Vitamin D and Chronic Diseases among First-Generation Immigrants: A Large-Scale Study Using Canadian Health Measures Survey (CHMS) Data.

Background: Nearly 22% of the Canadian population are first-generation immigrants. We investigated immigrants' health status and health deterioration over time in terms of the prevalence of chronic diseases (CDs) and their relationship to vitD status. Methods: We used cycles three (2012-2013) and four (2014-2015) of the Canadian Health Measures Survey. These data contained unique health information and direct physical/blood measures, including serum 25-hydroxyvitamin D (S-25(OH)D). Indicators of health status and deterioration were the prevalence of CDs diagnosed by healthcare professionals, self-reported general and mental health, and CD-related biomarkers. Results: The data (n = 11,579) included immigrants from more than 153 countries. Immigrants were healthier than non-immigrants for most health status measures. The prevalence of CDs was higher among those who migrated to Canada aged ≥ 18 years. A longer time in Canada after immigration was associated with a higher risk for CDs. The mean S-25(OH)D was lower among immigrants, higher among patients with CDs, and inversely associated with glycated hemoglobin, total cholesterol/high-density lipoprotein ratio, immunoglobulin E, serum ferritin, and blood hemoglobin. After adjusting for covariates, no association was found between S-25(OH)D and the prevalence of CDs. Conclusions: Lower levels of accumulated S-25(OH)D among immigrants may impact their health profile in terms of CD-related biomarkers, which partially explains immigrants' health deterioration over time. We recommend further longitudinal research to investigate immigrants' vitD and health deterioration.

Melanin levels in relation to vitamin D among first-generation immigrants from different ethnic groups and origins: A comparative national Canadian cross-sectional study.

Introduction: Immigrants to Western countries tend to have darker skin than native-born populations. We examined the relationship between skin melanin and serum vitamin D (vitD) [S-25(OH)D] levels and explored whether melanin levels explained S-25(OH)D variations between immigrants and native-born Canadians. This study offers novel findings as no such study has been conducted. Methods: We used a national cross-sectional population-based design with data from the Canadian Health Measures Survey (CHMS). Skin melanin levels among first-generation immigrants based on their ethnicity and origin/country of birth were compared with white and native-born populations. We assessed the association between S-25(OH)D and melanin after adjusting for independent variables related to S-25(OH)D, melanin level, and immigration status. Results: Of 11,579 participants, 21.9% were immigrants aged 3-79 years (mean age 39.23 years). Compared with non-immigrants, immigrants had lower S-25(OH)D levels (mean: 51.23 vs. 62.72; 95% CI: 8.37, 14.62; P < 0.001) but higher melanin levels (mean [SE]: 17.08 [0.25] vs. 16.29 [0.29]; 95% CI: -1.29, -0.281; P = 0.004). Melanin did not differ by length of stay in Canada but was weakly positively correlated (r = 0.088, P < 0.001) with S-25(OH)D. Sex (male), age (≥18 years), summer/fall seasons, sunlight exposure, sunscreen non-use, smoking, and alcohol consumption were associated with higher melanin levels, whereas indoor tanning use was not. Conclusion: Skin melanin levels were associated with sociodemographic and behavioral characteristics. Immigrants had higher melanin levels, but melanin did not differ by length of stay in Canada. The weak positive correlation between melanin and S-25(OH)D suggested confounding factors may impact the relationship between melanin levels, S-25(OH)D, and immigration status.

Assessment of the quality and content of clinical practice guidelines (CPGs) for vitamin D and for immigrants using the AGREE-II instrument: a protocol for systematic review.

INTRODUCTION: Worldwide, more immigrants experience vitamin D (vitD) deficiency than non-immigrants, which is attributed to ethnic variations, place or region of birth, skin pigmentation, clothing style, and resettlement-related changes in diet, physical activity, and sun exposure. Current recommendations in clinical practice guidelines (CPGs) concerning vitD are inadequate to address vitD deficiency among immigrants. CPGs may also lack guidance for physicians on vitD supplementation for immigrants. Moreover, there are concerns about the overall quality of these CPGs. OBJECTIVES: This systematic review will collate and critically appraise CPGs relevant to immigrants' health and vitD. Moreover, we will evaluate whether the CPGs of vitD including recommendations for immigrants and clarify whether the CPGs of immigrants include recommendations on vitD. METHODS: A systematic search of Ovid MEDLINE® ALL, EMBASE, and Turning Research Into Practice (TRIP) electronic databases, guideline repositories, and gray literature will be conducted to identify relevant CPGs. Two reviewers will independently evaluate the methodological quality of the retrieved guidelines using the Appraisal of Guidelines, Research, and Evaluation-II (AGREE-II) instrument. CPGs scoring ≥60% in at least four domains, including "rigor of development," will be considered high quality. CONCLUSION: Evaluating the quality and content of relevant CPGs may support researchers in developing national and global guidelines for immigrants. Furthermore, it may support vitD testing, nutritional counseling, and supplementation for vulnerable immigrant sub-populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021240562.

