Triangulation supports agricultural spread of the Transeurasian languages.

The origin and early dispersal of speakers of Transeurasian languages-that is, Japanese, Korean, Tungusic, Mongolic and Turkic-is among the most disputed issues of Eurasian population history1-3. A key problem is the relationship between linguistic dispersals, agricultural expansions and population movements4,5. Here we address this question by 'triangulating' genetics, archaeology and linguistics in a unified perspective. We report wide-ranging datasets from these disciplines, including a comprehensive Transeurasian agropastoral and basic vocabulary; an archaeological database of 255 Neolithic-Bronze Age sites from Northeast Asia; and a collection of ancient genomes from Korea, the Ryukyu islands and early cereal farmers in Japan, complementing previously published genomes from East Asia. Challenging the traditional 'pastoralist hypothesis'6-8, we show that the common ancestry and primary dispersals of Transeurasian languages can be traced back to the first farmers moving across Northeast Asia from the Early Neolithic onwards, but that this shared heritage has been masked by extensive cultural interaction since the Bronze Age. As well as marking considerable progress in the three individual disciplines, by combining their converging evidence we show that the early spread of Transeurasian speakers was driven by agriculture.

Willingness to use PrEP among PrEP naïve men who have sex with men: a meta-analysis.

This study aimed to measure the pooled estimate of willingness to use HIV pre-exposure prophylaxis (PrEP) (WTUP) among PrEP-naïve United States (U.S.)-based men who have sex with men (MSM). PubMed, Embase, Web of Science, CINAHL, and PsycINFO were searched. The search strategy contained the keyword willingness and interest and the MeSH terms for HIV and PrEP. Articles were included if they were published between January 2005 and May 2022, reported quantitative data on WTUP among PrEP-naïve US-based MSM, and were available as full text in English. Meta-analysis was conducted to assess the pooled effect size of WTUP prevalence using a random-effects model, heterogeneity in the pooled estimate was assessed, and subgroup analyzes were conducted. Fifteen studies were included based on the inclusion and exclusion criteria. Meta-analysis revealed a pooled prevalence proportion for WTUP of 0.58 (95% CI 0.54-0.61) (or 58 out of 100) among PrEP-naïve MSM. High inter-study heterogeneity (Q = 548.10, df = 19, p < 0.01, I2 = 96.53, τ2 = 0.09) was observed. Age of the study sample and region where the data were collected significantly moderated the pooled WTUP estimate. Age-appropriate PrEP related messaging and a focus on HIV priority areas of the U.S. would be important strategies to improve WTUP among MSM in the U.S. moving forward.

An assessment of the psychometric properties of the Coping Strategies Questionnaire - Sickle Cell Disease (CSQ-SCD) among adults in the United States.

BACKGROUND: Previous studies have reported conflicting factor structures of the Coping Strategies Questionnaire - Sickle Cell Disease (CSQ-SCD). This study examined the psychometric properties of the CSQ-SCD among adults with SCD in the United States. METHODS: This study implemented a cross-sectional study design with web-based self-administered surveys. Individuals with SCD were recruited via an online panel. Psychometric properties, including factorial and construct validity, and internal consistency reliability, of the CSQ-SCD were assessed. RESULTS: A total of 196 adults with SCD completed the survey. Confirmatory factor analysis (CFA), using maximum likelihood estimation and the 13 subscale scores as factor indicators, supported a three-factor model for the CSQ-SCD compared to a two-factor model. Model fit statistics for the three-factor model were: Chi-square [df] = 227.084 [62]; CFI = 0.817; TLI = 0.770; RMSEA [90% CI] = 0.117 [0.101-0.133]; SRMR = 0.096. All standardized factor loadings (except for the subscales isolation, resting, taking fluids, and praying and hoping) were > 0.5 and statistically significant, indicating evidence of convergent validity. Correlations between all subscales (except praying and hoping) were lower than hypothesized; however, model testing revealed that the three latent factors, active coping, affective coping, and passive adherence coping were not perfectly correlated, suggesting discriminant validity. Internal consistency reliabilities for the active coping factor (α = 0.803) and affective coping factor (α = 0.787) were satisfactory, however, reliability was inadequate for the passive adherence coping factor (α = 0.531). Given this overall pattern of results, a follow-up exploratory factor analysis (EFA) was also conducted. The new factor structure extracted by EFA supported a three-factor structure (based on the results of a parallel analysis), wherein the subscale of praying and hoping loaded on the active coping factor. CONCLUSIONS: Overall, the CSQ-SCD was found to have less than adequate psychometric validity in our sample of adults with SCD. These results provide clarification around the conflicting factor structure results reported in the literature and demonstrate a need for the future development of a SCD specific coping instrument.

Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth.

Acetylation of histones by lysine acetyltransferases (KATs) is essential for chromatin organization and function1. Among the genes coding for the MYST family of KATs (KAT5-KAT8) are the oncogenes KAT6A (also known as MOZ) and KAT6B (also known as MORF and QKF)2,3. KAT6A has essential roles in normal haematopoietic stem cells4-6 and is the target of recurrent chromosomal translocations, causing acute myeloid leukaemia7,8. Similarly, chromosomal translocations in KAT6B have been identified in diverse cancers8. KAT6A suppresses cellular senescence through the regulation of suppressors of the CDKN2A locus9,10, a function that requires its KAT activity10. Loss of one allele of KAT6A extends the median survival of mice with MYC-induced lymphoma from 105 to 413 days11. These findings suggest that inhibition of KAT6A and KAT6B may provide a therapeutic benefit in cancer. Here we present highly potent, selective inhibitors of KAT6A and KAT6B, denoted WM-8014 and WM-1119. Biochemical and structural studies demonstrate that these compounds are reversible competitors of acetyl coenzyme A and inhibit MYST-catalysed histone acetylation. WM-8014 and WM-1119 induce cell cycle exit and cellular senescence without causing DNA damage. Senescence is INK4A/ARF-dependent and is accompanied by changes in gene expression that are typical of loss of KAT6A function. WM-8014 potentiates oncogene-induced senescence in vitro and in a zebrafish model of hepatocellular carcinoma. WM-1119, which has increased bioavailability, arrests the progression of lymphoma in mice. We anticipate that this class of inhibitors will help to accelerate the development of therapeutics that target gene transcription regulated by histone acetylation.

Opioid tapering and mental health crisis in older adults.

BACKGROUND: Opioid tapering and discontinuation have increased in recent years with the implementation of national prescribing guidelines. This study aimed to examine the relationship between opioid tapering velocity and mental health crisis events in older Medicare beneficiaries. METHODS: A nested case-control study was conducted using the 2012-2018, 5% national Medicare claims data. Older adults with chronic non-cancer pain (CNCP) who were receiving long-term opioid therapy (LTOT) were included in the study. Cases were defined as individuals experiencing mental health crisis events; controls were identified using incidence density sampling. The opioid tapering velocity was measured in the 120-day hazard period that yielded a monthly percentage of dose change. Conditional logistic regression was used to assess the relationship of interest. RESULTS: A total of 42 091 older adults with CNCP were eligible for the study. Cases (n = 952) were matched with controls in a 1:2 ratio based on age (±1 year) and time of cohort entry (±30 days). A higher percentage of controls (67.65%) were on steady dose compared with cases (59.03%). In the adjusted model, tapering (aOR = 1.36; 95% CI: 1.02-1.83), rapid tapering (aOR = 1.45; 95% CI: 1.11-1.91), and dose escalation (aOR = 1.78; 95% CI: 1.32-2.39) were significantly associated with the mental health crisis, compared with steady dose. CONCLUSION: Both opioid tapering and dose escalation are associated with mental health crisis events. Patient-driven and gradual dose tapering, as recommended by prescribing guidelines, should be promoted to prevent mental health crisis events among older adults on LTOT.

Preferences for a community pharmacy-based pre-exposure prophylaxis (PrEP) delivery program: A discrete choice experiment.

