Dose de-intensified 3-day photon, proton, or brachytherapy: a nonrandomized controlled partial breast irradiation trial.

BACKGROUND: The optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy. METHODS: A multicenter nonrandomized controlled trial with primary outcome of adverse cosmesis at 3 years versus pre-PBI. Eligibility criteria were ≥ age 50 years treated with breast-conserving surgery for node-negative estrogen receptor positive (ER+) invasive breast cancer or any ductal carcinoma in-situ (DCIS) measuring ≤ 2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (RBE) and brachytherapy 21 Gy in 3 fractions. Radiotherapy technique and use of adjuvant endocrine therapy was selected at physician and patient discretion. RESULTS: Between June 17, 2015 and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. 126 (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). 54.0% of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline, 2.3% at 3 years (difference -12.2%, 95% CI (-100%, -6.4%)). Adverse cosmesis at last-follow-up, with median follow-up 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient reported outcomes, and just two grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. 5-year local recurrence-free and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences amongst 60 patients with invasive breast cancer and Ki67 ≤ 13.25%. CONCLUSIONS: De-intensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the pre-specified criteria for acceptability. This approach is an attractive option for small node-negative ER+ BC and DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02453737.

Baseline Normative and Test-Retest Reliability Data for Sideline Concussion Assessment Measures in Youth.

Tools used for the identification, evaluation, and monitoring of concussion have not been sufficiently studied in youth or real-world settings. Normative and reliability data on sideline concussion assessment measures in the youth athlete population is needed. Pre-season normative data for 515 athletes (93.5% male) aged 5 to 16 on the Standardized Assessment of Concussion (SAC/SAC-Child), modified Balance Errors Scoring System (mBESS), Timed Tandem Gait (TTG), and the King-Devick Test (KDT) are provided. A total of 212 non-injured athletes repeated the measures post-season to assess test-retest reliability. Mean performance on the SAC-C, mBESS, TTG, and KDT tended to improve with age. KDT was the only measure that demonstrated good to excellent stability across age ranges (ICC = 0.758 to 0.941). Concentration was the only SAC/SAC-C subtest to demonstrate moderate test-retest stability (ICC = 0.503 to 0.706). TTG demonstrated moderate to good (ICC = 0.666 to 0.811) reliability. mBESS demonstrated poor to moderate reliability (ICC = -0.309 to 0.651). Commonly used measures of concussion vary regarding test-retest reliability in youth. The data support the use of at least annual sport concussion baseline assessments in the pediatric population to account for the evolution in performance as the child ages. Understanding the variation in the stability and the evolution of baseline performance will enable improved identification of possible injury.

Measurable Residual Disease and Clinical Outcomes in Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis.

Importance: Measurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development. Objective: To assess the association between MRD and PFS in CLL using data from prospective clinical trials that studied targeted agents or obinutuzumab-based treatment. Data Sources: Clinical studies on CLL were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception through July 31, 2023. Study Selection: Prospective, single-arm, and randomized clinical trials that assessed targeted agents or obinutuzumab-based treatment and reported PFS by MRD status were included. Studies with insufficient description of MRD information were excluded. Data Extraction and Synthesis: Study sample size, median patient age, median follow-up time, line of treatment, MRD detection method and time points, and survival outcomes were extracted. Main Outcomes and Measures: Analyses of survival probabilities and hazard ratios (HRs) were conducted for PFS according to MRD status. Meta-analyses were performed using a random-effects model. Results: A total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40). Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.

Cost-effectiveness of patch testing allergens within the same group: A computational approach to optimize formaldehyde-related allergen selection.

