Educating students about volatile substance use in Australian schools: Is the current approach evidence-based, and how should we do it?

Australian national, state and territory school-based drug education policies advise that volatile substance use (VSU) should be excluded from general drug education curriculum for fear of alerting young people to the intoxicating properties of substances such as petrol, sprays and glues. We review evidence from the United States and United Kingdom on the effects of including volatile substances in school-based drug education, to argue that these policies are due for reconsideration. Nitrous oxide and nitrites are classified as volatile substances along with solvents such as those listed above, although their patterns of use, effects and harms are different. In an era of widespread social media access, more young people than in the past are likely to have heard about VSU. But because VSU is often short-term, parents and teachers may be unaware when young people in their care consume volatile substances. The general silence about VSU in schools, difficulty in detecting use and the varying sets of risks associated with inhaling different substances mean that young people may be unaware of toxicity or harm reduction strategies when they consume volatiles as drugs. We consider some implementation challenges to be negotiated if VSU education were introduced in Australian schools.

A Theory of Planned Behavior informed factorial survey of New York community pharmacists to determine their intentions to monitor antihypertensive medication adherence among older adults.

BACKGROUND: Older adults with uncontrolled hypertension can benefit from pharmacist-led interventions as they regularly access community pharmacies. However, several barriers to adherence interventions in a community pharmacy setting exist, and few studies have evaluated the feasibility of medication adherence monitoring within the community pharmacy workflow in the United States. OBJECTIVES: To undertake a factorial survey to determine medication adherence monitoring attitudes of pharmacists and the factors that facilitate or impede adherence counseling by pharmacists within a U.S. community pharmacy setting for antihypertensives in older adults. METHODS: The study was a Theory of Planned Behavior informed factorial survey of New York community pharmacists. The survey had (1) a factorial vignette, to determine how pharmacists make real-life decisions in response to complex situations; (2) questionnaires on medication monitoring attitudes, behavioral beliefs, normative beliefs, and perceived behavioral control regarding medication adherence monitoring, and (3) respondent and workplace characteristics. In response to vignettes, the adherence monitoring tasks were (1) examining patients dispensing records to assess adherence, (2) asking patients about their adherence behavior, and (3) exploring patient beliefs about their antihypertensives. RESULTS: From the 350 completed responses, more than the vignette characteristics, it was the pharmacist characteristics that explained the major variance in the 3 medication monitoring tasks. The respondents demonstrated modestly positive attitudes to medication monitoring, were less positive about their external perception of medication monitoring, and reported difficulty to perform the medication monitoring tasks. In factorial vignette analysis, these attitudes and beliefs significantly impacted adherence monitoring tasks as did situational factors such as time pressures, medication beliefs of patients, the relationship developed with patients, and staffing in the pharmacy, and respondent factors such as pharmacy type and location. CONCLUSION: Future community pharmacist-led adherence interventions should be designed to address pharmacist attitudes and beliefs and certain workplace characteristics to enable successful implementation.

Examining the Relationship Between Wound Complications and the Use of Resorbable Plates in Cranial Vault Reconstruction.

BACKGROUND: Resorbable plates are commonly used in cranial vault reconstruction surgery. There are few published papers examining their safety profile. The authors examined the prevalence of wound complications associated with the use of resorbable plates (Inion CPS Fixation System) in pediatric patients undergoing cranial vault reconstruction. METHODS: A retrospective review of patients (n = 182) who underwent cranial vault reconstruction using resorbable plate fixation was undertaken. All procedures were performed by a single Craniofacial Surgeon at the National Pediatric Craniofacial Center from 2008 to 2016. Wound complications were identified from a prospectively maintained database and medical note review. Several key patient characteristics and surgical variables were also recorded and tested for associations with wound complications. RESULTS: A total of 58.8% (107 of 182) of patients were male with a median age at surgery of 16.2 months. Overall, 12.1% (22 of 182) experienced a postoperative wound complication requiring hospital admission. A total of 2.73% (5 of 182) of the patients that returned to theatre had remnants of plates removed. The authors had a mean time from primary operation to secondary reoperation of 103 days. In univariate statistical analysis, females were more likely to develop a wound complication. However, in stratified analyses excluding patients with an underlying genetic syndrome, increasing age, and lower weight but not gender were associated with wound complications. CONCLUSIONS: A 12.1% (22 of 182) wound complication rate with the use of the Inion CPS Fixation System was observed. Inion plates appear to have an equivalent safety profile to other fixation devices. Increasing age and lower weight were associated with an increased risk of wound complications in nonsyndromic patients.

Determinants of intentions to monitor antihypertensive medication adherence in Irish community pharmacy: a factorial survey.

