Health care providers acceptance of default prescribing of TB preventive treatment for people living with HIV in Malawi: a qualitative study.

BACKGROUND: Tuberculosis (TB) preventive treatment (TPT) substantially reduces the risk of developing active TB for people living with HIV (PLHIV). We utilized a novel implementation strategy based on choice architecture (CAT) which makes TPT prescribing the default option. Through CAT, health care workers (HCWs) need to "opt-out" when choosing not to prescribe TPT to PLHIV. We assessed the prospective, concurrent, and retrospective acceptability of TPT prescribing among HCWs in Malawi who worked in clinics participating in a cluster randomized trial of the CAT intervention. METHODS: 28 in-depth semi-structured interviews were conducted with HCWs from control (standard prescribing approach) and intervention (CAT approach) clinics. The CAT approach was facilitated in intervention clinics using a default prescribing module built into the point-of-care HIV Electronic Medical Record (EMR) system. An interview guide for the qualitative CAT assessment was developed based on the theoretical framework of acceptability and on the normalization process theory. Thematic analysis was used to code the data, using NVivo 12 software. RESULTS: We identified eight themes belonging to the three chronological constructs of acceptability. HCWs expressed no tension for changing the standard approach to TPT prescribing (prospective acceptability); however, those exposed to CAT described several advantages, including that it served as a reminder to prescribe TPT and routinized TPT prescribing (concurrent acceptability). Some felt that CAT may reduce HCW´s autonomy and might lead to inappropriate TPT prescribing (retrospective acceptability). CONCLUSIONS: The default prescribing module for TPT has now been incorporated into the point-of-care EMR system nationally in Malawi. This seems to fit the acceptability of the HCWs. Moving forward, it is important to train HCWs on how the EMR can be leveraged to determine who is eligible for TPT and who is not, while acknowledging the autonomy of HCWs.

Delivery of TB preventive therapy to incarcerated people living with HIV in southern African correctional facilities.

TB preventive treatment (TPT) is recommended for high-risk and hard-to-reach populations such as incarcerated people living with HIV (PLHIV). To assess implementation of TPT delivery in correctional settings, we conducted an exploratory analysis of data from a multisite cohort study in South Africa and Zambia. From 975 participants, 648 were screened for TB, and 409 initiated TPT mostly within a month after initiation of antiretroviral therapy (190/409, 46.5%). We observed a median gap of one month (IQR 0.6-4.7) in TPT delivery to incarcerated PLHIV. Future research should examine standardised quality improvement tools and new strategies such as short-course regimens to improve TPT initiation in this population.

Le traitement préventif antituberculeux (TPT) est recommandé pour les populations à haut risque et difficiles à atteindre, telles que les personnes vivant avec le VIH (PLHIV) qui sont incarcérées. Afin d'évaluer la mise en place du TPT en centres correctionnels, nous avons réalisé une analyse exploratoire des données d'une étude de cohorte multisites en Afrique du Sud et en Zambie. Sur 975 participants, 648 ont subi un test de dépistage de la TB et 409 ont été mis sous TPT, dans le mois ayant suivi l'instauration du traitement antirétroviral pour la plupart (190/409 ; 46,5%). Nous avons observé un écart médian d'un mois (IQR 0,6­4,7) en matière de dispense du TPT aux PLHIV incarcérées. Les études futures devraient analyser l'utilisation d'outils standardisés d'amélioration de la qualité ainsi que de nouvelles stratégies, telles que les schémas thérapeutiques de courte durée, afin d'améliorer l'instauration du TPT dans cette population.

Mobile HIV testing in South Africa: maximizing yield through data-guided site selection.

