Prevalence and Correlates of Viral Load Suppression and Human Immunodeficiency Virus (HIV) Drug Resistance Among Children and Adolescents in South Rift Valley and Kisumu, Kenya.

BACKGROUND: Children and adolescents living with HIV (CALHIV) face unique challenges, including poorer treatment outcomes, risk for drug-resistance mutations (HIVDRMs), and limited drug formulations. We estimated viral suppression (VS) prevalence and evaluated predictors of VS and HIVDRMs in Kenya. METHODS: From 2018-2020, CALHIV 1-19 years on antiretroviral therapy (ART) >6 months were enrolled in this cross-sectional study. Participants underwent viral load (VL) testing; those with VL ≥1000 copies/mL had HIVDRM testing. Sociodemographic questionnaires and medical record abstraction were completed. VS prevalence (VL <1000 copies/mL) was estimated; robust Poisson regression models were used to estimate prevalence ratios (PRs) and 95% CIs for associations between potential predictors of VS. RESULTS: Nine hundred and sixty-nine participants were enrolled. VS prevalence was .80 (95% CI: .78-.83). Being on ART >24 months (adjusted PR [aPR]: 1.22; 95% CI: 1.06-1.41), an integrase strand transfer inhibitor-containing regimen (1.13; 1.02-1.26), and attending a level 3 health facility (1.23; 1.11-1.36) were associated with VS. Missing ≥3 doses of ART in the past month (aPR: .73; 95% CI: .58-.92), having a viremic mother with HIV (.72; .53-.98), and having 3-7 (.90; .83-.97), 8-13 (.89; .82-.97), or ≥14 (.84; .77-.92) compared with <2 adherence counseling referrals were inversely associated with VS. A high proportion (n = 119, 81.5%) of unsuppressed participants had evidence of any major HIVDRM. CONCLUSIONS: HIV treatment programs should target interventions for pediatric patients at risk for treatment failure-namely, those with a caregiver with failed VS and those struggling with adherence.

The pregnancy factor: the prevalence of depression among women living with HIV enrolled in the African Cohort Study (AFRICOS) by pregnancy status.

Among Sub-Saharan African women living with HIV (WLWH), pregnancy creates unique stressors that may cause depression. We describe the prevalence of depression among WLWH enrolled in the African Cohort Study (AFRICOS) by pregnancy status and describe factors associated with depression. WLWH < 45 years of age underwent six-monthly visits with depression diagnosed using the Center for Epidemiological Studies-Depression scale. Visits were categorized as "pregnant;" "postpartum" (the first visit made after the last pregnancy visit), and "non-pregnant." The prevalence of depression was calculated for each visit type and compared using prevalence odds ratios (POR) with 95% confidence intervals (CI). Logistic regression with generalized estimating equations was used to evaluate sociodemographic factors associated with depression. From January 2013 to March 1, 2020, 1333 WLWH were enrolled, and 214 had pregnancies during follow-up. As compared to the prevalence of depression during "non-pregnant" visits (9.1%), depression was less common at "pregnant" (6.3%; POR = 0.68 [CI: 0.42, 1.09]) and "postpartum" (3.4%; POR = 0.36 [CI: 0.17, 0.76]) visits. When controlling for other factors, the visit category was not independently associated with depression. Visit number, study site, employment status, and food security were independently associated with decreased odds of depression. We observed a lower prevalence of depression during pregnancy and the postpartum period than has been previously described among WLWH during similar time points. We observed protective factors against depression which highlight the impact that holistic and consistent health care at HIV-centered clinics may have on the well-being of WLWH in AFRICOS.

Medications for Opioid Use Disorder Utilization Among Oxford House Residents.

