Burden of osteoarthritis in India and its states, 1990-2019: findings from the Global Burden of disease study 2019.

OBJECTIVE: To describe the burden of osteoarthritis (OA) in India from 1990 to 2019. DESIGN: Data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The burden of OA -knee OA, hip OA, hand OA, and other OA- was estimated for India and its states from 1990 to 2019 through a systematic analysis of prevalence, incidence, years lived with disability (YLD), and disability-adjusted life years (DALY) using methods reported in GBD 2019 study. RESULT: Around 23.46 million individuals in India had OA in 1990; this increased to 62.35 million in 2019. The age-standardised prevalence of OA increased from 4,895 (95% uncertainty interval (UI):4,420-5,447) in 1990-5313 (95%UI:4,799-5,898) in 2019, per 100,000 persons. Similarly, DALYs due to OA increased from 0.79 million (95%UI:0.40-1.55) to 2.12 million (95%UI:1.07-4.23); while age-standardised DALYs increased from 164 (95%UI:83-325) to 180 (95%UI:91-361) per 100,000 persons from 1990 to 2019. OA was the 20th most common cause of YLDs in India in 2019, accounting for 1.48% (95%UI:0.88-2.78) of all YLDs; increasing from 23rd most common cause in 1990 (1.25%(95%UI:0.74-2.34)). Knee OA was the most common form of OA, followed by hand OA. The prevalence, incidence, and DALYs for OA and knee OA were consistently higher in females than males. CONCLUSION: The burden and impact of OA in India are substantial and is increasing. Adopting suitable control and preventive community measures to reduce modifiable risk factors (obesity, injuries, occupational stress) are needed to reduce the current and future burden of OA in India.

Association between osteoarthritis-related serum biochemical markers over 11 years and knee MRI-based imaging biomarkers in middle-aged adults.

OBJECTIVE: To describe the associations between osteoarthritis (OA)-related biochemical markers (COMP, MMP-3, HA) and MRI-based imaging biomarkers in middle-aged adults over 10-13 years. METHODS: Blood serum samples collected during the Childhood Determinants of Adult Health (CDAH)-1 study (year:2004-06; n = 156) and 10-13 year follow-up at CDAH-3 (n = 167) were analysed for COMP, MMP-3, and HA using non-isotopic ELISA. Knee MRI scans obtained during the CDAH-knee study (year:2008-10; n = 313) were assessed for cartilage volume and thickness, subchondral bone area, cartilage defects, and BML. RESULTS: In a multivariable linear regression model describing the association of baseline biochemical markers with MRI-markers (assessed after 4-years), we found a significant negative association of standardised COMP with medial femorotibial compartment cartilage thickness (ß:-0.070; 95%CI:-0.138,-0.001), and standardised MMP-3 with patellar cartilage volume (ß:-141.548; 95%CI:-254.917,-28.179) and total bone area (ß:-0.729; 95%CI:-1.340,-0.118). In multivariable Tobit regression model, there was a significant association of MRI-markers with biochemical markers (assessed after 6-9 years); a significant negative association of patellar cartilage volume (ß:-0.001; 95%CI:-0.002,-0.00004), and total bone area (ß:-0.158; 95%CI-0.307,-0.010) with MMP-3, and total cartilage volume (ß:-0.001; 95%CI:-0.001,-0.0001) and total bone area (ß:-0.373; 95%CI:-0.636,-0.111) with COMP. No significant associations were observed between MRI-based imaging biomarkers and HA. CONCLUSION: COMP and MMP-3 levels were negatively associated with knee cartilage thickness and volume assessed 4-years later, respectively. Knee cartilage volume and bone area were negatively associated with COMP and MMP-3 levels assessed 6-9 years later. These results suggest that OA-related biochemical markers and MRI-markers are interrelated in early OA.

Development and validation of the Flare-OA questionnaire for measuring flare in knee and hip osteoarthritis.

