Garnering effective telehealth to help optimize multidisciplinary team engagement (GET2HOME) for children with medical complexity: Protocol for a pragmatic randomized control trial.

BACKGROUND: Children and young adults with medical complexity (CMC) experience high rates of healthcare reutilization following hospital discharge. Prior studies have identified common hospital-to-home transition failures that may increase the risk for reutilization, including medication, technology and equipment issues, financial concerns, and confusion about which providers can help with posthospitalization needs. Few interventions have been developed and evaluated for CMC during this transition period. OBJECTIVE: We will compare the effectiveness of the garnering effective telehealth 2 help optimize multidisciplinary team engagement (GET2HOME) transition bundle intervention to the standard hospital-based care coordination discharge process by assessing healthcare reutilization and patient- and family-centered outcomes. DESIGNS, SETTINGS, AND PARTICIPANTS: We will conduct a pragmatic 2-arm randomized controlled trial (RCT) comparing the GET2HOME bundle intervention to the standard hospital-based care discharge process on CMC hospitalized and discharged from hospital medicine at two sites of our pediatric medical center between November 2022 and February 2025. CMC of any age will be identified as having complex chronic disease using the Pediatric Medical Complexity Algorithm tool. We will exclude CMC who live independently, live in skilled nursing facilities, are in custody of the county, or are hospitalized for suicidal ideation or end-of-life care. INTERVENTION: We will randomize participants to the bundle intervention or standard hospital-based care coordination discharge process. The bundle intervention includes (1) predischarge telehealth huddle with inpatient providers, outpatient providers, patients, and their families; (2) care management discharge task tracker; and (3) postdischarge telehealth huddle with similar participants within 7 days of discharge. As part of the pragmatic design, families will choose if they want to complete the postdischarge huddle. The standard hospital-based discharge process includes a pharmacist, social worker, and care management support when consulted by the inpatient team but does not include huddles between providers and families. MAIN OUTCOME AND MEASURES: Primary outcome will be 30-day urgent healthcare reutilization (unplanned readmission, emergency department, and urgent care visits). Secondary outcomes include 7-day urgent healthcare reutilization, patient- and family-reported transition quality, quality of life, and time to return to baseline using electronic health record and surveys at 7, 30, 60, and 90 days following discharge. We will also evaluate heterogeneity of treatment effect for the intervention across levels of financial strain and for CMC with high-intensity neurologic impairment. The primary analysis will follow the intention-to-treat principle with logistic regression used to study reutilization outcomes and generalized linear mixed modeling to study repeated measures of patient- and family-reported outcomes over time. RESULTS: This pragmatic RCT is designed to evaluate the effectiveness of enhanced discharge transition support, including telehealth huddles and a care management discharge tool, for CMC and their families. Enrollment began in November 2022 and is projected to complete in February 2025. Primary analysis completion is anticipated in July 2025 with reporting of results following.

Diagnosis Code and Health Care Utilization Patterns Associated With Diagnostic Uncertainty.

BACKGROUND AND OBJECTIVES: Diagnostic uncertainty is challenging to identify and study in clinical practice. This study compares differences in diagnosis code and health care utilization between a unique cohort of hospitalized children with uncertain diagnoses (UD) and matched controls. PATIENTS AND METHODS: This case-control study was conducted at Cincinnati Children's Hospital Medical Center. Cases were defined as patients admitted to the pediatric hospital medicine service and having UDs during their hospitalization. Control patients were matched on age strata, biological sex, and time of year. Outcomes included type of diagnosis codes used (ie, disease- or nondisease-based) and change in code from admission to discharge. Differences in diagnosis codes were evaluated using conditional logistic regression. Health care utilization outcomes included hospital length of stay (LOS), hospital transfer, consulting service utilization, rapid response team activations, escalation to intensive care, and 30-day health care reutilization. Differences in health care utilization were assessed using bivariate statistics. RESULTS: Our final cohort included 240 UD cases and 911 matched controls. Compared with matched controls, UD cases were 8 times more likely to receive a nondisease-based diagnosis code (odds ratio [OR], 8.0; 95% confidence interval [CI], 5.7-11.2) and 2.5 times more likely to have a change in their primary International Classification of Disease, 10th revision, diagnosis code between admission and discharge (OR, 2.5; 95% CI, 1.9-3.4). UD cases had a longer average LOS and higher transfer rates to our main hospital campus, consulting service use, and 30-day readmission rates. CONCLUSIONS: Hospitalized children with UDs have meaningfully different patterns of diagnosis code use and increased health care utilization compared with matched controls.

A comprehensive literature review and meta-analysis of the prevalence of pan-cancer BRCA mutations, homologous recombination repair gene mutations, and homologous recombination deficiencies.

