Background: Osteoarthritis of the hands is a prevalent musculoskeletal disease with a considerable effect on patients’ lives, but knowledge and research results in the field of hand osteoarthritis ...are limited. Therefore, the Disease Characteristics in Hand OA (DICHOA) initiative was founded in early 2005 with the aim of addressing key issues and facilitating research into hand osteoarthritis. Objective: To review and discuss current knowledge on hand osteoarthritis with regard to aetiopathogenesis, diagnostic criteria, biomarkers and clinical outcome measures. Methods: Recommendations were made based on a literature review. Results: Outcomes of hand osteoarthritis should be explored, including patient perspective on the separate components of disease activity, damage and functioning. All imaging techniques should be cross-validated for hand osteoarthritis with clinical status, including disease activity, function and performance, biomarkers and long-term outcome. New imaging modalities are available and need scoring systems and validation. The role of biomarkers in hand osteoarthritis has to be defined. Conclusion: Future research in hand osteoarthritis is warranted.
We conducted a systematic literature review to assess the adverse event (AE) profile of paracetamol.
We searched Medline and Embase from database inception to 1 May 2013. We screened for ...observational studies in English, which reported mortality, cardiovascular, gastrointestinal (GI) or renal AEs in the general adult population at standard analgesic doses of paracetamol. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation. Pooled or adjusted summary statistics were presented for each outcome.
Of 1888 studies retrieved, 8 met inclusion criteria, and all were cohort studies. Comparing paracetamol use versus no use, of two studies reporting mortality one showed a dose-response and reported an increased relative rate of mortality from 0.95 (0.92 to 0.98) to 1.63 (1.58 to 1.68). Of four studies reporting cardiovascular AEs, all showed a dose-response with one reporting an increased risk ratio of all cardiovascular AEs from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study reporting GI AEs reported a dose-response with increased relative rate of GI AEs or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Of four studies reporting renal AEs, three reported a dose-response with one reporting an increasing OR of ≥30% decrease in estimated glomerular filtration rate from 1.40 (0.79 to 2.48) to 2.19 (1.4 to 3.43).
Given the observational nature of the data, channelling bias may have had an important impact. However, the dose-response seen for most endpoints suggests a considerable degree of paracetamol toxicity especially at the upper end of standard analgesic doses.
Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 ...independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.
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•A multicohort study identifies 52 previously unknown osteoarthritis genetic risk variants•Similarities and differences in osteoarthritis genetic risk depend on joint sites•Osteoarthritis genetic components are associated with pain-related phenotypes•High-confidence effector genes highlight potential targets for drug intervention
A multicohort genome-wide association meta-analysis of osteoarthritis highlights the impact of joint site types on the features of genetic risk variants and the link between osteoarthritis genetics and pain-related phenotypes, pointing toward potential targets for therapeutic intervention.
Objective: To quantify the direct and indirect effects of fetal (position in family, weight, and social class at birth), childhood (breast feeding, growth, infections, and social class in childhood, ...age at menarche), and adult life (social class, alcohol consumption, smoking, diet, reproductive history, exercise, hormone replacement therapy use), and adult size (height, weight) on bone health at age 49–51 years, as measured by bone mineral density, total scanned bone area of the hip and lumbar spine, and femoral neck shaft angle. Design: Follow up study of the Newcastle thousand families birth cohort established in 1947. Participants: 171 men and 218 women who attended for dual energy x ray absorptiometry scanning. Main results: Fetal life explained around 6% of variation in adult bone mineral density for men, but accounted for less than 1% for women. Adult lifestyle, including effects mediated through adult weight accounted for over 10% of variation in density for men and around 6% for women. Almost half of variation in bone area for men was explained by early life. However, most of this was mediated through achieved adult height and weight. In women, less than 5% of variation in bone area was accounted for by early life, after adjusting for adult size. Most of the variation in each of the indicators for both sexes was contributed either directly or indirectly by adult lifestyle and achieved adult height and weight. Conclusions: The effect of fetal life on bone health in adulthood seems to be mediated through achieved adult height.
