Clinical investigator perspectives on patient outcomes in children with neuronopathic mucopolysaccharidosis II during intrathecal idursulfase-IT treatment.

BACKGROUND: Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by iduronate-2-sulfatase gene (IDS) deficiency and downstream glycosaminoglycan accumulation. Two-thirds of patients present with neuronopathic disease and evaluating cognitive function in these patients is challenging owing to limitations of currently available tests. During the clinical development of intrathecal idursulfase (idursulfase-IT), regulatory authorities requested qualitative data to further understand the neurocognitive changes observed by the investigators through the clinical trials. RESULTS: This qualitative study consisted of semi-structured interviews with all nine of the principal investigators who participated in the idursulfase-IT phase 2/3 (NCT02055118) and extension (NCT02412787) trials. These investigators enrolled the 56 patients with neuronopathic MPS II who qualified for the extension phase of the trial. The investigators were asked to rate the disease status of their patients. Of the 56 patients, 49 (88%) were rated as having disease that was improved/improving, stabilized or slowing progression compared with the expected outcomes with no treatment. Three patients were rated as worsening, while the remaining four patients were considered to have slowing progression or worsening disease. Similar results were demonstrated for patients aged from 3 to under 6 years at baseline, with 33 of 39 patients (85%) rated as having disease that was improved/improving, stabilized or slowing progression. Of the seven patients rated with slowing progression/worsening or worsening disease, five of them had an IDS variant other than missense, while two had a missense class variant. All the assigned improved/improving ratings were in patients receiving idursulfase-IT from the start of the phase 2/3 trial. Moreover, patients under 3 years of age at baseline were all rated as either improved/improving or stabilized disease. In a blinded review of patient profiles, investigators were requested to assign a disease status rating to 18 patients with large IDS deletions; 67% of these patients were rated as improved/improving or stabilized disease. CONCLUSIONS: This qualitative analysis provides a snapshot of clinicians' considerations when evaluating treatment in patients with neuronopathic MPS II, compared with the expected decline in cognitive function in the absence of treatment. The results highlight the importance of robust assessment tools in treatment evaluation.

Improvements in Patient-Reported Outcomes in Relapsed or Refractory Large B-Cell Lymphoma Patients Treated With Epcoritamab.

BACKGROUND: Patient-reported outcomes were evaluated in EPCORE NHL-1 in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) treated with epcoritamab monotherapy (NCT03625037). MATERIALS AND METHODS: Adults with R/R CD20+ LBCL and ≥2 prior systemic antilymphoma therapies, including anti-CD20, completed the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and EQ-5D-3L. A subgroup of patients provided additional feedback in one-on-one qualitative interviews. FACT-Lym and EQ-5D-3L score changes from baseline (CFB) to cycle 9 or end of treatment were interpreted using published minimally important differences (MID). RESULTS: In total, 157 patients (88.5% with diffuse LBCL) were treated (median age, 64 years). In total, 70.7% had ≥3 prior treatments, 61.1% had primary refractory disease, and 82.8% were refractory to last systemic therapy. FACT-Lym scores exceeded MID thresholds: mean (SD) CFB were 4.4 (15.2), MID 3.0 to 7.0 (FACT-General); 5.9 (7.6), MID 2.9 to 5.4 (FACT-Lymphoma subscale); 8.4 (15.2), MID 5.5 to 11.0 (FACT-Trial Outcome Index); 10.3 (20.2), MID 6.5 to 11.2 (FACT-Lym total score). EQ-5D-3L index scores, 0.09 (0.20), MID 0.08, and EQ-VAS scores, 16.6 (22.8), MID 7.0, improved. In 20 qualitative interviews, 88.2% reported symptom improvements; 80.0% were "very satisfied" or "satisfied" with epcoritamab. CONCLUSIONS: R/R LBCL patients reported consistent, clinically meaningful improvements in symptoms and HRQoL and satisfaction with epcoritamab.

