Perceived stigma related to TB preventive therapy.

BACKGROUND: TB preventative therapy (TPT) is crucial for reducing the burden of TB in endemic settings. We assessed stigma associated with TPT and the social groups from whom stigma was anticipated.METHODS: We conducted an anonymous cross-sectional survey of community-dwelling adults in rural South Africa. Descriptive statistics, exploratory factor analysis, χ² tests, Kruskal-Wallis tests, and Poisson regression were used to identify factors associated with TPT stigma.RESULTS: The mean age of the 104 participants was 35 years, 65% were female, and 26% had completed secondary school. The vast majority perceived stigma associated with TPT (71%; mean score 1.7, SD ± 1.4). Factor analysis identified a two-factor solution that explained 61.9% of the variance. Being single (P < 0.001), previously screened for TB (P = 0.04), worried about being infected by TB (P = 0.006), and interested in taking TPT (P = 0.01) were associated with higher perceived stigma scores. TPT stigma was perceived among 8%, 16%, and 66% of their family, friends, and other community members, respectively.CONCLUSION: The prevalence of TPT-related stigma in a rural South African community was high. Community members anticipated less stigma from family members compared to other social groups. Global expansion and implementation of TPT will require novel interventions, such as engaging patients´ families to support uptake and promote adherence.

Retinoblastoma: From genes to patient care.

Retinoblastoma is the most common paediatric neoplasm of the retina, and one of the earliest model of cancer genetics since the identification of the master tumour suppressor gene RB1. Tumorigenesis has been shown to be driven by pathogenic variants of the RB1 locus, but also genomic and epigenomic alterations outside the locus. The increasing knowledge on this "mutational landscape" is used in current practice for precise genetic testing and counselling. Novel methods provide access to pre-therapeutic tumour DNA, by isolating cell-free DNA from aqueous humour or plasma. This is expected to facilitate assessment of the constitutional status of RB1, to provide an early risk stratification using molecular prognostic markers, to follow the response to the treatment in longitudinal studies, and to predict the response to targeted therapies. The aim of this review is to show how molecular genetics of retinoblastoma drives diagnosis, treatment, monitoring of the disease and surveillance of the patients and relatives. We first recap the current knowledge on retinoblastoma genetics and its use in every-day practice. We then focus on retinoblastoma subgrouping at the era of molecular biology, and the expected input of cell-free DNA in the field.

Towards remote monitoring in pediatric care and clinical trials-Tolerability, repeatability and reference values of candidate digital endpoints derived from physical activity, heart rate and sleep in healthy children.

BACKGROUND: Digital devices and wearables allow for the measurement of a wide range of health-related parameters in a non-invasive manner, which may be particularly valuable in pediatrics. Incorporation of such parameters in clinical trials or care as digital endpoint could reduce the burden for children and their parents but requires clinical validation in the target population. This study aims to determine the tolerability, repeatability, and reference values of novel digital endpoints in healthy children. METHODS: Apparently healthy children (n = 175, 46% male) aged 2-16 were included. Subjects were monitored for 21 days using a home-monitoring platform with several devices (smartwatch, spirometer, thermometer, blood pressure monitor, scales). Endpoints were analyzed with a mixed effects model, assessing variables that explained within- and between-subject variability. Endpoints based on physical activity, heart rate, and sleep-related parameters were included in the analysis. For physical-activity-related endpoints, a sample size needed to detect a 15% increase was calculated. FINDINGS: Median compliance was 94%. Variability in each physical activity-related candidate endpoint was explained by age, sex, watch wear time, rain duration per day, average ambient temperature, and population density of the city of residence. Estimated sample sizes for candidate endpoints ranged from 33-110 per group. Daytime heart rate, nocturnal heart rate and sleep duration decreased as a function of age and were comparable to reference values published in the literature. CONCLUSIONS: Wearable- and portable devices are tolerable for pediatric subjects. The raw data, models and reference values presented here can be used to guide further validation and, in the future, clinical trial designs involving the included measures.

Synergism between diabetes and human immunodeficiency virus in increasing the risk of tuberculosis.

