Preoperative Circulating 11-Oxygenated Androgens Are Associated With Metastasis-free Survival in Localized Prostate Cancer.

PURPOSE: Adrenal 11-oxygenated androgens may support cancer progression in men with prostate cancer owing to their abundance and androgenic potential. We hypothesized that preoperative circulating levels of 11-oxygenated androgens influence clinical outcomes in men with newly diagnosed localized prostate cancer. MATERIALS AND METHODS: We studied 1,793 treatment-naïve patients and 155 patients who received preoperative treatment with 5α-reductase inhibitors in the prospective PROCURE cohort, for which preoperative plasma samples were obtained prior to radical prostatectomy. Adrenal 11-oxygenated precursors, potent 11-oxygenated androgens and their metabolites (n=7), were quantified using liquid chromatography-tandem mass spectrometry. Circulating levels were evaluated in relation to prognostic factors, disease-free survival, and metastasis-free survival using multivariable Cox proportional hazards models. RESULTS: At a median follow-up of 93.8 months after surgery, 583 patients experienced biochemical recurrence, 104 developed metastatic disease, and 168 deceased. Higher levels of 11-hydroxytestosterone and 11-ketotestosterone were observed in men with PSA >20 ng/mL and positive nodal status (P < .05). In multivariable analyses, no significant association between 11-oxygenated androgens and disease-free survival was observed. Adrenal 11ß-hydroxyandrostenedione, the predominant androgenic 11-ketotestosterone, and its metabolite 11-ketoandrosterone, modeled as quartiles, were associated with metastasis-free survival (P = .06, P = .03, and P = .008, respectively). Significant accumulation of 11-oxygenated androgen precursors and bioactive androgens, but reduced metabolite levels, was observed in patients on 5α-reductase inhibitors (P < .001). CONCLUSIONS: Preoperative circulating 11-oxygenated androgen levels are associated with metastasis-free survival in men with localized prostate cancer undergoing radical prostatectomy and are affected by 5α-reductase inhibitor treatment.

Does Growth Velocity Affect Associations between Birth Weight and Neurodevelopment for Infants Born Very Preterm?

OBJECTIVE: To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm. STUDY DESIGN: This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29 weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22 months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles). RESULTS: Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7 ± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (ß = -1.1; 95% CI, -2.2 to -0.02; P = .05) and language scores (ß = -2.1; 95% CI, -3.3 to -0.8; P = .002). An increase by 1 g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, -0.03 to 2.1; P = .06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P = .001), after adjustment for birth weight z-score. For children with birth weight <25th percentile, a 1 g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P = .02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P = .004). CONCLUSIONS: Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02371460.

Docosahexaenoic acid-rich algae oil supplementation in mothers of preterm infants is associated with a modification in breast milk oxylipins profile.

Oxylipins are derived from enzymatic and non-enzymatic oxidation of n-3 and n-6 long-chain polyunsaturated fatty acids. They are known to be involved in inflammatory processes. The aim of this study was to describe the breast milk oxylipin profile following a docosahexaenoic acid (DHA) supplementation of mothers of preterm infants. We examined the oxylipins profile in breast milk collected at day 14 post-delivery, of 40 mothers who delivered before 29 weeks of gestation and who were supplemented with either DHA-rich algae oil (S-DHA) or a placebo (PL). These mothers were selected from the MOBYDIck cohort (NCT02371460 registered on 25/05/2015 in ClinicalTrials.gov) according to the supplementation received (S-DHA vs. PL) and the DHA content quartiles as measured in breast milk (Low vs. High) to generate four study groups. Milk oxylipins, as ng/mL of milk, were analyzed by LC-MS/MS. Ten oxylipins derived from DHA were higher in the S-DHA-High group than the other three groups (P < 0.001). The 18-HEPE, was also higher in the S-DHA-High group (0.11 ± 0.01) compared to the other groups (P = 0.0001). Compared to the PL-Low group, there was a reduction in pro-inflammatory prostaglandins found in the S-DHA-High group with lower levels of prostaglandins PGF2α (0.21 ± 0.45 in the S-DHA-High group vs. 1.87 ± 0.44 in the PL-Low group, P = 0.03) and of PGE2 (0.33 ± 0.26 in the S-DHA-High group vs. 1.28 ± 0.25 in the PL-Low group, P = 0.04).In sum, the DHA supplementation was linked with a predominance of anti-inflammatory oxylipins in breast milk of mothers who delivered very preterm, like 17(S)-HDHA and 18-HEPE, precursors of D and E resolvins respectively. This was also accompanied with a lower level of pro-inflammatory prostaglandins.