Medications for opioid use disorder (MOUD) and recovery homes that have traditionally served those not taking medications for their recovery are important resources for treating opioid use disorder. However, little is known whether such recovery homes are a good fit for persons utilizing MOUD, and whether residents' characteristics such as drug histories and the composition of recovery homes in terms MOUD and non-MOUD residents are related to attitudes toward MOUD. The present investigation examined characteristics of persons utilizing MOUD, and attitudes regarding MOUD utilization among residents living in recovery homes (Oxford Houses, OH) in the U.S. consisting of MOUD and non-MOUD residents. Residents living with others who were utilizing MOUD reported more favorable attitudes than residents who were not living with such residents, but this was observed only among residents whose primary drug of choice involved heroin or opioids. There were no significant differences observed in terms of abstinence rates, involvement in 12-step groups, or previous MOUD treatments between residents utilizing or not utilizing MOUD. Findings suggest that persons utilizing MOUD benefit by recovery homes such as OHs whose residents have favorable attitudes toward MOUD, especially when living with fellow residents who utilize MOUD.

Persistent Low-level Viremia Predicts Subsequent Virologic Failure: Is It Time to Change the Third 90?

BACKGROUND: World Health Organization (WHO) guidelines identify human immunodeficiency virus (HIV) viral load <1000 copies/mL as the goal of antiretroviral therapy (ART). However, the clinical implications of viremia below this threshold are unclear in the African context. We examined factors associated with persistent low-level viremia (pLLV) and quantified the risk of subsequent virologic. METHODS: The African Cohort Study enrolled HIV-infected adults at clinics in Uganda, Kenya, Tanzania, and Nigeria, with assessments every 6 months. We evaluated participants prescribed ART for at least 6 months without virologic failure for pLLV. We used multinomial logistic regression to evaluate associations between prespecified factors of interest and 3 levels of pLLV (<200, 200-499, and 500-999 copies/mL). We used Anderson-Gill extended Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for viremia category associations with time to failure. RESULTS: We included 1511 participants with 4382 person-years of follow-up. PLLV <200 copies/mL was observed at 20% of visits while 2% of visits had pLLV 200-499 and 500-999 copies/mL each, with substantial variation by site. Protease inhibitor-containing ART was associated with increased risk of pLLV. Compared to undetectable viral load, pLLV ≥200 copies/mL doubled the risk of developing virologic failure (pLLV 200-499: HR, 1.81 [95% CI, 1.08-3.02]); pLLV 500-999: HR, 2.36 [95% CI, 1.52-3.67]). CONCLUSIONS: Participants with pLLV ≥200 copies/mL were at increased risk of subsequent virologic failure. Optimized HIV care in this setting should target viral suppression <200 copies/mL.

Noninfectious Comorbidity in the African Cohort Study.

BACKGROUND: Noninfectious comorbid diseases (NCDs) contribute to morbidity and mortality in human immunodeficiency virus (HIV)-infected populations in resource-rich countries. With antiretroviral therapy (ART) scale-up in Africa, understanding burden NCD informs public health strategy. METHODS: At enrollment, participants at 11 HIV clinics in Kenya, Uganda, Tanzania, and Nigeria underwent medical history, physical, laboratory, and neuropsychological assessments to identify elevated blood pressure, hypercholesterolemia, dysglycemia, renal insufficiency, and cognitive impairment. Poisson regression models estimated adjusted relative risks (ARRs) and 95% confidence intervals (CIs) for the number of NCDs associated with factors of interest. Logistic regression was used to evaluate each NCD separately among HIV-infected participants. RESULTS: Among 2720 participants with complete NCD data, 2159 (79.4%) were HIV-infected. Of those, 1426 (66.0%) were taking ART and 813 (37.7%) had at least 1 NCD. HIV infection was associated with more NCDs, especially with ART (ARR, 1.42; 95% CI, 1.22-1.66). In addition to age, body mass index, and program site, ART usage was associated with more NCDs (ARR, 1.50; 95% CI, 1.27-1.78 for virologically suppressed and ARR, 1.38; 95% CI, 1.13-1.68 for viremic) among HIV-infected participants. In participants taking ART, CD4 nadir below 200 cells/mm3 was associated with more NCDs (ARR, 1.43; 95% CI, 1.06-1.93). ART use was independently associated with hypercholesterolemia and dysglycemia. Program site was significantly associated with all comorbidities except renal insufficiency. CONCLUSIONS: HIV infection was a risk for NCDs, which were common in HIV-infected participants, geographically variable, and largely consistent with metabolic complications of first-line ART.

