Alternative dosing guidelines to improve outcomes in childhood tuberculosis : a mathematical modelling study

Background Malnourished and young children are particularly susceptible to severe forms of tuberculosis and poor treatment response. WHO dosing guidelines for drugs for tuberculosis treatment are based only on weight, which might lead to systematic underdosing and poor outcomes in these children. We aimed to assess and quantify the population effect of WHO guidelines for drug-susceptible tuberculosis in children in the 20 countries with the highest disease burden. Methods We used an integrated model that linked country-specific demographic data at the individual level from the 20 countries with the highest disease burden to pharmacokinetic, outcome, and epidemiological models. We estimated tuberculosis treatment outcomes in children younger than 5 years following WHO guidelines (children are dosed by weight bands corresponding to the number of fixed-dose combination tablets [75 mg rifampicin, 50 mg isoniazid, 150 mg pyrazinamide]) and two alternative dosing strategies: one based on a proposed algorithm that uses age, weight, and available formulations, in which underweight children would receive the same drug doses as would normal weight children of the same age; and another based on an individualised algorithm without dose limitations, in which derived doses results in target exposure attainment for the typical child. Findings We estimated that 57 234 (43%) of 133 302 children younger than 5 years who were treated for tuberculosis in 2017 were underdosed with WHO dosing and only 47% of children would reach the rifampicin exposure target. Underdosing and subtherapeutic exposures were more common among malnourished children than among age-matched healthy children. The proposed dosing approach improved estimated rifampicin target exposure attainment to 62% and equalised outcomes by nutritional status. An estimated third of unfavourable treatment outcomes might be resolved with this dosing strategy, saving the lives of a minimum of 2423 children in these countries annually. With individualised dosing approaches, almost all children could achieve adequate exposure for cure. Interpretation This work shows that a simple change in dosing procedure to include age and nutritional status, requiring no additional measurements or new drug formulations, is one approach to improve tuberculosis treatment outcomes in children, especially malnourished children who are at high risk of mortality

Attitudes and perceptions of next-of-kin/loved ones toward end-of-life HIV cure-related research: A qualitative focus group study in Southern California

As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants’ next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals (n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones’ altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK

Stability and collapse of localized solutions of the controlled three-dimensional Gross-Pitaevskii equation

On the basis of recent investigations, a newly developed analytical procedure is used for constructing a wide class of localized solutions of the controlled three-dimensional (3D) Gross-Pitaevskii equation (GPE) that governs the dynamics of Bose-Einstein condensates (BECs). The controlled 3D GPE is decomposed into a two-dimensional (2D) linear Schr\"{o}dinger equation and a one-dimensional (1D) nonlinear Schr\"{o}dinger equation, constrained by a variational condition for the controlling potential. Then, the above class of localized solutions are constructed as the product of the solutions of the transverse and longitudinal equations. On the basis of these exact 3D analytical solutions, a stability analysis is carried out, focusing our attention on the physical conditions for having collapsing or non-collapsing solutions.Comment: 21 pages, 14 figure

Practice level costs of office-based hypertension performance improvement: The Heart Healthy Lenoir study

Primary care practice leaderswho consider engaging in quality improvement (QI) need to understand the practice level costs incurred when asking staff to take on new tasks. The HeartHealthy Lenoir study is a prospective cohort trial in whichQImethods were used to enhance hypertension (HTN) care and reduce racial disparities in blood pressure control in small rural primary care practices inNorth Carolina. As part of this effort, we performed an activity-based costing analysis to describe the costs incurred to develop, implement, and maintain key tasks. We interviewed 20 practice stakeholders and phone-based health coaches during 2012-2014. We calculated the time invested by individuals to perform each task within each study phase and applied national hourly wages to generate cost estimates. Our descriptive analyses focus on four of themost widely used practices. Activities included time to abstract HTN control data, participate in project meetings, identify patients with uncontrolled HTN, create standardized work, and provide additional health coaching for patients with uncontrolled HTN. Despite practice and staffing differences, the developmental phase costs were similar, ranging from $879 to$1, 417. Implementation costs varied more widely as practices took different approaches to identifying patients with uncontrolled HTN. Practice-specific phone health coaching costs ranged from $19, 508 to more than$38, 000. This study adds to the growing literature regarding practice level costs of engaging in systems change. Understanding these costs and balancing them against practice incentives may be helpful as stakeholders make decisions regarding HTN QI

Perceived Social Standing, Medication Nonadherence, and Systolic Blood Pressure in the Rural South

Purpose: Little is known about how perceived social standing versus traditional socioeconomic characteristics influence medication adherence and blood pressure (BP) among African American and white patients with hypertension in the rural southeastern United States. Methods: Perceived social standing, socioeconomic characteristics, self-reported antihypertensive medication adherence, and BP were measured at baseline in a cohort of rural African American and white patients (n = 495) with uncontrolled hypertension attending primary care practices. Multivariate models examined the relationship of perceived social standing and socioeconomic indicators with medication adherence and systolic BP. Findings: Medication nonadherence was reported by 40% of patients. Younger age [β = 0.20; P = .001], African American race [β = -0.30; P = .03], and lower perceived social standing [β = 0.08; P = .002] but not sex or traditional socioeconomic characteristics including education and household income, were significantly associated with lower medication adherence. Race-specific analyses revealed that this pattern was limited to African Americans and not observed in whites. In stepwise modeling, older age [β = 0.57, P = .001], African American race [β = 4.4; P = .03], and lower medication adherence [β = -1.7, P = .01] but not gender, education, or household income, were significantly associated with higher systolic BP. Conclusions: Lower perceived social standing and age, but not traditional socioeconomic characteristics, were significantly associated with lower medication adherence in African Americans. Lower medication adherence was associated with higher systolic BP. These findings suggest the need for tailored, culturally relevant medication adherence interventions in rural communities