OBJECTIVE: Ability to assess flares in osteoarthritis (OA) of the knee and hip (KHOA) is important in clinical care and research. Using mixed methods, we developed a self-reported instrument measuring flare and assessed its psychometric properties. METHODS: We constructed questionnaire items from semi-structured interviews and a focus group (patients, clinicians) by using a dual-language (English-French) approach. A Delphi consensus method was used to select the most relevant items. Patients with OA from Australia, France and the United States completed the preliminary Flare-OA, HOOS, KOOS and Mini-OAKHQOL questionnaires online. We used a factor analysis and content approach to reduce items and determine structural validity. We tested the resulting questionnaire (score 0-100) for internal consistency, convergent and known-groups validity. RESULTS: Initially, 180 statements were generated and reduced to 33 items in five domains (response 0 = not at all, to 10 = absolutely) by Delphi consensus (50 patients, 116 professionals) and an expert meeting. After 398 patients (mean [SD] age 64 [8.5] years, 70.4% female, 86.7% knee OA) completed the questionnaire, it was reduced to 19 items by factor analysis and a content approach (RMSEA = 0.06; CFI = 0.96; TLI = 0.94). The Cronbach's alpha was >0.9 for the five domains and the whole questionnaire. Correlation coefficients between Flare-OA and other instrument scores were as predicted, supporting construct validity. The difference in Flare-OA score between patients with and without flare (31.8) largely exceeded 2 SEM (10.2). CONCLUSION: Flare-OA is a valid and reliable patient-reported instrument for assessing the occurrence and severity of flare in patients with KHOA in clinical research.

Sex differences in recovery of quality of life 12 months post-fracture in community-dwelling older adults: analyses of the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS).

In this study of 695 Australian older adults (aged ≥50 years), we found that men and women had a similar trajectory of health-related quality of life (HRQoL) recovery following fragility fracture at any skeletal site. These results provide us with critical knowledge that improves our understanding of health outcomes post-fracture. INTRODUCTION: Mortality is higher in men than that in women following a fragility fracture, but it is unclear whether recovery of patient-reported outcomes such as health-related quality of life (HRQoL) differs between sexes. This study aimed to identify sex differences in HRQoL recovery 12 months post-fracture. METHODS: Data were from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS). Participants recruited to AusICUROS were adults aged ≥50 years who sustained a fragility fracture. HRQoL was measured using the EQ-5D-3L at three time-points post-fracture: within 2 weeks (including pre-fracture recall) and at 4 and 12 months. Multivariate logistic regression analyses were undertaken, adjusting for confounders including age, education, income, and healthcare utilization post-fracture. RESULTS: Overall, 695 AusICUROS participants (536 women, 77.1%) were eligible for analysis with fractures at the hip (n = 150), distal forearm (n = 261), vertebrae (n = 61), humerus (n = 52), and other skeletal sites (n = 171). At the time of fracture, men were younger, reported a higher income, and were more likely to be employed, compared with women. For all fracture sites combined, there were no differences between men and women in recovery to pre-fracture HRQoL at 12-month follow-up (adjusted OR = 1.09; 95% CI: 0.75-1.61). When stratified by fracture site, no significant sex differences were seen for hip (OR = 1.02; 95% CI: 0.42-2.52), distal forearm (OR = 1.60; 95% CI: 0.68-3.78), vertebral (OR = 2.28; 95% CI: 0.61-8.48), humeral (OR = 1.62; 95% CI: 0.16-9.99), and other fractures (OR = 1.00; 95% CI: 0.44-2.26). CONCLUSION: Community-dwelling men and women who survived the 12 months following fragility fracture had a similar trajectory of HRQoL recovery at any skeletal site.

Can pain flares in knee osteoarthritis be predicted?