Psychometric Analysis of the Patient-Reported Hypoparathyroidism Symptom Diary Symptom Subscale Using Data from Two Clinical Trials.

Purpose: The hypoparathyroidism symptom diary (HypoPT-SD) is a disease-specific patient-reported outcome (PRO) tool comprising a 7-item symptom subscale, a 4-item impact subscale and 1-item anxiety, and sadness or depression components. This analysis assessed the psychometric properties of the HypoPT-SD symptom subscale scores using data from two open-label, single arm, Phase 4 studies (Study 402 and Study 404). Patients and Methods: Eligible patients were aged 18 years or older with a confirmed diagnosis of hypoparathyroidism. All patients received recombinant human parathyroid hormone (1-84) during the analysis period. Scores were recorded at baseline, and at months 6, 30 and 36 (end of treatment [EOT]) in Study 402, and at baseline and week 52 (EOT) in Study 404. The structure of the HypoPT-SD Symptom subscale was analyzed by measuring correlations between pairs of item scores; internal consistency and reliability were evaluated using Cronbach's coefficient α; test-retest reliability was assessed using intraclass correlation; and construct validity was determined by performing correlational analyses between scores recorded using the HypoPT-SD and those for other conceptually similar PRO tools. Results: A total of 60 patients were included in the analysis. Inter-item pairwise correlations were strong for all but 5 of the item pairs analysed. Cronbach's α values for the HypoPT-SD Symptom subscale were 0.88 using data from Study 402 and 0.92 using data from Study 404. In general, the HypoPT-SD Symptom subscale scores had moderate or strong correlations with scores recorded using PRO tools. Intraclass correlation coefficients exceeded 0.70 using test-retest data from all patients in Study 402 and from a subgroup of patients with stable disease from Study 404. Conclusion: This analysis demonstrated the test-retest reliability, internal consistency and construct validity of the HypoPT-SD using data from longitudinal prospective studies and supports the use of the HypoPT-SD in future clinical studies.

Managing Difficult Patient Encounters.

Family physicians commonly find themselves in difficult patient encounters that can result in dissatisfaction for the patient and physician. Successful navigation of these encounters includes recognizing common physician factors, such as systemic pressures, interpersonal communication, and situational issues. The practice of labeling patient types can lead to disparities in care and patient harm and should be avoided. When physicians recognize that they are in a difficult patient encounter, simple mindfulness approaches, such as the Name It to Tame It and CALMER approaches, can improve outcomes. CALMER approaches help physicians acknowledge which situations they can control, alter their thoughts about the situation, and tolerate uncertainty. Physicians working with patients to create a therapeutic bond can focus the encounter to understand the situation that the patient is experiencing and work to recognize and acknowledge strong emotions that are nonproductive. Negotiating an agenda can help manage expectations of what can reasonably be done during each visit. Supporting patients by validating their symptoms and helping them embrace uncertainty can enable them to take control of their diagnosis and focus on managing chronic conditions rather than curing them. Motivational interviewing is a useful tool to help patients take ownership of their illnesses and therapeutic goals. Self-care through reflection groups or personal coaching or counseling can help physicians feel supported and avoid burnout.

Implementing a Discharge Follow-up Phone Call Program Reduces Readmission Rates in an Integrated Health System.

ABSTRACT: In this study, we sought to determine the effect of implementing a large-scale discharge follow-up phone call program on hospital readmission rates. Previous work has shown that patients with unaddressed concerns during discharge have significantly higher rates of care complications and hospital readmissions. This study is an observational quality improvement project completed from April 17, 2020 to January 31, 2022 at 22 hospitals in a large, integrated academic health system. A nurse-led scripted discharge follow-up phone call program was implemented to contact all patients discharged from inpatient care within 72 hours of discharge. Readmission rates were tracked before and after project implementation. Over a 21-month span, 137,515 phone calls were placed, and 57.92% of patients were successfully contacted within 7 days of discharge. The 7-day readmission rate for contacted patients was 2.91% compared with 4.73% for noncontacted patients. The 30-day readmission rate for contacted patients was 11.00% compared with 12.17% for noncontacted patients. We have found that discharge follow-up phone calls targeting patients decreases risk of readmission, which improves overall patient outcomes.

