Drop‐offs in the isoniazid preventive therapy cascade among children living with HIV in western Kenya, 2015–2019

IntroductionIsoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) in children living with HIV (CLHIV), but data on the outcomes of the IPT cascade in CLHIV are limited.MethodsWe evaluated the IPT cascade among CLHIV aged <15 years and newly enrolled in HIV care in eight HIV clinics in western Kenya. Medical record data were abstracted from September 2015 through July 2019. We assessed the proportion of CLHIV completing TB symptom screening, IPT eligibility assessment, IPT initiation and completion. TB incidence rate was calculated stratified by IPT initiation and completion status. Risk factors for IPT non‐initiation and non‐completion were assessed using Poisson regression with generalized linear models.ResultsOverall, 856 CLHIV were newly enrolled in HIV care, of whom 98% ([95% CI 97–99]; n = 841) underwent screening for TB symptoms and IPT eligibility. Of these, 13 (2%; 95% CI 1–3) were ineligible due to active TB and 828 (98%; 95% CI 97–99) were eligible. Five hundred and fifty‐nine (68%; 95% CI 64–71) of eligible CLHIV initiated IPT; median time to IPT initiation was 3.6 months (interquartile range [IQR] 0.5–10.2). Overall, 434 (78%; 95% CI 74–81) IPT initiators completed. Attending high‐volume HIV clinics (aRR = 2.82; 95% CI 1.20–6.62) was independently associated with IPT non‐initiation. IPT non‐initiation had a trend of being higher among those enrolled in the period 2017–2019 versus 2015–2016 (aRR = 1.91; 0.98–3.73) and those who were HIV virally non‐suppressed (aRR = 1.90; 95% CI 0.98–3.71). Being enrolled in 2017–2019 versus 2015–2016 (aRR = 1.40; 1.01–1.96) was independently associated with IPT non‐completion. By 24 months after IPT screening, TB incidence was four‐fold higher among eligible CLHIV who never initiated (8.1 per 1000 person years [PY]) compared to CLHIV who completed IPT (2.1 per 1000 PY; rate ratio [RR] = 3.85; 95% CI 1.08–17.15), with a similar trend among CLHIV who initiated but did not complete IPT (8.2/1000 PY; RR = 4.39; 95% CI 0.82–23.56).ConclusionsDespite high screening for eligibility, timely IPT initiation and completion were suboptimal among eligible CLHIV in this programmatic cohort. Targeted programmatic interventions are needed to address these drop‐offs from the IPT cascade by ensuring timely IPT initiation after ruling out active TB and enhancing completion of the 6‐month course to reduce TB in CLHIV.     

Effects of rhein on human articular chondrocytes in alginate beads

This study was designed to investigate the effects of rhein, the active metabolite of diacerhein, on the metabolic functions of human chondrocytes cultured in alginate beads.Enzymatically isolated osteoarthritic (OA) chondrocytes were cultured in alginate beads in a well-defined culture medium for 12 days. Rhein was tested in a range of concentrations comprised between 10(-7) and 4 x 10(-5)M, in the presence or absence of 10(-10)M IL-1beta. Interleukin (IL)-6 and -8, macrophage inflammatory protein (MIP-1beta), stromelysin-1 (MMP-3), aggrecan (AGG), tissue inhibitor of metalloproteinases-1 (TIMP-1), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) productions were assayed. Cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) mRNA steady-state levels were also quantified. In the basal condition, 10(-5)M rhein increased by 46.5% the production of AGG, decreased by 17-30% the production of IL-6, MMP-3, NO and MIP-1beta but enhanced by 50% the production of PGE(2). IL-1beta increased IL-6, IL-8, MIP-1beta, NO, PGE(2) and MMP-3 productions, but inhibited AGG and TIMP-1 synthesis. Rhein partially reversed the effect of IL-1beta on TIMP-1 and NO production, had no effect on AGG, IL-6 and MIP-1beta production, but up-regulated the IL-1beta stimulated PGE(2) production. The COX-2 and iNOS mRNA levels and IL-8 production were not modified by rhein.Overall, these results contribute to explain the clinical efficiency of rhein and give new information on its mechanisms of action.     

