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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.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.A retrospective review of patient files suspected of brimonidine ocular allergy was performed. Patch testing method, brimonidine concentration and clinical symptoms were reviewed.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.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.

Preterm infants are deficient in long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), a fatty acid (FA) associated with an increase in bronchopulmonary dysplasia (BPD). In two previous randomized control trials, DHA supplementation did not reduce the risk of BPD. We examined the breast milk FA profile, collected 14 days after birth, of mothers who delivered before 29 weeks of gestation and who were supplemented with DHA-rich algae oil or a placebo within 72 h after birth as part of the MOBYDIck trial. Milk FA were analyzed by gas chromatography. The total amount of FA (mg/mL) was similar in both groups but the supplementation increased DHA (expressed as % of total FA, mean ± SD, treatment vs placebo, 0.95 ± 0.44% vs 0.34 ± 0.20%; P

BackgroundHealth 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).MethodsThis 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.ResultsPatients 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 ConclusionIn 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.

The androgen inactivating UGT2B28 pathway emerges as a predictor of progression in prostate cancer (PCa). However, the clinical significance of UGT2B28 tumoral expression and its contribution to PCa progression remain unclear. Using the Canadian Prostate Cancer Biomarker Network biobank (CPCBN; n = 1512), we analyzed UGT2B28 tumor expression in relation to clinical outcomes in men with localized PCa. UGT2B28 was overexpressed in tumors compared to paired normal adjacent prostatic tissue and was associated with inferior outcomes. Functional analyses indicated that UGT2B28 promoted cell proliferation, and its expression was regulated by the androgen receptor (AR)/ARv7. Mechanistically, UGT2B28 was shown to be a protein partner of the endocytic adaptor protein huntingtin-interacting protein 1 (HIP1), increasing its stability and priming AR/epidermal growth factor receptor (EGFR) pathways, leading to ERK1/2 activation triggering cell proliferation and epithelial-to-mesenchymal transition (EMT). HIP1 knockdown in UGT2B28 positive cells, and dual pharmacological targeting of AR and EGFR pathways, abolished cell proliferative advantages conferred by UGT2B28. In conclusion, UGT2B28 is a prognosticator of progression in localized PCa, regulates both AR and EGFR oncogenic signaling pathways via HIP1, and therefore can be therapeutically targeted by using combination of existing AR/EGFR inhibitors.

We aim to assess whether the docosahexaenoic acid (DHA)-containing lipid emulsion (LE) SMOFlipid 20% (Fresenius Kabi Canada Ltd) is associated with bronchopulmonary dysplasia (BPD)-free survival at 36 weeks' postmenstrual age in very preterm infants.This cohort study is nested in the MOBYDIck randomized clinical trial (NCT02371460), which investigated the effect of maternal DHA supplementation on BPD-free survival in breastfed very preterm infants born between 23 0/7 and 28 6/7 weeks' gestation in 16 Canadian neonatal intensive care units (2015-2018). Parenteral SMOF-LE was given to the infants according to the sites' routine care protocols. Relative risks (RRs) were estimated using a modified Poisson regression model with generalized estimating equations taking into account recruitment site, multiple birth, DHA supplementation, birth weight, sex, and gestational age.Among 528 infants (mean gestational age, 26.5 weeks [SD, 1.6]), 272 received SMOF-LE. Overall, 56.7% of the infants in the SMOF-LE group and 59.7% infants in the non-SMOF-LE group survived without BPD (adjusted RR, 0.94 [95% CI, 0.77-1.14]; P = 0.51). BPD rates were 39.3% in the SMOF-LE group vs 34.1% in the non-SMOF-LE group (adjusted RR, 1.10 [95% CI, 0.82-1.47]; P = 0.53). Severe BPD rates were 31.8% in the SMOF-LE group vs 28.8% in the non-SMOF-LE group (adjusted P = 0.59). Mortality was not significantly different between the SMOF-LE (6.7%) and non-SMOF-LE groups (9.5%; adjusted P = 0.40).In very preterm infants, intravenous DHA-containing SMOF-LE during the neonatal period was not associated with BPD-free survival.

