Voluntary Counselling, HIV Testing and Sexual Behaviour Among Patients with Tuberculosis in a Rural District of Malawi.

OBJECTIVES: A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi in order to 1) verify the acceptability of voluntary counselling and testing for human immunodeficiency virus (HIV) infection; 2) describe sexual behaviour and condom use; and 3) identify socio-demographic and behavioural risk factors associated with 'no condom use'. DESIGN: Cross-sectional study. METHODS: Consecutive patients diagnosed with TB between January and December 2000 were offered voluntary counselling and HIV testing (VCT) and were subsequently interviewed. RESULTS: There were 1,049 new TB patients enrolled in the study. Of these, 1,007 (96%) were pre-test counselled, 955 (91%) underwent HIV testing and 912 (87%) were post-test counselled; 43 (4%) patients refused HIV testing. The overall HIV infection rate was 77%. Of all HIV-positive TB patients, 691 (94%) were put on cotrimoxazole. There were 479 (49%) TB patients who reported sexual encounters, of whom only 6% always used condoms. Unprotected sex was associated with having TB symptoms for over 1 month, having had less than 8 years of school education, being single, divorced or widowed or having sex with the same partner. CONCLUSIONS: Offering VCT to TB patients in this setting has a high acceptance rate and provides an opportunity to strengthen and integrate TB and HIV programmes

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Cotrimoxazole prophylaxis in HIV-infected individuals after completing anti-tuberculosis treatment in Thyolo, Malawi.

SETTING: Thyolo, rural southern Malawi. OBJECTIVES: To determine 1) the proportion who continue with cotrimoxazole prophylaxis for the prevention of opportunistic infections, and 2) the reasons for continuing or stopping prophylaxis, in human immunodeficiency virus (HIV) infected individuals with tuberculosis (TB) who complete anti-tuberculosis treatment. DESIGN: A cross-sectional study. METHODS: A questionnaire study of all HIV-infected TB patients who had been registered over a 3-month period to receive anti-tuberculosis treatment and cotrimoxazole prophylaxis and who had completed antituberculosis treatment 3-6 months earlier. RESULTS: Of 82 HIV-infected individuals who were alive at the time of interview, 76 (93%) were continuing with cotrimoxazole and wished to do so indefinitely. The most common reason for continuing the drug was to prevent illness associated with HIV, while the most common reason for stopping was long distances to the health facility. Ninety-six percent of patients received cotrimoxazole free of charge from a health centre. Of those who wished to continue indefinitely, the majority (63%) could not afford to pay for the drug. CONCLUSIONS: In a rural setting, the great majority of HIV-infected individuals continued with cotrimoxazole after completing anti-tuberculosis treatment. Making the drug available and providing it free of charge is essential if it is to remain accessible for longer term prevention

Sexually Transmitted Infections and Sexual Behaviour Among Commercial Sex Workers in a Rural District of Malawi.

In Thyolo District, Malawi, a study was conducted among commercial sex workers (CSWs) attending mobile clinics in order to; determine the prevalence and pattern of sexually transmitted infections (STIs), describe sexual behaviour among those who have an STI and identify risk factors associated with 'no condom use'. There were 1817 CSWs, of whom 448 (25%) had an STI. Of these, the commonest infections included 237 (53%) cases of abnormal vaginal discharge, 109 (24%) cases of pelvic inflammatory disease and 95 (21%) cases of genital ulcer disease (GUD). Eighty-seven per cent had sex while symptomatic, 17% without condoms. Having unprotected sex was associated with being married, being involved with commercial sex outside a known rest-house or bar, having a GUD, having fewer than two clients/day, alcohol intake and having had no prior medication for STI. The high levels of STIs, particularly GUDs, and unprotected sex underlines the importance of developing targeted interventions for CSWs and their clients

Passive Versus Active Tuberculosis Case Finding and Isoniazid Preventive Therapy Among Household Contacts in a Rural District of Malawi.

SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with active case finding among household contacts of smear-positive pulmonary tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of child contacts aged under 6 years who are placed on isoniazid (INH) preventive therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding was conducted among household contacts, and the uptake of INH preventive therapy in children was assessed. RESULTS: There were 189 index TB cases and 985 household contacts. Human immunodeficiency virus (HIV) prevalence among index cases was 69%. Prevalence of TB by passive case finding among 524 household contacts was 0.19% (191/100000), which was significantly lower than with active finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113 children received the drug. Transport costs associated with chest X-ray (CXR) screening were the major reason for low INH uptake. CONCLUSIONS: Where the majority of TB patients are HIV-positive, active case finding among household contacts yields nine times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH prophylaxis

A spatially and temporally localized sub-laser-cycle electron source

We present an experimental and numerical study of electron emission from a sharp tungsten tip triggered by sub-8 femtosecond low power laser pulses. This process is non-linear in the laser electric field, and the non-linearity can be tuned via the DC voltage applied to the tip. Numerical simulations of this system show that electron emission takes place within less than one optical period of the exciting laser pulse, so that an 8 fsec 800 nm laser pulse is capable of producing a single electron pulse of less than 1 fsec duration. Furthermore, we find that the carrier-envelope phase dependence of the emission process is smaller than 0.1% for an 8 fsec pulse but is steeply increasing with decreasing laser pulse duration.Comment: 4 pages, 5 figure

Voluntary Counselling, HIV Testing and Adjunctive Cotrimoxazole Reduces Mortality in Tuberculosis Patients in Thyolo, Malawi.

OBJECTIVES: To assess the feasibility and effectiveness of voluntary counselling, HIV testing and adjunctive cotrimoxazole in reducing mortality in a cohort of tuberculosis (TB) patients registered under routine programme conditions in a rural district of Malawi. DESIGN: 'Before' and 'after' cohort study using historical controls. METHODS: Between 1 July 1999 and 30 June 2000 all TB patients were started on standardized anti-TB treatment, and offered voluntary counselling and HIV testing (VCT). Those found to be HIV-positive were offered cotrimoxazole at a dose of 480 mg twice daily, provided there were no contraindications. Side-effects were monitored clinically. End-of-treatment outcomes in this cohort (intervention group) were compared with a cohort registered between 1 July 1998 and 30 June 1999 in whom VCT and cotrimoxazole was not offered (control group). FINDINGS: A total of 1986 patients was registered in the study: 1061 in the intervention group and 925 in the control cohort. In the intervention group, 1019 (96%) patients were counselled pre-test, 964 (91%) underwent HIV testing and 938 (88%) were counselled post-test. The overall HIV-seroprevalence rate was 77%. A total of 693 patients were given cotrimoxazole of whom 14 (2%) manifested minor dermatological reactions. The adjusted relative risk of death in the intervention group compared with the control group was 0.81 (P < 0.001). The number needed to treat with VCT and adjunctive cotrimoxazole to prevent one death during anti-TB treatment was 12.5. INTERPRETATION: This study shows that VCT and adjunctive cotrimoxazole is feasible, safe and reduces mortality rates in TB patients under routine programme conditions

Single-cell profiling for advancing birth defects research and prevention

Cellular analysis of developmental processes and toxicities has traditionally entailed bulk methods (e.g., transcriptomics) that lack single cell resolution or tissue localization methods (e.g., immunostaining) that allow only a few genes to be monitored in each experiment. Recent technological advances have enabled interrogation of genomic function at the single-cell level, providing new opportunities to unravel developmental pathways and processes with unprecedented resolution. Here, we review emerging technologies of single-cell RNA-sequencing (scRNA-seq) to globally characterize the gene expression sets of different cell types and how different cell types emerge from earlier cell states in development. Cell atlases of experimental embryology and human embryogenesis at single-cell resolution will provide an encyclopedia of genes that define key stages from gastrulation to organogenesis. This technology, combined with computational models to discover key organizational principles, was recognized by Science magazine as the “Breakthrough of the year” for 2018 due to transformative potential on the way we study how human cells mature over a lifetime, how tissues regenerate, and how cells change in diseases (e.g., patient-derived organoids to screen disease-specific targets and design precision therapy). Profiling transcriptomes at the single-cell level can fulfill the need for greater detail in the molecular progression of all cell lineages, from pluripotency to adulthood and how cell–cell signaling pathways control progression at every step. Translational opportunities emerge for elucidating pathogenesis of genetic birth defects with cellular precision and improvements for predictive toxicology of chemical teratogenesis

