A Phase 2 Trial of Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma of the Bladder.

PURPOSE: Combination intravesical gemcitabine and docetaxel (GemDoce) has demonstrated efficacy as second-line therapy for patients with bacillus Calmette-Guérin (BCG)‒unresponsive nonmuscle-invasive urothelial carcinoma of the bladder (NMIBC). In the context of widespread BCG shortages, we performed a phase 2 prospective trial to assess GemDoce for BCG-naïve NMIBC. MATERIALS AND METHODS: This study is a prospective, single-arm, open-label phase 2 trial for patients with BCG-naïve high-risk NMIBC. Intravesical GemDoce was given weekly for 6 weeks as induction followed by monthly maintenance therapy for 2 years among responders. The primary end point was 3-month complete response, and key secondary end points included adverse events (AEs) and 12-month recurrence-free survival. RESULTS: Twenty-five patients were enrolled between August 2020 and August 2022 with median follow-up of 19.6 months. The pretreatment pathologic stages were high-grade (HG) T1 with carcinoma in situ (CIS; n = 7), HGT1 without CIS (n = 6), HGTa (n = 9), and CIS alone (n = 3). The 3-month complete response rate was 100% and recurrence-free survival at 12 months was 92%. Two patients with pretreatment HGT1 had HGT1 recurrences at 9 and 12 months. No patients progressed to T2 disease, underwent radical cystectomy, or had any radiographic evidence of progressive disease. Grade 1 AEs were common (23/25 patients) including hematuria, urinary frequency, urgency, and fatigue. Five patients (20%) experienced a grade 3 AE including hematuria and UTI. CONCLUSIONS: In this single-arm phase 2 trial, GemDoce was well tolerated with promising efficacy for patients with BCG-naïve high-risk NMIBC.

Surgical critical care: Is work-life expectancy increasing? An analysis of American Board of Surgery recertification rates across subspecialties.

The practice of surgical critical care (SCC) has traditionally necessitated additional in-house, extended night and weekend clinical commitments, which can be viewed as less desirable for many surgeons. Therefore, the authors have observed that some SCC surgeons elect to transition their practice to focus solely on general surgery (GS) rather than continuing practicing both SCC and GS. We hypothesized that surgeons with a practice focused on SCC are more likely to make the transition to a GS practice than those who have certification in other subspecialties that are certified through the American Board of Surgery.

Characteristics of Severe Non-Eosinophilic Asthma: Analysis of Data from 1075 Patients Included in the FASE-CPHG Study.

Purpose: Data on severe non-eosinophilic asthma are scarce. Moreover, as compared with eosinophilic asthma, non-eosinophilic asthma less frequently benefits from the latest therapeutic advances. This study aimed to highlight differences between non-eosinophilic and eosinophilic asthma as they may help the development of new therapeutic agents. Patients and Methods: Data from 1075 adult patients with severe asthma (GINA treatment: 4/5) collected during the cross-sectional non-interventional FASE-CPHG study were analyzed. Two groups of patients (EOS-/EOS+) were constituted based on blood eosinophil counts (cutoff value: 300 G/l). Characteristics of EOS- (N = 500) and EOS+ (N = 575) patients were described; EOS- patients were also described according to their allergic profile based on skin allergy or allergen-specific immunoglobulin E (IgE) assays (cutoff value: 150 IU/mL). Results: Percentages of patients with obesity (29%), allergen sensitization (57%), or ≥2 annual exacerbations in the last 12 months (68%) were similar in both groups. As compared with EOS+ patients, EOS- patients less frequently reported chronic rhinitis (41.1% vs 50.5%, p < 0.01) or nasal polyposis (13.6% vs 27.5%, p < 0.01), and more frequently reported GERD (45.2% vs 37.1%, p < 0.01), anxiety (45.5% vs 38.1%, p = 0.01), or depression (18.3% vs 13.3%, p = 0.02). EOS- patients had lower serum total IgE levels (median: 158 vs 319 IU/mL, p < 0.01) and were less frequently treated with long-term oral corticosteroid therapy (16.0% vs 23.7%; p < 0.01). Their asthma was more frequently uncontrolled (48% vs 40%, p < 0.01). Similar results were found with a cutoff value for blood eosinophil counts at 150 G/l. EOS- patients with allergic profile less frequently reported high serum IgE levels (35.6% vs 57.9%, p < 0.01). EOS- and EOS+ patients treated with long-term oral corticosteroids had similar profiles. Conclusion: In our patients with severe asthma, EOS- asthma was approximately as frequent as EOS+ asthma; EOS- asthma was frequently poorly controlled or uncontrolled, confirming the need for a better management. Allergy did not appear to worsen clinical profile.