BACKGROUND: Mobile community HIV testing can effectively reach undiagnosed people living with HIV in southern Africa. Variable yield in HIV test positivity has been a challenge with high- and low-yield sites often being closely situated. We sought to test whether easy-to-identify, site-level characteristics were associated with HIV positivity yield in a routine mobile HIV testing program. METHODS: We used routine testing program test data augmented with site-level characterization, either of the community or shopping site at which HIV testing was offered. Specifically, we described the local environment and interviewed key informants to gain additional information regarding the availability of HIV and other services in the locale. RESULTS: We included 122 residential and 26 shopping sites with median HIV-positive test yields of 7.6% and 6.9%, respectively. The range for community sites was from 2 to 55% with high and low yields at geographically proximal sites. Factors related to lower income and marginalization, including informal housing and the absence of name-brand stores in shopping venues, were associated with higher HIV-positive testing yield. CONCLUSIONS: Characterization of sites, particularly identifying factors related to marginalization, lack of services, and poverty, can aid in identifying sites with higher HIV-positive yield.

CONTEXTE: Le dépistage communautaire mobile du VIH est un moyen efficace pour atteindre les personnes vivant avec le VIH non diagnostiquées en Afrique australe. Les taux de positivité variables aux tests de dépistage du VIH constituent un défi puisque certains sites aux taux de positivité élevés sont souvent géographiquement proches de sites dont les taux de positivité sont faibles. Nous avons cherché à tester si certaines caractéristiques faciles à identifier et propres aux sites étaient associées aux taux de positivité des tests de dépistage du VIH dans un programme de dépistage du VIH mobile systématique. MÉTHODES: Nous avons utilisé les données des tests du programme de dépistage systématique et procédé à une caractérisation des sites, soit de la communauté soit de la zone commerciale où le dépistage du VIH était proposé. Plus précisément, nous avons décrit l'environnement local et interrogé des informateurs clés afin d'obtenir des informations supplémentaires sur la disponibilité de services anti-VIH et autres dans cette zone. RÉSULTATS: Nous avons inclus 122 résidents et 26 zones commerciales avec un taux médian de positivité aux tests de dépistage du VIH de 7,6% et 6,9%, respectivement. L'étendue allait de 2% à 55% pour les sites communautaires, avec des taux de positivité faibles ou élevés dans des sites géographiquement proches. Les facteurs liés à de faibles revenus et à une marginalisation (par ex., logement informel et absence de magasins de marque dans les zones commerciales) étaient associés à de plus forts taux de positivité aux tests de dépistage du VIH. CONCLUSIONS: La caractérisation des sites, notamment l'identification des facteurs liés à la marginalisation, au manque de services et à la pauvreté, peut aider à identifier les sites où les taux de positivité aux tests de dépistage du VIH sont plus élevés.

Choice architecture-based prescribing tool for TB preventive therapy: a pilot study in South Africa.

BACKGROUND: All people with HIV who screen negative for active tuberculosis (TB) should receive isoniazid preventive therapy (IPT). IPT implementation remains substantially below the 90% WHO target. This study sought to further understanding of IPT prescription by piloting a simplified prescribing approach. SETTING: Primary care clinics in Matlosana, South Africa. DESIGN: This was a mixed-methods implementation study. METHODS: Nine providers were recruited and underwent training on 2018 WHO guidelines. A simplified prescribing tool containing antiretroviral therapy (ART) and IPT prescriptions was introduced into the workflow for 2 weeks. Prescription data were collected from file review. Interviews were conducted with prescribers. RESULTS: During the study period, 41 patients were evaluated for ART initiation; 34 (83%) files used the simplified prescribing tool. Thirty-seven (90%) patients were eligible for same-day ART and IPT initiation, of whom 36 (97%) received IPT prescription. Qualitative interviews identified the following barriers to IPT prescription: cognitive burden, extensive documentation, limited management support, paucity of training, stock-outs, and patient-related factors. Provider acceptability of the tool was favorable, with unanimous recommendation to colleagues on the basis of streamlining documentation and reminding to prescribe. CONCLUSIONS: This simplified prescribing device for IPT was feasible to implement. Streamlining documentation and reminding providers to prescribe can reduce work-flow barriers to IPT provision.

Subclinical tuberculosis and adverse infant outcomes in pregnant women with HIV.

