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During the COVID-19 pandemic, home delivery of antiretrovirals for HIV treatment proved to be a feasible approach for ensuring treatment continuation amid facility closures and travel restrictions. Antiretroviral home delivery is a model warranting further consideration as an additional option for decentralized drug delivery for HIV treatment., Key Messages Across diverse contexts, home delivery of antiretroviral (ARV) medications was a feasible and acceptable approach for ensuring access to HIV treatment when COVID-19-related lockdowns and travel restrictions imposed barriers to treatment.The ARV home delivery models were rapidly designed and successfully implemented to meet emergency needs brought on by the pandemic. Home delivery of ARVs requires further attention before it can be implemented at greater scale in response to the current pandemic and when health services face future shocks. Key Implications Governments and their partners are urged to seek financing mechanisms and reinforcement to commodity management systems needed to sustain this mode of decentralized service delivery.National HIV program leaders are encouraged to advocate for official, permanent policy changes supportive of home delivery of ARVs. Health policy makers should consider the relevance of home delivery to all chronic health needs requiring long-term delivery of medication to clients., Introduction: Faced with the coronavirus disease (COVID-19) pandemic, governments worldwide instituted lockdowns to curtail virus spread. Health facility closures and travel restrictions disrupted access to antiretroviral (ARV) therapy for people living with HIV. This report describes how HIV programs in Indonesia, Laos, Nepal, and Nigeria supported treatment continuation by introducing home delivery of ARVs. Methods: Staff supporting the programs provided accounts of when and how decisions were taken to support ARV home delivery. They captured programmatic information about home delivery implementation using an intervention documentation tool. The 4 country experiences revealed lessons learned about factors favoring successful expansion of ARV home delivery. Results: Three of the countries relied on existing networks of community health workers for ARV delivery; the fourth country, Indonesia, relied on a private sector courier service. Across the 4 countries, between 19% and 51% of eligible clients were served by home delivery. The experiences showed that ARV home delivery is feasible and acceptable to health service providers, clients, and other stakeholders. Essential to success was rapid mobilization of stakeholders who led the design of the home delivery mechanisms and provided leadership support of the service innovations. Timely service adaptation was made possible by pre-existing differentiated models of care supportive of community-based ARV provision by outreach workers. Home delivery models prioritized protection of client confidentiality and prevention measures for COVID-19. Sustainability of the innovation depends on reinforcement of the commodity management infrastructure and investment in financing mechanisms. Conclusion: Home delivery of ARVs is a feasible client-centered approach to be included among the options for decentralized drug distribution. It serves as a measure for expanding access to care both when access to health services is disrupted and under routine circumstances.

Background Men who have sex with men (MSM) are a key group for HIV interventions in Malawi considering their high HIV prevalence (17.5% compared to 8.4% among men in the general population). The use of oral preexposure prophylaxis (PrEP) presents a new opportunity for MSM to be protected. We present the findings from a qualitative assessment designed to assess awareness of and willingness and barriers to using PrEP among MSM in Malawi. Objective The 3 main objectives of this assessment were to determine: (1) awareness of PrEP, (2) factors that influence willingness to use PrEP, and (3) potential barriers to PrEP use and adherence among MSM in order to guide the design and implementation of a PrEP program in Malawi. Methods Ahead of the introduction of PrEP in Malawi, a qualitative study using in-depth interviews (IDIs) and focus group discussions (FGDs) was conducted in October 2018 in Blantyre, Lilongwe, and rural districts of Mzimba North and Mangochi. With support of members of the population, study participants were purposively recruited from 4 MSM-friendly drop-in centers where MSM receive a range of health services to ensure representativeness across sites and age. Participants were asked what they had heard about PrEP, their willingness to use PrEP, their barriers to PrEP use, and their preferences for service delivery. The data were analyzed using a thematic content analysis framework that was predetermined in line with objectives. Results A total of 109 MSM were interviewed—13 through IDIs and 96 through FGDs. Most participants were aware of PrEP as a new HIV intervention but had limited knowledge related to its use. However, the majority were willing to use it and were looking forward to having access to it. IDI participants indicated that they will be more willing to take PrEP if the dosing frequency were appropriate and MSM were involved in information giving and distribution of the drug. FGD participants emphasized that places of distribution and characteristics of the service provider are the key factors that will affect use. Knowing the benefits of PrEP emerged as a key theme in both the IDIs and FGDs. Participants highlighted barriers that would hinder them from taking PrEP such as side effects which were cited in IDIs and FGDs. Key factors from FGDs include cost, fear of being outed, drug stockouts, fear of being known as MSMs by wives, and lack of relevant information. FGDs cited stigma from health care workers, forgetfulness, and community associated factors. Conclusions Despite having inadequate knowledge about PrEP, study participants were largely willing to use PrEP if available. Programs should include an effective information, education, and communication component around their preferences and provide PrEP in MSM-friendly sites.

