Increased Virtual Visits to Physicians During the COVID-19 Pandemic and Estimated Impact on Physician Compensation: The Case of Lung and Colorectal Cancers, Chronic Obstructive Pulmonary Diseases, and Heart Failure in Alberta, Canada.

Introduction: The COVID-19 pandemic started in Alberta in March 2020 and significantly increased telehealth service use and provision reducing the risk of virus transmission. We examined the change in the number and proportion of virtual visits by physician specialty and condition (chronic obstructive pulmonary diseases [COPD], heart failure [HF], colorectal and lung cancers), as well as associated changes in physician compensation. Methods: A population-based design was used to analyze all processed physician claims comparing the number and proportion of virtual visits and associated physician billings relative to in-person between pre- (2019/2020) and intra-pandemic (2020/2021). Physician compensations were the claim amounts paid by the health insurance. Results: Pre-pandemic (intra-), there were 8,981 (8,897) lung cancer, 9,245 (9,029) colorectal, 37,558 (36,292) HF, and 68,270 (52,308) COPD patients. Each patient had totally 2.3-4.7 (of which 0.4-0.6% were virtual) general practitioner (GP) visits and 0.9-2.3 (0.2-0.7% were virtual) specialist visits per year pre-pandemic. The average number and proportion of per-patient virtual visits to GPs and specialists grew significantly pre- to intra-pandemic by 2,138-4,567%, and 2,201-7,104%, respectively. Given the lower fees of virtual compared with in-person visits, the reduction in physician compensation associated with the increased use of virtual care was estimated at $3.85 million, with $2.44 million attributed to specialist and $1.41 million to GP. Discussion: Utilization of telehealth increased significantly, while the physician billings per patient and physician compensation declined early in the pandemic in Alberta for the four chronic diseases considered. This study forms the basis for future study in understanding the impact of virtual care, now part of the fabric of health care delivery, on quality of care and patient safety, overall health service utilization (such as diagnostic imaging and other investigations), as well as economic impacts to patients, health care systems, and society.

Treated versus self-reported prevalence of chronic pain and costs of patients' health services utilization: a population-based study of health administrative databases.

Objectives: To compare treated to self-reported prevalence of chronic pain (CP) and to estimate health services utilization (HSU) costs of patients treated for CP in Alberta, Canada. Methods: Patients treated for CP were identified by the physician billing codes of health services for CP from the practitioner claims database in fiscal year 2021/22. The treated prevalence of CP (number of these patients divided by the population) was compared to the self-reported prevalence of CP previously estimated (doi:10.1371/journal.pone.0272638). Costs of patients' HSU included costs for general practitioner (GP), specialist, inpatient, emergency department, outpatient clinic services, and prescription drugs. Results: The treated prevalence of CP was 6.0% (4.4% among males and 7.8% among females) which was 30% to 41% of the self-reported prevalence. The highest treated prevalence (7.2%) was found in the age group of 18-64 years, followed by age groups of >64 years (7.0%) and <18 years (2.1%). The average cost per patient per year was $5096 ($5878 for males and $4652 for females), of which hospitalizations accounted for 65.0%, outpatient clinic visits 16.4%, ED visits 9.5%, prescription drugs 4.7%, GP visits 3.9%, and specialist visits 0.4%. The total cost of patients with CP for the health system was $1.37 billion (∼7% of total health expenditure), of which males accounted for 41.7% and females for 58.3%. Discussion: Our findings suggest that the economic burden of CP is considerable and that many people with self-reported CP do not use the public healthcare services. This can be multifactorial, including lack of availability and accessibility of publicly funded services, people's lack of awareness of available services, lower utilization due to COVID-19 pandemic, and reliance on self-management, private services, and alternative treatments. Further studies are warranted to inform future policies and health system initiatives aiming to reduce the burden of CP and improve lives of people living with it.

Health Care Utilization and Costs in Lung Cancer Screening Participants-A Propensity-Matched Economic Analysis.