BACKGROUND: Community pharmacy represents an important setting to identify patients who may benefit from an adherence intervention, however it remains unclear whether it would be feasible to monitor antihypertensive adherence within the workflow of community pharmacy. The aim of this study was to identify facilitators and barriers to monitoring antihypertensive medication adherence of older adults at the point of repeat dispensing. METHODS: We undertook a factorial survey of Irish community pharmacists, guided by a conceptual model adapted from the Theory of Planned Behaviour (TPB). Respondents completed four sections, 1) five factorial vignettes (clinical scenario of repeat dispensing), 2) a medication monitoring attitude measure, 3) subjective norms and self-efficacy questions, and 4) demographic and workplace questions. Barriers and facilitators to adherence monitoring behaviour were identified in factorial vignette analysis using multivariate multilevel linear modelling, testing the effect of both contextual factors embedded within the vignettes (section 1), and respondent-level factors (sections 2-4) on likelihood to perform three adherence monitoring behaviours in response to the vignettes. RESULTS: Survey invites (n = 1543) were sent via email and 258 completed online survey responses were received; two-thirds of respondents were women, and one-third were qualified pharmacists for at least 15 years. In factorial vignette analysis, pharmacists were more inclined to monitor antihypertensive medication adherence by examining refill-patterns from pharmacy records than asking patients questions about their adherence or medication beliefs. Pharmacists with more positive attitudes towards medication monitoring and normative beliefs that other pharmacists monitored adherence, were more likely to monitor adherence. Contextual factors also influenced pharmacists' likelihood to perform the three adherence monitoring behaviours, including time-pressures and the number of days late the patient collected their repeat prescription. Pharmacists' normative beliefs and the number of days late the patient collected their repeat prescription had the largest quantitative influence on responses. CONCLUSIONS: This survey identified that positive pharmacist attitudes and normative beliefs can facilitate adherence monitoring within the current workflow; however contextual time-barriers may prevent adherence monitoring. Future research should consider these findings when designing a pharmacist-led adherence intervention to be integrated within current pharmacy workflow.

Assessing the Multidimensional Relationship Between Medication Beliefs and Adherence in Older Adults With Hypertension Using Polynomial Regression.

Background: The Necessity-Concerns Framework (NCF) is a multidimensional theory describing the relationship between patients' positive and negative evaluations of their medication which interplay to influence adherence. Most studies evaluating the NCF have failed to account for the multidimensional nature of the theory, placing the separate dimensions of medication "necessity beliefs" and "concerns" onto a single dimension (e.g., the Beliefs about Medicines Questionnaire-difference score model). Purpose: To assess the multidimensional effect of patient medication beliefs (concerns and necessity beliefs) on medication adherence using polynomial regression with response surface analysis. Methods: Community-dwelling older adults >65 years (n = 1,211) presenting their own prescription for antihypertensive medication to 106 community pharmacies in the Republic of Ireland rated their concerns and necessity beliefs to antihypertensive medications at baseline and their adherence to antihypertensive medication at 12 months via structured telephone interview. Results: Confirmatory polynomial regression found the difference-score model to be inaccurate; subsequent exploratory analysis identified a quadratic model to be the best-fitting polynomial model. Adherence was lowest among those with strong medication concerns and weak necessity beliefs, and adherence was greatest for those with weak concerns and strong necessity beliefs (slope ß = -0.77, p<.001; curvature ß = -0.26, p = .004). However, novel nonreciprocal effects were also observed; patients with simultaneously high concerns and necessity beliefs had lower adherence than those with simultaneously low concerns and necessity beliefs (slope ß = -0.36, p = .004; curvature ß = -0.25, p = .003). The difference-score model fails to account for the potential nonreciprocal effects. Conclusion: Results extend evidence supporting the use of polynomial regression to assess the multidimensional effect of medication beliefs on adherence.

Impact of financial burden, resulting from prescription co-payments, on antihypertensive medication adherence in an older publically insured population.

INTRODUCTION: Medication co-payments represent a financial barrier to antihypertensive medication adherence. The introduction of co-payments for Irish publically insured patients was associated with a 5% reduction in adherence. However there is socioeconomic variability within this population, and the impact may be greater for those on lower income. We evaluated medication-related financial burden of the co-payment in a cohort of Irish publically insured antihypertensive users and tested its association with adherence at 12 months. METHODS: This was a prospective cohort study of community dwelling older (> 65 yrs) adults (n = 1152) from 106 Irish community pharmacies. Participants completed a structured telephone interview at baseline, and a follow-up interview at 12-months, which we linked to pharmacy records. We assessed medication-related financial burden at baseline using a single questionnaire item, and adherence at 12 months via questionnaire and refill-adherence as Proportion of Days Covered (PDC). RESULTS: A third of participants (30.1%) reported financial burden due to medication costs. In adjusted linear regression models financially burdened participants had significantly lower self-reported adherence (ß = - 0.29, 95% CI -0.48 to - 0.11), although this was not evident with PDC (ß = - 2.76, 95% CI -5.65 to 0.14). CONCLUSION: This co-payment represents a financial barrier to antihypertensive adherence for many older Irish publically insured patients. The negative impact to adherence will potentially increase the risk of adverse outcomes, such as stroke, and increase long-term healthcare costs.

