Overweight 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.
A 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).
A 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)).
Both 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.
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The objective of this study is to review current measurement issues and valuation methods such as “human capital” and “friction cost” for estimating productivity loss due to illness. Since observed ...wages diverge from marginal productivity when allowances are made for sick days and workers are risk averse, or when a job type involves team production, unavailability of perfect substitutes, and/or time-sensitivity of output, productivity loss is likely to be underestimated. A multiplier adjusting wage to marginal productivity needs to be developed for practical use. We further consider the ramifications of measuring labour input loss due to illness in both paid and unpaid work as well as the inclusion of presenteeism to the more traditional approach of measuring only absenteeism. Although a number of instruments have been developed to measure presenteeism, they generate widely varying estimates of productivity loss. Further investigation is required to identify which instrument provides a better estimate. Finally, we provide recommendations on measurement methods such as using subjective measures due to the unavailability of objective measures and the appropriate recall periods. We conclude by proposing a generic measure instead of a disease-specific measure and discuss important perspective related issues.
► Lost productivity due to illness is substantial and should be appropriately measured and valued. ► Existing instruments generate widely varying estimates of productivity loss. ► We review the current methods of valuing productivity loss. ► We highlight issues and controversies related to the measurement and valuation of productivity loss. ► We suggest methodological guidelines to align economic theory with valuation approaches for productivity loss.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To inform World Health Organization (WHO) global guidelines, we updated and expanded the evidence base to assess the comparative efficacy, tolerability, and safety of first-line antiretroviral ...therapy (ART) regimens.
We searched Embase, Medline and CENTRAL on 28 February 2020 to update the systematic literature review of clinical trials comparing recommended first-line ART that informed previous WHO guidelines. Outcomes included viral suppression, change in CD4 cell counts, mortality, serious and overall adverse events (AEs), discontinuation, discontinuations due to AEs (DAEs); and new outcomes: drug-resistance, neuropsychiatric AEs, early viral suppression, weight gain and birth outcomes. Comparative effects were assessed through network meta-analyses and certainty in the evidence was assessed using the GRADE framework.
We identified 156 publications pertaining to 68 trials for the primary population. Relative to efavirenz, dolutegravir had improved odds of viral suppression across all time points (odds ratio OR: 1·94; 95% credible interval CrI: 1·48–2·56 at 96 weeks); was protective of drug-resistance (OR: 0·13; 95%CrI: 0·04–0·48); and led to fewer discontinuations (OR: 0·58; 95%CrI: 0·48–0·70). Evidence supported dolutegravir use among TB-HIV co-infected persons and pregnant women. Adverse birth outcomes were observed in 33.2% of dolutegravir-managed pregnancies and 35.0% of efavirenz-managed pregnancies. Low-dose efavirenz had comparable efficacy and safety to standard-dose efavirenz, but led to fewer DAEs (OR: 0·70; 95%CrI: 0·50–0·92).
The evidence supports choosing dolutegravir in combination with lamivudine/emtricitabine and tenofovir disoproxil fumarate as the preferred first-line regimen and low-dose efavirenz-based regimens as an alternative. Dolutegravir can be considered to be effective, safe and tolerable.
WHO.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Down syndrome (DS) is the most frequently occurring fetal chromosomal abnormality and different prenatal screening strategies are used for determining risk of DS worldwide. New non-invasive prenatal ...testing (NIPT), which uses cell-free fetal DNA in maternal blood can provide benefits due to its higher sensitivity and specificity in comparison to conventional screening tests. This study aimed to assess the cost-effectiveness of using population-level NIPT in fetal aneuploidy screening for DS.
We developed a microsimulation decision-analytic model to perform a probabilistic cost-effectiveness analysis (CEA) of prenatal screening and diagnostic strategies for DS. The model followed individual simulated pregnant women through the pregnancy pathway. The comparators were serum-only screening, contingent NIPT (i.e., NIPT as a second-tier screening test) and universal NIPT (i.e., NIPT as a first-tier screening test). To address uncertainty around the model parameters, the expected values of costs and quality-adjusted life-years (QALYs) in the base case and all scenario analyses were obtained through probabilistic analysis from a Monte Carlo simulation.
Base case and scenario analyses were conducted by repeating the micro-simulation 1,000 times for a sample of 45,605 pregnant women per the population of British Columbia, Canada (N = 4.8 million). Preliminary results of the sequential CEAs showed that contingent NIPT was a dominant strategy compared to serum-only screening. Compared with contingent NIPT, universal NIPT at the current test price was not cost-effective with an incremental cost-effectiveness ratio over $100,000/QALY. Contingent NIPT also had the lowest cost per DS case detected among these three strategies.
Including NIPT in existing prenatal screening for DS is shown to be beneficial over conventional testing. However, at current prices, implementation of NIPT as a second-tier screening test is more cost-effective than deploying it as a universal test.
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In a 48-week trial in patients with active rheumatoid arthritis despite treatment with methotrexate, adding sulfasalazine and hydroxychloroquine to methotrexate was not inferior to adding etanercept.
