Impact of allopurinol on risk of myocardial infarction.

BACKGROUND: Gout therapy includes xanthine oxidase inhibitors (XOI) and colchicine, which have both been associated with decreased cardiovascular risk. However, their effects on major cardiac events, such as myocardial infarction (MI), need to be investigated further. OBJECTIVES: To investigate whether XOIs and colchicine are associated with decreased risk of MI. METHODS: This case-control study compared patients with first-ever MI and matched controls. Cases were recruited from the Pharmacoepidemiological General Research on MI registry. Controls were selected from a referent population (n=8444) from general practice settings. RESULTS: The study sample consisted of 2277 MI patients and 4849 matched controls. Use of allopurinol was reported by 3.1% of cases and 3.8 of controls, and 1.1% of cases and controls used colchicine. The adjusted OR (95% CI) for MI with allopurinol use was 0.80 (0.59 to 1.09). When using less stringent matching criteria that allowed for inclusion of 2593 cases and 5185 controls, the adjusted OR was 0.73 (0.54 to 0.99). Similar results were found on analysis by sex and hypertension status. Colchicine used was not associated with a decreased risk of MI (aOR=1.17 (0.70 to 1.93)). CONCLUSIONS: Allopurinol may be associated with a reduced risk of MI. No decreased risk of MI was found in colchicine users. Besides its urate-lowering property, allopurinol might have a cardioprotective effect.

Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects.

OBJECTIVES: The aim of this study was to investigate whether the quadrivalent human papillomavirus (HPV) vaccine Gardasil is associated with a change in the risk of autoimmune disorders (ADs) in young female subjects. DESIGN: Systematic case-control study of incident ADs associated with quadrivalent HPV vaccination in young women across France. PARTICIPANTS AND SETTING: A total of 113 specialised centres recruited (from December 2007 to April 2011) females aged 14-26 years with incident cases of six types of ADs: idiopathic thrombocytopenic purpura (ITP), central demyelination/multiple sclerosis (MS), Guillain-Barré syndrome, connective tissue disorders (systemic lupus erythematosus, rheumatoid arthritis/juvenile arthritis), type 1 diabetes mellitus and autoimmune thyroiditis. Control subjects matched to cases were recruited from general practice. ANALYSIS: Multivariate conditional logistic regression analysis; factors included age, geographical origin, smoking, alcohol consumption, use of oral contraceptive(s) or vaccine(s) other than Gardasil received within 24 months before the index date and personal/family history of ADs. RESULTS: Overall, 211 definite cases of ADs were matched to 875 controls. The adjusted odds ratio (OR) for any quadrivalent HPV vaccine use was 0.9 [95% confidence interval (CI) 0.5-1.5]. The individual ORs were 1.0 (95% CI 0.4-2.6) for ITP, 0.3 (95% CI 0.1-0.9) for MS, 0.8 (95% CI 0.3-2.4) for connective disorders and 1.2 (95% CI 0.4-3.6) for type 1 diabetes. No exposure to HPV vaccine was observed in cases with either Guillain-Barré syndrome or thyroiditis. CONCLUSIONS: No evidence of an increase in the risk of the studied ADs was observable following vaccination with Gardasil within the time periods studied. There was insufficient statistical power to allow conclusions to be drawn regarding individual ADs.

The influence of venous thromboembolism on quality of life and severity of chronic venous disease.

BACKGROUND: It is not known whether burden-of-illness differs in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. OBJECTIVE: To compare severity of disease and quality of life in chronic venous disease patients with and without prior venous thromboembolism. PATIENTS AND METHODS: The VEINES Study population is an international cohort of 1531 outpatients with chronic venous disease in Belgium, France, Italy and Canada. Clinical severity of chronic venous disease graded using the seven-category 'CEAP' scale, and quality of life using standardized generic (SF-36) and venous disease-specific (VEINES-QOL/Sym) questionnaires were compared in patients with and without venous thromboembolism. Multivariable analyses with adjustment for known confounders were used to examine associations between venous thromboembolism and quality of life. RESULTS: One hundred and fifty-one (10%) patients had prior venous thromboembolism. These patients had more severe chronic venous disease than those without venous thromboembolism (P <0.0001), including a higher frequency of healed or active ulcers (29% vs. 7%, respectively). Multivariable analyses controlling for age, sex, country, education, body mass index, years of chronic venous disease and comorbid conditions demonstrated that prior venous thromboembolism was an independent predictor of poorer generic quality of life (SF-36 Mental Component Summary score, P=0.047; SF-36 Physical Component Summary score, P=0.012) and venous disease-specific quality of life (VEINES-QOL, P = 0.0002; VEINES-Sym, P=0.009). CONCLUSIONS: Disease severity is worse and quality of life poorer in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. Our findings support the need for further research of interventions to prevent and treat the long-term complications of venous thromboembolism.

Fatal pulmonary arterial hypertension associated with phenylpropanolamine exposure.

Exogenous substances such as the appetite suppressant fenfluramine are known to be causally related to the development of pulmonary arterial hypertension (PAH). In these cases, the clinical course as well as the pulmonary vascular disease pathologically is indistinguishable from idiopathic PAH. Other exogenous substances, such as amphetamines, cocaine, and meta-amphetamines, have been considered to be potential risk factors for inducing PAH. SOPHIA (the study of pulmonary hypertension in America), in addition to confirming previous reports of a causal association between the appetite suppressant fenfluramine and PAH, unexpectedly found a significantly increased risk for the development of PAH with exposure to over-the-counter antiobesity agents containing phenylpropanolamine. The first case is reported of fatal PAH in a child heavily treated with cold remedies containing phenylpropanolamine, which, in addition to the results of SOPHIA, strengthens the hypothesis that phenylpropanolamine is a risk factor for the development of PAH.

A case-control analysis of nonsteroidal anti-inflammatory drugs and Alzheimer's disease: are they protective?

In many studies of nonsteroidal anti-inflammatory drugs (NSAIDs) and Alzheimer's disease (AD), the exposure to NSAIDs was concurrent with AD or based on self (or surrogate) report. We conducted a case-control analysis of the Québec participants in the Canadian Study of Health and Aging who received a diagnosis of AD (cases) or were found to be cognitively unimpaired on screening (controls). Information on drug use was obtained from the Québec Provincial Pharmaceutical Services Database. There was no significant difference in the proportion of cases and controls who had received any NSAID prescriptions in the 3 years prior to the onset of symptoms of dementia; amongst NSAID users, there was no difference in mean dose or duration. Our findings, using a measure of drug use prior to symptom onset and not subject to recall bias, do not support a protective effect for NSAIDs.

Do varicose veins affect quality of life? Results of an international population-based study.

PURPOSE: This study assessed the impact of varicose veins (VV) on quality of life (QOL) and patient-reported symptoms. METHODS: A cross-sectional population-based study was held in 166 general practices and 116 specialist clinics for venous disorders of the leg in Belgium, Canada (Quebec), France, and Italy. Study subjects included a sample of 259 reference patients without VV (CEAP class 0 or 1) and 1054 patients with VV who were classified as having VV alone (367; 34.8%), VV with edema (125; 11.9%), VV with skin changes (431; 40.9%), VV with healed ulcer (100; 9.5%), and VV with active ulcer (31; 2.9%). The main outcome measure was generic and disease-specific QOL, as measured by means of the Short-Form Health Survey-36 (SF-36) and the VEINES-QOL scale, and patient-reported symptoms as measured by the VEINES-SYM scale. RESULTS: In patients with VV, age-standardized mean SF-36 physical (PCS) and mental (MCS) scores were 45.6 and 46.1 in men and 44.2 and 43.2 in women, respectively, compared with population norms of 50. PCS scores decreased according to increasing severity of concomitant venous disease, with the lowest mean scores of 37.3 and 35.5 found in patients with VV and active ulcer. However, adjusted analyses showed no statistically significant differences between patients with VV alone and patients without VV for PCS (0.0), MCS (1.0), VEINES-QOL (-0.1), or VEINES-SYM (0.0) scores. In comparison with patients without VV, the largest differences were seen in patients with VV and edema (PCS, VEINES-QOL, and VEINES-SYM score differences of -1.8, -2.5, and -2.9, respectively) and in patients with VV and ulceration (differences of -3.3, -3.4, and -2.7, respectively). The high prevalence of major symptoms of venous disorders in patients in CEAP class 0 or 1 being treated for venous disorders (76.1% of patients had heaviness, aching legs, or swelling) might have contributed to the impairment of QOL in the reference group. CONCLUSION: Results indicate that impairment in physical QOL in patients with VV is associated with concomitant venous disease, rather than the presence of VV per se. Findings concerning QOL in patients with VV can only be reliably interpreted when concomitant venous disease is taken into account. In patients with VV alone, the objectives of cosmetic improvement and the improvement of QOL should be considered separately.

Is hormone replacement therapy protective for venous ulcer of the lower limbs?

PURPOSE: Estrogen has been found to increase the risk of deep vein thrombosis (DVT), which is associated with venous ulcers. A matched case-control study was therefore performed to quantify the effect of hormone replacement therapy (HRT) on the occurrence of venous ulcers of the lower limbs. METHODS: Women presenting to a participating vascular surgery department between January and December 1997 with a first open venous ulcer served as cases. Controls were sampled among women with sub-acute conditions such as skin problems, cold, headache/migraine, sore throat and mild ear infections, and were matched on referral site and age (+/- 5 years). Subjects were eligible for this study if they were postmenopausal, and excluded if they had non-palpable pedal pulse or any chronic active diseases. The study consisted of an interviewer-administered risk factor questionnaire. Conditional multivariate logistic regression analyses were performed adjusting for history of DVT and unbalanced distributions in important covariates. RESULTS: Forty-four cases and 80 matched controls were recruited. The mean age of participants was 64 years. HRT users were significantly thinner (27% with body mass index (BMI = (kg/height (m2)) > or = 27 vs. 41%, p = 0.04) and less likely to have a history of DVT (12 vs. 33%, p = 0.02) and varicose veins (VV) (52 vs. 69%, p = 0.04) than non-users. A matched univariate logistic regression analysis was performed to quantify the effect of HRT on venous ulcers and generated an odds ratio (OR) of 0.14 with 95% confidence interval of (0.04, 0.49)95%: adjusting for prior DVT resulted in an OR of 0.29 (0.09, 0.93)95%. When adjusting for BMI, history of VV, exercise, education, and smoking, the OR observed was 0.03 (0.01, 0.13)95%: further adjustment for prior DVT gave an OR estimate of 0.06 (0.01, 0.50)95%CI. CONCLUSIONS: Our study demonstrates that HRT has a protective effect on the occurrence of venous ulcers of the lower limbs. Adjusting for prior DVT moves the estimate closer to the null. DVT is a strong contraindication for HRT and therefore must be considered in order to eliminate confounding by contraindication.

Public health impact of adverse bone effects of oral corticosteroids.

AIMS: The objective of this study was to estimate the number of fractures attributed to oral corticosteroid use. METHODS: Information was obtained from the General Practice Research Database which contains medical records of general practitioners in the UK. The total number of corticosteroid-related fractures during a course of treatment was estimated using the formula for attributable risk among the exposed. RESULTS: A total of 244 235 patients was prescribed an oral corticosteroid. The rate of hip fractures increased exponentially with age in both males and females. The excess number of hip fracture cases among females aged 85 years or older using 7.5 mg prednisolone per day or more was 1.4 cases per 100 patients per year. About 47% of all hip and 72% of all vertebral fractures that occurred can be attributed to oral corticosteroid use. Among 10 000 female users of higher doses, 99.7 nonvertebral, 31.6 hip and 45.8 vertebral fractures can be attributed to use of oral corticosteroids. CONCLUSIONS: The targeting of high-risk patients will be important for implementing preventative strategies in a cost-effective manner.

Risk factors for the development of low back pain in adolescence.

A previous history and earlier onset of low back pain are associated with chronic low back pain in adults, implying that prevention in adolescence may have a positive impact in adulthood. The study objectives were to determine the incidence of low back pain in a cohort of adolescents and to ascertain risk factors. A cohort of 502 high school students in Montreal, Canada, was evaluated during 1995-1996 at three separate times, 6 months apart. The outcome was low back pain occurrence at a frequency of at least once a week in the previous 6 months. Of the 377 adolescents who did not complain of low back pain at the initial evaluation, 65 developed low back pain over the year (cumulative incidence, 17 percent). Risk factors associated with development of low back pain were high growth (odds ratio = 3.09; 95 percent confidence interval (CI): 1.53, 6.01), smoking (odds ratio = 2.20; 95% CI: 1.38, 3.50), tight quadriceps femoris (odds ratio = 1.02; 95% CI: 1.00, 1.05), tight hamstrings (odds ratio = 1.04; 95% CI: 1.01, 1.06), and working during the school year (odds ratio = 1.33; 95% CI: 1.03, 1.71). Modifying such risk factors as smoking and poor leg flexibility may potentially serve to prevent the development of low back pain in adolescents.

Risk factors for development of lower limb pain in adolescents.

OBJECTIVE: Although many clinicians believe high growth leads to inflexibility, which may lead to lower extremity pain, the only prospective data suggest growth is unrelated to flexibility. However, it is still possible that growth and/or flexibility are related to pain even if they are not related to each other. We investigated the incidence of leg pain in adolescents to determine whether high growth spurt and/or poor flexibility are risk factors for the development of lower extremity pain. METHODS: Repeated measures, prospective cohort study of urban high school students aged 12-18. Subjects were measured at baseline and at 6 and 12 months for flexibility of hamstrings and quadriceps and with the sit-and-reach test. Participants completed a detailed questionnaire on recreational activity, occupational activities, psychosocial variables, and musculoskeletal pain. RESULTS: Poor hamstring flexibility (odds ratio 0.99, confidence interval 0.97-1.01), poor quadriceps flexibility (OR 1.01, CI 0.99-1.03), poor sit-and-reach flexibility (OR 0.99, CI 0.99-1.01), and growth (OR 0.93, CI 0.50-1.71) were not related to the development of lower extremity pain. There was an association between lower extremity pain and occupational activities (OR 2.08, CI 1.45-2.98) and poor mental health (per 1 SD change, OR 1.41, CI 1.19-1.67). CONCLUSION: Neither growth nor flexibility is related to the development of lower extremity pain in adolescents. A poor mental health score and occupational activities may be associated with the development of lower extremity pain.

Implementation of a participatory ergonomics program in the rehabilitation of workers suffering from subacute back pain.

This paper describes a participatory ergonomics program aimed at early return to regular work of workers suffering from subacute occupational back pain and assesses the perceptions of the participants on the implementation of ergonomic solutions in the workplace. The participatory ergonomics program was used in the rehabilitation of workers suffering from subacute back pain for more than 6 weeks, a program that was associated with an increased rate of return to work. The perceptions of the participatory ergonomics participants were assessed 6 months after completion of the ergonomic intervention through a questionnaire sent to employer representatives, union representatives and injured workers of participating workplaces. About half of the ergonomic solutions were implemented according to the perception of the participants, with a substantial agreement between respondents.

Multiple sclerosis and antecedent infections: a case-control study.

OBJECTIVES: To determine whether there is an excess of respiratory tract infections in the 5-week, 3-month, and 12-month periods before MS symptom onset and if there is an association between MS and a history of infectious mononucleosis (IM). BACKGROUND: The etiology of MS remains unknown, but infection is frequently suggested as a putative etiologic agent. Epidemiologic studies have produced inconsistent evidence for an etiologic role of respiratory tract infections (RTI) and IM in MS. METHODS: The authors performed a case-control study using the General Practice Research Database from the United Kingdom. There were 225 subjects with definite or probable MS, and 900 controls matched for age, sex, and physician practice. Using computerized patient records, the authors compared the mean rates of RTI per patient in the 5-week, 3-month, and 12-month periods before the date of onset of the first symptoms compatible with MS (index date). They also compared histories of IM. RESULTS: In all periods, an increased frequency of RTI was associated with a significantly increased risk of MS. A history of IM was associated with greater than five times the risk of MS (OR = 5.5 [95% CI 1.5 to 19.7]). CONCLUSIONS: These results support an association between a history of IM and subsequent MS. Respiratory tract infections may precipitate disease onset.

Long-term outcomes after deep vein thrombosis: postphlebitic syndrome and quality of life.

In this review, we critically assess the literature on the incidence of postphlebitic syndrome, risk factors for its occurrence, available therapeutic options, and its effects on quality of life. As well, we describe available tools to measure postphlebitic syndrome. Recent prospective studies indicate that postphlebitic syndrome, a chronic, potentially disabling condition characterized by leg swelling, pain, venous ectasia, and skin induration, is established by 1 year after deep vein thrombosis (DVT) in 17% to 50% of patients. The only prospectively identified risk factor for its occurrence is recurrent ipsilateral DVT. In the sole randomized study available, daily use of elastic compression stockings after proximal DVT reduced the incidence of postphlebitic syndrome by 50%. Treatment options for established postphlebitic syndrome are limited, but include compression stockings and intermittent compressive therapy with an extremity pump for severe cases. To date, quality of life after DVT has received little attention in the literature. The recent development of the VEINES-QOL questionnaire, a validated venous-disease-specific measure of quality of life, should encourage researchers to include quality of life as a routine outcome measure after DVT. There is no criterion standard for the diagnosis of postphlebitic syndrome, but a validated clinical scoring system does exist. More research on postphlebitic syndrome is needed to enable us to provide DVT patients with comprehensive, evidence-based information regarding their long-term prognosis, to help quantify the prevalence and health care burden of postphlebitic syndrome, and by identifying predictors of poor outcome, to develop new preventive strategies in patients at risk of developing this condition.

Use of oral corticosteroids and risk of fractures.

Treatment with oral corticosteroids is known to decrease bone density but there are few data on the attendant risk of fracture and on the reversibility of this risk after cessation of therapy. A retrospective cohort study was conducted in a general medical practice setting in the United Kingdom (using data from the General Practice Research Database [GPRD]). For each oral corticosteroid user aged 18 years or older, a control patient was selected randomly, who was matched by age, sex, and medical practice. The study comprised 244,235 oral corticosteroid users and 244,235 controls. The average age was 57.1 years in the oral corticosteroid cohort and 56.9 years in the control cohort. In both cohorts 58.6% were female. The most frequent indication for treatment was respiratory disease (40%). The relative rate of nonvertebral fracture during oral corticosteroid treatment was 1.33 (95% confidence interval [CI], 1.29-1.38), that of hip fracture 1.61 (1.47-1.76), that of forearm fracture 1.09 (1.01-1.17), and that of vertebral fracture 2.60 (2.31-2.92). A dose dependence of fracture risk was observed. With a standardized daily dose of less than 2.5 mg prednisolone, hip fracture risk was 0.99 (0.82-1.20) relative to control, rising to 1.77 (1.55-2.02) at daily doses of 2.5-7.5 mg, and 2.27 (1.94-2.66) at doses of 7.5 mg or greater. For vertebral fracture, the relative rates were 1.55 (1.20-2.01), 2.59 (2.16-3.10), and 5.18 (4.25-6.31), respectively. All fracture risks declined toward baseline rapidly after cessation of oral corticosteroid treatment. These results quantify the increased fracture risk during oral corticosteroid therapy, with greater effects on the hip and spine than forearm. They also suggest a rapid offset of this increased fracture risk on cessation of therapy, which has implications for the use of preventative agents against bone loss in patients at highest risk.