Glucose Ingestion Does Not Improve Maximal Isokinetic Force.

The purpose of this study was to assess maximal isokinetic leg extension force in response to glucose ingestion and to determine whether any performance changes occur in a time-dependent manner. Seventeen young (22.1 ± 3.9 years), lean (%body fat [%BF]: 14.3 ± 8.0; %BF males: 9.7 ± 4.2; %BF females: 23.7 ± 4.2), and recreationally active (>150 min · wk(-1) of physical activity) male (n = 11) and female participants completed the trials. Using a double-blinded crossover design, participants performed sets of 3 maximum isokinetic efforts on a dynamometer (HumacNorm) before and after (5, 15, 30, 45, 60, 75, and 90 minutes after) ingesting either a carbohydrate (75 g glucose) or isovolumic placebo (saccharin-flavored) drink. Blood glucose and electromyography (EMG) were recorded concurrent with force output (max peak force; mean peak force). Despite a significant rise in blood glucose (mean glycemic excursion = 4.01 ± 1.18 mmol · L(-1)), there were no significant interactions in any (absolute or percentage) force (mean peak force: p ≥ 0.683; max peak force: p ≥ 0.567) or EMG (mean peak EMG: p ≥ 0.119; max peak EMG: p ≥ 0.247) parameters measured. The ingestion of glucose resulted in a 3.4% reduction in mean force across subsequent time points (highest: +2.1% at 15 minutes; lowest: -8.6% at 90 minutes after ingestion); however, this effect was small (d < 0.1). The ingestion of glucose does not alter performance of maximal isokinetic efforts in recreationally active young individuals. Additionally, there were no differences in force when assessed as a function of time after glucose ingestion. Consequently, in the absence of fatigue, carbohydrate ingestion is unlikely to present any ergogenic benefits to athletes performing resistance-based exercise.

Prevalence of prescribing in pregnancy using the Irish primary care research network: a pilot study.

BACKGROUND: To establish the prevalence and patterns of prescribing to pregnant women in an Irish primary care setting. METHODS: We reviewed electronic healthcare records routinely collected in primary care, of pregnant women attending nine Dublin-based General Practices affiliated to the Irish Primary Care Research Network (IPCRN) for antenatal care between January 2007 and October 2013 (n = 2,361 pregnancies). RESULTS: Excluding folic acid, 46.8% (n = 1,104) of pregnant women were prescribed at least one medication. Amoxicillin (11.1%, n = 263) and co-amoxiclav (8.0%, n = 190) were the most commonly prescribed medication followed by topical clotrimazole (4.9%, n = 117), salbutamol inhalers (4.1%, n = 96) and paracetamol (4.0%, n = 95). General Medical Services (GMS) patients were more likely to receive a prescription than private patients (OR 2.81; 95%CI (2.28, 3.47)). We applied the US FDA pregnancy-risk categories as a proxy measure of prescribing appropriateness, with FDA Category D and X medications considered inappropriate. FDA Category D drugs were prescribed in 5.9% (n = 140) of pregnancies. FDA Category X drugs were prescribed in 4.9% (n = 116) of pregnancies but after exclusion of oral contraceptives, progestogens, infertility treatments Category X medications were prescribed in 0.6% (n = 13) of pregnancies. After the initial antenatal consultation the prescribing prevalence of FDA Category D medications reduced to 4.7% (n = 110) and Category X to 3.1% (n = 72). CONCLUSIONS: The overall prevalence of prescribing to pregnant women in our cohort is low compared to studies internationally, however similar levels of prescribing for FDA Category D and X were found. Following the initial antenatal consultation levels of prescribing of the FDA Category D and X medications reduced, however there is potential to further reduce their use in early pregnancy. The IPCRN database has provided valuable information on the current practice of antenatal prescribing within this pilot group of practices however it is limited by the absence of morbidity and pregnancy outcome data.

Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Obeticholic acid (OCA; INT-747, 6α-ethyl-chenodeoxycholic acid) is a semisynthetic derivative of the primary human bile acid chenodeoxycholic acid, the natural agonist of the farnesoid X receptor, which is a nuclear hormone receptor that regulates glucose and lipid metabolism. In animal models, OCA decreases insulin resistance and hepatic steatosis. METHODS: We performed a double-blind, placebo-controlled, proof-of-concept study to evaluate the effects of OCA on insulin sensitivity in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus. Patients were randomly assigned to groups given placebo (n = 23), 25 mg OCA (n = 20), or 50 mg OCA (n = 21) once daily for 6 weeks. A 2-stage hyperinsulinemic-euglycemic insulin clamp was used to measure insulin sensitivity before and after the 6-week treatment period. We also measured levels of liver enzymes, lipid analytes, fibroblast growth factor 19, 7α-hydroxy-4-cholesten-3-one (a BA precursor), endogenous bile acids, and markers of liver fibrosis. RESULTS: When patients were given a low-dose insulin infusion, insulin sensitivity increased by 28.0% from baseline in the group treated with 25 mg OCA (P = .019) and 20.1% from baseline in the group treated with 50 mg OCA (P = .060). Insulin sensitivity increased by 24.5% (P = .011) in combined OCA groups, whereas it decreased by 5.5% in the placebo group. A similar pattern was observed in patients given a high-dose insulin infusion. The OCA groups had significant reductions in levels of γ-glutamyltransferase and alanine aminotransferase and dose-related weight loss. They also had increased serum levels of low-density lipoprotein cholesterol and fibroblast growth factor 19, associated with decreased levels of 7α-hydroxy-4-cholesten-3-one and endogenous bile acids, indicating activation of farnesoid X receptor. Markers of liver fibrosis decreased significantly in the group treated with 25 mg OCA. Adverse experiences were similar among groups. CONCLUSIONS: In this phase 2 trial, administration of 25 or 50 mg OCA for 6 weeks was well tolerated, increased insulin sensitivity, and reduced markers of liver inflammation and fibrosis in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Longer and larger studies are warranted. ClinicalTrials.gov, Number: NCT00501592.

Cost and Quality of Life of Disability Progression in Multiple Sclerosis Beyond EDSS: Impact of Cognition, Fatigue, and Limb Impairment.

BACKGROUND AND OBJECTIVE: Understanding the socioeconomic burden of multiple sclerosis (MS) is essential to inform policymakers and payers. Real-world studies have associated increasing costs and worsening quality of life (QoL) with disability progression. This study aims to further evaluate the impact of cognition, fatigue, upper and lower limb function (ULF, LLF) impairments, and disease progression per Expanded Disability Status Scale (EDSS) level, on costs and QoL. METHODS: This was a cross-sectional cohort study including 20,988 patients from the German NeuroTransData MS registry from 2009 to 2019. QoL analyses were based on EQ-5D-5L. Cost analyses included indirect/direct medical and non-medical costs. Eight subgroups, ranging from 439 to 1812 patients were created based on presence of measures for disease progression (EDSS), cognition (Symbol Digit Modalities Test [SDMT]), fatigue (Modified Fatigue Impact 5-Item Scale [MFIS-5]), ULF (Nine-Hole Peg Test [9HPT]), and LLF (Timed 25-Foot Walk [T25FW]). Multivariable linear regression assessed the independent effect of each test's score on QoL and costs, while adjusting for EDSS and 12 other confounders. RESULTS: Lower QoL was associated with decreasing cognition (p < 0.001), worsening ULF (p = 0.025), and increasing fatigue (p < 0.0001); however, the negative impact of LLF worsening on QoL was not statistically significant (p = 0.54). Higher costs were associated with decreasing cognition (p < 0.001), worsening of ULF (p = 0.0058) and LLF (p = 0.049), and increasing fatigue (p < 0.0001). Each 1-scale-step worsening function of SDMT, MFIS-5, 9HPT, and T25FW scores resulted in €170, €790, €330, and €520 higher costs, respectively. Modeling disability progression based on SDMT, MFIS-5, 9HPT, and T25FW scores as an interaction with EDSS strata found associations with lower QoL and higher costs at variable EDSS ranges. CONCLUSIONS: Disease progression in MS measured by 9HPT, SDMT, and MFIS-5 had a significant negative impact on QoL and broad socioeconomic costs independent of EDSS. T25FW had a significant negative association with costs. Cognition, fatigue, ULF, and LLF have stronger impact on costs and QoL in patients with higher EDSS scores. Additional determinants of MS disability status, including SDMT, MFIS-5, 9HPT, and T25FW, should be considered for assessing cost effectiveness of novel therapeutics for MS.

Electronic health record data for assessing risk of hospitalization for COVID-19: Methodological considerations applied to multiple sclerosis.

