Assessment of the tuberculosis case-finding and prevention cascade among people living with HIV in Zambia - 2018: a cross-sectional cluster survey.

BACKGROUND: The Ministry of Health Zambia recommends tuberculosis preventive treatment (TPT) with 6 months daily isoniazid for all people living with human immunodeficiency virus (HIV) after ruling out active tuberculosis disease. We sought to estimate the percentage of people living with HIV who progress through each stage of the tuberculosis case-finding and prevention cascade in two provinces with the highest tuberculosis burden in Zambia. METHODS: In this cross-sectional survey, we used a two-stage cluster sampling method. We sampled 12 healthcare facilities with probability proportional to size. Patient volume determined facility cluster size. During October 2018, from each facility we systematically sampled medical records of adults and children living with HIV. Our primary outcome of interest was TPT initiation rate among eligible people living with HIV, weighted for complex survey design. The Rao-Scott adjusted chi-square test was used to test for differences in TPT initiation rate and other indicators from the tuberculosis prevention cascade by age group and province of residence. Additionally, we conducted semi-structured interviews with healthcare workers at each facility to assess TPT knowledge and identify challenges to its implementation. RESULTS: We sampled 482 records of people living with HIV (including 128 children living with HIV). Excluding two people diagnosed with tuberculosis disease before enrollment in HIV care, 93.4% underwent tuberculosis symptom screening. Of those, 4.7% were diagnosed with tuberculosis disease and 95.3% were TPT-eligible, of whom 24.7% initiated TPT. TPT initiation was lower among eligible children (7.7%) compared with adults (25.2%, p = 0.03) and Copperbelt residents (3.1%) compared with Lusaka residents (35.8%, p < 0.01). TPT completion rate was 38.4% among people living with HIV who initiated the 6-month course. Among interviewed healthcare workers, 58.3% (unweighted) incorrectly relayed the number of symptoms needed for a positive tuberculosis symptom screen, 83.3% (unweighted) reported insufficient isoniazid stockpile for completion at the time of TPT initiation, and only 27.3% (unweighted) reported receiving TPT-specific training. CONCLUSIONS: TPT uptake among people living with HIV in Zambia is challenged by inconsistent tuberculosis screening, lack of TPT training for healthcare workers, and supply chain inefficiencies. Addressing these barriers may increase TPT initiations and improve outcomes among people living with HIV.

The Detection of Opioid Misuse and Heroin Use From Paramedic Response Documentation: Machine Learning for Improved Surveillance.

BACKGROUND: Timely, precise, and localized surveillance of nonfatal events is needed to improve response and prevention of opioid-related problems in an evolving opioid crisis in the United States. Records of naloxone administration found in prehospital emergency medical services (EMS) data have helped estimate opioid overdose incidence, including nonhospital, field-treated cases. However, as naloxone is often used by EMS personnel in unconsciousness of unknown cause, attributing naloxone administration to opioid misuse and heroin use (OM) may misclassify events. Better methods are needed to identify OM. OBJECTIVE: This study aimed to develop and test a natural language processing method that would improve identification of potential OM from paramedic documentation. METHODS: First, we searched Denver Health paramedic trip reports from August 2017 to April 2018 for keywords naloxone, heroin, and both combined, and we reviewed narratives of identified reports to determine whether they constituted true cases of OM. Then, we used this human classification as reference standard and trained 4 machine learning models (random forest, k-nearest neighbors, support vector machines, and L1-regularized logistic regression). We selected the algorithm that produced the highest area under the receiver operating curve (AUC) for model assessment. Finally, we compared positive predictive value (PPV) of the highest performing machine learning algorithm with PPV of searches of keywords naloxone, heroin, and combination of both in the binary classification of OM in unseen September 2018 data. RESULTS: In total, 54,359 trip reports were filed from August 2017 to April 2018. Approximately 1.09% (594/54,359) indicated naloxone administration. Among trip reports with reviewer agreement regarding OM in the narrative, 57.6% (292/516) were considered to include information revealing OM. Approximately 1.63% (884/54,359) of all trip reports mentioned heroin in the narrative. Among trip reports with reviewer agreement, 95.5% (784/821) were considered to include information revealing OM. Combined results accounted for 2.39% (1298/54,359) of trip reports. Among trip reports with reviewer agreement, 77.79% (907/1166) were considered to include information consistent with OM. The reference standard used to train and test machine learning models included details of 1166 trip reports. L1-regularized logistic regression was the highest performing algorithm (AUC=0.94; 95% CI 0.91-0.97) in identifying OM. Tested on 5983 unseen reports from September 2018, the keyword naloxone inaccurately identified and underestimated probable OM trip report cases (63 cases; PPV=0.68). The keyword heroin yielded more cases with improved performance (129 cases; PPV=0.99). Combined keyword and L1-regularized logistic regression classifier further improved performance (146 cases; PPV=0.99). CONCLUSIONS: A machine learning application enhanced the effectiveness of finding OM among documented paramedic field responses. This approach to refining OM surveillance may lead to improved first-responder and public health responses toward prevention of overdoses and other opioid-related problems in US communities.