BACKGROUND: Tuberculosis (TB) in pregnant women with HIV is associated with adverse maternal and infant outcomes. Previous studies have described a substantial prevalence of subclinical TB in this group, but little is known about the impact of subclinical TB on maternal and pediatric outcomes.METHODS: The Tshepiso Study recruited 235 HIV-infected pregnant women with TB (and matched HIV-positive, TB-negative pregnant controls), in Soweto, South Africa, from 2011 to 2014. During enrolment screening, some women initially recruited as controls were subsequently diagnosed with prevalent TB. We therefore assessed the prevalence of subclinical TB, associated participant characteristics and outcomes.RESULTS: Of 162 women initially recruited as TB-negative controls, seven (4.3%) were found to have TB on sputum culture. All seven had negative WHO symptom screens, and six (86%) were smear-negative. Of their seven infants, one was diagnosed with TB, and three (43%) experienced complications compared to zero infants with TB and 11% experiencing complications in the control group of TB-negative mothers (P = 0.045).CONCLUSION: We discovered an appreciable prevalence of subclinical TB in HIV-infected pregnant women in Soweto, which had not been detected by screening algorithms based solely on symptoms. Infants of HIV-infected mothers with subclinical TB appear to have a higher risk of adverse outcomes than those of TB-negative mothers.

Symptom and digital chest X-ray TB screening in South African prisons: yield and cost-effectiveness.

BACKGROUND: Correctional inmates are at a high risk of tuberculosis (TB). The optimal approach to screening this population is unclear.METHODS: We retrospectively reviewed records from TB screening in 64 correctional facilities in South Africa between January 2015 and July 2016. Inmates received symptom screening (any of cough, fever, weight loss, or night sweats) combined with digital chest X-ray (CXR), when available. CXRs were assessed as 'abnormal' or with no abnormalities. Inmates with either a symptom or an 'abnormal' CXR were asked to provide a single spot sputum for Xpert® MTB/RIF testing. We estimated the incremental cost-effectiveness ratio (ICER) per additional TB case detected using CXR screening among asymptomatic inmates.RESULTS: Of 61 580 inmates, CXR screening was available for 41 852. Of these, 19 711 (47.1%) had TB symptoms. Among 22 141 inmates without symptoms, 1939/19 783 (9.8%) had an abnormal CXR, and 8 (1.2%) were Xpert-positive among those with Xpert tests done. Of 14 942 who received symptom screening only and had symptoms, 84% (12 616) had an Xpert result, and 105 (0.8%) were positive. The ICER for CXR screening was US$22 278.CONCLUSION: Having CXR in addition to symptom screening increased yield but added considerable cost. A major limitation of screening was the low specificity of the symptom screen.

[S2k-guideline Helicobacter pylori and gastroduodenal ulcer disease]. / S2k-Leitlinie Helicobacter pylori und gastroduodenale Ulkuskrankheit.

In the line "bismuth-containing quadruple therapy" of Table 7 (p 342), in the column "dosage" incorrectly at the three antibiotics respectively 1-1-1-1. The correct is: 3-3-3-3.

Chronic hepatitis B increases mortality and complexity among HIV-coinfected patients in South Africa: a cohort study.

OBJECTIVES: To assess the effect of chronic hepatitis B on survival and clinical complexity among people living with HIV following antiretroviral therapy (ART) initiation. METHODS: We evaluated mortality and single-drug substitutions up to 3 years from ART initiation (median follow-up 2.75 years; interquartile range 2-3 years) among patients with and without chronic hepatitis B (CHB) enrolled in a workplace HIV care programme in South Africa. RESULTS: Mortality was increased for CHB patients with hepatitis B virus (HBV) DNA levels > 10 000 copies/mL (adjusted hazard ratio 3.1; 95% confidence interval 1.2-8.0) compared with non-CHB patients. We did not observe a similar difference between non-CHB patients and those with CHB and HBV DNA < 10 000 copies/mL (adjusted hazard ratio 0.70; 95% confidence interval 0.2-2.3). Single-drug substitutions occurred more frequently among coinfected patients regardless of HBV DNA level. CONCLUSIONS: Our findings suggest that CHB may increase mortality and complicate ART management.

