Androgen deprivation therapy use and duration with definitive radiotherapy for localised prostate cancer: an individual patient data meta-analysis.

BACKGROUND: Randomised trials have investigated various androgen deprivation therapy (ADT) intensification strategies in men receiving radiotherapy for the treatment of prostate cancer. This individual patient data meta-analysis of relevant randomised trials aimed to quantify the benefit of these interventions in aggregate and in clinically relevant subgroups. METHODS: For this meta-analysis, we performed a systematic literature search in MEDLINE, Embase, trial registries, the Web of Science, Scopus, and conference proceedings to identify trials with results published in English between Jan 1, 1962, and Dec 30, 2020. Multicentre randomised trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localised prostate cancer receiving definitive radiotherapy, reported or collected distant metastasis and survival data, and used ADT for a protocol-defined finite duration. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was accessed to obtain individual patient data from randomised trials. The primary outcome was metastasis-free survival. Hazard ratios (HRs) were obtained through stratified Cox models for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension (ie, extension of total ADT duration in the neoadjuvant setting from 3-4 months to 6-9 months), and adjuvant ADT prolongation (ie, prolongation of total ADT duration in the adjuvant setting from 4-6 months to 18-36 months). Formal interaction tests between interventions and metastasis-free survival were done for prespecified subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiotherapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855. FINDINGS: Our search returned 12 eligible trials that provided individual patient data (10 853 patients) with a median follow-up of 11·4 years (IQR 9·0-15·0). The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77-0·89], p<0·0001), as did adjuvant ADT prolongation (0·84 [0·78-0·91], p<0·0001), but neoadjuvant ADT extension did not (0·95 [0·83-1·09], p=0·50). Treatment effects were similar irrespective of radiotherapy dose, patient age, or NCCN risk group. INTERPRETATION: Our findings provide the strongest level of evidence so far to the magnitude of the benefit of ADT treatment intensification with radiotherapy for men with localised prostate cancer. Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the magnitude of the benefit could vary and shared decision making with patients is recommended. FUNDING: University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology.

Quebec Health-related Quality of Life Population Norms in Adults Using the SF-6Dv2: Decomposition by Sociodemographic Data and Health Problems.

OBJECTIVE: The Short-Form 6-Dimension version 2 (SF-6Dv2) is the newest version of the Short-Form 6-Dimension (SF-6D) that is widely used to calculate quality-adjusted life-years (QALYs). The aim of this study was to produce Quebec population norms from the SF-6Dv2. METHODS: An online survey was conducted in the adult general population. Data was stratified by various sociodemographic characteristics, such as age, sex, body mass index, history of illness, and health problems. RESULTS: A total of 4175 respondents completed the SF-6Dv2. Mean (95% confidence interval) and median (interquartile range) utility scores were 0.692 (0.684-0.700) and 0.780 (0.607-0.866), respectively. Floor and ceiling effect corresponded to 0.05% and 3.1%, respectively. Men, nonsmoker, higher education, and employed people had significantly higher scores, while lower scores were found for those with a history of illness and a lower life satisfaction. Those reporting a health problem presented significant lower mean utility scores ranging from 0.340 (nervous problem) to 0.623 (diabetes) for men and from 0.207 (genitourinary) to 0.578 (diabetes) for women as compared with those without health problem (0.793 for men and 0.750 for women). CONCLUSION: This study is the first to provide utility score norms for SF-6Dv2 in the adult general population of Quebec. It also highlighted significant differences among various health problems that can be used to compare populations in studies that do not have a control group.

French adaptation and validation of the Panic Disorder Severity Scale-self-report.