Introduction: Lung cancer screening (LCS) for high-risk populations has been firmly established to reduce lung cancer mortality, but concerns exist regarding unintended downstream costs. Methods: Mean health care utilization and costs were compared in the Alberta Lung Cancer Screening Study in a cohort undergoing LCS versus a propensity-matched control group who did not. Results: A cohort of 651 LCS participants was matched to 336 unscreened controls. Over the study period (mean 3.6 y), a modest increase in the number of claims (22.4 versus 21.9 per person-year [PY]; Δ 0.50 [95% confidence interval: 0.15-0.86], p = 0.006) and outpatient visits (4.01 versus 3.50 per PY; Δ 0.51 [0.37-0.65], p <0.0001), but not in inpatient admissions, was noted in the screened cohort. Claims payments, inpatient costs, and cancer care costs were similar in the screening arm versus the unscreened. Outpatient encounter costs per participant were higher in the screened group ($2662.18 versus $2040.67 per PY; Δ -$621.51 [-1118.05 to -124.97], p = 0.014). Removing the additional computed tomography screening examinations rendered differences not significant. Mean total costs were not significantly different at $6461.10 per PY in the screening group and $6125.31 in the unscreened group (Δ -$335.79 [-2009.65 to 1338.07], p = 0.69). Conclusions: Modest increases in outpatient costs are noted in individuals undergoing LCS, in part attributable to the screening examinations, without differences in overall health care costs. Health care costs and utilization seem otherwise similar in individuals participating in LCS and those who do not.

Effects of Three-Hour Wearing Personal Protective Equipment on Heart Rate Variability in Healthcare Workers for the Treatment of COVID-19 Patients.

Background: Personal protective equipment (PPE), an essential shield to protect healthcare workers (HCWs) during the COVID-19 pandemic, has been reported to affect their heart rate variability (HRV). Objective: To investigate the changes of very short-term heart rate variability in HCWs after three hours of wearing PPE to treat COVID-19 patients at different working times and intensities, and related factors. Methods: Sixty-five healthy HCWs were enrolled at the Number 2 Infectious Field Hospital (formed by Military Hospital 103), Vietnam. Two-minute 12-lead electrocardiograms were recorded before wearing and after removing PPE. Results: After three hours of wearing PPE, the mean heart rate of HCWs increased (p = 0.048) meanwhile, the oxygen saturation decreased significantly (p = 0.035). Standard deviation of all normal to normal intervals (SDNN), mean intervals RR (mean NN), and root mean square successive difference (rMSSD) after wearing PPE was also reduced significantly. SDNN, Mean NN, and rMSSD decreased as the working intensity increased (as in mild, moderate, and severe patient departments). In univariate regression analysis, logSDNN, logmean NN and logrMSSD were positively correlated with SpO2 and QT interval (r = 0.14, r = 0.31, r = 0.25; r = 0.39, r = 0.77, r = 0.73, respectively) and were negatively correlated with ambient temperature inside PPE (r = -0.41, r = -0.405, r = -0.25, respectively) while logmean NN and log rMSSD were negatively correlated with diastolic blood pressure (r = -0.43, r = -0.39, respectively). In multivariable regression analysis, logSDNN and logmean NN were negatively correlated to ambient temperature inside PPE (r = -0.34, r = -0.18, respectively). Conclusion: Time-domain heart rate variability decreased after wearing PPE. Time-domain HRV parameters were related to ambient temperature inside PPE, diastolic blood pressure, QT interval, and SpO2.

Average lifespan shortened due to cancer in selected countries of North America, Europe, Asia and Oceania, 2006 and 2016.

PURPOSE: We applied a novel measure of average lifespan shortened (ALSS) to examine changes in lifespan among patients who died of cancer over a 10-year period from 2006 to 2016 in 20 selected high-income countries from North America, Europe, Asia, and Oceania. METHODS: We retrieved cancer deaths in each country from the World Health Organization mortality database. We calculated ALSS as a ratio of years of life lost to the expected lifespan among patients who died from cancer. RESULTS: Between 2006 and 2016, we observed modest changes in ALSS for overall cancer deaths over the study in many countries. The changes in the ALSS over time due to any cancer ranged between -1.7 and +0.4 percentage points (pps) among men and between -1.9 and +0.6 pps among women. Across countries, overall cancer deaths led to an average loss between 16% and 22% of their lifespan in men, and between 18% and 24% in women. Across cancer sites, patients who died of central nervous system cancers, for instance, lost a large proportion of their lifespan. CONCLUSIONS: In this study, we demonstrated the use of ALSS across selected high-income countries, which enables population-level assessment of premature mortality among cancer patients over time.

Economic burden of chronic pain in Alberta, Canada.

