PEER simplified lipid guideline 2023 update: Prevention and management of cardiovascular disease in primary care.

OBJECTIVE: To update the 2015 clinical practice guideline and provide a simplified approach to lipid management in the prevention of cardiovascular disease (CVD) for primary care. METHODS: Following the Institute of Medicine's Clinical Practice Guidelines We Can Trust, a multidisciplinary, pan-Canadian guideline panel was formed. This panel was represented by primary care providers, free from conflicts of interest with industry, and included the patient perspective. A separate scientific evidence team performed evidence reviews on statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 inhibitors, fibrates, bile acid sequestrants, niacin, and omega-3 supplements (docosahexaenoic acid with eicosapentaenoic acid [EPA] or EPA ethyl ester alone [icosapent]), as well as on 11 supplemental questions. Recommendations were finalized by the guideline panel through use of the Grading of Recommendations Assessment, Development and Evaluation methodology. RECOMMENDATIONS: All recommendations are presented in a patient-centred manner designed with the needs of family physicians and other primary care providers in mind. Many recommendations are similar to those published in 2015. Statins remain first-line therapy for both primary and secondary CVD prevention, and the Mediterranean diet and physical activity are recommended to reduce cardiovascular risk (primary and secondary prevention). The guideline panel recommended against using lipoprotein a, apolipoprotein B, or coronary artery calcium levels when assessing cardiovascular risk, and recommended against targeting specific lipid levels. The team also reviewed new evidence pertaining to omega-3 fatty acids (including EPA ethyl ester [icosapent]) and proprotein convertase subtilisin-kexin type 9 inhibitors, and outlined when to engage in informed shared decision making with patients on interventions to lower cardiovascular risk. CONCLUSION: These updated evidence-based guidelines provide a simplified approach to lipid management for the prevention and management of CVD. These guidelines were created by and for primary health care professionals and their patients.

Liver-related Events in Human Immunodeficiency Virus-infected Persons With Occult Cirrhosis.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown. METHODS: HIV-infected patients from 2 Canadian cohorts underwent transient elastography (TE) examination and were classified as (1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); or (3) noncirrhotic patients (TE <13 kPa). Incidence and risk factors of liver-related events were investigated through Kaplan-Meier and Cox regression analyses, respectively. We estimated monitoring rates according to screening guidelines for hepatocellular carcinoma (HCC) by OcC and OvC status. RESULTS: A total of 1092 HIV-infected patients (51% coinfected with hepatitis C virus) were included. Prevalence of OcC and OvC at baseline was 2.7% and 10.7%, respectively. During a median follow-up of 1.8 (interquartile range, 1.5-2.8) years, the incidence of liver-related events in noncirrhosis, OcC, and OvC was 3.4 (95% confidence interval [CI], 1.2-7.3), 34.0 (95% CI, 6.0-104.0), and 37.0 (95% CI, 17.0-69.1) per 1000 person-years, respectively. Baseline OcC (adjusted hazard ratio [aHR], 7.1 [95% CI, 1.3-38.0]) and OvC (aHR, 8.5 [95% CI, 2.8-26.0]) were independently associated with liver-related events. Monitoring rates for HCC were lower in patients with OcC (24%) compared to those with OvC (40%). CONCLUSIONS: HIV-infected patients with OcC have a high incidence of liver-related events. Greater surveillance and earlier recognition with appropriate screening strategies are necessary for improved outcomes.

Performance of a Bayesian Approach for Imputing Missing Data on the SF-12 Health-Related Quality-of-Life Measure.

BACKGROUND: Missing data in health-related quality-of-life outcomes are an ongoing problem. The 12-item short form health survey (SF-12) scores are no exception. Data imputation is complicated, because missingness may be partially predicted by the missing data themselves. OBJECTIVES: To compare the performance of a Bayesian method for imputing SF-12 data with previously described frequentist imputation methods. METHODS: SF-12 data were extracted from a trial assessing continence promotion on health-related quality of life in older women (n = 1052); the data set was split into a model development cohort for creating predictive models and a validation cohort to validate these models. Algorithms were constructed using data from the model development cohort to compute SF-12-related scores (physical health composite scale, the mental health composite scale, and the six-dimensional health state short form utilities). The Bayesian models used missing at random and missing not at random algorithms to impute missing SF-12 answers as categorical data. Comparative models replaced missing data with 0, used the mean weight of the sample, and regressed parameters from sociodemographic predictors. Data randomly deleted from the validation cohort were imputed with each algorithm, and the mean absolute error was used to gauge goodness of fit. RESULTS: Each cohort included 526 persons; mean age was 78.1 ± 7.8 years. In the model development cohort, 15.6% of the participants had missing data. For the physical health composite scale, the mental health composite scale, and the six-dimensional health state short form utilities, the Bayesian model with missing at random data significantly outperformed all five comparison models, including the Bayesian models with missing not at random data. CONCLUSIONS: Bayesian imputation was superior to other previously described methods for computing missing SF-12 data.

