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Abstract Background Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Examining gender (socio-cultural) in addition to sex (biological) is required to untangle socio-cultural characteristics contributing to inequities within or between sexes. This study aimed to develop a gender measure including four gender dimensions and examine the association between this gender measure and CVD incidence, across sexes. Methods A cohort of 9188 white-collar workers (49.9% females) in the Quebec region was recruited in 1991–1993 and follow-up was carried out 28 years later for CVD incidence. Data collection involved a self-administered questionnaire and extraction of medical-administrative CVD incident cases. Cox proportional models allowed calculations of hazard ratios (HR) and 95% confidence intervals (CI), stratified by sex. Results Sex and gender were partly independent, as discordances were observed in the distribution of the gender score across sexes. Among males, being in the third tertile of the gender score (indicating a higher level of characteristics traditionally ascribed to women) was associated with a 50% CVD risk increase compared to those in the first tertile (HR = 1.50; 95% CI: 1.24 to 1.82). This association persisted after adjustment for several CVD risk factors (HR = 1.42; 95% CI: 1.16 to 1.73). Conversely, no statistically significant association between the third tertile of the gender score and CVD incidence was observed in females (HR = 0.79, 95% CI: 0.60–1.05). Conclusions The findings suggested that males within the third tertile of the gender score were more likely to develop CVD, while females with those characteristics did not exhibit an increased risk. These findings underline the necessity for clinical and population health research to integrate both sex and gender measures, to further evaluate disparities in cardiovascular health and enhance the inclusivity of prevention strategies.

IntroductionCardiovascular disease (CVD) surveillance in Quebec and the rest of Canada is carried out using health administrative databases, which in Quebec includes the physician claims database. The presence of billing claims without diagnoses can lead to the number of CVD cases being underestimated. The purpose of this study is to estimate the proportion of CVD diagnoses and CVD cases that may be missing from these databases. MethodsThe study was conducted using a prospective cohort of 8781 participants living in the Québec City area. Access to health administrative databases was granted for the entire 28-year follow-up period. First, we performed frequency analyses to estimate the proportion of missing CVD diagnoses. Then we used validated algorithms to identify CVD cases and estimate the proportion of CVD cases that were potentially not captured over the 28-year period. ResultsAbout one-fifth (22.1%) of the diagnoses in the physician claims database were missing. The proportion of missing CVD cases was estimated at 12.7% for 1991–2018, although this varied with the period covered (1991–1996: 15.5%; 1997–2013: 10.7%; and 2014–2018: 16.3%). ConclusionApproximatively 1 in 10 CVD cases are not identified due to a missing diagnosis. This underestimation of CVD cases is a potential limitation that should be considered when using Quebec health administrative databases to identify CVD cases for surveillance work and epidemiological studies.

IntroductionLa surveillance des maladies cardiovasculaires (MCV) au Québec et dans le reste du Canada est effectuée à l’aide de fichiers médico-administratifs, parmi lesquels on retrouve, au Québec, le fichier des services médicaux rémunérés à l’acte. La présence d’actes facturés sans diagnostic peut entraîner une sous-estimation du nombre de cas de MCV. L’objectif de cette étude est d’estimer la proportion de diagnostics de MCV et de cas de MCV possiblement manquants dans ces fichiers. MéthodologieL’étude a été réalisée en utilisant une cohorte prospective comprenant 8 781 participants de la région de Québec. L'accès aux fichiers médico-administratifs a été obtenu pour l’ensemble des 28 années de suivi. Nous avons d’abord effectué des analyses de fréquence afin d’estimer la proportion de diagnostics de MCV manquants. Nous avons ensuite utilisé des algorithmes validés afin d’identifier les cas de MCV et d’estimer la proportion de cas de MCV possiblement manquants sur 28 ans. RésultatsEnviron un cinquième (22,1 %) des diagnostics du fichier des services médicaux rémunérés à l’acte était manquant. La proportion de cas de MCV manquants a été estimée à 12,7 % pour la période 1991-2018, avec des variations selon la période (1991-1996 : 15,5 %; 1997-2013 : 10,7 %; 2014-2018 : 16,3 %). ConclusionEnviron 1 cas de MCV sur 10 n’est pas identifié en raison des diagnostics manquants. Cette sous-estimation constitue une limite potentielle dont il faut tenir compte lors de l’utilisation des fichiers médico-administratifs québécois pour l’identification des cas de MCV dans un contexte de travaux de surveillance et d’études épidémiologiques.

Helicobacter pylori is a bacterium that may colonise and proliferate in human stomachs, leading invariably to chronic inflammation and, to a lesser extent, to peptic ulcers and cancer. The main objective of this study is to describe the epidemiology surrounding H. pylori in Nunavik’s Inuit population using the 2004 and 2017 Health Surveys. Estimated prevalences were 70.9% for bacterial colonisation using a stool antigens test (SAT), 72.5% for anti-H. pylori antibodies, 12.7% for faecal occult blood in participants aged ≥ 50 and respectively of 28.4%, 11.2% and 2.4% for a prior diagnosis of colonisation, gastritis and peptic ulcer in the medical charts, with under five cases of gastric cancer reported. Variables associated with higher SAT+ prevalence were the number of household members (prevalence ratio [PR] = 1.03) and age (quadratic relationship), whereas mainly drinking municipal (PR = 0.84) and natural water (PR = 0.72) compared to bottled water, and increasing alcohol consumption (PR = 0.96) were associated with reduced prevalence. Despite current regional guidelines targeting high risk individuals in the context of high prevalence, Nunavik’s health authorities must remain vigilant by following gastric cancer incidence and the rapid evolution of guidelines, while considering local realities.