Remoteness is associated with worse survival in adults with cancer. We aimed to determine whether remoteness is associated with cancer outcomes in pediatric acute lymphoblastic leukemia (ALL). Canadian children with ALL entered in the CYP-C registry were included. The predictive impact of remoteness on overall survival (OS), relapse, and treatment-related complications (infections, thrombosis, bleeding, and osteonecrosis) was estimated using multivariate regression models. We included 1383 children, of whom 277 (20.0%) lived remotely (200 km from the pediatric oncology center). The median latency to see a pediatric oncologist was longer in children living remotely. The 5-year OS (95% CI) was similar for both groups (remote: 95.2% [93.7-96.3%] vs close: 94.1% [90.5-95.2%]). No difference was found in the relapse rate between both groups and in treatment-related complications. Remoteness did not affect survival in pediatric ALL. Further research is needed to determine which models of healthcare organization optimize cancer outcomes and patients' satisfaction.

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.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.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.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.

To evaluate whether differences exist between men and women in response to intravesical BCG treatments. The incidence of urothelial carcinoma of the bladder is lower in women but they tend to present with more aggressive and advanced disease. Some prior studies also suggest there are sex-based differences in response to treatment for non-muscle invasive bladder tumors.In this retrospective study, we reviewed all consecutive patients who received BCG at the CHU de Québec - Laval University from 2009-2019. Men and women were treated with intravesical BCG therapy following pathologic confirmation of urothelial carcinoma. Outcomes evaluated include recurrence, progression, and treatment tolerability. Recurrence was defined as a pathology confirmed cancer whereas progression was the new development of high-grade (recurrence) pathology or an increase of stage. Tolerability was defined according to the proportion of prescribed BCG received. All clinical details were obtained through review of the medical records, collaborated by pharmacy records for BCG administration. Competing-risk analysis was used to compare outcomes.Among 613 patients who received BCG at our institution between 2009-2019, 472 (77.0%) were men and 141 (23.0%) were women. The recurrence rate was not different between sexes, with a 5-year recurrence risk of 52% (95% CI: 36.93-65.4) among women compared to 57.5% (CI 95%: 51.9-62.6) among men. The overall non-progression rate at 1,3 and 5 years was 97.3% (95% CI: 95.6%-98.3%), 93.6% (95% CI: 91.2%-95.4%), and 91.7% (95% CI: 88.4%-94.1%), respectively. The completion of ≥5 induction BCG instillations and maintenance BCG use was similar in both genders.We report a contemporary NMIBC cohort treated with BCG and find no clear evidence for sex-based differences in response to BCG treatment in regard of progression, recurrence, and tolerability.

Introduction: The aim of the study was to determine the effect of a maternal docosahexaenoic acid (DHA) supplementation during lactation, compared with a placebo, on the neonatal growth profile of breastfed very preterm infants. Methods: Preterm infants’ growth profile, growth velocity from birth to 36 weeks’ postmenstrual age (PMA), and growth at 36 weeks’ PMA were pre-specified secondary outcomes of a randomized placebo-controlled trial conducted in 16 Canadian neonatal intensive care units (2015–2018). Lactating mothers who delivered before 29 weeks’ gestation were given 1.2 g of DHA daily or a placebo within 72 h of delivery and up to 36 weeks’ PMA. Analyses were performed using a linear regression model with generalized estimating equations. Results: 461 mothers and their 528 infants (DHA, N = 273; placebo, N = 255) were included with mean gestational age of 26.5 weeks (standard deviation [SD] = 1.6); 275 (52.1%) were males; mean birth weight was 895 g (SD = 240). DHA interaction with sex was significant on weight profile (interaction p < 0.001), weight velocity (interaction p = 0.05), and weight at 36 weeks’ PMA (interaction p = 0.02). Females in the DHA group gained more weight compared to the placebo group (mean difference [MD], 52.6 g [95% confidence interval [CI]: 24.5–80.8], p < 0.001). Weight velocity was significantly higher in females of the DHA group (MD, 3.4 g/kg/day [95% CI: 0.6–6.2], p = 0.02). At 36 weeks’ PMA, the weight of males in the DHA group was significantly smaller (MD, −88.9 g [95% CI: −166.2 to −11.6], p = 0.02). Conclusion: DHA positively affected female infants’ neonatal weight profile and velocity and negatively affected male infants’ weight at 36 weeks’ PMA.

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.

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.

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.

