Shared decision-making approach to type 2 diabetes management.

OBJECTIVE: To provide an online interactive decision aid to facilitate shared decision making in the context of medication choices for patients with type 2 diabetes mellitus (T2DM). SOURCES OF INFORMATION: The best available clinical prediction model for patients with T2DM was selected based on a review of guidelines, DynaMed, and UpToDate and a search of PubMed. A list of pharmacotherapeutic options for T2DM was compiled based on a review of guidelines, narrative reviews, and expert opinion. To determine the benefits and harms of each treatment, federated search engines were searched for meta-analyses of randomized controlled trials, supplemented by individual randomized controlled trials for outcomes not reported in meta-analyses. MAIN MESSAGE: Approximately 2.1 million Canadians have T2DM, with a resulting increased risk of death, cardiovascular disease, and microvascular outcomes. While more than a dozen medication options are available, decisions regarding these medications are challenging, as patients vary in their preferences. Shared decision making has the potential to individualize these difficult decisions, but the number of diabetes-related outcomes and available treatment options have made this historically impractical. It is within this context that the PEER Diabetes Medication Decision Aid was developed. This decision aid provides patients with personalized 10-year risk estimates for 6 clinically important diabetes-related outcomes. The tool also allows patients to focus on the outcome that matters most to them and to compare the benefits and harms of up to 12 different treatment options. This information is displayed in personalized absolute numbers, along with practical considerations such as cost. CONCLUSION: The PEER Diabetes Medication Decision Aid provides a practical tool that can enable patients with T2DM to come to autonomous and well-informed medication decisions.

Quality of antibiotic prescribing for pediatric community-acquired Pneumonia in outpatient care.

BACKGROUND: Antibiotics remain the primary treatment for community acquired pneumonia (CAP), however rising rates of antimicrobial resistance may jeopardize their future efficacy. With higher rates of disease reported in the youngest populations, effective treatment courses for pediatric pneumonia are of paramount importance. This study is the first to examine the quality of pediatric antibiotic use by agent, dose and duration. METHODS: A retrospective cohort study included all outpatient/primary care physician visits for pediatric CAP (aged < 19 years) between January 1 2014 to December 31 2018. Relevant practice guidelines were identified, and treatment recommendations extracted. Amoxicillin was the primary first-line agent for pediatric CAP. Categories of prescribing included: guideline adherent, effective but unnecessary (excess dose and/or duration), under treatment (insufficient dose and/or duration), and not recommended. Proportions of attributable-antibiotic use were examined by prescribing category, and then stratified by age and sex. RESULT(S): A total of 42,452 episodes of pediatric CAP were identified. Of those, 31,347 (76%) resulted in an antibiotic prescription. Amoxicillin accounted for 51% of all prescriptions. Overall, 27% of prescribing was fully guideline adherent, 19% effective but unnecessary, 10% under treatment, and 44% not recommended by agent. Excessive duration was the hallmark of effective but unnecessary prescribing (97%) Macrolides accounted for the majority on non-first line agent use, with only 32% of not recommended prescribing preceded by a previous course of antibiotics. CONCLUSION(S): This study is the first in Canada to examine prescribing quality for pediatric CAP by agent, dose and duration. Utilizing first-line agents, and shorter-course treatments are targets for stewardship.

Lipid-lowering therapies for cardiovascular disease prevention and management in primary care: PEER umbrella systematic review of systematic reviews.