Programmable multi-kilobase RNA editing using CRISPR-mediated trans-splicing.

Current gene editing approaches in eukaryotic cells are limited to single base edits or small DNA insertions and deletions, and remain encumbered by unintended permanent effects and significant challenges in the delivery of large DNA cargo. Here we describe Splice Editing, a generalizable platform to correct gene transcripts in situ by programmable insertion or replacement of large RNA segments. By combining CRISPR-mediated RNA targeting with endogenous cellular RNA-splicing machinery, Splice Editing enables efficient, precise, and programmable large-scale editing of gene targets without DNA cleavage or mutagenesis. RNA sequencing and measurement of spliced protein products confirm that Splice Editing achieves efficient and specific targeted RNA and protein correction. We show that Splice Editors based on novel miniature RNA-targeting CRISPR-Cas systems discovered and characterized in this work can be packaged for effective delivery to human cells and affect different types of edits across multiple targets and cell lines. By editing thousands of bases simultaneously in a single reversible step, Splice Editing could expand the treatable disease population for monogenic diseases with large allelic diversity without the permanent unintended effects of DNA editing.

Evaluating meaningful changes in physical functioning and cognitive declines in metachromatic leukodystrophy: a caregiver interview study.

BACKGROUND: Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disease caused by deficient activity of arylsulfatase A (ASA). Treatment options for patients are limited; gene therapy based on haematopoietic stem cell transplantation is the only approved treatment for some subtypes of MLD. Any therapeutic benefit of treatments must be meaningful for patients and their families. We evaluated the clinical meaningfulness of slowing the decline in gross motor function as measured by the Gross Motor Function Classification in MLD (GMFC-MLD) from the caregiver perspective via semi-structured telephone interviews with caregivers of children with late-infantile MLD. We also evaluated the perceived significance of declines in communication abilities measured by the Expressive Language Function Classification in MLD (ELFC-MLD). This work could help to inform the endpoints of a phase 2 clinical trial (NCT03771898) assessing the efficacy of intrathecal recombinant human ASA in MLD. RESULTS: Twelve caregivers were recruited, reporting on 12 children with MLD. Children had a mean age of 6.1 years; mean age at symptom onset was 17.6 months. Most children (10/12) progressed from walking without support (categories 0-1) to a loss of locomotion (categories 5-6) in ≤ 2 years. Caregivers felt that GMFC-MLD and ELFC-MLD accurately described motor and language declines in their children, respectively. Most caregivers (10/12) reported that the idea of delaying disease progression would be meaningful. Further, a slowing of motor function decline in GMFC-MLD, from category 1 to category 3 or from category 2 to category 4 over 2 years, was seen as meaningful by all caregivers asked; however, only 3/12 caregivers reported that delayed decline would be meaningful if baseline category was ≥ 3. Caregivers also reported that delaying expressive language decline at any level that did not indicate a complete loss of expressive language (indicated by categories 1-3) would be meaningful. CONCLUSIONS: Caregivers of children with MLD felt that a delayed decline in gross motor function, as assessed by the GMFC-MLD, would be meaningful, supporting the selection of primary and secondary endpoints for the phase 2 clinical trial. Communication abilities were another area of significance for consideration in future clinical trial design.

A Current State Assessment on Nursing Work Activities: An Observational Study.

