Concomitant Cannabis Misuse and Associations with Depression, Pain and Substance Misuse among Patients Prescribed Opioids

Background: Cannabis use is common among individuals with pain who are prescribed opioids, occurring in approximately 10% of this population. This study aims to explore the relationship between non-medical cannabis use and other health risks among individuals filling opioids at community pharmacies. Methods: This study was an exploratory secondary data analysis of a National Drug Abuse Treatment Clinical Trials Network (CTN)-sponsored study, Validation of a Community Pharmacy-Based Prescription Drug Monitoring Program Risk Screening, examining the relationship between risky cannabis use and depressive symptoms, pain, overdose, and other substance misuse among individuals filling opioid prescriptions in community pharmacies (N = 1440). Results: Participants reporting moderate- to high-risk compared to low-risk cannabis use were more likely to report depressive symptoms (adjusted OR = 1.67, 95% CI = 1.11–2.56), history of overdose (adjusted OR = 2.15, 95% CI = 1.34–3.44), and moderate- to high-risk use of alcohol (adjusted OR = 2.10, 95% CI = 1.28–3.45), opioids (adjusted OR = 2.50, 95% CI = 1.67–3.76), sedatives (adjusted OR = 2.58, 95% CI = 1.72–3.86), stimulants (adjusted OR = 4.79, 95% CI = 2.83–8.01), and tobacco (adjusted OR = 3.60, 95% CI = 2.47–5.24). Conclusions: Community pharmacies may be valuable sites for identifying, studying, and intervening with substance use problems

Effects of supplemental degradable intake protein on intake and digestibility of low-quality brome hay

The effects of increasing levels of degradable intake and digestion of low-quality brome hay were evaluated using 16 ruminally fistulated beef steers. Trends were evident for small, positive changes in total intake and digestion with increasing level of DIP supplementation. As a result, total digestible to feeding forage to provide .041, .082, and OM intake (TDOMI) increased with DIP supplementation but tended to plateau below the highest supplementation level

Evaluation of Machine-Learning Algorithms for Predicting Opioid Overdose Risk Among Medicare Beneficiaries With Opioid Prescriptions

IMPORTANCE Current approaches to identifying individuals at high risk for opioid overdose target many patients who are not truly at high risk. OBJECTIVE To develop and validate a machine-learning algorithm to predict opioid overdose risk among Medicare beneficiaries with at least 1 opioid prescription. DESIGN, SETTING, AND PARTICIPANTS A prognostic study was conducted between September 1, 2017, and December 31, 2018. Participants (n = 560 057) included fee-for-service Medicare beneficiaries without cancer who filled 1 or more opioid prescriptions from January 1, 2011, to December 31, 2015. Beneficiaries were randomly and equally divided into training, testing, and validation samples. EXPOSURES Potential predictors (n = 268), including sociodemographics, health status, patterns of opioid use, and practitioner-level and regional-level factors, were measured in 3-month windows, starting 3 months before initiating opioids until loss of follow-up or the end of observation. MAIN OUTCOMES AND MEASURES Opioid overdose episodes from inpatient and emergency department claims were identified. Multivariate logistic regression (MLR), least absolute shrinkage and selection operator-type regression (LASSO), random forest (RF), gradient boosting machine (GBM), and deep neural network (DNN) were applied to predict overdose risk in the subsequent 3 months after initiation of treatment with prescription opioids. Prediction performance was assessed using the C statistic and other metrics (eg, sensitivity, specificity, and number needed to evaluate [NNE] to identify one overdose). The Youden index was used to identify the optimized threshold of predicted score that balanced sensitivity and specificity. RESULTS Beneficiaries in the training (n = 186 686), testing (n = 186 685), and validation (n = 186 686) samples had similar characteristics (mean [SD] age of 68.0 [14.5] years, and approximately 63% were female, 82% were white, 35% had disabilities, 41% were dual eligible, and 0.60% had at least 1 overdose episode). In the validation sample, the DNN (C statistic = 0.91; 95% CI, 0.88-0.93) and GBM (C statistic = 0.90; 95% CI, 0.87-0.94) algorithms outperformed the LASSO (C statistic = 0.84; 95% CI, 0.80-0.89), RF (C statistic = 0.80; 95% CI, 0.75-0.84), and MLR (C statistic = 0.75; 95% CI, 0.69-0.80) methods for predicting opioid overdose. At the optimized sensitivity and specificity, DNN had a sensitivity of 92.3%, specificity of 75.7%, NNE of 542, positive predictive value of 0.18%, and negative predictive value of 99.9%. The DNN classified patients into low-risk (76.2%[142 180] of the cohort), medium-risk (18.6%[34 579] of the cohort), and high-risk (5.2%[9747] of the cohort) subgroups, with only 1 in 10 000 in the low-risk subgroup having an overdose episode. More than 90% of overdose episodes occurred in the high-risk and medium-risk subgroups, although positive predictive values were low, given the rare overdose outcome. CONCLUSIONS AND RELEVANCE Machine-learning algorithms appear to perform well for risk prediction and stratification of opioid overdose, especially in identifying low-risk subgroups that have minimal risk of overdose.NIH/National Institute on Drug Abuse [R01DA044985]; Pharmaceutical Research and Manufacturers of America Foundation Research Starter AwardOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Non-adherence to the single dose nevirapine regimen for the prevention of mother-to-child transmission of HIV in Bindura town, Zimbabwe: a cross-sectional analytic study

