Occupational hazards and pregnancy in orthopaedics: female surgeons are at increased risk of infertility and pregnancy complications.

Female surgeons have increased rates of infertility and pregnancy complications compared to the general population. Reported infertility rates in surgeons are 32% compared to 10.9% in the general population. Reported pregnancy complication rates in surgeons range from 25% to 35%. In the orthopaedic operating theatre occupational hazards that have an effect on pregnancy outcomes include radiation, exposure to methyl methacrylate in bone cement, surgical smoke, sharps injuries, exposure to anaesthetic waste gases and the effects of the physical demands of surgery including prolonged work hours and night shift work. Outside the operating theatre exposure to nitrous oxide, formaldehyde, surgical scrub also have evidence of negative pregnancy outcomes. This review summarizes the available evidence as it relates to specific occupational hazards that face health workers in an orthopaedic operating theatre. This information, while targeted at orthopaedic health workers, is also relevant to anaesthetists, radiographers, nursing staff, medical device company representatives and female surgeons in other specialties.

Pregnancy Outcomes After Laparoscopic Radiofrequency Ablation of Uterine Leiomyomas Compared With Myomectomy.

OBJECTIVE: To compare pregnancy outcomes after laparoscopic radiofrequency ablation and myomectomy. METHODS: The ULTRA (Uterine Leiomyoma Treatment With Radiofrequency Ablation) study is an ongoing multicenter prospective cohort study with longitudinal follow-up up to 5 years comparing outcomes of radiofrequency ablation with myomectomy in premenopausal women older than age 21 years with symptomatic uterine leiomyomas. Participants were queried every 6 months after surgery to assess the incidence of pregnancy and pregnancy outcomes. RESULTS: Among 539 women enrolled in ULTRA, a total of 37 participants (mean age at first pregnancy 35.0±4.7 years) conceived 43 times as of March 2023 (22 radiofrequency ablation, 21 myomectomy). The average length of follow-up time after all procedures was 2.5±1.0 years. The baseline miscarriage rate in the study population was 33.3%. In participants who underwent radiofrequency ablation, 9 of 22 pregnancies (40.9%, 95% CI, 20.3-61.5%) ended in first-trimester miscarriage, 11 resulted in live births (50.0%, 95% CI, 29.1-70.9%), one resulted fetal death at 30 weeks of gestation, and one resulted in uterine rupture during miscarriage treatment with misoprostol 10 weeks after radiofrequency ablation. Among the live births in the radiofrequency ablation group, 45.5% were by vaginal delivery. In the myomectomy group, 9 of 21 pregnancies (42.9%, 95% CI, 21.7-64.0%) ended in first-trimester miscarriage and 12 resulted in live births (57.1%, 95% CI, 36.0-78.3%). There were no significant differences in the likelihood of live birth or miscarriage between the study groups. CONCLUSION: Full-term pregnancy and vaginal delivery are achievable after radiofrequency ablation of leiomyomas. However, in this interim analysis, the miscarriage rate in both radiofrequency ablation and myomectomy groups was higher than expected for women in this age group. Long-term data collection in the ongoing ULTRA study aims to further understand pregnancy outcomes after radiofrequency ablation compared with myomectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT0210094.

Outcomes of proximal humerus fractures in children: a retrospective cohort study.

OBJECTIVE: Paediatric proximal humerus fractures (PHFs) have historically been treated non-operatively. However, the management of severely displaced PHFs in older children has been debated over the years, with contemporary studies advocating for surgery. The purpose of this study was to review the outcomes of a cohort of paediatric patients treated for a PHF to guide management of future paediatric PHFs. METHODS: The records of the Women's and Children's Hospital in South Australia were reviewed to identify paediatric PHFs occurring between 1 January 2010 and 1 June 2020. Participants completed the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), the Shoulder Pain and Disability Index, and the Paediatric Outcomes Data Collection Instrument via phone interview. Participants' shoulder range-of-motion was assessed via telehealth using Zoom. Multivariable logistic regression was used to identify patient and clinical variables that were associated with a poorer outcome. RESULTS: Of 307 patients contacted, 125 participated. Forty-six patients met the definition of a poorer clinical outcome, defined as a QuickDASH score of ≥2. Fractures of greater severity were predictive of a poorer outcome, and patients aged ≥12 years old at the time of injury had higher total QuickDASH scores. The findings did not suggest that these subgroups of patients have superior outcomes if treated surgically. CONCLUSION: The majority of paediatric PHFs have an acceptable clinical outcome, irrespective of treatment methodology. Multicentre prospective studies are required to establish the indications for surgery for adolescent patients with severely displaced PHFs.