Background In Burundi, given the low testing numbers among key populations (KPs), peer-assisted HIV self-testing (HIVST) was initiated for female sex workers (FSWs), men who have sex with men (MSM), and transgender people to provide another testing option. HIVST was provided by existing peer outreach workers who were trained to provide support before, during, and after the administration of the test. People who screened reactive were referred and actively linked to confirmatory testing, and those confirmed positive were linked to treatment. Standard testing included HIV testing by clinical staff either at mobile clinics in the community or in facilities. Objective This study aims to improve access to HIV testing for underserved KPs, improve diagnoses of HIV serostatus among key populations, and link those who were confirmed HIV positive to life-saving treatment for epidemic control. Methods A descriptive analysis was conducted using routine programmatic data that were collected during a 9-month implementation period (June 2018 to March 2019) for peer-assisted HIVST among FSWs, MSM, and transgender people in 6 provinces where the US Agency for International Development–and US President’s Emergency Plan for AIDS Relief–funded LINKAGES (Linkage across the Continuum of HIV Services for KP Affected by HIV) Burundi project was being implemented. Chi-square tests were used to compare case-finding rates among individuals who were tested through HIVST versus standard testing. Multivariable logistic regression was performed to assess factors that were independently associated with HIV seropositivity among FSWs and MSM who used HIVST kits. Results A total of 2198 HIVST kits were administered (FSWs: 1791/2198, 81.48%; MSM: 363/2198, 16.52%; transgender people: 44/2198, 2%). HIV seropositivity rates from HIVST were significantly higher than those from standard testing for FSWs and MEM and nonsignificantly higher than those from standard testing for transgender people (FSWs: 257/1791, 14.35% vs 890/9609, 9.26%; P8 clients per week (adjusted odds ratio 1.3, 95% CI 1.0-1.8) were independently associated with HIV seropositivity. Conclusions The results demonstrate the potential effectiveness of HIVST in newly diagnosing underserved KPs and linking them to treatment.

This cross-sectional study assesses the frequency and thoroughness of reporting of sociodemographic variables in randomized clinical trials published in 5 high-impact health journals from January 2014 to July 2020.

KEY POINTS Public awareness regarding the importance of disclosing and managing conflicts of interest (COIs) during the development of clinical practice and public health guidelines is growing, owing to recent high-profile news stories within and outside Canada.[1][1]–[9][2] Despite the existence

ContextOpioid related deaths are at epidemic levels in many developed nations globally. Concerns about the contribution of prescribed opioids, and particularly high-dose opioids, continue to mount as do initiatives to reduce prescribing. Evidence around opioid tapering, which can be challenging and potentially hazardous, is not well developed. A recent national guideline has recognized this and recommended referral to multidisciplinary care for challenging cases of opioid tapering. However, multidisciplinary care for opioid tapering is not well understood or defined.ObjectiveIdentify the existing literature on any multidisciplinary care programs that evaluate impact on opioid use, synthesize how these programs work and clarify whom they benefit.Study designSystematic rapid realist review.DatasetBibliographic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library), grey literature, reference hand search and formal expert consultation.Results95 studies were identified. 75% of the programs were from the United States and the majority (n = 62) were published after 2000. A minority (n = 23) of programs reported on >12 month opioid use outcomes. There were three necessary but insufficient mechanisms common to all programs: pain relief, behavior change and active medication management. Programs that did not include a combination of all three mechanisms did not result in opioid dose reductions. A concerning 20-40% of subjects resumed opioid use within one year of program completion.ConclusionsProviding alternative analgesia is insufficient for reducing opioid doses. Even high quality primary care multidisciplinary care programs do not reduce prescribed opioid use unless there is active medication management accomplished by changing the primary opioid prescriber. Rates of return to use of opioids from these programs are very concerning in the current context of a highly potent and lethal street drug supply. This contextual factor may be powerful enough to undermine the modest benefits of opioid dose reduction via multidisciplinary care.