<p>Abstract</p> <p>Background</p> <p>The Prevention of Mother to Child Transmission of HIV (PMTCT) programme was introduced at Bindura Hospital in 2003. Seven additional satellite PMTCT clinics were set up in the district to increase service coverage but uptake of PMTCT interventions remained unsatisfactory. In this study we determined the prevalence of and factors associated with non-adherence to the single dose nevirapine (SD-NVP) regimen for PMTCT in Bindura town.</p> <p>Methods</p> <p>An analytic cross-sectional study was conducted in four health institutions in Bindura town. Participants were mother-baby pairs on the PMTCT programme attending routine six weeks post natal visits in the participating health institutions from March to July 2008. We interviewed 212 mothers using a structured questionnaire.</p> <p>Results</p> <p>The non-adherence rate to the maternal nevirapine dose was 30.7%, while non-adherence to the newborn nevirapine dose was 26.9%. The combined mother-baby pair nevirapine non-adherence was 42.9%. Non-adherence to the maternal dose of nevirapine was associated with lack of maternal secondary education (POR = 2.38; 95%CI: 1.05-3.39) and multi-parity (POR = 2.66; 95%CI: 1.05-6.72), while previous maternal exposure to the PMTCT programme (POR = 0.22; 95%CI: 0.08-0.57) and giving the mother a NVP tablet to take home during antenatal care (POR = 0.03; 95%CI: 0.01-0.09) were associated with improved maternal adherence to nevirapine. Non-adherence to the infant dose of nevirapine was associated with maternal non-disclosure of HIV results to sexual partner (POR = 2.75; 95%CI: 1.04-7.32) and home deliveries (POR = 48.76; 95%CI: 17.51-135.82).</p> <p>Conclusions</p> <p>Non-adherence to nevirapine prophylaxis for PMTCT was high in Bindura. Ensuring institutional deliveries, encouraging self-disclosure of HIV results by the mothers to their partners and giving HIV positive mothers nevirapine doses to take home early in pregnancy all play significant roles in improving adherence to PMTCT prophylaxis.</p

Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Tumour infiltrating lymphocytes (TIL) are generally considered to represent a host immune response directed against tumour antigens. TIL are also increasingly recognised as possible prognostic parameters. However, the effects observed are variable indicating that results cannot be extrapolated from type of tumour to another. Moreover, it has been suggested that primary solid tumours may be ignored by the immune system and that a meaningful immune response is only mounted in regional lymph nodes.</p> <p>Methods</p> <p>We have examined the local distribution of immune cells in tumour-related compartments in head and neck squamous cell carcinomas (HNSCC). In a second step, the prognostic impact of these cells on disease-free survival (DFS) was analysed. A total of 198 tissue cores from 33 patients were evaluated using tissue mircroarray technique and immunohistochemistry. Tumour-infiltrating immune cells were identified using antibodies specific for CD3, CD8, GranzymeB, FoxP3, CD20 and CD68 and quantified using an image analysis system.</p> <p>Results</p> <p>We demonstrate a relative expansion of FoxP3⁺regulatory T-cells (Treg) and of cytotoxic T-cells among tumour infitrating T-cells. We also show that intratumoural CD20⁺B-cells are significantly more frequent in metastatic deposits than in primary tumours. Furthermore, we observed a reduced number of peritumoural CD8⁺T-cells in metastatic lymph nodes as compared to univolved regional nodes suggesting a local down-modulation of cellular immunity. All other immune cells did not show significant alterations in distribution. We did not observe an association of tumour infiltrating immune cells at the primary site with outcome. However, increased numbers of intraepithelial CD8⁺TIL in metastatic tumours as well as large numbers of peritumoural B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect on patient outcome was observed for Treg in any compartment.</p> <p>Conclusion</p> <p>Our results suggest that alterations in lymphocyte distribution in regional lymph nodes rather than at the primary tumour site may be relevant for patient prognosis. Moreover, we demonstrate that in addition to cellular immunity humoral immune responses may be clinically relevant in anti-tumour immunity.</p

Prospective acceptability of digital phenotyping among pregnant and parenting people with opioid use disorder: A multisite qualitative study