Objectives: This study examined whether risk factors for knee osteoarthritis (KOA) pain such as age, gender, body mass index (BMI), baseline pain, and other putative risk factors for knee osteoarthritis pain flares (KOAF) (e.g. knee buckling, injury, mood/stress/social support scores, and footwear) could predict KOAF.Method: People with KOA and previous history of KOAF were selected from a 3 month web-based longitudinal study. KOAF was defined as an increase of ≥ 2 points on a numeric rating scale (compared with background pain) which resolved within 20 days. Predictors assessed at baseline were gender, age, duration of KOA, BMI, pain, knee injury (7 days before), knee buckling (2 days before), Lubben Social Support, Knee Injury and Osteoarthritis Outcome Score, Intermittent and Constant Osteoarthritis Pain score (ICOAP), Positive/Negative Affect Score, and footwear stability/heel height. Outcome was occurrence of any KOAF during the ensuing 30 days. The combined ability of the above variables to predict occurrence of any KOAF was evaluated by multiple logistic regression with a 10-fold cross-validation method to build and internally validate the model. Variables that assessed similar domains were eliminated using receiver operating characteristics curve assessment for best fit.Results: Complete data were available for 313 people (66.6% female, mean ± sd age 62.3 ± 8.2 years, BMI 29.7 ± 6.5 kg/m2). Increasing age, years of osteoarthritis, BMI, background/worst levels of pain, knee injury, knee buckling, ICOAP, and footwear category/heel height significantly predicted the occurrence of KOAF during the following 30 days, with an area under the curve of 0.73 (95% confidence interval 0.67-0.80).Conclusion: A combination of risk factors assessed at baseline, including exposures with potential to vary, successfully predicts the KOAF in the ensuing 30 days.

Association of childhood adiposity measures with adulthood knee cartilage defects and bone marrow lesions: a 25-year cohort study.

OBJECTIVE: To describe the associations between childhood adiposity measures and adulthood knee cartilage defects and bone marrow lesions (BMLs) measured 25 years later. METHODS: 327 participants from the Australian Schools Health and Fitness Survey (ASHFS) of 1985 (aged 7-15 years) were followed up 25 years later (aged 31-41 years). Childhood measures (weight, height and skinfolds) were collected in 1985. Body mass index (BMI), overweight status and fat mass were calculated. Participants underwent 1.5 T knee magnetic resonance imaging (MRI) during 2008-2010, and cartilage defects and BMLs were scored from knee MRI scans. Log binomial regressions were used to examine the associations. RESULTS: Among 327 participants (47.1% females), 21 (6.4%) were overweight in childhood. Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects (Weight relative risk (RR) 1.05/kg, 95% confidence interval (CI) 1.01-1.09; BMI 1.10/kg/m2, 1.01-1.19; Overweight 2.22/yes, 1.21-4.08; fat mass 1.11/kg, 1.01-1.22), but not tibiofemoral cartilage defects. Childhood adiposity measures were not significantly associated with adulthood knee BMLs except for the association between childhood overweight status and adulthood patellar BMLs (RR 2.87/yes, 95% CI 1.10-7.53). These significant associations persisted after adjustment for corresponding adulthood adiposity measure. CONCLUSION: Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects and, to a lesser extent, BMLs, independent of adulthood adiposity measures. These results suggest that adiposity in childhood has long-term effects on patellar structural abnormalities in young adults.

Factors associated with the orthopaedic surgeon's decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1905 patients.

OBJECTIVE: To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA). DESIGN: Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0-4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country. RESULTS: In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69-4.97] and 3.30 [2.17-5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32-2.06] and 1.38 [1.15-1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA. CONCLUSION: Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR.

Use of The Global Alliance for Musculoskeletal Health survey module for estimating the population prevalence of musculoskeletal pain: findings from the Solomon Islands.