Pooling sputum from multiple individuals for Xpert® MTB/RIF testing: a strategy for screening high-risk populations.

SETTING: Symptom-based screening for tuberculosis (TB) disease is limited by poor performance of symptom screening in several key populations. We tested the hypothesis that pooling sputum from multiple individuals for Xpert(®) MTB/RIF testing would reduce the number of tests required while retaining an acceptable sensitivity, thus allowing the use of Xpert for TB screening. METHODS: We compared pooling ratios that would require the least number of assays using Xpert and determined that for a population with a TB prevalence of approximately 3%, a 1:5 pooling ratio is optimal. To evaluate sensitivity, we generated pools of one specimen with known Mycobacterium tuberculosis culture positivity (smear microscopy-positive or -negative) with four culture-negative specimens. RESULTS: All 20 of the pools generated from a smear- and culture-positive sputum sample were positive using Xpert. Of the 22 pools with a smear-negative, culture-positive sample, we included 17 in the analysis, of which 13 (76%) were Xpert-positive. CONCLUSIONS: Pooling of sputum samples using Xpert achieved reasonable sensitivity and warrants further evaluation of the systematic screening of high TB prevalence populations.

Prevalence and associations with hepatitis B and hepatitis C infection among HIV-infected adults in South Africa.

We assessed prevalence and factors associated with hepatitis B in a cross section of HIV-infected primary care and antinatal clinic patients in South Africa and evaluated a rapid hepatitis B surface antigen (HBsAg) assay. We enrolled 998 patients; 88% were women, median age was 29 years and median CD4 count was 354 cells/mm(3). HBsAg enzyme-linked immunosorbent assay (ELISA), anti-hepatitis B core (HBc) antibodies and hepatitis C virus antibody were positive among 4.2%, 37% and 0.1% of subjects, respectively. Univariate and multivariate associations were assessed using logistic regression. Anti-HBc antibodies were associated with alcohol use, traditional medicines and higher CD4 counts; HBsAg positivity was associated with lower CD4. Compared with the HBsAg ELISA, a rapid HBsAg test had a sensitivity of 75.0% and specificity of 99.6%. In conclusion, we identified a moderate prevalence of both HBsAg and anti-HBc. Importantly, we found that subjects with HBsAg positivity had lower CD4 counts.

Emphysematous cystitis: a review of the spectrum of disease.

Emphysematous cystitis is an uncommon condition in which pockets of gas are formed in and around the bladder wall by gas-forming organisms. Persons with diabetes, neurogenic bladder and chronic urinary infection are predisposed to the disease. Severity of illness ranges from an asymptomatic condition to life-threatening cystitis. We present 2 cases of emphysematous cystitis. One case was an incidental finding on evaluation of abdominal discomfort with resolution upon removal of predisposing factors. The other patient presented with an acute abdomen that progressed to severe necrotizing cystitis ultimately requiring cystectomy. The initial involvement of the urologist as a consultant is emphasized. A complete review of the literature describes the incidence, various presentations, associated diseases and organisms, pathogenesis, and available methods for diagnosis and treatment reported for this disease. Successful management depends on early diagnosis with correction of underlying causes, administration of appropriate antibiotics, establishment of adequate bladder drainage and surgical excision of involved tissue when required. Early detection and prompt treatment are encouraged.

Altered 5'-nucleotidase specific activity and distribution between two plasma membrane domains of ascites tumor cells with modified lipid composition.

1. The cholesterol and phospholipid content of the surface membranes of ascites tumor cells cultivated in lipid-depleted medium was reduced to about 60(70)% of the control, but the relative composition of the individual phospholipids was not altered. 2. Differences in lipid composition were also observed between the two plasma membrane domains isolated from the cells cultured in normal and lipid-depleted medium respectively. 3. The fatty acid spectrum of the lipid-depleted membranes showed a greater fraction of saturated vs unsaturated acids. 4. The membrane lipid fluidity measured by fluorescence polarization was decreased in the modified surface membranes. 5. The 5'-nucleotidase specific activity was drastically reduced (46-66%) in the lipid-deleted membranes, and in addition its distribution between the two vesicle fractions was altered.