Factors Influencing Music Therapists' Retention of Clinical Hours with Autistic Clients over Telehealth During the COVID-19 Pandemic.

The 2019 coronavirus disease pandemic influenced music therapists to migrate services to online platforms, though some lost clinical hours during the pandemic when telehealth was not a viable option. This survey study aimed to ascertain factors that helped music-based therapists to continue serving autistic clients over telehealth during the pandemic. We surveyed 193 accredited music therapists located mainly in Canada and the US. In addition to gathering data on general perceptions of telehealth music therapy and Neurologic Music Therapy (NMT), one-way ANOVAs were applied to determine differences in percent-change loss of clinical hours for music therapists: (1) working in different employment settings; (2) serving children, youth, adults, or a mixture of ages; and (3) practicing NMT or not. The general perception of telehealth music therapy was positive, and NMTs believed that the clear protocols and transformation design model were helpful to them in adapting services to telehealth. There were no significant differences in percent-change of clinical hours among music therapists in different employment settings or serving different client age groups. Music therapists who said they practiced within the NMT treatment model lost a significantly lower percentage of clinical hours with autistic clients than those who did not practice NMT. Possible reasons for this result and the need for further research are discussed.

Language and pain predict persistent depression among seriously ill home care clients.

OBJECTIVES: This study examined potential predictors of persistent depressive symptoms in a cohort of seriously ill older adults (aged 65+ years) receiving home care services. METHODS: This was a retrospective cohort study using secondary data collected from the Resident Assessment Instrument for Home Care for all assessments completed between 2001 and 2020. The cohort included seriously ill individuals with depressive symptoms at baseline and who continued to have depressive symptoms on reassessment within 12 months (n = 8,304). Serious illness was defined as having severe health instability, a prognosis of less than 6 months, or a goal of care related to palliative care (PC) on admission to the home care program. RESULTS: The mean age of the sample was 80.8 years (standard deviation [SD] = 7.7), 61.1% were female, and 82.1% spoke English as their primary language. The average length of time between assessments was 4.9 months (SD = 3.3). During that time, 64% of clients had persistent symptoms of depression. A multivariate logistic regression model found that language, pain, caregiver burden, and cognitive impairment were the most significant predictors of experiencing persistent depressive symptoms. SIGNIFICANCE OF RESULTS: Persistent depressive symptoms are highly prevalent in this population and, left untreated, could contribute to the person experiencing a "bad death." Some of the risk factors for this outcome are amenable to change, making it important to continually assess and flag these factors so interventions can be implemented to optimize the person's quality of life for as long as possible.

Development and validation of risk of CPS decline (RCD): a new prediction tool for worsening cognitive performance among home care clients in Canada.

