The risk of deep venous thrombosis and pulmonary embolism in giant cell arteritis: a general population-based study.

IMPORTANCE: Patients with giant cell arteritis (GCA) may have an increased risk of pulmonary embolism (PE), similar to other systemic vasculitidies; however, no relevant population data are available to date. OBJECTIVE: To evaluate the future risk and time trends of new venous thromboembolism (VTE) in individuals with incident GCA at the general population level. DESIGN: Observational cohort study. SETTING: General population of British Columbia. PARTICIPANTS: 909 patients with incident GCA and 9288 age-matched, sex-matched and entry-time-matched control patients without a history of VTE. MAIN OUTCOME MEASURES: We calculated incidence rate ratios (IRR) overall, and stratified by GCA duration. We calculated HR of PE and deep vein thrombosis (DVT), adjusting for potential VTE risk factors. RESULTS: Among 909 individuals with GCA (mean age 76 years, 73% women), 18 developed PE and 20 developed DVT. Incidence rates (IR) of VTE, PE and DVT were 13.3, 7.7 and 8.5 per 1000 person-years (PY) in GCA cohort, versus 3.7, 1.9 and 2.2 per 1000 PY in the comparison cohort. The corresponding IRRs (95% CI) for VTE, PE and DVT were 3.58 (2.33 to 5.34), 3.98 (2.22 to 6.81) and 3.82 (2.21 to 6.34) with the highest IRR observed in the first year of GCA diagnosis (7.03, 7.23 and 7.85, respectively). Corresponding fully adjusted HRs (95% CI) were 2.49 (1.45 to 4.30), 2.71 (1.32 to 5.56) and 2.78 (1.39 to 5.54). CONCLUSIONS AND SIGNIFICANCE: These findings provide general population-based evidence that patients with GCA have an increased risk of VTE, calling for increased vigilance in preventing this serious, but preventable complication, especially within months after GCA diagnosis.

Validity of Diagnostic Codes for Acute Stroke in Administrative Databases: A Systematic Review.

OBJECTIVE: To conduct a systematic review of studies reporting on the validity of International Classification of Diseases (ICD) codes for identifying stroke in administrative data. METHODS: MEDLINE and EMBASE were searched (inception to February 2015) for studies: (a) Using administrative data to identify stroke; or (b) Evaluating the validity of stroke codes in administrative data; and (c) Reporting validation statistics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), or Kappa scores) for stroke, or data sufficient for their calculation. Additional articles were located by hand search (up to February 2015) of original papers. Studies solely evaluating codes for transient ischaemic attack were excluded. Data were extracted by two independent reviewers; article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: Seventy-seven studies published from 1976-2015 were included. The sensitivity of ICD-9 430-438/ICD-10 I60-I69 for any cerebrovascular disease was ≥ 82% in most [≥ 50%] studies, and specificity and NPV were both ≥ 95%. The PPV of these codes for any cerebrovascular disease was ≥ 81% in most studies, while the PPV specifically for acute stroke was ≤ 68%. In at least 50% of studies, PPVs were ≥ 93% for subarachnoid haemorrhage (ICD-9 430/ICD-10 I60), 89% for intracerebral haemorrhage (ICD-9 431/ICD-10 I61), and 82% for ischaemic stroke (ICD-9 434/ICD-10 I63 or ICD-9 434&436). For in-hospital deaths, sensitivity was 55%. For cerebrovascular disease or acute stroke as a cause-of-death on death certificates, sensitivity was ≤ 71% in most studies while PPV was ≥ 87%. CONCLUSIONS: While most cases of prevalent cerebrovascular disease can be detected using 430-438/I60-I69 collectively, acute stroke must be defined using more specific codes. Most in-hospital deaths and death certificates with stroke as a cause-of-death correspond to true stroke deaths. Linking vital statistics and hospitalization data may improve the ascertainment of fatal stroke.

Immunohistochemical Profile of Breast Cancer Patients at a Tertiary Care Hospital in New Delhi, India.

BACKGROUND: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics. MATERIALS AND METHODS: This is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated. RESULTS: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value<0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). CONCLUSIONS: The present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ.

Chronic kidney disease as a risk factor for incident gout among men and women: retrospective cohort study using data from the Framingham Heart Study.

OBJECTIVES: Historically, the nature of association between chronic kidney disease (CKD) and gouty arthritis has been unclear. The goal of the present study was to test the hypothesis that CKD is an independent risk factor for developing incident gout. DESIGN: Patients were from the original Framingham Heart Study cohort. Using Cox proportional hazard models we estimated the HR of CKD to incident gout among men and women separately after adjusting for age, alcohol consumption, smoking, hypertension, diabetes and body mass index. SETTINGS: Patients were all from Framingham, Massachusetts, USA. PARTICIPANTS: Excluding patients who had CKD in the first visit from this study, 2159 men and 2558 women were selected covering a 54-year period (1948-2002). RESULTS: There were 371 incident cases (231 men and 140 women) of gout over the follow-up of 140,421 person-years. Incidence rates of gout per 1000 person-years for participants with and without CKD were 6.82 (95% CI 5.10 to 9.10) and 2.43 (2.18 to 2.71), respectively. In multivariable Cox models, CKD was associated with gout, with a HR of 1.88 (1.13 to 3.13) among men and 2.31 (1.25 to 4.24) among women. Additional analyses using alternate definitions for CKD and cross-sectional study did not change the results. Sensitivity analysis suggested that the observed findings might be an underestimate of the true relative risk. CONCLUSIONS: The present study provides epidemiological evidence to support the notion that CKD is a risk factor for gout.

Impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review.

AIMS: While suboptimal adherence to statin medication has been quantified in real-world patient settings, a better understanding of its impact is needed, particularly with respect to distinct problems of medication taking. Our aim was to synthesize current evidence on the impacts of statin adherence, discontinuation and persistence on cardiovascular disease and mortality outcomes. METHODS: We conducted a systematic review of peer-reviewed studies using a mapped search of Medline, Embase and International Pharmaceutical Abstracts databases. Observational studies that met the following criteria were included: defined patient population;statin adherence exposure; defined study outcome [i.e. cardiovascular disease (CVD), mortality]; and reporting of statin-specific results. RESULTS: Overall, 28 studies were included, with 19 studies evaluating outcomes associated with statin adherence, six with statin discontinuation and three with statin persistence. Among adherence studies, the proportion of days covered was the most widely used measure, with the majority of studies reporting increased risk of CVD (statistically significant risk estimates ranging from 1.22 to 5.26)and mortality (statistically significant risk estimates ranging from 1.25 to 2.54) among non-adherent individuals. There was greater methodological variability in discontinuation and persistence studies. However, findings of increased CVD (statistically significant risk estimates ranging from 1.22 to 1.67) and mortality (statistically significant risk estimates ranging from 1.79 to 5.00) among nonpersistent individuals were also consistently reported. CONCLUSIONS: Observational studies consistently report an increased risk of adverse outcomes associated with poor statin adherence. These findings have important implications for patients and physicians and emphasize the importance of monitoring and encouraging adherence to statin therapy.

Validity of heart failure diagnoses in administrative databases: a systematic review and meta-analysis.

OBJECTIVE: Heart failure (HF) is an important covariate and outcome in studies of elderly populations and cardiovascular disease cohorts, among others. Administrative data is increasingly being used for long-term clinical research in these populations. We aimed to conduct the first systematic review and meta-analysis of studies reporting on the validity of diagnostic codes for identifying HF in administrative data. METHODS: MEDLINE and EMBASE were searched (inception to November 2010) for studies: (a) Using administrative data to identify HF; or (b) Evaluating the validity of HF codes in administrative data; and (c) Reporting validation statistics (sensitivity, specificity, positive predictive value [PPV], negative predictive value, or Kappa scores) for HF, or data sufficient for their calculation. Additional articles were located by hand search (up to February 2011) of original papers. Data were extracted by two independent reviewers; article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Using a random-effects model, pooled sensitivity and specificity values were produced, along with estimates of the positive (LR+) and negative (LR-) likelihood ratios, and diagnostic odds ratios (DOR = LR+/LR-) of HF codes. RESULTS: Nineteen studies published from 1999-2009 were included in the qualitative review. Specificity was ≥95% in all studies and PPV was ≥87% in the majority, but sensitivity was lower (≥69% in ≥50% of studies). In a meta-analysis of the 11 studies reporting sensitivity and specificity values, the pooled sensitivity was 75.3% (95% CI: 74.7-75.9) and specificity was 96.8% (95% CI: 96.8-96.9). The pooled LR+ was 51.9 (20.5-131.6), the LR- was 0.27 (0.20-0.37), and the DOR was 186.5 (96.8-359.2). CONCLUSIONS: While most HF diagnoses in administrative databases do correspond to true HF cases, about one-quarter of HF cases are not captured. The use of broader search parameters, along with laboratory and prescription medication data, may help identify more cases.

Validity of myocardial infarction diagnoses in administrative databases: a systematic review.

BACKGROUND: Though administrative databases are increasingly being used for research related to myocardial infarction (MI), the validity of MI diagnoses in these databases has never been synthesized on a large scale. OBJECTIVE: To conduct the first systematic review of studies reporting on the validity of diagnostic codes for identifying MI in administrative data. METHODS: MEDLINE and EMBASE were searched (inception to November 2010) for studies: (a) Using administrative data to identify MI; or (b) Evaluating the validity of MI codes in administrative data; and (c) Reporting validation statistics (sensitivity, specificity, positive predictive value (PPV), negative predictive value, or Kappa scores) for MI, or data sufficient for their calculation. Additonal articles were located by handsearch (up to February 2011) of original papers. Data were extracted by two independent reviewers; article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: Thirty studies published from 1984-2010 were included; most assessed codes from the International Classification of Diseases (ICD)-9th revision. Sensitivity and specificity of hospitalization data for identifying MI in most [≥50%] studies was ≥86%, and PPV in most studies was ≥93%. The PPV was higher in the more-recent studies, and lower when criteria that do not incorporate cardiac troponin levels (such as the MONICA) were employed as the gold standard. MI as a cause-of-death on death certificates also demonstrated lower accuracy, with maximum PPV of 60% (for definite MI). CONCLUSIONS: Hospitalization data has higher validity and hence can be used to identify MI, but the accuracy of MI as a cause-of-death on death certificates is suboptimal, and more studies are needed on the validity of ICD-10 codes. When using administrative data for research purposes, authors should recognize these factors and avoid using vital statistics data if hospitalization data is not available to confirm deaths from MI.

Medication adherence in gout: a systematic review.

OBJECTIVE: Recent data suggesting the growing problem of medication nonadherence in gout have called for the need to synthesize the burden, determinants, and impacts of the problem. Our objective was to conduct a systematic review of the literature examining medication adherence among patients with gout in real-world settings. METHODS: We conducted a search of Medline, Embase, International Pharmaceutical Abstracts, PsycINFO, and CINAHL databases and selected studies of gout patients and medication adherence in real-world settings. We extracted information on study design, sample size, length of followup, data source (e.g., prescription records versus electronic monitoring versus self-report), type of nonadherence problem evaluated, adherence measures and reported estimates, and determinants of adherence reported in multivariable analyses. RESULTS: We included 16 studies that we categorized according to methods used to measure adherence, including electronic prescription records (n = 10), clinical records (n = 1), electronic monitoring devices (n = 1), and self-report (n = 4). The burden of nonadherence was reported in all studies, and among studies based on electronic prescription records, adherence rates were all below 0.80 and the proportion of adherent patients ranged from 10-46%. Six studies reported on determinants, with older age and having comorbid hypertension consistently shown to be positively associated with better adherence. One study showed the impact of adherence on achieving a serum uric acid target. CONCLUSION: With less than half of gout patients in real-world settings adherent to their treatment, this systematic review highlights the importance of health care professionals discussing adherence to medications during encounters with patients.

Gout and the heart.

The association between gout and cardiovascular diseases has been noted for centuries but was not subjected to rigorous epidemiologic studies until recently. The published literature is almost unanimous in the strength and consistency of this association. However, the impact of gout over and above that conferred by hyperuricemia and other risk factors of cardiovascular disease has not been well studied. Future studies are expected to shed light on the pathophysiologic basis of this association.

Effectiveness of academic detailing to optimize medication prescribing behaviour of family physicians.

PURPOSE: To synthesize current knowledge about the effectiveness and the magnitude of the effect, of Academic Detailing (AD), as a stand-alone intervention, at modifying drug prescription behavior of Family Physicians (FPs) in primary care settings. METHODS: A search of MEDLINE, EMBASE, CENTRAL, and Web of Science databases of all English language articles between January 1983 and July 2010 was conducted. We hand-searched the bibliographies of articles retrieved from the electronic search to identify additional studies. Inclusion criteria were: full-length articles describing original research; randomized controlled trial (RCT), or observational study design with a control group; studies of AD delivered to FPs; AD as a stand-alone intervention; drug prescription as the target behavior. Data extraction was done independently by two reviewers. Outcomes evaluated were: the difference in relative change in prescription rate between the intervention and control groups; the difference in absolute change in prescription rate between the intervention and control groups; and effect size, calculated as the standardized mean difference. RESULTS: 11 RCTs and 4 observational studies were included. Five RCTS described results showing effectiveness, while 2 RCTs reported a positive effect on some of the target drugs. Two observational studies found AD to be effective, while 2 did not. The median difference in relative change among the studies reviewed was 21% (interquartile range 43.75%) for RCTs, and 9% (interquartile range 8.5%) for observational studies. The median effect size among the studies reviewed was - 0.09 (interquartile range 2.73). CONCLUSION: This systematic review demonstrates that AD can be effective at optimizing prescription of medications by FPs. Although variable, the magnitude of the effect is moderate in the majority of studies. This systematic review also provides evidence supportive of the use of AD as a strategy to promote evidence based prescription of medications or incorporation of clinical guidelines into clinical practice. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Differences in body mass index among individuals with PsA, psoriasis, RA and the general population.

OBJECTIVES: To compare obesity among individuals with PsA, psoriasis (PsO), RA and the general population (n), and identify correlates of obesity among individuals with PsO and PsA. METHODS: We compared the BMI of patients with PsA (n = 644), PsO (n = 448), RA (n = 350) and the general population using age- and sex-adjusted linear and logistic regression analyses. We conducted multivariate analyses limited to PsO and PsA to determine correlates of BMI and obesity. RESULTS: The mean BMI (kilogram per square metre) for individuals with PsA, PsO, RA and the general population were 29.6, 27.9, 27.3 and 26.1, respectively. The proportion with obesity was 37, 29, 27 and 18% for individuals with PsA, PsO, RA and the general population, respectively. The differences in BMI were significant between all categories (P < 0.05) except between PsO and RA. Age- and sex-adjusted linear and logistic regression confirmed that these differences were significant. In multivariate logistic regression analyses adjusted for age, sex, smoking, PsO duration, psoriasis area severity index score, use of DMARDs, glucocorticoids and biologics, the odds of obesity were 61% higher for PsA patients than PsO patients (95% CI 1.10, 2.37). When we additionally adjusted for the physical component summary of the short form-36, the association was attenuated and became insignificant. CONCLUSIONS: Individuals with PsA have a higher mean BMI than those with PsO, RA or the general population. The BMI difference between PsA and PsO correlates with physical health.

Serum uric acid levels and the risk of type 2 diabetes: a prospective study.

PURPOSE: To evaluate the impact of serum uric acid levels on the future risk of developing type 2 diabetes independent of other factors. METHODS: We used prospective data from the Framingham Heart Study original (n=4883) and offspring (n=4292) cohorts to examine the association between serum uric acid levels and the incidence of diabetes. We used Cox proportional hazards models to estimate the relative risk of incident diabetes adjusting for age, sex, physical activity, alcohol consumption, smoking, hypertension, body mass index, and blood levels of glucose, cholesterol, creatinine, and triglycerides. RESULTS: We identified 641 incident cases of diabetes in the original cohort and 497 cases in the offspring cohort. The incidence rates of diabetes per 1000 person-years for serum uric acid levels <5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9 and ≥8.0 mg/dL were 3.3, 6.1, 8.7, 11.5, and 15.9, respectively, in the original cohort; and 2.9, 5.0, 6.6, 8.7, and 10.9, respectively, in the offspring cohort (P-values for trends <.001). Multivariable relative risks per mg/dL increase in serum uric acid levels were 1.20 (95% confidence interval; 1.11-1.28) for the original cohort and 1.15 (95% confidence interval; 1.06-1.23) for the offspring cohort. CONCLUSIONS: These prospective data from 2 generations of the Framingham Heart Study provide evidence that individuals with higher serum uric acid; including younger adults, are at a higher future risk of type 2 diabetes independent of other known risk factors. These data expand on cross-sectional associations between hyperuricemia and the metabolic syndrome, and extend the link to the future risk of type 2 diabetes.

Independent impact of gout on the risk of acute myocardial infarction among elderly women: a population-based study.

BACKGROUND: Men with gout have been found to have an increased risk of acute myocardial infarction (AMI), but no corresponding data are available among women. OBJECTIVE: To evaluate the potential independent association between gout and the risk of AMI among elderly women, aged > or = 65 years. METHODS: A population-based cohort study was conducted using the British Columbia Linked Health Database and compared incidence rates of AMI between 9642 gout patients and 48 210 controls, with no history of ischaemic heart disease. Cox proportional hazards models stratified by gender were used to estimate the relative risk (RR) for AMI, adjusting for age, comorbidities and prescription drug use. RESULTS: Over a 7-year median follow-up, 3268 incident AMI cases, were identified, 996 among women. Compared with women without gout, the multivariate RRs among women with gout were 1.39 (95% CI 1.20 to 1.61) for all AMI and 1.41 (95% CI 1.19 to 1.67) for non-fatal AMI. These RRs were significantly larger than those among men (multivariate RRs for all AMI and non-fatal AMI, 1.11 and 1.11; p values for interaction, 0.003 and 0.005, respectively). CONCLUSION: These population-based data suggest that women with gout have an increased risk for AMI and the magnitude of excess risk is higher than in men.

Epidemiology of gout in women: Fifty-two-year followup of a prospective cohort.

OBJECTIVE: Despite the recent doubling of the incidence of gout among women and its substantial prevalence particularly in the aging female population, the risk factors for gout among women remain unknown. We undertook this study to evaluate purported risk factors for incident gout among women and to compare them with those among men. METHODS: Using prospective data from the Framingham Heart Study, we examined over a 52-year period (1950-2002) the relationship between purported risk factors and the incidence of gout in 2,476 women and 1,951 men. RESULTS: We documented 304 incident cases of gout, 104 of them among women. The incidence rates of gout for women per 1,000 person-years according to serum uric acid levels of <5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9, and > or = 8.0 mg/dl were 0.8, 2.5, 4.2, 13.1, and 27.3, respectively (P for trend < 0.0001). The magnitude of this association was lower than that among men (P for interaction = 0.0002). Multivariate relative risks conferred by increasing age (per 5 years), obesity (body mass index > or = 30 kg/m(2)), alcohol intake (> or = 7 ounces of pure alcohol/week), hypertension, and diuretic use were 1.24, 2.74, 3.10, 1.82, and 2.39, respectively (all P < 0.05), for women. CONCLUSION: These prospective data with long-term followup provide evidence that higher levels of serum uric acid increase the risk of gout in a graded manner among women, but the rate of increase is lower than that among men. Increasing age, obesity, alcohol consumption, hypertension, and diuretic use were associated with the risk of incident gout among women.