BACKGROUND: Community pharmacies are ideal venues for pre-exposure prophylaxis (PrEP) delivery. Pharmacists and pharmacy-based PrEP delivery programs have the potential to improve access. OBJECTIVES: This study elicited preferences for attributes of a hypothetical community pharmacy-based PrEP delivery program among US men who have sex with men (MSM) and assessed predictors of their preferences. METHODS: Data were collected via a cross-sectional anonymous survey of US MSM, who were aged 18-65 years, not transgender, reported HIV status negative/unknown, and PrEP eligible. A discrete choice experiment was conducted with seven attributes of a pharmacy-based PrEP program: initial PrEP eligibility screening mode, location for human immunodeficiency virus (HIV) tests, timing for HIV test results, PrEP decision-making style, location of PrEP consultations, PrEP medication fill method, and mode for ongoing monitoring. Latent class analysis was performed to analyze preference heterogeneity. Multinomial logistic regression assessed predictors of latent class membership. RESULTS: This study included 390 MSM. Time to receive HIV test results was the most important attribute; receiving results on the same day had the highest preference. The next most important attribute was PrEP screening mode; online questionnaires were the most preferred. Respondents' preferences clustered into four classes: 1) "Same day results and online monitoring" (SDROM) group (63.1%), 2) "Consumerist decision-making" (CDM) group (16.2%), 3) "Self-screening (online questionnaire)" (SOQ) group (11.3%), and 4) "Same day results preferring" (SDRP) group (9.5%). Hispanic MSM (adjusted odds ratio [aOR] =0.31, 95% confidence interval [CI] [0.12-0.84], P = 0.020), MSM of other races (aOR=0.38, 95% CI [0.15-0.97], P = 0.044) vs. White MSM; and those having a sexually transmitted disease recently (aOR=0.37, 95% CI [0.16-0.85], P = 0.018), had lower odds of being in the CDM group vs. the SDROM group. CONCLUSIONS: MSM's preferences for a pharmacy-based PrEP program are heterogeneous. Same day results for HIV tests and online PrEP screening are key components when designing a community pharmacy-based PrEP program.

Community pharmacists' readiness to take action to improve working conditions.

OBJECTIVE: The objective of this study was to assess pharmacists' readiness to take actions resulting in change at the individual level or systemic level. DESIGN/SETTING AND PARTICIPANTS/OUTCOME MEASURES: An online survey was distributed via pharmacy-related social media pages and several state pharmacy association newsletters and e-mail listservs. Fifteen items assessed participants' readiness to pursue change using a 5-point scale based on the transtheoretical model of behavior change (1 = Do not plan on doing, 2 = Plan to take in the next 6 months, 3 = Plan to take in the next month, 4 = Took in the past 6 months, 5 = Took more than 6 months ago). Categorical principal components analysis (CATPCA) was used as a data reduction technique to identify underlying components of the 15 items assessing readiness to improve working conditions. Component scores for each component were calculated and used as dependent variables in multivariable linear regression models to test associations between the components and sociodemographic and work-related predictors. RESULTS: CATPCA revealed a 12-item scale with 2 components accounting for 39.97% of the total variance. Pharmacists working in independent pharmacies had a significantly higher willingness than chain pharmacists to pursue actions with potential to result in systemic-level changes, such as contacting or joining an organization to attempt to improve their current working conditions (regression coefficient = 0.623, P < 0.001). Pharmacists working in independent pharmacies had a significantly lower willingness than chain pharmacists to pursue actions resulting in individual-level changes, such as changing their current job or quitting (regression coefficient = -0.485, P < 0.001). CONCLUSION: Pharmacists working in national chains may be less willing than independent pharmacists to pursue systemic-level changes owing to fear of discipline from employers. Future research should examine the effect of interventions intended to increase pharmacists' motivation and readiness to pursue changes to improve working conditions.

Coprescribing of opioids and psychotropic medications among Medicare-enrolled older adults on long-term opioid therapy.

