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.

Glycopyrronium 320 µg/mL in children and adolescents with severe sialorrhoea and neurodisabilities: A randomized, double-blind, placebo-controlled trial.

AIM: To investigate the efficacy, safety, and impact on quality of life (QoL) of an oral formulation of 320 µg/mL glycopyrronium designed for children. METHOD: A double-blind, placebo-controlled SALIVA (Sialanar plus orAl rehabiLitation against placebo plus oral rehabilitation for chIldren and adolescents with seVere sialorrhoeA and neurodisabilities) trial was conducted. Children (3-17 years) with neurodisabilities and severe sialorrhoea (modified Teachers Drooling Scale ≥6) were randomized to 320 µg/mL glycopyrronium or placebo, in addition to non-pharmacological standard care. RESULTS: Of 87 participants, 44 were aged 10 years or under and 43 had cerebral palsy. The primary endpoint, change in total Drooling Impact Scale (DIS) score from baseline to day 84, was significantly greater (improved) with 320 µg/mL glycopyrronium versus placebo (median [quartile 1, quartile 3] -29.5 [-44.5, 0] vs -1 [-16, 5]; p < 0.001), an effect also observed at day 28 (median - 25 vs -2; p < 0.01). Significant reduction in bibs/clothes used per day was seen with glycopyrronium versus placebo at day 84 (median - 2 vs 0; p < 0.01). Glycopyrronium significantly improved DIS items 9 and 10 related to the extent that drooling affects the child's and family's life (p ≤ 0.03). Adverse events were reported by 77.3% and 69.8% of children with glycopyrronium and placebo respectively; the most common treatment-related adverse event was constipation (20.5% and 16.3%). INTERPRETATION: The formulation of 320 µg/mL glycopyrronium significantly improved drooling and reduced its impact on QoL, with good tolerability in children with neurodisabilities. WHAT THIS PAPER ADDS: The formulation of 320 µg/mL glycopyrronium significantly improved Drooling Impact Scale score versus placebo at day 84. The formulation reduced the impact of drooling on the child's and family's quality of life. There were no safety or tolerability concerns with this specific formulation.

Perspectives on remote learning of orthotic fabrication by certified hand therapists.

BACKGROUND: The COVID-19 pandemic caused disruption to continuing educational opportunities for hand therapists. In response, some courses were offered via online platforms, including virtual orthotic fabrication courses. It is important to determine the effectiveness and benefits of these courses for educating certified hand therapists and examine if remote learning of orthotic fabrication skills has continued merit and relevance. PURPOSE: To investigate the value and effectiveness of orthotic fabrication courses taught in a virtual format. STUDY DESIGN: Cross-sectional, mixed methods survey study. METHODS: A 31-item survey consisting of Likert-type, direct response, and open-ended questions about experiences and opinions of virtual orthotics courses was electronically delivered to certified hand therapists. Data analysis included descriptive and correlational statistics to highlight frequencies, ranges, and relationships between the participant demographics and opinions/experiences. Thematic analysis guided the coding of the qualitative data. RESULTS: A total of 459 responded, with a response rate of 9.7%. Most respondents had not participated in online courses on orthotic fabrication. Those that did reported high satisfaction but noted that clinical experience and knowledge from previous courses influenced this experience. Most participants felt that novice clinicians and students would not gain enough skills and confidence from online courses. However, participants with all levels of experience found the courses to be of value. CONCLUSIONS: Results suggest that while online learning of this skill set is valuable and effective, it is most beneficial for experienced clinicians. Disadvantages included the lack of instructor feedback necessary for hands-on skill development and the lack of peer interaction. Advantages included convenience of time, cost, accessibility, and the ability to revisit the topic as needed. Online learning of orthotic fabrication skills is a sustainable option for clinicians seeking to advance their skills. Nevertheless, it is not a substitute for initial training for novice hand therapists due to the lack of feedback and skill development.

Relative motion orthoses: fabrication tips.

Relative Motion (RM) orthoses are an extremely important and beneficial intervention in hand rehabilitation. They can be used for a variety of hand conditions including for positioning, protection, alignment and exercise. In order to achieve the intended goals of this orthotic intervention, the clinician must pay attention to detail during its fabrication. The purpose of this manuscript is to offer some simple and practical fabrication tips for hand therapists who want to include the use of RM orthoses to manage these different clinical conditions. Photos are provided to reinforce some of the key concepts.

Utilization of 3D printed orthoses for musculoskeletal conditions of the upper extremity: A systematic review.