BACKGROUND: To develop and validate a prediction tool, or nomogram, for the risk of a decline in cognitive performance based on the interRAI Cognitive Performance Scale (CPS). METHODS: Retrospective, population-based, cohort study using Canadian Resident Assessment Instrument for Home Care (RAI-HC) data, collected between 2010 and 2018. Eligible home care clients, aged 18+, with at least two assessments were selected randomly for model derivation (75%) and validation (25%). All clients had a CPS score of zero (intact) or one (borderline intact) on intake into the home care program, out of a possible score of six. All individuals had to remain as home care recipients for the six months observation window in order to be included in the analysis. The primary outcome was any degree of worsening (i.e., increase) on the CPS score within six months. Using the derivation cohort, we developed a multivariable logistic regression model to predict the risk of a deterioration in the CPS score. Model performance was assessed on the validation cohort using discrimination and calibration plots. RESULTS: We identified 39,292 eligible home care clients, with a median age of 79.0 years, 62.3% were female, 38.8% were married and 38.6% lived alone. On average, 30.3% experienced a worsening on the CPS score within the six-month window (i.e., a change from 0 or 1 to 2, 3, 4, 5, or 6). The final model had good discrimination (c-statistic of 0.65), with excellent calibration. CONCLUSIONS: The model accurately predicted the risk of deterioration on the CPS score over six months among home care clients. This type of predictive model may provide useful information to support decisions for home care clinicians who use interRAI data internationally.

Phase Ib study of HSP90 inhibitor, onalespib (AT13387), in combination with paclitaxel in patients with advanced triple-negative breast cancer.

Background: Heat shock protein 90 (HSP90) is a molecular chaperone required for stabilization of client proteins over-activated in triple-negative breast cancer (TNBC). Over-expression of HSP90 client proteins has been implicated in paclitaxel resistance. Onalespib (AT13387) is a potent inhibitor of HSP90 that could improve paclitaxel efficacy when administered in combination. Design: This phase Ib trial administered onalespib with paclitaxel in patients with advanced TNBC to assess safety and establish a recommended phase II dose (RP2D). Objectives: The primary objectives were determining the dose-limiting toxicities and maximum tolerated dose of combination therapy. Secondary objectives included pharmacokinetic (PK) analysis and determination of overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Methods: Patients with advanced TNBC were treated with standard dose intravenous paclitaxel in combination with intravenous onalespib at doses ranging from 120 to 260 mg/m2 administered on days 1, 8, and 15 of a 28-day cycle using a standard 3 + 3 design. A total of 15 patients were enrolled to dose expansion cohort at RP2D to confirm safety profile. Results: Thirty-one patients were enrolled in the study, of which over 90% had received prior taxane therapy. Paclitaxel was given for metastatic disease in 23% of patients. Adverse events (AEs) included anemia (grade 3: 20%), lymphopenia (grade 3: 17%), and neutropenia (grade 3: 33%, grade 4: 4%). The most frequent grade ⩾3 non-hematologic AE was diarrhea (7%). The established RP2D was 260 mg/m2 onalespib when given with paclitaxel at 80 mg/m2. PK analysis revealed a modest drug interaction profile for onalespib in the combination regimen. ORR was 20%. Three patients achieved complete responses, all of whom had received prior taxane therapy. Median DOR was 5.6 months; median PFS was 2.9 months. Conclusion: Combination treatment with onalespib and paclitaxel had an acceptable toxicity profile and RP2D was determined to be 260 mg/m2 of onalespib. Combination therapy showed antitumor activity in patients with advanced TNBC. Trial registration: Onalespib and paclitaxel in treating patients with advanced TNBC https://clinicaltrials.gov/ct2/show/NCT02474173.

Phase 1b study of HSP90 inhibitor called onalespib in combination with paclitaxel in patients with advanced triple-negative breast cancer This Phase 1b study demonstrated that treatment with a combination of onalespib and paclitaxel was reasonably well tolerated by most patients. Onalespib at 260 mg/m² given intravenously on days 1, 8 and 15 on 28-day cycles in combination with standard dose and schedule of paclitaxel was established as the recommended phase 2 dose for further clinical development. Despite minor drug-drug interactions between these 2 agents, onalespib did not alter paclitaxel exposure and paclitaxel did not affect exposure to onalespib. While onalespib with paclitaxel combination therapy did not yield durable objective responses or prolonged progression-free survival, there were several patients with long-lasting benefit from this combination including patients who previously experienced progression on taxane therapy.

Retrospective cohort study of CDK4/6-inhibitor-induced alopecia in breast cancer patients.

