Effects of Multi-Month Dispensing on Clinical Outcomes: Retrospective Cohort Analysis Conducted in Kenya.

Multi-month dispensing (MMD) has been widely adopted by national HIV programs as a key strategy for improving the quality of HIV care and treatment services while meeting the unique needs of diverse client populations. We assessed the clinical outcomes of clients receiving MMD in Kenya by conducting a retrospective cohort study using routine programmatic data in 32 government health facilities in Kenya. We included clients who were eligible for multi-month antiretroviral therapy (ART) dispensing for ≥ 3 months (≥ 3MMD) according to national guidelines. The primary exposure was enrollment into ≥ 3MMD. The outcomes were lost to follow-up (LTFU) and viral rebound. Multilevel modified-Poisson regression models with robust standard errors were used to compare clinical outcomes between clients enrolled in ≥ 3MMD and those receiving ART dispensing for less than 3 months (< 3MMD). A total of 3,501 clients eligible for ≥ 3MMD were included in the analysis, of whom 65% were enrolled in ≥ 3MMD at entry into the cohort. There was no difference in LTFU of ≥ 180 days between the two types of care (aRR 1.1, 95% CI 0.7-1.6), while ≥ 3MMD was protective for viral rebound (aRR 0.1 95% CI 0.0-0.2). As more diverse client-focused service delivery models are being implemented, robust evaluations are essential to guide the implementation, monitor progress, and assess acceptability and effectiveness to deliver optimal people-centered care.

A simple model for the total number of SARS-CoV-2 infections on a national level.

This study aimed to identify an appropriate simple mathematical model to fit the number of coronavirus disease 2019 (COVID-19) cases at the national level for the early portion of the pandemic, before significant public health interventions could be enacted. The total number of cases for the COVID-19 epidemic over time in 28 countries was analysed and fit to several simple rate models. The resulting model parameters were used to extrapolate projections for more recent data. While the Gompertz growth model (mean R2 = 0.998) best fit the current data, uncertainties in the eventual case limit introduced significant model errors. However, the quadratic rate model (mean R2 = 0.992) fit the current data best for 25 (89%) countries as determined by R2 values of the remaining models. Projection to the future using the simple quadratic model accurately forecast the number of future total number of cases 50% of the time up to 10 days in advance. Extrapolation to the future with the simple exponential model significantly overpredicted the total number of future cases. These results demonstrate that accurate future predictions of the case load in a given country can be made using this very simple model.

Control of head lice with a coconut-derived emulsion shampoo.

OBJECTIVE: To evaluate a novel coconut-derived emulsion (CDE) shampoo against head lice infestation in children. DESIGN: A school trial in which pupils were treated on days 0 and 7 and checked on days 8 and 15 and a family trial where product was applied by parents three times in 2 weeks or used as a cosmetic shampoo and checked on days 14 and days 70. SETTING: UK schools in Bristol and Western-super-Mare and families in Northern Somerset. MAIN OUTCOME MEASURE: Numbers of children free from infestation after treatment. RESULTS: In the school trial, percentage cures at day 8 were 14% (permethrin, n=7) and 61% (CDE, n=37). In the family trial where all family members were treated, cure rate was 96% (n=28), and if the shampoo was subsequently used as a cosmetic shampoo, only 1 of 12 children became re-infested after 10 weeks. CONCLUSION: CDE shampoo is a novel effective method of controlling head lice and used after treatment as a cosmetic shampoo can aid in the reduction of re-infestation.

One amino acid in mouse activated factor VII defines its endothelial protein C receptor (EPCR) binding and modulates its EPCR-dependent hemostatic activity in vivo.