Influence of triethyl lead on the activity of enzymes of the ascites tumor cell plasma membrane and its microviscosity.

The influence of triethyl lead (TriEL) on the activity of plasma membrane-bound enzymes of Ehrlich ascites tumor cells and on membrane fluidity has been investigated. TriEL completely inhibits the (Na+-K+)-ATPase in its membrane-bound and even more pronounced in its solubilized form between 5 and about 20 microM. It also alters the microviscosity of the isolated plasma membrane up to a temperature of about 30 degrees C, but it does not have any influence on the fluidity of the membrane-derived liposomes. From these data it is concluded that the inhibitor may interact directly with the catalytic subunit of the (Na+ + K+)-ATPase, and may not exert its influence by interfering with the membrane lipids.

Cholesterol-induced growth stimulation, cell aggregation, and membrane properties of ascites tumor cells in culture.

Ascites tumor cells can be cultivated at a reduced serum concentration if cholesterol (2.50 mg per 100 ml of medium) is added to the culture medium. At serum concentrations of 3%, optimal growth properties are obtained; below 3%, cell cultures usually perish after a few days. Cells grown in the presence of added cholesterol have an elevated content of this molecule per cell as well as in the plasma membrane, and they also show a cholesterol concentration-dependent rate of proliferation. Precursors of the cholesterol-biosynthetic pathway like mevalonic acid, added in mM amounts, or squalene and lanosterol cannot be substituted for cholesterol itself. This is due to the observation that the biosynthetic pathway is blocked at the stage of lanosterol conversion to cholesterol. Cholesterol de novo synthesis from acetate is regulated by the cholesterol content of the cells, which also affects the production of ubiquinone and dolichol. Growth factors such as insulin, prostaglandin F2 alpha, and transferrin added to the medium do not mimic the cholesterol-induced effect. Distribution of DNA during cell cycle and the cell density-dependent reduction in macromolecule synthesis is very similar to the control cells. In contrast, cells without added cholesterol show reduced growth properties accompanied by the accumulation of cells in the mitotic and G2 phase. The cholesterol/phospholipid ratio of the plasma membranes of cholesterol-rich cells is about 15% lower than of the control cells and 40% higher compared to the cholesterol-poor cells, which, however, does not significantly alter the membrane fluidity between the cholesterol-rich and -poor cells as revealed by fluorescence polarization measurements. The most dramatic behavior of the cholesterol-rich cells is their tendency to form aggregates, which is demonstrated either by concanavalin A-induced agglutination or by cell density-dependent aggregation shown by interference microscopy in vivo.

Structural and functional alterations of lipid-depleted ascites tumor cells in culture.

Ascites tumor cells growth-arrested in lipid-depleted medium were modified with respect to their lipid composition, i.e. mainly cholesterol and the phospholipid fraction. These so-called lipid-depleted cells were generally smaller, had a surface area reduced by 55% compared to the control cells and had an altered cell surface architecture with large parts being smooth, interrupted by isolated bundles of microvilli and blebs as revealed by scanning electron microscopy. This deorganization process of the cells. Lectin-induced agglutination and receptor binding capacity was reduced, and also the receptor distribution was changed resulting in a cap-like formation on the surface as shown with FITC-labelled concanavalin A. The reduction in lipid content yielding a lower C/P ratio profoundly decreased the plasma membrane fluidity which was determined by fluorescence polarization measurements. Studies on fatty acid and cholesterol de novo synthesis revealed only small increases under lipid-free conditions not sufficient to meet the requirements of the lipid-depleted cells for these substances. It is therefore concluded that ascites tumor cells need exogenous preformed lipids for adequate functioning of the cell.