Radon is the second most important cause of lung cancer, ranked by the World Health Organization as the fifth leading cause of mortality in 2010. An updated database of national radon exposures for ...66 countries allows the global burden of lung cancer mortality attributable to radon to be estimated.
Our goal was to estimate the global population attributable burden of lung cancer mortality in 2012 from residential radon.
Estimates of the population attributable risk (PAR) of lung cancer mortality from radon were determined using the attributable fraction approach, using three models for excess relative risk of lung cancer from radon.
The estimates of the median PAR of lung cancer mortality from residential radon in 2012 for the 66 countries having representative national radon surveys were consistent, as 16.5%, 14.4%, and 13.6% for the exposure-age-concentration (EAC) model (BEIR VI), the Hunter model, and the Kreuzer model, respectively. The mean PAR using the EAC model ranged from 4.2% (95% CI: 0.9, 11.7) for Japan, to 29.3% (95% CI: 22.9, 35.7) for Armenia, with a median for the 66 countries of 16.5%. Radon-attributable lung cancer deaths for all 66 countries totaled 226,057 in 2012 and represent a median of 3.0% of total cancer deaths.
Consistent findings between the three models used to estimate excess relative risks of lung cancer from radon, and between the attributable fraction methodology and the life table analysis, confirm that residential radon is responsible for a substantial proportion of lung cancer mortality worldwide. https://doi.org/10.1289/EHP2503.
Introduction. Given the lack of independent analyses comparing numerous pharmacotherapies for osteoporosis, the study objective was to identify the optimal osteoporosis treatment based on a woman’s ...age, fracture history, and ability to tolerate oral bisphosphonates adopting practices recommended in the recently revised Canadian guidelines. Methods. A cost utility analysis from the health care system perspective compared alendronate, etidronate, risedronate, zoledronate, denosumab, and no pharmacotherapy using a Markov model incorporating data on fracture risk and their associated costs, mortality, and disutility and treatment effect. Stratified analysis was conducted based on age, fracture history, and ability to tolerate oral bisphosphonates. Expected lifetime outcomes were obtained through probabilistic analysis with scenario analyses addressing methodological and structural uncertainty. Results. For women able to tolerate oral bisphosphonates, risedronate and etidronate were dominated. Compared to no therapy, alendronate was either dominant or was associated with a low incremental cost per QALY (quality-adjusted life years) gained (ICER)—less than CAN$3,751 based on age and fracture history. In comparison with alendronate, both zoledronate and denosumab were either dominated or associated with a high ICER—greater than CAN$660,000 per QALY. For women unable to tolerate bisphosphonates, dependent on age and fracture history, the ICER for zoledronate versus no therapy ranged from CAN$17,770 to CAN$94,365 per QALY. For all strata, denosumab was dominated by zoledronate or had an ICER greater than CAN$3.0 million. Scenario analyses found consistent findings. Conclusions. Based on a threshold of CAN$50,000 per QALY, alendronate is optimal for osteoporotic women who can tolerate oral bisphosphonates regardless of age or fracture history. For women unable to tolerate oral bisphosphonates, zoledronate is optimal for women with previous fracture or aged 80 to 84 or over 90 with no previous fracture.
Summary Background Serious infections are a major concern for patients considering treatments for rheumatoid arthritis. Evidence is inconsistent as to whether biological drugs are associated with an ...increased risk of serious infection compared with traditional disease-modifying antirheumatic drugs (DMARDs). We did a systematic review and meta-analysis of serious infections in patients treated with biological drugs compared with those treated with traditional DMARDs. Methods We did a systematic literature search with Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to Feb 11, 2014. Search terms included “biologics”, “rheumatoid arthritis” and their synonyms. Trials were eligible for inclusion if they included any of the approved biological drugs and reported serious infections. We assessed the risk of bias with the Cochrane Risk of Bias Tool. We did a Bayesian network meta-analysis of published trials using a binomial likelihood model to assess the risk of serious infections in patients with rheumatoid arthritis who were treated with biological drugs, compared with those treated with traditional DMARDs. The odds ratio (OR) of serious infection was the primary measure of treatment effect and calculated 95% credible intervals using Markov Chain Monte Carlo methods. Findings The systematic review identified 106 trials that reported serious infections and included patients with rheumatoid arthritis who received biological drugs. Compared with traditional DMARDs, standard-dose biological drugs (OR 1·31, 95% credible interval CrI 1·09–1·58) and high-dose biological drugs (1·90, 1·50–2·39) were associated with an increased risk of serious infections, although low-dose biological drugs (0·93, 0·65–1·33) were not. The risk was lower in patients who were methotrexate naive compared with traditional DMARD-experienced or anti-tumour necrosis factor biological drug-experienced patients. The absolute increase in the number of serious infections per 1000 patients treated each year ranged from six for standard-dose biological drugs to 55 for combination biological therapy, compared with traditional DMARDs. Interpretation Standard-dose and high-dose biological drugs (with or without traditional DMARDs) are associated with an increase in serious infections in rheumatoid arthritis compared with traditional DMARDs, although low-dose biological drugs are not. Clinicians should discuss the balance between benefit and harm with the individual patient before starting biological treatment for rheumatoid arthritis. Funding Rheumatology Division at the University of Alabama at Birmingham.
Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate belongs to the bisphosphonate class of drugs, which act to inhibit bone ...resorption by interfering with the activity of osteoclasts.
To assess the efficacy of alendronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women.
We searched CENTRAL, MEDLINE and EMBASE for relevant randomized controlled trials published between 1966 to 2007.
Women receiving at least one year of alendronate, for postmenopausal osteoporosis, were compared to those receiving placebo and/or concurrent calcium/vitamin D. The outcome was fracture incidence.
We undertook study selection and data abstraction in duplicate. We performed meta-analysis of fracture outcomes using relative risks and a > 15% relative change was considered clinically important. We assessed study quality through reporting of allocation concealment, blinding and withdrawals.
Eleven trials representing 12,068 women were included in the review. Relative (RRR) and absolute (ARR) risk reductions for the 10 mg dose were as follows. For vertebral fractures, a significant 45% RRR was found (RR 0.55, 95% CI 0.45 to 0.67). This was significant for both primary prevention, with 45% RRR (RR 0.55, 95% CI 0.38 to 0.80) and 2% ARR, and secondary prevention with 45% RRR (RR 0.55, 95% CI 0.43 to 0.69) and 6% ARR. For non-vertebral fractures, a significant 16% RRR was found (RR 0.84, 95% CI 0.74 to 0.94). This was significant for secondary prevention, with 23% RRR (RR 0.77, 95% CI 0.64 to 0.92) and 2% ARR, but not for primary prevention (RR 0.89, 95% CI 0.76 to 1.04). There was a significant 40% RRR in hip fractures (RR 0.60, 95% CI 0.40 to 0.92), but only secondary prevention was significant with 53% RRR (RR 0.47, 95% CI 0.26 to 0.85) and 1% ARR. The only significance found for wrist was in secondary prevention, with a 50% RRR (RR 0.50 95% CI 0.34 to 0.73) and 2% ARR. For adverse events, we found no statistically significant differences in any included study. However, observational data raise concerns regarding potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw.
At 10 mg per day, both clinically important and statistically significant reductions in vertebral, non-vertebral, hip and wrist fractures were observed for secondary prevention ('gold' level evidence, www.cochranemsk.org). We found no statistically significant results for primary prevention, with the exception of vertebral fractures, for which the reduction was clinically important ('gold' level evidence).
Objectives: The research objectives were two-fold: first, to systematically review the literature on the cost-effectiveness of home telehealth for chronic diseases, and second to develop a framework ...for the conduct of economic evaluation of home telehealth projects for patients with chronic diseases. Methods: A comprehensive literature search identified twenty-two studies (n = 4,871 patients) on home telehealth for chronic diseases published between 1998 and 2008. Studies were reviewed in terms of their methodological quality and their conclusions. Results: Home telehealth was found to be cost saving from the healthcare system and insurance provider perspectives in all but two studies, but the quality of the studies was generally low. An evaluative framework was developed which provides a basis to improve the quality of future studies to facilitate improved healthcare decision making, and an application of the framework is illustrated using data from an existing program evaluation of a home telehealth program. Conclusions: Current evidence suggests that home telehealth has the potential to reduce costs, but its impact from a societal perspective remains uncertain until higher quality studies become available.
