Impact of the Withdrawal of Palivizumab Immunoprophylaxis on the Incidence of Respiratory Syncytial Virus (RSV) Hospitalizations Among Infants Born at 33 to 35 Weeks' Gestational Age in the Province of Quebec, Canada: The RSV-Quebec Study.

BACKGROUND: Infants born at 33-35 completed weeks' gestational age (wGA) aged <6 months at the start of or born during respiratory syncytial virus (RSV) season and classified as moderate/high risk of severe RSV disease were included in a palivizumab RSV prophylaxis program in the province of Quebec, Canada, until 2014-2015. We assessed the impact of withdrawal of this indication on lower respiratory tract infection (LRTI)/RSV hospitalizations (H) in this population. METHODS: We conducted a 4-year, retrospective, cohort study in 25 Quebec hospitals (2 seasons with and 2 without palivizumab prophylaxis for moderate- to high-risk infants). Our primary outcome was LRTI/RSV-H incidence. We compared LRTI/RSV-H incidence before (2013-2015; seasons 1 + 2 [S1/2]) and after (2015-2017; S3/4) the change in indication. RESULTS: We identified 6457 33-35 wGA births. LRTI/RSV-H occurred in 105/3353 infants (3.13%) in S1/2 and 130/3104 (4.19%) in S3/4. Among LRTI/RSV-H, 86.4% were laboratory-confirmed RSV-H. Adjusting for sex, wGA, and birth month, S3/4 was significantly associated with increased LRTI/RSV-H incidence (adjusted odds ratio [aOR], 1.36; 95% confidence interval [CI], 1.04-1.76) but not with laboratory-confirmed RSV-H (aOR, 1.19; 95% CI, 0.90-1.58). Mean duration of LRTI/RSV-H was 5.6 days; 22.6% required intensive care unit admission. Comparing S3/4 with S1/2, infant percentage with LRTI/RSV-H classified as moderate/high risk increased from 27.8% to 41.9% (P = .11). CONCLUSIONS: In a province-wide study, we observed a significant increase in LRTI/RSV-H incidence among infants born at 33-35 wGA in the 2 years after withdrawal of RSV prophylaxis.

Impact of Endometriosis on Fatigue and Productivity Impairment in a Cross-Sectional Survey of Canadian Women.

OBJECTIVE: To evaluate fatigue burden and productivity impairments in Canadian women with a self-reported diagnosis of endometriosis (DxE). METHODS: From December 2018 to January 2019, Canadian women aged 18-49 years completed an online survey assessing fatigue via the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 6a questionnaire. Fatigue T-scores were compared between women with and without a DxE, by age and endometriosis symptom severity, using t tests. Women with a DxE completed the Work Productivity and Activity Impairment - Specific Health Problem (WPAI-SHP) questionnaire. The effects of age and hallmark endometriosis symptoms on productivity impairments were assessed via analysis of variance. RESULTS: Survey data included 2004 women with and 26 528 women without a DxE. Mean fatigue T-scores were 58.5 ± 10.1 in women with a DxE and 59.2 ± 10.1 in women with hallmark endometriosis symptoms (i.e., menstrual or non-menstrual pelvic pain/cramping, dyspareunia) versus 55.2 ± 9.4 in women without a DxE (both P < 0.001). Women with moderate or severe endometriosis symptoms had a mean T-score of 61.2 ± 9.4 versus 55.9 ± 10.1 for women with mild symptoms (P < 0.001). Women with moderate or severe hallmark endometriosis symptoms had mean T-scores of 59.6-62.9 versus 57.0-58.2 for women with mild or no symptoms (all comparisons P < 0.01). Women with a DxE reported 17.1% of work time missed, 41.8% impaired work ability, 46.5% overall work impairment, and 41.4% activity impairment per the WPAI-SHP. Women with a DxE aged 30-34 and 35-39 years consistently experienced the greatest effects of fatigue and productivity impairments. CONCLUSIONS: Canadian women with a DxE experience a substantial fatigue burden and significant productivity impairments.

Cross-Sectional Survey of the Impact of Endometriosis Symptoms on Health-Related Quality of Life in Canadian Women.