BACKGROUND: Pressures to reduce opioid prescribing have potential to incentivize coprescribing of opioids (at lower dose) with psychotropic medications. Evidence concerning the extent of the problem is lacking. This study assessed trends in coprescribing and characterized coprescribing patterns among Medicare-enrolled older adults with chronic noncancer pain (CNCP) receiving long-term opioid therapy (LTOT). METHODS: A cohort study was conducted using 2012-2018 5% National Medicare claims data. Eligible beneficiaries were continuously enrolled and had no claims for cancer diagnoses or hospice use, and ≥ 2 claims with diagnoses for CNCP conditions within a 30-day period in the 12 months before the index date (LTOT initiation). Coprescribing was defined as an overlap between opioids and any class of psychotropic medication (antidepressants, benzodiazepines, antipsychotics, anticonvulsants, muscle relaxants, and nonbenzodiazepine hypnotics) based on their prescription fill dates and days of supply in a given year. The occurrence of coprescribing, coprescribing intensity, and number of days of overlap with psychotropic medications were calculated for each calendar year. RESULTS: The eligible study population of individuals on LTOT ranged from 2038 in 2013 to 1751 in 2018. The occurrence of coprescribing among eligible beneficiaries decreased from 73.41% in 2013 to 70.81% in 2015 and then increased slightly to 71.22% in 2018. Among eligible beneficiaries with at least one overlap day, the coprescribing intensity with any class of psychotropic medications showed minimal variation throughout the study period: 74.73% in 2013 and 72.67% in 2018. Across all the years, the coprescribing intensity was found to be highest with antidepressants (2013, 49.90%; 2018, 50.33%) followed by benzodiazepines (2013, 25.42%; 2018, 19.95%). CONCLUSION: Coprescribing was common among older adults with CNCP who initiated LTOT but did not rise substantially in the period studied. Future research should investigate drivers behind coprescribing and safety of various patterns of use.

Do Formulation and Dose of Long-Term Opioid Therapy Contribute to Risk of Adverse Events among Older Adults?

BACKGROUND: Chronic non-cancer pain (CNCP) is highly prevalent in older adults and long-term opioid therapy (LTOT) has been used to manage chronic pain. However, the safety of LTOT among older adults with CNCP is not well-established and there is a need to identify therapy-related risk factors of opioid-related adverse events among older adults. OBJECTIVE: To evaluate the relationship between opioid dose and formulation and the risk of opioid-related adverse events among Medicare-eligible older adults on LTOT. DESIGN: Nested case-control study. PARTICIPANTS: Older Medicare beneficiaries (N=35,189) who received > 3 opioid prescriptions with a total days-supply of >45 days within a 90-day period for CNCP between 2012 and 2016. MAIN MEASURES: This study utilized Medicare 5% medical and prescription claims data. Outcome measures included opioid-induced respiratory depression (OIRD), opioid overdose, all-cause mortality, and a composite outcome, defined as the first occurrence of any of the previous three events. Key independent variables were opioid formulation and opioid dose (measured in morphine milligram equivalents (MME)) prescribed during LTOT. KEY RESULTS: Seventy-four OIRD, 133 overdose, 982 all-cause mortality, and 1122 composite outcome events were observed during follow-up. In unadjusted analyses, the use of combination opioids (OR: 4.52 [95%CI: 1.51-13.47]) was significantly associated with OIRD compared to short-acting (SA) opioids. In adjusted analyses, opioid-related adverse events were significantly associated with the use of LA (overdose OR: 13.00 [95%CI: 1.30-130.16] and combination opioids (overdose OR: 6.27 [95%CI: 1.91-20.55]; mortality OR: 2.75 [95%CI: 1.87-4.04]; composite OR: 2.82 [95%CI: 2.01-3.96]) when compared to SA opioids. When compared to an average dose of less than 20 MME, outcomes were significantly associated with doses of 20-50 MME (mortality OR: 1.61 [95%CI: 1.24-2.10]; composite OR: 1.59 [95%CI: 1.26-2.01]) and >50 MME (mortality OR: 1.99 [95%CI: 1.28-3.10]; composite OR: 2.09 [95%CI: 1.43-3.04]). CONCLUSIONS: Older adults receiving medically prescribed opioids at higher doses and those using LA and combination of LA and SA opioids are at increased risks for opioid-related adverse events, highlighting the need for close patient supervision.

