Causal associations of central and peripheral risk factors with knee osteoarthritis: a longitudinal and Mendelian Randomisation study using UK Biobank data.

ABSTRACT: Our aim was to investigate relative contributions of central and peripheral mechanisms to knee osteoarthritis (OA) diagnosis and their independent causal association with knee OA. We performed longitudinal analysis using data from UK-Biobank participants. Knee OA was defined using International Classification of Diseases manual 10 codes from participants' hospital records. Central mechanisms were proxied using multisite chronic pain (MCP) and peripheral mechanisms using body mass index (BMI). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated, and proportional risk contribution (PRC) was estimated from receiver-operator-characteristic (ROC) analysis. To estimate the causal effects, we performed 2-sample multivariable Mendelian Randomisation (MR) analysis. We selected genetic instruments from the largest Genome Wide Association Study of BMI (N = 806,834) and MCP (N = 387,649) and estimated the instruments genetic associations with knee OA in the largest available dataset (62,497 cases and 333,557 control subjects). The multivariable MR was performed using modified inverse-variance weighting methods. Of the 203,410 participants, 6% developed knee OA. Both MCP (OR 1.23, 95% CI; 1.21-1.24) and BMI (1.10, 95% CI; 1.10-1.11) were associated with knee OA diagnosis. The PRC was 6.9% (95% CI; 6.7%-7.1%) for MCP and 21.9% (95% CI; 21.4%-22.5%) for BMI; the combined PRC was 38.8% (95% CI; 37.9%-39.8%). Body mass index and MCP had independent causal effects on knee OA (OR 1.76 [95% CI, 1.64-1.88] and 1.83 [95% CI, 1.54-2.16] per unit change, respectively). In conclusion, peripheral risk factors (eg, BMI) contribute more to the development of knee OA than central risk factors (eg, MCP). Peripheral and central factors are independently causal on knee OA.

Causal association between subtypes of osteoarthritis and common comorbidities: A Mendelian randomisation study.

Objective: To investigate the causal association between Osteoarthritis (OA) and five comorbidities: depression, tiredness, multisite chronic pain, irritable bowel syndrome (IBS) and gout. Design: This study used two-sample Mendelian Randomisation (MR). To select the OA genetic instruments, we used data from the largest recent genome-wide association study (GWAS) of OA (GO Consortium), with a focus on OA of the knee (62,497 cases, 333,557 controls), hip (35,445 cases, 316,943 controls) and hand (20,901 cases, 282,881 controls). Genetic associations for comorbidities were selected from GWAS for depression (246,363 cases, 561,190 controls), tiredness (449,019 participants), multisite chronic pain (387,649 participants), IBS (53,400 cases, 433,201 controls) and gout (6543 cases, 456,390 controls). We performed a bidirectional MR analysis using the inverse variance weighted method, for both joint specific and overall OA. Results: Hip OA had a causal effect on multisite chronic pain (per unit change 0.02, 95% CI 0.01 to 0.04). Multisite chronic pain had a causal effect on knee (odd ratio (OR) 2.74, 95% CI 2.20 to 3.41), hip (OR 2.12, 95% CI 1.54 to 2.92), hand (OR 2.24, 95% CI 1.59 to 3.16) and overall OA (OR 2.44, 95% CI, 2.06 to 2.86). In addition, depression and tiredness had causal effects on knee and hand, but not hip, OA. Conclusions: Apart from Hip OA to multisite chronic pain, other joint OA did not have causal effects on these comorbidities. In contrast, multisite chronic pain had a causal effect on any painful OA.

Healthcare utilisation and mortality in people with osteoarthritis in the UK: findings from a national primary care database.

