Real-Time and Wireless Assessment of Adherence to Antiretroviral Therapy With Co-Encapsulated Ingestion Sensor in HIV-Infected Patients: A Pilot Study.

Adherence with antiretroviral therapy is important for preventing disease progression and HIV transmission. The co-encapsulated pill sensor system sends a signal through a cutaneous patch and allows real-time monitoring of pill ingestion. A 16-week pilot study used a sensor system in 15 HIV-infected individuals with real-time monitoring of pill-taking with a personalized short message system text. System acceptability was assessed by survey at weeks 4, 8, 12, and 16. Follow-up occurred in 80% of subjects through 8 weeks. The system effectively collected measures of pill ingestion, which triggered text message reminders. Only 2 of 14 participants stated that co-encapsulated pills were "unable to take" or "poorly tolerated." At least 75% of respondents stated at each visit that the patch was very or somewhat comfortable. With regard to text message reminders, only 10-15% of the participants at any visit did not find the messages to be helpful. Larger studies will define the utility of this system to assess antiretroviral adherence relative to standard measures

Legal Advertising and Warranty Liability: “Let the Lawyer Beware”

This article will examine the realistic possibility of expanded lawyer liability by juxtaposing upon the clearly commercial flavor of legal advertising, the growing trend expanding warranty application under Article 2 of the Uniform Commercial Code by use of analogy

Inter- and intra-rater reliability of the Chicago Classification in pe-diatric high-resolution esophageal manometry recordings

This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'.Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.Background The Chicago Classification (CC) facilitates interpretation of high-resolution manometry (HRM) recordings. Application of this adult based algorithm to the pediatric population is unknown. We therefore assessed intra and interrater reliability of software-based CC diagnosis in a pediatric cohort. Methods Thirty pediatric solid state HRM recordings (13M; mean age 12.1 ± 5.1 years) assessing 10 liquid swallows per patient were analyzed twice by 11 raters (six experts, five non-experts). Software-placed anatomical landmarks required manual adjustment or removal. Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), contractile front velocity (CFV), distal latency (DL) and break size (BS), and an overall CC diagnosis were software-generated. In addition, raters provided their subjective CC diagnosis. Reliability was calculated with Cohen's and Fleiss’ kappa (κ) and intraclass correlation coefficient (ICC). Key Results Intra- and interrater reliability of software-generated CC diagnosis after manual adjustment of landmarks was substantial (mean κ = 0.69 and 0.77 respectively) and moderate-substantial for subjective CC diagnosis (mean κ = 0.70 and 0.58 respectively). Reliability of both software-generated and subjective diagnosis of normal motility was high (κ = 0.81 and κ = 0.79). Intra- and interrater reliability were excellent for IRP4s, DCI, and BS. Experts had higher interrater reliability than non-experts for DL (ICC = 0.65 vs ICC = 0.36 respectively) and the software-generated diagnosis diffuse esophageal spasm (DES, κ = 0.64 vs κ = 0.30). Among experts, the reliability for the subjective diagnosis of achalasia and esophageal gastric junction outflow obstruction was moderate-substantial (κ = 0.45–0.82). Conclusions & Inferences Inter- and intrarater reliability of software-based CC diagnosis of pediatric HRM recordings was high overall. However, experience was a factor influencing the diagnosis of some motility disorders, particularly DES and achalasia

Prevalence, risk and protective factors of alcohol use disorder during the COVID-19 pandemic in U.S. military veterans

BackgroundThere have been reports of increased alcohol consumption during the COVID-19 pandemic in the general population. However, little is known about the impact of the pandemic on the prevalence of alcohol use disorder (AUD), especially in high-risk samples such as U.S. military veterans.MethodsData were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative, prospective cohort of 3078 U.S. veterans. Pre-pandemic and 1-year peri-pandemic risk and protective factors associated with incident and chronic probable AUD were examined.ResultsA total of 6.9 % (n = 183) of veterans were classified as chronic probable AUD, 3.2 % (n = 85) as remitted from AUD, and 2.7 % (n = 71) as incident probable AUD during the pandemic; the prevalence of probable AUD in the full sample remained stable -10.1 % pre-pandemic and 9.6 % peri-pandemic. Younger age, greater pre-pandemic alcohol use severity, and COVID-related stressors were associated with incident AUD during the pandemic, whereas higher pre-pandemic household income was associated with lower risk of this outcome. Younger age, combat experience, lifetime substance use disorder, greater drug use severity, lower dispositional optimism, and more COVID-related worries and social restriction stress were associated with higher risk of chronic AUD.ConclusionsNearly 1-in-10 US veterans screened positive for AUD 1-year into the pandemic; however, the pre- and 1-year peri-pandemic prevalence of probable AUD remained stable. Veterans who are younger, have served in combat roles, endorse more COVID-related stressors, and have fewer socioeconomic resources may be at higher risk for AUD during the pandemic

Low-Abundance HIV Drug-Resistant Viral Variants in Treatment-Experienced Persons Correlate with Historical Antiretroviral Use