INTRODUCTION: During the COVID-19 pandemic, electronic health record (EHR) data has been used to investigate disease severity and risk factors for severe COVID-19 in people with multiple sclerosis (pwMS). Methodological challenges including sampling bias, and residual confounding should be considered when conducting EHR-based studies. We aimed to address these limitations related to the use of EHR data in order to identify risk factors, including the use of disease modifying therapies (DMTs), associated with hospitalization for COVID-19 amongst pwMS. METHODS: We performed a retrospective cohort study including a sample of 47,051 pwMS using a large US-based EHR and claims linked database. Follow-up started at the beginning of the pandemic, February 20th 2020, and continued until September 30th 2020. COVID-19 diagnosis was determined by the presence of ICD-10 diagnostic code for COVID-19, or a positive diagnostic laboratory test, or an ICD-10 diagnostic code for coronaviruses. We used Cox regression modeling to assess the impact of baseline demographics, MS disease history and pre-existing comorbidities on the risk of hospitalization for COVID-19. Then, we identified 5,169 pwMS using ocrelizumab (OCR) and 3,351 pwMS using dimethyl fumarate (DMF) at baseline, and evaluated the distribution of the identified COVID-19 risk factors between the two groups. Finally, we used Cox regression models, adjusted for the identified confounders, to estimate the risk of hospitalization for COVID-19 in pwMS treated with OCR compared to DMF. RESULTS: Among the pwMS cohort, we identified 799 COVID-19 cases (1.7%) which resulted in 182 hospitalizations for COVID-19 (0.4%). Population differences between the pwMS and COVID-19 cohorts were observed. Statistical modeling identified older age, male gender, African-American race, walking with assistance, non-ambulatory status, severe relapse requiring hospitalization in year prior to baseline, and specific comorbidities to be associated with a higher risk of COVID-19 related-hospitalization. Comparing the COVID-19 risk factors between OCR users and DMF users, MS characteristics including ambulatory status and MS subtype were highly imbalanced, likely arising from key differences in the labelled indications for these therapies. Compared to DMF use, in unadjusted (HR 1.58, 95% CI 0.73 - 3.44), adjusted (HR 1.28, 95% CI 0.58 - 2.83), propensity score weighted (HR 1.25, 95% CI 0.56 - 2.80), and doubly robust models (HR 1.29, 95% CI 0.57 - 2.89), no significantly increased risk of hospitalization for COVID-19 was associated with OCR use. CONCLUSION: We observed significant population differences when comparing all pwMS to COVID-19 cases, as well as significant differences in key confounders between OCR and DMF treated patients. In unadjusted analyses we did not observe a statistically significant higher risk of COVID-19 hospitalization in pwMS treated with OCR compared to DMF, with further attenuation of risk when adjusting for the key confounders. This study re-emphasises the importance to appropriately consider both sampling and confounding bias in EHR-based MS research.

The socioeconomic impact of disability progression in multiple sclerosis: A retrospective cohort study of the German NeuroTransData (NTD) registry.

Background: Multiple sclerosis (MS) is a progressively debilitating neurologic disease that poses significant costs to the healthcare system and workforce. Objective: To evaluate the impact of MS disease progression on societal costs and quality of life (QoL) using data from the German NeuroTransData (NTD) MS registry. Methods: Cross-sectional cohort study. The cost cohort included patients with MS disability assessed using Expanded Disability Status Scale (EDSS) in 2019 while the QoL cohort included patients assessed using EDSS and EuroQol-5 Dimension 5-Levels between 2009 and 2019. Direct and indirect medical, and non-medical resource use was quantified and costs derived from public sources. Results: Within the QoL cohort (n = 9821), QoL worsened with increasing EDSS. Within the cost cohort (n = 7286), increasing resource use with increasing EDSS was observed. Societal costs per patient, excluding or including disease-modifying therapies, increased from €5694 or €19,315 at EDSS 0 to 3.5 to €25,419 or €36,499 at EDSS 4 to 6.5, and €52,883 or €58,576 at EDSS 7 to 9.5. In multivariate modeling, each 0.5-step increase in EDSS was significantly associated with increasing costs, and worsening QoL. Conclusion: This study confirms the major socioeconomic burden associated with MS disability progression. From a socioeconomic perspective, delaying disability progression may benefit patients and society.

Alpha-Fetoprotein as a Potential Surrogate Biomarker for Atezolizumab + Bevacizumab Treatment of Hepatocellular Carcinoma.