BACKGROUND: Nationwide nursing shortages have led to higher patient-to-nurse ratios, nursing burnout, and decreased quality of care. LOCAL PROBLEM: Staffing challenges and nursing burnout were becoming growing concerns and success was contingent upon efficient use of existing resources. METHODS: Direct observation current state assessment was completed on medical-surgical specialty units to better understand work activities of registered nurses (RNs) and unlicensed assistive personnel (UAPs). RESULTS: RNs spent more time performing indirect care (eg, documentation) than direct patient care. Interruptions and problems consumed 17.4% and 5.6% of their time, respectively. UAPs performed more direct patient care but had a higher proportion of downtime. RNs underdelegated nonclinical tasks. CONCLUSIONS: Direct observation current state assessment offers a better understanding of workflow and workload inefficiencies. This information is critical to provide informed, evidence-based recommendations to develop future patient care models with more capacity to deliver high-quality care with greater efficiency and lessen nursing burden and burnout during the nursing shortage crisis.

Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis.

BACKGROUND: The associations of adiposity with aggressive prostate cancer risk are unclear. Using two-sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer. METHODS: We examined the association of these genetically predicted adiposity-related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases). RESULTS: In inverse-variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61-1.19), 0.80 (0.53-1.23) and 0.97 (0.88-1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer. CONCLUSIONS: We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies.

Development and evaluation of the Acromegaly Symptom Diary.

BACKGROUND: Patient-reported outcome (PRO) measures are important to consider when evaluating treatments, yet there are no PRO measures for patients with acromegaly that have been developed in accordance with US Food and Drug Administration guidance. Acromegaly is a rare, chronic condition caused by hypersecretion of growth hormone. Disease activity is monitored by measurement in serum of growth hormone and insulin-like growth factor-I. The objectives of this research were to develop the Acromegaly Symptom Diary (ASD), establish a scoring algorithm, and evaluate the psychometric measurement properties of the ASD. METHODS: Semistructured interviews consisting of concept elicitation and cognitive debriefing components were conducted with 16 adult participants with acromegaly. The concept elicitation component identified symptoms important to individuals with acromegaly. The cognitive debriefing component gathered information about the participants' experience with each proposed item of the ASD, their thought process for answering each question, and their interpretation of the items. The psychometric properties of the draft ASD were then evaluated using data from the ACROBAT Evolve (NCT03792555; n = 13) and ACROBAT Edge (NCT03789656; n = 47) clinical trials. RESULTS: The 16 participants from the interviews described ongoing symptoms, with the most frequently reported being joint pain (n = 13) and fatigue (n = 12), followed by swelling (n = 8), headache (n = 7), and mood swings (n = 6), and were able to interpret and understand the ASD items and had no issues with the 24-hour recall period. From data collected in the clinical studies, the psychometric properties of internal consistency (0.91 - 0.80), test-retest reliability with item-level and total ASD scores (> 0.70), baseline construct validity (r ≥ |0.38|) across scales, and responsiveness to change (r = 0.52-0.56) were supported for the ASD. The proposed preliminary threshold range to characterize a meaningful change from the patients' perspective for the ASD total is a 4- to 6-point change for improvement or worsening out of a total score of 70. CONCLUSION: These findings provide qualitative and quantitative evidence to support the ASD as fit for the purpose of evaluating the symptom experience of patients with acromegaly in clinical trials.

Using Serum Cystatin C to Predict Acute Kidney Injury Following Infant Cardiac Surgery.

Acute kidney injury (AKI) following cardiopulmonary bypass (CPB) is associated with increased morbidity and mortality. Serum Cystatin C (CysC) is a novel biomarker synthesized by all nucleated cells that may act as an early indicator of AKI following infant CPB. Prospective observational study of infants (< 1 year) requiring CPB during cardiac surgery. CysC was measured at baseline and 12, 24, 48, and 72 h following CPB initiation. Each post-op percent difference in CysC (e.g. %CysC12h) from baseline was calculated. Clinical variables along with urine output (UOP) and serum creatinine (SCr) were followed. Subjects were divided into two groups: AKI and non-AKI based upon the Kidney Disease Improving Global Outcomes (KDIGO) classification. AKI occurred in 41.9% (18) of the 43 infants enrolled. Patient demographics and baseline CysC levels were similar between groups. CysC levels were 0.97 ± 0.28 mg/L over the study period, and directly correlated with SCr (R = 0.71, p < 0.0001). Although absolute CysC levels were not significant between groups, the %CysC12h was significantly greater in the AKI group (AKI: - 16% ± 22% vs. Non-AKI - 28% ± 9% mg/L; p = 0.003). However, multivariate analysis demonstrated that a lower UOP (Odds Ratio:0.298; 95% CI 0.073, 0.850; p = 0.02) but not %CysC12h was independently associated with AKI. Despite a significant difference in the %CysC12h, only UOP was independently associated with AKI. Larger studies of a more homogenous population are needed to understand these results and to explore the variability in this biomarker seen across institutions.

