Excellent adherence to tuberculosis (TB) treatment is critical to cure TB and avoid the emergence of resistance. Wirelessly observed therapy (WOT) is a novel patient self-management system consisting of an edible ingestion sensor (IS), external wearable patch, and paired mobile device that can detect and digitally record medication ingestions. Our study determined the accuracy of ingestion detection in clinical and home settings using WOT and subsequently compared, in a randomized control trial (RCT), confirmed daily adherence to medication in persons using WOT or directly observed therapy (DOT) during TB treatment. We evaluated WOT in persons with active Mycobacterium tuberculosis complex disease using IS-enabled combination isoniazid 150 mg/rifampin 300 mg (IS-Rifamate). Seventy-seven participants with drug-susceptible TB in the continuation phase of treatment, prescribed daily isoniazid 300 mg and rifampin 600 mg, used IS-Rifamate. The primary endpoints of the trial were determination of the positive detection accuracy (PDA) of WOT, defined as the percentage of ingestions detected by WOT administered under direct observation, and subsequently the proportion of prescribed doses confirmed by WOT compared to DOT. Initially participants received DOT and WOT simultaneously for 2–3 weeks to allow calculation of WOT PDA, and the 95% confidence interval (CI) was estimated using the bootstrap method with 10,000 samples. Sixty-one participants subsequently participated in an RCT to compare the proportion of prescribed doses confirmed by WOT and DOT. Participants were randomized 2:1 to receive WOT or maximal in-person DOT. In the WOT arm, if ingestions were not remotely confirmed, the participant was contacted within 24 hours by text or cell phone to provide support. The number of doses confirmed was collected, and nonparametric methods were used for group and individual comparisons to estimate the proportions of confirmed doses in each randomized arm with 95% CIs. Sensitivity analyses, not prespecified in the trial registration, were also performed, removing all nonworking (weekend and public holiday) and held-dose days. Participants, recruited from San Diego (SD) and Orange County (OC) Divisions of TB Control and Refugee Health, were 43.1 (range 18–80) years old, 57% male, 42% Asian, and 39% white with 49% Hispanic ethnicity. The PDA of WOT was 99.3% (CI 98.1; 100). Intent-to-treat (ITT) analysis within the RCT showed WOT confirmed 93% versus 63% DOT (p < 0.001) of daily doses prescribed. Secondary analysis removing all nonworking days (weekends and public holidays) and held doses from each arm showed WOT confirmed 95.6% versus 92.7% (p = 0.31); WOT was non-inferior to DOT (difference 2.8% CI [−1.8%, 9.1%]). One hundred percent of participants preferred using WOT. WOT associated adverse events were <10%, consisting of minor skin rash and pruritus associated with the patch. WOT provided longitudinal digital reporting in near real time, supporting patient self-management and allowing rapid remote identification of those who needed more support to maintain adherence. This study was conducted during the continuation phase of TB treatment, limiting its generalizability to the entire TB treatment course. In terms of accuracy, WOT was equivalent to DOT. WOT was superior to DOT in supporting confirmed daily adherence to TB medications during the continuation phase of TB treatment and was overwhelmingly preferred by participants. WOT should be tested in high-burden TB settings, where it may substantially support low- and middle-income country (LMIC) TB programs. ClinicalTrials.gov NCT01960257.

The Salmonella SpvB protein possesses ADP-ribosyl transferase activity. SpvB, acting as an intracellular toxin, covalently modifies monomeric actin,

Few studies have investigated antiretroviral (ARV) knowledge and self-efficacy in limited literacy patients. Using a randomized controlled study design, we investigated the influence of a simple pre-tested patient information leaflet (PIL) containing both text and illustrations on HIV- and ARV-related knowledge and on self-efficacy over six months in a limited literacy African population. The recruited patients were randomly allocated to either control (standard care) or intervention group (standard care plus illustrated PIL). HIV and medicines-related knowledge was evaluated with a 22-question test at baseline, one, three, and six months. Self-efficacy was assessed using a modified version of the HIV Treatment Adherence Self-Efficacy Scale. Two-thirds of the patients were female, mean age was 39.0 ± 9.6 years and mean education was 7.3 ± 2.8 years. Patients who received the PIL showed a significant knowledge increase over the six-month period (62.0–94.4%), with improvement at each subsequent interview whereas the control group showed no improvement. At baseline, side effect knowledge was the lowest (50–56%) but increased in the intervention group to 92%. Similarly, other medicine-related knowledge at baseline (57–67%) improved significantly (93%) and was sustained over six months. Cohen's d values post-baseline ranged between 1.36 and 2.18, indicating a large intervention effect. Self-efficacy improved significantly over six months in intervention but not control patients. At baseline, patients with ≤3 years of education had lower knowledge and self-efficacy but this was not observed post-intervention, which we attribute to the PIL mitigating the effect of limited education. Knowledge and self-efficacy were significantly correlated in the intervention group. In conclusion, a low-cost intervention of a well-designed, pre-tested, simple, illustrated PIL significantly increased both ARV knowledge and self-efficacy in HIV patients with limited education.

