Comparative efficacy of sodium-glucose co-transporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta-analysis.

AIM: To compare the relative efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and non-steroidal mineralocorticoid receptor antagonists (nsMRAs) in improving the cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). MATERIALS AND METHODS: We searched PubMed, Embase and Cochrane Library from inception through 25 November 2022. We selected randomized controlled trials that studied patients with CKD and T2D with a follow-up of at least 24 weeks and compared SGLT-2is, GLP-1RAs and nsMRAs with each other and with placebo. Primary outcomes were major adverse cardiovascular events (MACE) and composite renal outcomes (CRO). Secondary outcomes were cardiovascular death, all-cause death, stroke, myocardial infarction and heart failure hospitalization (HFH). A frequentist approach was used to pool risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Twenty-nine studies with 50 938 participants for MACE and 49 965 participants for CRO were included. SGLT-2is did not significantly reduce MACE but were associated with significantly lower risks of CRO compared with GLP-1RAs (RR, 0.77; 95% CI, 0.64-0.91; P = .003) and nsMRAs (RR, 0.78; 95% CI, 0.68-0.90; P = .001). Compared with GLP-1RAs and nsMRAs, SGLT-2is significantly reduced risks of HFH by 31% (RR, 0.69; 95% CI, 0.55-0.88; P = .002) and 22% (RR, 0.78; 95% CI, 0.63-0.95; P = .016), respectively, but did not significantly reduce other secondary outcomes. There were no significant differences between GLP-1RAs and nsMRAs in lowering all outcomes. CONCLUSIONS: SGLT-2is were associated with better cardiorenal protection than GLP-1RAs and nsMRAs in patients with CKD and T2D.

Cost-effectiveness of canagliflozin and dapagliflozin for treatment of patients with chronic kidney disease and type 2 diabetes.

AIM: To examine the cost-effectiveness of adding canagliflozin or dapagliflozin to standard of care (SoC) versus SoC alone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). MATERIALS AND METHODS: We used a Markov microsimulation model to assess the cost-effectiveness of canagliflozin plus SoC (canagliflozin + SoC), dapagliflozin plus SoC (dapagliflozin + SoC) and SoC alone. Analyses were conducted from a healthcare system perspective. Costs were measured in 2021 Canadian dollars (C$), and effectiveness was measured in quality-adjusted life-years (QALYs). RESULTS: Over a patient's lifetime, canagliflozin + SoC and dapagliflozin + SoC yielded cost savings of C$33 460 and C$26 764 and generated 1.38 and 1.44 additional QALYs compared with SoC alone, respectively. While QALY gains with dapagliflozin + SoC were higher than those with canagliflozin + SoC, this strategy was also more costly with the incremental cost-effectiveness ratio exceeding the willingness to pay threshold of C$50 000 per QALY. Dapagliflozin + SoC, however, generated cost savings and QALY gains compared with canagliflozin + SoC over shorter time horizons of 5 or 10 years. CONCLUSIONS: Dapagliflozin + SoC was not cost-effective versus canagliflozin + SoC in patients with CKD and T2D over the lifetime horizon. However, adding canagliflozin or dapagliflozin to SoC was less costly and more effective relative to SoC alone for treatment of CKD and T2D.

Self-reported adherence to direct oral anticoagulants versus warfarin therapy in a specialized thrombosis service-a cross-sectional study of patients in a Canadian Health Region.