...The prognosis for patients with rheumatoid arthritis has improved dramatically over the past two decades.
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The reasons for the improved prognosis include earlier diagnosis, treatment targeted to low disease activity or remission, the use of disease-modifying antirheumatic drugs (DMARDs) in combinations, and the availability of biologic therapies.
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A substantial portion of patients who are diagnosed today will have a clinical remission with therapy.
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Unfortunately, the cost of treating rheumatoid arthritis has also risen dramatically, and this disease is now more expensive to treat than diabetes,
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largely as a consequence of the biologic therapies.
Most clinicians . . .
Objective
To elucidate the role of nonsteroidal antiinflammatory drugs (NSAIDs) in the increased risk of cardiovascular disease (CVD) among osteoarthritis (OA) patients.
Methods
This longitudinal ...study was based on linked health administrative data from British Columbia, Canada. From a population‐based cohort of 720,055 British Columbians, we selected 7,743 OA patients and 23,229 age‐ and sex‐matched non‐OA controls. We used multivariable Cox proportional hazards models to estimate the risk of developing incident CVD (primary outcome) as well as ischemic heart disease, congestive heart failure, and stroke (secondary outcomes). To estimate the mediating effect of NSAIDs, defined as current use of an NSAID according to linked PharmaNet data, in the OA–CVD relationship, we implemented a marginal structural model.
Results
OA patients had a higher risk of developing CVD than controls without OA. After adjusting for socioeconomic status, body mass index, hypertension, diabetes, hyperlipidemia, chronic obstructive pulmonary disease, and Romano comorbidity score, the adjusted hazard ratio (HR) was 1.23 (95% confidence interval 95% CI 1.17–1.28). The adjusted HRs for congestive heart failure, ischemic heart disease, and stroke were 1.42 (95% CI 1.33–1.51), 1.17 (95% CI 1.10–1.26), and 1.14 (95% CI 1.07–1.22), respectively. Approximately 41% of the total effect of OA on increased CVD risk was mediated through NSAIDs. For the secondary outcomes, the proportion mediated through NSAIDs was 23%, 56%, and 64% for congestive heart failure, ischemic heart disease, and stroke, respectively.
Conclusion
The findings of this first study to evaluate the mediating role of NSAIDs in the relationship between OA and CVD suggest that NSAID use contributes substantially to the OA–CVD association.
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The Work Productivity and Activity Impairment (WPAI) questionnaire is a well validated instrument to measure impairments in work and activities. However, its validation among patients with rheumatoid ...arthritis (RA) has not been well established. The present study's purpose is to evaluate the construct validity of the WPAI-general health version among RA patients and its ability to differentiate between RA patients with varying health status.
Patients who were enrolled in the Early Rheumatoid Arthritis Network cohort and were employed at their most recent follow-up were recruited into this sub-study. A questionnaire battery incorporating the WPAI was administered along with a number of health outcomes including the Multidimensional Health Assessment Questionnaire, fatigue and patient assessment of disease activity. The construct validity of the WPAI was tested by the correlations between the WPAI and the health outcomes and other measures of productivity. Student's t tests were used to identify whether the WPAI outcomes differed between the two levels of heath status based on the median of health outcomes.
A total of 150 patients completed the WPAI questionnaire. The average age was 52 years old and the disease duration was 37.5 months since the first rheumatology visit. Of the 137 patients who were working for pay, 26 reported missing work in the past week due to their health problem, accounting for 45.5% of their working time (absenteeism). While 123 patients were working, 24% of their work was impaired due to their health problem (presenteeism). In addition, 33% of the patients' regular daily activities (activity impairment) had been prevented due to their health problems. There were moderate correlations between the WPAI absenteeism and function, pain, fatigue, and disease severity (r = 0.34 to 0.39). The WPAI presenteeism and activity impairment were strongly correlated with the health outcomes (0.67 to 0.77). Patients with more severe disease status (for example, low/high functional disability by median) had significantly higher absenteeism (4%/15%), presenteeism (15%/39%), and activity impairment (19%/53%) than those with less severe disease status.
The WPAI is a valid questionnaire for assessing impairments in paid work and activities in RA patients and for measuring the relative differences between RA patients with different health status.