There is significant improvement in the outcomes following treatment with PARP inhibitors among patients with certain tumors that have BRCA mutations (BRCAm), homologous recombination repair (HRR) gene mutations, or homologous recombination deficiency (HRD) positivity. We performed a literature review and meta-analysis to evaluate the prevalence of BRCA1/2m, HRR gene mutations, and HRD positivity across multiple cancers. There were 265 publications on BRCA1/2 mutation prevalence, 189 on HRR gene mutation prevalence, and 7 on HRD positivity prevalence. The prevalences of germline BRCA1m and BRCA2m were 7.8% and 5.7% for breast cancer, 13.5% and 6.6% for ovarian cancer, 0.5% and 3.5% for prostate cancer, and 1.1% and 4.1% for pancreatic cancer, respectively. The prevalences of somatic BRCA1m and BRCA2m were 3.4% and 2.7% for breast cancer, 4.7% and 2.9% for ovarian cancer, 5.7% and 3.2% for prostate cancer, and 1.2% and 2.9% for pancreatic cancer, respectively. We identified 189 studies with over 418,649 samples across 25 tumor types that examined mutations in one or more HRR genes other than BRCA1/2. The prevalence of mutations among HRR genes remained low (less than 1%), with ATM (5.2%), CHEK2 (1.6%), and PALB2 (0.9%) exhibiting the highest prevalence. Seven studies evaluated HRD positivity in breast, ovarian, and prostate cancer patients. The prevalence of HRD positivity was 56% overall (95% CI = 48%-64%). The understanding of biomarker prevalence across tumor types and standardization of biomarker assays could have important clinical implications.

A Systematic Review and Meta-Analysis on the Prognostic Value of BRCA Mutations, Homologous Recombination Gene Mutations, and Homologous Recombination Deficiencies in Cancer.

Patients with BRCA1/2 mutations (BRCAm), loss-of-function mutations in other homologous recombination repair (HRRm) genes, or tumors that are homologous recombination deficiency positivity (HRD+) demonstrate a robust response to PARPi therapy. We conducted a systematic literature review and meta-analysis to evaluate the prognostic value of BRCAm, HRRm, and HRD+ on overall survival (OS) among those treated by chemotherapy or targeted therapy other than PARPi across tumor types. A total of 135 eligible studies were included. Breast cancer (BC) patients with BRCA1/2m had a similar overall survival (OS) to those with wild-type BRCA1/2 (BRCA1/2 wt) across 18 studies. Ovarian cancer (OC) patients with BRCA1/2m had a significantly longer OS than those with BRCA1/2 wt across 24 studies reporting BRCA1m and BRCA2m, with an HR of 0.7 (0.6-0.8). Less OS data were reported for other tumors: 6 studies for BRCA2m compared with BRCA2 wt in prostate cancer with an HR of 1.9 (1.1-3.2) and 2 studies for BRCA1/2m compared with BRCA1/2 wt in pancreatic cancer with an HR of 1.5 (0.8-3.1). Only 4 studies reported HRD+ by either BRCA m or genomic instability score (GIS) ≥ 42 and OS by HRD status. The HR was 0.67 (0.43-1.02) for OS with HRD+ vs. HRD-. A total of 15 studies reported the association between HRRm and OS of cancers in which one or more HRR genes were examined. The HR was 1.0 (0.7-1.4) comparing patients with HRRm to those with HRR wild-type across tumors. Our findings are useful in improving the precision and efficacy of treatment selection in clinical oncology.

Expression of human complement factor H prevents age-related macular degeneration-like retina damage and kidney abnormalities in aged Cfh knockout mice.

Complement factor H (CFH) is an important regulatory protein in the alternative pathway of the complement system, and CFH polymorphisms increase the genetic risk of age-related macular degeneration dramatically. These same human CFH variants have also been associated with dense deposit disease. To mechanistically study the function of CFH in the pathogenesis of these diseases, we created transgenic mouse lines using human CFH bacterial artificial chromosomes expressing full-length human CFH variants and crossed these to Cfh knockout (Cfh(-/-)) mice. Human CFH protein inhibited cleavage of mouse complement component 3 and factor B in plasma and in retinal pigment epithelium/choroid/sclera, establishing that human CFH regulates activation of the mouse alternative pathway. One of the mouse lines, which express relatively higher levels of CFH, demonstrated functional and structural protection of the retina owing to the Cfh deletion. Impaired visual function, detected as a deficit in the scotopic electroretinographic response, was improved in this transgenic mouse line compared with Cfh(-/-) mice, and transgenics had a thicker outer nuclear layer and less sub-retinal pigment epithelium deposit accumulation. In addition, expression of human CFH also completely protected the mice from developing kidney abnormalities associated with loss of CFH. These humanized CFH mice present a valuable model for study of the molecular mechanisms of age-related macular degeneration and dense deposit disease and for testing therapeutic targets.