Noncomparative contraceptive efficacy of cellulose sulfate gel

OBJECTIVE: To estimate the 6-month cumulative probability of pregnancy, short-term adverse effects, and acceptability of cellulose sulfate vaginal contraceptive gel. METHODS: Two hundred fertile heterosexual couples were enrolled in this single-center, phase II, 6-month noncomparative study conducted at the California Family Health Council in Los Angeles, California. Couples did not desire pregnancy, were at low risk for sexually transmitted diseases, and agreed to use 3.5 mL of cellulose sulfate gel intravaginally before each coital act as their primary means of contraception. Scheduled follow-up visits took place after one menstrual cycle and at study completion, which occurred after 6 months and six menstrual cycles had elapsed. In addition, participants were instructed to call the site at the onset of each menses to review their diary cards. RESULTS: The cumulative probabilities of pregnancy during 6 months and six cycles of typical use were 13.4% (95% confidence interval [CI] 7.5-19.4%) and 13.9% (95% CI 7.7-20.2%), respectively, and during 6 cycles of correct and consistent ("perfect") use: 3.9% (95% CI 0.0-9.2%). Slightly over one fourth of the women and one man reported experiencing gel-related adverse events, two thirds of which were mild and only possibly related to the gel. Three quarters of women and men reported that they would buy cellulose sulfate gel for contraception. CONCLUSION: Cellulose sulfate vaginal gel yields pregnancy rates comparable to nonoxynol-9 and few adverse events among couples at low risk for sexually transmitted diseases.     

Prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy in 76 pregnancies at risk

OBJECTIVE: Evaluation of results in a consecutive series of 76 prenatal diagnoses for xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) made since 1977. METHODS: UV-induced DNA repair synthesis was assessed by the autoradiographic measurement of the incorporation of (3)H-thymidine. RESULTS: XP was diagnosed in 19 of the 76 investigated pregnancies at risk; cultured chorionic villus (CV) cells were used in 33 pregnancies with ten affected fetuses and cultured amniocytes in 43 pregnancies with nine affected fetuses. In four cases, CVS results were corroborated by subsequent investigation of amniocytes because maternal cell contamination in the CV cell culture was either present or could not be excluded. Uncertain results in two other cases with intermediate DNA repair capacity and severe maternal cell contamination required further investigation. Median time needed for cell culture and analysis was 25 days. To reduce intra-assay variations, a modification of the DNA repair synthesis assay has recently been developed. In this assay, patients and controls are investigated simultaneously in mixed cultures of cells labelled with polystyrene beads. CONCLUSION: Reliable prenatal diagnosis for XP and TTD can be made by the demonstration of clearly reduced UV-induced DNA repair synthesis due to defective global genome nucleotide excision repair.     

Midwives' experiences of encountering women seeking an abortion

In order to gain knowledge about midwives' clinical and emotional experiences of working with termination of pregnancy (TOP) and their perception of women's motives for having an abortion questionnaires were mailed to a representative sample of Swedish midwives (n = 258), and 84% responded. Responses to 17 statements were studied and interpreted. It was found that every third midwife had not at all worked with TOP, and every fifth had not done so in the preceding two years. Among those who had experienced this work, few midwives had considered changing their job or had had misgivings or feelings of inadequacy caused by encountering women seeking an abortion. Both working currently with TOP and for a longer period of time were found to evoke positive experiences in every other midwife. Midwives' perception of motives for abortion corresponded very well to motives provided by women themselves. Half the midwives had had misgivings concerning late abortions and somewhat fewer regarding surgical abortions. In general, religious belief did not influence midwives' views of TOP. Those midwives who had themselves had an abortion reported fewer misgivings about late abortions than those without personal experience of TOP.     