PURPOSE: Dermatologic adverse events commonly result in the interruption of oncologic treatment, and targeted therapies are the most frequently interrupted class of anticancer agents. Alopecia is a common cutaneous adverse event reported with CK4/6i therapy. Though the clinical characteristics and therapeutic response of EIA have been well documented, few studies have characterized alopecia in patients treated with CDK4/6i. METHODS: This study analyzed a retrospective cohort of 28 breast cancer patients diagnosed with endocrine-induced alopecia (EIA) or CDKiA. Comparative analysis of the clinical characteristics of alopecia and therapeutic response to minoxidil was conducted. Therapeutic response to minoxidil (LDOM or topical [5%] solution or foam) was assessed by both Dean Scale and qualitative clinical improvement by comparison of pretreatment and posttreatment clinical images by single-blinded, board-certified academic dermatologists (ST and BD). RESULTS: CDKiA was clinically similar to androgenetic alopecia and specific vertex involvement was more common in patients treated with CDK4/6i + ET than endocrine monotherapy (n = 7 [70.0%] vs n = 4 [36.4%]; p = 0.04), respectively. After 4-6 months of minoxidil, there was a moderate to significant qualitative alopecia improvement in 80% of CDKiA patients versus 94.4% of EIA patients. Additionally, superior improvement of mean Dean Score grade was observed in EIA (with change from pre- to posttreatment - 0.44; p = 0.0002). CONCLUSION: Compared to endocrine monotherapy, patients on combination CDK4/6i + ET had greater extent of vertex involvement and were more recalcitrant to minoxidil. The preferential vertex involvement observed in CDKiA suggests that combination therapy with minoxidil and topical antiandrogens with poor systemic absorption should be studied in this setting.

Elucidating Novel Targets for Ovarian Cancer Antibody-Drug Conjugate Development: Integrating In Silico Prediction and Surface Plasmon Resonance to Identify Targets with Enhanced Antibody Internalization Capacity.

Antibody-drug conjugates (ADCs) constitute a rapidly expanding category of biopharmaceuticals that are reshaping the landscape of targeted chemotherapy. The meticulous process of selecting therapeutic targets, aided by specific monoclonal antibodies' high specificity for binding to designated antigenic epitopes, is pivotal in ADC research and development. Despite ADCs' intrinsic ability to differentiate between healthy and cancerous cells, developmental challenges persist. In this study, we present a rationalized pipeline encompassing the initial phases of the ADC development, including target identification and validation. Leveraging an in-house, computationally constructed ADC target database, termed ADC Target Vault, we identified a set of novel ovarian cancer targets. We effectively demonstrate the efficacy of Surface Plasmon Resonance (SPR) technology and in vitro models as predictive tools, expediting the selection and validation of targets as ADC candidates for ovarian cancer therapy. Our analysis reveals three novel robust antibody/target pairs with strong binding and favourable antibody internalization rates in both wild-type and cisplatin-resistant ovarian cancer cell lines. This approach enhances ADC development and offers a comprehensive method for assessing target/antibody combinations and pre-payload conjugation biological activity. Additionally, the strategy establishes a robust platform for high-throughput screening of potential ovarian cancer ADC targets, an approach that is equally applicable to other cancer types.

Survival outcomes seen with neoadjuvant chemotherapy in the management of locally advanced inflammatory breast cancer (IBC) versus matched controls.