Clinical Risk Factors Associated With Small Renal Mass Malignant Histology in a Multi-Ethnic Population Undergoing Partial Nephrectomy.

INTRODUCTION: Small renal masses (SRMs) are often incidentally diagnosed, and a large proportion are malignant. However, there is a paucity of data describing predictors of malignancy in minority patients with SRMs. Thus, our goal was to examine clinical risk factors associated with SRM malignant histology in patients undergoing partial nephrectomy (PN) a diverse, urban academic center. MATERIALS AND METHODS: Patients with a SRM undergoing PN at a single institution between 2010 to 2018 were reviewed. Demographic, clinical, and imaging characteristics were compared to pathology results. Logistic regression was used to examine associations between demographic/clinical variables for malignant and high-grade histology. RESULTS: In total, 331 patients who underwent PN for SRM were included. Of those, 264 (79.8%) had malignant histology while 67 (20.2%) had benign histology. The proportions of men and of current smokers were significantly higher among patients with malignant histology. In multivariate models, non-Hispanic Black (NHB) patients had increased odds of having malignant histology (OR 2.46, 95% CI: 1.01-5.99, P = .048) and current smokers (OR = 4.02; 95% CI 1.14-14.18, P = .031). Hispanic patients had a 3-fold increased risk of high-grade RCC (OR 3.06, 95% CI: 1.19-7.87, P = 0.02) compared to Non-Hispanic White patients. CONCLUSION: In our population, male sex, smoking, and NHB race/ethnicity was associated with an increased risk of malignancy in patients undergoing partial nephrectomy for SRM. Older age and Hispanic race/ethnicity were associated with high grade RCC. Our results suggest that urologists should exercise a higher level of vigilance in managing and treating SRM among NHB and Hispanic patients.

Increased Malignancy Rate in Children With IgE Deficiency: A Single-center Experience.

BACKGROUND: Immunoglobulin (Ig) E-deficient adults (IgE<2.5 kU/L) have increased susceptibility for developing malignancy. We evaluated the association between IgE deficiency and cancer diagnosis in children (age younger than 18 y), compared with those non-IgE-deficient (IgE≥2.5 kU/L). MATERIALS AND METHODS: Information about malignancy diagnosis were compared between 4 cohorts of children who had IgE levels measured at our institution: IgE-deficient (IgE<2.5 kU/L), normal IgE (2.5

Cognitive markers of dementia risk in middle-aged women with bilateral salpingo-oophorectomy prior to menopause.

Oophorectomy prior to menopause is associated with late-life dementia. Memory decline may start within 6 months after oophorectomy in middle-aged women, suggested by lower verbal and working memory performance. Unknown is whether such changes persist beyond 6 months, and whether they are reversed by estradiol. Short-term benefits of estradiol on verbal memory following oophorectomy were observed in one study, but longer term effects remain unknown. In the present study, middle-aged BRCA1/2 mutation carriers with early oophorectomy at least 1 year prior to study onset were tested on verbal and working memory with results stratified by (1) current estradiol use (n = 22) or (2) no history of estradiol use (n = 24), and compared to age-matched premenopausal controls (n = 25). Both memory abilities were adversely affected by oophorectomy, but only working memory was maintained by estradiol. Estrogen metabolite levels correlated with working memory, suggesting a role for estradiol in preserving this ability. Memory decline appears to persist after early oophorectomy, particularly for women who do not take estradiol.

Assessing the efficacy-effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population-based, real-world data for contemporary parenteral cancer therapeutics.

BACKGROUND: Although increasing evidence has suggested that an efficacy-effectiveness gap exists between clinical trial (CT) and real-world evidence (RWE), to the authors' knowledge, the magnitude of this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies. METHODS: Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population-based databases. The efficacy-effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1-year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan-Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates. RESULTS: Twenty-nine indications from 20 systemic therapies were included. Twenty-eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0-12.1 months). Lower effectiveness in RWE also was demonstrated through a meta-analysis of an OS hazard ratio of 1.58 (95% CI, 1.39-1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%-22%). CONCLUSIONS: An efficacy-effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2-month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real-world decision making regarding the use of cancer systemic therapies.

Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: A population-based propensity score-weighted analysis.

BACKGROUND: In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) have been publicly funded for first-line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic pancreatic cancer (mPC) since April 2015. We examined the real-world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC. METHODS: Patients receiving first-line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database. Baseline characteristics and outcomes were obtained through the Ontario Cancer Registry and other population-based databases. Overall survival (OS) was assessed using Kaplan-Meier and weighted Cox proportional hazard models, weighted by the inverse propensity score adjusting for baseline characteristics. Weighted odds ratio (OR) for hospitalization and emergency department visits (EDV) were estimated from weighted logistic regression models. RESULTS: For 1130 patients (632 FFX, 498 GnP), crude median OS was 9.6 and 6.1 months for FFX and GnP, respectively. Weighted OS was improved for FFX vs GnP (HR = 0.77, 0.70-0.85). Less frequent EDV and hospitalization were observed in FFX (EDV: 67.8%; Hospitalization: 49.2%) than GnP (EDV: 77.7%; Hospitalization: 59.3%). More frequent febrile neutropenia-related hospitalization was observed in FFX (5.8%) than GnP (3.3%). Risk of EDV and hospitalization were significantly lower for FFX vs GnP (EDV: OR = 0.68, P = .0001; Hospitalization: OR = 0.76, P = .002), whereas the risk of febrile neutropenia-related hospitalization was significantly higher (OR = 2.12, P = .001). Outcomes for uLAPC and mPC were similar. CONCLUSION: In the real world, FFX had longer OS, less frequent all-cause EDV and all-cause hospitalization, but more febrile neutropenia-related hospitalization compared to GnP.

Are population-based patient-reported outcomes associated with overall survival in patients with advanced pancreatic cancer?

BACKGROUND: Advanced pancreatic cancer (APC) patients often have substantial symptom burden. In Ontario, patients routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for nine symptoms (scale: 0-10), in cancer clinics. We explored the association between baseline patient-reported outcomes, via ESAS, and overall survival (OS). METHODS: Advanced pancreatic cancer patients with ESAS records prior to receiving publicly funded drugs from November 2008 to March 2016 were retrospectively identified from Cancer Care Ontario's administrative databases. We examined three composite ESAS scores: total symptom distress score (TSDS: 9 symptoms), physical symptom score (PHS: 6/9 symptoms), and psychological symptom score (PSS: 2/9 symptoms); Composite scores greater than defined thresholds (TSDS ≥36, PHS ≥24, PSS ≥8) were considered as high symptom burden. Crude OS was assessed using Kaplan-Meier method. Hazard ratios (HRs) were assessed using multivariable Cox models. Analysis was repeated in a sub-cohort with Eastern Cooperative Oncology Group (ECOG) status and metastasis. RESULTS: We identified 2199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving chemotherapy. Crude median survival was 4.5 and 7.3 months for high and low TSDS, respectively. High TSDS was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). In the sub-cohort (n = 393) with ECOG status and metastasis, high TSDS was also associated with lower OS (HR = 1.34, 95% CI: 1.04, 1.73). Similar trends were observed for PHS and PSS. CONCLUSIONS: Higher burden of patient-reported outcome was associated with reduced OS among APC patients. The effect was prominent after adjusting for ECOG status.

Improved survival in overweight and obese patients with aggressive B-cell lymphoma treated with rituximab-containing chemotherapy for curative intent.

The association between obesity and survival in non-Hodgkin lymphoma is unclear. Using the Ontario Cancer Registry we conducted a retrospective analysis of incident cases of aggressive-histology B-cell lymphoma treated with a rituximab-containing regimen with curative intent between 2008-2016. 6246 patients were included. On multivariable analysis the rate of all-cause mortality was lower for the overweight body mass index (BMI 25-29.9 kg/m2) (HR 0.85; 95%CI 0.77-0.95) and obese BMI (≥30 kg/m2) (HR 0.75; 95%CI 0.67-0.85) groups compared to the normal weight group (18.5-24.9 kg/m2). Binomial logistic regression analysis revealed a lower odds ratio (OR) of admission to hospital during treatment in the overweight (OR 0.84; 95%CI 0.75-0.95) compared to normal weight BMI group. In the largest cohort to date of aggressive-histology B-cell lymphoma patients treated with rituximab, increased BMI is associated with a survival advantage, and the magnitude of this effect increases from overweight to obese BMI.

