Christine Peloquin

Trajectories of Gait Speed Predict Mortality in Well-Functioning Older Adults: The Health, Aging and Body Composition Study

BACKGROUND Although gait speed slows with age, the rate of slowing varies greatly. To date, little is known about the trajectories of gait speed, their correlates, and their risk for mortality in older adults. METHODS Gait speed during a 20-m walk was measured for a period of 8 years in initially well-functioning men and women aged 70-79 years participating in the Health, Aging and Body Composition study. We described the trajectories of gait speed and examined their correlates using a group-based mixture model. Also risk associated with different gait speed trajectories on all-cause mortality was estimated using a Cox-proportional hazard model. RESULTS Of 2,364 participants (mean age, 73.5 ± 2.9 years; 52% women), we identified three gait speed trajectories: slow (n = 637), moderate (n = 1,209), and fast decline (n = 518). Those with fast decline slowed 0.030 m/s per year or 2.4% per year from baseline to the last follow-up visit. Women, blacks, and participants who were obese, had limited knee extensor strength, and had low physical activity were more likely to have fast decline than their counterparts. Participants with fast decline in gait speed had a 90% greater risk of mortality than those with slow decline. CONCLUSION Despite being well-functioning at baseline, a quarter of older adults experienced fast decline in gait speed, which was associated with an increased risk of mortality.

Risk for Cardiovascular Disease Early and Late After a Diagnosis of Giant-Cell Arteritis: A Cohort Study