COVID-19 accelerated continuing professional development (CPD) delivered online. We aimed to compare the impact of in-person versus online CPD courses on medical specialists’ behavioural intentions and subsequent behaviour. In this comparative before-and-after study, medical specialists attended in-person courses on nine clinical topics. A second group attended an adapted online version of these courses. Behavioural intention and its psychosocial determinants were measured before and immediately after the courses. Behaviour change was measured six months later. Generalised estimating equation (GEE) models were used to compare the impact of course formats. A total of 82/206 in-person registrants (mean age: 52±10 years; 50% men) and 318/506 on-line registrants (mean age: 49±12 years; men: 63%) participated. Mean intention before in-person courses was 5.99±1.31 and 6.43±0.80 afterwards (average intention gain 0.44, CI: 0.16–0.74; p=0.003); mean intention before online courses was 5.53±1.62 and 5.98±1.40 afterwards (average intention gain of 0.45, CI: 0.30–0.58; p

Abstract Background Randomized clinical trials have shown that, under optimal conditions, statins reduce the risk of cardiovascular events in older adults. Given the prevalence and consequences of suboptimal adherence to statin among older adults, it is essential to document strategies designed to increase statin adherence in this population. The objective of this systematic review is to describe and summarize the effectiveness of interventions to improve statin adherence in older adults (≥ 65 years old). Methods This review followed PRISMA guidelines. Studies were identified from PubMed, PsycINFO, Embase, CINAHL and Web of Science. Study selection was conducted independently by four reviewers working in pairs. Included studies reported data on interventions designed to increase adherence to statin therapy in older adults and were original trials or observational studies. Interventions were pragmatically regrouped into 8 different categories going from patient to administrative level. Two reviewers extracted study data and assessed study quality independently. Given the heterogeneity between the included studies, a narrative critique and summary was conducted. Results Twelve out of the 2889 identified articles were included in the review. Our review showed that simplifying patients’ drug regimen, administrative improvements and large-scale pharmacy-led automated telephone interventions show positive effects on patient adherence to statin therapy, with odds ratios between > 1.0 and 3.0, while education-based strategies and intensified patient care showed mixed results. Conclusions Current evidence suggests that some interventions can increase statin adherence in older adults, which could help in the reduction of the risk of a cardiovascular event in this population.

Abstract Background Health administrative databases play a crucial role in population-level multimorbidity surveillance. Determining the appropriate retrospective or lookback period (LP) for observing prevalent and newly diagnosed diseases in administrative data presents challenge in estimating multimorbidity prevalence and predicting health outcome. The aim of this population-based study was to assess the impact of LP on multimorbidity prevalence and health outcomes prediction across three multimorbidity definitions, three lists of diseases used for multimorbidity assessment, and six health outcomes. Methods We conducted a population-based study including all individuals ages > 65 years on April 1st, 2019, in Québec, Canada. We considered three lists of diseases labeled according to the number of chronic conditions it considered: (1) L60 included 60 chronic conditions from the International Classification of Diseases (ICD); (2) L20 included a core of 20 chronic conditions; and (3) L31 included 31 chronic conditions from the Charlson and Elixhauser indices. For each list, we: (1) measured multimorbidity prevalence for three multimorbidity definitions (at least two [MM2+], three [MM3+] or four (MM4+) chronic conditions); and (2) evaluated capacity (c-statistic) to predict 1-year outcomes (mortality, hospitalisation, polypharmacy, and general practitioner, specialist, or emergency department visits) using LPs ranging from 1 to 20 years. Results Increase in multimorbidity prevalence decelerated after 5–10 years (e.g., MM2+, L31: LP = 1y: 14%, LP = 10y: 58%, LP = 20y: 69%). Within the 5–10 years LP range, predictive performance was better for L20 than L60 (e.g., LP = 7y, mortality, MM3+: L20 [0.798;95%CI:0.797-0.800] vs. L60 [0.779; 95%CI:0.777–0.781]) and typically better for MM3 + and MM4 + definitions (e.g., LP = 7y, mortality, L60: MM4+ [0.788;95%CI:0.786–0.790] vs. MM2+ [0.768;95%CI:0.766–0.770]). Conclusions In our databases, ten years of data was required for stable estimation of multimorbidity prevalence. Within that range, the L20 and multimorbidity definitions MM3 + or MM4 + reached maximal predictive performance.

Background Psychosocial stressors at work, defined by the job strain and effort–reward imbalance at work (ERI) models, were shown to increase coronary heart disease risk. No previous study has examined the adverse effect of psychosocial stressors at work from both models on atrial fibrillation (AF) incidence. The objective of this study was to examine the separate and combined effect of psychosocial stressors at work from the job strain and ERI models on AF incidence in a prospective cohort study. Methods and Results A total of 5926 white‐collar workers (3021 women and 2905 men) free of cardiovascular disease at baseline were followed for an average of 18 years. Job strain (high psychological demands combined with low decision latitude) and ERI were assessed using validated instruments. AF events were identified in medical databases with universal coverage. Hazard ratios (HRs) with 95% CIs were estimated using Cox regression models, controlling for socioeconomic characteristics and lifestyle‐related and clinical risk factors. A total of 186 AF incident events were identified over 18 years. Workers exposed to job strain (HR, 1.83 [95% CI, 1.14–2.92]) and ERI (HR, 1.44 [95% CI, 1.05–1.98]) had a higher risk of AF in fully adjusted models. Combined exposure to job strain and ERI was associated with a 2‐fold AF risk increase (HR, 1.97 [95% CI, 1.26–3.07]). Conclusions Psychosocial stressors at work from the job strain and ERI models are associated with an increased risk of AF, separately and in combination. Workplace prevention strategies targeting these psychosocial stressors at work may be effective to reduce the burden associated with AF.

Objective To compare health outcomes and costs given in the emergency department (ED) and walk-in clinics for ambulatory children presenting with acute respiratory diseases.Design A retrospective cohort study.Setting This study was conducted from April 2016 to March 2017 in one ED and one walk-in clinic. The ED is a paediatric tertiary care centre, and the clinic has access to lab tests and X-rays.Participants Inclusion criteria were children: (1) aged from 2 to 17 years old and (2) discharged home with a diagnosis of upper respiratory tract infection (URTI), pneumonia or acute asthma.Main outcome measures The primary outcome measure was the proportion of patients returning to any ED or clinic within 3 and 7 days of the index visit. The secondary outcome measures were the mean cost of care estimated using time-driven activity-based costing and the incidence of antibiotic prescription for URTI patients.Results We included 532 children seen in the ED and 201 seen in the walk-in clinic. The incidence of return visits at 3 and 7 days was 20.7% and 27.3% in the ED vs 6.5% and 11.4% in the clinic (adjusted relative risk at 3 days (aRR) (95% CI) 3.17 (1.77 to 5.66) and aRR at 7 days 2.24 (1.46 to 3.44)). The mean cost (95% CI) of care (CAD) at the index visit was $C96.68 (92.62 to 100.74) in the ED vs $C48.82 (45.47 to 52.16) in the clinic (mean difference (95% CI): 46.15 (41.29 to 51.02)). Antibiotic prescription for URTI was less common in the ED than in the clinic (1.5% vs 16.4%; aRR 0.10 (95% CI 0.03 to 0.32)).Conclusions The incidence of return visits and cost of care were significantly higher in the ED, while antibiotic use for URTI was more frequent in the walk-in clinic. These data may help determine which setting offers the highest value to ambulatory children with acute respiratory conditions.