Leveraging Ethnic Backgrounds to Improve Collection of Race, Ethnicity, and Language Data.

INTRODUCTION: Healthcare disparities may be exacerbated by upstream incapacity to collect high-quality and accurate race, ethnicity, and language (REaL) data. There are opportunities to remedy these data barriers. We present the Denver Health (DH) REaL initiative, which was implemented in 2021. METHODS: Denver Health is a large safety net health system. After assessing the state of REaL data at DH, we developed a standard script, implemented training, and adapted our electronic health record to collect this information starting with an individual's ethnic background followed by questions on race, ethnicity, and preferred language. We analyzed the data for completeness after REaL implementation. RESULTS: A total of 207,490 patients who had at least one in-person registration encounter before and after the DH REaL implementation were included in our analysis. There was a significant decline in missing values for race (7.9%-0.5%, p < .001) and for ethnicity (7.6%-0.3%, p < .001) after implementation. Completely of language data also improved (3%-1.6%, p < .001). A year after our implementation, we knew over 99% of our cohort's self-identified race and ethnicity. CONCLUSIONS: Our initiative significantly reduced missing data by successfully leveraging ethnic background as the starting point of our REaL data collection.

Using 42 CFR part 2 revisions to integrate substance use disorder treatment information into electronic health records at a safety net health system.

BACKGROUND: Regulations put in place to protect the privacy of individuals receiving substance use disorder (SUD) treatment have resulted in an unintended consequence of siloed SUD treatment and referral information outside of the integrated electronic health record (EHR). Recent revisions to these regulations have opened the door to data integration, which creates opportunities for enhanced patient care and more efficient workflows. We report on the experience of one safety-net hospital system integrating SUD treatment data into the EHR. METHODS: SUD treatment and referral information was integrated from siloed systems into the EHR through the implementation of a referral order, treatment episode definition, and referral and episode-related tools for addiction therapists and other clinicians. Integration was evaluated by monitoring SUD treatment episode characteristics, patient characteristics, referral linkage, and treatment episode retention before and after integration. Satisfaction of end-users with the new tools was evaluated through a survey of addiction therapists. RESULTS: After integration, three more SUD treatment programs were represented in the EHR. This increased the number of patients that could be tracked as initiating SUD treatment by 250%, from 562 before to 1,411 after integration. After integration, overall referral linkage declined (74% vs. 48%) and treatment episode retention at 90-days was higher (45% vs. 74%). Addiction therapists appreciated the efficiency of having all SUD treatment information in the EHR but did not find that the tools provided a large time savings shortly after integration. CONCLUSIONS: Integration of SUD treatment program data into the EHR facilitated both care coordination in patient treatment and quality improvement initiatives for treatment programs. Referral linkage and retention rates were likely modified by a broader capture of patients and changed outcome definition criteria. Greater preparatory workflow analysis may decrease initial end-user burden. Integration of siloed data, made possible given revised regulations, is essential to an efficient hub-and-spoke model of care, which must standardize and coordinate patient care across multiple clinics and departments.