SETTING: Community health screenings in KwaZulu-Natal Province, South Africa. OBJECTIVE: To study the synergism between diabetes mellitus (DM) and human immunodeficiency virus (HIV) infection in increasing the risk of tuberculosis (TB). DESIGN: In this cross-sectional study, we analyzed data from two community health projects, one at congregate settings, and one at household settings (n = 7708), in a rural resource-limited region where integrated communicable and non-communicable disease screening services were offered. Odds ratios (ORs) for demographic factors, socio-economic factors, DM status, and HIV positivity were calculated using multivariate analysis, and the statistical interaction between HIV and DM was tested. The primary outcome was the presence of TB symptoms. RESULTS: Among 7708 individuals, age >65 years (OR 1.72, 95%CI 1.47-2.02), HIV infection (OR 1.66, 95%CI 1.40-1.97) and DM (OR 1.36, 95%CI 1.11-1.67) were independently associated with increased odds of TB symptoms. Receiving monthly grants (OR 0.78, 95%CI 0.66-0.91), access to a toilet (OR 0.54, 95%CI 0.35-0.83), and access to solar or electric energy (OR 0.86, 95%CI 0.77-0.97) reduced the odds. There was evidence of significant interaction between DM and HIV on the multiplicative scale. CONCLUSION: DM and HIV synergistically increased the odds of TB symptoms according to these retrospective data. Future studies should prospectively evaluate synergism between HIV and DM in increasing the risk of active TB.

Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

OBJECTIVES: The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. METHODS: Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. RESULTS: HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV-monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/µL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). CONCLUSIONS: We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration.

Light therapy: is it safe for the eyes?

OBJECTIVE: Light therapy has become an increasingly popular treatment for depression and a range of other neuropsychiatric conditions. Yet, concerns have been raised about the ocular safety of light therapy. METHOD: We conducted the first systematic review into the ocular safety of light therapy. A PubMed search on January 4, 2017, identified 6708 articles, of which 161 were full-text reviewed. In total, 43 articles reporting on ocular complaints and ocular examinations were included in the analyses. RESULTS: Ocular complaints, including ocular discomfort and vision problems, were reported in about 0% to 45% of the participants of studies involving light therapy. Based on individual studies, no evident relationship between the occurrence of complaints and light therapy dose was found. There was no evidence for ocular damage due to light therapy, with the exception of one case report that documented the development of a maculopathy in a person treated with the photosensitizing antidepressant clomipramine. CONCLUSION: Results suggest that light therapy is safe for the eyes in physically healthy, unmedicated persons. The ocular safety of light therapy in persons with preexisting ocular abnormalities or increased photosensitivity warrants further study. However, theoretical considerations do not substantiate stringent ocular safety-related contraindications for light therapy.

Similar efficacy and tolerability of raltegravir-based antiretroviral therapy in HIV-infected patients, irrespective of age group, burden of comorbidities and concomitant medication: Real-life analysis of the German 'WIP' cohort.

Only limited efficacy and tolerability data on raltegravir (RAL) use are currently available. Study objectives were to describe the efficacy and tolerability profile of RAL-based antiretroviral therapy (ART) in routine clinical practice in Germany. The WIP study (WIP = "Wirksamkeit von Isentress unter Praxisbedingungen", Efficacy of Isentress under routine clinical conditions) was a prospective, multi-centre cohort study in Germany. Human immunodeficiency virus (HIV)-infected patients aged ≥ 18 years in whom combinational ART with RAL 400 mg BID was indicated were enrolled. The primary endpoint was virologic response (HIV-RNA <50 copies/mL; non-completion equals failure) after 48 weeks. Of 451 patients, 85.1% (n = 384) were still receiving RAL at week 48. At baseline (BL), the prevalence of concomitant diseases was higher in patients of the age group ≥50 years (94.2% vs. 75.7%) as well as concomitant medications (74.8 % vs. 55.4%). Virologic response at week 48 was 74.7% (overall), 75.0% (naïve at BL), 81.5% (suppressed at BL), 47.1% (interrupted previous treatment at BL) and 64.9% (failing at BL), without significant differences by age group. A significant correlation of achievement of HIV-RNA <50 copies/mL was seen with treatment status at BL (p = 0.004). In addition, 77.3 % of the patients with a CD4 cell count >200 cells/µL at BL achieved HIV-RNA <50 copies/mL (p = 0.029). RAL was well tolerated with 80 adverse events (AEs) in 49 patients (10.9%) and 8 serious AEs (SAEs) in 6 patients (1.3%) reported to be drug related. A total of 22 patients (4.9%) discontinued treatment due to AEs. The WIP study shows that the previously reported efficacy and safety profile of RAL can be achieved in a population with multiple comorbidities and comedications, with no major difference observed in ageing patients (≥50 years) vs. younger patients. RAL is therefore an attractive treatment option in routine medical care in Germany.