Objective
To determine whether intensive combinations of conventional synthetic disease‐modifying antirheumatic drugs (csDMARDS) achieve similar clinical benefits more cheaply than high‐cost ...biologics such as tumor necrosis factor inhibitors (TNFi) in patients with active rheumatoid arthritis (RA) whose illness has failed to respond to methotrexate and another DMARD.
Methods
We used within‐trial cost‐effectiveness and cost‐utility analyses from health and social care and 2 societal perspectives. Participants were recruited into an open‐label, 12‐month, pragmatic, randomized, multicenter, 2‐arm, noninferiority trial in 24 rheumatology clinics in England and Wales. Costs were linked with the Health Assessment Questionnaire (HAQ; primary outcome) and quality‐adjusted life years derived from 2 measures (Short‐Form 36 health survey and EuroQol 5‐domain 3‐level instrument).
Results
In total, 205 participants were recruited, 104 in the csDMARD arm and 101 in the TNFi arm. Participants in the csDMARD arm with poor response at 6 months were offered TNFi; 46 participants (44%) switched. Relevant cost and outcome data were available for 93% of participants at 6‐month follow‐up and for 91–92% of participants at 12‐month follow‐up. The csDMARD arm had significantly lower total costs from all perspectives (6‐month health and social care adjusted mean difference –£3,615 95% confidence interval (95% CI) –4,104, –3,182; 12‐month health and social care adjusted mean difference –£1,930 95% CI –2,599, –1,301). The HAQ score showed benefit to the csDMARD arm at 12 months (–0.16 95% CI –0.32, –0.01); other outcomes/follow‐ups showed no differences.
Conclusion
Starting treatment with csDMARDs, rather than TNFi, achieves similar outcomes at significantly lower costs. Patients with active RA and who meet the National Institute for Health and Care Excellence criteria for expensive biologics can be treated with combinations of intensive csDMARDs in a cost‐effective manner.
Objective
To show the safety and efficacy of subcutaneous (SC) methotrexate (MTX) compared to oral MTX, alternative disease‐modifying antirheumatic drugs (DMARDs) monotherapy, biologic monotherapy, ...and combinations (conventional and biologic combination groups) in routine clinical practice.
Methods
Clinical and laboratory data were retrospectively analyzed for rheumatology clinic attendances at a large Northeast England hospital trust between January 2014 and January 2018. Rates of adverse events and stop events (transaminitis serum alanine aminotransferase level of >80 units/liter or neutropenia neutrophil count of <2.0 × 109/liter) were calculated, with adjustment for duration of DMARD exposure.
Results
In the present study, 8,394 patients received DMARDs, with 2,093 patients receiving oral MTX and 949 patients receiving SC MTX. The median dose was 15 mg (interquartile range IQR 10–20 mg) for oral MTX, and 20 mg (IQR 15–25 mg) for SC MTX (P < 0.0001). Continuation rates were higher for SC MTX therapy when adjusted for follow‐up duration, with a rate ratio (RR) of 1.54 (95% confidence interval 95% CI 1.40–1.70) (P < 0.0001). For the time period assessed, 2,382 patients experienced 4,358 adverse events, with 1,711 incidents of transaminitis and 2,647 incidents of neutropenia recorded. Significantly fewer adverse events were observed in patients who received SC MTX monotherapy versus those who received biologic and combination DMARD therapies (P < 0.01). Compared to oral MTX, SC MTX was associated with a nonsignificant trend toward lower rates of neutropenia, but only a slightly higher rate of transaminitis (RR 1.26 95% CI 1.07–1.48) (P = 0.006), despite significantly higher doses of MTX.
Conclusion
Subcutaneous MTX is safe in routine clinical practice. This is the largest study yet reported on SC MTX and provides observational data that SC MTX is continued longer and better tolerated in patients compared to other therapy groups, especially oral MTX.
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