BACKGROUND: Musculoskeletal (MSK) conditions are common and the biggest global cause of physical disability. The objective of the current study was to estimate the population prevalence of MSK-related pain using a standardized global MSK survey module for the first time. METHODS: A MSK survey module was constructed by the Global Alliance for Musculoskeletal Health Surveillance Taskforce and the Global Burden of Disease MSK Expert Group. The MSK module was included in the 2015 Solomon Islands Demographic and Health Survey. The sampling design was a two-stage stratified, nationally representative sample of households. RESULTS: A total of 9214 participants aged 15-49 years were included in the analysis. The age-standardized four-week prevalence of activity-limiting low back pain, neck pain, and hip and/or knee pain was 16.8, 8.9, and 10.8%, respectively. Prevalence tended to increase with age, and be higher in those with lower levels of education. CONCLUSIONS: Prevalence of activity-limited pain was high in all measured MSK sites. This indicates an important public health issue for the Solomon Islands that needs to be addressed. Efforts should be underpinned by integration with strategies for other non-communicable diseases, aging, disability, and rehabilitation, and with other sectors such as social services, education, industry, and agriculture. Primary prevention strategies and strategies aimed at self-management are likely to have the greatest and most cost-effective impact.

Self-perception of fracture risk: what can it tell us?

In this study, we report that self-perception of fracture risk captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is associated with improved medication uptake. It suggests that adequate appreciation of fracture risk may be beneficial and lead to greater healthcare engagement and treatment. INTRODUCTION: This study aimed to assess how well self-perception of fracture risk, and fracture risk as estimated by the fracture prediction tool FRAX, related to fracture incidence and uptake and persistence of anti-osteoporosis medication among women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). METHODS: GLOW is an international cohort study involving 723 physician practices across 10 countries in Europe, North America and Australia. Aged ≥ 55 years, 60,393 women completed baseline questionnaires detailing medical history, including co-morbidities, fractures and self-perceived fracture risk (SPR). Annual follow-up included self-reported incident fractures and anti-osteoporosis medication (AOM) use. We calculated FRAX risk without bone mineral density measurement. RESULTS: Of the 39,241 women with at least 1 year of follow-up data, 2132 (5.4%) sustained an incident major osteoporotic fracture over 5 years of follow-up. Within each SPR category, risk of fracture increased as the FRAX categorisation of risk increased. In GLOW, only 11% of women with a lower baseline SPR were taking AOM at baseline, compared with 46% of women with a higher SPR. AOM use tended to increase in the years after a reported fracture. However, women with a lower SPR who were fractured still reported lower AOM rates than women with or without a fracture but had a higher SPR. CONCLUSIONS: These results suggest that SPR captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is also associated with improved medication uptake.

The influence of weather on the risk of pain exacerbation in patients with knee osteoarthritis - a case-crossover study.

OBJECTIVE: To quantify the risk of knee pain exacerbation associated with temperature, relative humidity, air pressure and precipitation in persons with knee osteoarthritis. METHOD: A web-based case-crossover study was conducted. Participants with a diagnosis of symptomatic, radiographic knee osteoarthritis were measured at baseline and followed for 3 months. Participants were instructed to log on to the study website if they perceived experiencing knee pain exacerbation (hazard period). Pain exacerbation was defined as an increase of ≥2 on a 0-10 numeric rating scale (NRS) from the participant's mildest pain reported at baseline. A time-stratified case-crossover study was conducted to anchor the corresponding hazard date to four control periods within a particular 35-day interval. Data on maximum and minimum temperature (°C), relative humidity (%), barometric pressure (hPa) and precipitation (mm) were obtained for the hazard and control periods from the publicly available meteorological database of the Australian Bureau of Meteorology. The associations were assessed using conditional logistic regression. RESULTS: Of the 345 participants recruited, 171 participants (women: 64%, mean age: 62 years, mean BMI: 30.2 kg/m2) experienced at least one episode of pain exacerbation, yielding 1,425 observations included in the analyses. There was no apparent association between temperature, relative humidity, air pressure or precipitation and risk of knee pain exacerbation. CONCLUSION: Despite anecdotal reports from patients, change in weather factors does not appear to influence the risk of pain exacerbation in persons with knee osteoarthritis. Additional studies should quantify the association of weather and risk of pain exacerbation in regions with more extreme weather conditions.