BACKGROUND: The aims of this study were to conduct a cross-cultural validation of the Panic Disorder Severity Scale - Self-Report (PDSS-SR) and to examine psychometric properties of the French-Canadian version. METHODS: A sample of 256 adults were included in the validation study based on data from the baseline interview of a clinical trial on transdiagnostic cognitive-behavioral therapy for mixed anxiety disorders. Participants completed the Anxiety and Related Disorders Interview Schedule (ADIS-5), and self-report instruments including the PDSS-SR, Beck Anxiety Inventory (BAI), Mobility Inventory for Agoraphobia (MIA), Sheehan Disability Scale (SDS), Patient Health Questionnaire (PHQ-9), Social Phobia Inventory (SPIN), Insomnia Severity Index (ISI) and Penn State Worry Questionnaire (PSWQ). The cross-cultural adaptation in French of the PDSS-SR included a rigorous back-translation process, with an expert committee review. Sensitivity to change was also examined with a subgroup of patients (n = 72) enrolled in the trial. RESULTS: The French version of the PDSS-SR demonstrated good psychometric properties. The exploratory factor analysis supported a one factor structure with an eigenvalue > 1 that explained 64.9% of the total variability. The confirmatory factor analysis (CFA) corroborated a one-factor model with a good model fit. Internal consistency analysis showed a .91 Cronbach's alpha. The convergent validity was adequate with the ADIS-5 clinical severity ratings for panic disorder (r = .56) and agoraphobia (r = .39), as well as for self-report instruments [BAI (r = .63), MIA (accompanied: r = .50; alone: r = .47) and SDS (r = .37)]. With respect to discriminant validity, lower correlations were found with the SPIN (r = .17), PSWQ (r = .11), ISI (r = .19) and PHQ-9 (r = .28). The optimal threshold for probable diagnosis was 9 for the PDSS-SR and 4 for the very brief 2-item version. The French version showed good sensitivity to change. CONCLUSIONS: The French version of the PDSS-SR has psychometric properties consistent with the original version and constitutes a valid brief scale to assess the severity of panic disorder and change in severity over time, both in research and clinical practice.

Group transdiagnostic cognitive-behavior therapy for anxiety disorders: a pragmatic randomized clinical trial.

BACKGROUND: Transdiagnostic group cognitive-behavioral therapy (tCBT) is a delivery model that could help overcome barriers to large-scale implementation of evidence-based psychotherapy for anxiety disorders. The aim of this study was to assess the effectiveness of combining group tCBT with treatment-as-usual (TAU), compared to TAU, for the treatment of anxiety disorders in community-based mental health care. METHODS: In a multicenter single-blind, two-arm pragmatic superiority randomized trial, we recruited participants aged 18-65 who met DSM-5 criteria for principal diagnoses of generalized anxiety disorder, social anxiety disorder, panic disorder, or agoraphobia. Group tCBT consisted of 12 weekly 2 h sessions. There were no restrictions for TAU. The primary outcome measures were the Beck Anxiety Inventory (BAI) and clinician severity rating from the Anxiety and Related Disorders Interview Schedule for DSM-5 (ADIS-5) for the principal anxiety disorder at post-treatment, with intention-to-treat analysis. RESULTS: A total of 231 participants were randomized to either tCBT + TAU (117) or TAU (114), with outcome data available for, respectively, 95 and 106. Results of the mixed-effects regression models showed superior improvement at post-treatment for participants in tCBT + TAU, compared to TAU, for BAI [p < 0.001; unadjusted post-treatment mean (s.d.): 13.20 (9.13) v. 20.85 (10.96), Cohen's d = 0.76] and ADIS-5 [p < 0.001; 3.27 (2.19) v. 4.93 (2.00), Cohen's d = 0.79]. CONCLUSIONS: Our findings suggest that the addition of group tCBT into usual care can reduce symptom severity in patients with anxiety disorders, and support tCBT dissemination in routine community-based care.

Quebec Health-Related Quality-of-Life Population Norms Using the EQ-5D-5L: Decomposition by Sociodemographic Data and Health Problems.

OBJECTIVES: Population norms for the EQ-5D-5L were published in Canada but only for Alberta province. The purpose of this study was to derive Quebec population norms from the EQ-5D-5L. METHODS: The data came from a larger study conducted between September 2016 and March 2018 using elicitation techniques for a quality-adjusted life-year project. The online survey was distributed randomly in the province of Quebec. To best describe the entire population, data were stratified by various sociodemographic characteristics such as age, gender, urban and rural populations, whether disadvantaged or not, immigrant or nonimmigrant, and health problems. RESULTS: A total of 2704 (53.8%) respondents completed the EQ-5D-5L. Mean (95% confidence interval) and median (interquartile range) utility scores were 0.824 (0.818-0.829) and 0.867 (0.802-0.911), respectively. The EQ-VAS scores were estimated at 75.9 (75.2-76.6) and 80 (69-90). Subjects with lower scores were those who had a low or high body mass index; were smokers; were single, divorced, or widowed; had no children; were unemployed or sick; had lower education or lower annual income; and had a family or personal history of serious illness. Immigrants had higher scores. There was no difference in gender and urban or rural population. The score logically decreased with worsening health status, from a mean score of 0.896 (0.884-0.908) to 0.443 (0.384-0.501; P < .0001. Similar results were observed for subjects' satisfaction with their health or life. Subjects with lower scores were less willing to take risks. Subjects who declared they were affected by health problems presented significant lower utility scores, ranging from 0.554 (nervous problem) to 0.750 (cancer), compared with those without health problems (0.871; confidence interval: 0.867-0.876). CONCLUSION: This is the first study to present utility score norms for EQ-5D-5L for the Quebec population. These results will be useful for comparison with quality-adjusted life-year studies to better interpret their results. Moreover, utility norms were provided for 21 health problems, which was rarely done.