BACKGROUND: Although chronic pain (CP) is common, little is known about its economic burden in Alberta, Canada. AIMS: To estimate incremental (as compared to the general population or people without CP) societal (healthcare and lost productivity) costs of CP in Alberta. METHODS: We applied the prevalence estimated from the Canadian Community Health Survey data to the population retrieved from the Statistics Canada to estimate the number of people with CP in Alberta in 2019. We analyzed the Alberta Health administrative databases to estimate the healthcare costs of person with CP. Finally, we multiplied the number of people with the cost per person. RESULTS: The prevalence of any CP was 20.1% and of activity-preventing CP was 14.5% among people aged > = 12 years. Incremental cost per person with CP per year was CA$2,217 for healthcare services (among people aged > = 12 years) and CA$8,412 for productivity losses (among people aged 18-64 years). Of the healthcare cost, prescription drugs accounted for the largest share (32.8%), followed by inpatient services (31.0%), outpatient services (13.1%), physician services (9.8%), other services (7.4%), and diagnostic imaging (5.8%). Provincially, total incremental cost of CP ranges from CA$1.2 to 1.7 billion for healthcare services (6% to 8% of total provincial health expenditure); and CA$3.4 to 4.7 billion for productivity losses. Considering costs for long-term care services, the total societal cost of CP in Alberta was CA$6.3 to 8.3 billion per year, reflecting 2.0% to 2.7% of Alberta's GDP. CONCLUSIONS: Interventions improving CP prevention and management to reduce this substantial economic burden are urgently needed.

Expected Cost Savings From Low-Dose Computed Tomography Scan Screening for Lung Cancer in Alberta, Canada.

Introduction: The expensive modern therapeutic regimens for advanced lung cancer (LC) stages have been recently approved. We evaluated whether low-dose computed tomography (LDCT) LC screening of high-risk Albertans is cost saving. Methods: We used a decision analytical modeling technique with a health system perspective and a time horizon of 3 years to compare benefits associated with reduced health service utilization (HSU) from earlier diagnosis to the costs of screening. Using patient-level data, HSU costs by stage of disease were estimated for patients with LC, including inpatient, outpatient, and physician services, and costs for prescription drugs and cancer treatments. Results: Of 101,000 people aged 55 to 74 years eligible for screening, an estimated 88,476 scans would be performed in Alberta in 3 years. Given LDCT sensitivity and specificity of 90.5% and 93.1%, respectively, we estimated that a stage shift toward earlier diagnosis would be expected whereby 43% more patients would be identified at stage 1 or 2 as compared with without screening. The estimated cost of screening is $35.6 million (M), whereas the stage shift associated with screening would avoid $42M in HSU costs. The net cost avoidance associated with screening is therefore $6.65M. The probability for the screening to be cost saving is estimated at 72%. Conclusions: This study has revealed that LDCT LC screening is likely to be cost saving in Alberta. Adoption of this program into the provincial health care system is worth considering provided constraints in the system related to surgical capacity and CT wait times could be addressed.

Return on Investment in Endovascular Care: The Case of Endovascular Reperfusion Alberta.

OBJECTIVE: We examined the return on investment (ROI) from the Endovascular Reperfusion Alberta (ERA) project, a provincially funded population-wide strategy to improve access to endovascular therapy (EVT), to inform policy regarding sustainability. METHODS: We calculated net benefit (NB) as benefit minus cost and ROI as benefit divided by cost. Patients treated with EVT and their controls were identified from the ESCAPE trial. Using the provincial administrative databases, their health services utilization (HSU), including inpatient, outpatient, physician, long-term care services, and prescription drugs, were compared. This benefit was then extrapolated to the number of patients receiving EVT increased in 2018 and 2019 by the ERA implementation. We used three time horizons, including short (90 days), medium (1 year), and long-term (5 years). RESULTS: EVT was associated with a reduced gross HSU cost for all the three time horizons. Given the total costs of ERA were $2.04 million in 2018 ($11,860/patient) and $3.73 million in 2019 ($17,070/patient), NB per patient in 2018 (2019) was estimated at -$7,313 (-$12,524), $54,592 ($49,381), and $47,070 ($41,859) for short, medium, and long-term time horizons, respectively. Total NB for the province in 2018 (2019) were -$1.26 (-$2.74), $9.40 ($10.78), and $8.11 ($9.14) million; ROI ratios were 0.4 (0.3), 5.6 (3.9) and 5.0 (3.5). Probabilities of ERA being cost saving were 39% (31%), 97% (96%), and 94% (91%), for short, medium, and long-term time horizons, respectively. CONCLUSION: The ERA program was cost saving in the medium and long-term time horizons. Results emphasized the importance of considering a broad range of HSU and long-term impact to capture the full ROI.