A Patient-Centered Perspective of Molluscum Contagiosum as Reported by B-SIMPLE4 Clinical Trial Patients and Caregivers: Global Impression of Change and Exit Interview Substudy Results.

BACKGROUND: Molluscum contagiosum is often characterized by persistent lesions and bothersome symptomology. What patients with molluscum contagiosum and/or caregivers consider to be meaningful measures of therapeutic success is unknown. OBJECTIVE: We aimed to collect patient experience data and assess Global Impression of Change from patients and/or caregivers participating in a large phase III molluscum contagiosum interventional trial. METHODS: The Berdazimer Sodium In Molluscum Patients with LEsions (B-SIMPLE4) phase III study enrolled 891 patients with molluscum contagiosum. Patients were randomly assigned to berdazimer gel, 10.3% or vehicle gel applied once daily for 12 weeks. Assessments of participant and investigator perceptions of complete lesion clearance were collected at weeks 12 and 24 along with Global Impression of Change scores from 1 (very much improved) to 7 (very much worse). A subset of 30 B-SIMPLE4 patients participated in the patient/caregiver experience exit interview to evaluate bothersome signs and symptoms. RESULTS: At week 12, among participants with a ≥ 75% molluscum contagiosum lesion count reduction from baseline (as assessed by investigators), 99% (373/376) reported improvement. Perceptions of complete clearance at week 12 were nearly 40% for both participant-reported and investigator-reported Global Impression of Change in berdazimer group vs 20% in the vehicle group: 82% (322/392) of participants in the berdazimer group and 60% (237/394) in the vehicle group reported their molluscum contagiosum lesions were either very much improved or much improved at week 12. Similarly, investigators scored 80% (314/393) of berdazimer and 54% (215/396) of vehicle participants as very much improved or much improved. From the exit interview, the mean duration of participant-reported molluscum contagiosum was nearly 2 years. The most frequently reported molluscum contagiosum-related signs and symptoms were itch (n = 20), scarring (n = 18), and pain (n = 13). Visibility and contagiousness of molluscum contagiosum were the most bothersome aspects to participants. The most frequently reported psychosocial impacts were self-consciousness (n = 15) and embarrassment (n = 14). Lesion clearance was an expectation of 28/30 study participants. Overall, 26/30 reported being very satisfied (n = 18) or satisfied (n = 8) with the changes in their disease over the duration of the trial; 23/30 stated that the change in lesion count was meaningful. A mean reduction of 18 lesions (76% decrease) from the baseline lesion count was reported by participants (n = 28). Although 22 of 28 had less than complete lesion clearance, 17 of 22 reported that the reduction in the number of lesions was meaningful. CONCLUSIONS: Molluscum contagiosum lesion reductions, with or without complete clearance, may be considered a therapeutic "success" by the patient/caregiver. CLINICAL TRIAL REGISTRATION: NCT04535531 (registered 2 September, 2020).

Case report and review of the literature: Successful transition from acute continuous veno-venous hemodiafiltration therapy to chronic peritoneal dialysis in a chronically ventilated child with hypoplastic left heart syndrome following fontan.

