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      Do β-adrenoreceptor blocking drugs associate with reduced risk of symptomatic osteoarthritis and total joint replacement in the general population? A primary care-based, prospective cohort study using the Clinical Practice Research Datalink

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          To investigate if β-adrenoreceptor blocking drug (β-blocker) prescription reduces the risk of knee or hip osteoarthritis, total joint replacement and analgesic prescription.


          Primary care.

          Methods and analysis

          This is a cohort study using data from the Clinical Practice Research Datalink. Two separate analyses will be performed. Study 1 will be on the association between β-blocker prescription and incident knee/hip osteoarthritis. Inclusion criteria will be age ≥40 years. Exposed participants will be those with ≥2 continuous β-blocker prescriptions, and the index date will be the date of the first prescription of β-blocker. Unexposed participants will include up to four controls matched for age, sex, general practice surgery and propensity score for β-blocker prescription. Exclusion criteria will include contraindications to β-blockers, consultations for osteoarthritis or potent analgesic prescription before the index date. Outcomes will be knee osteoarthritis (primary outcome), hip osteoarthritis, knee pain and hip pain. Study 2 will be on the association between β-blocker prescription and total joint replacement and analgesic prescription in people with osteoarthritis. Inclusion criteria will be age ≥40 years, knee or hip osteoarthritis, and index date will be as in study 1. Unexposed participants will be as in study 1, additionally matched for consultation for knee or hip osteoarthritis prior to the index date. Exclusion criteria will include contraindications to β-blockers and osteoarthritis in other joints prior to the index date. Outcomes will be total knee replacement (primary outcome), total hip replacement and new analgesic prescription.

          Statistical analysis

          Kaplan-Meier curves will be plotted, and Cox proportional HRs and 95% CIs will be calculated. Stratified analysis will be performed by class of β-blocker, intrinsic sympathomimetic effect and indication(s) for prescription.

          Ethics and dissemination

          This study was ethically approved by the Independent Scientific Advisory Committee of the Medicines and Healthcare Authority (Ref 18_227R). The results of this study will be published in peer-reviewed journals and presented at conferences.


          This prospective cohort study will evaluate the analgesic potential of commonly used drugs for osteoarthritis pain.

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          Most cited references 48

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          Data Resource Profile: Clinical Practice Research Datalink (CPRD)

          The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.
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            Lifetime risk of symptomatic knee osteoarthritis.

            To estimate the lifetime risk of symptomatic knee osteoarthritis (OA), overall and stratified by sex, race, education, history of knee injury, and body mass index (BMI). The lifetime risk of symptomatic OA in at least 1 knee was estimated from logistic regression models with generalized estimating equations among 3,068 participants of the Johnston County Osteoarthritis Project, a longitudinal study of black and white women and men age >or=45 years living in rural North Carolina. Radiographic, sociodemographic, and symptomatic knee data measured at baseline (1990-1997) and first followup (1999-2003) were analyzed. The lifetime risk of symptomatic knee OA was 44.7% (95% confidence interval [95% CI] 40.0-49.3%). Cohort members with history of a knee injury had a lifetime risk of 56.8% (95% CI 48.4-65.2%). Lifetime risk rose with increasing BMI, with a risk of 2 in 3 among those who were obese. Nearly half of the adults in Johnston County will develop symptomatic knee OA by age 85 years, with lifetime risk highest among obese persons. These current high risks in Johnston County may suggest similar risks in the general US population, especially given the increase in 2 major risk factors for knee OA, aging, and obesity. This underscores the immediate need for greater use of clinical and public health interventions, especially those that address weight loss and self-management, to reduce the impact of having knee OA.
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              Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010.

              Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them.

                Author and article information

                BMJ Open
                BMJ Open
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                1 August 2019
                : 9
                : 8
                [1 ] departmentAcademic Rheumatology , University of Nottingham , Nottingham, UK
                [2 ] departmentDivision of Epidemiology and Public Health , University of Nottingham , Nottingham, UK
                [3 ] departmentNottingham NIHR BRC , University of Nottingham , Nottingham, UK
                [4 ] University of Bath , Bath, UK
                [5 ] departmentArthritis Research UK Primary Care Centre , Keele University , Keele, UK
                [6 ] departmentResearch Institute for Primary Care and Health Sciences , Keele University , Newcastle, UK
                Author notes
                [Correspondence to ] Dr Abhishek Abhishek; Abhishek.abhishek@
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

                Funded by: FundRef, Research Trainees Coordinating Centre;
                Award ID: NIHR-RP-2014-04-02
                Funded by: FundRef, National Institute for Health Research;
                Award ID: PB-PG-0816-20025
                Custom metadata


                analgesia, anti-hypertensives, total joint replacement, pain, osteoarthritis


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