Transcranial direct current stimulation improves visual acuity in amblyopic Long-Evans rats.

Transcranial direct current stimulation (tDCS) has proved to increase brain cortex plasticity and different models of brain damage. In this work, we have analyzed the effects of tDCS in an experimental model of amblyopia using Long-Evans rats. Animals were monocularly deprived between 12 and 75 postnatal days and visual cortex contralateral to the deprived eye was stimulated using anodal tDCS during 8days (20min/day). The effects of tDCS treatment on the visual function were evaluated by using the optomotor reflex of the animals as a measure of visual acuity. Results obtained indicate that monocular occlusion during the critical period lead to a reduction of visual acuity in monocular and binocular conditions. Stimulation with anodal tDCS produced a nearly full recovery in visual acuity of amblyopic animals. However, same stimulation protocol in healthy control animals produced a decrease of binocular visual acuity. These data indicate that tDCS can reverse the effects of monocular deprivation on visual acuity, although it is essential to use this technique in a controlled way due to the possible adverse effects on healthy individuals.

Impact of nurse-delivered community-based CD4 services on facilitating pre-ART care in rural South Africa.

BACKGROUND: HIV testing, diagnosis and treatment programs have expanded globally, particularly in resource-limited settings. Diagnosis must be followed by determination of treatment eligibility and referral to care prior to initiation of antiretroviral treatment (ART). However, barriers and delays along these early steps in the treatment cascade may impede successful ART initiation. New strategies are needed to facilitate the treatment cascade. We evaluated the role of on site CD4+ T cell count phlebotomy services by nurses in facilitating pre-ART care in a community-based voluntary counseling and testing program (CBVCT) in rural South Africa. METHODS: We retrospectively evaluated CBVCT services during five continuous time periods over three years: three periods when a nurse was present on site, and two periods when the nurse was absent. When a nurse was present, CD4 count phlebotomy was performed immediately after HIV testing to determine ART eligibility. When a nurse was absent, patients were referred to their local primary care clinic for CD4 testing. For each period, we determined the proportion of HIV-positive community members who completed CD4 testing, received notification of CD4 count results, as well as the time to test completion and result notification. RESULTS: Between 2010 and 2013, 7213 individuals accessed CBVCT services; of these, 620 (8.6 %) individuals were HIV-positive, 205 (33.1 %) were eligible for ART according to South African national CD4 count criteria, and 78 (38.0 % of those eligible) initiated ART. During the periods when a professional nurse was available to provide CD4 phlebotomy services, HIV-positive clients were significantly more likely to complete CD4 testing than during periods when these services were not available (85.5 % vs. 37.3 %, p < 0.001). Additionally, when nurses were present, individuals were significantly more likely to be notified of CD4 results (60.6 % vs. 26.7 %, p <0.001). The time from HIV screening to CD4 test completion was also significantly shorter during nurse presence than nurse absence (median 8 days (IQR 4-19) vs. 35 days (IQR 15-131), p < 0.001). CONCLUSIONS: These findings indicate that in addition to CBVCT, availability of on site CD4 phlebotomy may reduce loss along the pre-ART care cascade and facilitate timely entry into HIV care.

3D Orbital Reconstruction in a Patient with Microphthalmos and a Large Orbital Cyst-A Case Report.