Lignes directrices simplifiées de PEER sur les lipides : actualisation 2023: Prévention et prise en charge des maladies cardiovasculaires en soins primaires.

OBJECTIF: Actualiser le guide de pratique clinique de 2015 et présenter une approche simplifiée de la prise en charge des lipides dans la prévention des maladies cardiovasculaires (MCV) en première ligne. MÉTHODES: Conformément aux recommandations de l'Institute of Medicine dans Clinical Practice Guidelines We Can Trust, un panel pancanadien d'experts multidisciplinaires en lignes directrices a été formé. Ce panel était représentatif des cliniciens en soins primaires, libre de tout conflit d'intérêts avec l'industrie, et il tenait compte des points de vue des patients. Une équipe distincte, responsable des données probantes scientifiques, a passé en revue l'information sur les statines, l'ézétimibe, les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9, les fibrates, les chélateurs des acides biliaires, la niacine et les suppléments d'omega-3 (acide docosahexaénoïque avec acide eicosapentaénoïque [EPA] ou ester éthylique de l'EPA seul [icosapent]), ainsi que sur la réponse à 11 questions supplémentaires. Le panel des lignes directrices a finalisé les recommandations en utilisant la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation). RECOMMANDATIONS: Toutes les recommandations sont présentées de manière à être centrées sur le patient et conçues en ayant à l'esprit les besoins des médecins de famille et des autres cliniciens des soins primaires. De nombreuses recommandations sont semblables à celles publiées en 2015. Les statines demeurent le traitement de première intention pour la prévention tant primaire que secondaire des MCV, et le régime méditerranéen et l'activité physique sont recommandés pour réduire le risque cardiovasculaire (en prévention primaire et secondaire). Le panel des lignes directrices a recommandé de ne pas utiliser le dosage des lipoprotéines a, des apolipoprotéines B ou le score calcique coronarien (SCC) dans l'évaluation du risque cardiovasculaire, et de ne pas cibler de seuils précis de taux lipidiques. L'équipe a aussi passé en revue de nouvelles données concernant les acides gras omega-3 (y compris l'ester éthylique d'EAP [icosapent]) et les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9, et a précisé les moments où il convient de procéder à une prise de décision partagée avec les patients sur les interventions pour diminuer le risque cardiovasculaire. CONCLUSION: Ces lignes directrices actualisées et fondées sur des données probantes présentent une approche simplifiée de la prise en charge des lipides pour la prévention et le traitement des MCV. Ce guide de pratique clinique a été conçu par et pour des professionnels de la santé en soins primaires et leurs patients.

Implications of the minimal clinically important difference for health-related quality-of-life outcomes: a comparison of sample size requirements for an incontinence treatment trial.

BACKGROUND: Sample size calculations for treatment trials that aim to assess health-related quality-of-life (HRQOL) outcomes are often difficult to perform. Researchers must select a target minimal clinically important difference (MCID) in HRQOL for the trial, estimate the effect size of the intervention, and then consider the responsiveness of different HRQOL measures for detecting improvements. Generic preference-based HRQOL measures are usually less sensitive to gains in HRQOL than are disease-specific measures, but are nonetheless recommended to quantify an impact on HRQOL that can be translated into quality-adjusted life-years during cost-effectiveness analyses. Mapping disease-specific measures onto generic measures is a proposed method for yielding more efficient sample size requirements while retaining the ability to generate utility weights for cost-effectiveness analyses. OBJECTIVES: This study sought to test this mapping strategy to calculate and compare the effect on sample size of three different methods. METHODS: Three different methods were used for determining an MCID in HRQOL in patients with incontinence: 1) a global rating of improvement, 2) an incontinence-specific HRQOL instrument, and 3) a generic preference-based HRQOL instrument using mapping coefficients. RESULTS: The sample size required to detect a 20% difference in the MCID for the global rating of improvement was 52 per trial arm, 172 per arm for the incontinence-specific HRQOL outcome, and 500 per arm for the generic preference-based HRQOL outcome. CONCLUSIONS: We caution that treatment trials of conditions for which improvements are not easy to measure on generic HRQOL instruments will still require significantly greater sample size even when mapping functions are used to try to gain efficiency.

Government Direct-to-Consumer Education to Reduce Prescription Opioid Use: A Cluster Randomized Clinical Trial.