The benefit of scratch patch testing to demonstrate ocular contact allergy to brimonidine tartrate.

INTRODUCTION: Ocular allergies to brimonidine are frequent in patients treated for glaucoma. There is variability in reporting due to the lack of diagnostic criteria and the absence of cutaneous testing. Many false-negative patch tests (PT) have been described. Alternative methods, such as strip and scratch PT, have been used without a standardized method. OBJECTIVES: The primary objective is to identify the best method of cutaneous testing and brimonidine concentration for patch testing. The secondary objective is to identify clinical signs and symptoms suggestive of ocular allergy. PATIENTS AND METHODS: A retrospective review of patient files suspected of brimonidine ocular allergy was performed. Patch testing method, brimonidine concentration and clinical symptoms were reviewed. RESULTS: Of the 36 patients identified, half tested positive for brimonidine for at least one of the testing methods. The scratch PT demonstrated 17 positive reactions (94% detection rate). Three patients reacted with strip PT. No positive results were found with standard PT. The 5% brimonidine concentration demonstrated the highest sensitivity. The absence of eyelid pruritus was associated with negative testing. CONCLUSION: In the investigation of ocular allergy to brimonidine, scratch PT proved to be an essential tool. Brimonidine 5% pet. appeared as the most sensitive concentration for scratch PT.

Urinary oestrogen steroidome as an indicator of the risk of localised prostate cancer progression.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes. METHODS: Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery (n = 259) and validation (n = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives (n = 15), were measured using mass spectrometry (MS). RESULTS: The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-methoxyestrone were associated with an increased risk of development of metastasis/deaths. CONCLUSIONS: Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.

Androgen receptor and immune cell PD-L1 expression in bladder tumors predicts disease recurrence and survival.

PURPOSE: The impact of sex hormones on cancer immunotherapy remains controversial. Androgens, via the androgen receptor (AR), may impact the success of immune checkpoint blockade. This study characterizes AR and programmed death ligand-1 (PD-L1) expression in bladder tumors with long clinical follow-up. METHODS: AR and PD-L1 expression was analyzed using immunohistochemistry on 143 transurethral resection (TUR) and 203 radical cystectomy (RC) specimens. Descriptive statistics and survival analyses assessed the relationship of AR and PD-L1 staining with clinical outcomes of tumor recurrence, progression, and overall survival. RESULTS: AR expression was observed in a higher proportion of TUR than RC specimens (59% vs 35%, p < 0.001). High immune cell (IC) PD-L1 expression was associated with higher stage and grade. Patients with the combination of an absence of AR expression and the highest (> 10%) IC PD-L1 expression in TUR tumors had an increased risk of recurrence and progression. In RC specimens, the expression of AR increased the risk of local recurrence (adjusted hazard ratio (HR) 2.09, 95% CI 0.98-4.45), which was even higher among patients who also had IC PD-L1 expression (HR 4.16, 95% CI 1.28-13.52). For 28 paired metastatic lymph nodes among RC patients, tumor cell PD-L1 expression was significantly correlated (r = 0.48, p = 0.01), while no relationship with IC PD-L1 expression was observed. CONCLUSIONS: The expression of AR and its relationship to clinical outcomes appears to vary between non-muscle invasive and muscle-invasive bladder cancer. Our results support the role of IC PD-L1 expression as an independent risk factor for bladder cancer outcomes.

Health literacy level in a various nephrology population from Québec: predialysis clinic, in-centre hemodialysis and home dialysis; a transversal monocentric observational study.