Canadian French translation and linguistic validation of the child health utility 9D (CHU9D).

BACKGROUND: Several preference based measures are validated for adults in cost utility analysis, but less are available for children and many researchers have criticized the quality of pediatric economic studies. The objective of this study was to perform a Canadian French translation and linguistic validation of the Child Health Utility 9D (CHU9D) that was conceptually equivalent to the original English version for use in Canada. METHODS: The translation and linguistic validation were realized by ICON Clinical Research (UK) Limited in association with the developer of the CHU9D and Canadian collaborators. This was done in accordance with industry standards and the guidance of the Food and Drug Administration (FDA) for patient-reported outcome (PRO) instruments. Five steps were considered: concept elaboration; forward translation; back translation; linguistic validation; proofreading and final verification. RESULTS: The CHU9D Canadian French translation and linguistic validation were realized without any major difficulties. Only 3 changes were made after the forward translation and 5 after the back translation. The result of back translation was very similar to the original English version. Six additional changes suggested by the developer team were accepted and the linguistic validation with five children led to 2 additional changes. Most changes were generally to change one word to better sounding Canadian French. CONCLUSION: We produced a Canadian French translation and cross-cultural adaptation of the Child Health Utility 9D (CHU9D). Before being used in clinical settings and research projects, the final Canadian French translation needs to be validated for metrological qualities of reliability and validity.

A postpartum vaccination promotion intervention using motivational interviewing techniques improves short-term vaccine coverage: PromoVac study.

BACKGROUND: Due to the increasing number of vaccine-hesitant parents, new effective immunization promotion strategies need to be developed to improve the vaccine coverage (VC) of infants. This study aimed to assess the impact of an educational strategy of vaccination promotion based on motivational interviewing (MI) techniques targeting parents and delivered at the maternity ward, for the VC of infants at 3, 5, and 7 months of age. METHODS: An individual educational information session, administered using MI techniques, regarding immunization of infants aged 2, 4, and 6 months was (experimental group) or was not (control group) proposed to parents during the postpartum stay at the maternity ward. Immunization data were obtained through the Eastern Townships Public Health registry for infants at 3, 5, and 7 months of age. Absolute VC increases at 3, 5, and 7 months in the experimental group were calculated and the relative risks with the respective 95% confidence intervals were computed using univariate logistic regression with the generalized estimating equations (GEE) procedure. Multivariate regression using GEE was used to adjust for confounding variables. RESULTS: In the experimental and control groups, 1140 and 1249 newborns were included, respectively. A significant increase in VC of 3.2, 4.9, and 7.3% was observed at 3, 5, and 7 months of age (P < 0.05), respectively. The adjusted relative risk of the intervention's impact on vaccination status at 7 months of age was 1.08 (95% confidence interval: 1.03-1.14) (P = 0.002). CONCLUSIONS: An educational strategy using MI techniques delivered at the maternity ward may be effective in increasing VC of infants at ages 3, 5, and 7 months. MI could be an effective tool to overcome vaccine hesitancy.

HEALTH TECHNOLOGY ASSESSMENT UNIT PROCESSES FOR THE VALIDATION OF AN INFORMATION TOOL TO INVOLVE PATIENTS IN THE SAFETY OF THEIR CARE.