Inflammatory breast cancer (IBC) poses an ongoing challenge as rates of disease recurrence and mortality remain high compared to stage-matched controls. However, frontline therapy has evolved through the years, including the widespread use of neoadjuvant chemotherapy (NAC) given the prognostic importance of pathologic complete response (pCR). Due to these sweeping changes, we need new data to assess current recurrence and survival outcomes for locally advanced IBC in the context of matched non-inflammatory controls. We conducted a retrospective analysis of institutional IBC data from 2010 to 2016 with the primary objective of comparing overall survival (OS), relapse-free survival (RFS), and distant relapse-free survival (DRFS). We matched IBC patients to non-inflammatory controls based on age, receptor status, tumor grade, clinical stage, and receipt of prior NAC. Secondary objectives included assessing pCR rates and identifying prognostic factors. Among NAC recipients, we observed similar pCR rates (47.6 % vs. 49.4 %, p = 0.88) between IBC (n = 84) and matched non-IBC (n = 81) cohorts. However, we noted a significant worsening of OS (p = 0.0001), RFS (p = 0.0001), and DRFS (p = 0.001) in the IBC group. Specifically, 5-year OS in the IBC cohort was 58.9 % vs. 86.7 % for matched controls (p = 0.0003). Older age was a weak negative predictor for OS (HR 1.03, p = 0.001) and RFS (HR 1.02, p = 0.01). For DRFS, older age was also a weak negative predictor (HR 1.02, p = 0.02), whereas the use of NAC was a positive predictor (HR 0.47, p = 0.02). Despite no clear difference in pCR, survival outcomes remain poor for IBC compared to matched non-inflammatory controls.

Ethical Aspects of Physician Decision-Making for Deprescribing Among Older Adults With Dementia.

Importance: Physicians endorse deprescribing of risky or unnecessary medications for older adults (aged ≥65 years) with dementia, but there is a lack of information on what influences decisions to deprescribe in this population. Objective: To understand how physicians make decisions to deprescribe for older adults with moderate dementia and ethical and pragmatic concerns influencing those decisions. Design, Setting, and Participants: A cross-sectional national mailed survey study of a random sample of 3000 primary care physicians from the American Medical Association Physician Masterfile who care for older adults was conducted from January 15 to December 31, 2021. Main Outcomes and Measures: The study randomized participants to consider 2 clinical scenarios in which a physician may decide to deprescribe a medication for older adults with moderate dementia: 1 in which the medication could cause an adverse drug event if continued and the other in which there is no evidence of benefit. Participants ranked 9 factors related to possible ethical and pragmatic concerns through best-worst scaling methods (from greatest barrier to smallest barrier to deprescribing). Conditional logit regression quantified the relative importance for each factor as a barrier to deprescribing. Results: A total of 890 physicians (35.0%) returned surveys; 511 (57.4%) were male, and the mean (SD) years since graduation was 26.0 (11.7). Most physicians had a primary specialty in family practice (50.4% [449 of 890]) and internal medicine (43.5% [387 of 890]). A total of 689 surveys were sufficiently complete to analyze. In both clinical scenarios, the 2 greatest barriers to deprescribing were (1) the patient or family reporting symptomatic benefit from the medication (beneficence and autonomy) and (2) the medication having been prescribed by another physician (autonomy and nonmaleficence). The least influential factor was ease of paying for the medication (justice). Conclusions and Relevance: Findings from this national survey study of primary care physicians suggests that understanding ethical aspects of physician decision-making can inform clinician education about medication management and deprescribing decisions for older adults with moderate dementia.

Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship.

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression-another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n = 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein-a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239-246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression.

Prediction of Malnutrition and the Relationships Among Pain, Function, Depression, and Cancer Stage in Older Women With Breast Cancer.

BACKGROUND: Older women diagnosed with breast cancer are at risk for malnutrition. OBJECTIVES: This article aims to evaluate the relationships among cancer stage, pain, functional status, depression, and malnutrition, and to determine whether these symptoms predict nutritional status. METHODS: This cross-sectional study included women (N = 72) aged 70 years or older diagnosed with breast cancer at an academic medical center in the midwestern United States. The Timed Up and Go Test, Activities of Daily Living Scale, Numeric Pain Rating Scale, Geriatric Depression Scale, and Mini Nutritional Assessment were used. Demographic characteristics were evaluated using descriptive statistics. Bivariate and point-biserial correlations and linear regressions were used. FINDINGS: Participants' Mini Nutritional Assessment scores were significantly related to cancer stage, pain, depression, and Activities of Daily Living Scale scores.

Inflamed but not impulsive: Acute inflammatory cytokine response does not impact prepotent response inhibition.