OBJECTIVE: To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins. DATA SOURCES: MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search. STUDY SELECTION: Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected. Outcomes of interest included major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and adverse events. SYNTHESIS: A total of 76 systematic reviews were included. Four randomized controlled trials were also included for BAS because no efficacy systematic review was identified. Statins significantly reduced MACE (6 systematic reviews; median risk ratio [RR]=0.74; interquartile range [IQR]=0.71 to 0.76), cardiovascular mortality (7 systematic reviews; median RR=0.85, IQR=0.83 to 0.86), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.88 to 0.92). Major adverse cardiovascular events were also significantly reduced by ezetimibe (3 systematic reviews; median RR=0.93, IQR=0.93 to 0.94), PCSK9 inhibitors (14 systematic reviews; median RR=0.84, IQR=0.83 to 0.87), and fibrates (2 systematic reviews; mean RR=0.86), but these interventions had no effect on cardiovascular or all-cause mortality. Fibrates had no effect on any cardiovascular outcomes when added to a statin. Omega-3 combination supplements had no effect on MACE or all-cause mortality but significantly reduced cardiovascular mortality (5 systematic reviews; median RR=0.93, IQR=0.93 to 0.94). Eicosapentaenoic acid ethyl ester alone significantly reduced MACE (1 systematic review, RR=0.78) and cardiovascular mortality (2 systematic reviews; RRs of 0.82 and 0.82). In primary cardiovascular prevention, only statins showed consistent benefits on MACE (6 systematic reviews; median RR=0.75, IQR=0.73 to 0.78), cardiovascularall-cause mortality (7 systematic reviews, median RR=0.83, IQR=0.81 to 0.90), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.87 to 0.91). CONCLUSION: Statins have the most consistent evidence for the prevention of cardiovascular complications with a relative risk reduction of about 25% for MACE and 10% to 15% for mortality. The addition of ezetimibe, a PCSK9 inhibitor, or eicosapentaenoic acid ethyl ester to a statin provides additional MACE risk reduction but has no effect on all-cause mortality.

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.

PEER simplified chronic pain guideline: Management of chronic low back, osteoarthritic, and neuropathic pain in primary care.

OBJECTIVE: To develop a clinical practice guideline to support the management of chronic pain, including low back, osteoarthritic, and neuropathic pain in primary care. METHODS: The guideline was developed with an emphasis on best available evidence and shared decision-making principles. Ten health professionals (4 generalist family physicians, 1 pain management-focused family physician, 1 anesthesiologist, 1 physical therapist, 1 pharmacist, 1 nurse practitioner, and 1 psychologist), a patient representative, and a nonvoting pharmacist and guideline methodologist comprised the Guideline Committee. Member selection was based on profession, practice setting, and lack of financial conflicts of interest. The guideline process was iterative in identification of key questions, evidence review, and development of guideline recommendations. Three systematic reviews, including a total of 285 randomized controlled trials, were completed. Randomized controlled trials were included only if they reported a responder analysis (eg, how many patients achieved a 30% or greater reduction in pain). The committee directed an Evidence Team (composed of evidence experts) to address an additional 11 complementary questions. Key recommendations were derived through committee consensus. The guideline and shared decision-making tools underwent extensive review by clinicians and patients before publication. RECOMMENDATIONS: Physical activity is recommended as the foundation for managing osteoarthritis and chronic low back pain; evidence of benefit is unclear for neuropathic pain. Cognitive-behavioural therapy or mindfulness-based stress reduction are also suggested as options for managing chronic pain. Treatments for which there is clear, unclear, or no benefit are outlined for each condition. Treatments for which harms likely outweigh benefits for all or most conditions studied include opioids and cannabinoids. CONCLUSION: This guideline for the management of chronic pain, including osteoarthritis, low back pain, and neuropathic pain, highlights best available evidence including both benefits and harms for a number of treatment interventions. A strong recommendation for exercise as the primary treatment for chronic osteoarthritic and low back pain is made based on demonstrated long-term evidence of benefit. This information is intended to assist with, not dictate, shared decision making with patients.

Should the number of acute exacerbations in the previous year be used to guide treatments in COPD?