BACKGROUND: The burden of osteoarthritis (OA) in UK primary care has not been investigated thoroughly. AIM: To estimate healthcare use and mortality in people with OA (overall and joint specific). DESIGN AND SETTING: A matched cohort study of adults with an incident diagnosis of OA in primary care were selected for the study using UK national Clinical Practice Research Datalink (CPRD) electronic records. METHOD: Healthcare utilisation was measured as the annual average number of primary care consultations and admissions to hospital after the index date for any cause and all-cause mortality data in 221 807 people with OA and an equal number of controls (with no OA diagnosis) who were matched to the case patients by age (standard deviation 2 years), sex, practice, and year of registration. The associations between OA and healthcare utilisation and all-cause mortality were estimated using multinomial logistic regression and Cox regression, respectively, adjusting for covariates. RESULTS: The mean age of the study population was 61 years and 58% were female. In the OA group, the median number of primary care consultations per year after the index date was 10.91 compared with 9.43 in the non-OA control group (P = 0.001) OA was associated with an increased risk of GP consultation and admission to hospital. The adjusted hazard ratio for all-cause mortality was 1.89 (95% confidence interval [CI] = 1.85 to 1.93) for any OA, 2.09 (95% CI = 2.01 to 2.19) for knee OA, 2.08 (95% CI = 1.95 to 2.21) for hip OA, and 1.80 (95% CI = 1.58 to 2.06) for wrist/hand OA, compared with the respective non-OA control group. CONCLUSION: People with OA had increased rates of GP consultations, admissions to hospital, and all-cause mortality that varied across joint sites.

The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.

BACKGROUND: Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. METHODS AND FINDINGS: This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. CONCLUSIONS: Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

BLOod Test Trend for cancEr Detection (BLOTTED): protocol for an observational and prediction model development study using English primary care electronic health record data.

BACKGROUND: Simple blood tests can play an important role in identifying patients for cancer investigation. The current evidence base is limited almost entirely to tests used in isolation. However, recent evidence suggests combining multiple types of blood tests and investigating trends in blood test results over time could be more useful to select patients for further cancer investigation. Such trends could increase cancer yield and reduce unnecessary referrals. We aim to explore whether trends in blood test results are more useful than symptoms or single blood test results in selecting primary care patients for cancer investigation. We aim to develop clinical prediction models that incorporate trends in blood tests to identify the risk of cancer. METHODS: Primary care electronic health record data from the English Clinical Practice Research Datalink Aurum primary care database will be accessed and linked to cancer registrations and secondary care datasets. Using a cohort study design, we will describe patterns in blood testing (aim 1) and explore associations between covariates and trends in blood tests with cancer using mixed-effects, Cox, and dynamic models (aim 2). To build the predictive models for the risk of cancer, we will use dynamic risk modelling (such as multivariate joint modelling) and machine learning, incorporating simultaneous trends in multiple blood tests, together with other covariates (aim 3). Model performance will be assessed using various performance measures, including c-statistic and calibration plots. DISCUSSION: These models will form decision rules to help general practitioners find patients who need a referral for further investigation of cancer. This could increase cancer yield, reduce unnecessary referrals, and give more patients the opportunity for treatment and improved outcomes.

Classification of patients with osteoarthritis through clusters of comorbidities using 633 330 individuals from Spain.

OBJECTIVES: To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster. METHODS: This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards. RESULTS: We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]). CONCLUSION: Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.

The association between preexisting conditions and osteoarthritis development in peripheral joints: A population based nested case-control study.

Aim: To study the risk of receiving a new (incident) osteoarthritis (OA) diagnosis in different joint sites based on conditions diagnosed in the 20 years prior the OA diagnosis. Methods: We used register data for the entire population of the Skåne region (Sweden) to perform a nested case-control study. The outcome was newly diagnosed (incident) OA in peripheral joints, i.e. knee (ICD-10 code M17), hip (M16) and other joints (M15, M18, M19), diagnosed in 2018 or 2019 in persons aged 45+ years with 20 years of register coverage. For each OA case, we sampled 1 control matched on age (1-year strata), sex and residential area in the year of index date using incidence density sampling. The exposures of interest comprised 50 comorbidities. We used adjusted conditional logistic regression for analysis. Results: Between January 1st, 2018 and December 31st, 2019, we identified 7 201, 2 895, and 7863 persons, respectively, with newly diagnosed knee, hip and other OA. Hypertension, back pain, gout, allergy, depression, anxiety and migraine were all associated with increased risk of knee OA diagnosis, while only gastroesophageal reflux disease and back pain were associated with newly diagnosed hip OA. Interestingly, many of the analysed conditions were associated with increased risk of OA diagnosis in other peripheral joints, including diagnosed generalised OA. Conclusions: The risk of being diagnosed with OA increases with the presence of multimorbidity earlier in life, but the associations seem to differ between weight-bearing and non-weight-bearing joints.