PURPOSE: Atezolizumab + bevacizumab is the new standard of care for systemic treatment-naïve, unresectable hepatocellular carcinoma (HCC). This exploratory study investigated on-treatment alpha-fetoprotein (AFP) response as a potential surrogate biomarker of prognosis for the combination therapy. EXPERIMENTAL DESIGN: Data from Group A of the phase Ib GO30140 study were used to identify the optimal time for AFP measurement and AFP cutoffs to differentiate patients by their best confirmed response per independent review facility-assessed RECIST (IRF-RECIST) version 1.1: responders from nonresponders and patients with disease control from primary progressors. We applied these cutoffs to independent data from the atezolizumab + bevacizumab arm of the phase III IMbrave150 trial to distinguish patients based on (i) overall survival (OS) and progression-free survival (PFS) per IRF-RECIST 1.1 and (ii) best confirmed response per IRF-RECIST 1.1. RESULTS: We derived AFP cutoffs of ≥75% decrease and ≤10% increase from baseline at 6 weeks to identify responders and those who had disease control, respectively. These cutoffs had high sensitivity and specificity in GO30140. In IMbrave150 patients, sensitivity was 0.59 and specificity was 0.86 for the ≥75% decrease AFP cutoff; the sensitivity was 0.77 and specificity was 0.44 for the ≤10% increase AFP cutoff. Both AFP cutoffs were associated with longer OS and PFS, particularly in patients with hepatitis B virus etiology (HR < 0.5; P < 0.01). CONCLUSIONS: AFP response at 6 weeks after initiating treatment is a potential surrogate biomarker of prognosis for patients with HCC receiving atezolizumab + bevacizumab. See related commentary by Cappuyns and Llovet, p. 3405.

COVID-19 in ocrelizumab-treated people with multiple sclerosis.

BACKGROUND: There are limited data on the impact of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on people with multiple sclerosis (MS). OBJECTIVE: To better understand SARS-CoV-2 infection in ocrelizumab-treated people with MS. METHODS: Internal Roche/Genentech data sources: Cases of COVID-19 from ongoing Roche/Genentech clinical trials and from post-marketing use of ocrelizumab until July 31, 2020 were identified and assessed using descriptive statistics. External real-world data (RWD) source: An MS COVID-19 cohort and an ocrelizumab-treated MS COVID-19 cohort were identified and assessed from the OPTUMⓇ de-identified COVID-19 electronic health record (EHR) database. RESULTS: Roche/Genentech clinical trial data: There were 51 (1.3%) suspected or confirmed cases of COVID-19 identified from 4,000 patients ongoing in 10 Roche/Genentech clinical trials. Of these, 26 (51%) were confirmed COVID-19 and 25 (49%) were suspected COVID-19. Sixteen (31.4%) patients were hospitalized. COVID-19 severity was mild to moderate in most patients (35, 68.6%). Ten (19.6%) patients had severe disease and there were three (5.9%) fatal cases. Most patients (43, 84.3%) recovered or were recovering. There was no association apparent between duration of exposure to ocrelizumab and COVID-19. Among COVID-19 patients with previous serum immunoglobulin status (27/51, 52.9%), all (27/27, 100%) had IgG levels within the normal range. Roche/Genentech post-marketing safety database data: There were 307 post-marketing cases of COVID-19 in the Roche/Genentech global safety database. Of these, 263 (85.7%) were confirmed and 44 (14.3%) were suspected COVID-19. 100 (32.6%) patients were hospitalized. COVID-19 was asymptomatic, mild or moderate in 143 (46.6%) patients, severe in 52 (16.9%) patients, and critical in 15 (4.9%) patients. There were 17 (5.5%) fatal cases. Information on severity was not reported in 80 (26.1%) cases. Most patients (211, 68.7%) recovered or were recovering at the time of the report. External RWD data source: As of July 13, 2020, the OPTUMⓇ database included EHRs for almost 1.2 million patients with suspected COVID-19, 130,500 of whom met the criteria for confirmed/clinically diagnosed COVID-19. A total of 357 patients with MS with confirmed COVID-19 were identified. Forty-eight (13.4%) were treated with ocrelizumab, of whom 12 (25.0%) were hospitalized and one died (2.1%). Similar rates of hospitalization, invasive ventilation, and death were observed in the ocrelizumab-treated and non-ocrelizumab-treated MS cohorts. Across the Roche/Genentech and RWD sources assessed, age, male sex, and the presence of comorbidities such as hypertension were associated with a more severe disease course of COVID-19. There was a higher number of comorbidities present in hospitalized versus non-hospitalized patients. CONCLUSIONS: This assessment provides evidence that COVID-19 in ocrelizumab-treated people with MS is predominantly mild to moderate in severity with most patients not requiring hospitalization; in line with data reported from the general population and MS datasets. Risk factors known to be associated with severe COVID-19 outcomes in the general population also appear to influence COVID-19 severity in ocrelizumab-treated people with MS. Case fatality rates for ocrelizumab-treated people with MS were within published ranges for the general population and other MS cohorts.

Patterns and harms of pharmaceutical drug use among ecstasy users in Australia.