BACKGROUND: Prior evidence has linked inflammation with impulsivity, but most of this evidence is cross-sectional. In this study, we provoked an acute inflammatory cytokine response to see whether it lowered prepotent response inhibition on three cognitive tasks. METHOD: This study features secondary analyses from a randomized crossover trial in which 171 postmenopausal breast cancer survivors (Stage I-IIIA) each received a typhoid capsular polysaccharide vaccination and a saline placebo injection in a random sequence at two separate visits at least one month apart. Participants completed the Stroop Color-Discrepant Task, the 2-back, and the Conners Continuous Performance Test (CPT) on the computer between 5 and 7 h after the injections. They had their blood drawn once before and repeatedly after the injection to measure interleukin-1 receptor antagonist and interleukin-6 responses. RESULTS: Women committed marginally fewer errors on the Stroop color-discrepant trials after the typhoid vaccine (M = 0.36, SE = 0.08), compared to placebo (M = 0.54, SE = 0.09, p = .076). Injection type did not predict 2-back accuracy (p = .80) or CPT commission errors (p = .47). Inflammatory cytokine responses were also unrelated to the outcomes of interest (ps>.16). CONCLUSION: We found no evidence that an acute inflammatory cytokine response provokes response disinhibition - an important facet of impulsivity. In fact, our only marginally non-significant result suggested that women were better able to inhibit their prepotent responses on the Stroop after receiving the typhoid vaccine, compared to placebo. Further experimental tests of the acute inflammatory cytokine response's effect on other aspects of impulsivity are warranted. LIMITATIONS: The sample was female, primarily White, highly educated cancer survivors, and recruitment was not premised on impulsive traits or diagnosis with an impulsive-related disorder. Also, there are many facets of impulsivity, and this study only measured response inhibition.

Improvement of lipid and lipoprotein profiles in children and adolescents with cystic fibrosis on CFTR modulator therapy.

BACKGROUND: Association of a high-fat diet with increased risks of cardiovascular disease (CVD) and type 2 diabetes, has prompted evaluation of lipids in people with CF (pwCF). However, most evidence on dyslipidemia was published before CF transmembrane conductance regulator (CFTR) modulators became a standard of care. The main goal of this study was to investigate the effect of CFTR modulator therapies on lipid and lipoprotein profiles in children and adolescents with CF. METHODS: Blood samples were collected from 153 pwCF (10.1 ± 4.7 years of age) and 60 age-matched controls. Most pwCF were pancreatic insufficient on pancreatic enzyme replacement therapy. By the end of the study, 65% of CF participants were on CFTR modulator therapy for >1 month. The results of traditional and advanced lipid testing in pwCF were correlated with clinical and dietary information. RESULTS: Total cholesterol and low-density lipoprotein (LDL) cholesterol were significantly lower in pwCF compared to non-CF participants. Those not receiving CFTR modulators also had significantly lower high-density lipoprotein (HDL) cholesterol and HDL particle number than controls. Individuals with CF on modulator therapy had significantly higher concentrations of anti-atherogenic HDL cholesterol and HDL particles along with lower levels of atherogenic large very-low density lipoprotein (VLDL) particles, total and small LDL particles, and triglycerides compared to those without CFTR modulator therapy. CONCLUSION: CFTR modulator therapy has a beneficial effect on dyslipidemia in CF. It remains to be seen if these positive changes translate into decreased CVD risk later in life given the increasing life expectancy in CF.

Worry and Mindfulness Differentially Impact Symptom Burden Following Treatment Among Breast Cancer Survivors: Findings From a Randomized Crossover Trial.