BACKGROUND: Patch testing for multiple cross-reactive allergens for allergic contact dermatitis (ACD) may not be necessary because of copositivity. OBJECTIVES: We evaluated the formaldehyde group allergens to determine the optimal, most cost-effective allergens to test. METHODS: A retrospective analysis of Mayo Clinic (1997-2022) examined the well-established copositive formaldehyde group: formaldehyde, quaternium 15, hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, diazolidinyl urea, imidazolidinyl urea, toluenesulphonamide formaldehyde resin, DMDM hydantoin, and ethyleneurea melamine formaldehyde mix. Patch Optimization Platform identified which single formaldehyde-related allergen optimally captures patients with clinically relevant ACD. Next, Patch Optimization Platform determined the optimal additional 1, 2, 3, etc. allergens. Cost per patch test was $5.19 (Medicare 2022). RESULTS: A total of 9832 patients were tested for all listed allergens, with 830 having positive patch test results. Patch Optimization Platform determined that quaternium 15 alone captures 53% of patients with ACD to the formaldehyde group; adding the optimal second allergen (formaldehyde 1%) captures 78%; the optimal 5 top allergens capture >94% of patients. The incremental cost per additional diagnosis increased up to 44-fold as the number of allergens tested increased. LIMITATIONS: Data are from a single institution, and the cost per test was fixed according to Medicare Part B in 2022. CONCLUSIONS: For diagnosing ACD, we recommend considering an optimized allergen selection algorithm.

Impaired Suppression of Plasma Lipid Extraction and its Partitioning Away from Muscle by Insulin in Humans with Obesity.

Context: Humans with obesity and insulin resistance exhibit lipid accumulation in skeletal muscle, but the underlying biological mechanisms responsible for the accumulation of lipid in the muscle of these individuals remain unknown. Objective: We investigated how plasma insulin modulates the extraction of circulating triglycerides (TGs) and non-esterified fatty acids (NEFAs) from dietary and endogenous sources in the muscle of lean, insulin-sensitive humans (Lean-IS) and contrasted these responses to those in humans with obesity and insulin resistance (Obese-IR). Methods: The studies were performed in a postprandial state associated with steady-state plasma TG concentrations. The arterio-venous blood sampling technique was employed to determine the extraction of circulating lipids across the forearm muscle before and after insulin infusion. We distinguished kinetics of TGs and NEFAs from dietary sources across muscle from those from endogenous sources by incorporating stable isotope-labeled triolein in ingested fat. Results: Plasma insulin rapidly suppressed the extraction of plasma TGs from endogenous, but not dietary, sources in the Lean-IS, but same response was absent in the Obese-IR. Furthermore, in the muscle of Lean-IS, plasma insulin decreased the extraction of circulating NEFAs from both dietary and endogenous sources, but in Obese-IR subjects this response was absent for NEFAs from dietary sources. Conclusions: Partitioning of circulating lipids away from the skeletal muscle when plasma insulin increases, such as during the postprandial period, is impaired in humans with obesity and insulin resistance. Trial Registration: ClinicalTrials.gov ( NCT01860911 ).

Lower muscle protein synthesis in humans with obesity concurrent with lower expression of muscle IGF1 splice variants.

OBJECTIVE: This study tested the hypothesis that expression of insulin-like growth factor 1 (IGF-1) protein and mRNA splice variants is lower in skeletal muscle of humans with obesity who have a lower mixed-muscle protein fractional synthesis rate (MMP-FSR) when compared with individuals without obesity. METHODS: The study included nine participants with obesity (OB, mean [SD],  BMI = 35 [3] kg/m2 , MMP-FSR = 0.06%/h [0.02%/h]) and nine participants without obesity (W-OB, BMI = 24 [3] kg/m2 , MMP-FSR = 0.08%/h [0.02%/h]; for both BMI and MMP-FSR p < 0.05). MMP-FSR and mitochondrial protein FSR were measured following an overnight fast. RESULTS: Along with lower MMP-FSR, OB participants displayed lower mitochondrial protein FSR (p = 0.03) compared with W-OB participants. Expression of IGF-1 (p = 0.04) and IGF-1 receptor (p < 0.01) proteins was lower in muscle of OB participants. In addition, OB participants had lower (p < 0.05) mRNA expression of IGF1 variants Eb and Ec. This study demonstrates that lower protein synthesis in muscle of humans with obesity occurs concurrently with lower expression of muscle IGF-1 and IGF-1 receptor proteins, as well as lower mRNA expression of the IGF1 splice variants. CONCLUSIONS: These findings indicate that lower protein synthesis observed in muscle of humans with obesity may result from diminished muscle IGF1 gene expression.

Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis.

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.

Study of association between antibodies to non-HLA kidney self-antigens and progression to chronic immune injury after kidney transplantation.

BACKGROUND: Immune response to several kidney self-antigens (KSAg) such as Collagen IV (Col-IV), Perlecan (PL), and Fibronectin (FN) have been associated with antibody-mediated damage and poor allograft survival. Thus, the aim of this study was to determine if humoral immune responses to KSAg correlates with progression of chronic immune injury (CII) changes at 1 year or 2 years. METHODS: Kidney transplant recipients who underwent 1- or 2-year biopsies, with chronic interstitial inflammation (ci > 1) and/or glomerular membrane double contouring (cg > 0) were analyzed with matched controls. Sera were analyzed retrospectively for antibodies against KSAg using ELISA. The presence of antibodies to KSAg were compared at 0, 4, 12, and 24 months using logistic regression. RESULTS: We identified a cohort of 214 kidney transplant recipients. Of these, we identified 33 cases and matched 66 controls. Logistical regression showed an odds ratio of 1 with the confidence interval crossing 1 for the presence of response to KSAg at all the time points. CONCLUSIONS: Humoral immune responses to either KSAg alone or in combination with donor-specific anti-HLA antibodies are not associated with progression to CII at 1 and 2 years after kidney transplantation.

Human Trafficking Education: A Pilot Study of Integration into Medical School Curriculum.

OBJECTIVES: Few medical schools incorporate formal education on human trafficking (HT) and sex trafficking (ST) into their curriculum. Our objective was to develop, implement, and evaluate education on HT and ST in the first-year medical student curriculum. METHODS: The curriculum included a standardized patient (SP) experience and lecture. As part of their mandatory sexual health course, students interviewed an SP who presented with red flags for ST and then participated in a discussion led by a physician-facilitator in an observed small group setting. A multiple-choice survey to assess knowledge about HT and ST was developed and administered to students before and after the SP interview. RESULTS: Of the 50 first-year medical students, 29 (58%) participated in the survey. Compared with the students' baseline scores (according to the percentage of correct responses), scores after the educational intervention showed a significant increase in percentage correct on questions related to trafficking definition and scope (elder care, P = .01; landscaping, P = .03); victim identification (P < .001); referral to services (P < .001); legal issues (P = .01); and security (P < .001). On the basis of the feedback, a 2-hour lecture, which was adapted from the American Medical Women's Association-Physicians Against the Trafficking of Humans "Learn to Identify and Fight Trafficking" training, was presented the next year to all first-year medical students as part of their longitudinal clinical skills course and before the SP case. Curriculum objectives included learning trafficking definitions, victim/survivor identification, intersections with health care, the local impact of HT, and available resources. CONCLUSION: This curriculum fulfills course objectives and could be replicated at other institutions. Further evaluation of this pilot curriculum is necessary to evaluate its effectiveness.

Avoiding Blunders When Analyzing Correlated Data, Clustered Data, or Repeated Measures.

Rheumatology research often involves correlated and clustered data. A common error when analyzing these data occurs when instead we treat these data as independent observations. This can lead to incorrect statistical inference. The data used are a subset of the 2017 study from Raheel et al consisting of 633 patients with rheumatoid arthritis (RA) between 1988 and 2007. RA flare and the number of swollen joints served as our binary and continuous outcomes, respectively. Generalized linear models (GLM) were fitted for each, while adjusting for rheumatoid factor (RF) positivity and sex. Additionally, a generalized linear mixed model with a random intercept and a generalized estimating equation were used to model RA flare and the number of swollen joints, respectively, to take additional correlation into account. The GLM's ß coefficients and their 95% confidence intervals (CIs) are then compared to their mixed-effects equivalents. The ß coefficients compared between methodologies are very similar. However, their standard errors increase when correlation is accounted for. As a result, if the additional correlations are not considered, the standard error can be underestimated. This results in an overestimated effect size, narrower CIs, increased type I error, and a smaller P value, thus potentially producing misleading results. It is important to model the additional correlation that occurs in correlated data.

Prediction of permanent pacemaker implantation after transcatheter aortic valve replacement: The role of machine learning.

BACKGROUND: Atrioventricular block requiring permanent pacemaker (PPM) implantation is an important complication of transcatheter aortic valve replacement (TAVR). Application of machine learning could potentially be used to predict pre-procedural risk for PPM. AIM: To apply machine learning to be used to predict pre-procedural risk for PPM. METHODS: A retrospective study of 1200 patients who underwent TAVR (January 2014-December 2017) was performed. 964 patients without prior PPM were included for a 30-d analysis and 657 patients without PPM requirement through 30 d were included for a 1-year analysis. After the exclusion of variables with near-zero variance or ≥ 50% missing data, 167 variables were included in the random forest gradient boosting algorithm (GBM) optimized using 5-fold cross-validations repeated 10 times. The receiver operator curve (ROC) for the GBM model and PPM risk score models were calculated to predict the risk of PPM at 30 d and 1 year. RESULTS: Of 964 patients included in the 30-d analysis without prior PPM, 19.6% required PPM post-TAVR. The mean age of patients was 80.9 ± 8.7 years. 42.1 % were female. Of 657 patients included in the 1-year analysis, the mean age of the patients was 80.7 ± 8.2. Of those, 42.6% of patients were female and 26.7% required PPM at 1-year post-TAVR. The area under ROC to predict 30-d and 1-year risk of PPM for the GBM model (0.66 and 0.72) was superior to that of the PPM risk score (0.55 and 0.54) with a P value < 0.001. CONCLUSION: The GBM model has good discrimination and calibration in identifying patients at high risk of PPM post-TAVR.

Food-Specific IgG4 Is Elevated Throughout the Upper Gastrointestinal Tract in Eosinophilic Esophagitis.

BACKGROUND: Food-specific immunoglobulin G4 (FS-IgG4) is associated with eosinophilic esophagitis (EoE); however, it is not clear whether production is limited to the esophagus. AIMS: To assess FS-IgG4 levels in the upper gastrointestinal tract and plasma and compare these with endoscopic disease severity, tissue eosinophil counts, and patient-reported symptoms. METHODS: We examined prospectively banked plasma, throat swabs, and upper gastrointestinal biopsies (esophagus, gastric antrum, and duodenum) from control (n = 15), active EoE (n = 24), and inactive EoE (n = 8) subjects undergoing upper endoscopy. Patient-reported symptoms were assessed using the EoE symptom activity index (EEsAI). Endoscopic findings were evaluated using the EoE endoscopic reference score (EREFS). Peak eosinophils per high-power field (eos/hpf) were assessed from esophageal biopsies. Biopsy homogenates and throat swabs were normalized for protein content and assessed for FS-IgG4 to milk, wheat, and egg. RESULTS: Median FS-IgG4 for milk and wheat was significantly increased in the plasma, throat swabs, esophagus, stomach, and duodenum of active EoE subjects compared to controls. No significant differences for milk- or wheat-IgG4 were observed between active and inactive EoE subjects. Among the gastrointestinal sites sampled, FS-IgG4 levels were highest in the esophagus. Esophageal FS-IgG4 for all foods correlated significantly across all sites sampled (r ≥ 0.59, p < 0.05). Among subjects with EoE, esophageal FS-IgG4 correlated significantly with peak eos/hpf (milk and wheat) and total EREFS (milk). EEsAI scores and esophageal FS-IgG4 levels did not correlate. CONCLUSIONS: Milk and wheat FS-IgG4 levels are elevated in plasma and throughout the upper gastrointestinal tract in EoE subjects and correlate with endoscopic findings and esophageal eosinophilia.

Skin Cancer Knowledge, Attitudes and Sun Protection Practices in the Hispanic Population: A Cross-Sectional Survey.

Hispanics are more likely to be diagnosed with skin cancer at a later stage and experience worse overall survival than Whites. The objective of this cross-sectional study was to assess the skin cancer knowledge, attitudes, perceived risk, and sun protection practices among an underserved population in the Phoenix area. We recruited participants from the greater Phoenix area to undergo skin examination and complete a questionnaire. 208 participants were included. The majority were Hispanic (64.9%). Of this Hispanic group, most were from Mexico (87.9%). The Hispanic cohort had an overall mean skin cancer knowledge score of 3.68/6, the lowest of any other racial/ethnic group, but had the highest desire to learn more about skin cancer (64.6%, "strongly agree"). They were the most concerned about developing skin cancer (50.4%, "very concerned") but had relatively lower rates of sun protection practices (7.9% "always use" sunscreen, 22.0% "always use" sun-protective clothing). Limitations of this study include a small sample size, lack of validation for the skin cancer knowledge score, lack of season as a covariate in the multivariate analysis, lack of follow-up, and lack of robust skin cancer risk assessment. In conclusion, despite poorer skin cancer knowledge and sun protection practices, the Hispanic population had the highest concern for developing skin cancer and desire to learn more about skin cancer. Targeted and culturally relevant skin cancer and sun protection education for this group is needed.

Impact of Glomerulitis on Long-term Outcomes After Kidney Transplantation.

The Banff classification scheme provides a framework for interpreting transplant kidney biopsies and has undergone various updates in the past 2 decades especially related to antibody-mediated rejection. The clinical significance of early glomerulitis seen within 4 mo on protocol biopsies has received limited attention. We hypothesized that early glomerulitis seen on protocol biopsies will lead to significant adverse outcomes as assessed by histopathology and allograft outcome. Methods: A single-center retrospective study of a cohort of patients who underwent protocol biopsies within 4 mo after transplantation with timely follow-up protocol biopsies were assessed. Patients with recurrent glomerulonephritis were excluded. Results: We calculated glomerulitis (g) scores for 2212 biopsy specimens and identified 186 patients with glomerulitis (g > 0) and 2026 patients without glomerulitis (g = 0). The progression to chronic transplant glomerulopathy at 1 and 2 y was higher in patients with g > 0 as compared with g = 0 (year 1, 10.7% versus 2.3% [P < 0.001]' respectively; year 2, 17.2% versus 4.3% [P < 0.001], respectively) with no difference in other chronic lesions. The death-censored graft failure rate was higher in patients with g > 0 as compared with g = 0 (hazard ratio, 1.68 [95% CI, 1.07-2.65]; P = 0.02). We did not find any difference in outcomes in glomerulitis group based on donor-specific antibody. Conclusion: Our findings suggest that early glomerulitis (seen within 4 mo after transplantation) may lead to clinically significant long-term changes and thus could be a target for early intervention therapies.

Patient Versus Caregiver: Correlation and Differences in Pediatric Quality of Life Using a Prospective Registry in a Large-Volume, Multisite Practice.

PURPOSE: Patient-reported outcomes provide quality of life (QOL) data during and after radiation. When pediatric patients are unable to complete patient-reported outcomes, it is unknown whether caregiver responses are an accurate surrogate. We assessed whether caregiver scores for the Pediatric Quality of Life Inventory (PedsQL) Core and Brain Tumor Module questionnaires can substitute for missing child scores. METHODS AND MATERIALS: From 2016 to 2018, pediatric patients treated with radiation were followed in a prospective, institutional registry. Child and caregiver Core and Tumor PedsQL surveys were obtained at pretreatment, end of treatment, and in regular follow-up. The differences between the 2 scores at each time point were quantified using a linear mixed-model and the level of agreement was estimated with intraclass correlation coefficient (ICC). An ICC 95% confidence interval (CI) lower limit exceeding 0.75 was considered an acceptable threshold for using caregiver scores as imputed values for missing child scores. RESULTS: Ninety-one children completed 403 surveys. Caregivers underestimated QOL scores at baseline, but not at end of treatment or any follow-up time. The PedsQL Core total score had an ICC of 0.88 (95% CI, 0.81-0.92), and the emotional, physical, school, and social function subdomain scores were 0.81 (0.72-0.88), 0.72 (0.58-0.82), 0.79 (0.68-0.86), and 0.75 (0.62-0.83), respectively. The tumor total score ICC was 0.91 (0.85, 0.94), and each of the subdomains (cognitive problems, communication, movement and balance, nausea, pain and hurt, perceived physical appearance, procedural anxiety, treatment anxiety, and worry) had ICC lower bound 95% CI ≥0.75 except for communication (0.83, 0.74-0.89). Bland-Altman analysis demonstrated no visual change in discrepancy between child and caregiver estimates as overall QOL improved. CONCLUSIONS: Agreement between child- and caregiver-reported QOL was generally strong in the acute period after radiation, implying that caregiver scores may be imputed for child scores in future protocols and analyses of pediatric QOL.

Impact of timing of preoperative gabapentin administration on postoperative somnolence.

CONTEXT: Enhanced Recovery After Surgery (ERAS) is a multimodal protocol aimed to improve quality of postoperative recovery, minimize complications, and optimize overall self-regulation. Preoperative gabapentin decreases postoperative pain but can be associated with prolonged postoperative somnolence and respiratory depression risk. Although it is known that gabapentin affects the postoperative course, it is unclear if the timing of preoperative administration affects this finding. OBJECTIVES: This study aims to assess the optimal preoperative timing for gabapentin administration in patients undergoing gynecologic surgery to minimize postoperative somnolence risk. METHODS: A retrospective cohort study evaluated patients who underwent major gynecologic surgery and received preoperative gabapentin. Patients were grouped based on timing from gabapentin administration to surgical incision (<4 h group vs. ≥4 h group). Preoperative, intraoperative, and postoperative data were abstracted and compared. Univariate associations between the timing of gabapentin administration and the patient and surgical characteristics and outcomes were tested utilizing two-sample equal-variance t-tests, linear model ANOVA, or Fisher's exact tests. Associations between the timing of gabapentin administration and the time until the Richmond Agitation Sedation Scale (RASS) score of 0 were modeled utilizing linear regression, adjusted for age, initial postoperative anesthesia care unit (PACU), RASS score, and postoperative narcotics. RESULTS: Each group contained 127 patients. Demographics were similar except for age (<4 h group mean=44.2 years; ≥4 h group mean=40.5 years; p=0.021), chronic pain (<4 h group=17.6%; ≥4 h group=43.3%; p<0.001), and surgical indication (<4 h group=pelvic pain [29.1%]; ≥4 h group=pelvic pain [51.2%]; p=0.007). The <4 h group had a similar postoperative narcotic administration (<4 h group mean morphine milligram equivalents [MME]=3.667; ≥4 h group mean MME=4.833; p=0.185). The minutes from surgical closure until the patient received a RASS score of 0 and initial PACU pain score (Visual Analogue Scale [VAS]) were similar. The initial PACU oxygen administration volume, hours from surgical closure until the patient transitioned to room air, and initial PACU respiratory rate were similar. The PACU duration, admission secondary to somnolence, and initial PACU Glasgow Coma Scale (GCS) score showed no difference. Postoperative nausea/vomiting was decreased in the ≥4 h group (<4 h group=24.4%; ≥4 h group=13.4%; p-value=0.036), and urinary retention (<4 h group=14.2%; ≥4 h group=5.5%; p-value=0.033) was decreased in the ≥4 h group. CONCLUSIONS: The timing of gabapentin administration less than or more than 4 h preoperatively in patients ≥18 years does not significantly affect postoperative somnolence or respiratory depression. Further, it does not have a significant effect on GCS scores or VAS scores.

A Comparison of Perceived Lifetime Breast Cancer Risk to Calculated Lifetime Risk Using the Gail Risk Assessment Tool.

Background: Understanding the accuracy of a woman's perceived breast cancer risk can enhance shared decision-making about breast cancer screening through provider and patient discussion. We aim to report and compare women's perceived lifetime breast cancer risk to calculated lifetime breast cancer risk. Methods: Women presenting to Mayo Clinic in Arizona and Minnesota in July 2016 completed a survey assessing their perceived breast cancer risk. Lifetime Gail risk scores were calculated from questions pertaining to health history and were then compared with perceived breast cancer risk. Results: A total of 550 predominantly white, married, and well-educated (≥college) women completed surveys. Using lifetime Gail risk scores, 5.6% were classified as high risk (>20% lifetime risk), 7.7% were classified as intermediate risk (15%-20%), and 86.6% were classified as average risk (<15%). Of the 27 women who were classified as high risk, 18 (66.7%) underestimated their risk and of the 37 women who were intermediate risk, 12 (32.4%) underestimated risk. Women more likely to underestimate their risk had a reported history of an abnormal mammogram and at least one or more relative with a history of breast cancer. Surveyed women tended to overestimate risk 4.3 (130/30) times as often as they underestimated risk. Conclusion: In a group of predominantly white, educated, and married cohort of women, there was a large portion of women in the elevated risk groups who underestimated risk. Specific aspects of medical history were associated with underestimation including a history of abnormal mammogram and family history of breast cancer. Overall, in our sample, more women overestimated than underestimated risk.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.