Mobile and tablet apps, ubiquitous and pervasive computing, wearable computing and domotics for health.

Despite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown. In this cross-sectional study, children who were 3-12 years old, on antiretroviral therapy and pre-pubertal were recruited from a Family HIV Clinic in South Africa. Lipoatrophy was identified and graded by consensus between two HIV pediatricians using a standardized grading scale. A professional dietician performed formal dietary assessment and anthropometric measurements of trunk and limb fat. Previous antiretroviral exposures were recorded. In a Dual-Energy X-ray Absorbtiometry (DXA) substudy body composition was determined in 42 participants. Among 100 recruits, the prevalence of visually obvious lipoatrophy was 36% (95% CI: 27%-45%). Anthropometry and DXA measurements corroborated the clinical diagnosis of lipoatrophy: Both confirmed significant, substantial extremity fat loss in children with visually obvious lipoatrophy, when adjusted for age and sex. Adjusted odds ratio for developing lipoatrophy was 1.9 (95% CI: 1.3 - 2.9) for each additional year of accumulated exposure to standard dose stavudine. Cumulative time on standard dose stavudine was significantly associated with reductions in biceps and triceps skin-fold thickness (p=0.008). The prevalence of visually obvious lipoatrophy in pre-pubertal South African children on antiretroviral therapy is high. The amount of stavudine that children are exposed to needs review. Resources are needed to enable low-and-middle-income countries to provide suitable pediatric-formulated alternatives to stavudine-based pediatric regimens. The standard stavudine dose for children may need to be reduced. Diagnosis of lipoatrophy at an early stage is important to allow timeous antiretroviral switching to arrest progression and avoid stigmatization. Diagnosis using visual grading requires training and experience, and DXA and comprehensive anthropometry are not commonly available. A simple objective screening tool is needed to identify early lipoatrophy in resource-limited settings where specialized skills and equipment are not available.

Recurrent invasive nontyphoidal Salmonella (NTS) infection is an AIDS-defining illness that has become less common in the developed world in the era of highly active antiretroviral therapy (HAART), while it has emerged as a major public health problem in developing countries, particularly sub-Saharan Africa. We retrospectively analyzed Salmonella (NTS) infection in HIV/AIDS patients from June 2003 until December 2009 at the University of California, San Diego (UCSD), Medical Center. Bacterial isolates from all patients were tested for selected microbiological properties, including major Salmonella (NTS) virulence loci rpoS , sodCI , spvB , and sseI . Fourteen percent of all Salmonella (NTS) cases recorded at the UCSD Medical Center during this period occurred in known HIV/AIDS patients. The clinical presentations in HIV patients fell into two distinct groups, bacteremia and enteritis. There was little clinical overlap between these two syndromes. All strains were positive for the presence of the rpoS and sodCI virulence loci, and 75% of strains were positive for the presence of the spvB and sseI loci. Antibiotic susceptibility assay showed that all strains were susceptible to trimethoprim-sulfamethoxazole and ciprofloxacin. The clinical presentation did not have a clear relationship to the CD4 ⁺ cell count. Of the bacteremic isolates, all but one isolate, drawn from a patient with substantial enteric comorbidities, had all of the virulence genes tested, but 66% of nonbacteremic, enteritis strains also contained all the tested virulence loci. In conclusion, neither patients' CD4 ⁺ cell count nor bacterial strain properties necessarily predicted the clinical presentation of HIV/AIDS patients with Salmonella (NTS) infection, and AIDS patients can have episodes of Salmonella enteritis without dissemination.