Abstract Introduction Plasmode simulations are a type of simulations that use real data to determine the synthetic data-generating equations. Such simulations thus allow evaluating statistical methods under realistic conditions. As far as we know, no plasmode algorithm has been proposed for simulating longitudinal data. In this paper, we propose a longitudinal plasmode framework to generate realistic data with both a time-varying exposure and time-varying covariates. This work was motivated by the objective of comparing different methods for estimating the causal effect of a cumulative exposure to psychosocial stressors at work over time. Methods We developed two longitudinal plasmode algorithms: a parametric and a nonparametric algorithms. Data from the PROspective Québec (PROQ) Study on Work and Health were used as an input to generate data with the proposed plasmode algorithms. We evaluated the performance of multiple estimators of the parameters of marginal structural models (MSMs): inverse probability of treatment weighting, g-computation and targeted maximum likelihood estimation. These estimators were also compared to standard regression approaches with either adjustment for baseline covariates only or with adjustment for both baseline and time-varying covariates. Results Standard regression methods were susceptible to yield biased estimates with confidence intervals having coverage probability lower than their nominal level. The bias was much lower and coverage of confidence intervals was much closer to the nominal level when considering MSMs. Among MSM estimators, g-computation overall produced the best results relative to bias, root mean squared error and coverage of confidence intervals. No method produced unbiased estimates with adequate coverage for all parameters in the more realistic nonparametric plasmode simulation. Conclusion The proposed longitudinal plasmode algorithms can be important methodological tools for evaluating and comparing analytical methods in realistic simulation scenarios. To facilitate the use of these algorithms, we provide R functions on GitHub. We also recommend using MSMs when estimating the effect of cumulative exposure to psychosocial stressors at work.

Objective Arterial stiffness and exposure to psychosocial work-related factors increase the risk of developing cardiovascular disease. However, little is known about the relationship between psychosocial work-related factors and arterial stiffness. We aimed to examine this relationship.Design Prospective cohort study.Setting Public organisations in Quebec City, Canada.Participants The study included 1736 white-collar workers (women 52%) from 19 public organisations.Primary and secondary outcome measures Association between psychosocial work-related factors from the job strain and effort–reward imbalance (ERI) models assessed at study baseline (1999–2001) with validated instruments and arterial stiffness assessed using carotid–femoral pulse wave velocity at follow-up, on average 16 years later (2015–2018). Generalised estimating equations were used to estimate differences in arterial stiffness between exposed and unexposed participants. Subgroup analyses according to sex, age, blood pressure (BP), cardiovascular risk score and employment status were conducted.Results Among participants with high diastolic BP (≥90 mm Hg) at baseline, aged 47 on average, those exposed to high job strain had higher arterial stiffness (1.38 m/s (95% CI: 0.57 to 2.19)) at follow-up, 16 years later, following adjustment for a large set of potential confounders. The trend was similar in participants with high systolic BP (≥140 mm Hg) exposed to high job strain (0.84 m/s (95% CI: −0.35 to 2.03)). No association was observed for ERI in the total sample and counterintuitive associations were observed in subgroup analyses.Conclusions Job strain may have a long-term deleterious effect on arterial stiffness in people with high BP. Interventions at midlife to reduce job strain may mitigate arterial stiffness progression.

Abstract Given that flooding episodes are occurring at a greater rate due to climate change, individuals must adopt certain adaptation behaviors to prevent or mitigate the anticipated or negative impact of such events. However, few studies have assessed if and how households and individuals have actually taken action in this regard. Because some individual beliefs can be linked to facilitating factors and barriers to action, a better understanding of the adoption of adaptive behaviors requires a combined analysis of individual psychosocial factors. The purpose of this study was to develop a better understanding of the reasons underlying the adoption of behaviors related to structural adaptation to flooding by people living in or near flood‐prone areas in the Province of Québec (Canada). Results of a series of structural equation modeling showed that behavioral, normative and control beliefs were all significant predictors of the respondents' intention to adopt structural flood protective behaviors, with normative beliefs being the strongest. By identifying the best psychosocial predictors of the adoption of such behaviors, the results of this study provide valuable insights regarding the most effective factors to be used in public health messages to promote the adoption of behaviors related to structural adaptation to flooding.

Background: People with diabetes tend to use many medications to treat diabetes and comorbidities. Nevertheless, the evolution of polypharmacy in newly diagnosed males and females has been little studied. Objective: The objective of this paper was to identify and describe medication trajectories in incident diabetes cases according to sex. Methods: Data were obtained from the Quebec Integrated Chronic Disease Surveillance System. We built a population-based cohort of community-dwelling individuals aged >65 years diagnosed with diabetes in 2014 who were alive and covered with the public drug plan until March 31, 2019. Latent class models were used to identify medication trajectory groups in males and females separately. Results: Of the 10,363 included individuals, 51.4% were males. Females were older and more likely to have more medication claims than males. Four trajectory groups were identified for males and five for females. Most trajectories showed sustained and stable number of medications over time. For each sex, only one of the trajectory groups included a mean annual number of medications lesser than five. Slight increasing trends of medication use were detected in the trajectories composed of very high users, which included older, more comorbid individuals frequently exposed to potentially inappropriate medications. Conclusions: Most males and females with incident diabetes had a high burden of medication following the year of diagnosis and were classified in a group of sustained medication use over time. The largest increase in medication was among those who had higher level of polypharmacy of questionable quality at baseline, raising concerns about the innocuity of such medication trajectories.