PURPOSE: Direct oral anticoagulants (DOACs) have a better safety and efficacy profile than warfarin and are currently recommended for stroke prevention in non-valvular atrial fibrillation (AF) and treatment of venous thromboembolism (VTE). Given that DOACs do not require regular laboratory monitoring compared to warfarin, patients' interactions with the health care system is reduced. Adequate adherence to DOACs is important and reported adherence to anticoagulation is unclear in clinical practice. This study aims to assess self-reported adherence to oral anticoagulants in a specialized Adult Outpatient Thrombosis Service (TS).  METHODS: This cross-sectional study included patients aged ≥ 18 years who were prescribed an oral anticoagulant and had attended at least one appointment with an Adult Outpatient Thrombosis Service (TS) between October 10, 2017, and May 31, 2019. Adherence to oral anticoagulant therapy was assessed using the 12-item validated Adherence to Refills and Medications Scale (ARMS) score. Logistic regression analyses were used to evaluate association between patient characteristics and medication adherence. Adherence rates in DOACs and warfarin were compared. RESULTS: Three hundred and ninety-nine patients completed and returned the survey. Of the 399 who completed the survey, 74% were prescribed DOACs and 26% received warfarin. Most of the patients (89.3%) were ≥ 50 years of age and half (57.3%) were male. About two-thirds (67%) had at least post-secondary education. The duration of anticoagulation use differed between patients on DOAC and warfarin; a greater proportion of those who had used anticoagulants for less than 1 year was on DOACs compared to warfarin (20.9% vs 4.9%, p = 0.001). For patients who had been on anticoagulation for > 5 years, the proportion of warfarin patients was greater than DOAC (57.8% vs 20.5%, p = 0.001). Self-reported adherence to oral anticoagulant therapy using the 12-item ARMS scale for warfarin and DOACs were 87.3% and 90.9%, respectively. Among the warfarin users, patient satisfaction with TS was associated with medication adherence (OR = 0.22; 95% CI: 0.05-0.89). CONCLUSIONS: Self-reported medication adherence was similar between warfarin and DOACs. Since suboptimal adherence is associated with poor clinical outcomes and increased costs, various stakeholders should emphasize the importance of medication adherence to oral anticoagulants at each patient encounter.

Social determinants of the changing tuberculosis prevalence in Viet Nam: Analysis of population-level cross-sectional studies.

BACKGROUND: An ecological relationship between economic development and reduction in tuberculosis prevalence has been observed. Between 2007 and 2017, Viet Nam experienced rapid economic development with equitable distribution of resources and a 37% reduction in tuberculosis prevalence. Analysing consecutive prevalence surveys, we examined how the reduction in tuberculosis (and subclinical tuberculosis) prevalence was concentrated between socioeconomic groups. METHODS AND FINDINGS: We combined data from 2 nationally representative Viet Nam tuberculosis prevalence surveys with provincial-level measures of poverty. Data from 94,156 (2007) and 61,763 (2017) individuals were included. Of people with microbiologically confirmed tuberculosis, 21.6% (47/218) in 2007 and 29.0% (36/124) in 2017 had subclinical disease. We constructed an asset index using principal component analysis of consumption data. An illness concentration index was estimated to measure socioeconomic position inequality in tuberculosis prevalence. The illness concentration index changed from -0.10 (95% CI -0.08, -0.16; p = 0.003) in 2007 to 0.07 (95% CI 0.06, 0.18; p = 0.158) in 2017, indicating that tuberculosis was concentrated among the poorest households in 2007, with a shift towards more equal distribution between rich and poor households in 2017. This finding was similar for subclinical tuberculosis. We fitted multilevel models to investigate relationships between change in tuberculosis prevalence, individual risks, household socioeconomic position, and neighbourhood poverty. Controlling for provincial poverty level reduced the difference in prevalence, suggesting that changes in neighbourhood poverty contribute to the explanation of change in tuberculosis prevalence. A limitation of our study is that while tuberculosis prevalence surveys are valuable for understanding socioeconomic differences in tuberculosis prevalence in countries, given that tuberculosis is a relatively rare disease in the population studied, there is limited power to explore socioeconomic drivers. However, combining repeated cross-sectional surveys with provincial deprivation estimates during a period of remarkable economic growth provides valuable insights into the dynamics of the relationship between tuberculosis and economic development in Viet Nam. CONCLUSIONS: We found that with equitable economic growth and a reduction in tuberculosis burden, tuberculosis became less concentrated among the poor in Viet Nam.

Cost-effectiveness of using artificial intelligence versus polygenic risk score to guide breast cancer screening.