Abstract Objectives The primary objective was to assess the cost-effectiveness of new oral anticoagulants compared with warfarin in patients with nonvalvular atrial fibrillation. Secondary objectives ...related to assessing the cost-effectiveness of new oral anticoagulants stratified by center-specific time in therapeutic range, age, and CHADS2 score. Methods Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained. Analysis used a Markov cohort model that followed patients from initiation of pharmacotherapy to death. Transition probabilities were obtained from a concurrent network meta-analysis. Utility values and costs were obtained from published data. Numerous deterministic sensitivity analyses and probabilistic analysis were conducted. Results The incremental cost per QALY gained for dabigatran 150 mg versus warfarin was $20,797. Apixaban produced equal QALYs at a higher cost. Dabigatran 110 mg and rivaroxaban were dominated by dabigatran 150 mg and apixaban. Results were sensitive to the drug costs of apixaban, the time horizon adopted, and the consequences from major and minor bleeds with dabigatran. Results varied by a center’s average time in therapeutic range, a patient’s CHADS2 score, and patient age, with either dabigatran 150 mg or apixaban being optimal. Conclusions Results were highly sensitive to patient characteristics. Rivaroxaban and dabigatran 110 mg were unlikely to be cost-effective. For different characteristics, apixaban or dabigatran 150 mg were optimal. Thus, the choice between these two options may come down to the price of apixaban and further evidence on the impact of major and minor bleeds with dabigatran.
Introduction
Nous avons déterminé l’incidence des inhalateurs électroniques de nicotine sur les coûts et les résultats liés à la santé au Canada en fonction de leur effet sur les taux d’arrêt du ...tabagisme et d’initiation au tabagisme.
Méthodologie
Nous avons utilisé des modèles de Markov selon le genre pour estimer les années de vie actualisées sur un horizon à vie, les années de vie ajustées en fonction de la qualité (AVAQ) et les coûts des soins de santé liés au tabagisme pour des cohortes de garçons et de filles de 15 à 19 ans, selon des scénarios où 1) les inhalateurs électroniques de nicotine sont accessibles (statu quo), 2) les inhalateurs électroniques de nicotine ne sont aucunement accessibles et 3) les inhalateurs électroniques de nicotine sont accessibles sur ordonnance d’un fournisseur de soins de santé pour l’arrêt du tabagisme, en complément aux outils de cessation tabagique actuellement reconnus. L’analyse a été effectuée du point de vue d’un système de soins de santé financé par des fonds publics.
Résultats
Les résultats sont exprimés pour 1 000 personnes et reposent sur les valeurs attendues obtenues par une simulation de Monte-Carlo avec 10 000 itérations. Pour les garçons de 15 à 19 ans, les années de vie, les AVAQ et les coûts des soins de santé liés au tabagisme étaient de respectivement 41 553, 35 871 et 79 645 964 $ CA lorsque les inhalateurs électroniques de nicotine étaient accessibles, de respectivement 41 568, 35 894 et 79 645 960 $ CA lorsque les inhalateurs électroniques de nicotine n’étaient pas accessibles et de respectivement 41 570, 35 897 et 79 605 869 $ CA lorsque les inhalateurs électroniques de nicotine étaient accessibles sur ordonnance seulement. Pour les filles, les années de vie, les AVAQ et les coûts des soins de santé liés au tabagisme étaient de respectivement 43 596, 37 416 et 69 242 856 $ CA lorsque les inhalateurs électroniques de nicotine étaient accessibles, de respectivement 43 610, 37 438 et 69 085 926 $ CA lorsque les inhalateurs électroniques de nicotine n’étaient pas accessibles et de respectivement 43 611, 37 438 et 69 076 034 $ CA lorsque les inhalateurs électroniques de nicotine étaient accessibles sur ordonnance seulement. Ainsi, les scénarios dans lesquels les inhalateurs électroniques de nicotine ne sont pas accessibles ou ne sont accessibles que sur ordonnance l’emportent sur le statu quo.
Conclusion
Ces résultats montrent qu’un changement de politique qui rendrait les inhalateurs électroniques de nicotine inaccessibles à la population canadienne ou accessibles sur ordonnance seulement permettrait probablement d’améliorer la santé de la population et de réduire les coûts des soins de santé.
Most women with breast cancer are diagnosed at an early stage and more than 80% will be long-term survivors. Routine follow-up marks the transition from intensive treatment to survivorship. It is ...usual practice for routine follow-up to take place in specialist clinics. This study tested the hypothesis that follow-up by the patient's family physician is a safe and acceptable alternative to specialist follow-up.