Context Whether patients with giant-cell arteritis (GCA) are at increased risk for major cardiovascular events is not known. Contribution This population-based cohort study found increased risks for myocardial infarction, cerebrovascular accident, and peripheral vascular disease among patients with GCA, particularly in the first month after the diagnosis of GCA. Implication Clinicians should be alert to the potential for major cardiovascular events in patients with GCA. Whether preventative practices should be changed requires further study. The Editors Giant-cell arteritis (GCA) is a large-vessel vasculitis that has predilection for large and medium-sized arteries (1, 2). It can result in ischemic blindness (3, 4), and the mainstay of treatment is high doses of glucocorticoids for substantial periods. Imaging studies have described a high prevalence of large-artery stenoses and aneurysms in cohorts of patients with GCA (5, 6), but studies exploring the association of GCA with clinically important cardiovascular events have provided conflicting results (7, 8). A large population study from Canada of 1100 patients with GCA showed an increase in vascular events (coronary heart disease, stroke, peripheral artery disease, aneurysm, and dissection) compared with randomly selected reference participants from the same population (hazard ratio [HR], 2.1 [95% CI, 1.5 to 3.0] after limited adjustment for potential risk factors [medication use for hypertension and hyperlipidemia]) (7). In contrast, a preliminary report from a large cohort study in the United States using hospital discharge diagnoses of GCA in 4807 patients found an increase in thoracic aortic aneurysms (HR, 5.2 [95% CI, 1.5 to 9.0]) and a minimally increased risk for strokes (HR, 1.29 [CI, 1.15 to 1.45]), but not for other atherosclerotic disease (coronary heart disease, peripheral artery disease, or aortic abdominal aneurysm) compared with 19228 reference participants (8), with limited adjustment for cardiovascular risk factors. A few studies have suggested that traditional cardiovascular risk factors are associated with occurrence and complications of GCA (912). Therefore, information on cardiovascular risk factors is important when the association of GCA with cardiovascular disease is explored. The objective of this study was to determine the association between GCA and incident cardiovascular disease, defined as myocardial infarction (MI), cerebrovascular accident (CVA), or peripheral vascular disease (PVD), in an unselected population cohort with information on risk factors for cardiovascular disease. Methods Data Source Data were obtained from The Health Improvement Network (THIN), an electronic database derived from general practices in the United Kingdom that includes data on approximately 7.3 million patients (13). Database elements are obtained from visits with general practitioners, specialists, and from hospitalizations. Data on diagnoses (14), prescription medications, height, weight, smoking status, vaccinations, and other variables are entered into the THIN database by primary care physicians during clinical visits. This study was judged to be exempt from review by the Institutional Review Board at Boston University Medical Center and was approved by the THIN Scientific Review Committee. Study Design We performed a matched cohort study to examine the relation of patient with incident GCA to risk for MI, CVA, and PVD. Specifically, for each GCA, we selected up to 5 individuals without GCA at the time that the patient with GCA was diagnosed, matched by age, sex, and time of entry into the THIN database. Patients with cardiovascular disease (MI, CVA, or PVD) at baseline were excluded. GCA Definition Patients with GCA were those who had a diagnosis of GCA, temporal arteritis, or Horton disease that appeared at least 1 year after the patient was entered into the THIN database and who received and used a prescription for glucocorticoids. We defined glucocorticoid use as 2 prescriptions for oral glucocorticoids, the first within 6 months of the date of GCA diagnosis and the second within 6 months of the first prescription. The database used for analysis was compiled in 2012. Because historical diagnoses may be erroneously recorded as having occurred on the date of patient enrollment or the date when a general practice begins to use the database software, patients with incident cases were included only if GCA was first diagnosed at least 12 months after their records were computerized. Because GCA is exceptionally rare among persons younger than 50 years, we excluded persons in this age group from the analysis. In a supplemental analysis, we used a more stringent definition of GCA that required 10 or more prescriptions of glucocorticoids. Covariate Assessment We obtained information on cardiovascular risk factors as follows. Information on smoking status was obtained from the codes for smoking and smoking history. A categorical variable with the values current smoker, former smoker, or never smoker was created. Hypertension was handled as a dichotomous variable defined as the presence or absence of any of the following diagnoses: hypertension, essential hypertension, high blood pressure, malignant essential hypertension, benign essential hypertension, systolic hypertension, or diastolic hypertension. We obtained data on total cholesterol level in millimoles per liter and used this as a continuous variable. Diabetes mellitus was handled as a dichotomous variable defined as a diagnosis of diabetes mellitus or any of its subcodes or an outpatient prescription code for any form of insulin, sulfonylureas, or other drugs used to treat diabetes (excluding biguanides). Body mass index (BMI) was obtained from a corresponding code in the medical record. Only data on covariates that were recorded in the THIN database before patients contribution of follow-up time were included in the analysis. Assessment of Medications Used for Cardiovascular Disease We assessed baseline use of the following medications commonly prescribed to treat cardiovascular disease: antiplatelet agents, -blockers, nitrates, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). We defined medication use as 1 or more outpatient prescription codes for one of these medications. Follow-up and Outcomes Definitions Data collected from 1 January 1990 through 1 June 2010 were used for this study. We followed patients with GCA from the date of diagnosis and reference participants from the matched (index) date until occurrence of any cardiovascular event, death, migration of the THIN database, or 1 June 2010, whichever came first. Incident MI was defined as the presence of any of several diagnostic codes pertaining to MI, including myocardial infarction, heart attack, and codes pertaining to a specific anatomical site of the myocardium or specified pattern on an electrocardiogram. Incident PVD was defined as any of the following diagnoses: peripheral ischemic vascular disease, other specified peripheral vascular disease NOS, other peripheral vascular disease, or peripheral vascular disease. Incident CVA was defined as the first appearance of any of the following diagnoses: CVA unspecified, stroke unspecified, cerebrovascular accident unspecified, middle cerebral artery syndrome, anterior cerebral artery syndrome, posterior cerebral artery syndrome, brainstem stroke syndrome, cerebellar stroke syndrome, pure motor lacunar syndrome, pure sensory lacunar syndrome, or left- or right-sided CVA. Patients who had 1 type of cardiovascular event were censored in the analyses for the other types. Statistical Analysis We compared the characteristics of patients with GCA and reference participants by using the t test for continuous variables and a chi-square test for categorical variables. Person-years of follow-up for each patient were computed as the time from the index date to the end of follow-up. We calculated incidence rates of each outcome event for each group by dividing the number of cases of each outcome variable by the number of person-years. The associations between GCA and study outcomes are expressed as incidence rate ratios with 95% CIs. We plotted the cumulative incidence rate of each outcome variable for individuals with and without GCA and accounted for the competing risk for the other outcomes. We used the Markov-chain Monte Carlo method (15) to impute missing data on BMI, cholesterol level, and smoking status under the assumption that data were missing at random (MAR). Because there was a substantial amount of missing data on cholesterol level (>50%), 50 data sets with imputed data were created and data for the following variables were used for imputation of missing variables: age, sex, GCA status, smoking status, hypertension, diabetes mellitus, cholesterol level, BMI, and outcome. Because the MAR assumption was unverifiable, we performed the analysis using both the imputed data sets and those restricted to patients with complete data. We fitted Cox proportional hazards models to separately determine the relation of GCA to cardiovascular disease (MI, CVA, or PVD). In the multivariate Cox proportional hazards models, we adjusted for age, sex, smoking, hypertension, diabetes mellitus, BMI, and total cholesterol level. In the adjusted analysis, the effect of GCA on study outcomes is expressed with HRs with 95% CIs. The assumption of proportional hazards between patients with and without GCA was evaluated by a visual inspection of a diagnostic plot of the log of the minus log survival against log time and by testing an interaction term between time and GCA status for statistical significance, with a 2-sided P value less than 0.05 indicating statistical significance. In cases where the proportional hazards assumption was violated, series of average HRs for increasingly longer periods of follow-up are presented (16). We conducted 3 sensitivity analyses. First, to account f

Impact of Age, Sex, Obesity, and Steroid Use on Quinolone-associated Tendon Disorders

BACKGROUND Quinolone antibiotics are associated with increased risk of tendinopathy. Identifying at-risk individuals has important clinical implications. We examined whether age, sex, glucocorticoid use, obesity, diabetes, and renal failure/dialysis predispose individuals to the adverse effects of quinolones. METHODS Among 6.4 million patients in The Health Improvement Network (THIN) database, 28,907 cases of Achilles tendonitis and 7685 cases of tendon rupture were identified in a case-crossover study. For each participant, we ascertained whether there was a prescription of a quinolone and comparison antibiotic within 30 days before the diagnosis of tendon disorder (case period) and a prescription of the same medications within 30 days 1 year before disease diagnosis (control period). RESULTS Use of quinolones was strongly associated with an increased risk of Achilles tendonitis (odds ratio [OR], 4.3; 95% confidence interval [CI], 3.2-5.7) and tendon rupture (OR, 2.0; 95% CI, 1.2-3.3). No association was found between the use of other antibiotics and either outcome. The association with Achilles tendonitis was stronger among participants who were aged more than 60 years (OR, 8.3 vs 1.6), who were nonobese (OR, 7.7 vs 2.4), and who used oral glucocorticoids (OR, 9.1 vs 3.2). The association was nonsignificantly stronger in women (OR, 5.0 vs 3.6), diabetic persons (OR, 7.0 vs 4.1), and those in renal failure or receiving dialysis (OR, 20.0 vs 3.9). The effect for tendon rupture was stronger in women, with borderline significance in glucocorticoid users and nonobese persons. CONCLUSION Quinolone-associated tendinopathy is more pronounced among elderly persons, nonobese persons, and individuals with concurrent use of glucocorticoids.

The risk of cardiovascular disease in systemic sclerosis: a population-based cohort study

Objectives To evaluate the risk of incident myocardial infarction (MI), stroke and peripheral vascular disease (PVD) in individuals with systemic sclerosis (SSc) in a general population context. Methods We conducted a cohort study using a UK primary care database containing records from 1986 to 2011. SSc diagnoses, outcomes and cardiovascular risk factors were identified from electronic medical records. We conducted two cohort analyses: (1) MI and stroke, and (2) PVD, excluding individuals with prevalent disease at baseline for each analysis. We estimated HRs comparing SSc with age-, sex- and entry time-matched comparison cohorts, adjusting for potential cardiovascular risk factors. Results Among 865 individuals with SSc (85.8% women, mean age 58.7 years), the incidence rates (IRs) of MI and stroke were 4.4 and 4.8 per 1000 person-years (PY), versus 2.5 and 2.5 per 1000 PY in the comparison cohort. The corresponding adjusted HRs were 1.80 (95% CI 1.07 to 3.05) for MI and 2.61 (95% CI 1.54 to 4.44) for stroke. Among 858 individuals with SSc (85.3% female, mean age 58.9 years), the IR of PVD was 7.6 per 1000 PY versus 1.9 per 1000 PY in the comparison cohort, with an adjusted HR of 4.35 (95% CI 2.74 to 6.93). Conclusions These findings provide the first general population-based evidence that SSc is associated with an increased risk of developing MI, stroke and PVD. Further insight into disease mechanisms, as well as how disease subtype, organ involvement and medication use may alter these increased risks, is needed.

Improved survival in rheumatoid arthritis: a general population-based cohort study.

Objective Mortality trends of rheumatoid arthritis (RA) are largely unknown over the past decade when new drugs and management strategies have been adopted to effectively treat RA. Methods Using The Health Improvement Network, an electronic medical record database representative of the UK general population, we identified patients with incident RA and up to five individuals without RA matched for age, sex and year of diagnosis between 1999 and 2014. The RA cohort was divided in two sub-cohorts based on the year of RA diagnosis: the early cohort (1999–2006) and the late cohort (2007–2014). We compared mortality rates, HRs (using a Cox proportional hazard model) and rate differences (using an additive hazard model) between RA and non-RA cohorts adjusting for potential confounders. Results Patients with RA diagnosed between 1999 and 2006 had a considerably higher mortality rate than their comparison cohort (ie, 29.1 vs 18.0 deaths/1000 person-years), as compared with a moderate difference in patients with RA diagnosed between 2007 and 2014 and their comparison cohort (17.0 vs 12.9 deaths/1000 years). The corresponding absolute mortality rate differences were 9.5 deaths/1000 person-years (95% CIs 7.5 to 11.6) and 3.1 deaths/1000 person-years (95% CI 1.5 to 4.6) and the mortality HRs were 1.56 (95% CI 1.44 to 1.69) and 1.29 (95% CI 1.17 to 1.42), respectively (both p values for interaction <0.01). Conclusion This general population-based cohort study indicates that the survival of patients with RA has improved over the past decade to a greater degree than in the general population. Improved management of RA and its associated comorbidities over recent years may be providing a survival benefit.

Independent impact of gout on the risk of diabetes mellitus among women and men: a population-based, BMI-matched cohort study

Objective Evidence on the potential independent impact of gout on the risk of diabetes is limited to a single study of men with a high cardiovascular risk profile. Our objective was to examine this relation in the general population, particularly among women. Methods We conducted a sex-stratified matched cohort study using data from The Health Improvement Network (THIN), an electronic medical records database representative of the UK general population. Up to five non-gout individuals were matched to each case of incident gout by year of birth, year of enrolment and body mass index (BMI). Multivariate HRs for incident diabetes were calculated after additionally adjusting for smoking, alcohol consumption, physician visits, comorbidities and medication use. Results Among 35 339 gout patients (72.4% men, mean age of 62.7 years), the incidence rates of diabetes in women and men were 10.1 and 9.5 cases per 1000 person-years, respectively, whereas the corresponding rates were 5.6 and 7.2 cases per 1000 person-years among 137 056 non-gout subjects. The BMI-matched univariate and multivariate HRs of diabetes were higher among women compared with those among men (1.71; 95% CI 1.51 to 1.93 vs 1.22; 95% CI 1.13 to 1.31) and (1.48; 95% CI 1.29 to 1.68 vs 1.15; 95% CI 1.06 to 1.24), respectively (p values for interaction <0.001). This sex difference persisted across age-specific subgroups. Conclusions This general population-based study suggests that gout may be independently associated with an increased risk of diabetes and that the magnitude of association is significantly larger in women than in men.

Secular trend of adhesive capsulitis.

Adhesive capsulitis (AC) is a painful shoulder disorder resulting in restrictions of daily activities. Given the recent increase in risk factors for AC, such as diabetes mellitus, research is needed to examine if the incidence of AC has also increased. Therefore, the purpose of this study was to describe the secular trend of AC.

Effect of bisphosphonates on knee replacement surgery

Purpose Bone remodelling as a therapeutic target in knee osteoarthritis (OA) has gained much interest, but the effects of antiresorptive agents on knee OA have been conflicting, with no studies to date examining the effects of bisphosphonate use on the clinically relevant endpoint of knee replacement (KR) surgery. Methods We used data from The Health Improvement Network (THIN), a general practitioner electronic medical records representative of the general UK population. We identified older women who had initiated bisphosphonate use after their incident knee OA diagnosis. Each bisphosphonate initiator was propensity score-matched with a non-initiator within each 1-year cohort accrual block. The effect of bisphosphonates on the risk of KR was assessed using Cox proportional hazard regression. Sensitivity analyses to address residual confounding were also conducted. Results We identified 2006 bisphosphonate initiators, who were matched to 2006 non-initiators(mean age 76, mean body mass index 27), with mean follow-up time of 3 years. The crude incidence rate of KR was 22.0 per 1000 person-years among the initiators, and 29.1 among the non-initiators. Bisphosphonate initiators had 26% lower risk of KR than non-initiators(HR 0.74, 95% CI 0.59 to 0.93); these results were similar when additionally adjusted for potential confounders in the propensity score (HR 0.76, 95% CI 0.60 to 0.95). Results of sensitivity analyses supported this protective effect. Conclusions In this population-based cohort of older women with incident knee OA, those with incident bisphosphonate users had lower risk of KR than non-users of bisphosphonates, suggesting a potential beneficial effect of bisphosphonates on knee OA.

Validity of ankylosing spondylitis diagnoses in The Health Improvement Network.

Because ankylosing spondylitis (AS) is uncommon, large medical record databases offer important opportunities for pharmacoepidemiologic research. However, the validity of AS diagnoses recorded by a general practitioner (GP) is unknown. We assessed the validity of algorithms for identifying AS in The Health Improvement Network (THIN).

Sleep Apnea and the Risk of Incident Gout: A Population-Based, Body Mass Index–Matched Cohort Study

Sleep apnea is associated with hyperuricemia owing to hypoxia‐induced nucleotide turnover. We undertook this study to assess the relationship between incident sleep apnea and the risk of incident gout.