BACKGROUND: It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004-2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016). CONCLUSIONS/SIGNIFICANCE: Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with historical antiretroviral use. Ultra-deep sequencing can provide important historical resistance information for clinicians when planning subsequent antiretroviral regimens for highly treatment-experienced patients, particularly when their prior treatment histories and longitudinal genotypes are not available

Impact of the COVID-19 pandemic on participants in pragmatic clinical trials for chronic pain: implications for trial outcomes and beyond

ObjectiveThe COVID-19 pandemic had profound effects on society, including those living with chronic pain. This study sought to examine pandemic impacts on individuals enrolled in pragmatic clinical trials focused on nonpharmacological treatments for chronic pain.MethodsWe evaluated responses to a questionnaire on COVID-19 impacts that had been administered to participants (n=2024) during study enrollment in 3 pragmatic clinical trials for chronic pain treatment. All trials were part of the National Institutes of Health (NIH)-Department of Veterans Affairs (VA)-Department of Defense (DOD) Pain Management Collaboratory. COVID-19-related impacts on access to health care, mental health, finances, ability to meet basic needs, and social support were assessed.ResultsPandemic impacts were found in all domains assessed, including access to health care, mental and emotional health, ability to meet basic needs, finances, and social support. Impacts varied by demographic and clinical characteristics. The participants most negatively impacted by the pandemic were younger, Black or Latino, female, more educated, and unemployed and had screened positive for depression. No impact differences were found with regard to alcohol use disorder screenings or a prior history of COVID-19. Higher levels of pain were associated with worse pandemic impacts, and negative impacts declined over time.ConclusionsNegative impacts of the pandemic on individuals living with chronic pain cut across aspects of life that are also central to effective pain management, including access to health care, social support, and mental and emotional health, with differential impacts found across key demographic and clinical factors. These findings should yield consideration of pandemic impacts in clinical practice and as moderating effects of treatment outcomes in clinical trials conducted during the pandemic

Prospective functional classification of all possible missense variants in PPARG.

Clinical exome sequencing routinely identifies missense variants in disease-related genes, but functional characterization is rarely undertaken, leading to diagnostic uncertainty. For example, mutations in PPARG cause Mendelian lipodystrophy and increase risk of type 2 diabetes (T2D). Although approximately 1 in 500 people harbor missense variants in PPARG, most are of unknown consequence. To prospectively characterize PPARγ variants, we used highly parallel oligonucleotide synthesis to construct a library encoding all 9,595 possible single-amino acid substitutions. We developed a pooled functional assay in human macrophages, experimentally evaluated all protein variants, and used the experimental data to train a variant classifier by supervised machine learning. When applied to 55 new missense variants identified in population-based and clinical sequencing, the classifier annotated 6 variants as pathogenic; these were subsequently validated by single-variant assays. Saturation mutagenesis and prospective experimental characterization can support immediate diagnostic interpretation of newly discovered missense variants in disease-related genes.This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (1K08DK102877-01, to A.R.M.; 1R01DK097768-01, to D.A.), NIH/Harvard Catalyst (1KL2TR001100-01, to A.R.M.), the Broad Institute (SPARC award, to A.R.M. and T.M.), and the Wellcome Trust (095564, to K.C.; 107064, to D.B.S.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.370

Internet‐Based Pain Self‐Management for Veterans: Feasibility and Preliminary Efficacy of the Pain EASE Program

ObjectiveTo develop and test the feasibility and preliminary efficacy of a cognitive behavioral therapy–based, internet‐delivered self‐management program for chronic low back pain (cLBP) in veterans.MethodsPhase I included program development, involving expert panel and participant feedback. Phase II was a single‐arm feasibility and preliminary efficacy study of the Pain e‐health for Activity, Skills, and Education (Pain EASE) program. Feasibility (ie, website use, treatment credibility, satisfaction) was measured using descriptive methods. Mixed models were used to assess mean within‐subject changes from baseline to 10 weeks post‐baseline in pain interference (primary outcome, West Haven‐Yale Multidimensional Pain Inventory, scale of 0 to 6), pain intensity, mood, fatigue, sleep, and depression.ResultsPhase I participants (n = 15) suggested modifications including style changes, content reduction, additional “Test Your Knowledge” quizzes, and cognitive behavioral therapy skill practice monitoring form revisions for enhanced usability. In Phase II, participants (n = 58) were mostly male (93%) and White (60%), and had an average age of 55 years (standard deviation [SD] = 12) and moderate pain (mean score 5.9/10); 41 (71%) completed the post‐baseline assessment. Participants (N = 58) logged on 6.1 (SD = 8.6) times over 10 weeks, and 85% reported being very or moderately satisfied with Pain EASE. Pain interference improved from a mean of 3.8 at baseline to 3.3 at 10 weeks (difference 0.5 [95% confidence interval 0.1 to 0.9], P = 0.008). Within‐subject improvement also occurred for some secondary outcomes, including mood and depression symptoms.DiscussionVeterans with cLBP may benefit from technology‐delivered interventions, which may also reduce pain interference. Overall, veterans found that Pain EASE, an internet‐based self‐management program, is feasible and satisfactory for cLBP.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154929/1/papr12861.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154929/2/papr12861_am.pd