BACKGROUND: Health literacy refers to the ability of individuals to gain access to, use, and understand health information and services in order to maintain a good health. It is especially important in nephrology due to the complexity of chronic kidney disease (CKD). The present study sought to define health literacy levels in patients followed in predialysis clinic, in-center dialysis (ICHD), peritoneal dialysis (PD) and home hemodialysis (HHD). METHODS: This transversal monocentric observational study analysed 363 patients between October 2016 and April 2017. The Brief Health Literacy Screen (BHLS) and the Health Literacy Questionnaire (HLQ) were used to measure health literacy. Multivariate linear regressions were used to compare the mean scores on the BHLS and HLQ, across the four groups. RESULTS: Patients on PD had a significantly higher BHLS'score than patients on ICHD (p = 0.04). HLQ's scores differed across the groups: patients on HHD (p = 0.01) and PD (p = 0.002) were more likely to feel understood by their healthcare providers. Compared to ICHD, patients on HHD were more likely to have sufficient information to manage their health (p = 0.02), and patients in the predialysis clinic were more likely to report high abilities for health information appraisal (p < 0.001). CONCLUSION: In a monocentric study, there is a significant proportion of CKD patients, especially in predialysis clinic and in-centre hemodialysis, with limited health literacy. Patients on home dialysis (HHD and PD) had a higher level of health literacy compared to the other groups.

Furlow Palatoplasty: Should We Also Focus on the Size of the Nasopharynx?

OBJECTIVES: (1) To determine the incidence rate of velopharyngeal dysfunction (VPD) according to 7 speech criteria post-Furlow palatoplasty. (2) To find an anatomical measurement of the cleft palate (or combination of measurements) associated with the occurrence of VPD. STUDY DESIGN: Retrospective cohort study. PARTICIPANTS AND METHODS: Fifty-six patients with cleft palate ± cleft lip underwent palatoplasty with the Furlow technique at the age of 10 months. Pre-and post-palatoplasty cleft palate measurements were collected during the procedure. Three blinded speech-language pathologists (SLPs) retrospectively scored the patients from the chart data at age 4. Student t test and receiver operating characteristic curve analysis were used to evaluate the association and predictive capacity between cleft measurements and parameters (M&P) with all VPD criteria. RESULTS: The SLPs found an incidence of VPD according to 7 criteria: hypernasality (11%), audible nasal emission (4%), nasal rustle (14%), compensatory errors (4%), impairment of speech understandability (7%), and impairment of speech acceptability (16%). The SLPs recommended a secondary surgical procedure in 5 patients (9%). A statistically significant association was found between, respectively, 17 and 5 M&P and the occurrence of compensatory errors and audible nasal emission. Our data suggest that the length of the cleft, the cleft area, and the postoperative transversal size of the nasopharynx are the best indicators of the future positivity of VPD criteria. CONCLUSION: The size of the postoperative transverse nasopharyngeal area during the primary cleft palate procedure may become the focus of the next generation of cleft surgeons to reduce the incidence of VPD.

Alternative promoters control UGT2B17-dependent androgen catabolism in prostate cancer and its influence on progression.

BACKGROUND: Perturbation of the major UGT2B17-dependent androgen catabolism pathway has the potential to affect prostate cancer (PCa) progression. The objective was to evaluate UGT2B17 protein expression in primary tumours in relation to hormone levels, disease characteristics and cancer evolution. METHODS: We conducted an analysis of a high-density prostate tumour tissue microarray consisting of 239 localised PCa cases treated by radical prostatectomy (RP). Cox proportional hazard ratio analysis was used to evaluate biochemical recurrence (BCR), and a linear regression model evaluated variations in circulating hormone levels measured by mass spectrometry. The transcriptome of UGT2B17 in PCa was established by using RNA-sequencing data. RESULTS: UGT2B17 expression in primary tumours was associated with node-positive disease at RP and linked to circulating levels of 3α-diol-17 glucuronide, a major circulating DHT metabolite produced by the UGT2B17 pathway. UGT2B17 was an independent prognostic factor linked to BCR after RP, and its overexpression was associated with development of metastasis. Finally, we demonstrated that distinctive alternative promoters dictate UGT2B17-dependent androgen catabolism in localised and metastatic PCa. CONCLUSIONS: The androgen-inactivating gene UGT2B17 is controlled by overlooked regulatory regions in PCa. UGT2B17 expression in primary tumours influences the steroidome, and is associated with relevant clinical outcomes, such as BCR and metastasis.