Background: Residents of long-term care facilities (LTCFs) and private residences for seniors (PRSs) were given priority for vaccination against coronavirus disease 2019 (COVID-19). Given the shortage of vaccine in the winter of 2021, the Comité sur l’immunisation du Québec recommended postponing the administration of second doses to ensure more rapid and widespread administration of first doses. The objective of this study was to measure the impact of first-dose vaccination on 1) the incidence of cases and complications in LTCFs and PRSs and 2) the frequency of outbreaks in LTCFs. Methods: In this ecological study, COVID-19 incidence and complications in residents of LTCFs and PRSs in Québec were compared with the general (community) population at a point in time when there was still only limited eligibility for vaccination. Results: After vaccination in LTCFs, the incidence rate of COVID-19 decreased by 92% compared with 49% in the community, and deaths decreased by 95%. By six weeks post-vaccination, almost no facility reported five or more cases per 100 beds per week. The incidence rate decreased by 91% in PRSs compared with 2% in the community. Hospitalizations and deaths in PRSs decreased by 94% and 90%, respectively. Conclusion: As a result of 1) vaccination of residents with one dose, 2) natural immunity already acquired in LTCFs and PRSs, 3) vaccination of healthcare workers and 4) other non-pharmaceutical prevention measures implemented, the circulation of the coronavirus in these settings was largely interrupted.

Contexte : Les résidents de centres d’hébergement et de soins de longue durée (CHSLD) et de résidences privées pour aînés (RPA) ont été vaccinés en priorité contre la maladie à coronavirus 2019 (COVID-19). Vu la pénurie de vaccins de l’hiver 2021, le Comité sur l’immunisation du Québec a recommandé le report de l’administration des deuxièmes doses pour augmenter plus rapidement la couverture vaccinale avec une dose. L’objectif de cette étude est de mesurer l’impact de la vaccination avec une première dose sur 1) l’incidence des cas et des complications en CHSLD et en RPA ainsi que 2) sur la fréquence des éclosions en CHSLD. Méthodes : Dans cette étude écologique, le taux d’incidence et de complications de la COVID-19 chez les résidents de CHSLD et de RPA du Québec, ont été comparés à la population générale à un moment où l’éligibilité à la vaccination était encore limitée. Résultats : Après la vaccination en CHSLD, le taux d’incidence de la COVID-19 a diminué de 92 %, contre 49 % dans la communauté, et le nombre de décès a diminué de 95 %. À six semaines post-vaccination, presqu’aucune installation ne rapportait cinq cas ou plus par 100 lits par semaine. En RPA, le taux d’incidence a diminué de 91 %, contre 2 % dans la communauté durant la même période. Les hospitalisations et les décès ont diminué de 94 % et 90 %, respectivement. Conclusion : Suite à 1) la vaccination avec une dose des résidents 2) l’immunité naturelle déjà acquise en CHSLD et en RPA, 3) la vaccination des travailleurs de la santé ainsi que 4) d’autres mesures de prévention non-pharmaceutiques mises en place, la circulation du coronavirus dans ces milieux de vie a été largement interrompue.

OBJECTIVES: This systematic review and meta-analysis aimed to synthesize the available data on prospective associations between work-related stressors and the risk of type 2 diabetes mellitus (T2DM) among adult workers, according to the demand–control–support (DCS) and the effort–reward imbalance (ERI) models. METHOD: We searched for prospective studies in PubMed, EMBASE, Web of Science, Scopus, CINHAL and PsychInfo. After screening and extraction, quality of evidence was assessed using the ROBINS-I tool adapted for observational studies. The effect estimates extracted for each cohort were synthesized using random effect models. RESULTS: We included 18 studies (reporting data on 25 cohorts) in meta-analyses for job strain, job demands, job control, social support at work and ERI. Workers exposed to job strain had a higher risk of developing T2DM when compared to unexposed workers [pooled rate ratio (RR) 1.16, 95% confidence interval (CI) 1.07–1.26]. This association was robust in several supplementary analyses. For exposed women relative to unexposed women, the RR was 1.35 (95% CI 1.12–1.64). The RR of workers exposed to ERI was 1.24 (95% CI 1.08–1.42) compared to unexposed workers. CONCLUSIONS: This is the first meta-analysis to find an effect of ERI on the onset of T2DM incidence. It also confirms that job strain increases the incidence of T2DM, especially among women.

ObjectivesThere is evidence that both low socioeconomic status (SES) and psychosocial stressors at work (PSW) increase risk of depression, but prospective studies on the contribution of PSW to the socioeconomic gradient of depression are still limited.MethodsUsing a prospective cohort of Quebec white-collar workers (n = 9188 participants, 50% women), we estimated randomized interventional analogues of the natural direct effect of SES indicators at baseline (education level, household income, occupation type and a combined measure) and of their natural indirect effects mediated through PSW (job strain and effort-reward imbalance (ERI) measured at the follow-up in 1999-2001) on incident physician-diagnosed depression.ResultsDuring 3 years of follow-up, we identified 469 new cases (women: 33.1 per 1000 person-years; men: 16.8). Mainly in men, low SES was a risk factor for depression [education: hazard ratio 1.72 (1.08-2.73); family income: 1.67 (1.04-2.67); occupational type: 2.13 (1.08-4.19)]. In the entire population, exposure to psychosocial stressors at work was associated with increased risk of depression [job strain: 1.42 (1.14-1.78); effort-reward imbalance (ERI) 1.73 (1.41-2.12)]. The estimated indirect effects of socioeconomic indicators on depression mediated through job strain ranged from 1.01 (0.99-1.03) to 1.04 (0.98-1.10), 4-15% of total effects, and for low reward from 1.02 (1.00-1.03) to 1.06 (1.01-1.11), 10-15% of total effects.DiscussionOur study suggests that PSW only slightly mediate the socioeconomic gradient of depression, but that socioeconomic inequalities, especially among men, and PSW both increase the incidence of depression.

Abstract Objective: We described the evolution of SARS-CoV-2 source of infection in a cohort of healthcare workers (HCWs) of Quebec, Canada, during the first three pandemic waves. We also estimated their household secondary attack rate (SAR) and its risk factors. Design: Cross-sectional surveys. Participants: HCWs with a SARS-CoV-2 infection confirmed by polymerasa chain reaction and diagnosed between March 2020 and May 2021. Methods: We collected demographic, clinical, vaccination, and employment information, self-reported perceived source of infection, and transmission to household members during the first three pandemic waves. SAR was calculated for households with ≥2 members where the HCW was the index case. A Poisson regression model estimated the association between risk factors and SAR. Results: Among the 11,670 HCWs completing the survey, 91%, perceived their workplace as the source of infection during the first wave (March–July 2020), 71% during the second wave (July 2020–March 2021), and 40% during the third wave (March–May 2021). Conversely, HCWs reported an increasing proportion of household-acquired infections with each wave from 4% to 14% and 33%, respectively. The overall household SAR of 7,990 HCWs living with ≥1 person was 30% (95%CI: 29–30). SAR increased with the presence of symptoms, older age, and during Alpha-variant predominant period. Conclusions: HCWs and their household members were largely affected during the first pandemic waves of COVID-19, but the relative importance of occupational exposure changed overtime. Pandemic preparedness in healthcare settings is essential to protect HCWs from emerging biological hazard exposures.