A Substance Called Food: Long-Term Psychodynamic Group Treatment for Compulsive Overeating.

Obesity has proven difficult to treat. Many approaches neglect to address the deep-rooted underlying psychological issues. This paper describes a psychodynamically oriented approach to treating compulsive overeating as an addiction. Common to all addictions is a compulsion to consume a substance or engage in a behavior, a preoccupation with using behavior and rituals, and a lifestyle marked by an inability to manage the behavior and its harmful consequences. The approach represents a shift away from primarily medical models of intervention to integrated models focusing on the psychological underpinnings of obesity. Long-term psychodynamic group psychotherapy is recommended as a primary treatment.

Prenatal exposure to maternal cigarette smoking, amygdala volume, and fat intake in adolescence.

CONTEXT: Prenatal exposure to maternal cigarette smoking is a well-established risk factor for obesity, but the underlying mechanisms are not known. Preference for fatty foods, regulated in part by the brain reward system, may contribute to the development of obesity. OBJECTIVE: To examine whether prenatal exposure to maternal cigarette smoking is associated with enhanced fat intake and risk for obesity, and whether these associations may be related to subtle structural variations in brain regions involved in reward processing. DESIGN: Cross-sectional study of a population-based cohort. SETTING: The Saguenay Youth Study, Quebec, Canada. PARTICIPANTS: A total of 378 adolescents (aged 13 to 19 years; Tanner stage 4 and 5 of sexual maturation), half of whom were exposed prenatally to maternal cigarette smoking (mean [SD], 11.1 [6.8] cigarettes/d). MAIN OUTCOME MEASURES: Fat intake was assessed with a 24-hour food recall (percentage of energy intake consumed as fat). Body adiposity was measured with anthropometry and multifrequency bioimpedance. Volumes of key brain structures involved in reward processing, namely the amygdala, nucleus accumbens, and orbitofrontal cortex, were measured with magnetic resonance imaging. RESULTS: Exposed vs nonexposed subjects exhibited a higher total body fat (by approximately 1.7 kg; P = .009) and fat intake (by 2.7%; P = .001). They also exhibited a lower volume of the amygdala (by 95 mm3; P < .001) but not of the other 2 brain structures. Consistent with its possible role in limiting fat intake, amygdala volume correlated inversely with fat intake (r = -0.15; P = .006). CONCLUSIONS: Prenatal exposure to maternal cigarette smoking may promote obesity by enhancing dietary preference for fat, and this effect may be mediated in part through subtle structural variations in the amygdala.

The role of ovarian steroid hormones in mood.

Fluctuations in ovarian hormones across the menstrual cycle have long been considered a determinant of mood in women. The majority of studies, however, use menstrual cycle phase as proxy for hormone levels. We measured ovarian hormone levels directly in order to examine the relationship between daily hormone levels and mood in non-help-seeking women. Participants (n=19) provided daily information about their positive and negative moods, and collected their first morning-voided urine for 42days, which was analyzed for estrogen and progesterone metabolites (E1G and PdG). The independent contributions of daily E1G, PdG, stress, physical health, and weekly social support, were calculated for 12 daily mood items, and composite measures of positive and negative mood items, using linear mixed models. E1G or PdG contributed to few mood items: E1G measured 2days prior contributed negatively to the model for Motivation, while E1G measured 3days prior contributed negatively to Getting Along with Others, and E1G measured 4days prior contributed negatively to Anxiety. PdG, measured the same day and 1day prior, contributed positively to the models of Irritability, and PdG measured 5days prior contributed positively to Difficulty Coping. By contrast, the variables stress and physical health contributed significantly to all the mood items, as well as both composite positive and negative mood measures. These findings demonstrate that, compared to stress and physical health, ovarian hormones make only a small contribution to daily mood. Thus, fluctuations in ovarian hormones do not contribute significantly to daily mood in healthy women.

A randomized controlled study of contrast baths on patients with carpal tunnel syndrome.