Supplementation with omega-3 fish oil has no effect on bone mineral density in adults with knee osteoarthritis: a 2-year randomized controlled trial.

UNLABELLED: This study aimed to determine the effect of fish oil on bone mineral density (BMD). There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD. This randomized controlled trial did not demonstrate any efficacy of omega-3 fatty acids on bone loss in adults. INTRODUCTION: The purpose of this study is to investigate whether supplementation with high dose omega-3 fish oil could have an impact on BMD. METHODS: In a multicentre, double-blind randomized controlled trial (RCT) (ACTRN 12607000415404), 202 Australian participants aged ≥40 with knee osteoarthritis (mean age, 61.0 ± 10.0 years; 49 % female) were randomized to receive either high dose (4.5 g eicosapentaenoic acid and docosahexaenoic acid daily) or low dose (0.45 g/day) omega-3 fish oil for 2 years. BMD was assessed at baseline and 2 years by dual energy X-ray absorptiometry. RESULTS: In subjects with baseline and 2-year assessments, mean standardized BMD at baseline for low or high dose group was 1198 ± 198 and 1157 ± 169 mg/cm(2), respectively, for the lumbar spine and was 1035 ± 165 and 1017 ± 174 mg/cm(2), respectively, for the femoral neck. There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD in the complete case regression analyses (lumbar spine 3.7, 95 % confidence interval (CI) -7.9 to 15.3 mg/cm(2) and femoral neck -5.5, 95 % CI -14.9 to 3.9 mg/cm(2)). The findings did not change with additional adjustments of age, gender, study centre and uses of bone-related drugs during the study period as well as using the intention-to-treat analysis or limiting to older participants (≥55 years at the baseline) (all P ≥ 0.25). Mild adverse events such as headache and gastrointestinal intolerance were common but did not occur more frequently in either group. There were no serious adverse events related to the intervention. CONCLUSION: A 2-year supplementation with high-dose omega-3 fish oil did not alter bone loss among men and women with knee osteoarthritis.

Association of adipokines and joint biomarkers with cartilage-modifying effects of weight loss in obese subjects.

OBJECTIVES: To determine (1) the effects of weight loss in obese subjects on six adipokines and joint biomarkers; and (2) the relationship between changes in these markers with changes in cartilage outcomes. DESIGN: Plasma levels of adiponectin, leptin, IL-6, COMP, MMP-3 and urine levels of CTX-II were measured at baseline and 12 months from 75 obese subjects enrolled in two weight-loss programs. Magnetic resonance imaging (MRI) was used to assess cartilage volume and thickness. Associations between weight loss, cartilage outcomes and markers were adjusted for age, gender, baseline BMI, presence of clinical knee OA, with and without weight loss percent. RESULTS: Mean weight loss was 13.0 ± 9.5%. Greater weight loss percentage was associated with an increase in adiponectin (ß = 0.019, 95% CI 0.012 to 0.026,) and a decrease in leptin (ß = -1.09, 95% CI -1.37 to -0.82). Multiple regression analysis saw an increase in adiponectin associated with reduced loss of medial tibial cartilage volume (ß = 14.4, CI 2.6 to 26.3) and medial femoral cartilage volume (ß = 18.1, 95% CI 4.4 to 31.8). Decrease in leptin was associated with reduced loss of medial femoral volume (ß = -4.1, 95% CI -6.8 to -1.4) and lateral femoral volume (ß = -1.8, 95% CI -3.7 to 0.0). When weight loss percent was included in the model, only the relationships between COMP and cartilage volume remained statistically significant. CONCLUSIONS: Adiponectin and leptin may be associated with cartilage loss. Further work will determine the relative contributions of metabolic and mechanical factors in the obesity-related joint changes.