Spinal Cord Stimulation for Restless Legs Syndrome: Case Series and Mechanistic Hypothesis.

BACKGROUND: Spinal cord stimulation (SCS) is a well-established therapy for chronic pain syndromes, with growing applicability to other conditions. Restless legs syndrome (RLS) is a widespread, chronic movement disorder managed primarily and incompletely by medication, and its etiology can be classified as idiopathic or secondary. METHODS: Three patients underwent SCS implantation for chronic back and/or leg pain with concomitant targeting of RLS: (1) a 34-year-old man with sporadic RLS symptoms that strongly intensified after military-related spinal fractures, (2) a 54-year-old man with RLS likely secondary to meralgia paresthetica, and (3) a 42-year-old man with low back and right lower extremity pain after a military motor vehicle accident. RESULTS: Continuing through 40-month, 2-month, and 28-month follow-ups, respectively, the patients experienced exemplary relief of their RLS symptoms. Notably in the case of patient 1, this benefit appears separate from his pain relief, as during the 5-month period directly after surgery but before adjusted targeting, he only experienced pain alleviation. CONCLUSIONS: To our knowledge, this is the first reported case of using SCS as a potentially long-lasting, safe, and highly effective therapy for RLS of mixed etiology. Additionally, 2 patients with RLS possibly secondary to chronic pain also benefited from the therapy. This success may be due to increased inhibition from hypothalamic cells controlling dopaminergic input to the spine.

Nuclear dynamics in a fungal chimera.

A fungal colony is a syncytium composed of a branched and interconnected network of cells. Chimerism endows colonies with increased virulence and ability to exploit nutritionally complex substrates. Moreover, chimera formation may be a driver for diversification at the species level by allowing lateral gene transfer between strains that are too distantly related to hybridize sexually. However, the processes by which genomic diversity develops and is maintained within a single colony are little understood. In particular, both theory and experiments show that genetically diverse colonies may be unstable and spontaneously segregate into genetically homogenous sectors. By directly measuring patterns of nuclear movement in the model ascomycete fungus Neurospora crassa, we show that genetic diversity is maintained by complex mixing flows of nuclei at all length scales within the hyphal network. Mathematical modeling and experiments in a morphological mutant reveal some of the exquisite hydraulic engineering necessary to create the mixing flows. In addition to illuminating multinucleate and multigenomic lifestyles, the adaptation of a hyphal network for mixing nuclear material provides a previously unexamined organizing principle for understanding morphological diversity in the more-than-a-million species of filamentous fungi.

Comparison of Bilateral vs. Staged Unilateral Deep Brain Stimulation (DBS) in Parkinson's Disease in Patients Under 70 Years of Age.

OBJECTIVE: The most popular surgical method for deep brain stimulation (DBS) in Parkinson's disease (PD) is simultaneous bilateral DBS. However, some centers conduct a staged unilateral approach advocating that reduced continuous intraoperative time reduces postoperative complications, thus justifying the cost of a second operative session. To test these assumptions, we performed a retrospective analysis of the Truven Health MarketScan® Database. METHODS: Using the MarketScan Database, we retrospectively analyzed patients that underwent simultaneous bilateral or staged unilateral DBS between 2000 and 2009. The main outcome measures were 90-day postoperative complication rates, number of reprogramming hours one year following procedure, and annualized healthcare cost. The outcome measures were compared between cohorts using multivariate regressions controlling for appropriate covariates. RESULTS: A total of 713 patients that underwent DBS between 2000 and 2009 met inclusion criteria for the study. Of these patients, 556 underwent simultaneous bilateral DBS and 157 received staged unilateral DBS. No statistically significant differences were found between groups in the rate of infection (simultaneous: 4.3% vs. staged: 7.0%; p = 0.178), pneumonia (3.1% vs. 5.7%; p = 0.283), hemorrhage (2.9% vs. 2.5%; p = 0.844), pulmonary embolism (0.5% vs. 1.3%), and device-related complications (0.5% vs. 0.0%). Patients in the staged cohort had a higher rate of lead revision in 90 days (3.2% vs. 12.7%; RR = 3.07; p < 0.001). The staged cohort had a higher mean (SD) number of reprogramming hours within one year of procedure (6.0 ± 5.7 vs. 7.8 ± 8.1; RR = 1.17; p < 0.001). No significant difference was found between the mean (SD) annualized payments between the cohorts ($86,100 ± $94,700 vs. $102,100 ± $121,500; p = 0.148). CONCLUSION: Our study did not find a significant difference between 90-day postoperative complication rates or annualized cost between the staged and simultaneous cohorts. Thus, we believe that it is important to consider other factors when deciding between the staged and simultaneous DBS. Such factors include patient convenience and the laterality of symptoms.