Race-Specific Patterns of Treatment Intensification Among Hypertensive Patients Using Home Blood Pressure Monitoring: Analysis Using Defined Daily Doses in the Heart Healthy Lenoir Study

Background: Racial disparities in blood pressure (BP) control persist, but whether differences by race in antihypertensive medication intensification (AMI) contribute is unknown. Objective: To compare AMI by race for patients with elevated home BP readings. Methods: This prospective cohort study followed adult patients from 6 rural primary care practices who used home BP monitoring (HBPM) and recorded/reported values. For providers, AMI was encouraged when mean HBPM systolic blood pressure (SBP) values were ⩾135 mm Hg; patients received phone-based coaching on HBPM technique and sharing HBPM findings. AMI was assessed between baseline and 12 months using defined daily dose (DDD) and summed to create a total antihypertensive DDD value. Results: A total of 217 patients (mean age = 61.4 ± 10.2 years; 66% female; 57% black) provided usable HBPM data. Among 90 (41%) intensification-eligible hypertensive patients (ie, mean HBPM SBP values for 6-months ⩾135 mm Hg), mean total antihypertensive DDD was increased in 61% at 12 months. Blacks had significantly higher mean DDD at baseline and 12 months, but intensification (+0.72 vs +0.65; P = 0.83) was similar by race. However, intensification was greater in males than females (+1.1 vs +0.39; P = 0.031). Reduction in mean SBP following intensification was greater in white versus black patients (−8.2 vs −3.9 mm Hg; P = 0.14). Conclusion/Relevance: Treatment intensification in HBPM users was similar by race, differed significantly by gender, and may produce a greater response in white patients. Differential AMI in HBPM users does not appear to contribute to persistent racial disparities in BP control

Search for heavy neutrinos mixing with tau neutrinos

We report on a search for heavy neutrinos (\nus) produced in the decay D_s\to \tau \nus at the SPS proton target followed by the decay \nudecay in the NOMAD detector. Both decays are expected to occur if \nus is a component of $\nu_{\tau}$.\ From the analysis of the data collected during the 1996-1998 runs with $4.1\times10^{19}$ protons on target, a single candidate event consistent with background expectations was found. This allows to derive an upper limit on the mixing strength between the heavy neutrino and the tau neutrino in the \nus mass range from 10 to 190 $\rm MeV$. Windows between the SN1987a and Big Bang Nucleosynthesis lower limits and our result are still open for future experimental searches. The results obtained are used to constrain an interpretation of the time anomaly observed in the KARMEN1 detector.\Comment: 20 pages, 7 figures, a few comments adde

Final NOMAD results on nu_mu->nu_tau and nu_e->nu_tau oscillations including a new search for nu_tau appearance using hadronic tau decays

Results from the nu_tau appearance search in a neutrino beam using the full NOMAD data sample are reported. A new analysis unifies all the hadronic tau decays, significantly improving the overall sensitivity of the experiment to oscillations. The "blind analysis" of all topologies yields no evidence for an oscillation signal. In the two-family oscillation scenario, this sets a 90% C.L. allowed region in the sin^2(2theta)-Delta m^2 plane which includes sin^2(2theta)<3.3 x 10^{-4} at large Delta m^2 and Delta m^2 < 0.7 eV^2/c^4 at sin^2(2theta)=1. The corresponding contour in the nu_e->nu_tau oscillation hypothesis results in sin^2(2theta)<1.5 x 10^{-2} at large Delta m^2 and Delta m^2 < 5.9 eV^2/c^4 at sin^2(2theta)=1. We also derive limits on effective couplings of the tau lepton to nu_mu or nu_e.Comment: 46 pages, 16 figures, Latex, to appear on Nucl. Phys.

Lessons learned from implementing health coaching in the heart healthy lenoir hypertension study

Background: Health coaching is increasingly important in patient-centered medical homes. Objectives: Describe formative evaluation results and lessons learned from implementing health coaching to improve hypertension self-management in rural primary care. Methods: A hypertension collaborative was formed consisting of six primary care sites. Twelve monthly health coaching phone calls were attempted for 487 participants with hypertension. Lessons Learned: Participant engagement was challenging; 58% remained engaged, missing fewer than three consecutive calls. Multivariate analyses revealed that older age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01–1.05), African American race (O,R 1.73; 95% CI, 1.15–2.60), greater number of comorbidities (OR, 1.17; 95% CI, 1.05–1.30) and receiving coaching closer to enrollment (OR, 5.03; 95% CI, 2.53–9.99) were correlated independently with engagement. Participants reported the coaching valuable; 96% would recommend health coaching to others. Conclusions: Health coaching in hypertension care can be successful strategy for engaging more vulnerable groups. A more tailored approach may improve engagement with counseling