INTRODUCTION: Patients and families play an important role in preventing adverse events. The quality council at our hospital produced a communication tool in considering the main causes of adverse events and requested the health technology assessment (HTA) unit to validate it. OBJECTIVES: Assess the validity of the content of a tablemat sticker as an information tool for hospitalized patients. METHODS: A qualitative validation was first performed with individual interviews and focus groups to evaluate the understanding of the content. The tool was modified and as a second step, a survey was conducted on patients and their families from a surgical care unit to validate their understanding and relevance of the content. RESULTS: From the survey, patients and families found the tablemat attractive and stimulating (97 percent). It encouraged them to communicate with staff about the safety of their care (84 percent). They understood well the objective (79 percent) and text (90 percent), but less for the pictograms (30 percent to 62 percent). The communication and recommendations to avoid falling were good and 99 percent were wearing the medical identification. However, it was not clear that these indicators represented the real concerns of the patients and healthcare staff because no user evaluation was done when developing the tool. CONCLUSIONS: The tool was well understood, but some improvements are needed considering that pictograms were not always well understood and so need careful consideration from patient perspective. The HTA unit recommended conducting an unbiased survey to assess the concerns of patients and professionals to identify the most relevant indicators.

Indications for and clinical procedures resulting from magnetic resonance imaging of the knee in older patients: Are we choosing wisely?

OBJECTIVE: To analyze the indications for and clinical procedures resulting from knee magnetic resonance imaging (MRI) in older patients. DESIGN: We retrospectively analyzed 215 medical records of patients 50 years of age and older who had undergone a unilateral knee MRI in 2009. SETTING: Centre hospitalier universitaire de Sherbrooke in Quebec. PARTICIPANTS: Patients 50 years of age and older who underwent a knee MRI in 2009. MAIN OUTCOME MEASURES: The main outcome measure was an invasive procedure in the same knee that underwent an MRI. Medical charts were reviewed up to 2014 for patient characteristics, MRI indication, ordering physician specialty, radiography before MRI, MRI findings, and clinical procedures resulting from the MRI. RESULTS: The patients' mean (SD) age was 60.6 (7.5) years. The main MRI indications were meniscopathy (148 [68.8%]) and chronic pain (92 [42.8%]). The main MRI findings were osteoarthritis (OA) (185 [86.0%]) and meniscal lesions (170 [79.1%]). Only 82 (38.1%) patients had a plain radiograph in the 24 months preceding the MRI, usually without a standing anteroposterior view. Findings on pre-MRI radiography (n = 201) demonstrated OA in 144 (71.6%) patients. Overall, 87 (40.5%) patients were seen by an orthopedic surgeon and 27 (31.0%) of these patients underwent an invasive intervention. Among the 81 patients with moderate to severe OA on MRI, 36 (44.4%) had radiographic evidence of moderate to severe OA and only 3 (3.7%) underwent arthroscopic meniscectomy. CONCLUSION: Our study reproduces the known association between OA and degenerative meniscal changes in older patients. We have found a surprising underuse of the standing anteroposterior view on radiography. Most patients in our cohort could have been appropriately diagnosed and treated based on such radiographic information, as demonstrated by pre-MRI findings, thus avoiding the MRI and subsequent evaluation by an orthopedic surgeon. Meniscectomy was rarely performed, particularly in patients with advanced OA. Educational and pragmatic measures must be emphasized to encourage the use of radiography and to limit the inappropriate use of MRI, a costly technique.

Clinical correlates of faecal incontinence in systemic sclerosis: identifying therapeutic avenues.

Objectives: The aim was to establish the prevalence and severity of faecal incontinence (FI) in SSc, its association with other intestinal manifestations and potential predictors of FI, and its impact on quality of life. Methods: A multicentre, cross-sectional study of 298 SSc subjects followed in the Canadian Scleroderma Research Group cohort was performed using validated questionnaires: Jorge-Wexner score (an FI severity scale), Bristol stool scale (a visual scale of stool consistency) and FI Quality-of-Life scale. Constipation was defined by the Rome III criteria. Associations between the Jorge-Wexner score and other clinical variables were determined using multivariate regression analyses. Results: Eighty-one (27.2%) subjects had FI, which was mild in 37 (12.4%) and moderate to severe in 44 (14.8%). Most patients had well-formed stools, 111 (38.8%) reported constipation and 38 (13.4%) had been previously treated for small intestinal bacterial overgrowth (SIBO). Variables independently associated with FI were: loose vs well-formed stools [odds ratio (OR) = 7.01, 95% CI: 2.09, 23.51)], constipation (OR = 3.64, 95% CI: 1.61, 8.27, P = 0.002), history of SIBO (OR = 2.97, 95% CI: 1.06, 8.27) and urinary incontinence (OR = 2.45, 95% CI: 1.14, 5.27). Quality of life measured with the FI Quality-of-Life scale was inversely correlated with FI severity (correlation coefficients between -0.602 and -0.702, P < 0.001). Conclusion: FI was common and often severe in SSc. Loose stools, SIBO, constipation and urinary incontinence were strongly associated with FI. Other than targeting anorectal dysfunction, concomitant treatment of clinical correlates could lead to improvement in FI and quality of life in SSc.