Abstract Background Administrative data have several advantages over questionnaire and interview data to identify cases of depression: they are usually inexpensive, available for a long period of time and are less subject to recall bias and differential classification errors. However, the validity of administrative data in the correct identification of depression has not yet been studied in general populations. The present study aimed to 1) evaluate the sensitivity and specificity of administrative cases of depression using the validated Composite International Diagnostic Interview – Short Form (CIDI-SF) as reference standard and 2) compare the known-groups validity between administrative and CIDI-SF cases of depression. Methods The 5487 participants seen at the last wave (2015–2018) of the PROQ cohort had CIDI-SF questionnaire data linked to hospitalization and medical reimbursement data provided by the provincial universal healthcare provider and coded using the International Classification of Disease. We analyzed the sensitivity and specificity of several case definitions of depression from this administrative data. Their association with known predictors of depression was estimated using robust Poisson regression models. Results Administrative cases of depression showed high specificity (≥ 96%), low sensitivity (19–32%), and rather low agreement (Cohen’s kappa of 0.21–0.25) compared with the CIDI-SF. These results were consistent over strata of sex, age and education level and with varying case definitions. In known-groups analysis, the administrative cases of depression were comparable to that of CIDI-SF cases (RR for sex: 1.80 vs 2.03 respectively, age: 1.53 vs 1.40, education: 1.52 vs 1.28, psychological distress: 2.21 vs 2.65). Conclusion The results obtained in this large sample of a general population suggest that the dimensions of depression captured by administrative data and by the CIDI-SF are partially distinct. However, their known-groups validity in relation to risk factors for depression was similar to that of CIDI-SF cases. We suggest that neither of these data sources is superior to the other in the context of large epidemiological studies aiming to identify and quantify risk factors for depression.

Abstract Background Polypharmacy is common among older adults and it represents a public health concern, due to the negative health impacts potentially associated with the use of several medications. However, the large number of medication combinations and sequences of use makes it complicated for traditional statistical methods to predict which therapy is genuinely associated with health outcomes. The project aims to use artificial intelligence (AI) to determine the quality of polypharmacy among older adults with chronic diseases in the province of Québec, Canada. Methods We will use data from the Quebec Integrated Chronic Disease Surveillance System (QICDSS). QICDSS contains information about prescribed medications in older adults in Quebec collected over 20 years. It also includes diagnostic codes and procedures, and sociodemographic data linked through a unique identification number for each individual. Our research will be structured around three interconnected research axes: AI, Health, and Law&Ethics. The AI research axis will develop algorithms for finding frequent patterns of medication use that correlate with health events, considering data locality and temporality (explainable AI or XAI). The Health research axis will translate these patterns into polypharmacy indicators relevant to public health surveillance and clinicians. The Law&Ethics axis will assess the social acceptability of the algorithms developed using AI tools and the indicators developed by the Heath axis and will ensure that the developed indicators neither discriminate against any population group nor increase the disparities already present in the use of medications. Discussion The multi-disciplinary research team consists of specialists in AI, health data, statistics, pharmacy, public health, law, and ethics, which will allow investigation of polypharmacy from different points of view and will contribute to a deeper understanding of the clinical, social, and ethical issues surrounding polypharmacy and its surveillance, as well as the use of AI for health record data. The project results will be disseminated to the scientific community, healthcare professionals, and public health decision-makers in peer-reviewed publications, scientific meetings, and reports. The diffusion of the results will ensure the confidentiality of individual data.

Introduction: The progression of complications of type 2 diabetes (T2D) is unique to each patient and can be depicted through individual temporal trajectories. Latent growth modeling approaches (latent growth mixture models [LGMM] or latent class growth analysis [LCGA]) can be used to classify similar individual trajectories in a priori non-observed groups (latent groups), sharing common characteristics. Although increasingly used in the field of T2D, many questions remain regarding the utilization of these methods. Objective: To review the literature of longitudinal studies using latent growth modeling approaches to study T2D. Methods: MEDLINE (Ovid), EMBASE, CINAHL and Wb of Science were searched through August 25th, 2021. Data was collected on the type of latent growth modeling approaches (LGMM or LCGA), characteristics of studies and quality of reporting using the GRoLTS-Checklist and presented as frequencies. Results: From the 4,694 citations screened, a total of 38 studies were included. The studies were published beetween 2011 and 2021 and the length of follow-up ranged from 8 weeks to 14 years. Six studies used LGMM, while 32 studies used LCGA. The fields of research varied from clinical research, psychological science, healthcare utilization research and drug usage/pharmaco-epidemiology. Data sources included primary data (clinical trials, prospective/retrospective cohorts, surveys), or secondary data (health records/registries, medico-administrative). Fifty percent of studies evaluated trajectory groups as exposures for a subsequent clinical outcome, while 24% used predictive models of group membership and 5% used both. Regarding the quality of reporting, trajectory groups were adequately presented, however many studies failed to report important decisions made for the trajectory group identification. Conclusion: Although LCGA were preferred, the contexts of utilization were diverse and unrelated to the type of methods. We recommend future authors to clearly report the decisions made regarding trajectory groups identification.