Fontan palliation depends on low pulmonary vascular resistance in order to maintain pulmonary blood flow and adequate oxygenation. This physiology results in higher central venous pressures with limited renal perfusion pressure and cardiac output. Positive pressure ventilation with mechanical ventilation increases intrathoracic pressure and raises central venous pressure and can further limit pulmonary and renal perfusion. Fluid removal with intermittent hemodialysis can be challenging in Fontan patients and can cause intolerable hypotension, however the increased abdominal filling pressures during peritoneal dialysis dwells can exacerbate systemic venous hypertension seen in Fontan patients and threaten adequate pulmonary blood flow and cardiac output. Successful transition to peritoneal dialysis in a chronically ventilated patient with hypoplastic left heart syndrome, end-stage renal disease and Fontan physiology has not been described. We present details outlining the successful transition across multiple modalities of renal replacement therapy to assist other teams faced with similar challenges in chronically ventilated Fontan patients with end-stage renal disease.

Effectiveness of a targeted telephone-based case management service on activity in an Emergency Department in the UK: a pragmatic difference-in-differences evaluation.

BACKGROUND: This study evaluates the effectiveness of a targeted telephone-based case management service that aimed to reduce ED attendance amongst frequent attenders, known to disproportionately contribute to demand. Evidence on the effectiveness of these services varies. METHODS: A 24-month controlled before-and-after study, following 808 patients (128 cases and 680 controls (41 were non-compliant)) who were offered the service in the first four months of operation within a UK ED department. Patients stratified as high-risk of reattending ED within 6 months by a predictive model were manually screened. Those positively reviewed were offered a non-clinical, nurse-led, telephone-based health coaching, consisting of care planning, coordination and goal setting for up to 9 months. Service effectiveness was estimated using a difference-in-differences (DiD) analysis. Incident rate of ED and Minor Injury Unit (MIU) attendances and average length of stay in intervention recipients and controls over 12 months after receiving their service offer following ED attendance were compared, adjusting for the prior 12-month period, sex and age, to give an incidence rate ratio (IRR). RESULTS: Intervention recipients were more likely to be female (63.3% versus 55.4%), younger (mean of 69 years versus 76 years), and have higher levels of ED activity (except for MIU) than controls. Mean rates fell between periods for all outcomes (except for MIU attendance). The Intention-to-Treat analysis indicated non-statistically significant effect of the intervention in reducing all outcomes, except for MIU attendances, with IRRs: ED attendances, 0.856 (95% CI: 0.631, 1.160); ED admissions, 0.871 (95% CI: 0.628, 1.208); length of stay for emergency and elective admissions: 0.844 (95% CI: 0.619, 1.151) and 0.781 (95% CI: 0.420, 1.454). MIU attendance increased with an IRR: 2.638 (95% CI: 1.041, 6.680). CONCLUSIONS: Telephone-based health coaching appears to be effective in reducing ED attendances and admissions, with shorter lengths of stay, in intervention recipients over controls. Future studies need to capture outcomes beyond acute activity, and better understand how services like this provide added value.

Qualitative interviews in patients with lipodystrophy to assess the patient experience: evaluation of hunger and other symptoms.

BACKGROUND: New treatments are being evaluated for lipodystrophy; however, limited information is available on the patient experience. Results of a prior patient panel showed that hunger and temperature-related symptoms were an issue for participants. Therefore, evaluation of any changes in these symptoms is recommended for inclusion in new treatment options. The objective of this study was to further understand the patient experience and to evaluate newly developed items of hunger and temperature regulation. METHODS: Individual, in-depth telephone interviews were conducted via semi-structured discussion guide. Telephone interviews were conducted with 21 US patients with generalized lipodystrophy (GLD) or partial lipodystrophy (PLD). Eligibility requirements included self-reported PLD or GLD. Interviews included open-ended concept elicitation followed by a review of newly developed items assessing hunger, temperature sensations, and patient globals. Interviews were conducted in two rounds, with the newly developed items assessing hunger revised after each round of interviews based on participant feedback. RESULTS: Results indicated that hunger-related symptoms were considered a current issue for greater than half (N = 11) of participants, and all but one reported this as an issue at some point in their lives. Specifically, participants most often reported symptoms of increased appetite and not feeling full. The cognitive debriefing process indicated that the hunger-related symptoms, temperature, and global impression of change and severity items were correctly interpreted and easily completed by the participants. While not a focus of the interviews, the concept elicitation results demonstrated that pain was a frequently reported and bothersome symptom in this patient population. CONCLUSIONS: This qualitative research provided evidence to support the use of clinical outcomes assessments such as hunger and temperature-related items in clinical trials.