Depressive symptoms predict future simple disease activity index scores and simple disease activity index remission in a prospective cohort of patients with early inflammatory polyarthritis.

OBJECTIVE: To determine whether depressive symptoms assessed in treated patients with early inflammatory polyarthritis (EPA) influence disease activity during follow-up. METHODS: Consecutively recruited EPA patients were actively treated to remission. Simple disease activity index (SDAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores were calculated at inclusion and up to 42 months into disease. SDAI scores were log-transformed to compute univariate and multivariate linear regressions. Parametric interval-censored Kaplan-Meier and survival regressions using Weibull distribution were used to assess time to and predictors of SDAI remission. RESULTS: A total of 275 EPA patients were recruited at a median of 4 months into disease. In multivariate linear regression models, accounting for baseline demographic, clinical, serological and functional variables and 12-month inflammation markers, CES-D scores at 12 months into disease were correlated (r(2) = 0.14) with subsequent SDAI scores. Patients with 12-month high CES-D (≥19; suggestive of depression) had a lower proportion of SDAI remission (31.3% vs 84.3%; P < 0.001) and reached SDAI remission less rapidly [hazard ratio = 0.25 (95% CI 0.12, 0.53); P < 0.001]. CONCLUSION: Each follow-up SDAI correlated significantly with 12-month depressive symptoms, a median of 7 months after initiation of treatment. CES-D scores suggestive of depression at 12 months were strongly correlated with delay and failure to reach remission later on. Depressive symptoms in treated EPA patients represent important clinical issues with long-term association with disease activity. Interventions to alleviate persistent depressive symptoms in treated EPA warrant careful evaluation of their potential to improve disease remission rates.

[French scale validation of the Infant Behavior Questionnaire three months after birth]. / Validation en langue française de l'instrument Infant Behavior Questionnaire (IBQ) à trois mois de vie de l'enfant.

Breastfeeding is recognize to be the perfect food of mother and child's health. The child's temperament is one of the factors that may explain pursuing the breastfeeding. Few instruments are available in French to measure this factor. The objective of the study is to present and validate the French translation of the scale "Infant Behavior Questionnaire" (IBQ). The sample consists of 193 primaparous or multiparous women who gave birth in a maternity in Paris. The child's temperament questionnaire was sent by mail three months after the birth. The same questionnaire was sent to a sub-sample of 30 women 15 days later. Analyses were conducted to assess the temporal stability, internal consistency, construct validity and predictive. The different results tend to show a compliant validity to the french scale version. This first IBQ French-language validation is worth pursuing in order to confirm the scale factor structure and participate to studies supporting mothers in their breastfeeding project.

Testosterone recovery after androgen deprivation therapy in localised prostate cancer: Long-term data from two randomised trials.

BACKGROUND AND PURPOSE: To determine the rate and time of testosterone (T) recovery in patients (pts) with localised prostate cancer treated with radiotherapy plus 0-, 6-, 18- or 36-month of androgen deprivation therapy (ADT). MATERIALS AND METHODS: In 1230 pts with prostate cancer randomised into two phase III trials, serum T was measured at baseline, then regularly. T recovery rate was compared between normal vs. abnormal baseline T and with ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed. RESULTS: Overall, 87.4 % (167/191), 75.9 % (293/386), 54.8 % (181/330) and 43.2 % (80/185) of pts, recovered normal T on the 0-, 6-, 18- or 36-month schedule, respectively (p < 0.001). In patients recovering normal T, the median time to T recovery increased with ADT duration ranging from 0.31, 1.64, 3.06 to 5.0 years for the 0-, 6-, 18- or 36-month schedules, respectively (p < 0.001) and was significantly faster for those with a normal T at baseline (p < 0.001). On multivariable analysis, older age and longer ADT duration are associated with a lower T recovery. CONCLUSIONS: Testosterone recovery rate after ADT depends on several factors including hormonal duration, normal baseline T, age and medical comorbidities. A longer ADT duration is the most important variable affecting T recovery. The data from this report might be a valuable tool to help physicians and patients in evaluating risks and benefits of ADT.