Comorbidities and use of analgesics in people with knee pain: a study in the Nottingham Knee Pain and Health in the Community (KPIC) cohort.

Objectives: The aims were to examine the prevalence of comorbidities and role of oral analgesic use in people with knee pain (KP) compared with those without. Methods: The Knee Pain and related health In the Community (KPIC) cohort comprises community-derived adults aged ≥40 years, irrespective of knee pain. Thirty-six comorbidities across 10 systems were compared between people with KP and controls without KP or knee OA. Multivariable logistic regression analysis was used to determine the adjusted odds ratio (aOR) and 95% CI for multimorbidity (at least two chronic conditions) and each specific comorbidity. Both prescribed and over-the-counter analgesics were included in the model, and their interactions with KP for comorbidity outcomes were examined. Results: Two thousand eight hundred and thirty-two cases with KP and 2518 controls were selected from 9506 baseline participants. The mean age of KP cases was 62.2 years, and 57% were women. Overall, 29% of the total study population had multimorbidity (KP cases 34.4%; controls 23.8%). After adjustment for age, sex, BMI and analgesic use, KP was significantly associated with multimorbidity (aOR 1.35; 95% CI 1.17, 1.56) and with cardiovascular (aOR 1.25; 95% CI 1.08, 1.44), gastrointestinal (aOR 1.34; 95% CI 1.04, 1.92), chronic widespread pain (aOR 1.54; 95% CI 1.29, 1.86) and neurological (aOR 1.32; 95% CI 1.01, 1.76) comorbidities. For multimorbidity, the use of paracetamol and opioids interacted positively with KP, whereas the use of NSAIDs interacted negatively for seven comorbidities. Conclusion: People with KP are more likely to have other chronic conditions. The long-term benefits and harms of this change remain to be investigated. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02098070.

Comorbidities in osteoarthritis (ComOA): a combined cross-sectional, case-control and cohort study using large electronic health records in four European countries.

INTRODUCTION: Osteoarthritis (OA) is one of the leading chronic conditions in the older population. People with OA are more likely to have one or more other chronic conditions than those without. However, the temporal associations, clusters of the comorbidities, role of analgesics and the causality and variation between populations are yet to be investigated. This paper describes the protocol of a multinational study in four European countries (UK, Netherlands, Sweden and Spain) exploring comorbidities in people with OA. METHODS AND ANALYSIS: This multinational study will investigate (1) the temporal associations of 61 identified comorbidities with OA, (2) the clusters and trajectories of comorbidities in people with OA, (3) the role of analgesics on incidence of comorbidities in people with OA, (4) the potential biomarkers and causality between OA and the comorbidities, and (5) variations between countries.A combined case-control and cohort study will be conducted to find the temporal association of OA with the comorbidities using the national or regional health databases. Latent class analysis will be performed to identify the clusters at baseline and joint latent class analysis will be used to examine trajectories during the follow-up. A cohort study will be undertaken to evaluate the role of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and paracetamol on the incidence of comorbidities. Mendelian randomisation will be performed to investigate the potential biomarkers for causality between OA and the comorbidities using the UK Biobank and the Rotterdam Study databases. Finally, a meta-analyses will be used to examine the variations and pool the results from different countries. ETHICS AND DISSEMINATION: Research ethics was obtained according to each database requirement. Results will be disseminated through the FOREUM website, scientific meetings, publications and in partnership with patient organisations.

Reliability of detection of ultrasound and MRI features of hand osteoarthritis: a systematic review and meta-analysis.