Examining subjective well-being among older adults using pain medications.

PURPOSE: To examine the relationship between social participation and subjective well-being (SWB) among older adults using pain medications and evaluate the impact of sex on this relationship. METHODS: A cross-sectional analysis was conducted using the 2019 National Health and Aging Trends Study data, a nationally-representative sample of Medicare beneficiaries 65 years and older. Individuals were included if they reported taking pain medications for five days or more per week over the last month. Social participation was operationalized using the sum score of four items: visiting family and friends, going out for enjoyment, attending religious services, and participation in other organized activities. SWB was operationalized as a latent variable using four items reflecting positive and negative emotions, and three items reflecting self-evaluation. Structural equation modeling was used to test the relationship between key study constructs, as well as the moderating effect of sex on the relationship between social participation and SWB. RESULTS: A total of 964 (weighted N = 7,660,599) participants were included in the study. Most participants were female (61.3%), White (81.0%), community-dwelling (94.9%) older adults. Confirmatory factor analysis showed appropriate fit for SWB. Social participation had a statistically significant association with SWB (unstandardized regression coefficient = 0.133; 95% CI 0.071, 0.196; p < 0.001) after adjusting for covariates. However, this relationship was not moderated by sex (p = 0.836). CONCLUSION: Social participation is positively and significantly associated with SWB among older adults using pain medications. Interventions aimed at improving SWB should consider incorporating a social activities component.

Impact of pharmacist prescribing through direct pharmacy access policies on access to hormonal contraception.

BACKGROUND/OBJECTIVE: This study assesses the impact of direct pharmacy access (DPA) policies that allow pharmacists to prescribe hormonal contraceptives on women's access by comparing access among 3 groups: (1) women in a state without DPA (Indiana), (2) women in a state with DPA, but not using DPA, and (3) women in a state with DPA and using DPA. METHODS: This cross-sectional survey, including a scale to measure access to contraceptives, perception items, and demographics, was distributed through Amazon Mechanical Turk (Amazon.com, Inc). Kruskal-Wallis tests and linear regression analysis were used. RESULTS: The sample size was 316. When controlling for education, income, and age, the women not using DPA (in Indiana and a DPA state, respectively) reported significantly higher levels of approachability (P < 0.001 and P < 0.001, respectively), acceptability (P < 0.001 and P < 0.001, respectively), availability and accommodation (P < 0.001 and P = 0.009, respectively), affordability (P < 0.001 and P < 0.001, respectively), and appropriateness (P < 0.001 and P < 0.001) access than the women using DPA. The women using DPA reported significantly lower levels of privacy access than those not using DPA in a DPA state (P = 0.004) when controlling for education, income, and age. However, 78.9% of women using DPA agreed DPA made obtaining contraceptives easier. Most of the women who had never used DPA were previously unaware of DPA (81.1% in DPA states and 86.2% in Indiana) but felt that it would improve access (82.8% and 80.0%, respectively). CONCLUSION: Understanding the effects of DPA policies on women's access to contraceptives can inform future policies and support implementation. Lower levels of access across all dimensions among those using DPA may be influenced by imperfect implementation and failure to legislatively enable the sustainability of this service rather than pharmacists' ability to improve women's access.

Rates of genetic testing in patients prescribed drugs with pharmacogenomic information in FDA-approved labeling.