BACKGROUND: In contemporary management of chronic obstructive pulmonary disease (COPD), the frequent exacerbator phenotype, based on a 12-month history of acute exacerbation of COPD (AECOPD), is a major determinant of therapeutic recommendations. However, there is considerable debate as to the stability of this phenotype over time. METHODS: We used fundamental principles in time-to-event analysis to demonstrate that variation in the frequent exacerbator phenotype has two major sources: variability in the underlying AECOPD rate and randomness in the occurrence of individual AECOPDs. We re-analysed data from two large cohorts, the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study and the SubPopulations and InteRmediate OutcoMes In COPD Study (SPIROMICS), using a Bayesian model that separated these sources of variability. We then evaluated the stability of the frequent exacerbator phenotype based on these results. RESULTS: In both cohorts, the pattern of AECOPDs strongly supported the presence of an individual-specific underlying AECOPD rate which is stable over time (Bayes Factor less than 0.001). Despite this, the observed AECOPD rate can vary markedly year-to-year within individual patients. For those with an underlying rate of 0.8-3.1 events·year-1, the frequent exacerbator classification, based on the observed rate, changes more than 30% of the time over two consecutive years due to chance alone. This value increases to more than 45% for those with an underlying rate of 1.2-2.2 events·year-1. CONCLUSIONS: While the underlying AECOPD rate is a stable trait, the frequent exacerbator phenotype based on observed AECOPD patterns is unstable, so much so that its suitability for informing treatment decisions should be questioned. Whether evaluating AECOPD history over longer durations or using multivariate prediction models can result in more stable phenotyping needs to be evaluated.

PEER systematic review of randomized controlled trials: Management of chronic low back pain in primary care.

OBJECTIVE: To determine the proportion of chronic low back pain patients who achieve a clinically meaningful response from different pharmacologic and nonpharmacologic treatments. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, and gray literature search. STUDY SELECTION: Published randomized controlled trials (RCTs) that reported a responder analysis of adults with chronic low back pain treated with any of the following 15 interventions: oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs), exercise, acupuncture, spinal manipulation therapy, corticosteroid injections, acetaminophen, oral opioids, anticonvulsants, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors, cannabinoids, oral muscle relaxants, or topical rubefacients. SYNTHESIS: A total of 63 RCTs were included. There was moderate certainty that exercise (risk ratio [RR] of 1.71; 95% CI 1.37 to 2.15; number needed to treat [NNT] of 7), oral NSAIDs (RR = 1.44; 95% CI 1.17 to 1.78; NNT = 6), and SNRIs (duloxetine; RR = 1.25; 95% CI 1.13 to 1.38; NNT = 10) provide clinically meaningful benefits to patients with chronic low back pain. Exercise was the only intervention with sustained benefit (up to 48 weeks). There was low certainty that spinal manipulation therapy and topical rubefacients benefit patients. The benefit of acupuncture disappeared in higher-quality, longer (> 4 weeks) trials. Very low-quality evidence demonstrated that corticosteroid injections are ineffective. Patients treated with opioids had a greater likelihood of discontinuing treatment owing to an adverse event (number needed to harm of 5) than continuing treatment to derive any clinically meaningful benefit (NNT = 16), while those treated with SNRIs (duloxetine) had a similar likelihood of continuing treatment to attain benefit (NNT = 10) as those discontinuing the medication owing to an adverse event (number need to harm of 11). One trial each of anticonvulsants and topical NSAIDs found similar benefit to that of placebo. No RCTs of acetaminophen, cannabinoids, muscle relaxants, selective serotonin reuptake inhibitors, or tricyclic antidepressants met the inclusion criteria. CONCLUSION: Exercise, oral NSAIDs, and SNRIs (duloxetine) provide a clinically meaningful reduction in pain, with exercise being the only intervention that demonstrated sustained benefit after the intervention ended. Future high-quality trials that report responder analyses are required to provide a better understanding of the benefits and harms of interventions for patients with chronic low back pain.

PEER systematic review of randomized controlled trials: Management of chronic neuropathic pain in primary care.

OBJECTIVE: To determine the proportion of patients with neuropathic pain who achieve a clinically meaningful improvement in their pain with the use of different pharmacologic and nonpharmacologic treatments. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, and a gray literature search. STUDY SELECTION: Randomized controlled trials that reported a responder analysis of adults with neuropathic pain-specifically diabetic neuropathy, postherpetic neuralgia, or trigeminal neuralgia-treated with any of the following 8 treatments: exercise, acupuncture, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), topical rubefacients, opioids, anticonvulsant medications, and topical lidocaine. SYNTHESIS: A total of 67 randomized controlled trials were included. There was moderate certainty of evidence that anticonvulsant medications (risk ratio of 1.54; 95% CI 1.45 to 1.63; number needed to treat [NNT] of 7) and SNRIs (risk ratio of 1.45; 95% CI 1.33 to 1.59; NNT = 7) might provide a clinically meaningful benefit to patients with neuropathic pain. There was low certainty of evidence for a clinically meaningful benefit for rubefacients (ie, capsaicin; NNT = 7) and opioids (NNT = 8), and very low certainty of evidence for TCAs. Very low-quality evidence demonstrated that acupuncture was ineffective. All drug classes, except TCAs, had a greater likelihood of deriving a clinically meaningful benefit than having withdrawals due to adverse events (number needed to harm between 12 and 15). No trials met the inclusion criteria for exercise or lidocaine, nor were any trials identified for trigeminal neuralgia. CONCLUSION: There is moderate certainty of evidence that anticonvulsant medications and SNRIs provide a clinically meaningful reduction in pain in those with neuropathic pain, with lower certainty of evidence for rubefacients and opioids, and very low certainty of evidence for TCAs. Owing to low-quality evidence for many interventions, future high-quality trials that report responder analyses will be important to strengthen understanding of the relative benefits and harms of treatments in patients with neuropathic pain.

Experimental Measurement of Angular and Overlap Dependence of Conduction between Carbon Nanotubes of Identical Chirality and Diameter.

Measurement of the angular and overlap dependence of the conduction between two identical carbon nanotubes (CNTs), with the same diameter and chirality, has only been possible through theoretical calculations; however, our observation of increased resistance adjacent to the junction between two CNTs facilitates such measurements. Since electrical resistance was found to increase with increased diameter ratio, applying 10 V to one of dissimilar diameter CNTs results in cleavage at the junction. Manipulation of the resulting identical CNTs (created by cutting a single CNT) allows for the direct measurement of the angular and parallel overlap conduction. Angular (13° < θ < 63°) dependence shows two minima (22° and 44°) and a maximum at 30°, and conduction between parallel CNTs increases with overall tip separation but shows a sinusoidal relationship with contact length, consistent with the concept of atomic scale registry.

Masks for prevention of viral respiratory infections among health care workers and the public: PEER umbrella systematic review.

OBJECTIVE: To determine the effect of mask use on viral respiratory infection risk. DATA SOURCES: MEDLINE and the Cochrane Library. STUDY SELECTION: Randomized controlled trials (RCTs) included in at least 1 published systematic review comparing the use of masks with a control group, either in community or health care settings, on the risk of viral respiratory infections. SYNTHESIS: In total, 11 systematic reviews were included and 18 RCTs of 26 444 participants were found, 12 in the community and 6 in health care workers. Included studies had limitations and were deemed at high risk of bias. Overall, the use of masks in the community did not reduce the risk of influenza, confirmed viral respiratory infection, influenzalike illness, or any clinical respiratory infection. However, in the 2 trials that most closely aligned with mask use in real-life community settings, there was a significant risk reduction in influenzalike illness (risk ratio [RR] = 0.83; 95% CI 0.69 to 0.99). The use of masks in households with a sick contact was not associated with a significant infection risk reduction in any analysis, no matter if masks were used by the sick individual, the healthy family members, or both. In health care workers, surgical masks were superior to cloth masks for preventing influenzalike illness (RR = 0.12; 95% CI 0.02 to 0.98), and N95 masks were likely superior to surgical masks for preventing influenzalike illness (RR = 0.78; 95% CI 0.61 to 1.00) and any clinical respiratory infections (RR = 0.95; 95% CI 0.90 to 1.00). CONCLUSION: This systematic review found limited evidence that the use of masks might reduce the risk of viral respiratory infections. In the community setting, a possible reduced risk of influenzalike illness was found among mask users. In health care workers, the results show no difference between N95 masks and surgical masks on the risk of confirmed influenza or other confirmed viral respiratory infections, although possible benefits from N95 masks were found for preventing influenzalike illness or other clinical respiratory infections. Surgical masks might be superior to cloth masks but data are limited to 1 trial.