Examining the Implementation of Health-Related Social Need (HRSN) Screenings at a Pediatric Community Health Center.

INTRODUCTION: Social determinants of health (SDoH) influence health outcomes and screening for health-related social needs (HRSN) is a recommended pediatric practice. In 2018, Denver Health and Hospitals (DH) implemented the Accountable Health Communities (AHC) model under the Centers for Medicare and Medicaid Services (CMS) and began using the AHC HRSN screening tool during selected well child visits (WCVs) at a DH Federally Qualified Health Center (FQHC). The current evaluation aimed to examine the program implementation and identify key lessons learned to inform the expansion of HRSN screening and referral to other populations and health systems. METHODS: Patients who completed a WCV between June 1, 2020 and December 31, 2021 (N = 13 750) were evaluated. Frequencies and proportions were used to describe patient characteristics of those that had a WCV, were screened, and received resource information. Multivariable logistic regression models with odds ratios (OR) and 95% confidence intervals (CI) were used to determine the association between patient characteristics and completing HRSN screening and provision of resource information. RESULTS: The screening tool was completed by 80% (n = 11 004) of caregivers bringing children to a WCV at the DH Westside Clinic, with over one-third (34.8%; n = 3830) reporting >1 social need. Food insecurity was the most common concern (22.3%; n = 2458). Non-English, non-Spanish (NENS) speakers were less likely to be screened (OR 0.43, 95% CI 0.33, 0.57) and less likely to report a social need (OR 0.59, 95% CI 0.42, 0.82) than speakers of English, after adjusting for age, race/ethnicity, and health insurance. CONCLUSIONS: A high rate of screening indicates feasibility of administering HRSN screenings for pediatric patients in a busy FQHC. More than a third of patients reported one or more social needs, underscoring the importance to identity these needs and the opportunity to offer personalized resources. Comparatively lower rates of screening and potential underreporting among NENS may be indicative of the availability and acceptability of current translation procedures as well as how the tool translates linguistically and culturally. Our experience highlights the need to partner with community organizations and involve patients and families to ensure SDoH screening and care navigation is part of culturally-appropriate patient-centered care.

Impact of community tracer teams on treatment outcomes among tuberculosis patients in South Africa.

BACKGROUND: Tuberculosis (TB) indicators in South Africa currently remain well below global targets. In 2008, the National Tuberculosis Program (NTP) implemented a community mobilization program in all nine provinces to trace TB patients that had missed a treatment or clinic visit. Implementation sites were selected by TB program managers and teams liaised with health facilities to identify patients for tracing activities. The objective of this analysis was to assess the impact of the TB Tracer Project on treatment outcomes among TB patients. METHODS: The study population included all smear positive TB patients registered in the Electronic TB Registry from Quarter 1 2007-Quarter 1 2009 in South Africa. Subdistricts were used as the unit of analysis, with each designated as either tracer (standard TB program plus tracer project) or non-tracer (standard TB program only). Mixed linear regression models were utilized to calculate the percent quarterly change in treatment outcomes and to compare changes in treatment outcomes from Quarter 1 2007 to Quarter 1 2009 between tracer and non-tracer subdistricts. RESULTS: For all provinces combined, the percent quarterly change decreased significantly for default treatment outcomes among tracer subdistricts (-0.031%; p < 0.001) and increased significantly for successful treatment outcomes among tracer subdistricts (0.003%; p = 0.03). A significant decrease in the proportion of patient default was observed for all provinces combined over the time period comparing tracer and non-tracer subdistricts (p = 0.02). Examination in stratified models revealed the results were not consistent across all provinces; significant differences were observed between tracer and non-tracer subdistricts over time in five of nine provinces for treatment default. CONCLUSIONS: Community mobilization of teams to trace TB patients that missed a clinic appointment or treatment dose may be an effective strategy to mitigate default rates and improve treatment outcomes. Additional information is necessary to identify best practices and elucidate discrepancies across provinces; these findings will help guide the NTP in optimizing the adoption of tracing activities for TB control.