BACKGROUND: Orbital cysts are rare developmental anomalies that can occur in microphthalmic and anophthalmic patients. Such cysts can promote orbital growth and subsequently markedly increase the size of the orbit, which is commonly underdeveloped in these patients. Cyst removal is therefore generally dissuaded (at least) in the first 5 years. CLINICAL CASE: A 6-year-old boy with a microphthalmos and a cyst developed protrusion of his prosthetic eye and a swelling of the lower eyelid. MRI showed a large cyst causing distortion of the right orbit. Due to the expansive orbital growth and subsequent misfitting of the prosthesis, cystectomy and orbital floor reconstruction was performed using 3D technology. CONCLUSION: 3D imaging and printing enables exact delineation of orbital cysts and the adjacent bony structures. Furthermore it offers the possibility to plan an individual surgical approach and to design and fabricate a custom fit orbital floor implant.

Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: a randomized clinical trial (the BRDME study).

BACKGROUND: The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis. AIM: To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness. DESIGN: This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands. OUTCOMES: The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments.

Detection of calcifications in retinoblastoma using gradient-echo MR imaging sequences: comparative study between in vivo MR imaging and ex vivo high-resolution CT.

BACKGROUND AND PURPOSE: Intratumoral calcifications are very important in the diagnosis of retinoblastoma. Although CT is considered superior in detecting calcification, its ionizing radiation, especially in patients with hereditary retinoblastoma, should be avoided. The purpose of our study was to validate T2*WI for the detection of calcification in retinoblastoma with ex vivo CT as the criterion standard. MATERIALS AND METHODS: Twenty-two consecutive patients with retinoblastoma (mean age, 21 months; range, 1-71 months) with enucleation as primary treatment were imaged at 1.5T by using a dedicated surface coil. Signal-intensity voids indicating calcification on T2*WI were compared with ex vivo high-resolution CT, and correlation was scored by 2 independent observers as poor, good, or excellent. Other parameters included the shape and location of the signal-intensity voids. In 5 tumors, susceptibility-weighted images were evaluated. RESULTS: All calcifications visible on high-resolution CT could be matched with signal-intensity voids on T2*WI, and correlation was scored as excellent in 17 (77%) and good in 5 (23%) eyes. In total, 93% (25/27) of the signal-intensity voids inside the tumor correlated with calcifications compared with none (0/8) of the signal-intensity voids outside the tumor. Areas of nodular signal-intensity voids correlated with calcifications in 92% (24/26), and linear signal-intensity voids correlated with hemorrhage in 67% (6/9) of cases. The correlation of signal-intensity voids on SWI was better in 4 of 5 tumors compared with T2*WI. CONCLUSIONS: Signal-intensity voids on in vivo T2*WI correlate well with calcifications on ex vivo high-resolution CT in retinoblastoma. Gradient-echo sequences may be helpful in the differential diagnosis of retinoblastoma. The combination of funduscopy, sonography, and high-resolution MR imaging with gradient-echo sequences should become the standard diagnostic approach for retinoblastoma.

Fasting proinsulin levels are significantly associated with 20 year cancer mortality rates. The Hoorn Study.

AIMS/HYPOTHESIS: Proinsulin is possibly associated with cancer through activation of insulin receptor isoform A. We sought to investigate the associations between proinsulin and 20 year cancer mortality rates. METHODS: The study was performed within the Hoorn Study, a population-based study of glucose metabolism in individuals aged 50-75 years in the Dutch population. Fasting proinsulin levels were measured twice by a double-antibody radioimmunoassay. Participants were continuously followed to register mortality; causes of death were derived from medical records. Cox survival analyses were performed to assess the 20 year risk of death from cancer in relation to proinsulin. All analyses were adjusted for age and sex, with additional adjustments for traditional risk factors. The effect modification of glucose metabolism and sex was tested. RESULTS: Proinsulin levels were measured in 438 individuals (41% normal glucose tolerance, 35.7% impaired glucose metabolism, 23.3% type 2 diabetes). Of these participants, 53 died from cancer. After adjustment for age and sex, proinsulin >16.5 pmol/l (the upper tertile) was significantly associated with a twofold risk of cancer mortality (HR 2.01, 95% CI 1.16, 3.46) compared with individuals with lower proinsulin levels. Additional adjustment for glucose metabolism, BMI and smoking did not substantially change the results (HR 1.91, 95% CI 1.04, 3.52). No interaction with glucose metabolism or sex was observed. CONCLUSIONS/INTERPRETATION: Individuals with fasting proinsulin levels >16.5 pmol/l have a twofold risk of cancer mortality over a 20 year time span. These findings provide population-based evidence for the independent association between high proinsulin levels and cancer mortality rates.