PEER umbrella systematic review of systematic reviews: Management of osteoarthritis in primary care.

OBJECTIVE: To determine how many patients with chronic osteoarthritis pain respond to various non-surgical treatments. DATA SOURCES: PubMed and the Cochrane Library. STUDY SELECTION: Published systematic reviews of randomized controlled trials (RCTs) that included meta-analysis of responder outcomes for at least 1 of the following interventions were included: acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, cannabinoids, counseling, exercise, platelet-rich plasma, viscosupplementation, glucosamine, chondroitin, intra-articular corticosteroids, rubefacients, or opioids. SYNTHESIS: In total, 235 systematic reviews were included. Owing to limited reporting of responder meta-analyses, a post hoc decision was made to evaluate individual RCTs with responder analysis within the included systematic reviews. New meta-analyses were performed where possible. A total of 155 RCTs were included. Interventions that led to more patients attaining meaningful pain relief compared with control included exercise (risk ratio [RR] of 2.36; 95% CI 1.79 to 3.12), intra-articular corticosteroids (RR = 1.74; 95% CI 1.15 to 2.62), SNRIs (RR = 1.53; 95% CI 1.25 to 1.87), oral NSAIDs (RR = 1.44; 95% CI 1.36 to 1.52), glucosamine (RR = 1.33; 95% CI 1.02 to 1.74), topical NSAIDs (RR = 1.27; 95% CI 1.16 to 1.38), chondroitin (RR = 1.26; 95% CI 1.13 to 1.41), viscosupplementation (RR = 1.22; 95% CI 1.12 to 1.33), and opioids (RR = 1.16; 95% CI 1.02 to 1.32). Preplanned subgroup analysis demonstrated no effect with glucosamine, chondroitin, or viscosupplementation in studies that were only publicly funded. When trials longer than 4 weeks were analyzed, the benefits of opioids were not statistically significant. CONCLUSION: Interventions that provide meaningful relief for chronic osteoarthritis pain might include exercise, intra-articular corticosteroids, SNRIs, oral and topical NSAIDs, glucosamine, chondroitin, viscosupplementation, and opioids. However, funding of studies and length of treatment are important considerations in interpreting these data.

Simplified guideline for prescribing medical cannabinoids in primary care.