The Management of Young Children With a Likely Infectious Condition Presenting Moderate to Severe Neutropenia.

OBJECTIVE: The objective of this study was to describe the outcome of healthy children presenting with newly-diagnosed neutropenia in an infectious context. RESULTS: A total of 184 episodes of neutropenia were included in children 3 months to 5 years of age. There were 118 (64%) episodes of moderate neutropenia and 66 (36%) of severe neutropenia (SN). SN episodes were more likely related to intensification of antibiotic regimen used and further investigations. The median duration of neutropenia was 8.5 days. Chronic benign neutropenia occurred in 7 (4%) patients. CONCLUSION: SN led to intensification of antibiotic therapy, but no children encountered an unfavorable outcome and the neutropenia episodes were short-lived.

Effects of quadratus lumborum block regional anesthesia on postoperative pain after colorectal resection: a randomized controlled trial.

INTRODUCTION: Postoperative pain following colorectal surgery is associated with a significant use of opioids. Recently, regional anesthesia, such as the posterior quadratus lumborum block (QL2), has been proposed to improve pain relief and reduce opioid use. However, the benefit of the QL2 on postoperative pain control remains controversial. METHODS: We conducted a randomized controlled trial of patients undergoing colorectal surgery at the CHU de Québec-Université Laval. Patients were randomized to regional QL2 anesthesia with 150 mg of ropivacaine combined with standard analgesia or to QL2 with a sham intervention and standard analgesia. Our primary outcome was postoperative opioid administration at 24 h. Secondary outcomes included opioid administration in the post-anesthesia care unit (PACU), at 48 h and at hospital discharge, postoperative pain scores, delay in resumption of intestinal transit, nausea and vomiting, and hospital length of stay. RESULTS: A total of 62 patients were enrolled from November 2017 to February 2018. QL2 regional anesthesia compared with a sham intervention was not associated with a reduction in postoperative morphine dose equivalent (100.2 mg, 95% CI 68.9-131.5 versus 88.7 mg, 95% CI 59.3-118.0, p = 0.81, respectively). Compared to QL2 regional anesthesia, postoperative pain scores in the control group were lower although statistical significance was not consistent for all postoperative time points. Other secondary outcomes were comparable between both groups. CONCLUSION: We did not observe a reduction in postoperative opioid administration at 24 h with a posterior quadratus lumborum block regional anesthesia in patients undergoing elective colorectal surgery.

Factors Affecting Interindividual Variability of Hepatic UGT2B17 Protein Expression Examined Using a Novel Specific Monoclonal Antibody.

Accurate quantification of the metabolic enzyme uridine diphospho-glucuronosyltransferase (UGT) UGT2B17 has been hampered by the high sequence identity with other UGT2B enzymes (as high as 94%) and by the lack of a specific antibody. Knowing the significance of the UGT2B17 pathway in drug and hormone metabolism and cancer, we developed a specific monoclonal antibody (EL-2B17mAb), initially validated by the lack of detection in liver microsomes of an individual carrying no UGT2B17 gene copy and in supersomes expressing UGT2B enzymes. Immunohistochemical detection in livers revealed strong labeling of bile ducts and variable labeling of hepatocytes. Expression levels assessed by immunoblotting were highly correlated to mass spectrometry-based quantification (r = 0.93), and three major expression patterns (absent, low, or high) were evidenced. Livers with very low expression were carriers of the functional rs59678213 G variant, located in the binding site for the transcription factor forkhead box A1 (FOXA1) of the UGT2B17 promoter. The highest level of expression was observed for individuals carrying at least one rs59678213 A allele. Multiple regression analysis indicated that the number of gene copies explained only 8% of UGT2B17 protein expression, 49% when adding rs59678213, reaching 54% when including sex. The novel EL-2B17mAb antibody allowed specific UGT2B17 quantification and exposed different patterns of hepatic expression. It further suggests that FOXA1 is a key driver of UGT2B17 expression in the liver. The availability of this molecular tool will help characterize the UGT2B17 level in various disease states and establish more precisely the contribution of the UGT2B17 enzyme to drug and hormone metabolism.