The impact of COVID-19 on hospital admissions and emergency department visits: A population-based study.

BACKGROUND: As a result of the novel coronavirus disease 2019 (COVID-19), there have been widespread changes in healthcare access. We conducted a retrospective population-based study in Alberta, Canada (population 4.4 million), where there have been approximately 1550 hospital admissions for COVID-19, to determine the impact of COVID-19 on hospital admissions and emergency department (ED visits), following initiation of a public health emergency act on March 15, 2020. METHODS: We used multivariable negative binomial regression models to compare daily numbers of medical/surgical hospital admissions via the ED between March 16-September 23, 2019 (pre COVID-19) and March 16-September 23, 2020 (post COVID-19 public health measures). We compared the most frequent diagnoses for hospital admissions pre/post COVID-19 public health measures. A similar analysis was completed for numbers of daily ED visits for any reason with a particular focus on ambulatory care sensitive conditions (ACSC). FINDINGS: There was a significant reduction in both daily medical (incident rate ratio (IRR) 0.86, p<0.001) and surgical (IRR 0.82, p<0.001) admissions through the ED in Alberta post COVID-19 public health measures. There was a significant decline in daily ED visits (IRR 0.65, p<0.001) including ACSC (IRR 0.75, p<0.001). The most common medical/surgical diagnoses for hospital admissions did not vary substantially pre and post COVID-19 public health measures, though there was a significant reduction in admissions for chronic obstructive pulmonary disease and a significant increase in admissions for mental and behavioral disorders due to use of alcohol. CONCLUSIONS: Despite a relatively low volume of COVID-19 hospital admissions in Alberta, there was an extensive impact on our healthcare system with fewer admissions to hospital and ED visits. This work generates hypotheses around causes for reduced hospital admissions and ED visits which warrant further investigation. As most publicly funded health systems struggle with health-system capacity routinely, understanding how these reductions can be safely sustained will be critical.

Average Lifespan Shortened due to Stroke in Canada: A Nationwide Descriptive Study From 1990 to 2015.

BACKGROUND AND PURPOSE: There are challenges in comparability when using existing life lost measures to examine long-term trends in premature mortality. To address this important issue, we have developed a novel measure termed average lifespan shortened (ALSS). In the present study, we used the ALSS measure to describe temporal changes in premature mortality due to stroke in the Canadian population from 1990 to 2015. METHODS: Mortality data for stroke were obtained from the World Health Organization mortality database. Years of life lost was calculated using Canadian life tables. ALSS was calculated as the ratio of years of life lost in relation to the expected lifespan. RESULTS: Over a 25-year timeframe, the age-standardized rates adjusted to the World Standard Population for deaths from all strokes and stroke types substantially decreased in both sexes. The ALSS measure indicated that men who died of stroke lost 12.1% of their lifespan in 1990 and 11.4% in 2015, whereas these values among women were 11.1% and 10.0%, respectively. Patients with subarachnoid hemorrhagic stroke lost the largest portion whereby both sexes lost about one-third of their lifespan in 1990 and one-fourth in 2015. Men with intracerebral hemorrhagic stroke lost around 18% of their lifespan in 1990 and 14% in 2015 as compared to women who lost about 16% and 12% over the same timeframe. The loss of lifespan for patients with ischemic stroke and other stroke types combined was relatively stable at about 10% throughout the study period. CONCLUSIONS: Our study demonstrated a modest improvement in lifespan among patients with stroke in Canada between 1990 and 2015. Our novel ALSS measure provides intuitive interpretation of temporal changes in lifespan among patients with stroke and helps to enhance our understanding of the burden of strokes in the Canadian population.

Gross profits of Canadian pharmacies: A changing policy regime.

Recently, both the Canadian and provincial governments have instituted policies to reduce manufacturers' prices for generic ($250 million sales annually) and brand name ($1,300 million sales annually) drugs. Both government groups made estimates of the financial magnitude of changes in drug prices, but neither has estimated the impact on retail pharmacies. We used a Cost-Volume-Profit model combined with operational data collected nationally to estimate the national impact of the pricing policy changes on pharmacy gross profits. Results show the average value of gross profits per pharmacy per year was approximately $440,000. It is estimated that the policy changes will lead to a 6.8% reduction in gross profits. Adding reductions in rebates for generic drugs, the pharmacies' reductions in gross profits will be 7.2%. In conclusion, policy-makers often ignore how their pricing changes influence the financial position of pharmacies, even though the impact can be substantial.

Emerging Role of Circulating Tumor Cells in Gastric Cancer.

With over 1 million incidence cases and more than 780,000 deaths in 2018, gastric cancer (GC) was ranked as the 5th most common cancer and the 3rd leading cause of cancer deaths worldwide. Though several biomarkers, including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4), have been identified, their diagnostic accuracies were modest. Circulating tumor cells (CTCs), cells derived from tumors and present in body fluids, have recently emerged as promising biomarkers, diagnostically and prognostically, of cancers, including GC. In this review, we present the landscape of CTCs from migration, to the presence in circulation, biologic properties, and morphologic heterogeneities. We evaluated clinical implications of CTCs in GC patients, including diagnosis, prognosis, and therapeutic management, as well as their application in immunotherapy. On the one hand, major challenges in using CTCs in GC were analyzed, from the differences of cut-off values of CTC positivity, to techniques used for sampling, storage conditions, and CTC molecular markers, as well as the unavailability of relevant enrichment and detection techniques. On the other hand, we discussed future perspectives of using CTCs in GC management and research, including the use of circulating tumor microembolies; of CTC checkpoint blockade in immunotherapy; and of organoid models. Despite the fact that there are remaining challenges in techniques, CTCs have potential as novel biomarkers and/or a non-invasive method for diagnostics, prognostics, and treatment monitoring of GC, particularly in the era of precision medicine.

Sequestration of Cetyltrimethylammonium Bromide on Gold Nanorods by Human Serum Albumin Causes Its Conformation Change.

Serum albumin could potentially be exploited to form a protein corona on gold nanorods (AuNRs) for drug delivery because of its endogenous functionality as a small molecule carrier. However, the cetyltrimethylammonium bromide (CTAB) surfactant, which is a synthesis byproduct passivating AuNRs to confer colloidal stability, could also cause its conformational change upon interaction with serum albumin during the process of corona formation, thus altering its biological functions. Unfortunately, a clear understanding of how exactly human serum albumin (HSA) would change its conformation as it interacts with AuNR-CTAB is presently lacking. Here, we made use of coarse-grain molecular dynamics (CGMD) simulation to elucidate the interaction between HSA and AuNR-CTAB leading to its widely reported conformational change. We showed that HSA could sequester CTAB from the surface of AuNRs and form HSA-CTAB complexes, which could also interact with other adjacent complexes through "cross-linking" by the clusters of CTAB. Such a HSA-CTAB complex resulted in the observed conformational change of HSA, which we verified empirically with an esterase activity assay and by analyzing the root-mean-square-deviation of the HSA molecules from CGMD. The conformational change of HSA was not observed in AuNRs passivated with other negatively or positively charged surface ligands such as polystyrene sulfonate and polydiallyldimethylammonium chloride. Therefore, our study revealed that the conformational change experienced by HSA may not necessarily be attributed to protein unfolding on the surface of the AuNR due to charge interactions but rather to the instability of the surface ligands on the AuNRs which allows them to be sequestered by HSA to form HSA-CTAB complexes.

Comparative effectiveness and cost-effectiveness analysis of a urine metabolomics test vs. alternative colorectal cancer screening strategies.

PURPOSE: Despite the success of provincial screening programs, colorectal cancer (CRC) is still the third most common cancer in Canada and the second most common cause of cancer-related death. Fecal-based tests, such as fecal occult blood test (FOBT) and fecal immunochemical test (FIT), form the foundation of the provincial CRC screening programs in Canada. However, those tests have low sensitivity for CRC precursors, adenomatous polyps and have low adherence. This study evaluated the effectiveness and cost-effectiveness of a new urine metabolomic-based test (UMT) that detects adenomatous polyps and CRC. METHODS: A Markov model was designed using data from the literature and provincial healthcare databases for Canadian at average risk for CRC; calibration was performed against statistics data. Screening strategies included the following: FOBT every year, FIT every year, colonoscopy every 10 years, and UMT every year. The costs, quality adjusted life years (QALY) gained, and incremental cost-effectiveness ratios (ICERs) for each strategy were estimated and compared. RESULTS: Compared with no screening, a UMT strategy reduced CRC mortality by 49.9% and gained 0.15 life years per person at $42,325/life year gained in the base case analysis. FOBT reduced CRC mortality by 14.9% and gained 0.04 life years per person at $25,011/life year gained. FIT reduced CRC mortality by 35.8% and gained 0.11 life years per person at $25,500/life year while colonoscopy reduced CRC mortality by 24.7% and gained 0.08 life years per person at $50,875/life year. CONCLUSIONS: A UMT strategy might be a cost-effective strategy when used in programmatic CRC screening programs.

Corrigendum to "Cost-Effectiveness of the Aerobika® Oscillating Positive Expiratory Pressure Device in the Management of Chronic Obstructive Pulmonary Disease Exacerbations in Canada".

[This corrects the article DOI: 10.1155/2019/9176504.].

Cost-Effectiveness of the Aerobika® Oscillating Positive Expiratory Pressure Device in the Management of Chronic Obstructive Pulmonary Disease Exacerbations in Canada.

Background: The Aerobika® oscillating positive expiratory pressure (OPEP) device is a hand-held, drug-free medical device that has been shown to improve lung function and improve health-related quality of life in patients with chronic obstructive pulmonary disease (COPD). We estimated the cost-effectiveness of this device among postexacerbation COPD patients in the Canadian healthcare system. Methods: We performed a cost-utility analysis using a Markov model to compare both costs and outcome of patients with COPD who had recently experienced an exacerbation between 2 treatment arms: patients who used the Aerobika® device and patients who did not use the Aerobika® device. This cost-utility analysis included costs based on the Alberta healthcare system perspective as these represent Canadian experience. A one-year horizon with 12 monthly cycles was used. Results: For a patient after 1 year, the use of the Aerobika® device would save $694 in healthcare costs and produce 0.04 more in quality-adjusted life years (QALYs) in comparison with no positive expiratory pressure (PEP)/OPEP therapy. In other words, the economic outcome of the device was dominant (i.e., more effective and less costly). The probability for this device to be the dominant strategy was 72%. With a willingness to pay (WTP) threshold of $50,000 per QALY gained, the probability for the Aerobika® device to be cost-effective was 77%. Conclusions: Given one of the major treatment goals in the GOLD guidelines is to minimize the negative impact of exacerbations and prevent re-exacerbations, the Aerobika® OPEP device should be viewed as a potential component of a treatment strategy to improve symptom control and reduce the risk of re-exacerbations in patients with COPD.

Population Pharmacokinetic Properties of Piperaquine in Falciparum Malaria: An Individual Participant Data Meta-Analysis.

BACKGROUND: Artemisinin-based combination therapies (ACTs) are the mainstay of the current treatment of uncomplicated Plasmodium falciparum malaria, but ACT resistance is spreading across Southeast Asia. Dihydroartemisinin-piperaquine is one of the five ACTs currently recommended by the World Health Organization. Previous studies suggest that young children (<5 y) with malaria are under-dosed. This study utilised a population-based pharmacokinetic approach to optimise the antimalarial treatment regimen for piperaquine. METHODS AND FINDINGS: Published pharmacokinetic studies on piperaquine were identified through a systematic literature review of articles published between 1 January 1960 and 15 February 2013. Individual plasma piperaquine concentration-time data from 11 clinical studies (8,776 samples from 728 individuals) in adults and children with uncomplicated malaria and healthy volunteers were collated and standardised by the WorldWide Antimalarial Resistance Network. Data were pooled and analysed using nonlinear mixed-effects modelling. Piperaquine pharmacokinetics were described successfully by a three-compartment disposition model with flexible absorption. Body weight influenced clearance and volume parameters significantly, resulting in lower piperaquine exposures in small children (<25 kg) compared to larger children and adults (≥25 kg) after administration of the manufacturers' currently recommended dose regimens. Simulated median (interquartile range) day 7 plasma concentration was 29.4 (19.3-44.3) ng/ml in small children compared to 38.1 (25.8-56.3) ng/ml in larger children and adults, with the recommended dose regimen. The final model identified a mean (95% confidence interval) increase of 23.7% (15.8%-32.5%) in piperaquine bioavailability between each piperaquine dose occasion. The model also described an enzyme maturation function in very young children, resulting in 50% maturation at 0.575 (0.413-0.711) y of age. An evidence-based optimised dose regimen was constructed that would provide piperaquine exposures across all ages comparable to the exposure currently seen in a typical adult with standard treatment, without exceeding the concentration range observed with the manufacturers' recommended regimen. Limited data were available in infants and pregnant women with malaria as well as in healthy individuals. CONCLUSIONS: The derived population pharmacokinetic model was used to develop a revised dose regimen of dihydroartemisinin-piperaquine that is expected to provide equivalent piperaquine exposures safely in all patients, including in small children with malaria. Use of this dose regimen is expected to prolong the useful therapeutic life of dihydroartemisinin-piperaquine by increasing cure rates and thereby slowing resistance development. This work was part of the evidence that informed the World Health Organization technical guidelines development group in the development of the recently published treatment guidelines (2015).