OBJECTIVE: To characterize the health-related quality of life (HRQOL) of Canadian women with a self-reported diagnosis of endometriosis (DxE). METHODS: Canadian women aged 18-49 years completed a survey from December 2018 through January 2019 in which HRQOL was assessed via the 12-item Short Form Health Survey (SF-12) and Endometriosis Health Profile-30 (EHP-30) questionnaire. We used t tests to compare SF-12 scores between women with and without a self-reported DxE, as well as the severity of hallmark endometriosis symptoms, including menstrual pelvic pain/cramping, non-menstrual pelvic pain/cramping, and dyspareunia, for women with a DxE (moderate/severe vs. mild/none). The effects of overall endometriosis symptom severity on HRQOL were assessed via analysis of variance. RESULTS: In total, 26 528 women without a DxE and 2004 women with a self-reported DxE were included. SF-12 scores were significantly lower for women with versus without a DxE (Mental Component Summary: 38.6 vs. 41.2; Physical Component Summary: 47.3 vs. 52.1; both P < 0.001), indicating reduced HRQOL. Moderate/severe hallmark endometriosis symptoms were associated with low SF-12 scores (i.e., worse HRQOL), with the greatest impact from non-menstrual pelvic pain/cramping. EHP-30 scores for women with a DxE ranged from 40.6 to 46.8, with the greatest impairment in self-image. Women with severe endometriosis symptoms had EHP-30 scores 1.3- and >2-fold higher (i.e., worse) than those with moderate and mild symptoms, at 67.5-74.6 versus 51.3-56.9 and 25.6-32.9, respectively. CONCLUSION: Canadian women with a self-reported diagnosis of endometriosis had significantly impaired health-related quality of life, which was inversely correlated with endometriosis symptom severity. This finding highlights a substantial unmet need among women with endometriosis.

Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada: Cross-Sectional Survey of 30 000 Women.

OBJECTIVE: This study sought to estimate the prevalence of diagnosis of endometriosis (DxE) in Canada and to assess the symptomatic and diagnostic experience of Canadian women with DxE. METHOD: A cross-sectional, online survey of women in Canada aged 18 to 49 was conducted from December 7, 2018 through January 24, 2019. Survey data were weighted by Canadian population statistics to estimate the prevalence, symptomatic burden, and diagnostic experience of DxE. Logistic regressions were used to assess differences in symptom burden between women with and without DxE. RESULTS: The estimated prevalence of DxE was 7.0% (2004 women of 28 532 women surveyed). Almost half (47.5%) of women with DxE were aged 18 to 29 when they received an endometriosis diagnosis, and 84.1% experienced symptoms before diagnosis. More women with versus without DxE experienced menstrual pelvic pain or cramping (70.3% vs. 50.7%), non-menstrual pelvic pain or cramping (49.5% vs. 18.7%), dyspareunia (52.5% vs. 28.0%), and infertility (22.3% vs. 6.3%). Women with DxE were more likely to report severe menstrual pelvic pain or cramping (odds ratio [OR] 2.9; 95% confidence interval [CI] 2.5-3.3), non-menstrual pelvic pain or cramping (OR 3.4; 95% CI 2.8-4.2), general abdominal pain (OR 3.0; 95% CI 2.5-3.6), and pelvic pressure (OR 3.0; 95% CI 2.3-3.8). Women with DxE reported an average 5.4-year diagnostic delay, with a 3.1-year delay from onset of symptoms to physician consultation and a 2.3-year delay between physician consultation and diagnosis. CONCLUSION: Self-reported DxE is prevalent among Canadian women and is associated with a substantial symptomatic burden. The 5.4-year diagnostic delay reported here indicates an important unmet need for more timely diagnosis of endometriosis in Canada.

Burden of Respiratory Syncytial Virus Hospitalizations in Canada.

Objective: To examine the socioeconomic burden of respiratory syncytial virus (RSV) disease for Canadian infants hospitalized for the condition. Data and Methods: The descriptive study used data collected in Alberta, Canada, during 2 consecutive RSV seasons. Infants (<1 year of age) were included if they had not received palivizumab and were hospitalized with a confirmed diagnosis of RSV. Hospitalization resource use and parental time burden, out-of-pocket costs, lost work productivity, and stress and anxiety were assessed. Results: 13.4% of all infants (n = 67) had intensive care unit (ICU) admission, and average ICU stay for these infants was 6.5 days. Families had average out-of-pocket expenses of 736.69 Canadian dollars (CAD $), and the average time both parents spent in hospital was nearly 7 days (164.0 hours). For working parents (n = 43), average absenteeism was 49% and overall work impairment was 77.8%. Parents also exhibited significant parental stress (3.6 on the Parental Stressor Scale: 43.9 state anxiety and 36.9 trait anxiety scores). Conclusions: Results indicate a high burden associated with the hospitalization of an infant due to RSV disease in terms of resource use, time, productivity, costs, and stress, even among a population of infants not considered to be at risk for the condition.