'Cough officer' nurses in a general medical clinic successfully detect drug-susceptible and -resistant tuberculosis.

SETTING: Intensive case finding (ICF) for tuberculosis (TB) is recommended by the World Health Organization among known human immunodeficiency virus (HIV) patients. However, ICF may also be appropriate in generalized patient populations. OBJECTIVE: To evaluate the yield of ICF in a general medical clinic in a high HIV prevalence setting. METHODS: A nurse designated as a 'cough officer' identified clinic attendees with cough of >2 weeks and collected sputum for evaluation at the hospital and provincial referral laboratories. We retrospectively evaluated the number and proportion of patients with microbiologically confirmed TB identified in 2007-2008. RESULTS: Among 56 207 clinic attendees, 1442 (2.6%) TB suspects were identified and 122 (8.5%) were sputum Ziehl-Neelsen (ZN) positive. Of 389 available results, 72 (18.5%) were auramine-positive and 99 (25.4%) were culture-positive; multidrug-resistant and extensively drug-resistant TB were identified in 16 (16.2%). The number needed to screen was 11.8 patients to identify one ZN-positive case and 3.9 to identify one culture-positive case. CONCLUSIONS: A nurse-facilitated cough officer program successfully identified TB suspects and drug-susceptible and drug-resistant TB. Culture was more sensitive for TB screening and critical for identifying drug resistance. ICF is operationally feasible, and should be expanded to general medical clinics in high HIV and TB prevalence, resource-limited settings.

Integrated, home-based treatment for MDR-TB and HIV in rural South Africa: an alternate model of care.

SETTING: Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, in-patient treatment programs struggle to cope with rising prevalence and human immunodeficiency virus (HIV) co-infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. OBJECTIVE: To describe the design and preliminary results of an integrated, home-based MDR-TB-HIV treatment program created in rural KwaZulu-Natal. METHOD: In 2008, a decentralized center was established to provide out-patient MDR-TB and HIV treatment. Nurses, community health workers and family supporters have been trained to administer injections, provide adherence support and monitor adverse reactions in patients' homes. Physicians assess clinical response, adherence and the severity of adverse reactions to MDR-TB and HIV treatment at monthly follow-up visits. Treatment outcomes are assessed by monthly cultures and CD4 and viral load every 6 months. RESULTS: Of 80 patients initiating MDR-TB treatment from February 2008 to April 2010, 66 were HIV-co-infected. Retention has been high (only 5% defaults, 93% of visits attended), and preliminary outcomes have been favorable (77% cured/still on treatment, 82% undetectable viral load). Few patients have required escalation of care (9%), had severe adverse events (8%) or died (6%). CONCLUSION: Integrated, home-based treatment for MDR-TB and HIV is a promising treatment model to expand capacity and achieve improved outcomes in rural, resource-poor and high HIV prevalent settings.

Retinoblastoma: value of dynamic contrast-enhanced MR imaging and correlation with tumor angiogenesis.