National Randomized Controlled Trial of Virtual House Calls for People with Parkinson's Disease: Interest and Barriers.

BACKGROUND: Delivering specialty care remotely directly into people's homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. MATERIALS AND METHODS: Connect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinson's disease in the community with usual care augmented by virtual house calls with a Parkinson's disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinson's disease specialist over 1 year via secure, Web-based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. RESULTS: During recruitment, 11,734 individuals visited the study's Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinson's disease specialist within the previous year. CONCLUSIONS: Among individuals with Parkinson's disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms.

Experiences of Deployed Physicians in Support of Operation Allies Refuge/Operation Allies Welcome: Lessons to Inform Improvements in Training.

INTRODUCTION: Stability operations, including humanitarian assistance and disaster relief missions, are key functions of U.S. Military medicine and the Military Medical Humanitarian Assistance Course (MMHAC) is a 2-day course widely used to prepare military medical personnel for such missions. It focuses on caring for those most vulnerable in the wake of disasters, particularly children. The large-scale humanitarian deployment of military medical providers in support of Operation Allies Welcome/Operation Allies Refuge (OAW/OAR) presents an opportunity to evaluate the preparedness of these providers to care for the needs of the Afghan travelers, so we explored the experiences of military medical providers deployed in support of OAW/OAR to inform improvements in the MMHAC. MATERIALS AND METHODS: We conducted a qualitative study of military medical providers who were deployed in support of OAW/OAR using a series of three virtual focus groups. Focus group questions were structured around the main topics covered in the MMHAC (patient care, ethical considerations, logistical concerns, and preventive and public health) and explicitly asked about adaptive leadership challenges faced and strategies used to overcome them. We analyzed transcripts using inductive thematic analysis within a constructivist paradigm, with adaptive leadership as a sensitizing concept. The study was approved by the Institutional Review Board of Uniformed Services University. RESULTS: We constructed 4 themes from participant responses, each addressing challenges that medical providers faced during their mission: (1) Medical providers navigated tension between medical and public health priorities and military mission priorities; (2) Chronic and complex care needs posed unique challenges for medical personnel; (3) Challenges in patient care were compounded by logistical and system-based barriers; and (4) Cultural barriers led to ethical dilemmas that physicians felt inadequately prepared to handle, most notably with respect to gender-related concerns. Within each theme, participants described which aspects of MMHAC training were most helpful and which areas were inadequate. CONCLUSIONS: Physicians found the OAR/OAW mission meaningful but also identified challenges related to medical care provision, public health, logistics, and ethical dilemmas that hindered their ability to carry out their medical mission. Lessons learned from OAW/OAR highlight several areas in which the MMHAC training could be augmented and improved to further mitigate these challenges.

Piloting delivery of PfSPZ vaccines for malaria through a cryogenic vaccine cold chain to travel and military medicine clinics.