OBJECTIVES: To systematically review the literature on inter- and intra-rater reliability of scoring US and MRI changes in hand OA. METHODS: MEDLINE, EMBASE, CINHAL, Web of Science and AMED were searched from inception to January 2020. Kappa (κ), weighted kappa (κw) and intra-class correlation coefficients for dichotomous, semi-quantitative and summated scores, respectively, and their 95% CI were pooled using a random-effects model. Heterogeneity between studies was assessed and reliability estimates were interpreted using the Landis-Koch classification. RESULTS: Fifty studies met the inclusion criteria (29 US, 17 MRI, 4 involving both modalities). The pooled κ (95% CI) for inter-rater reliability was substantial for US-detected osteophytes [0.66 (0.54, 0.79)], grey-scale synovitis [0.64 (0.32, 0.97)] and power Doppler [0.76, (0.47, 1.05)], whereas intra-rater reliability was almost perfect for osteophytes [0.82 (0.80, 0.84)], central bone erosions (CBEs) [0.83 (0.78, 0.89)] and effusion [0.83 (0.74, 0.91)], and substantial for grey-scale synovitis [0.64 (0.49, 0.79)] and power Doppler [0.70 (0.59, 0.80)]. Inter-rater reliability for dichotomous assessment was substantial for MRI-detected CBEs [0.75 (0.67, 0.83)] and synovitis [0.69 (0.51, 0.87)], slight for osteophytes [0.14 (0.04, 0.25)], and almost perfect for sum score of osteophytes, CBEs, joint space narrowing (JSN), and bone marrow lesions (BMLs) (0.81-0.89). Intra-rater reliability was almost perfect for sum score of MRI synovitis [0.92 (0.87, 0.96)], BMLs [0.88 (0.78, 0.98)], osteophytes [0.86 (0.74, 0.98)], CBEs [0.83 (0.66, 1.00)] and JSN [0.91 (0.87, 0.91)]. CONCLUSION: US and MRI are reliable in detecting hand OA features. US may be preferred due to low cost and increasing availability.

Health care utilization and out-of-pocket expenditure of type 2 diabetic patients: A study in primary care in Bhubaneswar, India.

Background: Globally, noncommunicable diseases (NCD) demand a higher healthcare expenditure. Among NCDs, diabetes mellitus is often associated with multiple, co-existing chronic conditions. In low- and middle-income countries where most of the healthcare expenditure is borne out of pocket, diabetes management may pose a significant financial stress. Methods: A cross-sectional study was conducted in 17 urban primary healthcare facilities of Bhubaneswar to assess the healthcare utilization and out-of-pocket expenditure among type 2 diabetes patients attending these facilities. Healthcare utilization was determined by the number of visits to healthcare facilities in the last 6 months, and out-of-pocket expenditure was assessed by outpatient consultation fees, medicines, travels to health care facilities, and diagnostic tests. Total out-of-pocket expenditure was defined as the sum of these costs. Results: The median number of visits in 6 months for diabetes patients with any comorbidity was 4 and 5 for diabetes patients with more than 4 comorbidities. Among the comorbid conditions, depression, stroke, auditory impairment, and acid peptic disease were associated with higher healthcare utilization. The total out-of-pocket expense was 2.3 times higher among diabetes patients with any comorbid condition compared to patients with diabetes only. The total median expenditure was higher for diabetes patients having stroke, heart diseases, kidney diseases, and cancer compared with other comorbid conditions. The association of comorbidity in diabetes patients with health care utilization and out-of-pocket expenditure is statistically significant after adjustment for sociodemographic characteristics and diabetes duration. Conclusion: Considerable expenditure is incurred by diabetes patients attending primary healthcare facilities for the management of diabetes and other chronic conditions. This is a significant burden for diabetes patients below the poverty line and with limited or no insurance cover. There is a need to increase the coverage of insurance schemes to address the chronic conditions management expenditure of outpatients.

Reach, accessibility and acceptance of different communication channels for health promotion: a community-based analysis in Odisha, India.

INTRODUCTION: To achieve universal health coverage, improving demand generation at community is necessary. Media plays an important role by acting as a linking pin between health service providers and the community. This study intended to assess the penetration and acceptability of various forms of media for health communication in Odisha, India. METHODS: A cross-sectional mixed method study was conducted in 2016 in four districts. Following a desk review, a situational analysis was done at state, district and sub-district level. Data was collected through direct observation of study sites using a predefined checklist on knowledge awareness and practice, focussed group discussion and in-depth interviews using semi-structured questionnaire. Qualitative data was analyzed using framework approach while for quantitative data, we used SPSS 20.0. RESULTS: Major identified media houses were television (TV), radio and newspaper. Many health programs were being broadcasted in regional TV channels of the state, whereas leading public radio channel broadcasted highest number of health programs almost daily. The major source for information on disease symptoms and prevention was television (63.6%), remove hyphen (36.6%), newspaper (21.6%), health facility/service providers (17.7%), radio (9.2%), and other media like posters, pamphlets and folk dance (5.5%). Information on disease treatment or management was received mostly from television (61.2%), poster/leaflets (39.2%), remove hyphen (35.2%) and newspaper (19.7%). Only 8% of people received any health related message in mobile in past one year. Boards and hoarding provided information to 16.5% of study population. Nearly 36% respondents got information from health-wall, which are used to promote health awareness through wall paintings, graffiti etc. For immunization related information, interpersonal communication through frontline health workers was the most preferred. CONCLUSION: Interpersonal communication is believed to be most acceptable source of information on maternal and child health, immunization and neonatal care. For people with low literacy, remove hyphen campaign, folk media and interpersonal communication were found to be effective.

Temporal relationship between osteoarthritis and comorbidities: a combined case control and cohort study in the UK primary care setting.

OBJECTIVE: To determine the burden of comorbidities in OA and their temporal relationships in the UK. METHODS: The Clinical Practice Research Datalink (CPRD) GOLD was used to identify people with incident OA and age, gender and practice matched non-OA controls from UK primary care. Controls were assigned the same index date as matched cases (date of OA diagnosis). Associations between OA and 49 individual comorbidities and multimorbidities (two or more comorbidities excluding OA) both before and after OA diagnosis were estimated, adjusting for covariates, using odds ratios (aORs) and hazard ratios (aHRs), respectively. RESULTS: During 1997-2017, we identified 221 807 incident OA cases and 221 807 matched controls. Of 49 comorbidities examined, 38 were associated with OA both prior to and following the diagnosis of OA and 2 (dementia and systemic lupus erythematosus) were associated with OA only following the diagnosis of OA. People with OA had a higher risk of developing heart failure [aHR 1.63 (95% CI 1.56, 1.71)], dementia [aHR 1.62 (95% CI 1.56, 1.68)], liver diseases [aHR 1.51 (95% CI 1.37, 1.67)], irritable bowel syndrome [aHR 1.51 (95% CI 1.45, 1.58)], gastrointestinal bleeding [aHR 1.49 (95% CI 1.39, 1.59)], 10 musculoskeletal conditions and 25 other conditions following OA diagnosis. The aOR for multimorbidity prior to the index date was 1.71 (95% CI 1.69, 1.74), whereas the aHR for multimorbidity after the index date was 1.29 (95% CI 1.28, 1.30). CONCLUSIONS: People with OA are more likely to have other chronic conditions both before and after the OA diagnosis. Further study on shared aetiology and causality of these associations is needed.

Initial analgesic prescriptions for osteoarthritis in the United Kingdom, 2000-2016.

OBJECTIVES: To examine trends in the initial prescription of commonly-prescribed analgesics and patient- as well as practice-level factors related to their selection in incident OA. METHODS: Patients consulting with incident clinical OA between 2000-2016 were identified within The Health Improvement Network in the United Kingdom (UK) general practice. Excluded were patients who had history of cancer or were prescribed the analgesics of interest within 6 months before diagnosis of OA. Initial analgesic prescription included oral non-selective NSAID, oral selective cyclooxygenase-2 inhibitor, topical NSAID, paracetamol, topical salicylate or oral/transdermal opioid within 1 month after OA diagnosis. RESULTS: ∼44% of patients with incident OA (n = 125 696) were prescribed one of these analgesics. Incidence of oral NSAID prescriptions decreased whereas other analgesic prescriptions, including oral opioid prescriptions, increased (all P-for-trend < 0.001). Patients with a history of gastrointestinal disease were more likely to receive topical NSAIDs, paracetamol or oral/transdermal opioids. Only 38% of patients with history of gastrointestinal disease and 21% of patients without it had co-prescription of gastroprotective agent with oral NSAIDs. Oral/transdermal opioid prescription was higher among the elderly (≥65 years), women, obesity, current smoker, and patients with gastrointestinal, cardiovascular or chronic kidney disease. Prescription of oral opioids increased with social deprivation (P-for-trend < 0.05) and was highest in Scotland, whereas transdermal opioid prescription was highest in Northern Ireland (all P-for-homogeneity-test < 0.05). CONCLUSION: The initial prescription pattern of analgesics for OA has changed over time in the UK. Co-prescription of gastroprotective agents with oral NSAIDs remains suboptimal, even among those with prior gastrointestinal disease.

Constitutional morphological features and risk of hip osteoarthritis: a case-control study using standard radiographs.

OBJECTIVES: To evaluate the risk of association with hip osteoarthritis (OA) of 14 morphological features measured on standard antero-posterior pelvis radiographs. METHODS: A case-control study of 566 symptomatic unilateral hip OA cases and 1108 controls without hip OA, using the Genetics of OA and Lifestyle database. Unaffected hips of cases were assumed to reflect pre-OA morphology of the contralateral affected hip. ORs with 95% CI adjusted for confounding factors were calculated using logistic regression. Hierarchical clustering on principal component method was used to identify clusters of morphological features. Proportional risk contribution (PRC) of these morphological features in the context of other risk factors of hip OA was estimated using receiver operating characteristic analysis. RESULTS: All morphological features showed right-left symmetry in controls. Each feature was associated with hip OA after adjusting for age, gender and body mass index. Increased sourcil angle had the strongest association (OR: 6.93, 95% CI 5.16 to 9.32). Three clusters were identified. The PRC varied between individual features, as well as between clusters. It was 35% (95% CI 31% to 40%) for all 14 morphological features, compared to 21% (95% CI 19% to 24%) for all other well-established risk factors. CONCLUSIONS: Constitutional morphological variation strongly associates with hip OA development and may explain much of its heritability. Relevant morphological measures can be assessed readily on standard radiographs to help predict risk of hip OA. Prospective studies are required to provide further support for causality.

Barriers and facilitators to physical activity among ethnic Chinese children: a qualitative systematic review.

OBJECTIVE: The review aimed to synthesize the barriers and facilitators from the available studies that explored physical activity among ethnic Chinese children and uncover any differences or similarities in these barriers and facilitators. INTRODUCTION: Physical activity promotes overall health, fitness, and well-being in children, yet prevalence of this has been low among ethnic Chinese children who reside in either Chinese and non-Chinese territories. Research has been conducted to explore the barriers and facilitators to physical activity among ethnic Chinese children. However, no qualitative systematic review has been conducted to synthesize these barriers and facilitators. INCLUSION CRITERIA: Studies were considered for inclusion if they explored the barriers and facilitators to physical activity among ethnic Chinese children aged six to 17 years in either Chinese or non-Chinese territories, or among people who had responsibility for them in school, home, and community settings. The review included studies that focused on their views, experiences, attitudes, understandings, perceptions, and perspectives. Studies were included if they focused on qualitative data including, but not limited to, designs such as phenomenology, ethnography, grounded theory and action research. In addition, the authors considered cross-sectional surveys to find any free text relating to the review question. METHODS: MEDLINE, Embase, CINAHL, PsycINFO, BNI, AMED, Web of Science, Scopus, CNKI, Wanfang and VIP databases were searched to identify published studies. The search for unpublished studies included EThOS, OpenGrey, ProQuest Dissertations and Theses, CNKI and Wanfang. Databases were searched from their inception dates to 10 December 2018 and no language restrictions were applied. The JBI guidelines for qualitative systematic reviews were followed in conducting the review. The JBI process of meta-aggregation was used to identify categories and synthesize findings. RESULTS: Out of 9460 records identified, 11 qualitative studies met the eligibility criteria and were included in the review. Using the JBI checklist for qualitative research (10 criteria), the critical appraisal scores of the majority of studies ranged from a moderate score of 6 (n = 1) to a high score of 7 and above (n = 9). Seven studies were from China, two from Australia, one each from the United Kingdom and the United States. The sample size ranged from 12 to 115 participants. A total of 56 findings were extracted and aggregated into 21 categories, based on the similarity of meaning. From studies conducted in the Chinese territories, four synthesized findings (personal, socio-cultural, environmental, and policy- and program-related barriers and facilitators) were aggregated from 37 extracted findings and 14 aggregated categories. From studies conducted in the non-Chinese territories, only two synthesized findings (personal and socio-cultural barriers and facilitators) were derived from 19 extracted findings and seven aggregated categories. Based on the ConQual scores, confidence in the synthesized findings was moderate. CONCLUSIONS: Four broad themes emerged from the participants' accounts, namely personal, socio-cultural, environmental, and policy- and program-related factors. Barriers and facilitators at the personal and socio-cultural level (e.g., parents and teachers) were most frequently cited, reflecting the importance of children's self-influence and the role of adults. Future interventions are needed to address the identified barriers and enhance the facilitators. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42018097124.

Magnitude and determinants of multimorbidity and health care utilization among patients attending public versus private primary care: a cross-sectional study from Odisha, India.

BACKGROUND: Multimorbidity in primary care is a challenge not only for developing countries but also for low and medium income countries (LMIC). Health services in LMIC countries are being provided by both public and private health care providers. However, a critical knowledge gap exists on understanding the true extent of multimorbidity in both types of primary care settings. METHODS: We undertook a study to identify multimorbidity prevalence and healthcare utilization among both public and private primary care attendees in Odisha state of India. A total of 1649 patients attending 40 primary care facilities were interviewed using a structured multimorbidity assessment questionnaire collecting information on 22 chronic diseases, medication use, number of hospitalization and number of outpatient visits. RESULT: The overall prevalence of multimorbidity was 28.3% and nearly one third of patients of public facilities and one fourth from private facilities had multimorbidity. Leading diseases among patients visiting public facilities included acid peptic diseases, arthritis and chronic back pain. No significant difference in reporting of hypertension and diabetes across the facilities was seen. Besides age, predictors of multimorbidity among patients attending public facilities were, females [AOR: 1.6; 95% CI 1.1-1.3] and non-aboriginal groups [AOR: 1.6; 95%CI 1.1-2.3] whereas, in private females [AOR: 1.6; 95%CI 1.1-2.4], better socioeconomic conditions [AOR 1.4; 95% CI 1.0-2.1] and higher educational status [primary school completed [AOR 2.6; 95%CI 1.6-4.2] and secondary schooling and above [AOR 2.0; 95%CI 1.1-3.6] with reference to no education were seen to be the determinants of multimorbidity. Increased number of hospital visits to public facilities were higher among lower educational status patients [IRR: 1.57; 95% CI 1.13-2.18] whereas, among private patients, the mean number of hospital visits was 1.70 times more in higher educational status [IRR: 1.70; 95%CI 1.01-3.69]. The mean number of medicines taken per day was higher among patients attending private hospitals. CONCLUSION: Our findings suggest that, multimorbidity is being more reported in public primary care facilities. The pattern and health care utilization in both types of settings are different. A comprehensive care approach must be designed for private care providers.

Risk factors for dengue outbreaks in Odisha, India: A case-control study.

BACKGROUND: Environmental and climatic risk factors of dengue outbreak has been studied in detail. However, the socio-epidemiological association with the disease is least explored. The study aims to identify the social and ecological factors associated with emerging dengue in Odisha, India. METHODS: A population-based case-control study (age and sex matched at the ratio of 1:1) was conducted in six districts of the state in 2017. A structured validated questionnaire was used to collect information for each consenting participant. An ecological household survey was done using a checklist during the month of July-September. Along with the descriptive statistics, conditional logistic regression model was used to calculate the adjusted odds ratio using STATA. RESULTS: Of 380 cases, nearly 55% were male and the median age was 33years. The adjusted odds of having dengue was nearly three times higher among the people having occupation which demands long travel, presence of breeding sites (1.7; 95% CI 1.2-2.6), presence of swampy area near home (1.5; 95% CI 1.1-2.1) and having travel history close to the index date (1.6; 95% CI 1.1-2.4). People staying in thatched houses had three times higher risk of the disease, however, households keeping the swampy areas clean had 50% less risk for the disease (0.5; 95% CI 0.31-0.67). Nearly 22.2% of cases had a travel history during the index date. Of them, 36% had diagnosis before the travel, whereas, 64% developed the disease after the returning from the travel. CONCLUSION: Household factors such as occupation and ecological condition of households play important roles in dengue outbreaks in Odisha. However, our study suggests travel/commuting are also essential factors to be considered during disease prevention planning.

High- and low-inpatients' serum magnesium levels are associated with in-hospital mortality in elderly patients: a neglected marker?

BACKGROUND: Altered serum magnesium (Mg) level in the human body has been hypothesized to have a role in the prediction of hospitalization and mortality; however, the reported outcomes are not conclusive. AIMS: The present study aimed to analyze the relationship between serum Mg and in-hospital mortality (IHM) in patients admitted to the medical ward of two hospitals in the Veneto region (Italy). METHODS: Patients > 18 years hospitalized in the medical wards of the hospitals of Vittorio Veneto and Conegliano, Italy (from January 12, 2011, through December 27, 2016) with at least one measurement of serum Mg were included in the study. A logistic regression model was used to assess the unadjusted and adjusted (by age, gender, Charlson Comorbidity index, discharge diagnosis' class) association of serum Mg and IHM. RESULTS: In total 5024 patients were analyzed, corresponding to 6980 total admissions. The unadjusted analysis showed that IHM risk was significantly higher with 0.2 mg/dl incremental serum Mg level change from 2.4 mg/dl to 2.6, (OR 1.71 95% CI 1.55-1.89) and with 0.2 mg/dl change from serum Mg level of 1.4 mg/dl to 1.2 mg/dl, (OR 1.28 95% CI 1.17-1.40). Such results were confirmed at adjusted analysis. DISCUSSION: Present findings have relevant implications for the clinical management of patients suffering from medical conditions, highlighting the need for analyzing Mg concentration carefully. CONCLUSIONS: Serum Mg levels seem to be a good predictor of IHM.

At which temperature do the deleterious effects of ambient heat "kick-in" to affect all-cause mortality? An exploration of this threshold from an eastern Indian city.

Despite experiencing hot weathers, limited studies from India explored relationships between ambient heat and health. We studied associations between heat and all-cause mortality to estimate heat threshold(s) affecting health, and examine other affecting dimensions. We conducted time-series analysis with daily maximum temperature and all-cause mortality data of Bhubaneswar city (March-July, 2007-2017), and explored their interactions. Mortality risks rose when daily maximum temperatures were >36.2°C (lower threshold), and even more when >40.5°C (upper threshold). Every degree above36.2°C increased the mortality risk by 2% (mortality rate ratio: 1.02; 95% CI 1.01, 1.03). The effects of maximum temperature increased on days when minimum temperatures were >25.6°C (median). The effect of heat was immediate and lasted for 0-1 day with no lagged effect. Two temperature thresholds with varying mortality risks provided an opportunity for a graded heat warning system. The accentuation of the deleterious effects of heat by the higher minimum temperature calls for its inclusion in the heat warning system in future.