BACKGROUND: Current guidelines for mammography screening for breast cancer vary across agencies, especially for women aged 40-49. Using artificial Intelligence (AI) to read mammography images has been shown to predict breast cancer risk with higher accuracy than alternative approaches including polygenic risk scores (PRS), raising the question whether AI-based screening is more cost-effective than screening based on PRS or existing guidelines. This study provides the first evidence to shed light on this important question. METHODS: This study is a model-based economic evaluation. We used a hybrid decision tree/microsimulation model to compare the cost-effectiveness of eight strategies of mammography screening for women aged 40-49 (screening beyond age 50 follows existing guidelines). Six of these strategies were defined by combinations of risk prediction approaches (AI, PRS or family history) and screening frequency for low-risk women (no screening or biennial screening). The other two strategies involved annual screening for all women and no screening, respectively. Data used to populate the model were sourced from the published literature. RESULTS: Risk prediction using AI followed by no screening for low-risk women is the most cost-effective strategy. It dominates (i.e., costs more and generates fewer quality adjusted life years (QALYs)) strategies for risk prediction using PRS followed by no screening or biennial screening for low-risk women, risk prediction using AI or family history followed by biennial screening for low-risk women, and annual screening for all women. It also extendedly dominates (i.e., achieves higher QALYs at a lower incremental cost per QALY) the strategy for risk prediction using family history followed by no screening for low-risk women. Meanwhile, it is cost-effective versus no screening, with an incremental cost-effectiveness ratio of $23,755 per QALY gained. CONCLUSIONS: Risk prediction using AI followed by no breast cancer screening for low-risk women is the most cost-effective strategy. This finding can be explained by AI's ability to identify high-risk women more accurately than PRS and family history (which reduces the possibility of delayed breast cancer diagnosis) and fewer false-positive diagnoses from not screening low-risk women.

Patient satisfaction with quality of care of a multidisciplinary thrombosis service - a cross sectional survey.

BACKGROUND: In October 2017 we opened a multidisciplinary Adult Outpatient Thrombosis Service (Thrombosis Service) in a regional health authority servicing over 300 000 people. The Thrombosis Service is a comprehensive thrombosis and anticoagulation management program with unique, interrelated clinics providing a broad spectrum of care for this patient group. Evaluation of patient satisfaction with this new model of patient care is an important quality measurement. METHODS: We conducted a cross-sectional survey of patients who attended the Thrombosis Service between October 2017 and May 2019. We measured patient satisfaction with the seven-item Short Assessment of Patient Satisfaction (SAPS) which uses a 5 point scale (0-4) for responses. The continuous score range for SAPS is 0 to 28. Categorical responses for SAPS are defined as 0-10 very dissatisfied, 11-18 dissatisfied, 19-26 satisfied, and 27-28 very satisfied. We used linear regression analysis to examine the associations between patients' characteristics and their satisfaction with the Thrombosis Service. RESULTS: Of the 1058 surveys distributed, 563 were returned. The mean score for the SAPS was 22.1 (SD 4.1, range 8 to 28). For the categorical response, 85% were satisfied or very satisfied with the Thrombosis Service. The multivariate analysis showed patients with post-secondary education were more satisfied with the Thrombosis Service (ß-coefficient 1.6153, p = 0.024), and patients taking warfarin were less likely to be satisfied with the Thrombosis Service (ß-coefficient -1.5832, p = 0.0390). CONCLUSIONS: The majority of survey participants (85%) who attended an appointment in one of the Thrombosis Service clinics were satisfied or very satisfied with the care they received. This information may benefit other centres who are interested in developing a program to manage thrombosis and anticoagulation.

Changes in adults' vaping and smoking behaviours associated with aerosol-free laws.

OBJECTIVES: Banning e-cigarette use in public places has attracted considerable debate, with governments adopting different policies. However, little is known about the outcomes of such bans. We investigated the association of banning e-cigarette use in public places and workplaces in Canadian provinces with adults' vaping and smoking behaviours. DESIGN: Difference-in-differences. SETTING: Nationally representative Canadian Tobacco Use Monitoring Survey (CTUMS) and Canadian Tobacco, Alcohol and Drugs Survey (CTADS). PARTICIPANTS: Adults aged 19 and older from CTADS 2013-2017 for e-cigarette outcomes (N=36 562) and from CTUMS/CTADS 2004-2017 for combustible cigarette outcomes (N=178 654). INTERVENTIONS: Bans on e-cigarette use in public places and workplaces in Canadian provinces. MAIN OUTCOME MEASURES: Past 30-day e-cigarette use, current combustible cigarette use, use of e-cigarettes when unable to smoke combustible cigarettes. RESULTS: After the bans, e-cigarette use in the past 30 days did not change significantly in provinces with a ban compared with provinces without a ban (0.004; 95% CI -0.025 to 0.032; p=0.783). The bans also had no impact on current combustible cigarette use (0.009; 95% CI -0.019 to 0.037; p=0.488). There is evidence of ban evasion among young people aged 19-24 who, after the bans, reported higher use of e-cigarettes when unable to smoke combustible cigarettes (0.114; 95% CI -0.023 to 0.250; p=0.092). CONCLUSIONS: Two years after implementation, the aerosol-free laws in Canada had no impacton adults' vaping and smoking behaviours. Policy efforts are urgently needed to improve the ban enforcement and to deal with discreet vaping among young adults.

Shock and awe or incentive-compatible harm reduction? Graphic health warnings on tobacco packages.

BACKGROUND: Graphic Health Warnings (GHWs) on cigarette packages were first introduced in Canada in 2001 and will become mandatory in the US as of January 2022. While previous studies have evaluated the impacts of GHWs, the data used in these studies have several shortcomings. The objective of this paper was to investigate the likely impact of such warnings in the US based upon the experience of Canada using hitherto unexplored monthly cigarette sales data, and to explore if alternative approaches involving risk-reduced products might be more successful in reducing smoking. METHODS: We used quasi-experimental segmented regression and difference-in-differences analyses. Data on monthly sales (i.e., shipments) of cigarettes from Canadian manufacturers to Canadian retailers during 1995-2005 were obtained from Statistics Canada. RESULTS: We found that GHWs did not have a significant impact on the sales of cigarettes in Canada. We propose an alternative type of graphical health messaging that actively combines information on how to quit with the legally required messaging. The novelty of the proposal is that it is incentive compatible for the supply side of the market and if adopted in several states, the measure could be tested by using a suitable treatment-control design. CONCLUSIONS: Our findings imply that we should not expect any notable decline in sales or consumption as a result of implementation of GHWs in the US. The main impact of GHWs will be to add to the anti-smoking culture that has grown steadily over several decades, and this may impact smoking in the longer term.

Too young for Cannabis? Choice of minimum legal age for legalized non-medical Cannabis in Canada.

BACKGROUND: Choice of minimum legal age (MLA) for cannabis use is a critical and contentious issue in legalization of non-medical cannabis. In Canada where non-medical cannabis was recently legalized in October 2018, the federal government recommended age 18, the medical community argued for 21 or even 25, while public consultations led most Canadian provinces to adopt age 19. However, no research has compared later life outcomes of first using cannabis at these different ages to assess their merits as MLAs. METHODS: We used doubly robust regression techniques and data from nationally representative Canadian surveys to compare educational attainment, cigarette smoking, self-reported general and mental health associated with different ages of first cannabis use. RESULTS: We found different MLAs for different outcomes: 21 for educational attainment, 19 for cigarette smoking and mental health and 18 for general health. Assuming equal weight for these individual outcomes, the 'overall' MLA for cannabis use was estimated to be 19 years. Our results were robust to various robustness checks. CONCLUSION: Our study indicated that there is merit in setting 19 years as MLA for non-medical cannabis.

Incremental Cost-Effectiveness of Aspiration Therapy vs Bariatric Surgery and No Treatment for Morbid Obesity.

INTRODUCTION: Despite its recent approval by the US Food and Drug Administration and Health Canada, aspiration therapy-one of the latest weight loss treatments-remains controversial. Critics have expressed concerns that the therapy could lead to bulimia and other binge eating disorders. Meanwhile, proponents argue that the therapy is less invasive, reversible, and cheaper than bariatric surgery. Cost-effectiveness of this therapy, however, is not yet established. METHODS: We developed a Markov model to estimate the incremental cost-effectiveness of aspiration therapy relative to 2 most common bariatric surgery procedures (gastric bypass and sleeve gastrectomy) and no treatment over a lifetime horizon. Costs were estimated from the health system's perspective using US data. Effectiveness was measured in terms of quality-adjusted life-years (QALYs). RESULTS: Despite being a cheaper procedure than bariatric surgery, aspiration therapy costs more than bariatric surgery in the long term because of its high maintenance costs (i.e., periodic replacement of device parts). It also yields lower QALYs than bariatric surgery because of its smaller weight loss effects. Thus, the therapy is dominated by bariatric surgery. In particular, compared with gastric bypass, it costs US$5,318 more and yields 1.31 fewer QALYs. However, aspiration therapy is cost-effective relative to no treatment with an incremental cost-effectiveness ratio of US$17,532 per QALY gained. DISCUSSION: Given its high lifetime costs and its modest weight loss effects, aspiration therapy is not cost-effective relative to bariatric surgery. However, it is a cost-effective treatment option for patients who lack access to bariatric surgery.

Association between asthma control and asthma cost: Results from a longitudinal study in a primary care setting.

BACKGROUND AND OBJECTIVE: Asthma control can be assessed with the Asthma Control Test (ACT) and a score of 20 or higher indicates good asthma control. Patients pay for their consultation and treatment in the fee-for-service primary healthcare system in Singapore. We hypothesized that achieving asthma control would result in lower asthma costs through reduced acute exacerbations, fewer physician consultations and lower lost productivity. The study compared the healthcare costs of patients who achieved asthma control and those with suboptimal asthma control based on ACT scores. Factors influencing asthma control and healthcare expenditure over time were also examined. METHODS: A total of 736 patients were enrolled into an asthma care programme in two polyclinics during 2008 and 2013. Direct costs of asthma management were derived from the frequency of polyclinic consultations, medication costs and hospitalization. Indirect costs were estimated from lost workdays due to exacerbations. The generalized estimating equation (GEE) approach was used to longitudinally model the factors associated with total healthcare expenditure. RESULTS: Patients with asthma control spent S$48 (US$36) more per doctor visit on asthma drugs (P < 0.01) but incurred S$65 (US$48) less per doctor visit in total costs (P < 0.01) than those with suboptimal asthma control. The savings from achieving asthma control for obese patients were greater than for normal-weight patients (S$42 or the equivalent of US$31; P < 0.05). CONCLUSION: Optimal asthma control was associated with reduced healthcare costs. An effective treatment regimen should also consider other modifiable factors such as weight control to achieve asthma control and eventually reduce asthma costs.

Is bronchial thermoplasty cost-effective as treatment for problematic asthma patients? Singapore's perspective on a global model.

BACKGROUND AND OBJECTIVE: Bronchial thermoplasty (BT) has been shown to be effective at reducing asthma exacerbations and improving asthma control for patients with severe persistent asthma but it is also expensive. Evidence on its cost-effectiveness is limited and inconclusive. In this study, we aim to evaluate the incremental cost-effectiveness of BT combined with optimized asthma therapy (BT-OAT) relative to OAT for difficult-to-treat and severe asthma patients in Singapore, and to provide a general framework for determining BT's cost-effectiveness in other healthcare settings. METHODS: We developed a Markov model to estimate the costs and quality-adjusted life years (QALYs) gained with BT-OAT versus OAT from the societal and health system perspectives. The model was populated using Singapore-specific costs and transition probabilities and utilities from the literature. Sensitivity analyses were conducted to identify the main factors determining cost-effectiveness of BT-OAT. RESULTS: BT-OAT is not cost-effective relative to OAT over a 5-year time horizon with an incremental cost-effectiveness ratio (ICER) of $US138 889 per QALY from the societal perspective and $US139 041 per QALY from the health system perspective. The cost-effectiveness of BT-OAT largely depends on a combination of the cost of the BT procedure and the cost of asthma-related hospitalizations and emergency department (ED) visits. CONCLUSION: Based on established thresholds for cost-effectiveness, BT-OAT is not cost-effective compared with OAT in Singapore. Given its current clinical efficacy, BT-OAT is most likely to be cost-effective in a setting where the cost of BT procedure is low and costs of hospitalization and ED visits are high.

Trends and predictors of asthma costs: results from a 10-year longitudinal study.

Research on asthma costs often focuses on estimating average asthma costs. Trends in asthma costs and patterns of medication use, especially for those who have been followed up and under treatment, have received much less attention. This study's objective was to document asthma costs over time for asthma patients who are enrolled in an asthma care programme in Singapore and to identify its predictors, using a 10-year longitudinal dataset.The study population comprised different cohorts of 939 asthma patients entering the programme at different times during 2004-2013. Average asthma costs were estimated and the trends over time examined graphically, within and across patient cohorts. Regression analyses were conducted to examine cost predictors, with a focus on the relationship between risk factors at programme enrolment and subsequent asthma costs.The results indicate that 10-year average annual asthma cost was GBP 341 per patient. The main drivers of costs were asthma medications and consultation fees. Use of combined inhaled corticosteroid/long-acting ß-agonist medications increased over time, but this was accompanied by declines in controller drug use, doctor visits and total asthma drug costs. Obesity, smoking and asthma severity were the main predictors of subsequent asthma costs, especially for females.

Cost-effectiveness of a National Telemedicine Diabetic Retinopathy Screening Program in Singapore.