Associations Between Implementation of the Caregiver Advise Record Enable (CARE) Act and Health Service Utilization for Older Adults with Diabetes: Retrospective Observational Study.

BACKGROUND: The Caregiver Advise Record Enable (CARE) Act is a state level law that requires hospitals to identify and educate caregivers ("family members or friends") upon discharge. OBJECTIVE: This study examined the association between the implementation of the CARE Act in a Pennsylvania health system and health service utilization (ie, reducing hospital readmission, emergency department [ED] visits, and mortality) for older adults with diabetes. METHODS: The key elements of the CARE Act were implemented and applied to the patients discharged to home. The data between May and October 2017 were pulled from inpatient electronic health records. Likelihood-ratio chi-square tests and multivariate logistic regression models were used for statistical analysis. RESULTS: The sample consisted of 2591 older inpatients with diabetes with a mean age of 74.6 (SD 7.1) years. Of the 2591 patients, 46.1% (n=1194) were female, 86.9% (n=2251) were White, 97.4% (n=2523) had type 2 diabetes, and 69.5% (n=1801) identified a caregiver. Of the 1801 caregivers identified, 399 (22.2%) received discharge education and training. We compared the differences in health service utilization between pre- and postimplementation of the CARE Act; however, no significance was found. No significant differences were detected from the bivariate analyses in any outcomes between individuals who identified a caregiver and those who declined to identify a caregiver. After adjusting for risk factors (multivariate analysis), those who identified a caregiver (12.2%, 219/1801) was associated with higher rates of 30-day hospital readmission than those who declined to identify a caregiver (9.9%, 78/790; odds ratio [OR] 1.38, 95% CI 1.04-1.87; P=.02). Significantly lower rates were detected in 7-day readmission (P=.02), as well as 7-day (P=.03) and 30-day (P=.01) ED visits, among patients with diabetes whose identified caregiver received education and training than those whose identified caregiver did not receive education and training in the bivariate analyses. However, after adjusting for risk factors, no significance was found in 7-day readmission (OR 0.53, 95% CI 0.27-1.05; P=.07), 7-day ED visit (OR 0.63, 95% CI 0.38-1.03; P=.07), and 30-day ED visit (OR 0.73, 95% CI 0.52-1.02; P=.07). No significant associations were found for other outcomes (ie, 30-day readmission and 7-day and 30-day mortality) in both the bivariate and multivariate analyses. CONCLUSIONS: Our study found that the implementation of the CARE Act was associated with certain health service utilization. The identification of caregivers was associated with higher rates of 30-day hospital readmission in the multivariate analysis, whereas having identified caregivers who received discharge education was associated with lower rates of readmission and ED visit in the bivariate analysis.

Estimation of Effect Heterogeneity in Rare Events Meta-Analysis.

The paper outlines several approaches for dealing with meta-analyses of count outcome data. These counts are the accumulation of occurred events, and these events might be rare, so a special feature of the meta-analysis is dealing with low counts including zero-count studies. Emphasis is put on approaches which are state of the art for count data modelling including mixed log-linear (Poisson) and mixed logistic (binomial) regression as well as nonparametric mixture models for count data of Poisson and binomial type. A simulation study investigates the performance and capability of discrete mixture models in estimating effect heterogeneity. The approaches are exemplified on a meta-analytic case study investigating the acceptance of bibliotherapy.