Eosinophilic keratitis in 46 eyes of 27 horses in the Mid-Atlantic United States (2008-2012).

OBJECTIVE: To review the signalment, clinical characteristics, treatment, and outcome of equine EK cases in the Mid-Atlantic United States; to evaluate the effects of topical or systemic corticosteroid treatment, oral cetirizine treatment and secondary corneal infection on disease duration; and to evaluate the association between corticosteroid and cetirizine treatment and likelihood of recurrence. ANIMALS: Twenty-seven horses (47 eyes) diagnosed with EK from 2008 to 2012. PROCEDURE: Retrospective medical record review followed by phone interview to obtain recurrence data. RESULTS: Average age of affected horses was 8.2 years, SD 5.8 years. Eleven of 27 horses (41%) were diagnosed with EK in July. Twelve horses (44%) had been affected in previous years. Time to resolution averaged 3.7 months, SD 2.3 months. Ten horses (18 eyes) were treated with systemic dexamethasone, with a significantly shorter time to resolution, P = 0.03, averaging 2.23 months, SD 1.13 months, relative to horses not so treated, averaging 4.20 months, SD 1.47 months. Secondary infection led to a significant increase in time to resolution, P = 0.03, average 4.1 months, SD 1.7 months, relative to horses without secondary infection, average 3.0 months, SD 1.5 months. All eyes were visual at resolution. Horses treated with cetirizine were less likely to have recurrence during the follow-up period (1/13, or 8%) relative to horses not so treated (8/14, or 57%). CONCLUSIONS: Eosinophilic keratitis has a seasonal occurrence in summer in the Mid-Atlantic United States. Systemic but not topical corticosteroid treatment may decrease therapy duration. Treatment with cetirizine may be associated with a decreased risk of recurrence.

Evaluation of the effects of age and pituitary pars intermedia dysfunction on corneal sensitivity in horses.

OBJECTIVE: To determine effects of age and pituitary pars intermedia dysfunction (PPID) on corneal sensitivity in horses. ANIMALS: 20 adult horses allocated into 3 groups (PPID group, old [> 15 years old] horses with PPID [n = 5]; old group, old [> 15 years old] horses without PPID [9]; and young group, young [≤ 10 years old] horses without PPID [6]). All horses with PPID had hirsutism and abnormal fat deposition or laminitis; none of the old or young horses had hirsutism, abnormal fat deposition, or laminitis. PROCEDURES: A Cochet-Bonnet aesthesiometer was used to measure the corneal touch threshold (CTT) in both eyes of each horse. The nylon monofilament was applied at a maximum length of 60 mm to the central region of the cornea and length was decreased by 5-mm increments until a consistent blink response was elicited. Tear production was assessed in all eyes via the Shirmer tear test (STT). RESULTS: Mean ± SD CTT was significantly greater for young horses (47.50 ± 4.52 mm) than for horses in the old (28.06 ± 5.72 mm) and PPID (21.5 ± 3.37 mm) groups. Old horses had significantly higher CTT values than did horses with PPID. The STT values were within the reference range for all groups and did not differ significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Corneal sensitivity decreased with both age and PPID. Because decreased corneal sensitivity is associated with impaired wound healing, increasing age and PPID may increase the risk for nonhealing or recurrent corneal ulcers in horses.

A retrospective comparison of surgical removal and subsequent CO2 laser ablation versus topical administration of mitomycin C as therapy for equine corneolimbal squamous cell carcinoma.

OBJECTIVE: To compare the complications and nonrecurrence rate following topical mitomycin C (MMC) therapy vs. CO(2) laser ablation for treating equine corneolimbal squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Twenty-five horses with corneolimbal SCC. PROCEDURES: Medical records of horses undergoing surgical tumor resection followed by either topical MMC therapy (0.04%) or CO(2) laser ablation between the years of 2004 and 2010 were reviewed. Recurrence and complications were compared between groups and within MMC subgroups defined by the time at which treatment was initiated relative to surgery. RESULTS: Therapy with topical MMC resulted in a nonrecurrence rate comparable to that achieved with CO(2) laser ablation (82.4% vs. 85.7%, respectively). Initiation of MMC following epithelialization of the surgical site a mean of 15 days postoperatively did not result in increased recurrence rates relative to treatment in the immediate postoperative period. Vision- or globe-threatening complications tended to occur with greater frequency in horses receiving topical MMC in the immediate postoperative period (5 of 6 major complications) relative to following epithelialization of the surgical site (1 of 6 major complications). CONCLUSIONS: Horses receiving adjunctive topical MMC therapy were no more likely to experience tumor recurrence than were horses undergoing CO(2) laser ablation in the horses in this study. Initiation of two to three rounds of MMC following epithelialization of the surgical site results in fewer major complications and achieves comparable disease resolution relative to treatment in the immediate postoperative period.