PURPOSE: To determine the incremental cost-effectiveness of a new telemedicine technician-based assessment relative to an existing model of family physician (FP)-based assessment of diabetic retinopathy (DR) in Singapore from the health system and societal perspectives. DESIGN: Model-based, cost-effectiveness analysis of the Singapore Integrated Diabetic Retinopathy Program (SiDRP). PARTICIPANTS: A hypothetical cohort of patients aged 55 years with type 2 diabetes previously not screened for DR. METHODS: The SiDRP is a new telemedicine-based DR screening program using trained technicians to assess retinal photographs. We compared the cost-effectiveness of SiDRP with the existing model in which FPs assess photographs. We developed a hybrid decision tree/Markov model to simulate the costs, effectiveness, and incremental cost-effectiveness ratio (ICER) of SiDRP relative to FP-based DR screening over a lifetime horizon. We estimated the costs from the health system and societal perspectives. Effectiveness was measured in terms of quality-adjusted life-years (QALYs). Result robustness was calculated using deterministic and probabilistic sensitivity analyses. MAIN OUTCOME MEASURES: The ICER. RESULTS: From the societal perspective that takes into account all costs and effects, the telemedicine-based DR screening model had significantly lower costs (total cost savings of S$173 per person) while generating similar QALYs compared with the physician-based model (i.e., 13.1 QALYs). From the health system perspective that includes only direct medical costs, the cost savings are S$144 per person. By extrapolating these data to approximately 170 000 patients with diabetes currently being screened yearly for DR in Singapore's primary care polyclinics, the present value of future cost savings associated with the telemedicine-based model is estimated to be S$29.4 million over a lifetime horizon. CONCLUSIONS: While generating similar health outcomes, the telemedicine-based DR screening using technicians in the primary care setting saves costs for Singapore compared with the FP model. Our data provide a strong economic rationale to expand the telemedicine-based DR screening program in Singapore and elsewhere.

Incremental cost-utility of sevelamer relative to calcium carbonate for treatment of hyperphosphatemia among pre-dialysis chronic kidney disease patients.

BACKGROUND: Sevelamer is an alternative to calcium carbonate for the treatment of hyperphosphatemia among non-dialysis dependent patients with chronic kidney disease (CKD). Although some studies show that it may reduce mortality and delay the onset of dialysis when compared to calcium carbonate, it is also significantly more expensive. Prior studies looking at the incremental cost-effectiveness of sevelamer versus calcium carbonate in pre-dialysis patients are based on data from a single clinical trial. The goal of our study is to use a wider range of clinical data to achieve a more contemporary and robust cost-effectiveness analysis. METHODS: We used a Markov model to estimate the lifetime costs and quality-adjusted life years (QALYs) gained for treatment with sevelamer versus calcium carbonate. The model simulated transitions among three health states (CKD not requiring dialysis, end-stage renal disease, and death). Data on transition probabilities and utilities were obtained from the published literature. Costs were calculated from a third party payer perspective and included medication, hospitalization, and dialysis. Sensitivity analyses were also run to encompass a wide range of assumptions about the dose, costs, and effectiveness of sevelamer. RESULTS: Over a lifetime, the average cost per patient treated with sevelamer is S$180,724. The estimated cost for patients treated with calcium carbonate is S$152,988. A patient treated with sevelamer gains, on average, 6.34 QALYs relative to no treatment, whereas a patient taking calcium carbonate gains 5.81 QALYs. Therefore, sevelamer produces an incremental cost-effectiveness ratio (ICER) of S$51,756 per QALY gained relative to calcium carbonate. CONCLUSION: Based on established benchmarks for cost-effectiveness, sevelamer is cost effective relative to calcium carbonate for the treatment of hyperphosphatemia among patients with chronic kidney disease initially not on dialysis.

Effects of a Driver Cellphone Ban on Overall, Handheld, and Hands-Free Cellphone Use While Driving: New Evidence from Canada.

We provide new evidence on the effects of increasingly common driver cellphone bans on self-reported overall, handheld, and hands-free cellphone use while driving by studying Ontario, Canada, which instituted a 3-month education campaign in November 2009 followed by a binding driver cellphone ban in February 2010. Using residents of Alberta as a control group in a difference-in-differences framework, we find visual and regression-based evidence that Ontario's cellphone ban significantly reduced overall and handheld cellphone use. We also find that the policies significantly increased hands-free cellphone use. The reductions in overall and handheld use are driven exclusively by women, whereas the increases in hands-free use are much larger for men. Our results provide the first direct evidence that cellphone bans have the unintended effect of inducing substitution to hands-free devices.