The disparate impact of age-based COVID-19 vaccine prioritization by race/ethnicity in Denver, Colorado.

COVID-19 vaccines are an effective tool in preventing severe disease. Most states used an age-based prioritization for vaccine rollout. We examined the impact of a primarily age-based prioritization policy on reductions of severe disease in different racial and ethnic groups. We calculated age-specific rates of COVID-19 hospitalization and death by race/ethnicity in Denver, Colorado. To assess potentially averted hospitalizations and deaths by race/ethnicity, we then applied the first three phases of Colorado's primarily age-based vaccine rollout criteria to historical 2020 COVID-19 hospitalizations and deaths in Denver, Colorado. In the first 3 phases, 40% (1403/3473) of hospitalizations and 83% (503/604) of deaths occurred among those meeting age and long-term care facility criteria and could have been averted. Impacts varied by race/ethnicity with only 28% (440/1587) of hospitalizations and 74% (131/178) of deaths averted among Hispanic or Latino residents, compared to 57% (619/1094) of hospitalizations and 92% (252/274) of deaths among non-Hispanic White residents. We demonstrate using local data and policy that early age-based prioritization decisions disproportionately promoted reductions in severe disease among non-Hispanic White residents irrespective of COVID-19 risk in Denver, Colorado. These findings suggest that more equitable future vaccine prioritization policies, which lead with a goal of reducing health disparities through prioritizing susceptibility to adverse health outcomes rather than overall population-based cutoffs, are necessary. Our results have implications for future vaccination rollouts in limited vaccine resource conditions.

Perspectives of Latinx Individuals Who Were Unvaccinated And Hospitalized for COVID-19: A Qualitative Study.

Importance: Latinx individuals in the United States have lower COVID-19 vaccination rates and higher rates of COVID-19 infections, hospitalizations, and deaths than non-Latinx White individuals. Little is known about the perspectives of Latinx adults who had not received the COVID-19 vaccination and were hospitalized for COVID-19. Objective: To describe the perspectives of Latinx individuals who were unvaccinated and subsequently hospitalized for COVID-19. Design, Setting, and Participants: This qualitative study was conducted using semistructured phone interviews with 25 Latinx adults who were unvaccinated and survived a COVID-19 hospitalization in a public safety net hospital in Colorado from February to November 2021. Interviews were audio recorded, and transcripts were analyzed using thematic analysis. Main Outcomes and Measures: Themes and subthemes of perspectives on vaccination. Results: Among 25 adults (14 [56.0%] women, 11 [44.0%] men; mean [SD] age, 51 [15] years) who participated, all participants self-identified as Latino, Latina, or Latinx or Hispanic. There were 11 individuals who relied on emergency Medicaid (hospital coverage for Denver residents who are undocumented), while 10 individuals (40.0%) were essential workers and 13 individuals (52.0%) were unemployed. In interviews, 3 themes (with subthemes) were identified: factors associated with vaccination after hospitalization (subthemes: fear of death, avoiding hospitalization and reinfection, convinced COVID-19 is real, and responded to pressure from others), concerns about the COVID-19 vaccine (subthemes: experimental status and short timeline for production, contents of vaccine unknown or concerning, vaccine considered ineffective, worrisome immediate and long-term adverse effects, mixed and conflicting information, and government aimed to control or mark population through vaccination), and opportunities to improve vaccine uptake (subthemes; sharing personal experiences through social media, testimonials about minimal vaccine adverse effects, connecting with friends and family about the hospitalization experience, making the vaccine more accessible, and connecting with trusted sources of information). Conclusions and Relevance: This study found that Latinx individuals who were unvaccinated and subsequently hospitalized for COVID-19 were motivated to engage in advocacy to encourage vaccination in their communities. These findings suggest that supporting patient advocacy after hospital discharge and continued efforts to create low-barrier, patient-informed public health strategies may be associated with increased vaccine uptake in Latinx communities.