Vitamin D Status among First-Generation Immigrants from Different Ethnic Groups and Origins: An Observational Study Using the Canadian Health Measures Survey.

One in five Canadians are first-generation immigrants. Evidence suggests the baseline risk for vitamin D (vitD) deficiency is increased among immigrants who move from equatorial to northern countries. We investigated the prevalence and determinants of vitD deficiency/insufficiency among first-generation immigrants compared with native-born Canadians and identified explanatory covariables. We used a cross-sectional design with data from the national Canadian Health Measures Survey (Cycles 3 and 4) (11,579 participants aged 3-79 years). We assessed serum 25-hydroxyvitamin D (S-25(OH)D) levels, sociodemographic and environmental factors, immigration status, length of time in Canada, vitD-rich food intake, ethnicity, and place of birth. Immigrants had lower mean S-25(OH)D than non-immigrants (51.23 vs. 62.72 nmol/L, p < 0.001). Those with younger age at the time of immigration (<18 years) had a high risk for low vitD, and S-25(OH)D levels increased with the length of time they had lived in Canada. The highest deficiency levels were in immigrants born in Morocco, India, and Lebanon compared with native-born Canadians. Ethnicity was the factor most strongly associated with S-25(OH)D. Compared with the white ethnic grouping, the Japanese had the highest level of vitD deficiency, followed by Arabs and Southeast Asians. Ethnic variations, dietary intake, and lifestyle factors are the main predictors of/explanatory factors for vitD status among Canadian immigrants.

EQ-5D-5L Health-State Values for the Mexican Population.

OBJECTIVE: To generate a value set for the Mexican adult general population to support and facilitate the inclusion of quality-adjusted life years (QALYs) into the health technology assessment process of the Mexican healthcare authorities. METHODS: A representative sample of the Mexican adult population stratified by age, sex and socio-economic status was used. Following version 2.0 of the EuroQol EQ-5D-5L valuation protocol, trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete-choice experiment (DCE) tasks included in the EQ-VT software. Generalized least squares, Tobit and Bayesian models were used for cTTO data. The choice of value set model was based on criteria that included: theoretical considerations, parsimony, logical ordering of coefficients, and statistical significance. RESULTS: Based on quality control criteria and interviewer judgment, 1000 out of 1032 participants provided useable responses. Participants' demographic characteristics were similar to the 2010 Mexican Population Census and followed the socioeconomic structure defined by the Mexican Association of Marketing Research and Public Opinion Agencies (AMAI). The predicted index values in the final cTTO model (a heteroscedastic censored model with Bayesian estimation) ranged from - 0.5960 to 1, with 19.7% of all predicted health state scores less than 0 (i.e., worse than dead). CONCLUSION: This study has generated the first value set representing the stated preferences of the Mexican adult population for use in estimating QALYs. The resulting EQ-5D-5L value set is technically robust and will facilitate health economic analyses as well as quality-of-life studies.

Resource Utilization and Costs Associated With Percutaneous Coronary Intervention When Treating Patients With Acute Coronary Syndrome in the Mexican National Institute of Cardiology "Ignacio Chávez".

BACKGROUND: The treatment of acute coronary syndrome (ACS) using percutaneous coronary intervention (PCI) is a frequent intervention with a high economic impact. OBJECTIVE: This study investigates the resource use and cost of PCI in Mexico where heart disease is a leading cause of death, and a large segment of the population does not have formal healthcare coverage. METHODS: This retrospective observational study obtained resource utilization data from patient files and itemized costs from the pharmacy registry at the National Institute of Cardiology. Patients were aged >18 years, diagnosed with ACS, and treated with PCI and secondary prophylaxis with aspirin plus clopidogrel or prasugrel. Patients had a follow-up of >12 months at the institute. Statistical analysis was descriptive. RESULTS: The sample included 156 patients (mean age: 58.66 years; male: 77.9%). Patients were diagnosed with ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction, and unstable angina 64.9%, 27.2%, and 7.9%, respectively. The mean (standard deviation [SD]) total medical cost was estimated to be $145 677 ($98 326) Mexican pesos 2018. The highest category of spending was surgical materials (mean [SD]: $47 834 [$32 569], comprising 32.8% of total costs); medications and access to the operating room represented 14.2% and 11.8%, respectively. Mean (SD) hospital stay was 9.07 (6.2) days; for the 11.5% of patients admitted to the intensive care unit, the mean (SD) stay was 4.61 (2.06) days. The mean cost of standard hospitalization was $12 572, or 8.6% of spending; intensive care unit hospitalization comprised 17.7% of total costs (mean: $25 802). The cost of the intervention is subsidized up to 95% for patients with a low social economic status, with the exception of surgical materials such as stents. This results in the highest burden component of the intervention being placed on the patient and not the institute. CONCLUSION: The mean cost per patient shows that PCI is an expensive procedure in Mexico. A lack of subsidies for surgical equipment places a high economic burden on the patient and represents a barrier of access for a vulnerable population that likely increases mortality and morbidity rates in those patients unable to pay for treatment and a potential high burden of debt for those who do pay.