Intended and unintended effects of restrictions on the sale of cigarillos to youth: evidence from Canada.

BACKGROUND: Youth consumption of cigarillos (ie, little cigars) has increased markedly in recent years. In July 2010, the Canadian government banned the sale of flavoured cigarillos and required unflavoured cigarillos to be sold in packs of at least 20 units. This paper assesses changes in young persons' use of cigarillos and regular cigars, which are potential substitutes, following the policy. METHODS: To investigate of the change in cigar smoking following the policy, we constructed a segmented regression model that allowed the policy to change the height and the slope of the trend in the outcome variables. The model was estimated using data from the 2007-2011 Canadian Tobacco Use Monitoring Surveys. RESULTS: We obtained visual and regression-based evidence that use of cigarillos among youth declined following the policy. We also found a small, gradual increase in their use of regular cigars, possibly due to their compensatory switching from cigarillos to regular cigars. Overall, there was a net reduction in cigar use among youth after the intervention. INTERPRETATION: The policy achieved its goal of reducing youth's consumption of cigarillos, but may have an unintended consequence of increasing their use of regular cigars. Policymakers should address the possibility that youth switch to regular cigars in response to restricted access to cigarillos. Possible ways of discouraging this substituting behaviour include extending the ban to cover all flavoured cigars and mandating a minimum pack size for all cigars, or raising taxes on flavoured cigars.

Economic evaluation of a hospital-initiated intervention for smokers with chronic disease, in Ontario, Canada.

INTRODUCTION: Cigarette smoking causes many chronic diseases that are costly and result in frequent hospitalisation. Hospital-initiated smoking cessation interventions increase the likelihood that patients will become smoke-free. We modelled the cost-effectiveness of the Ottawa Model for Smoking Cessation (OMSC), an intervention that includes in-hospital counselling, pharmacotherapy and posthospital follow-up, compared to usual care among smokers hospitalised with acute myocardial infarction (AMI), unstable angina (UA), heart failure (HF), and chronic obstructive pulmonary disease (COPD). METHODS: We completed a cost-effectiveness analysis based on a decision-analytic model to assess smokers hospitalised in Ontario, Canada for AMI, UA, HF, and COPD, their risk of continuing to smoke and the effects of quitting on re-hospitalisation and mortality over a 1-year period. We calculated short-term and long-term cost-effectiveness ratios. Our primary outcome was 1-year cost per quality-adjusted life year (QALY) gained. RESULTS: From the hospital payer's perspective, delivery of the OMSC can be considered cost effective with 1-year cost per QALY gained of $C1386, and lifetime cost per QALY gained of $C68. In the first year, we calculated that provision of the OMSC to 15 326 smokers would generate 4689 quitters, and would prevent 116 rehospitalisations, 923 hospital days, and 119 deaths. Results were robust within numerous sensitivity analyses. DISCUSSION: The OMSC appears to be cost-effective from the hospital payer perspective. Important consideration is the relatively low intervention cost compared to the reduction in costs related to readmissions for illnesses associated with continued smoking.

Structural analysis of the essential self-cleaving type III secretion proteins EscU and SpaS.

During infection by Gram-negative pathogenic bacteria, the type III secretion system (T3SS) is assembled to allow for the direct transmission of bacterial virulence effectors into the host cell. The T3SS system is characterized by a series of prominent multi-component rings in the inner and outer bacterial membranes, as well as a translocation pore in the host cell membrane. These are all connected by a series of polymerized tubes that act as the direct conduit for the T3SS proteins to pass through to the host cell. During assembly of the T3SS, as well as the evolutionarily related flagellar apparatus, a post-translational cleavage event within the inner membrane proteins EscU/FlhB is required to promote a secretion-competent state. These proteins have long been proposed to act as a part of a molecular switch, which would regulate the appropriate chronological secretion of the various T3SS apparatus components during assembly and subsequently the transported virulence effectors. Here we show that a surface type II beta-turn in the Escherichia coli protein EscU undergoes auto-cleavage by a mechanism involving cyclization of a strictly conserved asparagine residue. Structural and in vivo analysis of point and deletion mutations illustrates the subtle conformational effects of auto-cleavage in modulating the molecular features of a highly conserved surface region of EscU, a potential point of interaction with other T3SS components at the inner membrane. In addition, this work provides new structural insight into the distinct conformational requirements for a large class of self-cleaving reactions involving asparagine cyclization.