OBJECTIVE: To develop a clinical practice guideline for a simplified approach to medical cannabinoid use in primary care; the focus was on primary care application, with a strong emphasis on best available evidence and a promotion of shared, informed decision making. METHODS: The Evidence Review Group performed a detailed systematic review of 4 clinical areas with the best evidence around cannabinoids: pain, nausea and vomiting, spasticity, and adverse events. Nine health professionals (2 generalist family physicians, 2 pain management-focused family physicians, 1 inner-city family physician, 1 neurologist, 1 oncologist, 1 nurse practitioner, and 1 pharmacist) and a patient representative comprised the Prescribing Guideline Committee (PGC), along with 2 nonvoting members (pharmacist project managers). Member selection was based on profession, practice setting, location, and lack of financial conflicts of interest. The guideline process was iterative through content distribution, evidence review, and telephone and online meetings. The PGC directed the Evidence Review Group to address and provide evidence for additional questions as needed. The key recommendations were derived through consensus of the PGC. The guideline was drafted, refined, and distributed to a group of clinicians and patients for feedback, then refined again and finalized by the PGC. RECOMMENDATIONS: Recommendations include limiting medical cannabinoid use in general, but also outline potential restricted use in a small subset of medical conditions for which there is some evidence (neuropathic pain, palliative and end-of-life pain, chemotherapy-induced nausea and vomiting, and spasticity due to multiple sclerosis or spinal cord injury). Other important considerations regarding prescribing are reviewed in detail, and content is offered to support shared, informed decision making. CONCLUSION: This simplified medical cannabinoid prescribing guideline provides practical recommendations for the use of medical cannabinoids in primary care. All recommendations are intended to assist with, not dictate, decision making in conjunction with patients.

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.

Are potentially clinically meaningful benefits misinterpreted in cardiovascular randomized trials? A systematic examination of statistical significance, clinical significance, and authors' conclusions.

BACKGROUND: While journals and reporting guidelines recommend the presentation of confidence intervals, many authors adhere strictly to statistically significant testing. Our objective was to determine what proportions of not statistically significant (NSS) cardiovascular trials include potentially clinically meaningful effects in primary outcomes and if these are associated with authors' conclusions. METHODS: Cardiovascular studies published in six high-impact journals between 1 January 2010 and 31 December 2014 were identified via PubMed. Two independent reviewers selected trials with major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death) as primary outcomes and extracted data on trial characteristics, quality, and primary outcome. Potentially clinically meaningful effects were defined broadly as a relative risk point estimate ≤0.94 (based on the effects of ezetimibe) and/or a lower confidence interval ≤0.75 (based on the effects of statins). RESULTS: We identified 127 randomized trial comparisons from 3200 articles. The primary outcomes were statistically significant (SS) favoring treatment in 21% (27/127), NSS in 72% (92/127), and SS favoring control in 6% (8/127). In 61% of NSS trials (56/92), the point estimate and/or lower confidence interval included potentially meaningful effects. Both point estimate and confidence interval included potentially meaningful effects in 67% of trials (12/18) in which authors' concluded that treatment was superior, in 28% (16/58) with a neutral conclusion, and in 6% (1/16) in which authors' concluded that control was superior. In a sensitivity analysis, 26% of NSS trials would include potential meaningful effects with relative risk thresholds of point estimate ≤0.85 and/or a lower confidence interval ≤0.65. CONCLUSIONS: Point estimates and/or confidence intervals included potentially clinically meaningful effects in up to 61% of NSS cardiovascular trials. Authors' conclusions often reflect potentially meaningful results of NSS cardiovascular trials. Given the frequency of potentially clinical meaningful effects in NSS trials, authors should be encouraged to continue to look beyond significance testing to a broader interpretation of trial results.

Lignes directrices simplifiées de PEER sur la douleur chronique: Gestion de la douleur chronique lombaire, arthrosique et neuropathique en première ligne.