Prostate-Specific Antigen Response to Androgen Deprivation Therapy in the Neoadjuvant Setting for High-Risk Prostate Adenocarcinoma (PIRANHA): Pooled Analysis of Two Randomized Clinical Trials.

PURPOSE: A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer. METHODS AND MATERIALS: This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiation therapy, at least 18 months of ADT, and had a preradiation therapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival. RESULTS: Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P = .02), worse biochemical recurrence (subdistribution HR, 2.39; P = .003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P = .005), and worse overall survival (HR, 4.51; P = .05). CONCLUSIONS: Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.

SARS-CoV-2 mRNA vaccine-induced immune responses in rheumatoid arthritis.

Our objective was to characterize T and B cell responses to vaccination with SARS-CoV-2 antigens in immunocompromised rheumatoid arthritis (RA) patients. In 22 RA patients, clinical and biological variables were analyzed before and 4 weeks after each of 3 messenger RNA (mRNA) vaccine doses and compared with unmatched healthy individuals. Sequentially sampled peripheral blood mononuclear cells and sera were collected to determine immune profiles and to analyze the T cell response to a spike peptide pool and B cell specificity to the receptor-binding domain (RBD). Anti-spike antibodies were detectable in 6 of 22 RA patients after 1 dose of vaccine with increasing titers after each booster dose, although the overall response was lower compared with that in healthy control individuals. Responding patients after the first dose were more likely to have RA antibodies and a higher baseline proportion of circulating follicular B cells. In RA patients, the mRNA vaccine elicited a robust CD4+ T response to a spike peptide pool following the first and second doses. Consistent with the serologies, RBD-specific B cells exhibited a modest increase after the first dose and the second dose resulted in marked increases only in a fraction of the RA patients to both ancestral and omicron RBD. Our results highlight the importance of multidose COVID-19 vaccination in RA patients to develop a protective humoral response. However, these patients rapidly develop specific T CD4+ responses, despite delayed B cell responses.

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate.

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials.

PURPOSE: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS: Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. RESULTS: Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION: ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.

Women's preferences for water immersion during labor and birth: Results from a discrete choice experiment.

BACKGROUND AND AIM: No discrete choice experiment study has been conducted to elicit women's preferences for water immersion during labor and birth. METHODS: An online survey including sociodemographic questions and choice cards was conducted to explore women's preferences (i.e., factors that may influence their decision). Each participant responded to 12 choice cards with 6 attributes/factors (i.e., birth mode, duration of the labor phase, pain sensation, risk of severe perineal tears, risk of death of the newborn, and newborn general condition). Utilities were estimated using logit, latent class, and hierarchical Bayesian analyses. FINDINGS: A total of 1088 subjects completed the survey in 2019. The risk of death of the newborn was given high priority by women in all but one analyses, while the risk of severe perineal tears was always considered the least important attribute. The latent class analysis clearly revealed three classes of women. The largest class including 52.9% of women was interested in water birth if it could reduce pain and would be risk-free for the newborn. The second class included 30.8% of women interested in water immersion but only during the labor phase. Finally, the third class (16.2%) did not want to consider water immersion during labor and birth, regardless of its risks and benefits. Follow-up questions revealed that many women were interested in water birth only if they could be assured that there would be no risk for the newborn. DISCUSSION AND CONCLUSION: This study provided insights in favor of water immersion during labor and birth contingent upon the safety of the procedure for the newborn. STATEMENT OF SIGNIFICANCE: No discrete choice experiment on women's preference for water immersion during childbirth was previously conducted. Six attributes/factors were used for the discrete choice experiment. Water immersion is poorly used in Quebec with only 49 (7.9%) women over 621 with childbirth experience reporting such immersion. A majority of women (70-80%) were in favor of water immersion.