STUDY DESIGN: Systematic Review INTRODUCTION: 3D printed orthoses are emerging as a possible option in the field of hand therapy to fabricate conventional casts and orthoses. It is unknown how this technology is currently being used to treat upper extremity musculoskeletal conditions, and if 3D orthoses are comparable to custom- made low temperature thermoplastic orthoses fabricated by hand therapists. PURPOSE OF THE STUDY: The primary aim of this review was to investigate the utilization, effectiveness and feasibility of 3D printed technology to manufacture custom orthoses for musculoskeletal conditions of the upper extremity. METHODS: Studies describing 3D printed orthoses or casts used in treatment with patients were included following a comprehensive literature search using CINAHL, PubMed, Medline, ProQuest, and EBSCO databases. The selected studies had to address musculoskeletal conditions of the elbow, wrist, hand and/or digits that would typically be immobilized with a cast or brace or orthotic or orthosis. RESULTS: Ten studies met the inclusion criteria. Study designs included case studies, case series, and 1 randomized clinical trial. 3D printed orthoses/casts appear to be comfortable, provide adequate immobilization, and have pleasing aesthetics. However, expensive equipment, lack of appropriate software and scanning tools and lack of highly skilled clinicians are all factors preventing the implementation of 3D printed orthoses into current clinical practice. DISCUSSION: 3D printed orthoses appear to be effective at immobilization of a limb, aesthetically pleasing, and utilize lightweight and well -ventilated materials. However, the feasibility of implementing 3D printing technology in hand therapy settings remains challenging in part due to the resources required. CONCLUSIONS: While 3D printing shows promise, the high cost of equipment, lack of training and skill of clinicians and the long time required for production are all factors that need to be improved to make 3D printing a viable option in the hand therapy setting.

Comparison of Neuropsychological Assessment by Videoconference and Face to Face.

OBJECTIVE: To compare the administration of neuropsychological tests by teleneuropsychology (TeleNP) and face to face (F-F) in order to determine the feasibility and reliability of TeleNP. METHOD: At the inclusion visit, all participants underwent a traditional F-F neuropsychological assessment as part of their standard care. Four months after inclusion, they were randomized to undergo an additional neuropsychological assessment either by F-F administration or by TeleNP. RESULTS: A total of 150 adults with cognitive complaints, but with no major cognitive or sensorial impairment were included. At 4 months, 69 participants were randomized in the F-F arm and 71 in TeleNP arm (10 lost in the follow-up). The overall satisfaction was high: 87.1% in the TeleNP arm were "very satisfied", and 82.9% indicated no preference between F-F and TeleNP. In agreement with previous data from the literature, neuropsychological assessments gave similar results across both administration conditions for a large majority of tests [Mini-Mental State Examination (MMSE), Free and Cued Selective Reminding Test (FCSRT) French version, Mahieux gestural praxis battery, Frontal Assessment Battery (FAB), time of completion of the Trail making Test (TMT) A and B, number of errors of the TMT B, Rey complex figure test, categorical et phonological verbal fluency tests] and minor differences for others [80-picture naming test (DO-80), FAB, Digit Span forward and backward and number of errors in the TMT A]. CONCLUSIONS: TeleNP is a promising method to be able to test patients as an alternative to F-F condition. Before this procedure can be generalized, it is now necessary to standardize the adaptation of certain tests and to test them in populations with more significant cognitive disorders.

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

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.

Teaching orthotic design and fabrication content in occupational therapy curricula: Faculty perspectives.

STUDY DESIGN: Cross-sectional survey study. INTRODUCTION: Occupational therapy (OT) programs must provide students with the skills necessary to fabricate orthoses. Input from OT educators can provide valuable insight into how these skills are taught and the resources used. PURPOSE OF THE STUDY: Explore how instruction in orthotic fabrication is addressed in OT education programs. METHODS: Surveys were distributed to all accredited OT programs in the United States. Quantitative data were analyzed using descriptive statistics, and content analysis was done on qualitative data to identify themes. RESULTS: Overall response rate was 25%. Most programs teach orthotic fabrication with demonstration and hands-on laboratory time. Almost half add digital videos in their orthotic course content. The average number of orthoses made ranged from 2 to 5, and the resting hand, wrist, and short opponens immobilization orthoses are the most commonly taught. DISCUSSION: This study examined the orthotic fabrication curricula in OT programs in the United States, including the time devoted to this topic, types of orthoses covered, course structure and pedagogical strategies used, and whether faculty anticipated changes in their orthotic content. The majority of programs offer this content within other existing courses within the curriculum, including coursework in physical dysfunction, OT interventions, orthopedics, and biomechanics. Only 15% of participants in the current study reported teaching orthotic content as a separate course in their curricula. Interestingly, some participants reported that they plan to offer a full separate orthotics course in their future curricula, whereas others reported combining orthotics content with other coursework or reducing the time spent making custom orthoses in the classroom. It would appear that there is still considerable variability in course structure and content in current OT programs. CONCLUSION: Participants feel that orthotic fabrication is an essential and integral component of their curricula and that the importance of hands-on learning experiences contributes to students' preparedness and ability to use this knowledge. Student feedback indicated that more time and instruction is desired. Sharing teaching experiences can enhance emerging OT curricula and can impact future practice. Educators must strive to improve and refine curricular content to ensure that graduates have the skills necessary to meet the orthotic needs of their clients.