Originalpräparate und Ersatzmittel

Ohne Zusammenfassung     

Beiträge zu Einer Physiologischen und Pathologischen Chemie der Haut

Zusammenfassung Die Quaddelprobe nachMc Clure undAldrich ist nicht imstande, die chemische Bestimmung des Wassergehaltes intravital entnommener Haut zu ersetzen. Dies ergibt sich aus der Tatsache, daß eine Kongruenz zwischen hohem Wassergehalt der Cutis und verkürzter QRZ. nur in ungefähr der Hälfte der untersuchten Fälle vorhanden ist, während der Rest ein wechselndes Verhalten zeigt. Ein Drittel dieses Restes weist sogarverlängerte QRZ, bei gleichzeitig erhöhtem H₂O-Gehalt der Cutis auf.Während wir die Quaddelprobe als Ersatz für die chemische Ermittelung des H₂O-Wertes der Cutis, d. h. also für die Bestimmung desaktuellen Wassergehaltes der Haut ablehnen, kommt ihr für die Frage, ob eine normale oder pathologisch veränderteWasserresorptionsfähigkeit der Cutis vorliegt, eine gewisse Bedeutung zu. Dies zeigt sich besonders deutlich im gegensätzlichen Verhalten des H₂O-Gehaltes und der QRZ. bei der senilen Haut, bei einzelnen Fällen von Adipositas, der Pemphigusgruppe usw.Die Wasserresorptionsfähigkeit der Cutis, ausgedrückt durch das Verhalten der QRZ., scheint weniger vomaktuellen Wassergehalt der Haut abzuhängen, als vielmehr von lokalen, wahrscheinlich physikalisch-chemisch bedingtengewebsstrukturellen Verhältnissen.Der Wassergehalt der Haut ist bei Adipösen in ungefähr zwei Drittel unseres Materiales erhöht, und zwar wie wir feststellten, fast ausnahmslos in der Cutis und nicht im subcutanen Fettgewebe; damit fällt die oftmals geäußerte Annahme, daß bei Adipositas das subcutane Fettgewebe das Wasserspeicherorgan darstellt. Auch bei Fettleibigen geht die QRZ. mit dem Wassergehalt der Cutis nicht ausnahmslos parallel, im Gegenteil, es fanden sich auch hier nicht so selten verlängerte QRZ. bei hohem H₂O-Gehalt der Cutis.     

Vitamin D Status among Women in a Rural District of Nepal: Determinants and Association with Metabolic Profile—A Population-Based Study

Hypovitaminosis D is prevalent worldwide, and especially in South-Asia. According to the Institute of Medicine (IOM), 25(OH)D levels below 30 nmol/L are defined as vitamin D deficiency (VDD) and levels between 30–50 nmol/L as insufficiency (VDI). Besides its role in calcium homeostasis, it has been postulated that vitamin D is involved in metabolic syndrome. Given the scarcity of data on vitamin D status in Nepal, we aimed to examine the prevalence of VDD and VDI, as well as the determinants and association with metabolic parameters (lipids, HbA1c), in a cohort of women in rural Nepal. Altogether, 733 women 48.5 ± 11.7 years of age were included. VDD and VDI were observed in 6.3 and 42.4% of the participants, respectively, and the prevalence increased by age. Women reporting intake of milk and eggs > 2 times weekly had higher 25(OH)D levels than those reporting intake < 2 times weekly. Women with vitamin D levels < 50 nmol/L displayed higher levels of cholesterol, LDL-cholesterol, triglycerides, and HbA1c. Additionally, a regression analysis showed a significant association between hypovitaminosis D, dyslipidemia, and HbA1c elevation. In conclusion, VDI was prevalent and increased with age. Milk and egg intake > 2 times weekly seemed to decrease the risk of VDI. Moreover, hypovitaminosis D was associated with an adverse metabolic profile.