Changes in quality of life associated with fragility fractures: Australian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (AusICUROS).

UNLABELLED: We investigated change in health-related quality of life due to fracture in Australian adults aged over 50 years. Fractures reduce quality of life with the loss sustained at least over 12 months. At a population level, the loss was equivalent to 65 days in full health per fracture. PURPOSE: We aimed to quantify the change in health-related quality of life (HRQoL) that occurred as a consequence of a fracture using the EQ-5D-3 L questionnaire. METHODS: Adults aged ≥50 years with a low to moderate energy fracture were recruited from eight study centres across Australia. This prospective study included an 18-month follow-up of participants recruited within 2 weeks of a fracture (hip, wrist, humerus, vertebral and ankle). Information collected at baseline and 4, 12 and 18 months included characteristics of participants such as income level, education and prior fracture status. At 12 months post-fracture, the cumulative loss of quality of life was estimated using multivariate regression analysis to identify the predictors of HRQoL loss. RESULTS: Mean HRQoL for all participants before fracture was 0.86, with wrist fracture having the highest pre-fracture HRQoL (0.90), while vertebral fracture had the lowest (0.80). HRQoL declined to 0.42 in the immediate post-fracture period. Only participants with a wrist, humerus or ankle fracture returned to their pre-fracture HRQoL after 18 months. An increased loss of HRQoL over 12 months was associated with HRQoL prior to the fracture, hospitalisation, education and fracture site. The multiple regression explained 30 % of the variation in the cumulative HRQoL loss at 12 months post-fracture for all fractures. CONCLUSION: Low to moderate energy fractures reduce HRQoL, and this loss is sustained for at least 12 months or, in the case of hip and spine fractures, at least 18 months. At a population level, this represents an average loss of 65 days in full health per fragility fracture. This significant burden reinforces the need for cost-effective fracture prevention strategies.

Risk factors for herpes zoster in rheumatoid arthritis patients: the role of tumour necrosis factor-α inhibitors.

AIM: To determine whether exposure to tumour necrosis factor (TNF)-α inhibitors increases the risk of herpes zoster (HZ) among people with rheumatoid arthritis (RA). METHODS: We performed a cohort study of people with RA participating in the Australian Rheumatology Association Database. We identified self-reported cases of HZ and verified using medical records. For the primary analysis, we only included doctor-verified cases. For TNF-α inhibitor exposed groups, we excluded HZ episodes that occurred before TNF-α inhibitor initiation, and for the control group we excluded HZ episodes that occurred prior to 2000 or RA diagnosis. The risk of HZ among participants exposed versus not exposed to TNF-α inhibitors was compared using Cox proportional hazards models including significant covariates affecting the risk. Adjusted hazard ratios (HR) were calculated for TNF inhibitors as a class and for individual agents. RESULTS: Among 2157 active RA participants, there were 442 self-reported cases of HZ. From 346 responses from doctors, 249 cases were verified and four were false positives (false positive rate 1.6%). Crude incidence of verified HZ in the entire RA cohort was 15.9/1000 person-years (95% confidence interval (CI): 13.5-18.8). An increased risk of HZ was found for all TNF-α inhibitors combined (fully adjusted HR 1.71; 95% CI: 1.00-2.92) and adalimumab (fully adjusted HR 2.33; 95% CI: 1.22-4.45), but in the fully adjusted model was not increased with etanercept (fully adjusted HR 1.65; 95% CI: 0.90-3.03). No increased risk was found with infliximab (HR 1.29; 95% CI: 0.37-4.47). CONCLUSIONS: TNF-α inhibitors are associated with an increased risk of HZ in people with RA compared with those who have not been exposed.

Statin utilisation patterns in older Australians living in residential care: 1-year prevalence study.