Electrocardiographic and haemodynamic alterations caused by three different test solutions of local anaesthetics to detect accidental intravascular injection in children

Background The aim of this study was to investigate ECG and haemodynamic alterations provoked by a test dose of bupivacaine, epinephrine, and their combination. Methods Paediatric patients undergoing general anaesthesia were randomized into three groups. After anaesthesia induction and tracheal intubation, 0.2 ml kg−1 (max. 3 ml) of the corresponding test solution was i.v. injected: bupivacaine 0.125% (Group B), bupivacaine 0.125% plus epinephrine 1:200 000 (Group BE), or epinephrine 1:200 000 (Group E). ECG was printed and analysed post hoc. Non-invasive arterial pressure (AP) was measured at 1 and 2 min after test dose injection. Increases in T-wave of ≥25%, in heart rate (HR) of ≥10 beats min−1, and in systolic AP of ≥15 mm Hg above baseline value were considered a positive result. Results A total of 105 children aged 0.2-16 (median 6.8) yr were enrolled. Test dose injection provoked T-wave elevation in 0%, 85%, and 89% of patients in Groups B, BE, and E, respectively. A positive increase in HR was found in 0%, 68%, and 76%. A positive increase in AP at 1 min was found in 0%, 88%, and 94% and at 2 min in 0%, 42%, and 59%. A decrease in HR of ≥10 beats min−1 was observed in 6%, 76%, and 69%. Alterations in T-wave and HR were significantly influenced by age. Conclusions ECG and haemodynamic alterations after i.v. injection of a local anaesthetic test dose were significantly influenced by epinephrine. T-wave elevation, increase in AP, and changes in HR are highly reliable variables, particularly when age is taken into accoun

Effect of tracheal tube cuff shape on fluid leakage across the cuff: an in vitro study

Background This study compared the fluid leakage in the new ‘tapered' shaped against the classic ‘cylindrical' shaped tracheal tube cuffs when placed in different sized tracheas. Methods The 7.5 mm internal diameter (ID) tracheal tube cuffs—Tapered Seal Guard (TSG), Standard Seal Guard (SSG), Hi-Lo, Microcuff, Ruesch, and Portex Profile—were compared in an in vitro apparatus. Vertical artificial tracheas with 16, 20, and 22 mm ID were intubated, 5 ml clear water was applied above the unlubricated tube cuffs, and fluid leakage was measured up to 60 min. Data of tapered vs non-tapered tube cuffs (16 observations) were compared for each tracheal diameter using the Mann-Whitney test. Results Median (range) fluid leakage (ml) at 60 min was 2.14 (0.05-4.88), 1.14 (0.00-4.84), and 0.13 (0.00-1.32), respectively, for 16, 20, and 22 mm tracheas in the TSG tube studies when compared with 4.58 (0.44-4.88), 2.21 (0.00-4.81), and 0.00 (0.00-4.81) in the SSG tube and 4.54 (1.54-4.82), 0.90 (0.00-4.49), and 4.85 (4.40-4.99) in the Microcuff tube studies. Leakage in all polyvinylchloride (PVC) tube cuffs was almost complete (5 ml) within 5 min (P<0.001). Conclusions The tapered PU tube cuff was as effective as the cylindrical PU cuffs in smaller tracheal diameters and was more efficient than the cylindrical Microcuff PU tube cuff in larger tracheal diameter in preventing subglottic fluid leakage across the tube cuff tested in this in vitro study. PVC tube cuffs leaked much more and faster than PU cuff