Cognitive change in donepezil treated patients with vascular or mixed dementia.

BACKGROUND: vascular dementia (VaD) and mixed Alzheimer's disease (AD/VaD) are common. How best to monitor treatment is not clear. Our objective was to compare responsiveness and construct validity of change scores, following donepezil treatment, of the standardized Mini-Mental State Examination (sMMSE) and other measures potentially usable in primary care. METHODS: A six-month, outcome measurement study. The Disability Assessment for Dementia (DAD), CLOX-1 and 2, Phonetic Fluency, a short Neuropsychiatric Inventory, (the NPI-Q), Clinical Global Impression (CGI) and the SymptomGuide™ (SG) were measured. Construct validity was tested by correlating change scores, and responsiveness by calculating standardized response means (SRMs). RESULTS: Of 148 treated patients, 116 completed. The mean sMMSE increased by 0.7 (95% Confidence Interval (CI) = -0.005, 1.41; p=0.06; SRM= 0.15). There was no statistically significant difference in the DAD. The NPI-Q (-1.4; 95% CI = -2.08, -0.72; p<0.01; SRM=0.24), CLOX-1 (0.9; 95% CI = 0.19, 1.61; p<0.01; SRM=0.21), CLOX-2 (0.9; 95% CI = 0.17, 1.63; p=0.03; SRM=0.26), Phonetic Fluency (0.9; 95% CI = 0.19, 1.61; p=0.02; SRM=0.21) and SG (0.35; 95% CI = 0.20,0.51; p<0.01; SRM=0.28) each detected significant improvement. The CGI suggested improvement in 74 completers (64%) - mostly "minimal" (44/116, 38%) - while 21/116 (18%) were worse. Change scores at 24 weeks were at best modestly correlated with each other (range -0.22 to 0.30). DISCUSSION: Different measures showed different responsiveness, in a setting in which the mean treatment effect seems to have been small, but clinically detectable. Patient-centered and executive function measures might be useful in vascular and mixed dementia.

A multicenter, double-blind, placebo-controlled study of sildenafil citrate in Canadian men with erectile dysfunction and untreated symptoms of depression, in the absence of major depressive disorder.

Depression and erectile dysfunction (ED) often co-occur. Phosphodiesterase type 5 inhibitors are effective in men with ED and untreated depression, or ED secondary to antidepressants. This study evaluated sildenafil treatment in Canadian men with clinically diagnosed ED (Sexual Health Inventory for Men score ≤ 21) and mild-to-moderate untreated depressive symptoms [Beck Depression Inventory II (BDI-II) score 14-28], but excluding major depressive disorder. Pretreatment screening using the Sexual Health Inventory for Men and BDI-II showed that men with ED were more likely to have depression than men without ED, and ED severity was a predictor of depression (P=0.0226). Two hundred and two men were randomized to 6 weeks of double-blind treatment with placebo (n=98) or sildenafil (n=104), initial dose of 50 mg, adjustable to 25 or 100 mg. The men were evaluated on all domains of the International Index of Erectile Function and the Sex Effects Questionnaire, Global Efficacy Questions, and Event-log data. Compared with placebo, patients treated with sildenafil had significantly greater changes from baseline in BDI-II scores (P<0.001). All International Index of Erectile Function domains and the Sex Effects Questionnaire components were also significantly improved in sildenafil group (P<0.01). The most common adverse events included headache, dyspepsia, vasodilatation, and respiratory tract infections and were generally mild in intensity.

Do men with mild erectile dysfunction have the same risk factors as the general erectile dysfunction clinical trial population?