BACKGROUND: PfSPZ vaccines comprising Plasmodium falciparum (Pf) sporozoites (SPZ) have demonstrated > 90% protection against variant Pf malaria infections for at least 12 weeks; they are the only vaccines with the level of efficacy necessary to protect travellers. PfSPZ are eukaryotic cells stabilized by cryopreservation and distributed using a cryogenic (below -150 °C) cold chain. The Ebola vaccine and mRNA vaccines against SARS-CoV-2 pioneered uptake of vaccines requiring non-standard ultra-low temperature cold chains. The cryogenic cold chain using liquid nitrogen (LN2) vapour phase (LNVP) cryoshippers, is simpler, more efficient than -80, -20 or 2-8 °C cold chains, and does not use electricity. This study was conducted to evaluate implementation and integration of a cryogenically distributed vaccine at travel and military immunization clinics. METHODS: We conducted sequential 28-day studies evaluating vaccine shipping, storage, maintenance and accession at two US military and two civilian travel health/immunization clinics. In each clinic, personnel were trained in equipment use, procurement and handling of LN2, temperature monitoring and inventory record keeping by in-person or video instruction. RESULTS: Sites required 2-4 h/person for two persons to assimilate and develop the expertise to manage vaccine storage and LNVP operations. LN2 for recharging cryoshippers was delivered every 1-2 weeks. Vaccine ordering, receipt, storage and inventory control was conducted effectively. Simulated single dose vaccine cryovial retrieval and thawing were performed successfully in different travel clinic settings. Continuous temperature monitoring at each site was maintained with only one short excursion above -150 °C (-145 °C) through shipping, use and reverse logistics. Staff, during and at study conclusion, provided feedback that has been incorporated into our models for cold chain logistics. CONCLUSIONS: These studies demonstrated that the training in delivery, storage, administration and integration of PfSPZ vaccines can be successfully managed in different immunization clinic settings for travellers and military personnel.

Access to Healthcare and Unmet Needs in the Canadian Lesbian-Gay-Bisexual Population.

Individuals who identify as a sexual minority, including those who are lesbian, gay, or bisexual (LGB), face barriers to healthcare as well as increased discrimination, stigmatization, and negative experiences during healthcare use. Further, few healthcare providers have education and training focused on the specific healthcare needs of individuals who are part of a sexual minority group. Given the limited research on Canadian healthcare access for sexual minorities, our purpose was to use data (n > 2,800) from the 2015-16 Canadian Community Health Survey (CCHS) to investigate the perceptions of healthcare access for LGB and non-LGB Canadians. Although non-LGB and LGB participants reported comparable access to a regular care provider and were equally likely to have consulted with a general practitioner in the past 12 months, LGB respondents were more likely to have seen a specialist and reported more unmet health needs. Although we expected the linear effects of both race and sex to vary by LGB status, this effect only occurred in one model. Current results have implications for addressing health inequalities for sexual minorities, including poorer health outcomes and greater discrimination.

Evaluating Intersite Consistency Across 11 Geographically Distinct Pediatric Clerkship Training Sites: Providing Assurance That Educational Comparability Is Possible.

INTRODUCTION: We compared core pediatric clerkship student assessments across 11 geographically distinct learning environments following a major curriculum change. We sought to determine if intersite consistency existed, which can be used as a marker of program evaluation success. METHODS: We evaluated students' overall pediatric clerkship performance along with individual assessments that target our clerkship learning objectives. Using the data of graduating classes from 2015 to 2019 (N = 859), we conducted an analysis of covariance and multivariate logistic regression analysis to investigate whether the performance varied across training sites. RESULTS: Of the students, 833 (97%) were included in the study. The majority of the training sites did not show statistically significant differences from each other. After controlling for the Medical College Admission Test total score and the average pre-clerkship National Board of Medical Examiners final exam score, the clerkship site only explained a 3% additional variance of the clerkship final grade. CONCLUSIONS: Over the ensuing 5-year period after a curriculum overhaul to an 18-month, integrated module pre-clerkship curriculum, we found that student pediatric clerkship performance in clinical knowledge and skills did not differ significantly across 11 varied geographic teaching sites when controlling for students' pre-clerkship achievement. Specialty-specific curriculum resources, faculty development tools, and assessment of learning objectives may provide a framework for maintaining intersite consistency when faced with an expanding network of teaching facilities and faculty.

The Burden of Arboviral Infections in the Military Health System 2012-2019.