Despite controversy over the risks and benefits of statin therapy, statins continue to be commonly used medicines by older people. In a cohort study of participants aged ≥70 years (n = 540) living in residential care, Sydney, we found that the proportion of statin users decreased gradually from the baseline of 33.1% to 31.3% at 6 months (P = 0.13) and to 28.7% over 1 year (P = 0.002). Prevalence of statin use decreased with increasing age, with individuals aged ≥90 years being more likely to discontinue or deprescribe statins. The patterns of statin use did not change according to increasing baseline dose or baseline indication.

The global burden attributable to low bone mineral density.

INTRODUCTION: The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors by calculating disability-adjusted life years (DALYs). Osteoporosis was not considered as a disease, and bone mineral density (BMD) was analysed as a risk factor for fractures, which formed part of the health burden due to falls. OBJECTIVES: To calculate (1) the global distribution of BMD, (2) its population attributable fraction (PAF) for fractures and subsequently for falls, and (3) the number of DALYs due to BMD. METHODS: A systematic review was performed seeking population-based studies in which BMD was measured by dual-energy X-ray absorptiometry at the femoral neck in people aged 50 years and over. Age- and sex-specific mean ± SD BMD values (g/cm(2)) were extracted from eligible studies. Comparative risk assessment methodology was used to calculate PAFs of BMD for fractures. The theoretical minimum risk exposure distribution was estimated as the age- and sex-specific 90th centile from the Third National Health and Nutrition Examination Survey (NHANES III). Relative risks of fractures were obtained from a previous meta-analysis. Hospital data were used to calculate the fraction of the health burden of falls that was due to fractures. RESULTS: Global deaths and DALYs attributable to low BMD increased from 103 000 and 3 125 000 in 1990 to 188 000 and 5 216 000 in 2010, respectively. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). Around one-third of falls-related deaths were attributable to low BMD. CONCLUSIONS: Low BMD is responsible for a growing global health burden, only partially representative of the real burden of osteoporosis.

Patterns of adherence to antiretroviral therapy and HIV drug resistance over time in the Stratall ANRS 12110/ESTHER trial in Cameroon.

OBJECTIVES: The emergence of HIV drug resistance is a crucial issue in Africa, where second-line antiretroviral therapy (ART) is limited, expensive and complex. We assessed the association between adherence patterns and resistance emergence over time, using an adherence measure that distinguishes low adherence from treatment interruptions, in rural Cameroon. METHODS: We performed a cohort study among patients receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART in nine district hospitals, using data from the Stratall trial (2006-2010). Genotypic mutations associated with antiretroviral drug resistance were assessed when 6-monthly HIV viral loads were > 5000 HIV-1 RNA copies/mL. ART adherence data were collected using face-to-face questionnaires. Combined indicators of early (1-3 months) and late (6 months to t - 1; t is the time point when the resistance had been detected) adherence were constructed. Multivariate logistic regression and Cox models were used to assess the association between adherence patterns and early (at 6 months) and late (after 6 months) resistance emergence, respectively. RESULTS: Among 456 participants (71% women; median age 37 years), 45 developed HIV drug resistance (18 early and 27 late). Early low adherence (< 80%) and treatment interruptions (> 2 days) were associated with early resistance [adjusted odds ratio (95% confidence interval) 8.51 (1.30-55.61) and 5.25 (1.45-18.95), respectively]. Early treatment interruptions were also associated with late resistance [adjusted hazard ratio (95% confidence interval) 3.72 (1.27-10.92)]. CONCLUSIONS: The emergence of HIV drug resistance on first-line NNRTI-based regimens was associated with different patterns of adherence over time. Ensuring optimal early adherence through specific interventions, adequate management of drug stocks, and viral load monitoring is a clinical and public health priority in Africa.

Use of dermal injection of activated protein C for treatment of large chronic wounds secondary to pyoderma gangrenosum.