OBJECTIVE: • To compare the underlying risk for diseases associated with erectile dysfunction (ED; i.e. cardiovascular disease and diabetes) in a population of men with mild ED relative to a general ED clinical trial population. PATIENTS AND METHODS: • Men enrolled in a randomized, double-blind placebo-controlled (DBPC) trial of sildenafil for the treatment of mild ED were compared with a database of men enrolled in 67 of the manufacturer's other DBPC sildenafil trials. • The main outcome measures were baseline demographics, comorbidities and concomitant medications. RESULTS: • In both populations, most men were white, approximately one quarter were smokers, and most had an organic component to their ED etiology. • In the mild ED population (N = 176) versus the database population (N = 14,537), mean ± sd (range) age was 50 ± 12 (19-84) versus 55 ± 11 (18-89) years, body mass index was 29 ± 5 (20-48) versus 28 ± 5 (11-64) kg/m² and ED duration was 3.5 ± 3.2 (< 1-18) versus 4.6 ± 4.7 (< 1-45) years. • The prevalence of comorbidities associated with ED was similar (hypertension 26.1% (n = 46) vs 32.8%; diabetes mellitus 13.6% (n = 24) vs 22.1%; dyslipidemias 12.5% (n = 22) vs 11.7%; hypercholesterolemia 12.5% (n = 22) vs 9.5%; gastro-esophageal reflux disease 10.8% (n = 19) vs 6.0%; benign prostatic hyperplasia 9.7% (n = 17) vs 9.9%; depression 6.3% (n = 11) vs 5.6%; and anxiety 4.0% (n = 7) vs 1.6%), as was the rate of use of medications for those comorbidities. CONCLUSIONS: • Men with mild ED have similar risk factors to a general ED clinical trial population. Thus, mild ED is an important indicator of risk for underlying disease associated with ED. • Inquiry into ED should be part of routine clinical evaluation to facilitate rapid identification and early intervention. • Men complaining of mild ED should be evaluated adequately for underlying cardiovascular risk.

Men with mild erectile dysfunction benefit from sildenafil treatment.

INTRODUCTION: Sildenafil treatment has not been evaluated in a double-blind, placebo-controlled (DBPC) trial specific to men with mild erectile dysfunction (ED), defined by a 22-25 score on the International Index of Erectile Function-erectile function domain (IIEF-EF). AIM: To assess sildenafil efficacy in sexually dissatisfied men with mild ED. MAIN OUTCOME MEASURES: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), IIEF, Quality of Erection Questionnaire (QEQ), Erection Hardness Score (EHS 4=completely hard/fully rigid), general efficacy questions (GEQs), event log questions (hardness sufficient for penetration, duration sufficient for successful intercourse, ejaculation/orgasm, and second erection within 24 hours), and analog scales (erection firmness, reliability, and maintenance, and general sexual performance). METHODS: Eight-week DBPC flexible-dose (25, 50, or 100 mg) trial with 6-week, open-label (OL) extension. RESULTS: One hundred and seventy-six men were randomized (mean±standard deviation: age, 50±12 year; ED duration, 3.5±3.2 year). Most had organic or mixed ED. For sildenafil vs. placebo, 66% vs. 89% titrated to 100 mg and efficacy at DBPC end was better, including the EDITS Index score (least squares mean [standard error], 80.3 [2.3] vs. 62.1 [2.5]; P<0.0001); treatment satisfaction (EDITS Index score >50 in 89% vs. 63%; P=0.0001); no ED (IIEF-EF ≥26 in 58% vs. 39%; P<0.05); GEQs (≥4.9-fold greater odds of improved erections and ability to have sexual intercourse); and EHS 4 (47.2% vs. 25.2% of occasions; P<0.0001). At OL end, 93% of men were satisfied (EDITS Index score>50), 77% had no ED, and ≥89% were GEQ responders; mean scores on IIEF domains, the QEQ, and analog scales were >80% of the maximum; 60% of occasions had EHS 4; and event log responses were positive on >80% of occasions, except for second erections (41.9%). Headache, nasal congestion, and flushing, mostly mild to moderate, were the most common adverse events. CONCLUSION: Men with mild ED derive substantial benefit from sildenafil treatment.

Treatment satisfaction with sildenafil in a Canadian real-life setting. A 6-month prospective observational study of primary care practices.