Objectives Chronic metabolic disturbances related to cancer treatment are well reported among survivors of pediatric acute lymphoblastic leukemia (ALL). However, few studies have investigated the incidence of these complications during the phase of chemotherapy. We evaluated the incidence of acute metabolic complications occurring during therapy in our cohort of patients diagnosed with ALL. Methods A prospective study involving 50 ALL pediatric patients diagnosed and treated between 2012 and 2016 in our oncology unit. We collected weight, blood pressure, fasting plasma glucose and hemoglobin A1C (HBA1c) levels during the two years of therapy. Results Obesity and overweight occurred in 43 and 25%, respectively among patients and have been reached at 12 months of chemotherapy. About 26% of the patients developed high blood pressure and 14% experienced hyperglycemias without meeting diabetes criteria. There was a significant decrease of HBA1c levels between the beginning and the end of therapy (p Conclusions Increase of body mass index in our ALL pediatric patients occurred during the first months of therapy and plateaued after a year of treatment. We should target this population for early obesity prevention. HbA1c levels measured during therapy did not reveal diabetes criteria. Hence, fasting blood glucose levels are sufficient to monitor ALL pediatric patients’ glycemia.

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 aged 3 months to 5 years. 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.

This study evaluated early and medium-term changes in bone turnover markers, and their associations with weight loss, total bone mineral density (BMD), and hormonal changes after biliopancreatic diversion (BPD). Ancillary study from a one-year prospective cohort of 16 individuals assessed before, 3 days, 3 and 12 months after BPD. Bone turnover markers (C-terminal telopeptide (CTX), intact osteocalcin (OC), sclerostin, and osteoprotegerin (OPG)) and several hormones were measured at each visit. Total BMD by DXA was assessed at baseline, 3 and 12 months after BPD. Three participants were lost to follow-up. CTX increased significantly at 3 days (+ 66%), 3 months (+ 219%), and 12 months (+ 295%). OC decreased at 3 days (− 19%) then increased at 3 months (+ 69%) and 12 months (+ 164%). Change in sclerostin was only significant between 3 days and 3 months (+ 13%), while change in OPG was significant between baseline and 3 days (+ 48%) and baseline and 12 months (+ 45%). CTX increase correlated negatively with weight loss at 3 (r = − 0.63, p = 0.009) and 12 months (r = − 0.58, p = 0.039), and total BMD decrease (r = − 0.67, p = 0.033) at 12 months. Change in insulin and adiponectin correlated with changes in bone turnover markers independently of weight loss. BPD causes an earlier and greater increase in bone resorption over bone formation markers and a decrease in total BMD. Sclerostin did not increase as expected following extensive weight loss. Changes in insulin and adiponectin seem to play a role in the activation of bone remodeling after BPD.

Bisphosphonate use has been associated with atypical femoral fractures (AFFs), defined by the American Society of Bone and Mineral Research (ASBMR) Task Force criteria, which currently exclude periprosthetic fractures. The objectives of this study were to establish the prevalence of atypical periprosthetic femoral fractures (APFFs) in patients with hip and knee arthroplasties and to determine the clinical and radiological risk factors associated with these fractures. We performed a retrospective radiological review of all femoral fractures between January 1, 2006, and March 31, 2015, in Quebec City, Canada. Patients who sustained a periprosthetic femoral fracture (PFF) were identified and included in this study. We used the ASBMR Task Force criteria to identify atypical fractures and establish their prevalence. Data from medical records and radiological assessments of the femoral anatomy, the characteristics of the fracture, and the positioning of the prosthesis were collected. The prevalence of APFFs among PFFs was 8.3% (11/133). A strong association with bisphosphonates (p = 0.007) was observed, as well as an increased risk of APFFs among alendronate users compared to risedronate users (p = 0.04). A transverse fracture (p < 0.0001), a periosteal thickening of the lateral cortex at the fracture (p < 0.0001), a unicortical fracture (p = 0.02), and prodromal symptoms (p = 0.03) were associated with APFFs. The type of implant, its positioning, and the femoral geometry did not appear to be risk factors for APFFs compared to PFFs. © 2018 American Society for Bone and Mineral Research.

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. Electronic supplementary material The online version of this article (10.1007/s00277-018-3356-z) contains supplementary material, which is available to authorized users.