This study examined rates of genetic testing in two cohorts of publicly insured individuals who have newly prescribed medication with FDA pharmacogenomic labeling guidance. Genetic testing was rare (4.4% and 10.5% in Medicaid and Medicare cohorts, respectively) despite the fact that all participants selected were taking medications that contained pharmacogenomic labeling information. When testing was conducted it was typically done before the initial use of a target medication. Factors that emerged as predictors of the likelihood of undergoing genetic testing included White ethnicity (vs. Black), female gender, and age. Cost analyses indicated higher expenditures in groups receiving genetic testing vs. matched comparators with no genetic testing, as well as disparities between proactively and reactively tested groups (albeit in opposite directions across cohorts). Results are discussed in terms of the possible reasons for the low base rate of testing, mechanisms of increased cost, and barriers to dissemination and implementation of these tests.

Approaches to assessing the provider experience with clinical pharmacogenomic information: a scoping review.

PURPOSE: Barriers to the implementation of pharmacogenomics in clinical practice have been thoroughly discussed over the past decade. METHODS: The objective of this scoping review was to characterize the peer-reviewed literature surrounding the experiences and actions of prescribers, pharmacists, or genetic counselors when using pharmacogenomic information in real-world or hypothetical research settings. RESULTS: A total of 33 studies were included in the scoping review. The majority of studies were conducted in the United States (70%), used quantitative or mixed methods (79%) with physician or pharmacist respondents (100%). The qualitative content analysis revealed five major methodological approaches: hypothetical clinical case scenarios, real-world studies evaluating prescriber response to recommendations or alerts, cross-sectional quantitative surveys, cross-sectional qualitative surveys/interviews, and a quasi-experimental real-world study. CONCLUSION: The findings of this scoping review can guide further research on the factors needed to successfully integrate pharmacogenomics into clinical care.

Porous Tungsten Oxide: Recent Advances in Design, Synthesis, and Applications.

Tungsten oxide (WO3 ) has received ever more attention and has been highly researched over the last decade due to its being a low-cost transition metal semiconductor with tunable, yet widely stable, band gaps. This minireview briefly highlights the challenges in the design and synthesis of porous WO3 including methods, precursors, solvent effects, crystal phases, and surface activities of the porous WO3 base material. These topics are explored while also drawing a connection of how the morphology and crystal phase affect the band gap. The shifts in band gap not only impact the optical properties of tungsten but also allow tuning to operate on different energy levels, which makes WO3 highly desirable in many applications such as supercapacitors, batteries, solar cells, catalysts, sensors, smart windows, and bioapplications.

Predictors of pharmacists' likelihood to query prescription drug monitoring program databases.

BACKGROUND: Low rates of enrollment and querying of the prescription drug monitoring programs (PDMPs) may be detrimental to the effectiveness of controlling prescription drug misuse. A number of individual-level, organizational, and regulatory factors may affect a community pharmacist's likelihood to query their statewide PDMP. OBJECTIVE: To identify predictors of pharmacists' likelihood to query the PDMP. METHODS: A self-administered survey was used to collect data from community pharmacists from a national panel. Measures were identified from previous literature assessing provider likelihood to query PDMPs. A principal components analysis of items pertaining to pharmacists' likelihood to query PDMPs was conducted as a data reduction technique to identify underlying dimensions. Multivariable linear regression was conducted to examine relationships between 5 predictor variables (state regulations, practice setting, workload, perceived barriers, and attitude) and the identified components. RESULTS: A total of 148 completed survey responses were included for final analysis. The pharmacists'-likelihood-to-query scale comprised 2 components accounting for 71% of the total variance. The 2 components were labeled as higher-risk situations and lower-risk situations. Multivariable linear regression indicated that pharmacists' likelihood to query the PDMP for the higher-risk situations was not statistically significant for any predictor variables. For the lower-risk situations, pharmacists who had a more positive attitude toward the effectiveness of the PDMP were more likely to query it in these situations (unstandardized coefficient = 0.167; P = 0.018). CONCLUSION: The factors affecting pharmacists' likelihood to query the PDMP may differ depending on the situations faced by the pharmacist. On the basis of the study results, it seems that pharmacists are currently aware of the importance of checking the PDMP and regularly query it. Overall, the respondent pharmacists had a positive attitude toward the effectiveness of the PDMP, which seems to have a role in their likelihood to query it in lower-risk situations.

