3% using the current regimen to 60.6%, at a cost $US2.6 million over a 10-year horizon, less than 1% of the estimated $US425 million SA NTP annual budget.

The Effect of Access to Information on Beliefs Surrounding Breast Cancer in South Africa.

Breast cancer is the most common cancer affecting women in South Africa. There is little knowledge of beliefs to help identify key areas to improve support and education in this demographically and culturally diverse population. Women with a variety of demographic and socioeconomic characteristics accessing care for breast cancer were asked their agreement to statements of knowledge and beliefs about breast cancer. Of the 259 participants, positive statements of medical cure (87.9%) and family support (90.5%) were most commonly believed. Beliefs in faith-based cure and alternative treatments were also present (79.5 and 24.9%, respectively). Negative beliefs were initially more likely in black patients (RR: 11.57, 95%CI: 1.37-97.69) as was belief of cancer as a punishment (RR: 6.85, 95%CI: 1.41-33.21). However, in multivariate analysis adjusting for age, education and access to information (by newspaper, Internet and confidence in reading and writing), there was no difference between racial groups or hospital attended. Reading a newspaper or accessing the Internet was the most protective against belief that cancer was a punishment or curse (Internet use: aRR: 0.12, 95%CI: 0.02-0.99), belief in alternative methods of cure (newspaper use: aRR: 0.51, 95%CI: 0.27-0.96) and the negative beliefs of death and disfigurement (Internet use: aRR: 0.00, 95%CI: 0.00-0.00). Positive expressions of cure and beating cancer were found equally in all women. Attitudes and beliefs about cancer showed little independent demographic or socioeconomic variance. Negative beliefs were mitigated by access to information and confidence in literacy.

Estimating the cost-per-result of a national reflexed Cryptococcal antigenaemia screening program: Forecasting the impact of potential HIV guideline changes and treatment goals.

INTRODUCTION: During 2016, the National Health Laboratory Service (NHLS) introduced laboratory-based reflexed Cryptococcal antigen (CrAg) screening to detect early Cryptococcal disease in immunosuppressed HIV+ patients with a confirmed CD4 count of 100 cells/µl or less. OBJECTIVE: The aim of this study was to assess cost-per-result of a national screening program across different tiers of laboratory service, with variable daily CrAg test volumes. The impact of potential ART treatment guideline and treatment target changes on CrAg volumes, platform choice and laboratory workflow are considered. METHODS: CD4 data (with counts < = 100 cells/µl) from the fiscal year 2015/16 were extracted from the NHLS Corporate Date Warehouse and used to project anticipated daily CrAg testing volumes with appropriately-matched CrAg testing platforms allocated at each of 52 NHLS CD4 laboratories. A cost-per-result was calculated for four scenarios, including the existing service status quo (Scenario-I), and three other settings (as Scenarios II-IV) which were based on information from recent antiretroviral (ART) guidelines, District Health Information System (DHIS) data and UNAIDS 90/90/90 HIV/AIDS treatment targets. Scenario-II forecast CD4 testing offered only to new ART initiates recorded at DHIS. Scenario-III projected all patients notified as HIV+, but not yet on ART (recorded at DHIS) and Scenario-IV forecast CrAg screening in 90% of estimated HIV+ patients across South Africa (also DHIS). Stata was used to assess daily CrAg volumes at the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles across 52 CD4-laboratories. Daily volumes were used to determine technical effort/ operator staff costs (% full time equivalent) and cost-per-result for all scenarios. RESULTS: Daily volumes ranged between 3 and 64 samples for Scenario-I at the 5th and 95th percentile. Similarly, daily volumes ranges of 1-12, 2-45 and 5-100 CrAg-directed samples were noted for Scenario's II, III and IV respectively. A cut-off of 30 CrAg tests per day defined use of either LFA or EIA platform. LFA cost-per-result ranged from $8.24 to $5.44 and EIA cost-per-result between $5.58 and $4.88 across the range of test volumes. The technical effort across scenarios ranged from 3.2-27.6% depending on test volumes and platform used. CONCLUSION: The study reported the impact of programmatic testing requirements on varying CrAg test volumes that subsequently influenced choice of testing platform, laboratory workflow and cost-per-result. A novel percentiles approach is described that enables an overview of the cost-per-result across a national program. This approach facilitates cross-subsidisation of more expensive lower volume sites with cost-efficient, more centralized higher volume laboratories, mitigating against the risk of costing tests at a single site.

