Antidepressants for hip and knee osteoarthritis.

BACKGROUND: Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has resulted in the investigation of medications affecting pain processing with central effects. Antidepressants contribute to pain management in other conditions where pain sensitisation is present. OBJECTIVES: To assess the benefits and harms of antidepressants for the treatment of symptomatic knee and hip osteoarthritis in adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was January 2021. SELECTION CRITERIA: We included randomised controlled trials of adults with osteoarthritis that compared use of antidepressants to placebo or alternative comparator. We included trials that focused on efficacy (pain and function), treatment-related adverse effects and had documentation regarding discontinuation of participants. We excluded trials of less than six weeks of duration or had participants with concurrent mental health disorders. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Major outcomes were pain; responder rate; physical function; quality of life; and proportion of participants who withdrew due to adverse events, experienced any adverse events or had serious adverse events. Minor outcomes were proportion meeting the OARSI (Osteoarthritis Research Society International) Response Criteria, radiographic joint structure changes and proportion of participants who dropped out of the study for any reason. We used GRADE to assess certainty of evidence. MAIN RESULTS: Nine trials (2122 participants) met the inclusion criteria. Seven trials examined only knee osteoarthritis. Two also included participants with hip osteoarthritis. All trials compared antidepressants to placebo, with or without non-steroidal anti-inflammatory drugs. Trial sizes were 36 to 388 participants. Most participants were female, with mean ages of 54.5 to 65.9 years. Trial durations were 8 to 16 weeks. Six trials examined duloxetine. We combined data from nine trials in meta-analyses for knee and hip osteoarthritis. One trial was at low risk of bias in all domains. Five trials were at risk of attrition and reporting bias. High-certainty evidence found that antidepressants resulted in a clinically unimportant improvement in pain compared to placebo. Mean reduction in pain (0 to 10 scale, 0 = no pain) was 1.7 points with placebo and 2.3 points with antidepressants (mean difference (MD) -0.59, 95% confidence interval (CI) -0.88 to -0.31; 9 trials, 2122 participants). Clinical response was defined as achieving a 50% or greater reduction in 24-hour mean pain. High-certainty evidence demonstrated that 45% of participants receiving antidepressants had a clinical response compared to 28.6% receiving placebo (RR 1.55, 95% CI 1.32 to 1.82; 6 RCTs, 1904 participants). This corresponded to an absolute improvement in pain of 16% more responders with antidepressants (8.9% more to 26% more) and a number needed to treat for an additional beneficial effect (NNTB) of 6 (95% CI 4 to 11). High-certainty evidence showed that the mean improvement in function (on 0 to 100 Western Ontario and McMaster Universities Arthritis Index, 0 = best function) was 10.51 points with placebo and 16.16 points with antidepressants (MD -5.65 points, 95% CI -7.08 to -4.23; 6 RCTs, 1909 participants). This demonstrates a small, clinically unimportant response. Moderate-certainty evidence (downgraded for imprecision) showed that quality of life measured using the EuroQol 5-Dimension scale (-0.11 to 1.0, 1.0 = perfect health) improved by 0.07 points with placebo and 0.11 points with antidepressants (MD 0.04, 95% CI 0.01 to 0.07; 3 RCTs, 815 participants). This is clinically unimportant. High-certainty evidence showed that total adverse events increased in the antidepressant group (64%) compared to the placebo group (49%) (RR 1.27, 95% CI 1.15 to 1.41; 9 RCTs, 2102 participants). The number needed to treat for an additional harmful outcome (NNTH) was 7 (95% CI 5 to 11). Low-certainty evidence (downgraded twice for imprecision for very low numbers of events) found no evidence of a difference in serious adverse events between groups (RR 0.94, 95% CI 0.46 to 1.94; 9 RCTs, 2101 participants). The NNTH was 1000.  Moderate-certainty evidence (downgraded for imprecision) showed that 11% of participants receiving antidepressants withdrew from trials due to an adverse event compared to 5% receiving placebo (RR 2.15, 95% CI 1.56 to 2.97; 6 RCTs, 1977 participants). The NNTH was 17 (95% CI 10 to 35). AUTHORS' CONCLUSIONS: There is high-certainty evidence that use of antidepressants for knee osteoarthritis leads to a non-clinically important improvement in mean pain and function. However, a small number of people will have a 50% or greater important improvement in pain and function. This finding was consistent across all trials. Pain in osteoarthritis may be due to a variety of causes that differ between individuals. It may be that the cause of pain that responds to this therapy is only present in a small number of people. There is moderate-certainty evidence that antidepressants have a small positive effect on quality of life with heterogeneity between trials. High-certainty evidence indicates antidepressants result in more adverse events and moderate-certainty evidence indicates more withdrawal due to adverse events. There was little to no difference in serious adverse events (low-certainty evidence due to low numbers of events). This suggests that if antidepressants were being considered, there needs to be careful patient selection to optimise clinical benefit given the known propensity for adverse events with antidepressant use. Future trials should include alternative antidepressant agents or phenotyping of pain in people with osteoarthritis, or both.

Antiphospholipid syndrome: a clinical review.