BackgroundWhile medications for opioid use disorder (MOUD) effectively treat OUD during pregnancy and the postpartum period, poor treatment retention is common. Digital phenotyping, or passive sensing data captured from personal mobile devices, namely smartphones, provides an opportunity to understand behaviors, psychological states, and social influences contributing to perinatal MOUD non-retention. Given this novel area of investigation, we conducted a qualitative study to determine the acceptability of digital phenotyping among pregnant and parenting people with opioid use disorder (PPP-OUD).MethodsThis study was guided by the Theoretical Framework of Acceptability (TFA). Within a clinical trial testing a behavioral health intervention for PPP-OUD, we used purposeful criterion sampling to recruit 11 participants who delivered a child in the past 12  months and received OUD treatment during pregnancy or the postpartum period. Data were collected through phone interviews using a structured interview guide based on four TFA constructs (affective attitude, burden, ethicality, self-efficacy). We used framework analysis to code, chart, and identify key patterns within the data.ResultsParticipants generally expressed positive attitudes about digital phenotyping and high self-efficacy and low anticipated burden to participate in studies that collect smartphone-based passive sensing data. Nonetheless, concerns were noted related to data privacy/security and sharing location information. Differences in participant assessments of burden were related to length of time required and level of remuneration to participate in a study. Interviewees voiced broad support for participating in a digital phenotyping study with known/trusted individuals but expressed concerns about third-party data sharing and government monitoring.ConclusionDigital phenotyping methods were acceptable to PPP-OUD. Enhancements in acceptability include allowing participants to maintain control over which data are shared, limiting frequency of research contacts, aligning compensation with participant burden, and outlining data privacy/security protections on study materials

Usual Primary Care Provider Characteristics of a Patient-Centered Medical Home and Mental Health Service Use

BACKGROUND: The benefits of the patient-centered medical home (PCMH) over and above that of a usual source of medical care have yet to be determined, particularly for adults with mental health disorders. OBJECTIVE: To examine qualities of a usual provider that align with PCMH goals of access, comprehensiveness, and patient-centered care, and to determine whether PCMH qualities in a usual provider are associated with the use of mental health services (MHS). DESIGN: Using national data from the Medical Expenditure Panel Survey, we conducted a lagged cross-sectional study of MHS use subsequent to participant reports of psychological distress and usual provider and practice characteristics. PARTICIPANTS: A total of 2,358 adults, aged 18–64 years, met the criteria for serious psychological distress and reported on their usual provider and practice characteristics. MAIN MEASURES: We defined “usual provider” as a primary care provider/practice, and “PCMH provider” as a usual provider that delivered accessible, comprehensive, patient-centered care as determined by patient self-reporting. The dependent variable, MHS, included self-reported mental health visits to a primary care provider or mental health specialist, counseling, and psychiatric medication treatment over a period of 1 year. RESULTS: Participants with a usual provider were significantly more likely than those with no usual provider to have experienced a primary care mental health visit (marginal effect [ME] = 8.5, 95 % CI = 3.2–13.8) and to have received psychiatric medication (ME = 15.5, 95 % CI = 9.4–21.5). Participants with a PCMH were additionally more likely than those with no usual provider to visit a mental health specialist (ME = 7.6, 95 % CI = 0.7–14.4) and receive mental health counseling (ME = 8.5, 95 % CI = 1.5–15.6). Among those who reported having had any type of mental health visit, participants with a PCMH were more likely to have received mental health counseling than those with only a usual provider (ME = 10.0, 95 % CI = 1.0–19.0). CONCLUSIONS: Access to a usual provider is associated with increased receipt of needed MHS. Patients who have a usual provider with PCMH qualities are more likely to receive mental health counseling

Rogue Logics: Organization in the Grey Zone

This paper explores the concept of the ‘rogue’ through an examination of how the figure appears in business ethics and as the rogue trader. Reading the rogue trader through institutional logics and Jacques Derrida’s book Rogues, we suggest that the rogue is not on the dark side of organization so much as in an indeterminate grey zone, where the boundary between acceptable behaviour and misconduct is unclear. We further argue that this boundary is necessarily unclear as it is in the nature of organization, at least within capitalist trading systems, to push the boundaries of what is possible and acceptable. The rogue thus helps produce the boundaries of ethically acceptable organizational behaviour in the very act of transgressing them. The location-bound specificity of the rogue, as well as the symbolic process of naming an individual or a state a rogue finds a relevant correlate in the villain, as Derrida suggests. But what we call ‘rogue organization’ may be constitutive of organization per se. As such, there is a potential roguishness in organization that should be addressed when considering the dark side of ethics in organization studies

Search for Darkonium in e+e- Collisions

Collider searches for dark sectors, new particles interacting only feebly with ordinary matter, have largely focused on identifying signatures of new mediators, leaving much of dark sector structures unexplored. In particular, the existence of dark matter bound states (darkonia) remains to be investigated. This possibility could arise in a simple model in which a dark photon (A0 ) is light enough to generate an attractive force between dark fermions. We report herein a search for a JPC ¼ 1−− darkonium state, the ϒD, produced in the reaction eþe− → γϒD, ϒD → A0 A0 A0 , where the dark photons subsequently decay into pairs of leptons or pions, using 514 fb−1 of data collected with the BABAR detector. No significant signal is observed, and we set bounds on the γ − A0 kinetic mixing as a function of the dark sector coupling constant for 0.001 < mA0 < 3.16 GeV and 0.05 < mϒD < 9.5 GeV.publishedVersio

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms