Aslam H. Anis

The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis

BackgroundOverweight and obese persons are at risk of a number of medical conditions which can lead to further morbidity and mortality. The primary objective of this study is to provide an estimate of the incidence of each co-morbidity related to obesity and overweight using a meta-analysis.MethodsA literature search for the twenty co-morbidities identified in a preliminary search was conducted in Medline and Embase (Jan 2007). Studies meeting the inclusion criteria (prospective cohort studies of sufficient size reporting risk estimate based on the incidence of disease) were extracted. Study-specific unadjusted relative risks (RRs) on the log scale comparing overweight with normal and obese with normal were weighted by the inverse of their corresponding variances to obtain a pooled RR with 95% confidence intervals (CI).ResultsA total of 89 relevant studies were identified. The review found evidence for 18 co-morbidities which met the inclusion criteria. The meta-analysis determined statistically significant associations for overweight with the incidence of type II diabetes, all cancers except esophageal (female), pancreatic and prostate cancer, all cardiovascular diseases (except congestive heart failure), asthma, gallbladder disease, osteoarthritis and chronic back pain. We noted the strongest association between overweight defined by body mass index (BMI) and the incidence of type II diabetes in females (RR = 3.92 (95% CI: 3.10–4.97)). Statistically significant associations with obesity were found with the incidence of type II diabetes, all cancers except esophageal and prostate cancer, all cardiovascular diseases, asthma, gallbladder disease, osteoarthritis and chronic back pain. Obesity defined by BMI was also most strongly associated with the incidence of type II diabetes in females (12.41 (9.03–17.06)).ConclusionBoth overweight and obesity are associated with the incidence of multiple co-morbidities including type II diabetes, cancer and cardiovascular diseases. Maintenance of a healthy weight could be important in the prevention of the large disease burden in the future. Further studies are needed to explore the biological mechanisms that link overweight and obesity with these co-morbidities.

Therapies for Active Rheumatoid Arthritis after Methotrexate Failure

BACKGROUND Few blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate--a common scenario in the management of rheumatoid arthritis. METHODS We conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48. RESULTS Both groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications. CONCLUSIONS With respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275.)

Diacetylmorphine versus Methadone for the Treatment of Opioid Addiction

BACKGROUND Studies in Europe have suggested that injectable diacetylmorphine, the active ingredient in heroin, can be an effective adjunctive treatment for chronic, relapsing opioid dependence. METHODS In an open-label, phase 3, randomized, controlled trial in Canada, we compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment. Long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction (including at least one methadone treatment) were randomly assigned to receive methadone (111 patients) or diacetylmorphine (115 patients). The primary outcomes, assessed at 12 months, were retention in addiction treatment or drug-free status and a reduction in illicit-drug use or other illegal activity according to the European Addiction Severity Index. RESULTS The primary outcomes were determined in 95.2% of the participants. On the basis of an intention-to-treat analysis, the rate of retention in addiction treatment in the diacetylmorphine group was 87.8%, as compared with 54.1% in the methadone group (rate ratio for retention, 1.62; 95% confidence interval [CI], 1.35 to 1.95; P<0.001). The reduction in rates of illicit-drug use or other illegal activity was 67.0% in the diacetylmorphine group and 47.7% in the methadone group (rate ratio, 1.40; 95% CI, 1.11 to 1.77; P=0.004). The most common serious adverse events associated with diacetylmorphine injections were overdoses (in 10 patients) and seizures (in 6 patients). CONCLUSIONS Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. (ClinicalTrials.gov number, NCT00175357.)

Evaluating health-related quality-of-life studies in paediatric populations: some conceptual, methodological and developmental considerations and recent applications.