Importance: Direct-to-consumer education reduces chronic sedative use. The effectiveness of this approach for prescription opioids among patients with chronic noncancer pain remains untested. Objectives: To evaluate the effectiveness of a government-led educational information brochure mailed to community-dwelling, long-term opioid consumers to reduce prescription opioid use compared with usual care. Design, Setting, and Participants: This cluster randomized clinical trial was conducted from July 2018 to January 2019 in Manitoba, Canada. All adults with long-term opioid prescriptions were enrolled (n = 4225). Participants were identified via the Manitoba Drug Program Information Network. Individuals receiving palliative care or with a diagnosis of cancer or dementia were excluded. Data were analyzed from July 2019 to March 2020. Intervention: Participants were clustered according to their primary care clinic and randomized to the intervention (a codesigned direct-to-consumer educational brochure sent by mail) or usual care (comparator group). Main Outcomes and Measures: The main outcome was discontinuation of opioid prescriptions at the participant level after 6 months, ascertained by pharmacy drug claims. Secondary outcomes included dose reduction (in morphine milligram equivalents [MME]) and/or therapeutic switch. Reduction in opioid use was assessed using generalized estimating equations to account for clustering, with prespecified subgroup analyses by age and sex. Analysis was intention to treat. Results: Of 4206 participants, 2409 (57.3%) were male; mean (SD) age was 60.0 (14.4) years. Mean (SD) baseline opioid use was comparable between groups (intervention, 157.7 [179.7] MME/d; control, 153.4 [181.8] MME/d). After 6 months, 235 of 2136 participants (11.0%) in 127 clusters in the intervention group no longer filled opioid prescriptions compared with 228 of 2070 (11.0%) in 124 clusters in the comparator group (difference, 0.0%; 95% CI, -1.9% to 1.9%). More participants in the intervention group than in the control group reduced their dose (1410 [66.0%] vs 1307 [63.1%]; difference, 2.8% [95% CI, 0.0%-5.7%]). Receipt of the brochure led to greater dose reductions for participants who were male (difference, 3.9%; 95% CI, 0.1%-7.7%), aged 18 to 64 years (difference, 3.7%; 95% CI, 0.2%-7.2%), or living in urban areas (difference, 5.9%; 95% CI, 1.9%-9.9%) compared with usual care. Conclusions and Relevance: In this cluster randomized clinical trial, no significant difference in the prevalence of opioid cessation was observed after 6 months between the intervention and usual care groups; however, the intervention resulted in more adults reducing their opioid dose compared with usual care. Trial Registration: ClinicalTrials.gov Identifier: NCT03400384.

Uncovering the source of new benzodiazepine prescriptions in community-dwelling older adults'.

OBJECTIVE: Initiatives to reduce benzodiazepine use have been largely unsuccessful despite strong associations with adverse outcomes. Curtailing incident use of benzodizepines is an alternate strategy that has yet to be explored. This study aims to determine the source of incident benzodiazepine prescriptions by comparing the risk of receiving a new prescription upon hospital discharge versus after an ambulatory care clinic visit. METHODS: Data were derived from 1189 community-dwelling adults aged 65 years naive to benzodiazepine consumption, enrolled in the Étude sur la Santé des Ainés, a prospective 3-year cohort study conducted in Québec, Canada. Health survey questionnaires were linked with provincial administrative databases of prescription and health service claims. Analysis with multivariate Poisson regression models compared the risk of incident benzodiazepine use post-hospitalization versus after an ambulatory care visit. Models were adjusted for sex, age, antidepressant use, and concomitant drugs. Sub-analyses were conducted for chronic prescriptions. RESULTS: Incident benzodiazepine use was 11% over a 2-year period, with 18.3% of prescriptions leading to chronic use (> 90 days). Hospitalization conferred a 2.7-fold greater risk of incident use than an outpatient visit (OR 2.66, 95% CI 1.78-3.98) and a 4.7-fold (OR 4.74, 95% CI 1.63-13.78) increased risk of chronic use, after adjusting for potential confounders. Despite the increased risk, only 13% of new prescriptions originated post-hospital discharge, with the remainder prescribed during outpatient visits. CONCLUSION: Interventions are required to curb incident benzodiazepine prescriptions at their source both in hospitals and in ambulatory care settings.

A case of acute kidney injury secondary to black cherry concentrate in a patient with chronic kidney disease secondary to type 2 diabetes mellitus.

There are many herbal products which are accessible to patients, and they may provide with many health benefits. Nevertheless, some of these supplements can lead to significant morbidity as they can also have important side effects and impact patient's organ systems. In this case report, we present a patient with chronic kidney disease secondary to type II diabetes mellitus who develops acute kidney injury and metabolic disturbances secondary to consuming black cherry concentrate as a mean to self-manage his gout flare. The most likely mechanism of injury was cyclooxygenase inhibition by anthocyanins, molecular compounds found in cherries that have a similar mechanism of action to nonsteroidal anti-inflammatory medications. Patient's kidney injury and metabolic disturbances improved after the discontinuation of black cherry concentrate. This is the second case report that presents a correlation between consumption of cherry concentrate in a patient with chronic kidney disease and acute kidney injury.