BACKGROUND: There has been a significant incursion of prescription drugs in to the club scene worldwide. The concomitant use of ecstasy and pharmaceutical drugs is associated with potentially serious health-related harms. This has ramifications for people who deliberately combine pharmaceutical drugs with ecstasy to achieve a specific effect and for people legitimately using pharmaceutical drugs for a health condition who may incidentally use ecstasy. This exploratory study had the broad aim to investigate the patterns and harms of concomitant use of pharmaceutical drugs and ecstasy, and to explore participants' experiences when visiting a General Practitioner (GP). METHODS: In-depth interviews were conducted with 30 ecstasy/pharmaceutical drug users. RESULTS: Users reported deliberately combining stimulants (dexamphetamine, methylphenidate (e.g. Ritalin), antidepressants and sildenafil (e.g. Viagra) for non-medical purposes with ecstasy. A wide range of effects were reported. Several clear relationships emerged between the use of pharmaceutical drugs and ecstasy, and the distinctions between these in terms of motivations for use and consequences are discussed. The attitudes of GPs were professional and non-judgemental and there was little reluctance among participants to disclose illicit drug use. Screening for illicit drug use was limited. IMPLICATIONS: Findings have important implications for clubbers in regard to harm reduction strategies and highlight a number of areas for future research.

Medication monitoring attitudes and perceived determinants to offering medication adherence advice to older hypertensive adults: a factorial survey of community pharmacy interns.

INTRODUCTION: Community pharmacy is an ideal setting to monitor medication adherence, however, barriers to pharmacist-led interventions exist. Preparing future pharmacists for enhanced roles may overcome such barriers. Our objective was to identify medication monitoring attitudes and contextual factors that influence adherence monitoring by pharmacy interns to inform educational activities on medication adherence. METHODS: An online factorial survey of all pharmacy interns (N = 123) in the Republic of Ireland, completing advanced community pharmacy experiential learning in May 2016 was undertaken to evaluate attitudes to medication monitoring and to identify respondent characteristics and contextual factors which influence adherence monitoring of older hypertensive adults during repeat dispensing. The medication monitoring attitude measure (MMAM) was used to evaluate interns' attitudes, and factorial vignette analysis was performed to identify factors influencing behavioural intention to offer adherence advice. RESULTS: There were 121 completed online surveys. Half of interns reported they felt uncomfortable and confrontational discussing adherence with patients. In factorial vignette analysis, higher medication monitoring attitudes resulted in higher likelihood to offer adherence advice; experiential-learning characteristics such as pharmacy ownership-type (nonchain store) and contextual factors including patients being treated for longer and time-pressures had a significant negative influence on pharmacy interns' likelihood to offer adherence advice. DISCUSSION: Medication monitoring attitudes and contextual factors influenced responses to offer adherence advice in hypothetical scenarios. Ensuring pharmacy students are educated on patterns of adherence and appropriate skills to address nonadherence, and engage in structured programmes to facilitate patient interactions during experiential learning, may improve medication monitoring attitudes and adherence monitoring.

The association between pharmacy refill-adherence metrics and healthcare utilisation: a prospective cohort study of older hypertensive adults.

AIMS: Methods that enable targeting and tailoring of adherence interventions may facilitate implementation in clinical settings. We aimed to determine whether community pharmacy refill-adherence metrics are useful to identify patients at higher risk of healthcare utilisation due to low antihypertensive adherence, who may benefit from an adherence intervention. METHODS: We conducted a prospective cohort study, recruiting participants (n = 905) from 106 community pharmacies across the Republic of Ireland. Participants completed a structured interview at baseline and 12 months. Antihypertensive medication adherence was evaluated from linked pharmacy records using group-based trajectory modelling (GBTM) and proportion of days covered (PDC). Healthcare utilisation included self-reported number of hospital visits (emergency department visits and inpatient admissions) and general practitioner (GP) visits, over a 6-month period. Separate regression models were used to estimate the association between adherence and number of hospital/GP visits. The relative statistical fit of each model using different adherence metrics was determined using the Bayesian information criterion (BIC). RESULTS: For the number of hospital visits, significant associations were observed only for PDC but not for GBTM. Each 10% increase in refill-adherence by PDC was significantly associated with a 16% lower rate of hospital visits (adjusted incidence rate ratio 0.84, 95% CI 0.72-0.98, P = 0.036). Poorer adherence using both measures was associated with higher GP visits. Improvements in BIC favoured models using PDC. CONCLUSIONS: Medication refill-adherence, measured using PDC in community pharmacy settings, could be used to recognise poor antihypertensive adherence to enable effective targeting of clinical interventions to improve hypertension management and outcomes.

Association between gaps in antihypertensive medication adherence and injurious falls in older community-dwelling adults: a prospective cohort study.