Arboviral infections, including dengue (DNV), chikungunya (CHIKV), and Zika (ZIKV), impact both travelers and native populations of endemic regions. We sought to assess the disease burden of arboviral infections in the Military Health System, the validity of arboviral diagnostic codes, and the role of pretravel counseling on insect avoidance precautions. We searched for diagnostic codes consistent with arboviral infection and grouped them into DNV, CHIKV, ZIKV, Japanese encephalitis virus (JEV), and Other. Demographic data were evaluated. A subset of charts in each category were reviewed for diagnostic validity and travel characteristics. In all, 10,547 unique subjects carried 17,135 arboviral diagnostic codes, including 1,606 subjects (15.2%) coded for DNV, 230 (2.2%) for ZIKV, 65 (0.6%) for CHIKV, and 4,317 (40.9%) for JEV. A chart review was performed on 807 outpatient charts, yielding outpatient diagnostic code positive predictive values of 60.5% (DNV), 15.3% (ZIKV), and 64.5% (CHIKV); there were no valid cases of JEV. Dengue represented the greatest burden of arboviral infections with 2.2 cases per 100,000 military healthcare enrollees over the 2012-2019 fiscal years. More than 80% of subjects with arboviral infection did not have documented pretravel counseling. Arboviral infections represent a significant disease burden in young travelers to endemic regions. After adjustment for diagnostic validity, DNV represented the greatest burden. Diagnostic codes for ZIKV and JEV overestimate the burden of these diseases. Low rates of pretravel visits represent an opportunity for increased emphasis on insect exposure precautions.

Strongyloides stercoralis in the US Military Health System.

Background: Strongyloides stercoralis is an intestinal nematode most commonly found in subtropical and tropical locations. Military service members are believed to be at increased risk of exposure due to their unique occupational exposures in endemic regions. Methods: Burden, clinical course, and risk factors associated with all Strongyloides infections within the US Military Health System from fiscal years 2012 to 2019 were assessed by manual chart review of records with International Classification of Diseases, Ninth Revision/Tenth Revision codes for Strongyloides infection. Infection risk in demographic subgroups based on region of birth, military occupation, and age was quantified with univariate analysis and multivariate logistic regression. Results: We reviewed 243 charts based on diagnosis coding, yielding 210 confirmed diagnoses (86.4%). Immigrant patients born in Latin America/Caribbean, sub-Saharan Africa, and East Asia/Pacific regions had statistically significant increased risk ratios of infection at 34.4, 32.0, and 22.4, respectively, when compared to patients born in Europe and North America. In univariate analysis, active duty members in the healthcare occupational category had a statistically significant increased risk ratio of infection at 2.31 compared to those outside this occupation. Multivariate logistic regression analysis demonstrated that occupational categories of healthcare, admininstrative/support, warfighter/combat specialist, and engineering/repair/maintenance occupations, being an immigrant patient, and age ≥65 were all associated with statistically significant increased odds ratios for infection. Conclusions: In the Military Health System, occupational exposures, region of birth, and age serve as risk factors for Strongyloides infection. Because infections may be chronic, the impact of targeted screening programs to complement routine medical care should be considered.

Factors Associated With Viral Suppression and Drug Resistance in Children and Adolescents Living With HIV in Care and Treatment Programs in Southern Tanzania.