Treatment initiation among persons diagnosed with drug resistant tuberculosis in Johannesburg, South Africa.

BACKGROUND: In South Africa, roughly half of the drug-resistant TB cases diagnosed are reported to have been started on treatment. We determined the proportion of persons diagnosed with rifampicin resistant (RR-) TB who initiated treatment in Johannesburg after the introduction of decentralized RR-TB care in 2011. METHODS: We retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 with records of patients initiating RR-TB treatment at one of the city's four public sector treatment sites (one centralized, three decentralized). Patients were followed from date of diagnosis until the earliest of RR-TB treatment initiation, death, or 6 months' follow-up. We report diagnostic methods and outcomes, proportions initiating treatment, and median time from diagnosis to treatment initiation. RESULTS: 594 patients were enrolled (median age 34 (IQR 29-42), 287 (48.3%) female). Diagnosis was by GenoType MTBDRplus (Hain-Life-Science) line probe assay (LPA) (281, 47.3%), Xpert MTB/RIF (Cepheid) (258, 43.4%), or phenotypic drug susceptibility testing (DST) (30, 5.1%) with 25 (4.2%) missing a diagnosis method. 320 patients (53.8%) had multi-drug resistant TB, 158 (26.6%) rifampicin resistant TB by Xpert MTB/RIF, 102 (17.2%) rifampicin mono-resistance, and 14 (2.4%) extensively drug-resistant TB. 256/594 (43.0%) patients initiated treatment, representing 70.7% of those who were referred for treatment (362/594). 338/594 patients (57.0%) did not initiate treatment, including 104 (17.5%) who died before treatment was started. The median time from sputum collection to treatment initiation was 33 days (IQR 12-52). CONCLUSION: Despite decentralized RR-TB treatment, fewer than half the patients diagnosed in Johannesburg initiated appropriate treatment. Offering treatment at decentralized sites alone is not sufficient; improvements in linking patients diagnosed with RR-TB to effective treatment is essential.

Fear of Treatments Surpasses Demographic and Socioeconomic Factors in Affecting Patients With Breast Cancer in Urban South Africa.

PURPOSE: Breast cancer is the most common cause of cancer in women in South Africa, and often patients present late. There is little understanding of the psychosocial stresses affecting women with breast cancer in Africa. METHODS: A questionnaire was distributed to 263 patients with breast cancer at two sites (one government and one private facility) in Johannesburg. Self-reported levels of fear were recorded on summative scales and their relationship to demographic variables assessed through univariable and multivariable modified Poisson regression. RESULTS: Fears related to treatments and prognosis, particularly radiation, loss of hair, and loss of breast, were far stronger than those related to socioeconomic barriers. Relative risk (RR) of most fears was higher in women younger than age 40 years, including treatment affordability (RR, 1.80; 95% CI, 1.26 to 2.56), hair loss (RR, 1.48; 95% CI, 1.12 to 2.95), and surgery (RR, 1.31; 95% CI, 1.02 to 1.68). Difficulty taking time off work predicted fear of job loss (RR, 2.59; 95% CI, 1.59 to 4.21) and missing appointments because of transport (RR, 2.46; 95% CI, 1.52 to 3.96) or family commitments (RR, 2.46; 95% CI, 1.52 to 3.96). Women with dependents and black women were more afraid of dying (RR, 1.73; 95% CI, 1.03 to 2.90; and RR, 1.79; 95% CI, 1.33 to 2.24, respectively); however, socioeconomic status in this sample was a strong confounder of race and explained most of the racial differences in levels of fear. CONCLUSION: The most significant fears around breast cancer were related to treatment modalities and adverse effects rather than transport, financial, or work concerns. Young age and job insecurity were predictive of increased fears. Education about treatments has a key role to play in improving access to breast cancer care in South Africa.

Adverse drug reactions during drug-resistant TB treatment in high HIV prevalence settings: a systematic review and meta-analysis.