Age- and sex-related variations in vocal-tract morphology and voice acoustics during adolescence.

Distinct differences in the human voice emerge during adolescence, with males producing deeper and more resonant voices than females by the end of sexual maturation. Using magnetic resonance images of heads and voice recordings obtained in 532 typically developing adolescents, we investigate what might be the drivers of this change in voice, and the subjective judgment of the voice "maleness" and "femaleness". We show clear sex differences in the morphology of voice-related structures during adolescence, with males displaying strong associations between age (and puberty) and both vocal-fold and vocal-tract length; this was not the case in female adolescents. At the same time, males (compared with females) display stronger associations between age (and puberty) with both fundamental frequency and formant position. In males, vocal morphology was a mediator in the relationship between bioavailable testosterone and acoustic indices. Subjective judgment of the voice sex could be predicted by the morphological and acoustic parameters in males only: the length of vocal folds and its acoustic counterpart, fundamental frequency, is a larger predictor of subjective "maleness" of a voice than vocal-tract length and formant position.

An alternative fabrication method of the dart thrower's motion orthosis (also known as the dart orthosis).

To allow safe early wrist motion after wrist injury, this author has modified an earlier version of a dart thrower's motion orthotic device using material that is currently available on the market and an inexpensive paper fastener as the rivet. - KristinValdes, OTD, OT, CHT, Practice Forum Editor.

Adiposity is associated with structural properties of the adolescent brain.

Obesity, a major risk factor for cardiometabolic disease, is associated with variations in a number of structural properties in the adult brain, as assessed with magnetic resonance imaging (MRI). In this study, we investigated the cross-sectional relationship between visceral fat (VF), total body fat (TBF) and three MRI parameters in the brains of typically developing adolescents: (i) T1-weighted (T1W) signal intensity; (ii) T1W signal contrast between white matter (WM) and gray matter (GM); and (iii) magnetization transfer ratio (MTR). In a community-based sample of 970 adolescents (12-18 years old, 466 males), VF was quantified using MRI, and total body fat was measured using a multifrequency bioimpedance. T1W images of the brain were used to determine signal intensity in lobar GM and WM, as well as WM:GM signal contrast. A magnetization transfer (MT) sequence of MT(ON) and MT(OFF) was used to obtain MTR in GM and WM. We found that both larger volumes of VF and more TBF were independently associated with higher signal intensity in WM and higher WM:GM signal contrast, as well as higher MTR in both GM and WM. These relationships were independent of a number of potential confounders, including age, sex, puberty stage, household income and height. Our results suggest that both visceral fat and fat deposited elsewhere in the body are associated independently with structural properties of the adolescent brain. We speculate that these relationships suggest the presence of adiposity-related variations in phospholipid composition of brain lipids.

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.

The use of joint mobilization to improve clinical outcomes in hand therapy: a systematic review of the literature.

STUDY DESIGN: Systematic review. INTRODUCTION: Joint mobilizations are used as an intervention for improving range of motion, decreasing pain and ultimately improving function in patients with a wide variety of upper extremity diagnoses. However, there are only a limited number of studies describing this treatment for conditions affecting the elbow, wrist, and hand. Furthermore, it is unclear as to the most effective joint mobilization technique utilized and the most beneficial functional outcomes gained. PURPOSE: Examine the current evidence describing joint mobilizations for treatment of conditions of the elbow, wrist and hand, and offer informative practical clinical guidance. METHODS: Twenty-two studies dated between 1980 and 2011 were included in the systematic review for analysis. RESULTS: The current evidence provides moderate support for the inclusion of joint mobilizations in the treatment of lateral epicondylalgia (LE). In particular, mobilization with movement as described by Mulligan is supported with evidence from nine randomized clinical trials as an effective technique for the treatment of pain. Other described techniques include those known as Kaltenborn, Cyriax physical therapy, and Maitland, but the evidence for these techniques is limited. There is also limited evidence for the joint mobilizations in the treatment of wrist and hand conditions. CONCLUSIONS: The current literature offers limited support for joint mobilizations of the wrist and hand, and moderate support for joint mobilizations of the elbow for LE. There is moderate support for mobilization with movement. .

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.

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.