BACKGROUND: Breast cancer survivors often experience many somatic and cognitive side effects resulting from their cancer diagnosis and treatment, including higher rates of pain, fatigue, and memory/concentration problems. Emotion regulation offers opportunities to either enhance or dampen physical health. PURPOSE: In a secondary analysis of a double-blind randomized controlled trial (RCT) using a typhoid vaccine to assess factors associated with breast cancer survivors' inflammatory responses, we assessed how two specific aspects of emotion regulation, mindfulness, and worry, corresponded to acute changes in focus problems, memory problems, and fatigue along with performance on pain sensitivity and cognitive tasks across two visits among breast cancer survivors. METHODS: Breast cancer survivors (N = 149) completed two 8.5-hr visits at a clinical research center. Survivors were randomized to either the vaccine/saline placebo or a placebo/vaccine sequence. Worry and mindfulness questionnaires provided data on trait-level emotion regulation abilities. Fatigue, memory problems, and focus difficulties were assessed via Likert scales six times-once before the injections and then every 90 min for 7.5 hr thereafter. Women also completed a pain sensitivity task and several cognitive tasks at each visit. RESULTS: Findings from this study showed that breast cancer survivors who worried more and were less mindful experienced subjective memory problems, focus problems, and cold pain sensitivity across two visits and irrespective of injection type. Lower mindfulness also corresponded to higher subjective fatigue and hot pain sensitivity and objective ratings. Emotion regulation skills did not predict objective pain sensitivity or cognitive problems. CONCLUSION: Results from this study highlight the benefits of adaptive emotion regulation in helping mitigate symptoms associated with breast cancer survivorship.

Breast cancer survivors experience side effects resulting from their cancer diagnosis and treatment, including higher rates of pain, fatigue, and memory/concentration problems. Emotion regulation offers the possibility to either better or worse physical health. This study assessed how two emotion regulation strategies, mindfulness and worry, corresponded to changes in focus problems, memory problems, and fatigue along with performance on pain sensitivity and cognitive tasks across two visits among breast cancer survivors. A total of 149 survivors completed 2 day-long visits in the laboratory where they rated their fatigue and memory problems six times across the day, completed cognitive tests, and a pain sensitivity test. Findings from this study showed that breast cancer survivors who worried more and were less mindful experienced subjective memory problems, focus problems, and cold pain sensitivity across two visits. Emotion regulation skills did not predict objective pain sensitivity or cognitive problems. Results from this study highlight the benefits of adaptive emotion regulation skills like mindfulness in helping improve the cognitive and physical symptoms commonly experienced by breast cancer survivorship.

Evaluation of symptoms in respiratory syncytial virus infection in adults: psychometric evaluation of the Respiratory Infection Intensity and Impact Questionnaire™ symptom scores.

BACKGROUND: The Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) is a patient-reported outcome measure designed to assess symptoms and impacts of respiratory syncytial virus (RSV) infection. This study evaluated the construct validity, reliability, and responsiveness of the RiiQ™ Respiratory and Systemic Symptoms Scale scores. METHODS: Prospective data were analyzed from a total of 1795 participants, including from non-hospitalized patients with acute respiratory infection (ARI) and no coinfections enrolled in a Phase 2b RSV vaccine study (RSV-positive: n = 60; RSV-negative: n = 1615), and two observational studies of patients hospitalized with RSV (n = 20; n = 100). Descriptive statistics, confirmatory factor analysis (CFA), test-retest intraclass correlation coefficients (ICCs), construct validity correlations (between a clinician-assessed clinical questionnaire and the RiiQ™ symptoms scale), known-groups validity, and responsiveness (correlations of change scores) were evaluated. RESULTS: Mean patient age ranged from 66.5 to 71.5 years and the majority of patients were female. Initial assessments in the vaccine trial (ARI Day 1) were suggestive of less severe illness than in the observational studies with hospitalized patients. CFA loadings (> 0.40) supported summary scores. ICCs exceeding the recommended threshold of 0.70 supported test-retest reliability for Respiratory and Systemic Symptoms, except in the small observational study. At the scale level, correlations were moderate to strong (|r| ≥ 0.3) and positive between the Respiratory Symptoms Scale and the related clinical questionnaire scores, reflecting measurement of similar symptoms in support of convergent validity. Correlations with change in Patient Global Impression of Severity > 0.30 supported responsiveness. CONCLUSIONS: Psychometric tests applied to the RiiQ™ Symptoms scales provide evidence of its reliability, construct validity, discriminating ability, and responsiveness for use in clinical studies to assess the onset and severity of RSV symptoms.