IMPORTANCE: Diacetylmorphine hydrochloride (the active ingredient in heroin), delivered under supervision, is effective for the treatment of severe opioid use disorder. However, owing to political ...and regulatory barriers, it is not available in many settings around the world, which limits the options for many long-term street opioid injectors not attracted into or retained in available treatments. OBJECTIVE: To test if injectable hydromorphone hydrochloride is noninferior to injectable diacetylmorphine in reducing illicit heroin use for chronic injection opioid users after 6 months of intervention. DESIGN, SETTING, AND PARTICIPANTS: The Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) was a phase 3, double-blind, noninferiority trial. The study randomized 202 long-term street opioid injectors in Vancouver, British Columbia, Canada. Eligible participants were recruited between December 19, 2011, and December 18, 2013. Both intent-to-treat (ITT) and per-protocol (PP) analyses were conducted. INTERVENTIONS: Participants were randomly assigned to receive injectable diacetylmorphine or hydromorphone (up to 3 times daily) for 6 months under supervision. MAIN OUTCOMES AND MEASURES: Primary and coprimary efficacy outcomes were self-reported days of street heroin use (primary), days of any street-acquired opioids in the prior 30 days (noninferiority margin, 4 days), and the proportion of urinalyses positive for street heroin markers (margin, 10% of the observed rate in the diacetylmorphine group). The mean differences between diacetylmorphine and hydromorphone for the ITT and PP analyses were reported. RESULTS: The study included 202 participants; 100 randomized to receive hydromorphone and 102 to diacetylmorphine. Their mean (SD) age was 44.33 (9.63) years, and 30.7% (62 of 202) were women. Noninferiority of hydromorphone was confirmed in the PP analysis (−1.44; 90% CI, −3.22 to 0.27) for street heroin use, although the margin of 4 days was not excluded in the ITT analysis (−2.34; 90% CI, −4.14 to −0.52). Noninferiority was confirmed for any street opioids in the ITT analysis (−0.85; 90% CI, −2.97 to 1.25) and the PP analysis (−0.15; 90% CI, −2.09 to 1.76), as well as for the urinalyses (0.09; 90% CI, −0.02 to 0.19 for the ITT analysis and 0.13; 90% CI, 0.02-0.24 for the PP analysis). There were 29 SAEs considered to have some relationship with the injection medication, 5 in the hydromorphone group and 24 in the diacetylmorphine group (rate ratio, 0.21; 95% CI, 0.06-0.69). Seizures and overdoses accounted for 25 of the 29 related SAEs. CONCLUSIONS AND RELEVANCE: This study provides evidence to suggest noninferiority of injectable hydromorphone relative to diacetylmorphine for long-term opioid dependence. In jurisdictions where diacetylmorphine is currently not available or for patients in whom it is contraindicated or unsuccessful, hydromorphone could be offered as an alternative. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01447212
The Patented Medicine Prices Review Board (PMPRB), the agency that regulates the prices of patented medicines in Canada, published proposed amendments to the regulatory framework in December 2017. ...Because of a series of changes and delays, the revised policy has not yet been finalized. We sought to evaluate the potential early impact of the uncertainty about the PMPRB policy on patented-medicine launches.
We developed a retrospective cohort of patented medicines (molecules) sold in Canada and the 13 countries that the PMPRB currently uses or has proposed to use as price comparators, from sales data from the IQVIA MIDAS database for 2012-2021. The outcome was whether a molecule was launched (i.e., sold) in a specific country within 2 years of its global first launch (2-yr launch). We compared the change of 2-year launch before (2012-2017) and after the proposed amendments were published ("uncertain period," 2018-2021) in Canada with the change in the United States and the other 12 countries as a group ("other-countries group"), using interrupted time series and logistic regressions, respectively. We further conducted analyses for each individual country and subgroups by molecule characteristics, such as therapeutic benefit, separately.
We included 242 and 107 new molecules launched before publication of the proposed amendments and during the uncertain period, respectively. The corresponding 2-year launch proportions were 45.0% and 30.8% in Canada, 81.4% and 82.2% in the US, and 83.9% and 70.1% in the other-countries group. All analyses showed changes in 2-year launch during the uncertain period in the US and in the other-countries group that were similar to the changes in Canada. Greater decreases were observed in Norway and Sweden than in Canada. The 2-year launch proportion for molecules with major therapeutic benefit decreased from 45.8% to 31.3% in Canada during the uncertain period and from 87.5% to 62.5% in the other-countries group, but increased from 91.7% to 100% in the US.
No negative impact of the PMPRB-policy uncertainty on molecule launches was observed when comparing Canada with price-comparator countries, except for molecules with major therapeutic benefit. The reduction in launches of medicines with major therapeutic benefit in Canada requires continuing investigation.
Drug plans take different approaches to determining reimbursement prices for generic drugs. One common approach is to set the maximum reimbursement price as a percentage of the price of the ...interchangeable branded drug. In many countries this percentage depends on the number of generic entrants, a model we call “tiered pricing.” This paper seeks to enhance understanding of how to set the tiers.
We construct a simple model of tiered pricing and set parameters to match evidence on generic drug costs and the distribution of revenues. Using simulation methods, we then assess different tier structures in terms of total surplus and average drug cost.
We find when tiers are bunched tightly together welfare outcomes are poor. Moreover, there are large welfare gains from increasing the number of tiers from one to two, and only small welfare gains from increasing the number of tiers beyond four.
The choice of tiers has substantial welfare and cost implications. While it is possible to refine the simulation analysis based on specific market characteristics, an optimal tier structure, such as the one we propose in the paper, should have at least two tiers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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