Objectives: This study in female sex workers (FSWs) aimed to: (1) estimate type-specific incidence and persistence of human papillomavirus (HPV) infection in Cotonou (Benin) and Bamako (Mali); and (2) identify the factors associated with type-specific incidence and persistence of high-risk HPV (HR-HPV) infection. Methods: A 1-year prospective cohort study on cervical cancer screening, and HPV and human immunodeficiency virus (HIV) infections was conducted among FSWs in Cotonou and Bamako from 2017 to 2019. Poisson regression models assessed factors associated with the incidence of HR-HPV infection, while log-binomial regression was performed to identify factors associated with the persistence of HR-HPV infection. Adjusted relative risks (ARR) and 95% confidence intervals (95% CI) were estimated. Results: The incidence of HR-HPV infection was 46.98 per 1000 women-months (predominant types HPV16, HPV35 and HPV59). Factors associated with the incidence of HR-HPV infection were age

Abstract Climate change is predicted to increase the frequency and intensity of floods in the province of Quebec, Canada. Therefore, in 2015, to better monitor the level of adaptation to flooding of Quebec residents living in or near a flood-prone area, the Quebec Observatory of Adaptation to Climate Change developed five indices of adaptation to flooding, according to the chronology of events. The present study was conducted 4 years later and is a follow-up to the 2015 one. Two independent samples of 1951 (2015) and 974 (2019) individuals completed a questionnaire on their adoption (or non-adoption) of flood adaptation behaviors, their perception of the mental and physical impacts of flooding, and their knowledge of the fact that they lived in a flood-prone area. The results of the study demonstrated the measurement invariance of the five indices across two different samples of people over time, ensuring that the differences (or absence of differences) observed in flood-related adaptive behaviors between 2015 and 2019 were real and not due to measurement errors. They also showed that, overall, Quebeckers’ flood-related adaptive behaviors have not changed considerably since 2015, with adaptation scores being similar in 2019 for four of the five flood indices. Moreover, the results indicated an increase in self-reported physical and mental health issues related to past flooding events, as well as a larger proportion of people having consulted a health professional because of these problems. Thus, this study provides a better understanding of flood adaptation in Quebec over the past 4 years and confirms that the five adaptive behavior indices developed in 2015 are appropriate tools for monitoring changes in flood adaptation in the province. Finally, our results showed that little has changed in Quebeckers’ adoption of adaptive behaviors, highlighting the need for awareness raising in order to limit the impacts that climate change will have on the population.

Abstract Background Recent evidence suggests that climate change and other factors are leading to the emergence of Lyme disease in the province of Quebec, where it previously did not exist. As risk areas expand further north, the population can adopt specific preventive behaviors to limit chances of infection. The objectives of this study were to (1) create an index of Lyme disease prevention behaviors (LDPB), and (2) use the theory of planned behavior (TPB) to explain the decision-making process of people who choose to adopt LDPB. Methods A sample of 1959 adults living in a Lyme disease risk area completed a questionnaire by phone (n = 1003) or on the Web (n = 956). The questionnaire measured whether they did or did not adopt the LDPB proposed by public health officials. It also measured some TPB variables, including their attitude or perceived social norms regarding LDPB. Results Our findings led to the creation of a Lyme disease prevention index consisting of 10 behaviors, down from the 19 behaviors initially considered for inclusion in the index. Rates of adoption of each behavior varied tremendously, from 4.30 to 83.80%. All variables of the TPB model (attitude, social norms, and perceived control) were significantly associated with intention to adopt preventive behaviors. Intention itself was significantly associated with adoption of LDPB. Likewise, risk perception was positively correlated with the adoption of LDPB. Conclusions This study led to the creation of a Lyme disease prevention index that can be used by public health agencies, researchers, and professionals to monitor the evolution over time of individuals’ LDPB adoption rates. It also showed the usefulness of the TPB in understanding the adoption of LDPB and how intention to adopt such behaviors is formed.

Abstract Background To monitor the adoption of climate change adaptive behaviors in the population, public health authorities have to conduct national surveys, which can help them target vulnerable subpopulations. To ensure reliable estimates of the adoption of these preventive behaviors, many data collection methods are offered by polling firms. The aim of this study was to compare a telephone survey with a web survey on Lyme disease with regard to their representativeness. Methods The data comes from a cross-sectional study conducted in the Province of Québec (Canada). In total, 1003 people completed the questionnaire by telephone and 956 filled in a web questionnaire. We compared the data obtained from both survey modes with the census data in regard to various demographic characteristics. We then compared the data from both samples in terms of self-reported Lyme disease preventive behaviors and other theoretically associated constructs. We also assessed the measurement invariance (equivalence) of the index of Lyme disease preventive behaviors across the telephone and web samples. Results Findings showed that neither the telephone nor the web panel modes of data collection can be considered more representative of the target population. The results showed that the proportion of item non-responses was significantly higher with the web questionnaire (5.6%) than with the telephone survey (1.3%), and that the magnitude of the differences between the two survey modes was nil for 19 out of the 30 items related to Lyme disease, and small for 11 of them. Results from invariance analyses confirmed the measurement invariance of an index of adaptation to Lyme disease, as well as the mean invariance across both samples. Conclusions Our results suggested that both samples provided similar estimates of the level of adaptation to Lyme disease preventive behaviors. In sum, the results of our study showed that neither survey mode was superior to the other. Thus, in studies where adaptation to climate change is monitored over time, using a web survey instead of a telephone survey could be more cost-effective, and researchers should consider doing so in future surveys on adaptation to climate. However, we recommend conducting a pretest study before deciding whether to use both survey modes or only one of them.

Background and objectives: Growing evidence indicates that the nurse navigator-pivot (NN)*, is key to optimizing care processes and outcomes. However, large scale studies are needed to examine how patients exposed to NNs (as opposed to non-NN) differentially perceived their cancer care experiences. Method: Participants (N = 2,858) treated for cancer in the last six months at university-affiliated cancer centres in Montréal, Québec, completed the Ambulatory Oncology Patient Satisfaction Survey (AOPSS). Results: Cancer care experiences and satisfaction were significantly higher in the NN group (n = 2,003) for all six care domains (Ds from 3.32 to 8.95) and all four nursing functions (Ds from 5.64 to 10.39) when compared to the non-NN group (n = 855). Discussion: The NN role is significantly related to enhanced cancer care experiences and higher patient satisfaction. Future research should explore potential causal effects between NNs and care processes, as well as patient outcomes. *NN includes both terms: nurse navigator and nurse pivotKey words: cancer, oncology, nurse navigator, nurse pivot, patient satisfaction, patient cancer care experiences