BACKGROUND: Pyoderma gangrenosum (PG) is a systemic disease that presents with cutaneous necrotizing ulceration, producing deep necrotic ulcers, usually with a raised, undermined, violaceous border. Treatment typically involves high dose immunosuppressive drugs, but more recently anti-tumour necrosis factor and monoclonal antibodies have been used. Activated protein C (APC) stimulates wound healing in patients with treatment-refractory skin ulcers, possibly by stimulating angiogenesis and re-epithelialization, and preventing inflammation. AIM: To investigate whether APC may be beneficial as a treatment for ulcers related to cutaneous PG. METHODS: Two patients were recruited with a clinical history and physical and histopathological evidence of acute PG. A total of 400 µg (1.0 mL) of APC was injected subcutaneously into the dermal edge of necrotic PG ulcers weekly for a total treatment period of 6 weeks. Photographs were taken, and clinical progress, ulcer size and pain score were monitored during this period and after the cessation of treatment, at weeks 8 and 12. RESULTS: Over the 12 weeks of the trial, APC led to a reduction in wound size from 3.8 cm(2) to 0.8 cm(2) in patient 1 (78.9% decrease) and from 41 cm(2) to 16 cm(2) in patient 2 (70.0% decrease, respectively), and a reduction in pain scores from 10 to 0 (100% decrease) in both patients. CONCLUSION: Although this study has limited because of its small sample size and lack of a true placebo group, it does indicate that APC has potential as a therapeutic option for patients with chronic skin ulcers from PG.

Assessing domain match and feasibility of candidate instruments matching with OMERACT endorsed domains to measure flare in knee and hip osteoarthritis.

PURPOSE: To evaluate the domain match (truth) and feasibility of candidate instruments assessing flare in knee and hip osteoarthritis (OA) according to the identified domains. MATERIAL AND METHODS: From a literature review (575 papers), instruments were selected and evaluated using the truth and feasibility elements of the OMERACT Filter 2.2. These were evaluated by 26 experts, including patients, in two Delphi survey rounds. The final selection was obtained by a vote. RESULTS: 44 instruments were identified. In Delphi Round 1, five instruments were selected. In Round 2, all instruments obtained at least 75 % in terms of content match with the endorsed domains and feasibility. In the final selection, the Flare-OA questionnaire obtained 100 % favorable votes. CONCLUSION: Through consensus of the working group, the Flare-OA questionnaire was selected as the best candidate instrument to move into a full assessment of its measurement properties using the OMERACT Filter 2.2.

Models of care for the secondary prevention of osteoporotic fractures: a systematic review and meta-analysis.

Most people presenting with incident osteoporotic fractures are neither assessed nor treated for osteoporosis to reduce their risk of further fractures, despite the availability of effective treatments. We evaluated the effectiveness of published models of care for the secondary prevention of osteoporotic fractures. We searched eight medical literature databases to identify reports published between 1996 and 2011, describing models of care for secondary fracture prevention. Information extracted from each publication included study design, patient characteristics, identification strategies, assessment and treatment initiation strategies, as well as outcome measures (rates of bone mineral density (BMD) testing, osteoporosis treatment initiation, adherence, re-fractures and cost-effectiveness). Meta-analyses of studies with valid control groups were conducted for two outcome measures: BMD testing and osteoporosis treatment initiation. Out of 574 references, 42 articles were identified as analysable. These studies were grouped into four general models of care-type A: identification, assessment and treatment of patients as part of the service; type B: similar to A, without treatment initiation; type C: alerting patients plus primary care physicians; and type D: patient education only. Meta-regressions revealed a trend towards increased BMD testing (p = 0.06) and treatment initiation (p = 0.03) with increasing intensity of intervention. One type A service with a valid control group showed a significant decrease in re-fractures. Types A and B services were cost-effective, although definition of cost-effectiveness varied between studies. Fully coordinated, intensive models of care for secondary fracture prevention are more effective in improving patient outcomes than approaches involving alerts and/or education only.