Assessment of SARS-CoV-2 Seroprevalence by Community Survey and Residual Specimens, Denver, Colorado, July-August 2020.

OBJECTIVES: The number of SARS-CoV-2 infections is underestimated in surveillance data. Various approaches to assess the seroprevalence of antibodies to SARS-CoV-2 have different resource requirements and generalizability. We estimated the seroprevalence of antibodies to SARS-CoV-2 in Denver County, Colorado, via a cluster-sampled community survey. METHODS: We estimated the overall seroprevalence of antibodies to SARS-CoV-2 via a community seroprevalence survey in Denver County in July 2020, described patterns associated with seroprevalence, and compared results with cumulative COVID-19 incidence as reported to the health department during the same period. In addition, we compared seroprevalence as assessed with a temporally and geographically concordant convenience sample of residual clinical specimens from a commercial laboratory. RESULTS: Based on 404 specimens collected through the community survey, 8.0% (95% CI, 3.9%-15.7%) of Denver County residents had antibodies to SARS-CoV-2, an infection rate of about 7 times that of the 1.1% cumulative reported COVID-19 incidence during this period. The estimated infection-to-reported case ratio was highest among children (34.7; 95% CI, 11.1-91.2) and males (10.8; 95% CI, 5.7-19.3). Seroprevalence was highest among males of Black race or Hispanic ethnicity and was associated with previous COVID-19-compatible illness, a previous positive SARS-CoV-2 test result, and close contact with someone who had confirmed SARS-CoV-2 infection. Testing of 1598 residual clinical specimens yielded a seroprevalence of 6.8% (95% CI, 5.0%-9.2%); the difference between the 2 estimates was 1.2 percentage points (95% CI, -3.6 to 12.2 percentage points). CONCLUSIONS: Testing residual clinical specimens provided a similar seroprevalence estimate yet yielded limited insight into the local epidemiology of COVID-19 and might be less representative of the source population than a cluster-sampled community survey. Awareness of the limitations of various sampling strategies is necessary when interpreting findings from seroprevalence assessments.

Performance of GeneXpert MTB/RIF for Diagnosing Tuberculosis Among Symptomatic Household Contacts of Index Patients in South Africa.

BACKGROUND: We describe the performance of GeneXpert MTB/RIF (Xpert) for diagnosing tuberculosis (TB) among symptomatic household contacts (HHCs) of rifampicin-resistant and drug-sensitive index cases. METHODS: We conducted a cross-sectional study among HHCs of recently diagnosed (<2 weeks) smear-positive and Xpert-positive index cases in the Bojanala District, South Africa. The HHCs were screened for TB symptoms; persons with ≥1 TB symptom provided 1 sputum for smear microscopy, Xpert, and mycobacterial growth indicator tube (MGIT) culture. Diagnostic test performance of Xpert was determined using MGIT as the reference standard. RESULTS: From August 2013 to July 2015, 619 HHCs from 216 index cases were enrolled: 60.6% were female, median age was 22 years (interquartile range, 9-40), and 126 (20.4%) self-reported/tested human immunodeficiency virus positive. A total of 54.3% (336 of 619) of contacts had ≥1 TB symptom (cough, fever, night sweats, weight loss), 297 of 336 (88.4%) of which provided a sputum; 289 (97.3%) had complete testing and 271 were included in the analysis. In total, 42 (6.8%) of 619 HHCs had microbiologically confirmed TB. The MGIT identified 33 HHCs as positive for Mycobacterium tuberculosis; of these, 7 were positive on Xpert resulting in a sensitivity of 21.2% (95% confidence interval [CI], 9.0-38.9), specificity of 98.3% (95% CI, 95.6-99.5), positive predictive value of 63.6% (95% CI, 30.8-89.1), and negative predictive value of 90.0 (95% CI, 85.7-93.4). CONCLUSIONS: Among symptomatic HHCs investigated for TB, Xpert performed suboptimally compared with MGIT culture. The poor performance of Xpert for diagnosing TB suggests that a more sensitive test, such a Xpert Ultra or culture, may be needed to improve yield of contact investigation, where feasible.