The impact of medication synchronization programs on medication adherence: A meta-analysis.

BACKGROUND: Medication nonadherence is associated with more than $100 billion in preventable medical costs each year in the United States. Medication synchronization (med sync) programs have emerged as a potential solution to addressing nonadherence. OBJECTIVES: To assess the impact of med sync programs on adherence in adults on chronic medications through a meta-analysis. METHODS: A comprehensive literature search was conducted for studies of med sync and adherence in adults published in English from database inception to May 2020. Studies were included if they provided a description of the med sync program, reported a quantitative measure of medication adherence using the proportion of days covered metric, and were conducted in the United States. The search terms included "medication synchronization," "med sync," "adherence," and "PDC." Pooled odds ratios (ORs) and 95% CIs using random-effects models were calculated to assess overall impact and subgroup analyses. The risk of bias of individual studies was assessed using the Downs and Black checklist. RESULTS: Nine studies reporting 30 effect sizes were included in the meta-analysis. On the basis of the Downs and Black checklist, the methodological quality of the studies was fair (mean [SD] 17.6 [1.7]). Med sync was associated with greater odds of adherence (pooled OR 2.29 [95% CI 1.99-2.64], I2 = 93.3%, τ2 = 1.11). In addition, the type of med sync program influenced the variation in effect sizes (Cochran Q statistic [Qbetween] = 45.4, P < 0.001), with appointment-based med sync programs having the largest impact on adherence (3.14 [95% CI 2.72-3.63]). CONCLUSION: In this meta-analysis of the impact of med sync on adherence, med sync was associated with statistically significant improvement in adherence. Policy makers and payers should consider reimbursement to pharmacies to support med sync programs in efforts to combat medication nonadherence and improve health outcomes.

Does Transient Opioid Use Increase Risk of Short-Term Respiratory Exacerbation among Older Adults with Chronic Obstructive Pulmonary Disease?

The objective of this study was to examine the association between transient opioid use and acute respiratory exacerbations among older Medicare beneficiaries with COPD. This study was conducted using national Medicare 5% sample administrative claims data between 2012 and 2016 and employed a case-crossover design. The date of eligible COPD exacerbation events was defined as the index date and the presence of opioid prescriptions during a 7-day exposure window prior to index date was compared to a set of 10 control periods, each 7-days long. The association between opioid exposure and COPD exacerbation was estimated using a conditional logistic regression with robust sandwich estimators, after accounting for known time-varying confounders. Among 16,290 eligible COPD exacerbations included in the study sample, the average patient age was 77.08 years, and 64.2% of events occurred in women. Transient exposure to opioids was associated with a 76% increase in the odds of an acute COPD exacerbation (OR: 1.76, 95%CI: 1.67-1.84), and each 25 mg increase in morphine milligram equivalent dose was associated with a 18% increase in the odds of exacerbation (OR: 1.18, 95% CI: 1.15-1.21). Effect estimates were consistent across subgroup analyses conducted among events identified in the emergency department versus hospital, and among individuals with a single exacerbation event versus those with multiple exacerbations. Transient exposure to opioids was associated with an increased short-term risk of respiratory exacerbation among older adults with COPD. Treatment decisions for breathlessness among individuals with COPD need to account for the benefit-risk profile of opioids.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.2013460 .

Objectively Measured Physical Activity in Migraine as a Function of Headache Activity.