Objectives: To estimate the prevalence of adverse drug reactions or events (ADR) during drug-resistant TB (DR-TB) treatment in the context of settings with high HIV prevalence (at least 20% of patients). Methods: We conducted a systematic review and meta-analysis of articles in PubMed and Scopus. Pooled proportions of patients experiencing adverse events and relative risk with 95% CI were calculated. Results: The search yielded 24 studies, all observational cohorts. Ten reported on the number of patients experiencing ADR and were included in the meta-analysis representing 2776 study participants of whom 1943 were known to be HIV infected (70.0%). An average of 83% (95% CI: 82%-84%) of patients experienced one or more ADR. Among the seven articles ( n = 664 study participants) with information on occurrence of severe ADR, 24% (95% CI: 21%-27%) of patients experienced at least one severe ADR during drug-resistant TB treatment. Sixteen of the 24 studies analysed the relative risk of ADR by HIV infection, nine of which found no statistically significant association between HIV infection and occurrence of drug-related ADR. There was insufficient information to disaggregate risk by concomitant treatment with HIV antiretrovirals or by immunosuppression (CD4 count). Conclusions: No randomized clinical trials were found for WHO-recommended treatment of drug-resistant TB treatment where at least 20% of the cohort was coinfected with HIV. Nearly all patients (83%) experience ADR during DR-TB treatment. While no significant association between ADR and HIV coinfection was found, further research is needed to determine whether concomitant antiretrovirals or immunosuppression increases the risks for HIV-infected patients.

Establishing a cost-per-result of laboratory-based, reflex Cryptococcal antigenaemia screening (CrAg) in HIV+ patients with CD4 counts less than 100 cells/µl using a Lateral Flow Assay (LFA) at a typical busy CD4 laboratory in South Africa.

INTRODUCTION: Cryptococcal meningitis is a major cause of mortality and morbidity in countries with high HIV prevalence, primarily affecting patients whose CD4 are < = 100 cells/µl. Routine Cryptococcal Antigen (CrAg) screening is thus recommended in the South African HIV treatment guidelines for all patients with CD4 counts < = 100 cells/µl, followed by pre-emptive anti-fungal therapy where CrAg results are positive. A laboratory-based reflexed CrAg screening approach, using a Lateral Flow Assay (LFA) on remnant EDTA CD4 blood samples, was piloted at three CD4 laboratories. OBJECTIVES: This study aimed to assess the cost-per-result of laboratory-based reflexed CrAg screening at one pilot CD4 referral laboratory. METHODS: CD4 test volumes from 2014 were extracted to estimate percentage of CD4 < = 100 cells/µl. Daily average volumes were derived, assuming 12 months per/year and 21.73 working days per/month. Costing analyses were undertaken using Microsoft Excel and Stata with a provider prospective. The cost-per-result was estimated using a bottom-up method, inclusive of test kits and consumables (reagents), laboratory equipment and technical effort costs. The ZAR/$ exchange of 14.696/$1 was used, where applicable. One-way sensitivity analyses on the cost-per-result were conducted for possible error rates (3%- 8%, reductions or increases in reagent costs as well as test volumes (ranging from -60% to +60%). RESULTS: The pilot CD4 laboratory performed 267000 CD4 tests in 2014; ~ 9.3% (27500) reported CD4< = 100 cells/µl, equivalent to 106 CrAg tests performed daily. A batch of 30-tests could be performed in 1.6 hours, including preparation and analysis time. A cost-per-result of $4.28 was reported, with reagents contributing $3.11 (72.8%), while technical effort and laboratory equipment overheads contributed $1.17 (27.2%) and $0.03 (<1%) respectively. One-way sensitivity analyses including increasing or decreasing test volumes by 60% revealed a cost-per-result range of $3.84 to $6.03. CONCLUSION: A cost-per-result of $4.28 was established in a typical CD4 service laboratory to enable local budgetary cost projections and programmatic cost-effectiveness modelling. Varying reagent costs linked to currency exchange and varying test volumes in different levels of service can lead to varying cost-per-test and technical effort to manage workload, with an inverse relationship of higher costs expected at lower volumes of tests.