HIV prevalence and the cascade of care in five South African correctional facilities.

BACKGROUND: South Africa is home to the world's largest HIV epidemic. Throughout the world, incarcerated individuals have a higher prevalence of HIV than the general public, and South Africa has one of the highest rates of incarceration in sub-Saharan Africa. In spite of this, little has been published about the burden of HIV and how care is delivered in South African correctional facilities. OBJECTIVE: To estimate the prevalence of people living with HIV and identify initiation and retention in the HIV cascade of care across five correctional facilities. METHODS: Cross-sectional retrospective analysis of 30,571 adult inmates who participated in a tuberculosis screening and HIV counseling and testing campaign in South African correctional facilities (January 1, 2014-January 31, 2015). Descriptive statistics were used to estimate the proportion and 95% confidence intervals of HIV. Proportions of persons retained and lost at each step in the HIV cascade of care under this intervention were calculated. Poisson regression with robust variance estimates were used, and clustering by facility was accounted for in all analyses. RESULTS: Results of the screening campaign found previously undiagnosed HIV among 13.0% of those consenting to screening, with a total estimated HIV prevalence of 17.7% (n = 3,184, 95% CI: 17.2-18.3%) in the sample. When examining the overall cascade of care, 48.3% of those with HIV initiated care, and overall 45.6% of persons who entered care qualified for ART initiated treatment. A Poisson regression accounting for clustering by facility found HIV high risk groups within the population such as women (aRR = 1.72, 95% CI: 1.57, 1.89), those over 35 years of age (aRR = 2.43, 95% CI: 1.53, 3.85), and people incarcerated less than one year (aRR = 1.41, 95% CI: 1.19, 1.67). CONCLUSION: In this setting, routine screening is recommended, and measures are needed to ensure that persons diagnosed are adequately linked to and retained in care.

Pre-treatment loss to follow-up among children with multidrug-resistant tuberculosis in South Africa, 2008-2010.

Multidrug-resistant (MDR) TB is more difficult to diagnose and treat compared with drug-susceptible TB. Young children are at greater risk of severe TB disease and death when treatment is delayed compared to adults. We sought to describe characteristics of children (<13 years) diagnosed with MDR TB between 2008-2010 in three South African provinces and assess factors associated with pre-treatment loss to follow-up. We matched laboratory and medical records at treatment facilities to identify pre-treatment loss and examined demographic and clinical characteristics for association with loss. Categorical variables were examined for association using Pearson's x2 or Fisher's exact test, employing Bonferroni correction for multiple pairwise comparisons. Between 2008-2010, 156 children were diagnosed with laboratory-confirmed MDR TB. Only 44% (n = 69) were documented as having received treatment. Young children (<2 years) (47/59, 80%), children with extrapulmonary (EP) TB (27/34, 79%), and children diagnosed at general hospitals (60/97, 62%) were most likely to be lost before treatment. Children most vulnerable to death from TB are most likely to be lost before treatment, possibly leading to underestimates of disease burden, case notifications, and poor outcomes among this population. Point-of-care diagnosis and robust follow-up may reduce pre-treatment loss in this population.

Assessing Local Risk of Rifampicin-Resistant Tuberculosis in KwaZulu-Natal, South Africa Using Lot Quality Assurance Sampling.