Background Patient-Reported Outcomes tools are becoming the gold standard in the evaluation of results in orthopaedic surgery. In 2012, the International Hip Outcome Tool-12 (iHOT-12) was developed. This self-administered questionnaire was designed to address the day-to-day clinical setting with faster completion and easier patient flow. In 2021, a French translation of the iHOT-33 questionnaire, from which the iHOT-12 is derived, proved to be valid. Since there is not data in French regarding iHOT-12, we performed a prospective study aiming to answer: (1) is this French version of the iHOT-12 questionnaire as valid, (2) can the minimal clinically important difference (MCID) value for patients undergoing hip arthroscopy for femoro-acetabular impingement (FAI) be defined? Hypothesis It is hypothesized that the iHOT-12-Fr would be valid and responsive to change in a cohort treated for FAI. Patients and methods Using the COSMIN recommendations, a multicentric prospective cohort study was conducted to evaluate the reliability, validity, responsiveness and MCID of the iHOT-12-Fr. Results In total, 101 patients were recruited for participation in the project. The reliability of the iHOT-12-Fr questionnaire was assessed with the intraclass correlation coefficient (ICC = 0.84) and the internal consistency with a Cronbach's alpha (α = 0.86). The standard error of measurement (SEM = 6.7) and the smallest detectable change (SDC = 1.8) were calculated. Construct validity was evaluated with Pearson's correlation coefficients (r) by comparing the iHOT-12-Fr with the iHOT-33-Fr (r = 0.96), the Hip disability and Osteoarthritis Outcome Score-Fr (r = 0.68) and Nonarthritic Hip Score-Fr (r = 0.82). Responsiveness was shown with a standardized effect size of 1.18, standardized response mean of 0.73, responsiveness ratio of 1.4 and an MCID of 11 points. Discussion Metrological qualities of the iHOT-12-Fr are comparable to the original version and other versions translated into different languages. This study proves that the French translation of the iHOT-12 is valid, reliable and compares to the original iHOT-12. Level of evidence IV prospective study.

Aim: Germline variants could modify survival of metastatic colorectal cancer patients (mCRC). Patients & methods: The association of 285 haplotype-tagging SNPs in 11 candidate genes and overall survival (OS) was tested in two cohorts totalizing 417 FOLFIRI-treated mCRC. Gene expression was investigated in vitro and in public datasets. Results: In the combined cohort, CES1 rs9921399T>C was associated with prolonged OS (hazard ratio [HR] = 0.40) whereas ABCC1 rs17501011G>A (HR = 2.08) and UGT1 rs1113193G>A (HR = 2.12) were associated with shorter OS (p ≤ 0.005). A combined effect of these polymorphisms was observed with HR of 1.98–2.97 (p < 0.05). The ABCC1 rs17501011A variant reduced reporter-gene activity (p < 0.05) whereas ABCC1 tumor expression was associated with shorter survival (p ≤ 0.013). Conclusion: We identified a combination of genetic determinants that could predict mCRC survival.

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.

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. We conducted a randomized controlled trial of patients undergoing colorectal surgery at the CHU de Quebec-Universite 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. 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. 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.

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 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.

Introduction To evaluate the effectiveness of new treatments, whether conservative or surgical, a self-administered questionnaire for hip pain targeted at physically active patients 18 to 60 years of age, named the international Hip Outcome Tool-33 (iHOT-33), was developed and validated in 2012. Since there is no French version available and we are acutely aware of transcultural variations, we conducted a prospective study to: 1) translate, and then 2) validate this questionnaire into international French. Hypothesis The iHOT-33-Fr questionnaire is a valid and reliable tool for evaluating hip pain in a young, francophone population. Materials and methods Translation of the questionnaire was done according to the standardized method described by Beaton and the final version of the iHOT-33-Fr was validated using the COSMIN methodology. The data were collected prospectively at multiple sites. The reliability of the iHOT-33-Fr questionnaire was evaluated using the intraclass correlation coefficient (ICC) and its internal consistency using Cronbach's alpha. The standard error of measurement and minimum detectable change were calculated. The construct validity was evaluated using Pearson's correlation coefficient by comparing the iHOT-33-Fr with the Hip disability and Osteoarthritis Outcome Score (HOOS-Fr) and Nonarthritic Hip Score (NAHS-Fr). Results In all, 101 patients filled out the questionnaires. The ICC was 0.87. The Cronbach alpha was 0.95. The standard error of measurement was 6.4 and the minimum detectable change was 1.8. The correlation between the iHOT-33-Fr and the HOOS-Fr was 0.86, while the correlation between the iHOT-33-Fr and the NAHS-Fr was 0.75. Discussion Our results show that the metrological qualities of the iHOT-33-Fr are comparable to those of the original version and the versions translated into other languages. This study demonstrates that the iHOT-33-Fr is valid, reproducible and comparable to the original iHOT-33. It can be used by francophone surgeons treating symptomatic hip disease in young, active patients. Level of evidence IV.

Objective.Microparticles (MP) are small extracellular vesicles present in body fluids. MP originate from different cellular lineages, principally from platelets in blood, and may expose phosphatidylserine (PS). In systemic lupus erythematosus (SLE), MP harbor immunoglobulin G (IgG), thereby forming MP-containing immune complexes (mpIC). We aimed to verify an association between SLE disease activity, damage, and surrogate markers of atherosclerosis and MP harboring IgG, taking into account the platelet origin and PS exposure of MP.Methods.MP expressing surface IgG, platelet antigen (CD41+), and PS were quantified using flow cytometry in plasma of 191 women with SLE. Carotid ultrasounds (US) were available in 113 patients. Spearman correlation analysis was used to analyze whether levels of MP were associated with the following outcomes: SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and carotid US plaques and intima-media thickness (CIMT) as surrogates for vascular damage.Results.We found CD41+ MP harboring IgG present in SLE. A positive correlation was found between SLEDAI-2K and levels of CD41+ MP harboring IgG and exposing (p = 0.027) and non-exposing PS (p = 0.001). Conversely, SDI (p = 0.024) and CIMT (p = 0.016) correlated with concentrations of CD41− MP harboring IgG and exposing PS. Associations were independent of low-density lipoprotein cholesterol level, body mass index, and antimalarial drug use.Conclusion.Different subtypes of mpIC are produced in SLE and are associated with distinct clinical characteristics such as disease activity and vascular damage. The assessment of MP subtypes might serve for the design of predictive markers of disease activity and vascular damage in patients.

Background: In men with localized prostate cancer who are undergoing radical prostatectomy (RP), it is uncertain whether their systemic hormonal environment is associated with outcomes. The objective of the study was to examine the association between the circulating steroid metabolome with prognostic factors and progression. Methods: The prospective PROCURE cohort was recruited from 2007 to 2012, and comprises 1,766 patients with localized prostate cancer who provided blood samples prior to RP. The levels of 15 steroids were measured in plasma using mass spectrometry, and their association with prognostic factors and disease-free survival (DFS) was established with logistic regression and multivariable Cox proportional hazard models. Results: The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and androsterone levels were higher in low-risk disease. Associations were observed between adrenal precursors and risk of cancer progression. In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 (P = 0.0017; q = 0.026) and 1.24 (P = 0.043; q = 0.323), respectively. Although the number of metastatic events was limited, trends with metastasis-free survival were observed for A5diol (HR = 1.51; P = 0.057) and DHEA-S levels (HR = 1.43; P = 0.054). Conclusions: In men with localized prostate cancer, our data suggest that the preoperative steroid metabolome is associated with the risk of recurrence of high-risk disease. Impact: The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.

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.

BACKGROUND: HIV testing constitutes an entry point for HIV prevention and access to care. Although access to tests has increased in most low- and middle-income countries in recent years regular HIV testing among high-risk populations remains a challenge. Understanding the determinants of regular HIV testing is the key to improving treatment-as-prevention programs and access to care. This study aimed to identify psychosocial factors associated with the intention to be HIV tested every 3 months among female sex workers (FSWs) in Benin. METHODS: We developed an interview questionnaire based on the Theory of Planned Behavior and other theoretical variables. We interviewed 450 FSWs in their work place. Using Amos software we applied structural equation modeling to identify the determinants of intention. RESULTS: Previous testing was reported by 87% of FSWs 40% of whom reported having been tested in the last 3 months. More than half of the FSWs (69%) showed a strong intention to be HIV tested during the next 3 months. The structural model indicates that 55% of the variance in intention is explained in descending order of importance (standardized coefficient weight beta) by perceived control descriptive norms control beliefs habits attitude risk perception and normative beliefs. CONCLUSIONS: This is the first theoretically based study identifying determinants of intention to undergo regular HIV testing among FSWs in sub-Saharan Africa. The results can inform development of interventions to maintain and increase regular HIV testing among FSWs thus reinforcing primary prevention and supporting early access to care.