BACKGROUND: Achieving viral suppression (VS) for persons living with HIV is key to reaching epidemic control. We assessed the prevalence of VS and the frequency of HIV drug resistance mutations (HIVDRM) among children and adolescents living with HIV (CALHIV) in the Southern Highland zone of Tanzania. METHODS: From 2019 to 2021, we enrolled CALHIV aged 1-19 years on ART for >6 months in a cross-sectional study. Participants had viral load (VL) testing; those with VL ≥ 1000 copies/mL underwent HIVDRM testing. VS (<1000 copies/mL) prevalence estimates were calculated and robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations with potential predictors of VS. RESULTS: Of 707 participants, 595 had VS (PR: 0.84, 95% CI: 0.81-0.87). Use of an integrase strand transfer inhibitor-containing regimen (aPR 1.15, 95% CI: 0.99-1.34), age 5-9 years (aPR 1.16, 95% CI: 1.07-1.26), and seeking care at a referral center (aPR 1.12, 95% CI: 1.04-1.21) were associated with VS. Factors inversely associated with VS included having one (aPR 0.82, 95% CI: 0.72-0.92) or two or more (aPR 0.79, 95% CI: 0.66-0.94) referrals for adherence counselling, and self-reporting missing one to two (aPR 0.88, 95% CI: 0.78-0.99) or three or more (aPR 0.77, 95% CI: 0.63-0.92) doses of ART in the past month. Of 74 participants with PRRT and INT sequencing done, 60 (81.1%) had HIVDRMs at the following frequencies: 71.6%, 67.6%, 1.4%, and 4.1% for major NNRTI, NRTI, PI, and INSTI respectively. CONCLUSIONS: Higher rates of VS were observed in this cohort, and HIVDRMs were common in those without VS. This evidence supports ART optimization using dolutegravir-based regimens. However, better strategies to improve adherence are needed.

Adenosine A2A antagonists in Parkinson's disease: what's next?

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, affecting up to 10 million people worldwide. Current treatment primarily involves symptom management with dopaminergic replacement therapy. Levodopa remains the most effective oral treatment, although long-term use is associated with complications such as wearing off, dyskinesias, and on-off fluctuations. Non-dopaminergic medications that improve PD symptoms and motor fluctuations are in demand. Adenosine A2A receptors are abundantly expressed within the basal ganglia and offer a unique target to modify abnormal striatal signaling associated with PD. Preclinical animal models have shown the ability of adenosine A2A receptor antagonists to improve PD motor symptoms, reduce motor fluctuations and dyskinesia, as well as protect against toxin-induced neuronal degeneration. Both istradefylline and preladenant have demonstrated moderate efficacy in reducing off time in PD patients with motor fluctuations. The safety and efficacy of this class of compounds continues to be defined and future studies should focus on non-motor symptoms, dyskinesias, and neuroprotection.

Recommendations for diarrhea management during medical stability operations.

Training and planning for medical stability operations, to include humanitarian assistance, disaster relief, and medical readiness training exercises, has taken on new importance for today's military forces. Deployed medical forces providing care to local populations are presented with the challenge of limited resources and complex public health needs. In this paper, we review the epidemiology of diarrhea as one of the leading causes of mortality in these settings and provide an evidence based-approach for management within the framework of military medical stability operations.

Destination based errors in chloroquine malaria chemoprophylaxis vary based on provider specialty and credentials.

BACKGROUND: The Deployment and Travel Medicine Knowledge, Attitudes, Practices, and Outcomes Study (KAPOS) evaluates health outcomes and provider practices associated with travel and deployments within the US Military Health System. We analyzed prescribing errors for chloroquine malaria chemoprophylaxis between travel medicine specialists and non-specialists over a five-year period. METHODS: A sample of 291 chloroquine prescriptions were reviewed to determine if malaria chemoprophylaxis was appropriate for destination of travel based on both transmission and chloroquine resistance risk. We included non-active-duty beneficiaries of all ages seeking care at military treatment facilities. RESULTS: 10.3% (n = 30) of patients were prescribed chloroquine inappropriately. Non-travel medicine specialists prescribed chloroquine inappropriately more frequently than travel medicine specialists with 16.5% vs 2.3% error, respectively. Physicians were less likely to erroneously prescribe chloroquine as compared to non-physicians with 6.4% vs 22.2% error, respectively. 93.3% of prescribing errors were due to chloroquine-resistance presence at the travel destination. Africa was the most common destination of erroneous prescriptions, creating significant risk for travelers. CONCLUSIONS: While chloroquine is infrequently prescribed, this analysis demonstrates travel medicine proficiency is associated with reduced errors, highlighting the need to supply travel medicine education and decision support tools to non-specialists, to safeguard patients who seek pre-travel medical care.