BACKGROUND: KwaZulu-Natal (KZN) has the highest burden of notified multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant (XDR) TB cases in South Africa. A better understanding of spatial heterogeneity in the risk of drug-resistance may help to prioritize local responses. METHODS: Between July 2012 and June 2013, we conducted a two-way Lot Quality Assurance Sampling (LQAS) study to classify the burden of rifampicin (RIF)-resistant TB among incident TB cases notified within the catchment areas of seven laboratories in two northern and one southern district of KZN. Decision rules for classification of areas as having either a high- or low-risk of RIF resistant TB (based on proportion of RIF resistance among all TB cases) were based on consultation with local policy makers. RESULTS: We classified five areas as high-risk and two as low-risk. High-risk areas were identified in both Southern and Northern districts, with the greatest proportion of RIF resistance observed in the northernmost area, the Manguzi community situated on the Mozambique border. CONCLUSION: Our study revealed heterogeneity in the risk of RIF resistant disease among incident TB cases in KZN. This study demonstrates the potential for LQAS to detect geographic heterogeneity in areas where access to drug susceptibility testing is limited.

Assessing the utility of Xpert(®) MTB/RIF as a screening tool for patients admitted to medical wards in South Africa.

Many hospital inpatients in South Africa have undiagnosed active and drug-resistant tuberculosis (TB). Early detection of TB is essential to inform immediate infection control actions to minimize transmission risk. We assessed the utility of Xpert(®) MTB/RIF (GeneXpert) as a screening tool for medical admissions at a large public hospital in South Africa. Consecutive adult patients admitted to medical wards between March-June 2013 were enrolled; sputum specimens were collected and tested by GeneXpert, smear microscopy, and culture. Chest X-rays (CXRs) were conducted as standard care for all patients admitted. We evaluated the proportion of patients identified with TB disease through each diagnostic method. Among enrolled patients whose medical charts were available for review post-discharge, 61 (27%) were diagnosed with TB; 34 (56% of diagnosed TB cases) were GeneXpert positive. When patients in whom TB was identified by other means were excluded, GeneXpert yielded only four additional TB cases. However, GeneXpert identified rifampicin-resistant TB in one patient, who was initially diagnosed based on CXR. The utility of GeneXpert for TB screening was limited in an institution where CXR is conducted routinely and which serves a population in which TB and TB/HIV co-infection are highly prevalent, but it allowed for rapid detection of rifampicin resistance.

Programmatic Management of Drug-Resistant Tuberculosis: An Updated Research Agenda.

INTRODUCTION: There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey. METHODS: Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings. RESULTS: Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR-TB patients were also top priorities in their respective categories. Results were internally consistent and robust. DISCUSSION: Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data. CONCLUSION: There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.

Exercise manages fatigue during breast cancer treatment: a randomized controlled trial.

Fatigue is the most prevalent and debilitating symptom experienced by breast cancer patients receiving adjuvant chemotherapy or radiation therapy and few evidence-based treatments are available to manage this distressing side-effect. The purpose of this multi-institutional randomized controlled trial was to determine the effects of exercise on fatigue levels during treatment for breast cancer. Sedentary women (N=119) with Stage 0-III breast cancer receiving outpatient adjuvant chemotherapy or radiation therapy were randomized to a home-based moderate-intensity walking exercise program or to usual care for the duration of their cancer treatment. Of participants randomized to exercise, 72% adhered to the exercise prescription; 61% of the usual care group adhered. The intention-to-treat analysis revealed no group differences in part because of a dilution of treatment effect as 39% of the usual care group exercised and 28% of the exercise group did not. When exercise participation was considered using the data analysis method of instrumental variables with principal stratification, a clinically important and statistically significant (p=0.03) effect of exercise on pretest-to-posttest change in fatigue levels was demonstrated. Adherence to a home-based moderate-intensity walking exercise program may effectively mitigate the high levels of fatigue prevalent during cancer treatment.