This work is supported by grant 381409 from the Canadian Institutes for Health Research, the Ontario SPOR Support Unit that is supported by the Canadian Institutes of Health Research and the Province of Ontario, the Canada Research Chairs program, and the St Michael’s Hospital Foundation. Importance: Nonadherence to treatment with medicines is common globally, even for life-saving treatments. Cost is one important barrier to access, and only some jurisdictions provide medicines at no charge to patients. Objective: To determine whether providing essential medicines at no charge to outpatients who reported not being able to afford medicines improves adherence. Design, Setting, and Participants: A multicenter, unblinded, parallel, 2-group, superiority, outcomes assessor-blinded, individually randomized clinical trial conducted at 9 primary care sites in Ontario, Canada, enrolled 786 patients between June 1, 2016, and April 28, 2017, who reported cost-related nonadherence. Follow-up occurred at 12 months. The primary analysis was performed using an intention-to-treat principle. Interventions: Patients were randomly allocated to receive free medicines on a list of essential medicines in addition to otherwise usual care (n = 395) or usual medicine access and usual care (n = 391). Main Outcomes and Measures: The primary outcome was adherence to treatment with all medicines that were appropriately prescribed for 1 year. Secondary outcomes were hemoglobin A1c level, blood pressure, and low-density lipoprotein cholesterol levels 1 year after randomization in participants taking corresponding medicines. Results: Among the 786 participants analyzed (439 women and 347 men; mean [SD] age, 51.7 [14.3] years), 764 completed the trial. Adherence to treatment with all medicines was higher in those randomized to receive free distribution (151 of 395 [38.2%]) compared with usual access (104 of 391 [26.6%]; difference, 11.6%; 95% CI, 4.9%-18.4%). Control of type 1 and 2 diabetes was not significantly improved by free distribution (hemoglobin A1c, -0.38%; 95% CI, -0.76% to 0.00%), systolic blood pressure was reduced (-7.2 mm Hg; 95% CI, -11.7 to -2.8 mm Hg), and low-density lipoprotein cholesterol levels were not affected (-2.3 mg/dL; 95% CI, -14.7 to 10.0 mg/dL). Conclusions and Relevance: The distribution of essential medicines at no charge for 1 year increased adherence to treatment with medicines and improved some, but not other, disease-specific surrogate health outcomes. These findings could help inform changes to medicine access policies such as publicly funding essential medicines. Trial Registration: ClinicalTrials.gov identifier: NCT02744963. Publisher PDF

Introduction: The opioid epidemic has been influenced by immense marketing campaigns produced by pharmaceutical companies. These campaigns include advertisements aimed at emergency medicine (EM) physicians, which may have influenced overprescription. This study is a part of a larger effort to systematically assess opioid ads published in major medical journals in North America. To our knowledge, this is the first study to systematically assess the volume, claims, and levels of evidence for opioid ads aimed at EM physicians. Methods: Up to two issues per year from 1996 to 2016 of ten major North American medical journals were hand-searched for opioid advertisements. Specifically, we assessed random samples of issues from five major North American emergency medicine journals, including Annals of Emergency Medicine, Emergency Medicine, Canadian Journal of Emergency Medicine, Emergency Medicine Journal, and American Journal of Emergency Medicine. Five generalist medical journals were assessed including Journal of the American Medical Association, New England Journal of Medicine, Canadian Medical Association Journal, American Family Physician, and Canadian Family Physician. The volume of advertisements, nature of the claims, and cited evidence were collected by independent reviewers. The referenced evidence was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence rubric. Results: Of the 269 issues across the ten journals, opioid ads compromised 95 of the 3392 pharmaceutical advertisements with 79 opioid ads available for analysis. When analysis was completed with two reviewers, inter-rater agreement was rated as 99.87 (Cohen's kappa of 0.976). 37/79 ads did not mention the addictive potential of opioids, with 60/79 not mentioning the possibility of death. The tamper potential of medications was mentioned in 27/79 ads. Positive claims included efficacy (47/79), fast-acting ability (16/79), patient preference (5/79), convenience (26/79) and reduced side effects (22/79). 26/79 cited references directly in their text. Citations were provided for a total of 19 available original studies, of which a majority (16/19) were Level 2 evidence. Upon examination of conflicts of interest, 100% (19/19) of the referenced studies were funded by a pharmaceutical company. Conclusion: A variety of claims were published in medical journals through opioid advertisements, which cite industry studies. Many ads did not mention key negative information, which may have influenced EM physician prescribing.

ObjectivesOpioid-related deaths continue to increase in North America, an epidemic that was initiated by high rates of opioid prescribing. We designed a multifaceted, theory-informed Opioid Self-Assessment (OSA) package, to increase adherence to the Canadian Opioid Guideline among family physicians. This study aimed to assess changes in Canadian family physicians’ knowledge and practices after completing the OSA package.DesignWe conducted a mixed-method evaluation using a pre-test and post-test design that involved the collection of both qualitative and quantitative data.SettingThis research was conducted in the primary care setting in Ontario, Canada.ParticipantsWe recruited a purposive sample of nine family physicians in Ontario who use long-term opioid therapy to treat patients with chronic pain.InterventionsThe OSA package included four components: an online knowledge test, an online learning programme, a safe medication practice self-assessment questionnaire and chart audit with feedback.Outcome measuresOur measures included changes in knowledge, opioid safety practices and physicians’ perspectives on the OSA package.ResultsWe found statistically significant improvements between pre-test and post-test knowledge scores at both baseline and 6-month follow-up. Physicians’ scores improved significantly on five of the seven core characteristics of the practice self-assessment questionnaire. On the chart audits, we observed an improvement in patient education between baseline and 6 months. Qualitative interviews showed that participants appreciated embedded resources in the OSA package. The completion of the package stimulated identification of gaps or deficits in practice and served as a useful reminder to discuss risk and safety with patients. Participants described the chart review as helpful in prompting discussions with their patients, identifying deficits and strengths and a ‘primary motivator’ for project participation.ConclusionsThe OSA package has the potential to improve medication safety practices in primary care related to opioid monitoring and adherence to current opioid guidelines.