Inhaled Epoprostenol for Pulmonary Hypertension Treatment in Neonates: A 12-Year Experience.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) occurs in 10% of neonatal respiratory insufficiency. To selectively reduce pulmonary vascular resistance, several treatments have been tried. Inhaled epoprostenol (iPGI2) has been used for 12 years in our institution for the management of refractory PPHN despite the gaps in the literature to support this use. OBJECTIVES: The primary objective was to evaluate the efficacy of iPGI2 for PPHN. The secondary objectives were to describe its use in neonates and assess side effects. STUDY DESIGN: This retrospective cohort study included infants < 28 days with PPHN treated with iPGI2 in the neonatal or pediatric intensive care units of our institution between 2004 and 2016. RESULTS: We reviewed 43 patient' care episodes (mean gestational age of 36 weeks). This was an extremely ill population with 54% mortality rate. Oxygenation index improved significantly after 12-hour treatment (p = 0.047), with a rebound effect when discontinuing nebulization. By the end of the therapy, the fraction of inspired oxygen had significantly dropped (p = 0.0018). Echocardiographic markers tended to normalize during treatment. No potential side effects were reported. CONCLUSION: In these sick newborns, we observed an improvement in PPHN under iPGI2 without significant adverse effects. To our knowledge, this is the largest neonatal cohort reported to have received iPGI2 for PPHN.

Sex-dependent association of circulating sex steroids and pituitary hormones with treatment-free survival in chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is not considered a hormone-regulated cancer although sex is a recognized risk factor with men more frequently diagnosed and developing progressive disease. We hypothesized that variable hormonal exposure may have a sexually dimorphic influence on treatment-free survival (TFS). In 156 CLL cases, we quantitatively profiled 29 circulating steroids (progesterone, adrenal precursors, androgens, estrogens, and catechol estrogens) as well as luteinizing hormone (LH) and follicle-stimulating hormone. Median TFS was shorter for men than that for women (80.7 vs. 135.0 months, P = 0.033). Circulating hormone profiles in CLL patients were significantly different from those of healthy donors. In male CLL cases, higher LH levels were associated with shorter TFS (adjusted hazard ratio (HRadj) 2.11; P = 0.004). In female CLL cases, high levels of the potent androgens testosterone and dihydrotestosterone and the sum of methoxy estrogens were associated with an improved TFS with HRadj values of 0.24 (P = 0.007), 0.54 (P = 0.023), and 0.31 (P = 0.034), respectively. Reduced TFS was observed for women with CLL exhibiting high expression of the steroid-inactivating UGT2B17 enzyme. This study is the first to establish a link between the outcome of CLL patients, sex steroids, and pituitary hormones, revealing a sex-specific hormonal imbalance associated with disease progression.

Family medicine residents' training in, knowledge about, and perceptions of digital rectal examination.

OBJECTIVE: To evaluate family medicine residents' training in, knowledge about, and perceptions of digital rectal examination (DRE). DESIGN: Descriptive study, using an online survey that was available in French and English. SETTING: Quebec. PARTICIPANTS: A total of 217 residents enrolled in a family medicine program. MAIN OUTCOME MEASURES: Residents' demographic characteristics; the DRE teaching they received throughout their medical training; their reasons for omitting DRE; their recognition of DRE indications (strong vs weak) and application of DRE for 10 anorectal complaints; and their perceptions of the overall quality of the DRE training they received. RESULTS: Of the 879 residents contacted, 217 (25%) responded to the survey. Throughout their training, one-third of respondents did not receive any supervision for or feedback on DRE technique. Seventy-one percent of respondents expressed their inability to identify the nature of abnormal examination findings at least once during their training. The most frequently reported reasons to omit DRE were patient refusal, inadequate setting, and lack of time. CONCLUSION: Most of the residents in this study had omitted DRE at least once in their clinical work despite recognizing its importance. There was discordance between recognition of a complaint requiring DRE and execution of this technique in a clinical setting. Family medicine education programs and continuing medical education committees should consider including DRE training.