Mindfulness-based stress reduction to improve depression, pain and high patient global assessment in controlled rheumatoid arthritis.

Objective: The aim was to improve distressing patient-reported outcomes (PROs) that persisted in RA patients with clinically controlled inflammation (controlled RA). Methods: In a pragmatic pilot study, we offered mindfulness-based stress reduction (MBSR), a group intervention, to controlled RA patients who had high (≥16) Centre for Evaluation Studies depression (CES-D) scores and/or patient general assessment of disease activity (PGA) at least 2/10 larger than evaluator general assessment (EGA) (PGA-EGA: Delta). Evaluations before, 6 and 12 months after MBSR included CES-D, PGA, modified HAQ, simple disease activity index (SDAI), anxiety (general anxiety disorder 7; GAD-7), coping strategies (coping with health injuries and problems; CHIP), sleep disturbance and pain. Facilitators and obstacles to recruitment and participation were identified. A subset of patients was interviewed for qualitative analysis of their experience. Results: Out of 306 screened patients, 65 were referred, 39 (60%) agreed and 28 (43%) completed MBSR. Anticipated burden, timing and frequency of group meetings, commuting issues, age extremes and co-morbidities were barriers to participation. Up to 12 months after MBSR, anxiety, depression, emotion-oriented coping, sleep and function significantly improved. Nonetheless, no significant impact was observed on pain, PGA, Delta or SDAI. The interviews revealed that benefits, including integration of effective coping strategies, were maintained. Conclusion: We addressed MBSR feasibility issues and selection of outcomes in controlled RA patients with distressing PROs. For patients who chose to participate in MBSR, lasting benefits were evident for anxiety, depression, sleep and function. Larger studies are required to evaluate the weaker impact of MBSR on RA-related pain and PGA.

High-dose Radiotherapy or Androgen Deprivation Therapy (HEAT) as Treatment Intensification for Localized Prostate Cancer: An Individual Patient-data Network Meta-analysis from the MARCAP Consortium.

BACKGROUND: The relative benefits of radiotherapy (RT) dose escalation and the addition of short-term or long-term androgen deprivation therapy (STADT or LTADT) in the treatment of prostate cancer are unknown. OBJECTIVE: To perform a network meta-analysis (NMA) of relevant randomized trials to compare the relative benefits of RT dose escalation ± STADT or LTADT. DESIGN, SETTING, AND PARTICIPANTS: An NMA of individual patient data from 13 multicenter randomized trials was carried out for a total of 11862 patients. Patients received one of the six permutations of low-dose RT (64 to <74 Gy) ± STADT or LTADT, high-dose RT (≥74 Gy), or high-dose RT ± STADT or LTADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Metastasis-free survival (MFS) was the primary endpoint. Frequentist and Bayesian NMAs were performed to rank the various treatment strategies by MFS and biochemical recurrence-free survival (BCRFS). RESULTS AND LIMITATIONS: Median follow-up was 8.8 yr (interquartile range 5.7-11.5). The greatest relative improvement in outcomes was seen for addition of LTADT, irrespective of RT dose, followed by addition of STADT, irrespective of RT dose. RT dose escalation did not improve MFS either in the absence of ADT (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.80-1.18) or with STADT (HR 0.99, 95% CI 0.8-1.23) or LTADT (HR 0.94, 95% CI 0.65-1.37). According to P-score ranking and rankogram analysis, high-dose RT + LTADT was the optimal treatment strategy for both BCRFS and longer-term outcomes. CONCLUSIONS: Conventionally escalated RT up to 79.2 Gy, alone or in the presence of ADT, does not improve MFS, while addition of STADT or LTADT to RT alone, regardless of RT dose, consistently improves MFS. RT dose escalation does provide a high probability of improving BCRFS and, provided it can be delivered without compromising quality of life, may represent the optimal treatment strategy when used in conjunction with ADT. PATIENT SUMMARY: Using a higher radiotherapy dose when treating prostate cancer does not reduce the chance of developing metastases or death, but it does reduce the chance of having a rise in prostate-specific antigen (PSA) signifying recurrence of cancer. Androgen deprivation therapy improves all outcomes. A safe increase in radiotherapy dose in conjunction with androgen deprivation therapy may be the optimal treatment.