Contexte et objectifs : Un nombre croissant de résultats probants indique que l’infirmière pivot en oncologie (IPO)* joue un rôle de premier plan dans l’optimisation des processus et des résultats de soins. Il faudra toutefois mener des études d’envergure pour comparer les perceptions de l’expérience de soins liés au cancer des patients traités par des infirmières pivots et de ceux qui n’ont pas bénéficié de ce type de suivi. Méthodologie : Des participants (N = 2 858) traités au cours des six derniers mois dans un centre de traitement du cancer situé à Montréal, au Québec, et affilié à une université ont répondu au sondage sur la satisfaction des patients en traitement anticancéreux ambulatoire, c’est-à-dire le Ambulatory Oncology Patient Satisfaction Survey (AOPSS). Résultats : L’expérience des soins oncologiques était significativement plus positives et la satisfaction plus élevée dans le groupe suivi par une infirmière pivot (n = 2 003) pour les six domaines de soins (différences moyennes de 3,32 à 8,95) et les quatre fonctions infirmières (différences moyennes de 5,64 à 10,39), comparativement au groupe sans IPO (n = 855). Discussion : L’infirmière pivot joue un rôle important dans l’amélioration de l’expérience de soins et la satisfaction des patients. Les recherches futures devront explorer les potentielles relations de cause à effet entre les infirmières pivots, les processus de soins et les résultats des patients.* Les termes « infirmière pivot » et « infirmière navigatrice » sont synonymes.Mots-clés : cancer, oncologie, infirmière pivot, satisfaction des patients, expérience des soins oncologiques

Research has focused on the relations between television (TV) viewing time and children’s reading achievement. Two hypotheses have been proposed to explain this relation. The substitution hypothesis proposes that TV viewing distracts students from activities that are important for their learning. The inhibition hypothesis proposes that watching television inhibits important affective/cognitive skills. In this study, we test both hypotheses by estimating the relation between TV viewing time and reading achievement. We use the frequency of students’ leisure reading and the frequency of interactions between students and their parents as potential mediators to test the substitution hypothesis, whereas for the inhibition one, we use students’ intrinsic motivation to read and their level of inattention. Data come from the Québec Longitudinal Study of Child Development (QLSCD). Designed by the Institut de la statistique du Québec, QLSCD covers a wide range of themes. The QLSCD is representative of children in Québec and contains 2223 participants who were followed from 0 to 21 years old. The four structural models tested are built as follows: the TV viewing time at 6 years old predicts the four mediating variables at 8 years old, which in turn predicts reading achievement at 10 years old. In addition, we have tested models’ gender invariance. Results indicate that TV viewing time is not directly or indirectly associated with reading achievement. Specifically, it is not associated with the mediating variables of child-parent interactions, intrinsic motivation, and inattention. However, the frequency of leisure reading is negatively associated with the time spent watching TV. This association is very small (−0.07) and has no indirect effect on reading achievement. Finally, results do not vary according to the gender of the participants. Our results are in line with those of previous studies in the field and cast some doubts on the potential negative effects of TV viewing time on reading achievement.

Abstract Background In the current context of climate change, climate forecasts for the province of Quebec (Canada) are a lengthening of the thunderstorm season and an increase in episodes of intense precipitations. These changes in the distribution of precipitations could heighten the intensity or frequency of floods, a natural hazard that concerns 80% of Quebec’s riverside municipalities. For the health and safety of the at-risk population, it is very important to make sure they have acquired necessary adaptive behaviors against flooding hazard. However, there has been no assessment of these flood adaptation behaviors to date. Thus, the aim of this study was to develop and validate five indices of adaptation to flooding. Methods A sample of 1951 adults completed a questionnaire by phone. The questionnaire, specifically developed for this study, measured whether they did or did not adopt the behaviors that are proposed by public health officials to protect themselves against flooding. Results The results of the item, confirmatory factor, and multiple correspondence analyses contributed to the development of five indices corresponding to the adaptation behaviors to adopt according to the chronology of events: (a) pre-alert preventive behaviors, (b) behaviors to carry out after the alert is issued, (c) behaviors to adopt during a flood not requiring evacuation, (d) behaviors to adopt during a flood requiring evacuation, and (e) post-flood behaviors. The results of this study also showed that people who perceive a risk of flooding in their home in the next 5 years tend to adopt more preventive behaviors and adaptation behaviors than those who perceive little or no risk at all. They also reveal that people who feel more adverse effects on their physical or mental health tend to adopt more adaptive behaviors than those who feel little or no adverse effects on their health. Conclusion Across a series of psychometric analyses, the results showed that these flood adaptation indices could properly measure a vast range of adaptive behaviors according to the chronology of events. Therefore, researchers, public health agencies, and professionals can use them to monitor the evolution of individuals’ adaptive behaviors during floods.

Background: The standard therapy for advanced stage non-small cell lung cancer (NSCLC) with no actionable gene alterations is a platinum-based chemotherapy doublet and immune checkpoint blocker (ICB), either concurrently or sequentially, followed by docetaxel at the time of tumor progression. However, more effective treatments are needed. We evaluated the nab-paclitaxel and durvalumab combination in patients with previously treated advanced stage NSCLC.Methods: Patients with advanced stage NSCLC previously treated with one line of platinum-based doublet with or without an ICB and no activating EGFR mutations or ALK translocations received nab-paclitaxel 100 mg/m2 (days 1 and 8) plus durvalumab 1,125 mg (day 15) every 21 days. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and safety.Results: Between February 2016 and December 2016, 79 patients were enrolled. The median age was 63 years. Most patients were males (68.4%), had non-squamous histology (69.6%), and had no prior ICB treatment (88.6%). The median PFS was 4.5 months; median OS was 10.1 months. A post hoc analysis of survival by prior ICB treatment revealed a median PFS and OS of 4.4 and 9.9 months, respectively, in ICB-naive patients and 6.9 months and not estimable, respectively, in patients previously treated with ICB. The most common treatment-emergent adverse events were asthenia (46.2%) and diarrhea (34.6%); four treatment-related deaths (5.1%) occurred.Conclusions: The nab-paclitaxel and durvalumab combination is feasible and demonstrated antitumor activity without new safety signals. Additional studies using taxanes and ICB in patients with previously treated NSCLC are warranted.Clinical Trial Registration:ClinicalTrials.gov registration (NCT02250326).EudraCT number: 2014-001105-41