Essentials The lack of factor (F) VIIa-endothelial protein C receptor (EPCR) binding in mice is unresolved. A single substitution of Leu4 to Phe in mouse FVIIa (mFVIIa) enables its interaction with EPCR. mFVIIa with a Phe4 shows EPCR binding-dependent enhanced hemostatic function in vivo vs. mFVIIa. Defining the FVIIa-EPCR interaction in mice allows for further investigating its biology in vivo. SUMMARY: Background Human activated factor VII (hFVIIa), which is used in hemophilia treatment, binds to the endothelial protein C (PC) receptor (EPCR) with unclear hemostatic consequences. Interestingly, mice lack the activated FVII (FVIIa)-EPCR interaction. Therefore, to investigate the hemostatic consequences of this interaction in hemophilia, we previously engineered a mouse FVIIa (mFVIIa) molecule that bound mouse EPCR (mEPCR) by using three substitutions from mouse PC (mPC), i.e. Leu4→Phe, Leu8→Met, and Trp9→Arg. The resulting molecule, mFVIIa-FMR, modeled the EPCR-binding properties of hFVIIa and showed enhanced hemostatic capacity in hemophilic mice versus mFVIIa. These data implied a role of EPCR in the action of hFVIIa in hemophilia treatment. However, the substitutions in mFVIIa-FMR only broadly defined the sequence determinants for its mEPCR interaction and enhanced function in vivo. Objectives To determine the individual contributions of mPC Phe4, Met8 and Arg9 to the in vitro/in vivo properties of mFVIIa-FMR. Methods The mEPCR-binding properties of single amino acid variants of mFVIIa or mPC at position 4, 8 or 9 were investigated. Results and conclusions Phe4 in mFVIIa or mPC was solely critical for interaction with mEPCR. In hemophilic mice, administration of mFVIIa harboring a Phe4 resulted in a 1.9-2.5-fold increased hemostatic capacity versus mFVIIa that was EPCR binding-dependent. This recapitulated previous observations made with triple-mutant mFVIIa-FMR. As Leu8 is crucial for hFVIIa-EPCR binding, we describe the sequence divergence of this interaction in mice, now allowing its further characterization in vivo. We also illustrate that modulation of the EPCR-FVIIa interaction may lead to improved FVIIa therapeutics.

A new Saccharomyces cerevisiae ankyrin repeat-encoding gene required for a normal rate of cell proliferation.

We have characterized a new ankyrin (ANK) repeat-containing Saccharomyces cerevisiae gene, YAR1, located between the HSP82 and SUI3 genes on chromosome XVI. YAR1 encodes a 200-amino-acid (aa) protein with two ANK repeat motifs and an acidic C terminus rich in PEST-like sequences. The Yar1 ANK repeats are most similar to the conserved ANK repeats in the yeast cell cycle transcription factor, Swi6. We show that YAR1 is transcribed as an 800-nucleotide (nt) poly(A)+ mRNA from a promoter lacking a consensus TATA sequence. YAR1 is transcribed in both haploid and diploid cells, and in haploid cells arrested in G1 with alpha-factor or in S phase with hydroxyurea. YAR1 shares an intergenic region with HSP82, and while HSP82 transcription is induced 15-fold by heat shock, transcription of YAR1 is transiently repressed by heat shock. We show that YAR1 is not an essential gene, but that haploid cells bearing a yar1 deletion grow significantly more slowly than do isogenic wild-type cells, especially at low temperature.

Determination of extent and location of coronary artery disease in patients without prior myocardial infarction by thallium-201 tomography with pharmacologic stress.

Seventy-six patients undergoing pharmacologic stress 201TI tomography and coronary angiography within 14 +/- 12 days were studied to determine how well coronary artery disease extent and location could be determined by this scintigraphic technique. No patient had prior myocardial infarction or revascularization. Scintigrams were scored visually and quantitatively. Angiographic lesions > or = 50% were considered significant. Receiver operating characteristic curves were generated for the scintigrams against the angiographic gold standard. Predictive accuracies were determined and compared with the quantitative results. Predictive accuracy was 0.49 for visual and 0.58 for computer identification of single-vessel disease, 0.52 for both visual and computer identification of multivessel disease, 0.64 for both in correctly localizing left anterior descending artery disease, 0.78 versus 0.70 for the right coronary artery and 0.72 versus 0.68 for the left circumflex artery. For the overall detection of disease, the predictive accuracies were 0.79 and 0.80. Although high diagnostic accuracy for detection of coronary artery disease by this approach has been previously documented, the assessment of extent of disease in patients without prior myocardial infarction appears limited.

The in vitro response of sheep scab mites to pyrethroid insecticides.

The response of sheep scab mites to pyrethroid insecticides and organophosphate compounds was studied in vitro with the objective of finding a simple test for detecting insecticide resistance in scab mites. Psoroptes cuniculi from rabbits or P. ovis from sheep were enclosed in small 'tea bags' made from heat sealable paper prior to dipping in insecticide. Mites failed to die 24 h after a 1 min dip in working concentrations of insecticidal sheep dips. With flumethrin a variety of different conditions were tested but most failed to improve the efficacy of flumethrin. It is suggested with freshly collected mites pyrethroids may be taken up by ingestion.