Health services utilization of people having and not having a regular doctor in Canada.

Canada having a universal health insurance plan that provides hospital and physician benefits offers a natural experiment of whether continuity of care actually provides lower or higher utilization of services. The question we are evaluating is whether Canadians, who have a regular physician, use more health resources than those who do not have one? Using two statistical methods, including propensity score matching and zero-inflated negative binomial regression, we analyzed data from the 2010 and 2007/2008 Canadian Community Health Surveys separately to document differences between people self-reportedly having and not having a regular doctor in the utilization of general practitioner, specialist, and hospital services. The results showed, consistently for all two statistical methods and two datasets used, that people reportedly having a regular doctor used more healthcare services than a matched group of people who was self-reportedly not having a regular doctor. For specialist and hospital utilization, the statistically significant differences were in the likelihood if the service was used but not in the number of specialist visits or hospital nights among users. Copyright © 2016 John Wiley & Sons, Ltd.

The economic burden of inadequate consumption of vegetables and fruit in Canada.

OBJECTIVE: Public health decision makers not only consider health benefits but also economic implications when articulating and issuing lifestyle recommendations. Whereas various estimates exist for the economic burden of physical inactivity, excess body weight and smoking, estimates of the economic burden associated with our diet are rare. In the present study, we estimated the economic burden attributable to the inadequate consumption of vegetables and fruit in Canada. DESIGN: We accessed the Canadian Community Health Survey to assess the inadequacy in the consumption of vegetables and fruit and published meta-analyses to assemble risk estimates for chronic diseases. Based on these inadequacy and risk estimates, we calculated the population-attributable fraction and avoidable direct and indirect costs to society. Direct costs include those for hospital care, physician services and drugs in 2015. RESULTS: About 80 % of women and 89 % of men consume inadequate amounts of vegetables and fruit. We estimated this to result in an economic burden of $CAN 3·3 billion per year, of which 30·5 % is direct health-care costs and 69·5 % is indirect costs due to productivity losses. A modest 1 percentage point annual reduction in the prevalence of inadequate vegetables and fruit consumption over the next 20 years would avoid approximately $CAN 10·8 billion, and an increase of one serving of vegetables and fruit per day would avoid approximately $CAN 9·2 billion. CONCLUSIONS: Further investments in the promotion of vegetables and fruit will prevent chronic disease and substantially reduce direct and indirect health-care costs.

Real-Life Treatment Paradigms Show Adalimumab Is Cost-Effective for the Management of Ulcerative Colitis.

Background. Adalimumab is effective for the maintenance of remission in patients with moderate-to-severe ulcerative colitis (UC). Currently, biologic therapies are used in cases where patients fail conventional medical therapies. If biologic therapies are not available, patients often choose to remain in an unwell state rather than undergo colectomy. Objective. The aim of the study was to evaluate the cost-effectiveness of adalimumab in patients with UC where adalimumab was readily available compared to not available. Methods. A previously validated Markov model was used to simulate disease progression of patients with UC who are corticosteroid-dependent and/or did not respond to thiopurine therapy. Utility scores and transition probabilities between health states were determined by using data from randomized controlled trials and real-life observational studies. Costs were obtained from the Ontario Case Costing Initiative and the Alberta Health Schedule of Medical Benefits. Results. The incremental cost-effectiveness ratios for readily available adalimumab treatment of UC were $40,000 and $59,000 per quality-adjusted life year, compared with ongoing medical therapy in an unwell state, at 5-year and 10-year treatment time horizons, respectively. Conclusion. Considering real-life patient preferences to avoid colectomy, adalimumab is cost-effective according to a willingness-to-pay threshold of $80,000 for treatment of UC.