OBJECTIVES: The American Academy of Pediatrics recommends universal screening for anemia using hemoglobin at 12 months. However, hemoglobin lacks diagnostic accuracy for iron deficiency, and the optimal age for screening has not been determined. Our objective was to assess a screening strategy for iron deficiency using serum ferritin. METHODS: We conducted a cross-sectional study of children 1 to 3 years old attending a health supervision visit. We examined the relationship between child age and serum ferritin, age and hemoglobin, hemoglobin and serum ferritin, and the prevalence of elevated C-reactive protein (CRP). RESULTS: Restricted cubic spline analysis (n = 1735) revealed a nonlinear relationship between age and serum ferritin (P < .0001). A linear spline model revealed that from 12 to 15 months, for each 1-month increase in age, serum ferritin levels decreased by 9% (95% confidence interval [CI]: 5 to 13). From 15 to 24 months, the rate of change was nonsignificant. From 24 to 38 months, for each month increase in age, serum ferritin increased by 2% (95% CI: 1 to 2). For hemoglobin, from 12 to 24 months, the rate of change was nonsignificant. From 24 to 38 months, for each 1-month increase in age, hemoglobin increased by 20% (95% CI: 9 to 32). Compared with the serum ferritin cutoff of CONCLUSIONS: Screening for iron deficiency using serum ferritin at 15 or 18 months may be a promising strategy. For children at low risk for acute inflammation, concurrent measurement of CRP may not be necessary.

Objectives: The research compared the comprehensiveness and accuracy of two online resources that provide drug information: Lexicomp and Wikipedia.Methods: Medication information on five commonly prescribed medications was identified and comparisons were made between resources and the relevant literature. An initial content comparison of the following three categories of medication information was performed: dose and instructions, uses, and adverse effects or warnings. The content comparison included sixteen points of comparison for each of the five investigated medications, totaling eighty content comparisons. For each of the medications, adverse reactions that appeared in only one of the resources were identified. When primary, peer-reviewed literature was not referenced supporting the discrepant adverse reactions, a literature search was performed to determine whether or not evidence existed to support the listed claims.Results: Lexicomp consistently provided more medication information, with information provided in 95.0% (76/80) of the content, compared to Wikipedia’s 42.5% (34/80). Lexicomp and Wikipedia had information present in 91.4% (32/35) and 20.0% (7/35) of dosing and instructions content, respectively. Adverse effects or warning content was provided in 97.5% (39/40) of Lexicomp content and 55.0% (22/40) of Wikipedia content. The “uses” category was present in both Lexicomp and Wikipedia for the 5 medications considered. Of adverse reactions listed solely in Lexicomp, 191/302 (63.2%) were supported by primary, peer-reviewed literature in contrast to 7/7 (100.0%) of adverse reactions listed only in Wikipedia. A review of US Food and Drug Administration Prescribing Information and the Adverse Event Reporting System dashboard found support for a respective 17/102 (16.7%) and 92/102 (90.2%) of Lexicomp’s adverse reactions that were not supported in the literature.Conclusion: Lexicomp is a comprehensive medication information tool that contains lists of adverse reactions that are not entirely supported by primary-peer reviewed literature.

Chronic noncancer pain includes any painful condition that persists for at least three months and is not associated with malignant disease.[1][1] According to seven national surveys conducted between 1994 and 2008, 15%–19% of Canadian adults live with chronic noncancer pain.[2][2] Chronic