OBJECTIVE: This study sought to compare ambulatory physical activity (PA) between young adults with migraine, tension-type headache (TTH), and non-headache controls and determine if differences in PA were attributable to headache activity or other relevant covariates. BACKGROUND: PA has been implicated in the development, manifestation, and treatment of various headache disorders. However, objective quantification of PA across headache types is lacking, and no study has quantified both prospective PA and the influence of headache occurrence on PA. METHODS: A prospective cohort study followed university participants with migraine, with TTH, or without headache for 7 days using an Omron HJ-112 pedometer and daily headache diaries. Daily free-living PA was compared between groups, and differences in PA as a function of headache day vs non-headache day were compared among those with migraine and TTH. RESULTS: The final sample consisted of 516 observations from 100 young adults (81/100 female, mean age = 19.0 ± 1.7) comprised of 28 individuals with migraine, 37 individuals with TTH, and 35 non-headache controls. On average, individuals with migraine engaged in less total PA than non-headache controls (6847 vs 8573 steps/day; mean difference = -1726 [95% CI: -3135 to -318], P = .017) across the 7-day monitoring period. After adjusting for relevant covariates (psychological symptoms, body mass index, weekend vs weekday), this difference was evident on both non-headache days (adjusted mean = 5987 vs 8610, P = .002) and headache days (adjusted mean = 6986 vs 9958, P = .017). In contrast, PA of individuals with TTH (mean = 7691 steps/day) did not significantly differ from those with migraine. PA within groups as a function of headache day (vs non-headache day) did not significantly differ for individuals with migraine (mean = 7357 vs 6191, P = .061) or individuals with TTH (mean = 7814 vs 7641, P = .736). CONCLUSIONS: Consistent with other studies, individuals with migraine reported lower levels of PA compared to non-headache controls. Notably, relative reductions in PA occurred even on days in which headache was not experienced and were not attributable to the examined covariates, instead supporting a more global pattern of reduced PA. Further research is needed to isolate the mechanisms underlying interictal reductions in PA among those with migraine.

Association Between Transient Opioid Use and Short-Term Respiratory Exacerbation Among Adults With Chronic Obstructive Pulmonary Disease: A Case-Crossover Study.

The association of historical opioid use with health care use and death among patients with chronic obstructive pulmonary disease (COPD) has been tested. Using Mississippi Medicaid data, we examined the association of transient or short-term opioid use and acute respiratory exacerbations among adults with COPD. We used a case-crossover design and 2013-2017 Mississippi Medicaid administrative claims data. A total of 1,972 qualifying exacerbation events occurred in 1,354 beneficiaries. The frequency and dose of opioid exposure in the 7 days before the exacerbation were examined and compared with the opioid exposure in 10 control windows, each 7 days long, before the exacerbation. Adjusted odds ratios were estimated using conditional logistic regression models to estimate the risk of opioid use on exacerbations after accounting for use of bronchodilators, corticosteroids, benzodiazepines, and ß-blockers. Overall, opioid exposure in the 7 days before an exacerbation was significantly associated with acute respiratory exacerbation (odds ratio = 1.81; 95% confidence interval: 1.60, 2.05). Each 25-mg increase in morphine equivalent daily dose was associated with an 11.2% increase in the odds of an acute respiratory exacerbation (odds ratio = 1.11; 95% confidence interval: 1.04, 1.20). Transient use of opioids was significantly associated with acute respiratory exacerbation of COPD.

Perceptual changes to progressive resistance training with and without blood flow restriction.

The purpose was to examine changes in the perceptual responses to lifting a very low load (15% one repetition maximum (1RM)) with and without (15/0) different pressures [40% (15/40) and 80% (15/80) arterial occlusion pressure] and compare that to traditional high load (70/0) resistance exercise. Ratings of perceived exertion (RPE) and discomfort were measured following each set of exercise. In addition, resting arterial occlusion pressure was measured prior to exercise. Assessments were made in training sessions 1, 9, and 16 for the upper and lower body. Data are presented as means and 95% CI. There were changes in RPE in the upper body with condition 15/40 [-2.1 (-3.4, -0.850)] and 15/80 [-2.4 (-3.6, -1.1)] decreasing by the end of training. In the lower body, RPE decreased in condition 15/40 [-1.4 (-2.3, -0.431)] by the end of the training study. There was a main effect of time in the upper body with all conditions decreasing discomfort. In the lower body, all conditions decreased except for 15/80. For arterial occlusion pressure, there were differences across time in the 15/40 condition and the 15/80 condition in the upper body. Repeated exposure to blood flow restriction may dampen the perceptual responses over time.