The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer.

INTRODUCTION: The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, steroids play an essential role in chemotherapy tolerance through the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions. Given these conflicting roles, we wanted to evaluate this interplay more rigorously in the context of early-stage TNBC. METHODS: We performed a retrospective analysis of patients with operable TNBC who received neoadjuvant chemotherapy (NAC) between January 2012 and November 2018, with the primary goal of examining the dose-dependent relationship between pathological complete response (pCR) rates and corticosteroid use. Secondary endpoints included the impact of steroid dosing on overall survival (OS) and recurrence-free survival (RFS), along with a breakdown in pCR rates based on steroid doses provided during each chemotherapy phase. Further adjusted analyses were performed based on patient age, diabetic status, and anatomical stage. Finally, we explored the relationship between tumor-infiltrating lymphocytes (TILs) seen on tissue samples at baseline and dexamethasone doses in terms of pCR rates. RESULTS: In total, of the 174 patients screened within this study period, 116 met full eligibility criteria. Of these eligible patients, all were female, with a median age of 51.5 years (27.0 to 74.0) and a mean body mass index (BMI) of 29.7 [standard deviation (SD) 7.04]. The majority were nondiabetic (80.2%). For cancer stage, 69.8% (n = 81) had stage 2 breast cancer. We found no statistically significant association between pCR rates and dexamethasone use, both in terms of the total dose (p = 0.55) and mean dose per NAC cycle (p = 0.74). Similarly, no difference was noted when adjusting for diabetic status, metformin use, or age at diagnosis, regardless of the total steroid dose provided (p = 0.72) or mean dose per cycle (p = 0.49). No meaningful changes to pCR rate were seen with higher mean or higher total steroid doses during the paclitaxel (T) phase (adjusted p = 0.16 and p = 0.76, respectively) or doxorubicin and cyclophosphamide (AC) phase (adjusted p = 0.83 and p = 0.77, respectively). Furthermore, we found no clinically significant association between dexamethasone dose and either RFS (p = 0.45) or OS (p = 0.89). Of the 56 patients who had available pre-treatment biopsy tissue samples, 27 achieved pCR, with higher TILs at baseline being associated with higher pCR rates, regardless of the mean dexamethasone dose used. CONCLUSION: Our findings demonstrate that dexamethasone has no clinically significant impact on pCR, RFS, or OS when given concurrently with NAC in patients with curative TNBC, regardless of diabetic status.

Return to sport after forearm fractures in children: A scoping review and survey.

Purpose: A common question faced by clinicians is when a child may return to sport after treatment for a pediatric forearm fracture. There are few published recommendations and fewer supported by evidence. The aims of this study were to summarize existing published recommendation for return to sport after pediatric forearm fractures and to conduct a survey to determine usual clinical recommendations. Methods: A scoping review was performed on Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Scopus, and Google Scholar in accordance with the Joanna Briggs Institute guidelines. In addition, 64 orthopedic surgeons were anonymously surveyed asking for recommendations regarding return to sport after pediatric forearm fractures. Participants were to assume children were 9 years old and played a sport with an average risk of forearm injury. Results: Twenty-two publications for return to sport were retrieved. Children with distal radius buckle fractures safely commonly returned to sport by 4 weeks after initial injury, while survey respondents recommended over 6 weeks. Survey respondents valued fracture stability the highest when making return to sport recommendations. Children with simple, metaphyseal, single-bone fractures were usually allowed to return to sport at 8-10 weeks post-injury. Diaphyseal and complete fractures were prescribed longer return to sport intervals. Australian respondents also prescribed longer return to sport intervals. Conclusion: Children with distal radius buckle fractures may return to sport by 4 weeks after initial injury, sooner than recommended. Published recommendations remain limited for other fractures. However, our survey suggests children with simple, metaphyseal, single-bone fractures may return to sport at 8-10 weeks. Children with diaphyseal and complete fractures should abstain from sport for longer than metaphyseal and greenstick fractures, respectively. Level of evidence: level V.