STUDY DESIGN: Randomized clinical trial. INTRODUCTION: Contrast baths are a treatment modality commonly used in hand clinics. Yet the benefits of contrast baths have been poorly substantiated. Contrast baths have been suggested for the purposes of reducing hand volume, alleviating pain, and decreasing stiffness in affected extremities. PURPOSE OF THE STUDY: To determine the effects of specific contrast bath protocols on hand volume in patients diagnosed with Carpal Tunnel Syndrome. METHODS: Study participants were randomly assigned to one of three treatment group protocols--contrast baths with exercise, contrast baths without exercise, and an exercise-only control treatment group. Study participants were evaluated with hand volumetry, before and after treatment at two different data collection periods-pre- and postoperatively. RESULTS: Data were gathered on 58 participants before Carpal Tunnel Release surgery and on 56 participants after Carpal Tunnel Release surgery, for a total of 114 treatments. The changes in hand volume (the after treatment volume minus the before treatment volume) were analyzed using one-way and multi-way analysis of variance (ANOVA). Although all three treatments resulted in a slight increase in hand volume both pre- and postsurgery, the increase was not clinically significant with regard to hand volumes. Also no significant differences were noted among the three treatments. Specifically, the ANOVA for presurgery differences among treatments had F=0.155 (2 and 55 df), p=0.857. The ANOVA for postsurgery difference among treatments had F=0.544 (2 and 53 df), p=0.584. CONCLUSIONS: The use of contrast bath treatment has no significant effect on increase or decrease of hand volume in Carpal Tunnel Syndrome patients, pre- and/or postoperatively. LEVEL OF EVIDENCE: 1B.

Tracking chronic disease and risk behavior prevalence as survey participation declines: statistics from the behavioral risk factor surveillance system and other national surveys.

INTRODUCTION: Response rates for the Behavioral Risk Factor Surveillance System (BRFSS) have declined in recent years. The response rate in 1993 was approximately 72%; in 2006, the response rate was approximately 51%. To assess the impact of this decline on the quality of BRFSS estimates, we compared selected health and risk factor estimates from BRFSS with similar estimates from the National Health Interview Survey (NHIS) and the National Health and Nutrition Examination Survey (NHANES). METHODS: We reviewed questionnaires from the 3 surveys and identified a set of comparable measures related to smoking prevalence, alcohol consumption, medical conditions, vaccination, health status, insurance coverage, cost barriers to medical care, testing for human immunodeficiency virus, and body measurements (height and weight). We compared weighted estimates for up to 15 outcome measures, including overall measures and measures for 12 population subgroups. We produced design-appropriate point estimates and carried out statistical tests of hypotheses on the equality of such estimates. We then calculated P values for comparisons of NHIS and NHANES estimates with their BRFSS counterparts. RESULTS: Although BRFSS and NHIS estimates were statistically similar for 5 of the 15 measures examined, BRFSS and NHANES estimates were statistically similar for only 1 of 6 measures. The observed differences for some of these comparisons were small, however. CONCLUSION: These surveys produced similar estimates for several outcome measures, although we observed significant differences as well. Many of the observed differences may have limited consequences for implementing related public health programs; other differences may require more detailed examination. In general, the range of BRFSS estimates examined here tends to parallel those from NHIS and NHANES, both of which have higher rates of participation.

Hands across the water: clinical observations of hand therapy practices in Great Britain and Norway.

The Evelyn Mackin Traveling Hand Therapist Award is a new award established in 2004 by the American Hand Therapy Foundation. This award was named in honor of Evelyn Mackin, a distinguished leader in hand therapy rehabilitation. Ms. Mackin enthusiastically endorses worldwide networking among hand therapists. She strongly believes in the value of sharing knowledge and technical skills. This award enables members of the ASHT to travel, learn new concepts or skills, and share them with the American hand therapy community. Visits to clinics in Great Britain and Norway revealed similarities and differences between European and American hand therapy practice. Clinical observations explore tendon transfer rehabilitation, cold sensitivity, sensory desensitization and re-education, Dupuytren's contracture, and clinic design. Other highlighted topics include delivery of health care services, hand therapist certification, and the unique contributions of Occupational Therapy and Physiotherapy to the practice of hand therapy. A hand therapy practice survey focuses on treatment and practice issues, continuing education, and challenges facing hand therapist colleagues abroad.