Antiphospholipid syndrome is characterised by recurrent thrombosis (arterial, venous, microvascular) and/or pregnancy complications in the presence of persistent antiphospholipid antibodies (lupus anticoagulant, anti-ß2-glycoprotein 1 and anticardiolipin). It can be a primary disease or associated with another autoimmune disease (especially systemic lupus erythematosis). Testing for antiphospholipid antibodies should be considered in patients < 50 years of age with unprovoked venous or arterial thromboembolism, thrombosis at unusual sites or pregnancy complications. The mainstay of treatment is antithrombotic therapy and recommendations vary based on arterial, venous or pregnancy complications. If associated with systemic lupus erythematosis, hydroxychloroquine is recommended both as primary and secondary prophylaxis. Antithrombotic treatment is gold standard and effective.

Patients' perceived health information needs in inflammatory arthritis: A systematic review.

OBJECTIVES: To identify the breadth of the literature regarding patients' perceived health information needs related to inflammatory arthritis care. METHODS: A systematic scoping review of MEDLINE, EMBASE, CINAHL and PsycINFO was performed to identify relevant articles (1990 -2016) examining patients' perceived needs relating to health information in inflammatory arthritis. Data and themes were identified and categorised and risk of bias assessed. RESULTS: Twenty nine studies (11 quantitative, 14 qualitative and 4 mixed methods) from 4121 identified articles were relevant for inclusion. Most focussed on rheumatoid arthritis. Key findings included: (1) Reasons for seeking health information often focussed on gaining ownership over their condition and facilitating self-management. (2) Demographic differences in information needs were inconsistent, but women and younger patients generally reported more needs. (3) Desired information content was broad, and included targeted and practical information covering disease treatment and psychosocial wellbeing. (4) Preferred information delivery method was consultation with a Rheumatologist; however group sessions had advantages for psychosocial issues while written information provided useful supplementation. (5) Barriers to meeting health information needs were around timely access. CONCLUSIONS: Patients with inflammatory arthritis have high information needs, desiring practical and individualised information. When developing strategies to meet patients' information needs, aligning patient expectations with delivery methods that are accessible, cost-effective and flexible may help to optimize patient outcomes.

Patient-perceived health service needs in inflammatory arthritis: A systematic scoping review.

BACKGROUND: Care that is patient-centred is more likely to be sustainable and associated with improved health outcomes. This approach to care requires an understanding of patients' health service needs, yet few studies have directly investigated the perceived health service needs of people with inflammatory arthritis. OBJECTIVES: To systematically identify the existing literature relating to patient perceived health service needs for inflammatory arthritis. METHODS: A systematic review of MEDLINE, EMBASE, CINAHL, and PsycINFO was conducted (1990-2016). Studies examining patients' perceived needs relating to health services for inflammatory arthritis were identified. Descriptive data regarding study design and methodology were extracted and risk of bias assessed. Findings were collated and categorized thematically. RESULTS: In total, 27 of 1405 (16 qualitative, 9 quantitative, and 2 mixed-methods) studies were relevant. The main areas of perceived need related to (1) Communication: consumers wanted clear, empathic communication, and to be involved with decision-making. (2) Characteristics of ongoing care: adequate consultation length with continuity and timely care were valued. (3) Factors influencing care-seeking included individual attitudes, disease severity, finances and family expectations. (4) Allied health and complementary and alternative medicines (CAM) were perceived as useful by many. The reporting of CAM use to doctors was variable, with several factors contributing to under-reporting. CONCLUSIONS: This review identified patients' perceived needs for better communication with their health providers, the heterogeneity of influences determining when care is sought and preferences regarding non-pharmacologic therapies. Aligning patients' perceived needs with evidence-based therapy for people with inflammatory arthritis will be important in optimizing patient outcomes.

Incidence of normal white cell count and C-reactive protein in adults with acute appendicitis.

BACKGROUND: Normal C-reactive protein (CRP) and white cell count (WCC) are often used to exclude a diagnosis of acute appendicitis in the Emergency Department (ED). Retrospective review of 281 adult patients with acute appendicitis was performed to study the incidence of normal CRP and WCC on admission and examine any possible predisposing factors. METHOD: Retrospective analysis of patient clinical records yielded CRP, WCC, operative diagnosis, time of symptom onset, imaging results and history and examination features. Case-control analysis was performed with patients with normal CRP and WCC considered the case group and those with raised CRP or WCC considered controls. Groups were compared using Mann-Whitney U-test and chi-squared analysis. RESULTS: Of 281 consecutive patients with histologically proven appendicitis, 24 (8.54%) had normal CRP and WCC on presentation to ED. There were no significant differences in age, sex or time to blood collection between groups. Three patients had normal WCC and CRP and an Alvarado score of 4 or less on presentation. Three patients had persistently normal CRP and WCC on repeated testing. There was a trend towards earlier presentation in patients with normal CRP and WCC with 75.0% versus 58.4% presenting within 24 h of symptom onset (OR 2.14, P = 0.112). CONCLUSION: Acute appendicitis remains diagnostically challenging and cannot be excluded on the basis of normal CRP and WCC. Serial clinical and biochemical assessment is warranted in patients with acute abdominal pain, particularly in those presenting early after symptom onset.