BACKGROUND AND PURPOSE: Noninvasive evaluation of retinoblastoma treatment response has become more important due to increased use of eye-sparing treatments. We evaluated the relation between DCE-MR imaging and histopathologic parameters to determine the value of DCE-MR imaging in assessing tumor angiogenesis and prognostic features. MATERIALS AND METHODS: Fifteen consecutive patients with retinoblastoma (mean age, 24 months; range, 2-70 months) undergoing enucleation as the primary treatment (15 eyes) were scanned at 1.5T by using dedicated surface coils. Pretreatment DCE-MR imaging of the most affected eye was evaluated by 2 observers by using curve-pattern analysis, with the first 5 minutes of each curve and the full time-series described as κ(5min) and κ(17min), respectively. Assessed histopathologic and immunologic parameters included optic nerve invasion, choroid invasion, MVD, tumor necrosis, and expression of VEGF and Flt-1. RESULTS: The median value of κ(5min) was 1.28 (range, 0.87-2.07) and correlated positively with MVD (P = .008). The median value of κ(17min) was 1.33 (range, 0.35-3.08) and correlated negatively with tumor necrosis (P = .002). Other histopathologic and immunohistopathologic parameters did not correlate with DCE-MR imaging parameters. Interobserver agreement was 0.53 for κ(5min) and 0.91 for κ(17min). CONCLUSIONS: In retinoblastoma, the early phase of the DCE time curve positively correlates with MVD, while the presence of late enhancement is correlated with necrosis. Thus, the potential for DCE-MR imaging to noninvasively assess tumor angiogenesis and necrosis in retinoblastoma is promising and warrants further investigation.

Tuberculosis infection control in a high drug-resistance setting in rural South Africa: information, motivation, and behavioral skills.

BACKGROUND: Tuberculosis (TB) is transmitted in resource-limited facilities where TB infection control (IC) is poorly implemented. Theory-based behavioral models can potentially improve IC practices. METHODS: The present study used an anonymous questionnaire to assess healthcare worker (HCW) TB IC information, motivation, and behavioral skills (IMB) and implementation in two resource-limited rural South African hospitals with prevalent drug-resistant TB. RESULTS: Between June and August 2010, 198 surveys were completed. Although the respondents demonstrated information proficiency and positive motivation, 22.8% did not consider TB IC to be worthwhile. Most tasks were rated as easy by survey participants, but responding HCWs highlighted challenges in discrete behavioral skills. The majority of responding HCWs reported that they always wore respirators (54.3%), instructed patients on cough hygiene (63.0%), and ensured natural ventilation (67.4%) in high-risk areas. Most respondents (74.0%) knew their HIV status. Social support items correlated with the implementation of the first three aforementioned practices but not with the respondents' knowledge of their HIV status. In most cases, motivation and behavioral skills, but not information, were associated with implementation. CONCLUSION: HCWs in rural South African hospitals with high drug-resistance demonstrated moderate IMB and implementation of TB IC. Improvement efforts should emphasize the development of HCW motivation and behavioral skills as well as social support from colleagues and supervisors. Such interventions should be informed by baseline IMB assessments. In the present study, a trimmed/modified IMB model helped characterize TB IC implementation.

Risk factors for mortality among MDR- and XDR-TB patients in a high HIV prevalence setting.

SETTING: Recent studies suggest that the prevalence of drug-resistant tuberculosis (TB) in sub-Saharan Africa may be rising. This is of concern, as human immunodeficiency virus (HIV) co-infection in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has been associated with exceedingly high mortality rates. OBJECTIVE: To identify risk factors associated with mortality in MDR- and XDR-TB patients co-infected with HIV in South Africa. DESIGN: Case-control study of patients who died of all causes within 2 years of diagnosis with MDR- or XDR-TB. RESULTS: Among 123 MDR-TB patients, 78 (63%) died following diagnosis. CD4 count ≤ 50 (HR 4.64, P = 0.01) and 51-200 cells/mm(3) (HR 4.17, P = 0.008) were the strongest independent risk factors for mortality. Among 139 XDR-TB patients, 111 (80%) died. CD4 count ≤ 50 cells/mm(3) (HR 4.46, P = 0.01) and resistance to all six drugs tested (HR 2.54, P = 0.04) were the principal risk factors. Use of antiretroviral therapy (ART) was protective (HR 0.34, P = 0.009). CONCLUSIONS: Mortality due to MDR- and XDR-TB was associated with greater degree of immunosuppression and drug resistance. Efforts to reduce mortality must focus on preventing the amplification of resistance by strengthening TB treatment programs, as well as reducing the pool of immunosuppressed HIV-infected patients through aggressive HIV testing and ART initiation.