OBJECTIF: Formuler des lignes directrices de pratique clinique pour soutenir la prise en charge de la douleur chronique, y compris la douleur lombaire, arthrosique et neuropathique, dans les soins primaires. MÉTHODES: Ces lignes directrices ont été élaborées en mettant l'accent sur les meilleures données probantes disponibles et sur les principes de décision partagée. Dix professionnels de la santé (4 omnipraticiens, 1 médecin de famille spécialisée en gestion de la douleur, 1 anesthésiste, 1 physiothérapeute, 1 pharmacienne, 1 infirmière praticienne et 1 psychologue), 1 représentant des patients, et 1 pharmacienne et spécialiste de la méthodologie des lignes directrices sans droit de vote composaient le comité des lignes directrices. Les membres ont été sélectionnés en fonction de leur profession, de leur milieu de pratique, et de l'absence d'un conflit d'intérêts de nature financière. Les lignes directrices sont le fruit d'un processus itératif incluant la détermination des questions clés, l'examen des données probantes et la formulation des recommandations des lignes directrices. Trois revues systématiques, totalisant 285 études avec répartition aléatoire et contrôlées ont été réalisées. Ces études n'étaient incluses que si elles avaient rapporté une analyse des répondants (p. ex. combien de patients ont obtenu un soulagement d'au moins 30% de la douleur). Le comité a confié à une équipe d'examen des données (composée de spécialistes des données probantes) la tâche de répondre à 11 autres questions complémentaires. Les principales recommandations découlent d'un consensus au sein du comité. Des cliniciens et des patients ont minutieusement examiné les lignes directrices et les outils de décision partagée avant leur publication. RECOMMANDATIONS: L'activité physique est recommandée comme fondement de la gestion de la douleur arthrosique et lombaire chronique; les données probantes étayant un bienfait ne sont pas concluantes dans le cas de la douleur neuropathique. La thérapie cognitivo-comportementale ou la réduction du stress basée sur la pleine conscience sont également suggérées comme des options pour gérer la douleur chronique. Les traitements pour lesquels le bienfait est clair, non concluant ou absent sont décrits sous chaque affection. Les traitements dont les préjudices surpassent probablement les bienfaits pour toutes les affections étudiées, ou la plupart d'entre elles, sont les opioïdes et les cannabinoïdes. CONCLUSION: Ces lignes directrices sur la gestion de la douleur chronique, y compris la douleur arthrosique, lombaire et neuropathique, met en lumière les meilleures données probantes disponibles, y compris les bienfaits et préjudices pour un certain nombre d'interventions thérapeutiques. Une forte recommandation en faveur de l'exercice comme principal traitement de la douleur arthrosique et lombaire chronique repose sur des données probantes ayant démontré un bienfait depuis longtemps. Cette information vise à contribuer au processus de décision partagée avec le patient et non à le dicter.

Vitamin D: A Narrative Review Examining the Evidence for Ten Beliefs.

Over the past decade, a large body of observational evidence has suggested an association between lower vitamin D status (25-hydroxyvitamin D) and multiple acute and chronic disorders, including cancer, multiple sclerosis, depression and respiratory tract infections. This evidence has fostered the hypothesis that increasing vitamin D intake may treat and prevent such disorders. Our objective was to perform a critical analysis of the highest-level evidence for ten common beliefs regarding vitamin D for the prevention of falls, fractures and respiratory tract infections, the reduction of cancer incidence/mortality and overall mortality, and the prevention or treatment of depression/mental well-being, rheumatoid arthritis and multiple sclerosis, as well as maximum dosing and regular testing. We searched the Cochrane Database of Systematic Reviews and PubMed (up to August 2014) for randomized controlled trials and systematic reviews/meta-analyses based on those studies. All searches were performed, all evidence reviewed and each section written by at least two authors. The evidence shows that vitamin D supplementation provides some benefit in fracture prevention (likely ∼10-15 % relative reduction), particularly at a dose ≥800 IU and with calcium; a likely benefit in the rate of falls, though it is less clear whether the number of fallers changes; and a possible small (∼5 %) relative reduction in mortality. Evidence does not support the use of vitamin D supplementation for the prevention of cancer, respiratory infections or rheumatoid arthritis. Similarly, evidence does not support vitamin D supplementation for the treatment of multiple sclerosis and rheumatoid arthritis or for improving depression/mental well-being. Regular testing of 25-hydroxyvitamin D is generally not required, and mega-doses (≥300,000 IU) appear to increase harms. Much of the evidence is at high risk of bias, with multiple flaws, including analyses of secondary endpoints, small and underpowered studies, inconsistent results and numerous other issues. Therefore, enthusiasm for a vitamin D panacea should be tempered.