Weight-based targeted selective treatment of gastrointestinal nematodes in a commercial sheep flock.

Targeted selective treatment (TST) strategies, in which a proportion of the flock or herd is left untreated so that anthelmintic-susceptible genotypes are preserved, are increasingly advocated as a means of prolonging the effective life of current anthelmintic drugs. The major limitation to this approach is a lack of efficient indicators for selection, which can be applied effectively on commercial farms to identify individuals that can be left untreated without fear of disease or production loss. With the advent of electronic identification and automated weighing technology, monitoring of short-term changes in weight gain shows promise as such an indicator, but its operation in the field as part of TST has yet to be evaluated. Widespread deployment of weight-based TST will be highly dependent on the likely production penalty from leaving the fastest growing animals untreated. On a commercial flock in south-west UK, the weight gain of 508 lambs of various breeds was tracked using an automated identification and weighing system, every one to ten weeks from June to December (one to four weeks in summer), and a variable proportion of the fastest growing individuals that also appeared to be in good condition with little breech soiling was left untreated during whole-flock dosing in June, July and August. In total, 51 lambs were selected for non-treatment on at least one occasion, while the other lambs were treated two or three times during the summer. Subsequent weight gain of untreated animals was not reduced relative to their peers in either the short-term or over the whole grazing season. Faecal egg counts from untreated individuals did not differ significantly from those of the rest of the flock, suggesting that animals left untreated on the basis of weight gain can contribute effectively to refugia. The application of TST in this case is cautious in its extent, but this is appropriate on a commercial farm with associated aversion to production loss. Results suggest that such losses can be avoided while leaving part of the flock untreated, and should encourage wider application of this approach to slow the development of anthelmintic resistance. Since the cost of investment in weighing and recording systems is likely to prove prohibitive to many farmers, other selective indicators should also be investigated. The co-ordination of TST with pasture use to maximise the benefit in terms of environmental refugia, and its integration with other control strategies, also requires further attention.

Octopamine distribution in the tsetse fly Glossina morsitans.

Tissues of Glossina morsitans were assayed for octopamine using an enzymatic technique. Octopamine was detected at the highest concentration in the brain (7.06-7.99 ng mg-1 tissue protein) and thoracic ganglion (10.9-13.89 ng mg-1 tissue protein). Octopamine was present in haemolymph at a concentration of 1.0-1.27 X 10(-7) M. This was not found to vary when insects were flown or mechanically stressed. Nervous tissue, flight muscle and haemolymph showed a significant ability to metabolize octopamine. The greatest enzyme activity was present in the haemolymph.

Susceptibility of British head lice, Pediculus capitis, to imidacloprid and fipronil.

The head louse, Pediculus capitis De Geer (Phthiraptera: Pediculidae) has developed resistance to organochlorines, the organophosphate malathion and to pyrethroids in the U.K. Therefore, headlice from Bristol school children were bioassayed against two new insecticides, fipronil and imidacloprid. Pediculus capitis was fully susceptible to imidacloprid, but it required a relatively high dose and acted slowly. Fipronil acted faster at lower dose, but seemed to be affected by cross-resistance in a small proportion of P. capitis.

Evidence for double resistance to permethrin and malathion in head lice.

A rising prevalence of head lice among school children and rising sales of insecticides with anecdotal evidence of their treatment failure, led us to examine whether head lice in Bristol and Bath were resistant to the insecticides available for treating head lice. Ten schools in Bristol and Bath were visited to collect field samples of head lice. A comparison was made of the survival rates of fully sensitive laboratory reared body lice and field samples of head lice on insecticide exposure. To confirm the in vitro relevance of these tests we performed supervised treatments of affected subjects with malathion or permethrin. There were significant differences (P < 10-6 Fishers exact test) between head and body lice survival for malathion and permethrin exposure, but not for carbaryl. There was an 87% failure rate for permethrin and a 64% failure rate for malathion with the topical treatment of a selected number of infested school children. We conclude that there is a high resistance to permethrin and malathion, but head lice remain fully sensitive to carbaryl. This is the first report of doubly resistant head lice. As permethrin, phenothrin (a very similar synthetic pyrethroid) or malathion are the active ingredients in all the over-the-counter head lice treatments in the U.K., then it is likely that head lice prevalence will continue to increase. The resistance against permethrin employed by the head louse is probably the kdr (knockdown resistance) mechanism, and an enzyme-mediated malathion-specific esterase is the likely mechanism against malathion.