Adaptation and Evaluation of Online Self-learning Modules to Teach Critical Appraisal and Evidence-Based Practice in Nursing: An International Collaboration.

Healthcare professionals need to update their knowledge and acquire skills to continually inform their practice based on scientific evidence. This study was designed to evaluate online self-learning modules on critical appraisal skills to promote the use of research in clinical practice among nurses from Quebec (Canada) and the Basque Country (Spain). The teaching material was developed in Quebec and adapted to the Basque Country as part of an international collaboration project. A prospective pre-post study was conducted with 36 nurses from Quebec and 47 from the Basque Country. Assessment comprised the administration of questionnaires before and after the course in order to explore the main intervention outcomes: knowledge acquisition and self-learning readiness. Satisfaction was also measured at the end of the course. Two of the three research hypotheses were confirmed: (1) participants significantly improved their overall knowledge score after the educational intervention; and (2) they were, in general, satisfied with the course, giving it a rating of seven out of 10. Participants also reported a greater readiness for self-directed learning after the course, but this result was not significant in Quebec. The study provides unique knowledge on the cultural adaptation of online self-learning modules for teaching nurses about critical appraisal skills and evidence-based practice.

Electronic health record acceptance by physicians: testing an integrated theoretical model.

OBJECTIVE: Several countries are in the process of implementing an Electronic Health Record (EHR), but limited physicians' acceptance of this technology presents a serious threat to its successful implementation. The aim of this study was to identify the main determinants of physician acceptance of EHR in a sample of general practitioners and specialists of the Province of Quebec (Canada). METHODS: We sent an electronic questionnaire to physician members of the Quebec Medical Association. We tested four theoretical models (Technology acceptance model (TAM), Extended TAM, Psychosocial Model, and Integrated Model) using path analysis and multiple linear regression analysis in order to identify the main determinants of physicians' intention to use the EHR. We evaluated the modifying effect of sociodemographic characteristics using multi-group analysis of structural weights invariance. RESULTS: A total of 157 questionnaires were returned. The four models performed well and explained between 44% and 55% of the variance in physicians' intention to use the EHR. The Integrated model performed the best and showed that perceived ease of use, professional norm, social norm, and demonstrability of the results are the strongest predictors of physicians' intention to use the EHR. Age, gender, previous experience and specialty modified the association between those determinants and intention. CONCLUSIONS: The proposed integrated theoretical model is useful in identifying which factors could motivate physicians from different backgrounds to use the EHR. Physicians who perceive the EHR to be easy to use, coherent with their professional norms, supported by their peers and patients, and able to demonstrate tangible results are more likely to accept this technology. Age, gender, specialty and experience should also be taken into account when developing EHR implementation strategies targeting physicians.

Epidemiology of Pediatric Tumors in Quebec: A 17-Year Report of Cancer in Young People in the Canada Registry.