Male Breast Cancer Has Limited Effect on Survivor's Perceptions of Their Own Masculinity.

The purpose of the current study was to describe male breast cancer in Johannesburg, South Africa, and assess whether male breast cancer patients' perception of their own masculinity was affected by having a cancer commonly seen in women. A retrospective file review was carried out at two hospitals, one private and one government, of male breast cancer patients from 2007 to 2012 followed by a telephone survey of patients identified during review. Of approximately 3,000 breast cancer patients seen in the 5 years reviewed, 23 cases of male breast cancer were identified. Most were diagnosed with invasive ductal carcinoma ( n = 19, 83%). Stage at presentation was from stages 0 to 3 (Stage 0 [ n = 2, 9%], Stage 1 [ n = 3, 13%], Stage 2 [ n = 12, 52%], Stage 3 [ n = 6, 26%]) and no patients were metastatic at presentation. The telephonic survey was completed by 18 patients (78%). Nearly all ( n = 17/18) shared their diagnosis with family and close friends. Two thirds of patients delayed presentation and government hospital patients were more likely to present later than private sector hospital patients. Although most male breast cancer patients sampled did not perceive the breast cancer diagnosis as affecting their masculinity, Black men and those treated in government hospitals were less likely to be aware of male breast cancer, and were more likely to have their perception of their own masculinity affected.

Early Outcomes Of Decentralized Care for Rifampicin-Resistant Tuberculosis in Johannesburg, South Africa: An Observational Cohort Study.

OBJECTIVE: We describe baseline characteristics, time to treatment initiation and interim patient outcomes at a decentralized, outpatient treatment site for rifampicin-resistant TB (RR-TB). METHODS: Prospective observational cohort study of RR-TB patients from March 2013 until December 2014. Study subjects were followed until completion of the intensive phase of treatment (6 months), transfer out, or a final outcome (loss from treatment (LFT) or death). RESULTS: 214 patients with RR-TB were enrolled in the study. Xpert MTB/RIF was the diagnostic test of rifampicin resistance for 87% (n = 186), followed by direct PCR on AFB positive specimen in 14 (7%) and indirect PCR on cultured isolate in 5 (2%). Median time between sputum testing and treatment initiation was 10 days (IQR 6-21). Interim outcomes were available in 148 patients of whom 78% (n = 115) were still on treatment, 9% (n = 13) had died, and 14% (n = 20) were LFT. Amongst 131 patients with culture positive pulmonary TB, 85 (64.9%) were culture negative at 6 months, 12 were still sputum culture positive (9.2%) and 34 had no culture documented or contaminated culture (26%). Patients who initiated as outpatients within 1 week of sputum collection for diagnosis of RR-TB had a significantly lower incidence of LFT (IRR 0.30, 95% CI: 0.09-0.98). HIV co-infection occurred in 178 patients (83%) with a median CD4 count 88 cells/ml3 (IQR 27-218). CONCLUSIONS: Access to decentralized treatment coupled with the rapid diagnosis of RR-TB has resulted in short time to treatment initiation. Despite the lack of treatment delays, early treatment outcomes remain poor with high rates of death and loss from care.

A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis.

OBJECTIVE: Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. METHODS: We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. FINDINGS: Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient ß1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (ß1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (ß1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low-income households (ß1 = -0.048, p < 0.0001, R2 = 0.084). Municipalities with more low-income households also have marginally higher TB testing rates, however, this association is not statistically significant (ß1 = -0.025, p = 0.676, R2 = 0.001). There is no relationship between TB prevalence and the proportion of informal settlement households (ß1 = 0.021, p = 0.136, R2 = 0.014). CONCLUSIONS: These analyses reveal that the set of characteristics identified by the Global Plan as defining key populations do not adequately predict populations with high TB burden. For example, we find that higher TB prevalence is correlated with more urbanized municipalities but not with informal settlements. We highlight several factors that are counter-intuitively those most associated with high TB burdens and which should therefore play a large role in any effective targeting strategy. Targeting active case finding to key populations at higher risk of infection or poor clinical outcomes may prove more cost effective than broad efforts. However, these results should increase caution in current targeting of active case finding interventions.