INTRODUCTION: While the efficacy of sildenafil for the management of erectile dysfunction (ED) has been demonstrated in randomized clinical trials, few data exist on its effectiveness in a real-life setting. AIM: The objective of this study was to examine the treatment satisfaction and effectiveness with sildenafil in a real-life setting in Canada. METHODS: A multicenter, prospective study, using an educational program aimed at optimizing sildenafil treatment, was conducted at 231 primary care sites across Canada. Patients who received their first prescription of sildenafil for ED within the usual practice of medicine were invited to participate in the study. Data were collected through patient self-administered questionnaires. MAIN OUTCOME MEASURES: The Sexual Health Inventory for Men (SHIM) questionnaire was used to determine the erectile function at baseline, month 3 and month 6. Treatment satisfaction at months 3 and 6 was assessed using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. RESULTS: The intent-to-treat population consisted of 2,573 patients. The mean age was 55 years (18 to 92 years). At baseline, the mean SHIM score was 11.9 with 21.7% of men having severe ED, 22.9% moderate ED, 36.5% mild-to-moderate ED, and 16.9% mild ED. At month 3, the mean SHIM score improved significantly to 18.0 (P < 0.0001) and 33.3% of patients had a SHIM score above 21 (no ED). At 6 months, the mean SHIM score was 18.7. At both months 3 and 6, approximately 89% of patients were satisfied with their treatment (i.e., EDITS score >or= 50), suggesting no attenuation of the satisfaction over the 6 months of use. CONCLUSIONS: The effectiveness of sildenafil in the management of ED was demonstrated in a large cohort of men treated in a primary care setting in this Canadian real-life study. Persistence with therapy and lack of attenuation over time among the vast majority of men was shown.

Can an educational program optimize PDE5i therapy? A study of Canadian primary care practices.

INTRODUCTION: The importance of patient instructions, designed to optimize therapy with phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction (ED), has recently been demonstrated. AIM: To evaluate the impact of an educational program for new sildenafil users against usual ED management in Canadian primary care practices. METHODS: This multicenter, 6-month cluster randomized prospective study was conducted across Canada in general practitioners' offices where sites were randomized to receive a treatment optimization program (TOP) tool at visit 1 (TOP sites) or not to receive the TOP tool (non-TOP sites) while continuing with usual practice. Study participants were men seeking medical attention for ED and who were sildenafil naïve. The TOP tool consisted of a tear-off sheet, a brochure, and a video. Study drug was not provided to the patients. Sildenafil samples and prescriptions were dispensed as per usual care practices. MAIN OUTCOME MEASURES: The Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire was used to determine treatment satisfaction at visit 2 (month 3) and visit 3 (month 6). Patient and physician satisfaction with the TOP tool was assessed using self-reported questionnaires. RESULTS: The intent-to-treat (ITT) population consisted of 2,573 patients from 231 primary care sites. At visits 2 and 3, treatment satisfaction with sildenafil was high with almost 9 patients out of 10 satisfied with treatment. No significant statistical differences were observed in the EDITS scores between the TOP and the non-TOP groups at visits 2 and 3. More than 80% of the participants were satisfied or very satisfied with the video and the brochure. More than 8 out of 10 participating physicians (84%) would use the TOP tool in their current practice if available. CONCLUSIONS: TOP is a valuable and time-efficient ED management tool providing benefits to newly diagnosed ED patients and to their physicians.

The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease.

BACKGROUND: The prevalence of erectile dysfunction (ED) and associated risk factors has been described in many clinical settings, but there is little information regarding men seen by primary care physicians. We sought to identify independent factors associated with ED in a primary care setting. METHODS: We surveyed a cross-sectional sample of 3921 Canadian men, aged 40 to 88 years, seen by primary care physicians. Participants completed a full medical history, physical examination, and measurement of fasting blood glucose and lipid levels. We used the International Index of Erectile Function to define ED as a score of less than 26 on the erectile function domain. RESULTS: The overall prevalence of ED was 49.4%. The presence of cardiovascular disease (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.16-1.81; P<.01) or diabetes (OR, 3.13; 95% CI, 2.35-4.16; P<.001) increased the probability of ED after adjustment for other confounders. Among those individuals without cardiovascular disease or diabetes, the calculated 10-year Framingham coronary risk (OR, 1.03 per 1% increase; 95% CI, 1.02-1.05; P<.001) and fasting blood glucose levels (OR, 1.14 per 18-mg/dL [1-mmol/L] increase; 95% CI, 1.04-1.24; P<.01) were independently associated with ED. Erectile dysfunction was also independently associated with undiagnosed hyperglycemia (OR, 1.46; 95% CI, 1.02-2.10; P = .04), impaired fasting glucose (OR, 1.26; 95% CI, 1.08-1.46; P = .004), and the metabolic syndrome (OR, 1.45; 95% CI, 1.24-1.69; P<.001). CONCLUSIONS: Cardiovascular disease, diabetes, future coronary risk, and increasing fasting glucose levels are independently associated with ED. It remains to be determined if ED precedes the development of these conditions.