BACKGROUND: Cancer is the leading cause of disease-related death among children of more than 1 year of age. However, childhood cancer risk factors and etiology are yet to be fully understood. The goal of this study is to identify geographic variation among children and adolescents diagnosed with pediatric tumors between 2001 and 2018 in the province of Quebec. METHODS: We analyzed pediatric patients less than 15 years of age from the Cancer in Young People in Canada (CYP-C) surveillance system who were diagnosed between 2001 and 2018 with cancer in the province of Quebec. The age-standardized age-adjusted incidence rates (AAIR) per 100,000 person years were calculated for all childhood cancers by cancer subgroups, Quebec Health regions, and age groups. RESULTS: Overall, 3904 pediatric patients less than 15 years old were diagnosed with cancer in the province of Quebec in 2001-2018. The overall incidence rate (IR) in the province of Quebec was 16.14 (95%CL [15.56-16.73]) per 100,000 person years. For childhood cancers, regions that presented a higher AAIR were Chaudière-Appalaches and Capitale-Nationale with 18.2 and 17.5 per 100,000 person years, respectively. The incidence rates (IRs) in Chaudière-Appalaches (95% CI 1.0439-1.3532) and in Capitale-Nationale (95% CI 1.0124-1.2942) were statistically higher than the incidence in the province of Quebec (p = 0.0090 and p = 0.0310, respectively). When comparing the AAIR of the CNS tumor subgroup in Chaudière-Appalaches and in Capitale-Nationale, with the provincial average, we noticed a statistically higher incidence in Chaudière-Appalaches and a trend for Capitale-Nationale (p < 0.0001 and p = 0.0602, respectively). CONCLUSION: There is evidence of spatial clusters in Chaudière-Appalaches and Capitale-Nationale as areas for all childhood cancers. Further studies should be performed to investigate potential risk factors in these regions.

Cancer anorexia-cachexia syndrome is characterized by more than one inflammatory pathway.

BACKGROUND: The interdependence of cytokines and appetite-modifying hormones implicated in cancer anorexia-cachexia syndrome (CACS) remains unclear. This study aimed to regroup these cytokines and hormones into distinct inflammatory (or non-inflammatory) pathways and determine whether these pathways can classify patients with CACS phenotypes. METHODS: Clinical characteristics of 133 patients [61.7% male; mean age = 63.4 (SD: 13.1) years] with advanced cancer prior to oncology treatments were documented, including weight loss history. Patients completed the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) questionnaire and Timed Up and Go test and had their sex-standardized skeletal muscle index (z-SMI) and fat mass index (z-FMI) derived using computed tomography scans. Their plasma levels of cytokines and appetite-modifying hormones were also determined. Date of death was recorded. Exploratory factor analysis (EFA) was used to regroup 15 cytokines and hormone into distinct inflammatory pathways (factors). For each patient, regression factor scores (RFS), which tell how strongly the patient associates with each factor, were derived. Two-step cluster analysis on the RFS was used to classify patients into groups. CACS phenotypes were correlated with RFS and compared between groups. Groups' survival was estimated using Kaplan-Meier analysis. RESULTS: Patients had low z-SMI (mean = -3.78 cm2/m2; SD: 8.88) and z-FMI (mean = 0.08 kg2/m2; SD: 56.25), and 62 (46.6%) had cachexia. EFA identified three factors: (F-1) IFN-γ, IL-1ß, Il-4, IL-6, IL-10, IL-12, TGFß1 (positive contribution), and IL-18 (negative); (F-2) IL-8, IL-18, MCP-1, TGFß1, TNF-α (positive), and ghrelin (negative); and (F-3) TRAIL and leptin (positive), and TGFß1 and adiponectin (negative). RFS-1 was associated with cachexia (P = 0.002); RFS-2, with higher CRP (P < 0.0001) and decreased physical function (P = 0.01); and RFS-3 with better appetite (P = 0.04), lower CRP (P = 0.002), higher z-SMI (P = 0.04) and z-FMI (P < 0.0001), and less cachexia characteristics (all P < 0.001). Four patient groups were identified with specific RFS clusters aligning with the CACS continuum from no cachexia to pre-cachexia, cachexia, and terminal cachexia. Compared to the other two groups, groups 1 and 2 had higher plasma levels of IL-18 and TRAIL. Group 1 also had lower inflammatory cytokines, adiponectin, and CRP compared to the other three groups. Group 3 had inflammatory cytokine levels similar to group 2, except for TNF-α and leptin which were lower. Group 4 had very high inflammatory cytokines, adiponectin, and CRP compared to the other 3 groups (all P < 0.0001). Groups 3 and 4 had worse cachexia characteristics (P < 0.05) and shorter survival (log rank: P = 0.0009) than the other two groups. CONCLUSIONS: This exploratory study identified three distinct pathways of inflammation, or lack thereof, characterizing different CACS phenotypes.