Study protocol: Worldwide comparison of vitamin D status of immigrants from different ethnic origins and native-born populations-a systematic review and meta-analysis.

BACKGROUND: A growing body of literature indicates that, worldwide, immigrants experience health deterioration after their arrival into their adopted country, and moreover, they have lower vitamin D compared to the native-born population. We plan to review if the levels of vitamin D are comparable between different ethnic groups in different regions of the world with those of native-born populations and to identify the possible associations between vitamin D deficiency and disease status among immigrants. METHODS/DESIGN: A systematic review and meta-analysis will be conducted following the methods of the Cochrane handbook for systematic reviews. A literature search was performed to identify studies on immigrants and vitamin D. The primary outcome is vitamin D levels, and the secondary outcome is any vitamin D deficiency-related disease. Study design and participant characteristics will be extracted, including ethnicity, country of birth and/or origin, and the host country. Descriptive and meta-analytic summaries of the outcomes will be derived. Distiller-SR and RevMan will be used respectively for data management and meta-analysis. DISCUSSION: This systematic review may partially help clarify vitamin D-related health deterioration in migrants; moreover, to develop a global guideline that specifies sub-populations, in which the evidence and vitamin D-related recommendations might differ from the overall immigrant population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018086729.

Meta-Analysis of Pregnancy Outcomes after Exposure to TNF-α Inhibitors During Pregnancy for the Treatment of Arthritic Diseases.

TITLE: Pregnancy Outcomes after Exposure to TNF-α Inhibitors During Pregnancy for the Treatment of Arthritic Diseases: A Meta-Analysis   Authors: Mirdamadi K, Salinas T, Vali R, Papadimitripulous M, Piquette-Miller M Background: Auto-immune arthritic diseases affect many women of child-bearing age. Tumor necrosis factor (TNF)-α inhibitors are currently used for the treatment of various immune-mediated diseases during pregnancy. However, there has been no evaluation of safety in the treatment of arthritic diseases during gestation.     Objective: To analyze the risk of adverse pregnancy and neonatal outcomes after treatment of arthritic diseases with TNF-α inhibitors.     Methods: Major databases including Ovid MEDLINE, Embase, and Web of Science, were searched inclusive to April 2016. Observational prospective cohort studies evaluating pregnancy outcomes after exposure to TNF-α inhibitors for the treatment of arthritic diseases during pregnancy were included. Data on pregnancy and neonatal outcomes was extracted from all included studies. A meta-analysis was performed using inverse-variance random effect with a 95% confidence interval (95%CI) and p<0.05.     Results: Eight prospective studies with comparison groups were included in the meta-analysis. TNF-α inhibitors were associated with significantly higher risks of low birth weight (odds ratio (OR), 1.43; 95%CI, 1.00-2.04) and significantly lower rates of live birth (OR, 0.61; 95%CI, 0.38-0.98). However, birth defects, therapeutic abortion, spontaneous abortion, and preterm birth were not significantly different between the two groups.     Conclusion: Treatment of arthritic diseases with TNF-α inhibitors during pregnancy increases the risk of lower birth weight and decreases the rate of live birth in this population. While duration of treatment and gestational age at exposure may play a role in these outcomes, evaluation of risk versus benefit is crucial in this patient population.   Key words: TNF-α inhibitors, pregnancy outcomes, arthritic disease, meta-analysis.

The opportunity cost of capital: development of new pharmaceuticals.

The opportunity cost of the capital invested in pharmaceutical research and development (R&D) to bring a new drug to market makes up as much as half the total cost. However, the literature on the cost of pharmaceutical R&D is mixed on how, exactly, one should calculate this "hidden" cost. Some authors attempt to adopt models from the field of finance, whereas other prominent authors dismiss this practice as biased, arguing that it artificially inflates the R&D cost to justify higher prices for pharmaceuticals. In this article, we examine the arguments made by both sides of the debate and then explain the cost of capital concept and describe in detail how this value is calculated. Given the significant contribution of the cost of capital to the overall cost of new drug R&D, a clear understanding of the concept is critical for policy makers, investors, and those involved directly in the R&D.

Supportive Care Costs Associated with Second-Line Chemotherapy in Chinese Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Cohort Study.

PURPOSE: To compare supportive care costs associated with second-line chemotherapy for advanced non-squamous non-small cell lung cancer (advNS-NSCLC) in Chinese patients. METHODS: This retrospective cohort study included patients receiving pemetrexed or docetaxel-based second-line chemotherapy for advNS-NSCLC in four Chinese hospitals from 2007 to 2012. The best matched pairs between pemetrexed and other regimens were identified using propensity score methods for head-to-head comparisons of supportive care costs per treatment cycle. Linear regression analyses were performed to rank log10 scale of supportive care costs per treatment cycle associated with chemotherapy by tumor response and hematologic toxicity. RESULTS: 384 patients were included to create propensity score-matched treatment groups for pemetrexed singlet versus docetaxel singlet, platinum/pemetrexed, and platinum/docetaxel, respectively. Pemetrexed singlet was associated with significantly less supportive care costs per treatment cycle than the two doublets (platinum/pemetrexed: median difference -RMB 9,877, p = 0.003; platinum/docetaxel: median difference -RMB 8,370, p = 0.009; 1 RMB = 0.16 USD) but not docetaxel singlet in matched patients. Of the four studied chemotherapy regimens, pemetrexed singlet was associated with the lowest log10 scale of supportive care costs per treatment cycle in patients with tumor control (coefficient relative to docetaxel singlet -1.049, p < 0.001) or leukopenia (coefficient relative to docetaxel singlet -0.991, p = 0.034). CONCLUSION: Pemetrexed singlet cost significantly less for supportive care than pemetrexed or docetaxel-based doublets when treating Chinese patients with AdvNS-NSCLC in the second-line setting. Pemetrexed singlet was also associated with significantly less supportive care costs per treatment cycle than docetaxel singlet in patients with tumor control or leukopenia.

Toward more specific and transparent research and development costs: the case of seasonal influenza vaccines.

BACKGROUND: The ability to calculate the development costs for specific medicines and vaccines is important to inform investments in innovation. Unfortunately, the literature is predominated by non-reproducible studies only measuring aggregate level drug research and development (R&D) costs. We describe methodology that improves the transparency and reproducibility of primary indication expected R&D expenditures. METHODS: We used publically accessible clinical trial data to investigate the fate of all seasonal influenza vaccine candidates that entered clinical development post year 2000. We calculated development times and probabilities of success for these candidates through the various phases of clinical development. Clinical trial cost data obtained from university based clinical researchers were used to estimate the costs of each phase of development. The cost of preclinical development was estimated using published literature. RESULTS: A vaccine candidate entering pre-clinical development in 2011 would be expected to achieve licensure in 2022; all costs are reported in 2022 Canadian dollars (CAD). After applying a 9% cost of capital, the capitalized total R&D expenditure amounts to $474.88 million CAD. CONCLUSION: Clinical development costs for vaccines and drugs can be estimated with increased specificity and transparency using public sources of data. The robustness of these estimates will only increase over time due to public disclosure incentives first introduced in the late 1990s. However, preclinical development costs remain difficult to estimate from public data.

Clinical response and hospital costs associated with the empirical use of vancomycin and linezolid for hospital-acquired pneumonia in a Chinese tertiary care hospital: a retrospective cohort study.

AIMS: To evaluate clinical outcomes and allocation of hospital costs associated with empirical use of vancomycin or linezolid for hospital-acquired pneumonia (HAP) in the People's Republic of China. METHODS: Hospital episodes including HAP treated by vancomycin or linezolid between 2008 and 2012 in a Chinese tertiary care hospital were retrospectively identified from hospital administrative databases. Propensity score methods created best-matched pairs for the antibiotics. The matched pairs were used for adjusted comparisons on clinical response and allocation of hospital costs. Multiple regression analyses adjusting residual imbalance after matching were performed to confirm adjusted comparisons. RESULTS: Sixty matched pairs were created. Adjusted comparisons between vancomycin and linezolid showed similar clinical response rates (clinical cure: 30.0% versus 31.7%, respectively; P=0.847; treatment failure: 55.0% versus 45.0%, respectively; P=0.289) but a significantly lower in-hospital mortality rate for vancomycin (3.3% versus 18.3%, respectively; P=0.013). After further adjusting for the imbalanced variables between matched treatment groups, the risks of treatment failure associated with the two antibiotics were comparable (odds ratio: 1.139; P=0.308) and there was a nonsignificant trend of lower risk of in-hospital mortality associated with vancomycin (odds ratio: 0.186; P=0.055). The total hospital costs associated with vancomycin had a nonsignificant trend of being lower, likely because of its significantly lower acquisition costs (median: RMB 2,880 versus RMB 8,194; P<0.001; 1 RMB =0.16 USD). CONCLUSION: In tertiary care hospitals in the People's Republic of China, empirical treatment of patients with HAP with vancomycin had a comparable treatment failure rate but likely had a lower in-hospital mortality rate when compared with linezolid. Vancomycin also costs significantly less for drug acquisition than linezolid when treating HAP empirically.

Tumor response and clinical toxicity associated with second-line chemotherapy regimens for advanced non-squamous non-small cell lung cancer: A retrospective cohort study.

BACKGROUND: Previously reported superior tumor response of pemetrexed in the second-line setting for advanced non-squamous non-small cell lung cancer (advNS-NSCLC) has never been confirmed in real-world studies. Platinum-based doublet is frequently used in the second-line setting for advanced NSCLC in China. METHODS: A retrospective cohort study was conducted including patients receiving pemetrexed or docetaxel-based chemotherapy in the second-line setting for advNS-NSCLC in four Chinese tertiary care hospitals. Propensity score matched treatment groups were created for head-to-head comparisons on best tumor response and clinical toxicity. Multiple regression analyses were performed to rank the impact of the four regimens on the risks of tumor progression and hematological adverse events. RESULTS: Three hundred and eighty-four patients were included for creating matched treatment groups for pemetrexed versus platinum/pemetrexed (33 pairs), docetaxel (17 pairs), and platinum/docetaxel (29 pairs), respectively. No significant differences were identified for best tumor response between pemetrexed and the other three regimens. However, pemetrexed was associated with significantly fewer patients experiencing anemia (39.4% vs. 69.7%, P = 0.004) and neutropenia (6.1% vs. 30.3%, P = 0.021) than platinum/pemetrexed. Multiple regression analyses indicated that pemetrexed was associated with significantly slower tumor progression (hazard ratio 0.628, P = 0.040) and a significantly lower risk of neutropenia (odds ratio 0.132, P = 0.019) than docetaxel. CONCLUSIONS: Pemetrexed was associated with significantly postponed tumor progression and significantly less hematological toxicity than docetaxel in the real-world second-line setting for advNS-NSCLC in Chinese patients. Pemetrexed monotherapy had comparable tumor response, but significantly less hematological toxicity than pemetrexed-based doublet.

A markov model approach assessing the cost of illness of generalized anxiety disorder in Canada.

INTRODUCTION: Generalized anxiety disorder (GAD) is a chronic disease with waxing and waning of symptoms. This is the first comprehensive economic model developed to reflect the nature and course of GAD. METHODS: An incidence-based probabilistic Markov model was developed reflecting nine GAD health states (HS): clinical assessments (three HS), maintenance therapies (four HS), discontinuation (one HS), and death (one HS). A probability curve of the GAD onset (ages 18-80) determined entry into the model and assumed patients retained the diagnoses until death. Canadian Psychiatric Association (CPA) guidelines determined pharmacotherapy, with revisions/validation by an expert panel. Direct costs (clinician, pharmacotherapy, hospitalization) were retrieved from government publications. Remission was based on pooled-analysis of CPA-cited evidence. Remaining clinical rates, absenteeism, and hospitalization were retrieved from the literature. Direct costs were attributed throughout the model except for the discontinuation and death HS. Indirect costs (wage rate) were retrieved from government publications and the literature (absenteeism), and were attributed to patients with GAD ≤65 years of age. Results were discounted at 5% and results expressed in 2008 Canadian dollars. RESULTS: The mean lifetime cost of illness (COI) was estimated to be $31,213 (SD $9,100) per patient. The cost of absenteeism accounted for 96% of the mean COI. The mean age of onset was 31 years and approximately 19% did not respond to pharmacotherapy. Over 85% of patients discontinued treatment by the fourth cycle (2nd year of therapy). Over the course of the model, a mean of 53% of patients relapsed, with an average rate of 0.79 relapses per patient. On average and over a lifetime, the disorder went unmanaged over a period of 14 (SD 9) years. The model was most sensitive to absenteeism. CONCLUSION: GAD is a costly disease with a lifetime COI <$32k/patient, with absenteeism exerting a significant impact.