Although numerous paediatric-based health-related quality-of-life (HR-QOL) instruments are currently in use, there still remain conceptual, methodological and developmental issues to address. This paper provides an up-to-date critical review of the HR-QOL literature in paediatric medicine.Our analysis indicates that there is no consensus on how HR-QOL and overall QOL should be defined and measured in children. It is recommended that future studies focus on operationalising and distinguishing these constructs from each other and from traditional health-status measures. A clear empirical basis for generating instrument items and for prioritising specific domains must be described. Researchers should consider using the data gathered during their first interviews as a springboard from which to test their ideas of HR-QOL and QOL, reformulate concepts and subsequently retest their notions before developing instruments.Related to methodological challenges, consistency and agreement are still used interchangeably when comparing child and parent reports of children’s HR-QOL. The Pearson correlation is a measure of co-variation in scores, and not a measure of agreement. We recommend that researchers focus on determining agreement as opposed to consistency. Few, if any, attempts have been made to account for the possibility that a response shift may have occurred in the evaluation of HR-QOL. Most studies have compared HR-QOL scores of children with illness with their healthy peers. As such, there is a dearth of knowledge regarding the normative process of adaptation within the context of illness. It is recommended that researchers focus on gathering data using a relative standard of comparison. We further recommend that researchers interpret HR-QOL data in line with their intended purpose. Regarding developmental consideration, particular attention ought to be paid to developing instruments that consider children’s emerging sense of self, cognitive capacity and emotional awareness. Instruments that include items that are age appropriate are more likely to maximise reliability and validity of reports.The results of many HR-QOL instruments are applied in pharmacotherapeutic and pharmacoeconomic assessments. However, there has been relative infrequent application of economically valid HR-QOL tools (utility scales) and the use of HR-QOL scales as outcome measures in paediatric drug trials. As such, few cost-utility analyses have been performed to inform paediatric decision making. In addition, many of the concerns in the development of HR-QOL instruments should also be applied to the utility scales such that they reflect adequately children’s preferences for health states.

Obesity and overweight in Canada: an updated cost-of-illness study.

This study is to update the estimates of the economic burden of illness because of overweight and obesity in Canada by incorporating the increase in prevalence of overweight and obesity, findings of new related comorbidities and rise in the national healthcare expenditure. The burden was estimated from a societal perspective using the prevalence‐based cost‐of‐illness methodology. Results from a literature review of the risks of 18 related comorbidities were combined with prevalence of overweight and obesity in Canada to estimate the extent to which each comorbidity is attributable to overweight and obesity. The direct costs were extracted from the National Health Expenditure Database and allocated to each comorbidity using weights principally from the Economic Burden of Illness in Canada. The study showed that the total direct costs attributable to overweight and obesity in Canada were

The indirect costs of arthritis resulting from unemployment, reduced performance, and occupational changes while at work.

6.0 billion in 2006, with 66% attributable to obesity. This corresponds to 4.1% of the total health expenditures in Canada in 2006. The inclusion of newly identified comorbidities increased the direct cost estimates of obesity by 25%, while the rise in national healthcare expenditure accounted for a 19% increase. Policies to reduce being overweight and obese could potentially save the Canadian healthcare system millions of dollars.

Use of nonbiologic disease-modifying antirheumatic drugs and risk of infection in patients with rheumatoid arthritis

Objective:The objective of this study was to assess the cost attributable to lost productivity from arthritis and the association between the degree of loss and demographic, disease-related, occupational, and psychosocial variables for people. Methods:In a prospective study, 383 employed individuals with arthritis were recruited from southwestern Ontario, Canada. Respondents completed structured questionnaires assessing demographic, disease-related, workplace, and psychosocial variables as well as employment-related transitions at 2 time points 18 months apart. Indirect costs resulting from arthritis-related absences, reduced performance, decreased work hours, job change, and work disability were estimated. A proportional odds model was used to assess the impact of the various variables on lost productivity. Results:The average cost attributable to arthritis was CAN

A comparison of four indirect methods of assessing utility values in rheumatoid arthritis.

11,553 (

Safety and efficiency of emergency department assessment of chest discomfort

CAN = 0.75

Using a discrete choice experiment to estimate health state utility values

US) per person per year. The largest component of the loss was the result of reduced performance at work, which accounted for 41% (