Endometrial cancer (EC) is the most common gynecologic malignancy prevailing after menopause. Defining steroid profiles may help predict the risk of recurrence after hysterectomy, which remains limited due to the lack of reliable markers. Adrenal precursors, androgens, parent estrogens and catechol estrogen metabolites were measured by mass spectrometry (MS) in preoperative serums and those collected one month after hysterectomy from 246 newly diagnosed postmenopausal EC cases. We also examined the associations between steroid hormones and EC status by including 110 healthy postmenopausal women. Steroid concentrations were analyzed in relation to clinicopathological features, recurrence and overall survival (OS). The mean follow-up time was 65.5 months and 26 patients experienced relapse after surgery for a recurrence incidence of 10.6% (6.4% Type I and 29.5% Type II). Recurrence and OS were related to a more aggressive disease but not linked to body mass index. Preoperative levels of estriol (E3) and estrone-sulfate (E1-S) were inversely associated with recurrence in a multivariate logistic regression analysis (Hazard ratios (HRs) of 0.31, P=0.039 and 3.01, P=0.024; respectively). All circulating steroids declined considerably after surgery almost reaching those of healthy women, except 4-methoxy-E2 (4MeO-E2) for which postoperative levels increased by 35% and were associated to a 68% decreased risk of recurrence (HR=0.32, P=0.015). Women diagnosed with both histological types of EC present significantly higher levels of steroids, in support of their mitogenic effects. The estrogen precursor E1-S, the anticancer metabolite 4MeO-E2, and E3 that exert mixed antagonist and agonist estrogenic activities and immunological effects, are potential independent prognostic factors.

To evaluate family medicine residents' training in, knowledge about, and perceptions of digital rectal examination (DRE).Descriptive study, using an online survey that was available in French and English.Quebec.A total of 217 residents enrolled in a family medicine program.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.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.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.

Pesinet is a non-profit organisation which operates a microinsurance programme combined with a monitoring service in low-income countries to increase primary healthcare utilisation for children. We studied the association between enrolment in the Pesinet programme and changes in utilisation of health services. We conducted a prospective controlled study in Bamako (Mali) in children under five years old. Participants in the Pesinet service were recruited from a neighbourhood of Bamako (n = 91) and participants in the control group (usual care) came from two other neighbouring districts (n = 89). Eight questionnaires were completed at 2-week intervals for each child in the study. We performed logistic regression modelling to assess the effect of the Pesinet programme on health service utilisation, adjusting for confounding variables (age and socio-economic status). During the study, families reported 206 episodes of disease in the intervention group and 168 in the control group. Children from the intervention group had 85 medical consultations and those in the control group had 28. Based on the logistic regression model, there was increased utilisation of health care services among children enrolled in the Pesinet programme, with an adjusted Odds Ratio for medical consultations of 2.2. Membership of the Pesinet telehealth programme increased primary healthcare utilisation among children under five years old in Mali.

Background Androgen inactivation occurs mainly through the glucuronidation conjugative reaction mediated by UDP-glucuronosyltransferases (UGTs). This metabolic process is involved in the control of systemic and local androgen bioavailability. Objective To examine the relationship among expression of the androgen-inactivating UGT2B28 enzyme, circulating steroid hormone levels, and clinical phenotype in prostate cancer (PCa). Design, setting, and participants We conducted an analysis of a high-density prostate tumor tissue microarray consisting of 239 localized PCa cases. The study of 51 additional PCa patients with no copies of UDP glucuronosyltransferase 2B subfamily, polypeptide B28 ( UGT2B28 ) in their genomes was performed to confirm the importance of the enzyme on circulating hormone levels. Outcome measurements and statistical analysis Steroid hormones were measured by mass spectrometry. Multivariate Cox proportional hazard models assessed the influence of UGT2B28 on progression, and general linear model regression evaluated variations in hormone levels. Results and limitations Tumor overexpression of UGT2B28 was associated with lower prostate-specific antigen levels at diagnosis, higher Gleason scores, margin and nodal invasion status, and it was shown to be an independent prognostic factor associated with progression. Enzyme overexpression correlated with 30% higher circulating levels of testosterone (T) and dihydrotestosterone (DHT). Patients with no copies of UGT2B28 in their genomes have lower levels of T (19%), DHT (17%), its glucuronide metabolites (18–38%), and enhanced levels of the adrenal precursor androstenedione (36%). Conclusions The UGT2B28 steroid-inactivating pathway modifies circulating T and DHT levels, and UGT2B28 overexpression is associated with high-grade PCa. Our work has uncovered the role of UGT2B28 as a regulator of steroidogenesis and underscores the interconnectivity among the steroid-inactivation capacity of cancer cells, hormone levels, disease characteristics, and the risk of cancer progression. Patient summary The androgen-inactivating UGT2B28 enzyme influences hormone levels, clinical and pathologic factors, and the risk of cancer progression.

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.