"Application of five different strategies to define a cohort of patients with knee osteoarthritis in a large primary care database".

BACKGROUND: Electronic health records (EHR) are frequently used for epidemiological research including drug utilisation studies in a defined population such as the population with knee osteoarthritis (KOA). We sought to describe the process of defining a cohort of patients with KOA from a large UK primary care database and estimate the annual incidence of diagnosed KOA between 2000 and 2015. METHOD: This was a retrospective study using data from the clinical practice research datalink (CPRD). CPRD is a large primary care longitudinal electronic medical records' database that contains anonymous records of patients from general practices across United Kingdom. Five different cohort definition strategies were applied including symptoms-based or diagnosis-based strategies or a combination of both. To validate results, the annual incidence of KOA was estimated and compared to published data. RESULTS: The study defined 898,690 patients when symptoms-based strategy was applied, 137,541 patients when diagnosis based and 83,294 when a combination of both strategies were applied. The final cohort was defined using a diagnosis-based strategy that avoided overestimation (with symptoms-based definition) or underestimation (with a combination of symptoms and diagnosis). The incidence of KOA ranged from 1.33 per 1000 CPRD registrants in 2000, 1.76 in 2008 and 1.45 patients in 2015. CONCLUSION: This study logically/sensibly defined a cohort of patients with diagnosed KOA through the application of several strategies. This was an essential step to avoid subsequent over or underestimation of the prevalence of drug utilisation and the associated adverse clinical outcomes within primary care patients with KAO.

Acceptability of a proposed practice pharmacist-led review for opioid-treated patients with persistent pain: A qualitative study to inform intervention development.

Introduction: Regular review of patients prescribed opioids for persistent non-cancer pain (PCNP) is recommended but not routinely undertaken. The PROMPPT (Proactive clinical Review of patients taking Opioid Medicines long-term for persistent Pain led by clinical Pharmacists in primary care Teams) research programme aims to develop and test a pharmacist-led pain review (PROMPPT) to reduce inappropriate opioid use for persistent pain in primary care. This study explored the acceptability of the proposed PROMPPT review to inform early intervention development. Methods: Interviews (n = 15) and an online discussion forum (n = 31) with patients prescribed opioids for PCNP and interviews with pharmacists (n = 13), explored acceptability of a proposed PROMPPT review. A prototype PROMPPT review was then tested and refined through 3 iterative cycles of in-practice testing (IPT) (n = 3 practices, n = 3 practice pharmacists, n = 13 patients). Drawing on the Theoretical Framework of Acceptability (TFA), a framework was generated (including a priori TFA constructs) allowing for deductive and inductive thematic analysis to identify aspects of prospective and experienced acceptability. Results: Patients felt uncertain about practice pharmacists delivering the proposed PROMPPT review leading to development of content for the invitation letter for IPT (introducing the pharmacist and outlining the aim of the review). After IPT, patients felt that pharmacists were suited to the role as they were knowledgeable and qualified. Pharmacists felt that the proposed reviews would be challenging. Although challenges were experienced during delivery of PROMPPT reviews, pharmacists found that they became easier to deliver with time, practise and experience. Recommendations for optimisations after IPT included development of the training to include examples of challenging consultations. Conclusions: Uptake of new healthcare interventions is influenced by perceptions of acceptability. Exploring prospective and experienced acceptability at multiple time points during early intervention development, led to mini-optimisations of the prototype PROMPPT review ahead of a non-randomised feasibility study.

Designing a primary care pharmacist-led review for people treated with opioids for persistent pain: a multi-method qualitative study.

BACKGROUND: Opioids are frequently prescribed for persistent non-cancer pain despite limited evidence of long-term effectiveness and risk of harm. Evidence-based interventions to address inappropriate opioid prescribing are lacking. AIM: To explore perspectives of people living with persistent pain to understand barriers and facilitators in reducing opioids in the context of a pharmacist-led primary care review, and identify review components and features for optimal delivery. DESIGN & SETTING: Primary care multi-method qualitative study. METHOD: Adults with experience of persistent pain and taking opioids participated in semi-structured interviews (n=15, 73% female) and an online discussion forum (n=31). The Theoretical Domains Framework (TDF) provided a framework for data collection and thematic analysis, involving deductive analysis to TDF domains, inductive analysis within-domains to generate subthemes, and subtheme comparison to form across-domain overarching themes. The behaviour change technique taxonomy v.1 and motivational behaviour change technique classification system were used to systematically map themes to behaviour change techniques to identify potential review components and delivery features. RESULTS: 32 facilitator and barrier subthemes for patients reducing opioids were identified across 13 TDF domains. These combined into six overarching themes: learning to live with pain, opioid reduction expectations, assuming a medical model, pharmacist-delivered reviews, pharmacist-patient relationship and patient engagement. Subthemes mapped to 21 unique behaviour change techniques, yielding 17 components and five delivery features for the proposed PROMPPT review. CONCLUSION: This study generated theoretically-informed evidence for design of a practice pharmacist-led PROMPPT review. Future research will test the feasibility and acceptability of the PROMPPT review and pharmacist training.

Pandemic impact and adaptation to telehealth in chronic pain treatment providers across two COVID-19 pandemic years.

OBJECTIVES: The COVID-19 pandemic has had substantial impacts for both people using pain services and healthcare professionals delivering them. While the effects on service users have been studied, less is known about the effects for service providers. This study aimed to assess the impact of the pandemic on providers and the evolving role of telemedicine in treatment. DESIGN & METHODS: An electronic survey was distributed to the professional membership of the European Pain Federation (EFIC). The survey evaluated impact and adjustment to the COVID-19 pandemic separately across two pandemic years (March 2020-February 2021 and March 2021 to February 2022) and assessed worry about COVID-19, disruption and adjustment of pain services, and use of telehealth services. The change between the first and second pandemic years and the degree to which telehealth services were adopted was evaluated. RESULTS: From 149 respondents, 131 (88%) participants provided sufficient data to be included in the analysis. Both providers worry about the pandemic and service disruption decreased significantly from the first to the second year of the pandemic. Prior to the pandemic, only 30% of providers offered telehealth appointments but this increased to 64% and 83%, respectively, in the first and second years of the pandemic. CONCLUSIONS: Although provider worry and disruption to delivery of pain services decreased during the second year of COVID-19 pandemic, waiting times for appointments continued to lengthen. The pandemic has hastened the adoption of telemedicine in pain services and plans to continue telehealth services seem common.

Temporal trends and patterns in initial opioid prescriptions after hospital discharge following colectomy in England over 10 years.

BACKGROUND: While opioid analgesics are often necessary for the management of acute postoperative pain, appropriate prescribing practices are crucial to avoid harm. The aim was to investigate the changes in the proportion of people receiving initial opioid prescriptions after hospital discharge following colectomy, and describe trends and patterns in prescription characteristics. METHODS: This was a retrospective cohort study. Patients undergoing colectomy in England between 2010 and 2019 were included using electronic health record data from linked primary (Clinical Practice Research Datalink Aurum) and secondary (Hospital Episode Statistics) care. The proportion of patients having an initial opioid prescription issued in primary care within 90 days of hospital discharge was calculated. Prescription characteristics of opioid type and formulation were described. RESULTS: Of 95 155 individuals undergoing colectomy, 15 503 (16.3%) received opioid prescriptions. There was a downward trend in the proportion of patients with no prior opioid exposure (opioid naive) who had a postdischarge opioid prescription (P <0.001), from 11.4% in 2010 to 6.7% in 2019 (-41.3%, P <0.001), whereas the proportions remained stable for those prescribed opioids prior to surgery, from 57.5% in 2010 to 58.3% in 2019 (P = 0.637). Codeine represented 44.5% of all prescriptions and prescribing increased by 14.5% between 2010 and 2019. Prescriptions for morphine and oxycodone rose significantly by 76.6% and 31.0% respectively, while tramadol prescribing dropped by 48.0%. The most commonly prescribed opioid formulations were immediate release (83.9%), followed by modified release (5.8%) and transdermal (3.2%). There was a modest decrease in the prescribing of immediate-release formulations from 86.0% in 2010 to 82.0% in 2019 (P <0.001). CONCLUSION: Over the 10 years studied, there was a changing pattern of opioid prescribing following colectomy, with a decrease in the proportion of opioid-naive patients prescribed postdischarge opioids.

Estimating the cost and epidemiology of mild to severe chronic pain associated with osteoarthritis in England: a retrospective analysis of linked primary and secondary care data.

OBJECTIVE: Osteoarthritis (OA) affects 10% of adults in the UK. Despite over one-third of people with OA experiencing chronic pain, few studies have examined the population-level impact of chronic pain associated with OA. We compared resource-use and epidemiological outcomes in patients with mild, moderate and severe chronic OA-associated pain and matched controls without known OA. DESIGN: Retrospective, longitudinal, observational cohort study (July 2008 to June 2019). SETTING: Electronic records extracted from Clinical Practice Research Datalink GOLD primary care linked to Hospital Episode Statistics (HES). PARTICIPANTS: Patients (cases; n=23 016) aged ≥18 years with chronic OA-associated pain. Controls (n=23 016) without OA or chronic pain matched on age, sex, comorbidity burden, general practitioner practice and available HES data. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: Total healthcare resource use (HCRU), direct healthcare costs in 0-12, 12-24 and 24-36 months postindex. Secondary outcomes included incidence and prevalence of chronic OA-associated pain and pharmacological management. RESULTS: HCRU was consistently greater in cases versus controls for all resource categories during preindex and postindex periods. Across follow-up periods, resource use was greatest in patients with severe pain. In the first 12 months postindexing, mean total costs incurred by cases were four times higher versus matched controls (£256 vs £62); costs were approximately twice as high in cases vs controls for months 12-24 (£166 vs £86) and 24-36 (£150 vs £81; all p<0.0001). The incidence of new cases of chronic pain associated with OA was 2.64 per 1000 person-years; the prevalence was 1.4%. CONCLUSIONS: This study highlights the real-world cost of chronic pain associated with OA in cases versus matched controls. We included patients with mild, moderate and severe pain associated with OA, and showed HCRU in discrete 1-year time frames. The true economic burden of pain associated with OA is likely to be considerably higher when indirect costs are considered.

Chronic Low Back Pain with and without Concomitant Osteoarthritis: A Retrospective, Longitudinal Cohort Study of Patients in England.

Objective: Despite the high prevalence of chronic low back pain (CLBP) and osteoarthritis (OA), few estimates of the economic cost of these conditions in England have been published. The aim of the present analysis was to characterise the economic burden of moderate-to-severe pain associated with CLBP + OA and CLBP alone compared with general population-matched controls without CLBP or OA. The primary objective was to describe the total healthcare resource use (HCRU) and direct healthcare costs associated with the target patient populations. Secondary objectives were to describe treatment patterns and surgical procedures. Methods: This was a retrospective, observational cohort study of patients receiving healthcare indicative of moderate-to-severe chronic pain associated with CLBP, with or without OA. We used linked longitudinal data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics (HES). Patients (cases) were matched 1 : 1 with controls on age, sex, comorbidity burden, GP practice, and HES data availability. Results: The CLBP-alone cohort comprised 13 554 cases with CLBP and 13 554 matched controls; the CLBP + OA cohort comprised 7803 cases with both OA and CLBP and 7803 matched controls. Across all follow-up periods, patients with CLBP alone and those with CLBP + OA had significantly more GP consultations, outpatient attendances, emergency department visits, and inpatient stays than controls (all p < 0.0001). By 36 months after indexing, the mean (SD) per-patient total direct healthcare cost in the CLBP-alone cohort was £5081 (£5905) for cases and £1809 (£4451) for controls (p < 0.0001); in the CLBP + OA cohort, the mean (SD) per-patient total direct healthcare cost was £8819 (£7143) for cases and £2428 (£4280) for controls (p < 0.0001). Conclusion: Moderate-to-severe chronic pain associated with CLBP-with or without OA-has a substantial impact on patients and healthcare providers, leading to higher HCRU and costs versus controls among people with CLBP alone or together with OA.

Is there a difference in the analgesic response to intra-articular bupivacaine injection in people with knee osteoarthritis pain with or without central sensitisation? Protocol of a feasibility randomised controlled trial.

INTRODUCTION: Pain is the main symptom of osteoarthritis (OA) with approximately 50% of patients reporting moderate-to-severe pain. Total knee replacement (TKR) is the ultimate treatment option to alleviate pain in knee OA. Nevertheless, TKR does not provide complete relief for all as approximately 20% of patients experience chronic postoperative pain. Painful peripheral stimuli may alter the central nociceptive pathways leading to central sensitisation that can influence treatment response in patients with OA. Currently, there is no objective protocol for detecting whether a patient will respond to a given treatment. Therefore, there is a need for a better mechanistic understanding of individual factors affecting pain relief, consequently informing personalised treatment guidelines. The purpose of this research is to examine the feasibility of conducting a full-scale mechanistic clinical trial in painful knee OA investigating the analgesic response to intra-articular bupivacaine between those with or without evidence of central sensitisation. METHODS AND ANALYSIS: The Understanding Pain mechanisms in KNEE osteoarthritis (UP-KNEE) study is a feasibility, double-blinded, placebo-controlled randomised parallel study in participants with radiographically defined knee OA and with self-reported chronic knee pain. The study involves the following assessments: (1) a suite of psychometric questionnaires; (2) quantitative sensory testing; (3) magnetic resonance imaging (MRI) scan of the knee and brain; (4) a 6-minute walk test; and (5) an intra-articular injection of bupivacaine or placebo (sodium chloride 0.9%) into the index knee. Assessments will be repeated post intra-articular injection apart from the MRI scan of the knee. Our aim is to provide proof of concept and descriptive statistics to power a future mechanistic trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Health Research Authority (HRA) (REC: 20/EM/0287). Results will be disseminated via peer-reviewed journals and scientific conferences. The results will also be shared with lay audiences through relevant channels, such as Pain Centre Versus Arthritis website and patient advocacy groups. TRIAL REGISTRATION NUMBER: NCT05561010.

Health economic impact of moderate-to-severe chronic pain associated with osteoarthritis in England: a retrospective analysis of linked primary and secondary care data.

OBJECTIVE: Despite the prevalence of osteoarthritis (OA) in England, few studies have examined the health economic impact of chronic pain associated with OA. The aim of this study was to compare outcomes in patients with moderate-to-severe chronic pain associated with OA and matched controls without known OA. DESIGN: Retrospective, longitudinal, observational cohort study. SETTING: Electronic records extracted from the Clinical Practice Research Datalink GOLD primary care database linked to Hospital Episode Statistics (HES) data set. PARTICIPANTS: Patients (cases; n=5931) ≥18 years and with existing diagnosis of OA and moderate-to-severe pain associated with their OA, and controls matched on age, sex, comorbidity burden, general practitioner (GP) practice and availability of HES data. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: Total healthcare resource use (HCRU) and direct healthcare costs during 0-6, 0-12, 0-24 and 0-36 months of follow-up. Secondary outcomes measures included pharmacological management and time to total joint replacement. RESULTS: Patients with moderate-to-severe chronic pain associated with OA used significantly more healthcare services versus matched controls, reflected by higher HCRU and significantly higher direct costs. During the first 12 months' follow-up, cases had significantly more GP consultations, outpatient attendances, emergency department visits and inpatient stays than matched controls (all p<0.0001). Total mean costs incurred by cases during 0-12 months' follow-up were five times higher in cases versus controls (mean (SD): £4199 (£3966) vs £781 (£2073), respectively). Extensive cycling through pharmacological therapies was observed; among cases, 2040 (34.4%), 1340 (22.6%), 841 (14.2%), 459 (7.7%) and 706 (11.9%) received 1-5, 6-10, 11-15, 16-20 and >20 lines of therapy, respectively. CONCLUSIONS: This wide-ranging, longitudinal, observational study of real-world primary and secondary care data demonstrates the impact of moderate-to-severe chronic pain associated with OA in patients compared with matched controls. Further studies are required to fully quantify the health economic burden of moderate-to-severe pain associated with OA.

Frequency and impact of medication reviews for people aged 65 years or above in UK primary care: an observational study using electronic health records.

BACKGROUND: Medication reviews in primary care provide an opportunity to review and discuss the safety and appropriateness of a person's medicines. However, there is limited evidence about access to and the impact of routine medication reviews for older adults in the general population, particularly in the UK. We aimed to quantify the proportion of people aged 65 years and over with a medication review recorded in 2019 and describe changes in the numbers and types of medicines prescribed following a review. METHODS: We used anonymised primary care electronic health records from the UK's Clinical Practice Research Datalink (CPRD GOLD) to define a population of people aged 65 years or over in 2019. We counted people with a medication review record in 2019 and used Cox regression to estimate associations between demographic characteristics, diagnoses, and prescribed medicines and having a medication review. We used linear regression to compare the number of medicines prescribed as repeat prescriptions in the three months before and after a medication review. Specifically, we compared the 'prescription count' - the maximum number of different medicines with overlapping prescriptions people had in each period. RESULTS: Of 591,726 people prescribed one or more medicines at baseline, 305,526 (51.6%) had a recorded medication review in 2019. Living in a care home (hazard ratio 1.51, 95% confidence interval 1.40-1.62), medication review in the previous year (1.83, 1.69-1.98), and baseline prescription count (e.g. 5-9 vs 1 medicine 1.41, 1.37-1.46) were strongly associated with having a medication review in 2019. Overall, the prescription count tended to increase after a review (mean change 0.13 medicines, 95% CI 0.12-0.14). CONCLUSIONS: Although medication reviews were commonly recorded for people aged 65 years or over, there was little change overall in the numbers and types of medicines prescribed following a review. This study did not examine whether the prescriptions were appropriate or other metrics, such as dose or medicine changes within the same class. However, by examining the impact of medication reviews before the introduction of structured medication review requirements in England in 2020, it provides a useful benchmark which these new reviews can be compared with.

Analgesic utilization in people with knee osteoarthritis: A population-based study using primary care data.

PURPOSE: Osteoarthritis (OA) is a chronic painful condition that often affects large joints such as the knee. Treatment guidelines recommend paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. Antidepressants and anti-epileptic drugs (AEDs) are commonly prescribed for chronic noncancer pain conditions including OA, as an off-label use. This study describes analgesic utilization in patients with knee OA at population level using standard pharmaco-epidemiological methods. METHOD: This was a cross-sectional study between 2000 and 2014 using data from the U.K. Clinical Practice Research Datalink (CPRD). The use of antidepressants, AEDs, opioids, NSAIDs, and paracetamol was studied in adults with knee OA using the following measures: annual number of prescriptions, defined daily doses (DDD), oral morphine equivalent dose (OMEQ), and days' supply. RESULTS: In total, there were 8,944,381 prescriptions prescribed for 117,637 patients with knee OA during the 15-year period. There was a steady increase in the prescribing of all drug classes, except for NSAIDs, over the study period. Opioids were the most prevalent class prescribed in every study year. Tramadol was the most commonly prescribed opioid, with the number of DDD increasing from 0.11 to 0.71 DDDs per 1000 registrants in 2000 and 2014, respectively. The largest increase in prescribing was for AEDs, where the number of prescriptions increased from 2 to 11 per 1000 CPRD registrants. CONCLUSION: There was an overall increase in the prescribing of analgesics apart from NSAIDs. Opioids were the most frequently prescribed class; however, the greatest increase in prescribing between 2000 and 2014 was observed in AEDs.

Logic model for opioid safety in chronic non-malignant pain management, an in-depth qualitative study.