Doxylamine-pyridoxine is the first-line agent for the treatment of nausea and vomiting of pregnancy (NVP) according to Canadian guidelines, and this combination is commonly prescribed to pregnant women. There is limited evidence that doxylamine-pyridoxine is more effective than pyridoxine alone. There is stronger support for the safety of pyridoxine monotherapy than for the combination of doxylamine-pyridoxine during pregnancy, and some conflicting evidence links doxylamine-pyridoxine use to pyloric stenosis and childhood malignancies. The role of doxylamine-pyridoxine as the first-line pharmacological treatment for NVP in Canada should be reconsidered.La combinaison doxylamine-pyridoxine constitue l’agent de première intention à utiliser pour la prise en charge de la nausée et des vomissements de la grossesse (NVG), selon les lignes directrices canadiennes traitant de la question, et cette combinaison est couramment prescrite aux femmes enceintes. Les données qui indiquent que la combinaison doxylamine-pyridoxine est plus efficace que la pyridoxine utilisée seule sont limitées. En fait, les données qui soutiennent l’innocuité de la monothérapie à la pyridoxine pendant la grossesse sont plus solides que les données qui soutiennent celle de la combinaison doxylamine-pyridoxine; de plus, certaines données contradictoires établissent des liens entre la combinaison doxylamine-pyridoxine et les tumeurs malignes de l’enfance et la sténose du pylore. Le rôle de la combinaison doxylamine-pyridoxine à titre de traitement pharmacologique de première intention pour contrer la nausée et les vomissements de la grossesse au Canada devrait être remis en question.

Finding new HIV-positive cases remains a priority to achieve the UNAIDS goals. An enhanced peer outreach approach (EPOA) was implemented to expand the delivery of HIV services to female sex workers (FSWs) and men who have sex with men (MSM) in three countries in West and Central Africa. The aim of EPOA is to identify new HIV-positive cases. EPOA was implemented in Burundi among FSWs, and in Cote d'Ivoire and Democratic Republic of the Congo (DRC) among both FSWs and MSM. Implementation ranged from five to nine weeks and was nested within a three-month reporting period. Standard outreach was suspended for the duration of EPOA implementation but was resumed thereafter. Summary service statistics were used to compare HIV seropositivity during standard outreach and EPOA. Trends were analyzed during the quarter in which EPOA was implemented, and these were compared with the two preceding quarters. Differences in proportions of HIV seropositivity were tested using Pearson's chi-square test; p-values of less than 0.05 were considered statistically significant. Overall, EPOA resulted in a higher proportion of new HIV-positive cases being found, both within and between quarters. In Burundi, HIV seropositivity among FSWs was significantly higher during EPOA than during standard outreach (10.8% vs. 4.1%, p

To examine the association between body mass index (BMI) and iron deficiency in early childhood, while considering the influence of low-grade systemic inflammation.Healthy children ages 1-3 years were included in a cross-sectional analysis. Age- and sex-standardized World Health Organization BMI z score (zBMI) was calculated using height/length and weight measurements; iron status was assessed by serum ferritin; inflammation was assessed by C-reactive protein (CRP). Children with CRP ≥10 mg/L were excluded because this may indicate acute systemic inflammation. Adjusted multivariable regression analyses were used to investigate the association between zBMI and both serum ferritin (µg/L), and iron deficiency (serum ferritin12 µg/L). We performed prespecified subgroup analyses according to CRP level (normal [≤1.0 mg/L] and low-grade inflammation [1.0 mg/L to10.0 mg/L]).Of 1607 children included, 20% were categorized as with zBMI1, 13% had iron deficiency, and 18% had low-grade inflammation. Higher zBMI was associated with lower serum ferritin (-1.51 µg/L, 95% CI -2.23, -0.76, P .0001) and increased odds of iron deficiency (OR 1.28, 95% CI 1.10, 1.50, P = .002). Though there was no interaction between zBMI and CRP for the adjusted linear regression model (P = .79) or logistic regression model (P = .43), children with low-grade inflammation had a higher serum ferritin (P .0001).Higher zBMI is associated with increased risk for iron deficiency in children between 1 and 3 years, and should be considered as a risk factor in targeted screening. Further research is needed to better understand the relationship between serum ferritin and CRP for children in all weight categories.ClinicalTrials.gov: NCT01869530.

Background: Modifiable behaviours during early childhood may provide opportunities to prevent disease processes before adverse outcomes occur. Our objective was to determine whether young children’s eating behaviours were associated with increased risk of cardiovascular disease in later life. Methods: In this cross-sectional study involving children aged 3–5 years recruited from 7 primary care practices in Toronto, Ontario, we assessed the relation between eating behaviours as assessed by the NutriSTEP (Nutritional Screening Tool for Every Preschooler) questionnaire (completed by parents) and serum levels of non–high-density lipoprotein (HDL) cholesterol, a surrogate marker of cardiovascular risk. We also assessed the relation between dietary intake and serum non-HDL cholesterol, and between eating behaviours and other laboratory indices of cardiovascular risk (low-density lipoprotein [LDL] cholesterol, apolipoprotein B, HDL cholesterol and apoliprotein A1). Results: A total of 1856 children were recruited from primary care practices in Toronto. Of these children, we included 1076 in our study for whom complete data and blood samples were available for analysis. The eating behaviours subscore of the NutriSTEP tool was significantly associated with serum non-HDL cholesterol ( p = 0.03); for each unit increase in the eating behaviours subscore suggesting greater nutritional risk, we saw an increase of 0.02 mmol/L (95% confidence interval [CI] 0.002 to 0.05) in serum non-HDL cholesterol. The eating behaviours subscore was also associated with LDL cholesterol and apolipoprotein B, but not with HDL cholesterol or apolipoprotein A1. The dietary intake subscore was not associated with non-HDL cholesterol. Interpretation: Eating behaviours in preschool-aged children are important potentially modifiable determinants of cardiovascular risk and should be a focus for future studies of screening and behavioural interventions.

BACKGROUND Eating habits formed during childhood may contribute to the increasing prevalence of cardiometabolic disorders. Assessing nutritional risk in young children may help to prevent later cardiometabolic disease. The objective of this study was to determine whether parent-reported nutritional risk in preschool-aged children was associated with laboratory indices of cardiometabolic risk, namely leptin and insulin. METHODS In this cross-sectional study, the relationship between nutritional risk as determined by the parent-completed NutriSTEP® questionnaire was assessed and compared to the serum leptin and insulin concentrations, hormones involved in regulation of food intake and biomarkers of adiposity and cardiometabolic risk. The community-based primary care research network for children in Toronto, Canada (TARGet Kids!) was used. The participants were children aged 3-5 years recruited from TARGet Kids! A total of 1856 children were recruited from seven primary care practices. Of these, 1086 children completed laboratory testing. Laboratory data for leptin and insulin were available for 714 and 1054 of those individuals, respectively. RESULTS The total NutriSTEP® score was significantly associated with serum leptin concentrations (p=0.003); for each unit increase in the total NutriSTEP® score, there was an increase of 0.01 ng/mL (95% confidence interval [CI] 0.004-0.018) in serum leptin concentrations after adjusting for potential confounders. The total NutriSTEP® score was not significantly associated with serum insulin concentration. CONCLUSIONS Parent reported nutritional risk is associated with serum leptin, but not insulin, concentrations in preschool-aged children. The NutriSTEP® questionnaire may be an effective tool for predicting future cardiometabolic risk in preschool-aged children.

Objective To determine if there is an association between longer breast-feeding duration and dental caries in healthy urban children. Methods We conducted a cross-sectional study of urban children aged 1 to 6 years recruited through The Applied Research Group for Kids (TARGet Kids!) practice-based research network between September 2011 and August 2013. The main outcome measure was parental report of dental caries. Results The adjusted predicted probability of dental caries was 7%, 8%, 11%, and 16% with total duration of breast-feeding duration of 12, 18, 24, and 36 months, respectively. In the adjusted logistic regression analyses, relative to breast-feeding 0 to 5 months, the odds of dental caries with total breast-feeding duration >24 months was 2.75 (95% confidence interval 1.61–4.72). Conclusions Among healthy urban children, longer breast-feeding duration was associated with higher odds of dental caries. These findings support heightened awareness and enhanced anticipatory guidance for preventive dental care, particularly among children who breast-feed beyond 2 years of age.

Background Doxylamine-pyridoxine is recommended as a first line treatment for nausea and vomiting during pregnancy and it is commonly prescribed. We re-analysed the findings of a previously reported superiority trial of doxylamine-pyridoxine for the treatment of nausea and vomiting during pregnancy using the clinical study report obtained from Health Canada. Methods and findings We re-analysed individual level data for a parallel arm randomized controlled trial that was conducted in six outpatient obstetrical practices in the United States. Pregnant women between 7 and 14 weeks of gestation with moderate nausea and vomiting of pregnancy symptoms. The active treatment was a tablet containing both doxylamine 10 mg and pyridoxine 10 mg taken between 2 and 4 times per day for 14 days depending on symptoms. The control was an identical placebo tablet taken using the same instructions. The primary outcome measure was improvement in nausea and vomiting of symptoms scores using the 13-point pregnancy unique quantification of emesis scale between baseline and 14 days using an ANCOVA. 140 participants were randomized into each group. Data for 131 active treatment participants and 125 control participants were analysed. On the final day of the trial, 101 active treatment participants and 86 control participants provided primary outcome measures. There was greater improvement in symptoms scores with doxylamine-pyridoxine compared with placebo (0.73 points; 95% CI 0.21 to 1.25) when last observation carried forward imputation was used for missing data but the difference is not statistically significant using other approaches to missing data (e.g. 0.38; 95% CI -0.08 to 0.84 using complete data). Conclusions There is a trend towards efficacy for nausea and vomiting symptoms with doxylamine-pyridoxine compared with placebo but the statistical significance of the difference depends on the method of handling missing data and the magnitude of the difference suggests that there is no clinically important benefit employing the prespecified minimal clinically important difference or “expected difference” of 3 points. Trial registration Clinical Trial NCT00614445

Objective To evaluate the association between breastfeeding duration and early childhood cardiometabolic risk. Study design A cross-sectional study of 1539 healthy children, 3-6 years of age, recruited through The Applied Research Group for Kids! practice-based research network between October 2009 and August 2015. Adjusted multivariable linear regression was used to examine the association between breastfeeding duration and cardiometabolic risk z score and individual cardiometabolic risk factors of waist circumference, systolic blood pressure, glucose, high-density lipoprotein cholesterol, and triglycerides. Results The mean breastfeeding duration was 12.5 months (SD = 8.4). Breastfeeding duration was associated with lower cardiometabolic risk z score (beta = −0.03; 95% CI −0.05, −0.01). In analysis of cardiometabolic risk factors, each additional 3 months of breastfeeding was associated with a 0.13 cm (95% CI −0.20, −0.05) lower waist circumference and 0.16 mm Hg (95% CI −0.30, −0.02) lower systolic blood pressure. Compared with children who breastfed for 6-12 months, those who breastfed for 12-24 months had a lower systolic blood pressure of 1.07 mm Hg (95% CI −2.04, −0.10). There was no association between breastfeeding duration and cardiometabolic risk for those who breastfed beyond 24 months. Conclusions Breastfeeding duration is associated with lower cardiometabolic risk, although the magnitude of association is small. Causation cannot be inferred. Breastfeeding beyond 24 months may not have an added benefit for cardiometabolic health.

Objective To prevent iron deficiency, 2014 Canadian recommendations for healthy term infants from 6 to 24 months recommend iron-rich complementary foods such as meat and meat alternatives 2 or more times a day. The purpose of our study was to evaluate the association between meat and meat-alternative consumption and iron status in young children and the association between red meat consumption and iron status among children meeting recommendations. Methods Healthy children aged 12 to 36 months were recruited. A cross-sectional study was conducted. Meat and meat-alternative consumption was measured using the NutriSTEP questionnaire. Adjusted multivariable regression analyses were used to evaluate an association between meat consumption and serum ferritin, and iron deficiency (serum ferritin Results A total of 1043 children were included. Seventy-three percent of children met the recommended daily intake of meat and meat alternatives, and 66% ate red meat in the past 3 days. Eating meat and meat alternatives was not associated with serum ferritin (0.13 μg/L, 95% confidence interval −0.05, 0.31, P = .16), but it was associated with a decreased odds of iron deficiency (odds ratio 0.97, 95% confidence interval 0.94, 0.99, P = .03). Associations between red meat consumption and iron status were not statistically significant. Statistically significant covariates associated with increased odds of iron deficiency included longer breast-feeding duration, daily cow's milk intake of >2 cups, and a higher body mass index z score. Conclusions Daily cow's milk intake of >2 cups, longer breast-feeding duration, and a higher body mass index z score were modifiable risk factors associated with iron deficiency. Eating meat according to recommendations may be a promising additional target for the prevention of iron deficiency in early childhood.

Background: The effectiveness of helmets at preventing cycling fatalities, a leading cause of death among young adults worldwide, is controversial, and safety regulations for cycling vary by jurisdiction. We sought to determine whether nonuse of helmets is associated with an increased risk of fatal head injury. Methods: We used a case–control design involving 129 fatalities using data from a coroner’s review of cycling deaths in Ontario, Canada, between 2006 and 2010. We defined cases as cyclists who died as a result of head injuries; we defined controls as cyclists who died as a result of other injuries. The exposure variable was nonuse of a bicycle helmet. Results: Not wearing a helmet while cycling was associated with an increased risk of dying as a result of sustaining a head injury (adjusted odds ratio [OR] 3.1, 95% confidence interval [CI] 1.3–7.3). We saw the same relationship when we excluded people younger than 18 years from the analysis (adjusted OR 3.5, 95% CI 1.4–8.5) and when we used a more stringent case definition (i.e., only a head injury with no other substantial injuries; adjusted OR 3.6, 95% CI 1.2–10.2). Interpretation: Not wearing a helmet while cycling is associated with an increased risk of sustaining a fatal head injury. Policy changes and educational programs that increase the use of helmets while cycling may prevent deaths.

OBJECTIVESWe report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published.DESIGNDouble blinded, multi-centred, randomized placebo-controlled study.SETTING14 clinics in the United States.PARTICIPANTS2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled.INTERVENTIONSEach patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights.OUTCOMESReported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians.RESULTSData from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were "evaluated moderate or excellent" was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity.CONCLUSIONThe available information about this "8-way Bendectin" trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias.TRIAL REGISTRATIONNot registered.