OBJECTIVE: Growing evidence suggests that older adults are at an increased risk of injurious falls when initiating antihypertensive medication, while the evidence regarding long-term use of antihypertensive medication and the risk of falling is mixed. However, long-term users who stop and start these medications may have a similar risk of falling to initial users of antihypertensive medication. Our aim was to evaluate the association between gaps in antihypertensive medication adherence and injurious falls in older (≥65 years) community-dwelling, long-term (≥≥1 year) antihypertensive users. DESIGN: Prospective cohort study. SETTING: Irish Community Pharmacy. PARTICIPANTS: Consecutive participants presenting a prescription for antihypertensive medication to 106 community pharmacies nationwide, community-dwelling, ≥65 years, with no evidence of cognitive impairment, taking antihypertensive medication for ≥1 year (n=938). MEASURES: Gaps in antihypertensive medication adherence were evaluated from linked dispensing records as the number of 5-day gaps between sequential supplies over the 12-month period prior to baseline. Injurious falls during follow-up were recorded via questionnaire during structured telephone interviews at 12 months. RESULTS: At 12 months, 8.1% (n=76) of participants reported an injurious fall requiring medical attention. The mean number of 5-day gaps in medication refill behaviour was 1.47 (SD 1.58). In adjusted, modified Poisson models, 5-day medication refill gaps at baseline were associated with a higher risk of an injurious fall during follow-up (aRR 1.18, 95% CI 1.02 to 1.37, p=0.024). CONCLUSION: Each 5-day gap in antihypertensive refill adherence increased the risk of self-reported injurious falls by 18%. Gaps in antihypertensive adherence may be a marker for increased risk of injurious falls. It is unknown whether adherence-interventions will reduce subsequent risk. This finding is hypothesis generating and should be replicated in similar populations.

Cannabis potency and contamination: a review of the literature.

AIMS: Increased potency and contamination of cannabis have been linked in the public domain to adverse mental health outcomes. This paper reviews the available international evidence on patterns of cannabis potency and contamination and potential associated harms, and discusses their implications for prevention and harm reduction measures. METHODS: A systematic literature search on cannabis potency and contamination was conducted. RESULTS: Cannabis samples tested in the United States, the Netherlands, United Kingdom and Italy have shown increases in potency over the last 10 years. Some countries have not shown significant increases in potency, while other countries have not monitored potency over time. While there are some grounds to be concerned about potential contaminants in cannabis, there has been no systematic monitoring. CONCLUSION: Increased potency has been observed in some countries, but there is enormous variation between samples, meaning that cannabis users may be exposed to greater variation in a single year than over years or decades. Claims made in the public domain about a 20- or 30-fold increase in cannabis potency and about the adverse mental health effects of cannabis contamination are not supported currently by the evidence. Systematic scientific testing of cannabis is needed to monitor current and ongoing trends in cannabis potency, and to determine whether cannabis is contaminated. Additionally, more research is needed to determine whether increased potency and contamination translates to harm for users, who need to be provided with accurate and credible information to prevent and reduce harms associated with cannabis use.

Injecting risk behaviour and related harm among men who use performance- and image-enhancing drugs.

INTRODUCTION AND AIMS: Performance- and image-enhancing drugs have the potential to be a significant public health issue. Detailed data on PIEDs injection are difficult to obtain because of the illicit and unsupervised way in which many PIEDs are used, and the hidden nature of the group. Our study examines the patterns of use, risk behaviours and related harm associated with PIEDs injection. We also report the ways in which PIEDs users currently seek injecting equipment and harm-reduction advice. DESIGN AND METHOD: Data were obtained via a structured questionnaire administered in face-to-face interviews with 60 men who used PIEDs (primarily anabolic androgenic steroids) for non-medical purposes. RESULTS: Although the rates of needle sharing were low (5%), the men more frequently reported re-use of needles/equipment, injecting from a shared container (bladders, vials, etc.), injecting other illicit drugs, injecting insulin and targeting small muscle groups. Self-reports of being hepatitis C antibody positive were associated with lifetime use of heroin and injection of other illicit drugs. All HIV positive participants were gay/bisexual men. Participants reported a range of other injection-related injuries and diseases such as fevers, scarring and abscesses. 'Risky' injectors (38% of participants) were more likely to initiate PIEDs use at a younger age, use PIEDs in a larger number of cycles per year and report involvement in a violent/aggressive incident than 'low risk' injectors and report involvement in a violent/aggressive incident than 'low risk' injectors. Participants mainly reported seeking information about PIEDs from internet sites (62%) and friends (55%). CONCLUSIONS: An over-reliance on personal networks and internet forums limits this groups' access to objective harm reduction advice and primary care services. Targeted, PIEDs-specific interventions are needed.