IntroductionDespite improvements in the treatment of advanced non-small cell lung cancer (NSCLC), certain patient populations remain underrepresented in clinical trials. Many patients have benefited from platinum doublets, including nab-paclitaxel–based regimens, but there are patients with comorbidities who particularly require careful balancing of efficacy and safety. Clinical trial data are limited for patients who are elderly or have renal impairment, diabetes, or impaired performance status.MethodsTo better understand outcomes in these patient populations, we performed a pooled analysis using data from the ABOUND clinical trial program (ABOUND.SQM, ABOUND.PS2, ABOUND.70+) and the key phase III trial of nab-paclitaxel/carboplatin in advanced NSCLC. The populations included in this pooled analysis consisted of elderly patients (≥ 70 years) and patients with renal impairment (eGFR < 60 ml/min/1.73 m2), diabetes, or poor performance status (ECOG PS 2).ResultsMedian progression-free survival (PFS) ranged from 4.1 months in patients with ECOG PS 2 (95% CI, 2.04–5.09 months) to 7.7 months in patients with diabetes (95% CI, 5.88–10.12 months). PFS for elderly patients and patients with renal impairment was 6.9 months each (95% CI, 6.01–7.98 months and 4.47–9.79 months, respectively). Median overall survival (OS) was 18.2 months (95% CI, 10.94–28.22 months), 17.4 months (95% CI, 14.59–20.14 months), and 16.1 months (95% CI, 14.09–18.50 months) in patients with renal impairment, patients with diabetes, and elderly patients, respectively. Patients with ECOG PS 2 exhibited the shortest median OS: 5.6 months (95% CI, 3.98–11.37 months). Overall response rates were 56.9%, 54.6%, 45.9%, and 29.4% in patients with diabetes, elderly patients, patients with renal impairment, and patients with ECOG PS 2, respectively. Most treatment-related adverse events were hematologic. The most common grade 3/4 hematologic adverse events in patients with renal impairment, elderly patients, patients with diabetes, and patients with poor performance status included neutropenia, anemia, and thrombocytopenia.ConclusionsAlthough survival data in patients with ECOG PS 2 were notably inferior to the other cohorts, our findings are consistent with those previously reported in the population-specific studies of the ABOUND trials and lend additional support for the use of nab-paclitaxel–based regimens in historically understudied and vulnerable populations.

There is inconsistency among published guidelines for the optimal diagnostic and management pathways for patients with typical (TC) or atypical (AC) pulmonary carcinoid tumours. We conducted a UK-wide clinician survey to assess current practice for the diagnosis, management, and follow-up of patients with TC/AC and descriptively compared management between European Neuroendocrine Tumor Society (ENETS) accredited centres of excellence (CoE) and nonaccredited centres (non-CoE). Twenty-seven clinicians (10 CoE; 17 non-CoE) participated. Computed tomography of thorax, abdomen, and pelvis was the most commonly reported diagnostic tool (96% of respondents), and bone scans and gallium somatostatin receptor scintigraphy positron emission tomography (SRS PET) were the least commonly reported (30% and 37% of respondents, respectively). Adjuvant therapy is considered for resected TC/AC by

Abstract Background Timeliness in the administration of recommended vaccines is often evaluated using vaccine delays and provides more information regarding the susceptibility of children to vaccine-preventable diseases compared with vaccine coverage at a given age. The importance of on-time administration of vaccines scheduled at the first visit is well documented, but data are scarce about the impact of vaccine delays at other visits on vaccination status by 24 months of age. Using vaccine delays for the first three doses of DTaP-containing vaccines and for the first dose of measles-containing vaccines as markers of timeliness at the 2, 4, 6 and 12 month visits, we estimated the proportion of incomplete vaccination status by 24 months of age attributable to a vaccine delay at each of these visits. Methods We used the data from six cross-sectional coverage surveys conducted in the Province of Quebec from 2006 to 2016 which included 7183 children randomly selected from the universal health insurance database. A vaccine dose was considered delayed if received 30 days or more after the recommended age. The impact of new vaccine delays at each visit on incomplete vaccination status by 24 months of age was estimated with the attributable risk in the population. Results The proportion of children with vaccine delay was 5.4% at 2 months, 13.3% at 4 months, 23.1% at 6 months and 23.6% at 12 months. Overall, 72.5% of all 2-year-old children with an incomplete status by 24 months were attributable with a vaccine delay, of which 16.1% were attributable with a first vaccine delay at 2 months, 10.6% at 4 months, 14.0% at 6 months and 31.8% at 12 months. Conclusions While great emphasis has been put on vaccine delays at the first vaccination visit, the prevalence of vaccine delays was greater with later visits and most children with an incomplete vaccination status by 24 months had a vaccine delay occurring during these later visits. Interventions to improve timeliness should address vaccine delays at each visit and not only focus on the first visit.

Background Studies have shown that the majority of endurance athletes do not achieve the minimal recommended carbohydrate (CHO) intake of 6 g/kg of body weight (BW), with potentially negative impacts on recovery and performance. The purpose of this study was to develop and validate a rapid and easy to use dietary screener to identify athletes who do and do not achieve a CHO intake > 6 g/kg BW in the context of endurance sports. Methods The dietary screener was developed using multiple logistic regression modeling of data from a sample of 1571 non-athlete adults (826 women and 745 men, mean age 44.75 ± 14.2 years) among whom dietary intake was assessed using a validated web-based food frequency questionnaire (web-FFQ). Three models were developed based on whole food intake using the 5, 10 and 15 most significant variables predicting CHO intake. The three models were then validated in a target population of non-elite endurance athletes having taken part in multisport events (n = 175, 64 women and 111 men, mean age 37.1 ± 11.3 years) and compared using sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) and c-statistics. Results The 15-variables model provided significantly better accuracy in predicting CHO intake adequacy in non-elite endurance athletes (c-statistic = 0.94) compared with the 10- and 5-variables model (c-statistic = 0.90 and 0.71 respectively). The 15-variables model predicts CHO intake adequacy in the target population of endurance athlete with a sensitivity of 89.5%, a specificity of 87.3% and PPV and NPV of 77.3 and 94.5%, respectively. Conclusion We have successfully developed a short and valid dietary screener that identifies endurance athletes at risk of not achieving a CHO intake > 6 g/kg BW. Use of this rapid screener may help alleviate the highly prevalent issue of suboptimal CHO consumption in the endurance sports realm.

BackgroundSingle gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing.Methods and findingsWe validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of "real world" data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds.ConclusionsThis study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers.