Inpatient management of epidermolysis bullosa: Consensus-based hands-on instructions for neonates and postneonates.

BACKGROUND: Epidermolysis bullosa (EB), characterized by skin fragility and blistering, often requires hospitalization. Training for inpatient management of EB is limited, with no unified recommendations available in North America. OBJECTIVE: To develop consensus-derived best practices for hands-on inpatient management of EB in both the neonatal and postneonatal period. METHODS: A modified Delphi method (expert-based input via 2 surveys and a final review) was implemented. Available guidelines from EB Clinical Research Consortium centers were analyzed to determine areas of focus and formulate statements to be voted on by EB Clinical Research Consortium members, experienced EB nurses, and select family members. Study participants evaluated statements using a Likert scale: statements with at least 70% agreement were accepted; statements with 30% or more disagreement were rejected. RESULTS: Ten areas of focus were identified. Delphi participants included 15 dermatologists, 8 nurses, and 6 nonhealth care caregivers. Consensus was established on 103/119 neonatal statements and 105/122 postneonatal statements; no statements were rejected. Most recommendations applied to both age groups. LIMITATIONS: Recommendations may require adjustment based on individual patient's clinical context. CONCLUSION: Using the Delphi method, a consensus-derived resource for hospital-based health care professionals who manage patients with EB has been developed to improve the quality of inpatient care.

Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: An International, Multicenter, Retrospective Study.

PURPOSE: Outcomes for Richter transformation (RT) are poor with current therapies. The efficacy and safety of anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) for RT are not established. METHODS: We performed an international multicenter retrospective study of patients with RT who received CAR-T. Patient, disease, and treatment characteristics were summarized using descriptive statistics, and modeling analyses were used to determine association with progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated from the date of CAR-T infusion. RESULTS: Sixty-nine patients were identified. The median age at CAR-T infusion was 64 years (range, 27-80). Patients had a median of four (range, 1-15) previous lines of therapy for CLL and/or RT, including previous Bruton tyrosine kinase inhibitor and/or BCL2 inhibitor therapy in 58 (84%) patients. The CAR-T product administered was axicabtagene ciloleucel in 44 patients (64%), tisagenlecleucel in 17 patients (25%), lisocabtagene maraleucel in seven patients (10%), and brexucabtagene autoleucel in one patient (1%). Eleven patients (16%) and 25 patients (37%) experienced grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, respectively. The overall response rate was 63%, with 46% attaining a complete response (CR). After a median follow-up of 24 months, the median PFS was 4.7 months (95% CI, 2.0 to 6.9); the 2-year PFS was 29% (95% CI, 18 to 41). The median OS was 8.5 months (95% CI, 5.1 to 25.4); the 2-year OS was 38% (95% CI, 26 to 50). The median duration of response was 27.6 months (95% CI, 14.5 to not reached) for patients achieving CR. CONCLUSION: CAR-T demonstrates clinical efficacy for patients with RT.

Cabozantinib and Axitinib After Vascular Endothelial Growth Factor Therapy in Patients with Advanced Renal Cell Carcinoma: A Retrospective Cohort Study from England.

BACKGROUND AND OBJECTIVE: The tyrosine kinase inhibitors cabozantinib and axitinib have been widely used in England to treat advanced renal cell carcinoma following prior vascular endothelial growth factor-targeted therapy, but data on real-world usage remain limited. Our objective was to describe the real-world treatment patterns and outcomes of patients with advanced renal cell carcinoma who received second-line or later-line (≥ 2L) cabozantinib or axitinib after vascular endothelial growth factor-targeted therapy in clinical practice in England. METHODS: This retrospective cohort study used clinical practice data (collected 2011-20) from the English Cancer Analysis System database. Patient characteristics, treatment sequence and duration, and overall survival (time from initiation of cabozantinib/axitinib treatment to death) were evaluated. RESULTS: Data from 1485 eligible adults with advanced renal cell carcinoma were analyzed: 440 received ≥  2L cabozantinib (2L for 88.6% of them); 1045 received ≥  2L axitinib (2L for 89.5%). The most common first-line treatments were sunitinib (2L cabozantinib subcohort, 48%; 2L axitinib subcohort, 46%) and pazopanib (46% and 54%, respectively); nivolumab was the most common third-line treatment (18% and 19%, respectively). Median (interquartile range) 2L therapy duration was 5.52 (2.73-11.74) months for cabozantinib and 4.60 (1.45-12.36) months for axitinib. Following adjustment for potential confounders using inverse probability weighting, overall survival (median [interquartile range]) was longer for ≥ 2L cabozantinib (11.2 [5.7-28.0] months) than for ≥  2L axitinib (10.4 [4.7-22.0] months; log-rank p = 0.0034). CONCLUSIONS: The Cancer Analysis System database is a valuable research resource providing extensive real-world clinical data. Real-world overall survival was longer with ≥  2L cabozantinib than with axitinib. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04637204; registered November 2020.

Cabozantinib and axitinib are anticancer drugs called tyrosine kinase inhibitors. They work by blocking the activity of proteins that cancer cells use to help them divide and grow. Cabozantinib and axitinib are treatment options for a common type of kidney cancer called renal cell carcinoma (RCC). There is evidence about how well cabozantinib and axitinib work in clinical trials, but it is less clear how well they work in standard practice outside of clinical trials. We investigated how cabozantinib and axitinib are used and how well they work as part of 'real-world' RCC care. We did this by analyzing patient data from an English cancer database. All patients in the study had advanced RCC and had been treated with at least one previous anticancer drug. This includes a type of drug that blocks new blood vessels forming, which tumors need for rapid growth. Most of the 1485 patients received cabozantinib or axitinib after receiving only one previous anticancer drug. These patients were treated for a median of 5.5 months with cabozantinib and 4.6 months with axitinib. Patients lived for a median of 11.2 months after starting cabozantinib treatment and a median of 10.4 months after starting axitinib treatment. This study provides new evidence showing how well cabozantinib and axitinib work in everyday RCC care. The results add to those from clinical trials and show the value of the English cancer registry for conducting studies of routine cancer care.

Behavioral Sleep Interventions and Cardiovascular Risk Factors: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND/OBJECTIVES: Chronic sleep disturbance has been consistently associated with cardiovascular disease. We sought to determine whether behavioral interventions to improve sleep have been associated with improvements in 4 common cardiovascular disease risk factors: hypertension, diabetes mellitus (DM), obesity, and smoking. METHODS: Randomized controlled trials evaluating the prospective effect of behavioral sleep interventions on (a) blood pressure in participants with hypertension/prehypertension, (b) glycemic control in participants with DM/pre-DM, (c) anthropometrics in participants who were overweight/obese, and (d) smoking status in smokers were eligible. Where feasible, we undertook random-effects meta-analyses of standardized mean differences in cardiovascular disease risk factor change. RESULTS: Overall, 3 trials met the inclusion criteria for blood pressure, 4 for glycemic control, 9 for overweight/obesity, and 2 for smoking. On meta-analysis, interventions with sleep as the sole behavioral target were associated with a significant reduction in hemoglobin A1c% (-0.84; 95% confidence interval [CI], -1.34 to -0.34), but not a significant reduction in systolic blood pressure (-0.18; 95% CI, -0.55 to 0.20) versus controls. In addition, any interventions with sleep as a behavioral target were associated with significant reductions in hemoglobin A1c% (-0.71; 95% CI, -1.01 to -0.42) and weight (-0.78; 95% CI, -1.11 to -0.45), but not systolic blood pressure (-0.72; 95% CI, -1.82 to 0.37). Trials evaluating smoking status were not amenable to meta-analysis. CONCLUSION: Behavioral interventions to improve sleep were associated with improved glycemic control in patients with DM. It is also possible that these interventions improve weight in individuals who were overweight/obese. A low number of trials and small sample sizes indicate that further large, well-designed randomized controlled trials of interventions are warranted.

A comparative analysis of the Irish post-graduate geriatric medicine training scheme with the European post-graduate curriculum in geriatric medicine.

PURPOSE: Minimum training recommendations to become a specialist geriatrician in the EU have been published and in this study we compared these recommendations with content from the post-graduate training scheme in Geriatric Medicine in Ireland. METHODS: We examined the content of didactic study-day lectures delivered during Geriatric medicine training in Ireland. We compared how both the formal Irish curriculum and the content of the study days match up with the 36 items that are identified as core knowledge content areas. RESULTS: The Irish geriatric medicine curriculum outlined that 30 of the 36 knowledge areas from the European curriculum should be covered. Formal teaching was delivered on 33 of the 36 knowledge components that are outlined in the European curriculum. 24 of 36 topics were covered at least twice. CONCLUSION: There was a high concordance between the content of the Irish and European post-graduate curriculum in Geriatric medicine.

Household-level lifestyle interventions for the prevention of cognitive decline; A Systematic review.

BACKGROUND: Lifestyle interventions targeting households may be an effective means of promoting healthier cognitive function in later life, with extended benefit to other household members. In this systematic review and meta-analysis, we sought to assess the effect of targeting lifestyle behaviours of households on cognitive outcomes METHODS: An electronic search strategy was designed to identify randomised controlled trials (RCTs) where households were randomised to receive a lifestyle intervention for the prevention of cognitive decline, from database inception until April 2020. Our initial search identified no eligible studies, so we revised our search strategy to include trials enroling dyads. We reported the cognitive outcomes, functional outcomes, caregiver outcomes and long-term care (LTC) admissions for eligible studies. FINDINGS: We identified no RCTs which randomised households to receive a lifestyle intervention for preventing cognitive decline. We identified five RCTs (n = 1721, with mean follow-up of 9.6 months) which randomised dyads, which evaluated diet (two trials) and physical activity (three trials). CONCLUSION: Trials evaluating dietary and exercise interventions in dyads were identified. No trial demonstrated a significant association of interventions with change in cognitive testing, functional outcomes or long-term care admissions, although trials were small with short-term follow-up. Future studies should consider targeting lifestyle behaviours of households for prevention of dementia.

Prevalence and predictors of continence containment products and catheter use in an acute hospital: A cross-sectional study.

Although incontinence is common in hospital, the prevalence and predictors of continence aid use (continence wear and catheters) are poorly described. A one-day cross-sectional study was conducted in a large university hospital assessing consecutive inpatients (≥55) for their pre-admission and current use of continence aids. Barthel Index, Clinical Frailty Scale and Charlson Co-morbidity scores were recorded. Appropriateness was defined by local guidelines. 355 inpatients, median age 75±17 years, were included; 53% were male. Continence aid use was high; prevalence was 46% increasing to 58% for those ≥75. All-in-one pads were the most common, an overall prevalence of 31%. Older age, lower Barthel and higher frailty scores were associated with continence aid use in multivariate analysis. Inappropriate use of aids was high at 45% with older age being the only independent predictor. Continence aids are often used inappropriately during hospitalisation by older patients. Concerted efforts are required to address this issue.

Double-hit Signature with TP53 Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-cell Lymphoma Treated with R-CHOP.

PURPOSE: We performed detailed genomic analysis on 87 cases of de novo diffuse large B-cell lymphoma of germinal center type (GCB DLBCL) to identify characteristics that are associated with survival in those treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). EXPERIMENTAL DESIGN: The cases were extensively characterized by combining the results of IHC, cell-of-origin gene expression profiling (GEP; NanoString), double-hit GEP (DLBCL90), FISH cytogenetic analysis for double/triple-hit lymphoma, copy-number analysis, and targeted deep sequencing using a custom mutation panel of 334 genes. RESULTS: We identified four distinct biologic subgroups with different survivals, and with similarities to the genomic classifications from two large retrospective studies of DLBCL. Patients with the double-hit signature, but no abnormalities of TP53, and those lacking EZH2 mutation and/or BCL2 translocation, had an excellent prognosis. However, patients with an EZB-like profile had an intermediate prognosis, whereas those with TP53 inactivation combined with the double-hit signature had an extremely poor prognosis. This latter finding was validated using two independent cohorts. CONCLUSIONS: We propose a practical schema to use genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies.

Renal dysfunction and chronic kidney disease in ischemic stroke and transient ischemic attack: A population-based study.

Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 for ≥3 months, chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR < 60 mL/min per 1.73 m2, renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan-Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m2 (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR < 45 mL/min/1.73 m2 (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3-5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p < 0.001). After adjusting for age, stroke severity and pre-stroke disability, renal dysfunction (OR 2.17, p = 0.04) predicted poor functional outcome. Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.

Teaching Radiology to Medical Students-There Is a Need for Change to Better Prepare Students for Clinical Practice.

RATIONALE AND OBJECTIVES: Deriving maximum benefit from radiology rotations in medical schools is challenging. Lack of education on appropriate imaging renders students feeling unprepared. This study compares the ability of undergraduate medical students to identify appropriate radiological investigations, both at the beginning and end of their final year of education, to those of residents in their first year of clinical practice. MATERIALS AND METHODS: Twelve scenarios were extracted from the American College of Radiology's Appropriateness Criteria (ACR-AC) and a questionnaire was generated. One topic was selected from each of the 10 sections in the diagnostic section and two from the interventional section. The questionnaire was distributed to three groups. Group A was composed of medical students at the beginning of final year. Group B was composed of medical students at the end of final year. Group C was composed of residents at the end of their first year of clinical practice. Radiology residents were surveyed to assess familiarity with the ACR-AC among trainees in Ireland. RESULTS: The total cohort included 160 participants. Group C (n = 35) performed significantly better than group A (n = 72) and group B (n = 53). There was no statistical difference in the mean scores achieved by group A and group B. Sixteen (73%) of 22 radiology trainees were familiar with the ACR-AC. CONCLUSIONS: A minimal improvement in the knowledge of medical students in requesting radiological investigations over the course of the final medical year, yet a significant impact of a relatively short period of "on-the-job" learning in the clinical setting, was indicated. Emphasis on education on appropriateness may offer an improvement in the utilization of radiology services and improve patient care.

Integrating advanced practice providers into medical critical care teams.

Because there is increasing demand for critical care providers in the United States, many medical ICUs for adults have begun to integrate nurse practitioners and physician assistants into their medical teams. Studies suggest that such advanced practice providers (APPs), when appropriately trained in acute care, can be highly effective in helping to deliver high-quality medical critical care and can be important elements of teams with multiple providers, including those with medical house staff. One aspect of building an integrated team is a practice model that features appropriate coding and billing of services by all providers. Therefore, it is important to understand an APP's scope of practice, when they are qualified for reimbursement, and how they may appropriately coordinate coding and billing with other team providers. In particular, understanding when and how to appropriately code for critical care services (Current Procedural Terminology [CPT] code 99291, critical care, evaluation and management of the critically ill or critically injured patient, first 30-74 min; CPT code 99292, critical care, each additional 30 min) and procedures is vital for creating a sustainable program. Because APPs will likely play a growing role in medical critical care units in the future, more studies are needed to compare different practice models and to determine the best way to deploy this talent in specific ICU settings.

Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program.

OBJECTIVE: To better define the efficacy and safety of rimonabant, the first selective cannabinoid type 1 (CB(1)) receptor antagonist, in a large population of overweight and obese patients using pooled efficacy data from three Phase III nondiabetes Rimonabant in Obesity and Related Metabolic Disorders (RIO) studies, selected efficacy data from the RIO-Diabetes study, and pooled safety data for all four RIO studies. RESEARCH DESIGN AND METHODS: The RIO studies enrolled patients who were either overweight (BMI >27 kg/m(2)) with at least one comorbidity (i.e., hypertension, dyslipidemia, or, for RIO-Diabetes, type 2 diabetes) or obese. All patients received daily treatment with rimonabant (5 or 20 mg) or placebo for 1 year plus a hypocaloric diet (600 kcal/day deficit) and advice on increased physical activity. RIO-Europe (n = 1,508), RIO-North America (n = 3,045), and RIO-Lipids (n = 1,036) excluded patients with type 2 diabetes; untreated dyslipidemia was an entry requirement for RIO-Lipids. RIO-Diabetes (n = 1,047) required the presence of type 2 diabetes inadequately controlled by sulfonylurea or metformin monotherapy. RESULTS: The pooled intention-to-treat population comprised 5,580 patients without diabetes (3,165 completed treatment) and 1,047 patients with diabetes (692 completed treatment). Most efficacy measures improved during the 4-week placebo run-in period, except that HDL cholesterol decreased as expected in the early phase of a hypocaloric diet. After 1 year of randomized treatment, changes from baseline with 20 mg rimonabant in the nondiabetic population were as follows: body weight -6.5 kg, waist circumference -6.4 cm, HDL cholesterol +16.4%, triglycerides -6.9%, fasting insulin -0.6 muU/ml, and homeostasis model assessment for insulin resistance (HOMA-IR) -0.2 (all P < 0.001 vs. placebo). In the diabetic population, 20 mg rimonabant reduced A1C levels by 0.6% (P < 0.001 vs. placebo). Regression analysis of change in HDL cholesterol, triglycerides, adiponectin (in RIO-Lipids), and A1C (in RIO-Diabetes) versus body weight at 1 year by ANCOVA suggested that 45-57% of the effect of rimonabant could not be explained by the observed weight loss. At 1 year, adverse events more frequently reported with rimonabant were gastrointestinal, neurological, and psychiatric in nature. Serious adverse events were infrequent and almost equivalent to placebo. Overall discontinuation rates were similar across treatment groups, except discontinuation from adverse events, which occurred more frequently with 20 mg rimonabant versus placebo (most commonly, depressive disorders [1.9 vs. 0.8%], nausea [1.4 vs. 0.1%], mood alterations with depressive symptoms [1.0 vs. 0.6%], and anxiety [1.0 vs. 0.3%]). A thorough review of psychiatric and neurological adverse events was performed. CONCLUSIONS: In overweight/obese patients, 20 mg/day rimonabant produced weight loss and significant improvements in multiple cardiometabolic risk factors such as waist circumference, A1C, HDL cholesterol, and triglycerides. Rimonabant was generally well tolerated, with more frequently reported adverse events being gastrointestinal, neurological, and psychiatric in nature.