A multicenter, randomized, controlled trial was conducted involving 968 patients with early-stage breast cancer who had completed adjuvant treatment, were disease free, and were between 9 and 15 months after diagnosis. Patients may have continued receiving adjuvant hormonal therapy. Patients were randomly allocated to follow-up in the cancer center according to usual practice (CC group) or follow-up from their own family physician (FP group). The primary outcome was the rate of recurrence-related serious clinical events (SCEs). The secondary outcome was health-related quality of life (HRQL).
In the FP group, there were 54 recurrences (11.2%) and 29 deaths (6.0%). In the CC group, there were 64 recurrences (13.2%) and 30 deaths (6.2%). In the FP group, 17 patients (3.5%) compared with 18 patients (3.7%) in the CC group experienced an SCE (0.19% difference; 95% CI, -2.26% to 2.65%). No statistically significant differences (P < .05) were detected between groups on any of the HRQL questionnaires.
Breast cancer patients can be offered follow-up by their family physician without concern that important recurrence-related SCEs will occur more frequently or that HRQL will be negatively affected.
Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Risedronate belongs to the bisphosphonate class of drugs which act to inhibit bone ...resorption by interfering with the activity of osteoclasts.
To assess the efficacy of residronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women.
We searched CENTRAL, MEDLINE and EMBASE. Relevant randomized controlled trials published between 1966 to 2007 were identified.
Women receiving at least one year of risedronate for postmenopausal osteoporosis were compared to those receiving placebo or concurrent calcium/vitamin D or both. The outcome was fracture incidence.
We carried out study selection and data abstraction in duplicate. Study quality was assessed through the reporting of allocation concealment, blinding and withdrawals. Meta-analysis was preformed using relative risks and a >15% relative change was considered clinically important.
Seven trials were included in the review representing 14,049 women. Relative (RRR) and absolute (ARR) risk reductions for the 5 mg dose were as follows. Risk estimates for primary prevention were available only for vertebral and non vertebral fractures and showed no statistically significant effect of risedronate on fractures. For secondary prevention, a significant 39% RRR in vertebral fractures (RR 0.61, 95% CI 0.50 to 0.76) with 5% ARR was found. For non-vertebral fractures, a significant 20% RRR (RR 0.80, 95% CI 0.72 to 0.90) with 2% ARR and for hip fractures there was a significant 26% RRR (RR: 0.74, 95% CI 0.59 to 0.94) with a 1% ARR. When primary and secondary prevention studies were combined, the reduction in fractures remained statistically significant for both vertebral (RR 0.63, 0.51 to 0.77) and non vertebral fractures (RR 0.80, 0.72 to 0.90)For adverse events, no statistically significant differences were found in any of the included studies. However, observational data has led to concerns regarding the potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw.
At 5 mg/day a statistically significant and clinically important benefit in the secondary prevention of vertebral, non-vertebral and hip fractures was observed, but not for wrist. The level of evidence for secondary prevention is Gold (www.cochranemsk.org) for vertebral and non-vertebral and Silver for hip and wrist. There were no statistically significant reductions in the primary prevention of vertebral and non-vertebral fractures. The level of evidence is Silver.
Network meta-analysis is increasingly used to allow comparison of multiple treatment alternatives simultaneously, some of which may not have been compared directly in primary research studies. The ...majority of network meta-analyses published to date have incorporated data from randomized controlled trials (RCTs) only; however, inclusion of non-randomized studies may sometimes be considered. Non-randomized studies can complement RCTs or address some of their limitations, such as short follow-up time, small sample size, highly selected population, high cost, and ethical restrictions. In this paper, we discuss the challenges and opportunities of incorporating both RCTs and non-randomized comparative cohort studies into network meta-analysis for assessing the safety and effectiveness of medical treatments. Non-randomized studies with inadequate control of biases such as confounding may threaten the validity of the entire network meta-analysis. Therefore, identification and inclusion of non-randomized studies must balance their strengths with their limitations. Inclusion of both RCTs and non-randomized studies in network meta-analysis will likely increase in the future due to the growing need to assess multiple treatments simultaneously, the availability of higher quality non-randomized data and more valid methods, and the increased use of progressive licensing and product listing agreements requiring collection of data over the life cycle of medical products. Inappropriate inclusion of non-randomized studies could perpetuate the biases that are unknown, unmeasured, or uncontrolled. However, thoughtful integration of randomized and non-randomized studies may offer opportunities to provide more timely, comprehensive, and generalizable evidence about the comparative safety and effectiveness of medical treatments.