Antihistamines are commonly used to treat nausea and vomiting of pregnancy (NVP). We re-analyzed the 24 primary studies cited in a 1997 meta-analysis that concluded antihistamine use for NVP was safe as they had been studied in more than 200,000 participating women and the pooled odds ratio for congenital malformations was 0.76 (95% confidence interval [CI]: 0.60–0.94). Our analysis of this meta-analysis showed that 139,414 women were included in 22 original studies involving antihistamines, 129,108 of which were in studies involving doxylamine. In these studies, 23,485 women were exposed to antihistamines, 14,624 of which were exposed to doxylamine. The summary relative risk (cohort studies) and odds ratio (case–control studies) for congenital malformations from antihistamine exposure were 1.09 (95% CI: 1.01–1.18) and 1.04 (95% CI: 0.91–1.19), and for doxylamine exposure, the summary relative risk and odds ratio were 0.94 (95% CI: 0.80–1.10) and 1.07 (95% CI: 0.93–1.23), respectively. Although not a new systematic review, our re-analysis demonstrates that the safety data for antihistamines, and doxylamine in particular, are based on many fewer than 200,000 participating women and exposures, and that doxylamine use is not associated with a decreased risk of malformations as previously reported.

Background Some evidence suggests that chlorthalidone may be superior to hydrochlorothiazide for the treatment of hypertension. Objective To compare the effectiveness and safety of chlorthalidone and hydrochlorothiazide in older adults. Design Propensity score-matched observational cohort study with up to 5 years of follow-up. Setting Ontario, Canada. Patients All individuals aged 66 years or older who were newly treated with chlorthalidone or hydrochlorothiazide and were not hospitalized for heart failure, stroke, or myocardial infarction in the prior year were eligible for inclusion. Each chlorthalidone recipient was matched to up to 2 hydrochlorothiazide recipients on the basis of age, sex, year of treatment initiation, and propensity score. Measurements The primary outcome was a composite of death or hospitalization for heart failure, stroke, or myocardial infarction. Safety outcomes included hospitalization with hypokalemia or hyponatremia. Results A total of 29 873 patients were studied. During follow-up, chlorthalidone recipients (n = 10 384) experienced the primary outcome at a rate of 3.2 events per 100 person-years of follow-up, and hydrochlorothiazide recipients experienced 3.4 events per 100 person-years of follow-up (adjusted hazard ratio, 0.93 [95% CI, 0.81 to 1.06]). Patients treated with chlorthalidone were more likely to be hospitalized with hypokalemia (adjusted hazard ratio, 3.06 [CI, 2.04 to 4.58]) or hyponatremia (adjusted hazard ratio, 1.68 [CI, 1.24 to 2.28]). In 9 post hoc analyses comparing patients initially prescribed 12.5, 25, or 50 mg of chlorthalidone per day with those prescribed 12.5, 25, or 50 mg of hydrochlorothiazide per day, the former were more likely to be hospitalized with hypokalemia for all 6 comparisons in which a statistically significant association was found. The results of other effectiveness and safety outcomes were also consistent with those of the main analysis. Limitation Unmeasured differences in baseline characteristics or physician treatment approaches or an insufficiently large sample may have limited the ability to detect small differences in the comparative effectiveness of the drugs. Conclusion As typically prescribed, chlorthalidone in older adults was not associated with fewer adverse cardiovascular events or deaths than hydrochlorothiazide. However, it was associated with a greater incidence of electrolyte abnormalities, particularly hypokalemia. Primary funding source Ontario Ministry of Health and Long-Term Care.

Background There is an increased risk of death due to drug toxicity after release from incarceration. The purpose of this study was to describe the timing, rate and circumstances of drug toxicity deaths following release from incarceration. This information can be used to help design potential preventive interventions. Methods and Findings We reviewed coroner’s files to identify deaths in adults in Ontario between 2006 and 2013 caused by drug toxicity (n = 6,978) and these records were matched with provincial correctional records to identify individuals who died within one year of being released from incarceration (n = 702). Twenty percent (n = 137) of the 702 deaths occurred within one week of release. The majority (77%, n = 538) of deaths after release involved one or more opioids. Of the deaths involving opioids, intervention by another person may have been possible in 318 cases. Conclusions Between 2006 and 2013 in Ontario, one in ten drug toxicity deaths in adults occurred within one year of release from provincial incarceration. These findings may help to inform the implemention and assessment of interventions aimed at reducing drug toxicity deaths following release from incarceration.

Cigarettes might have been a blockbuster treatment for ulcerative colitis if they were After the 20-year patent ran out, prescription rates would have been buoyed by randomized control trials showing that cigarettes treat a host of previously unrecognized ailments. Then products containing only one enantiomer of nicotine would obligingly be given the nod by guideline writers in response to newer trials. It would take decades to overturn the vigorously defended argument that lung cancer was caused by the underlying illnesses and not by cigarettes.