BACKGROUND: Opioids are commonly used for the management of chronic non-malignant pain in Pakistan; but there is a lack of literature around precursors or motivators in the use of opioids. AIM: The study holistically explored factors contributing towards the unsafe use of opioids and identifies strategies to overcome them. METHOD: Exploratory qualitative methods using interviews, focus groups and non-participant observational case studies were used. Interviews and focus groups were carried out face-to-face as well as virtually and observations were conducted in community pharmacies in Islamabad and Khyber Pukhtoon Khuwa province, Pakistan. Data were collected from 4 stakeholder groups; pharmacy policy makers (n = 11), people with chronic non-malignant pain (n = 14), doctors (n = 31) and community pharmacists (n = 36) by purposive critical case sampling method. Data were analysed inductively using reflexive thematic analysis and then deductively mapped to a social ecological framework. Non-participant observations were analysed using a cross case synthesis using explanation building technique. Data from all three methods were triangulated to develop a logic model. RESULTS: Identified factors at macro (regulation), meso (social perceptions of pain and opioids) and micro levels (uncontrolled pain, self-medication, health literacy) and strategies are presented holistically and were used to develop a logic model for the prevention and mitigation of factors currently causing unsafe use of opioids. CONCLUSION: The study provides an in-depth view of factors contributing towards diversion of pharmaceutical opioids and can help guide national and international policy makers in their future initiatives to promote safe use of opioids in the management of chronic non-malignant pain in Pakistan.

Phenotyping Post-COVID Pain as a Nociceptive, Neuropathic, or Nociplastic Pain Condition.

Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a "neuroanatomically plausible" distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive-emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.

Misappropriation of the 1986 WHO analgesic ladder: the pitfalls of labelling opioids as weak or strong.

Opioids have a vital role in alleviating pain from cancer and surgery. Despite good intentions, it is now recognised that the original WHO Cancer Pain Relief guidance from 1986, in which opioids were classified as either weak or strong, has been both inadvertently and purposefully misused, thereby contributing to harm from opioid use and misuse. However, the recommendation in the 2018 update of the WHO analgesic ladder that a combination of a high-potency opioid with simple analgesics is better than alternative analgesics for the maintenance of pain relief is also applicable to patients who require short-term opioids. Furthermore, because potential harm through opioid use and misuse is intrinsic to all opioids, whether weak or strong, we argue that the arbitrary classification of opioids either as weak or strong should be discontinued, as this description is not helpful to either prescribers or consumers.

System-level policies on appropriate opioid use, a multi-stakeholder consensus.

BACKGROUND: This consensus statement was developed because there are concerns about the appropriate use of opioids for acute pain management, with opposing views in the literature. Consensus statement on policies for system-level interventions may help inform organisations such as management structures, government agencies and funding bodies. METHODS: We conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level. We aimed to provide consensus statements for current developments and priorities for future developments. RESULTS: Twenty-five experts from a variety of fields with experience in acute pain management were invited to join a review panel, of whom 23 completed a modified Delphi survey of policies designed to improve the safety and quality of opioids prescribing for acute pain in the secondary care setting. Strong agreement, defined as consistent among> 75% of panellists, was observed for ten statements. CONCLUSIONS: Using a modified Delphi study, we found agreement among a multidisciplinary panel, including patient representation, on prioritisation of policies for system-level interventions, to improve governance, pain management, patient/consumers care, safety and engagement.

Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records.

BACKGROUND: Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants. OBJECTIVES: To compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments. DESIGN AND SETTING: Cohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018. PARTICIPANTS: 24 516 people diagnosed with depression, aged 18-99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine. MAIN OUTCOME MEASURES: Hospitalisation or death due to deliberate self-harm. Age-sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates. RESULTS: Standardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose. CONCLUSIONS: There was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm. CLINICAL IMPLICATIONS: Addressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm.

Evidence-based clinical practice guidelines on the management of pain in older people - a summary report.

OBJECTIVE: The objective of this study is to develop an update of the evidence-based guidelines for the management of pain in older people. DESIGN: Review of evidence since 2010 using a systematic and consensus approach is performed. RESULTS: Recognition of the type of pain and routine assessment of pain should inform the use of specific environmental, behavioural and pharmacological interventions. Individualised care plans and analgesic protocols for specific clinical situations, patients and health care settings can be developed from these guidelines. CONCLUSION: Management of pain must be considered as an important component of the health care provided to all people, regardless of their chronological age or severity of illness. By clearly outlining areas where evidence is not available, these guidelines may also stimulate further research. To use the recommended therapeutic approaches, clinicians must be familiar with adverse effects of treatment and the potential for drug interactions.