A risk-based monitoring approach to source data monitoring and documenting monitoring findings.

BACKGROUND: Clinical trial monitoring is evolving from labor-intensive to targeted approaches. The traditional 100% Source Data Monitoring (SDM) approach fails to prioritize data by significance, diverting attention from critical elements. Despite regulatory guidance on Risk-Based Monitoring (RBM), its widespread implementation has been slow. METHODS: Our study teams assess the study's overall risk, document heightened and critical risks, and create a study-specific risk-based monitoring plan, integrating SDM and Central Data Monitoring (CDM). SDM combines a fixed list of pre-identified variables and a list of randomly identified variables to monitor. Identifying variables follows a two-step approach: first, a random sample of participants is selected, second, a random set of variables for each participant selected is identified. Sampling weights prioritize critical variables. Regular team meetings are held to discuss and compile significant findings into a Study Monitoring Report. RESULTS: We present a random SDM sample and a Study Monitoring Report. The random SDM output includes a look-up table for selected database elements. The report provides a holistic view of the study issues and overall health. CONCLUSIONS: The proposed random sampling method is used to monitor a representative set of critical variables, while the Study Monitoring Report is written to summarize significant monitoring findings and data trends. The report allows the sponsor to assess the current status of the study and data effectively. Communicating and sharing emerging insights facilitates timely adjustments of future monitoring activities, optimizing efficiencies, and study outcomes.

Prevalence, Demographic, and Clinical Factors Associated With Cognitive Dysfunction in Patients With Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a chronic CNS demyelinating autoimmune disorder targeting the astrocyte antigen aquaporin-4 (AQP4), typically presenting with optic neuritis, transverse myelitis, and brain syndromes. Cognitive dysfunction (CD) in NMOSD is under-recognized and poorly understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with CD in NMOSD. METHODS: This observational retrospective study with longitudinal follow-up describes a clinical cohort seen in the Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD. Serial Montreal Cognitive Assessments (MoCAs) were performed upon enrollment and at 6-month intervals to evaluate longitudinal cognitive function relative to demographic and disease-related factors. We used 2-tailed t test, analysis of variance, the χ2 test, linear regression for univariable and adjusted analyses and simultaneous linear regression and mixed-effects model for multivariable analyses. RESULTS: Thirty-four percent (75/219) of patients met criteria for CD (MoCA <26); 29% (64/219) showed mild dysfunction (MoCA 20-26/30), and 5% (11/219) showed moderate (MoCA <20/30) dysfunction. Patients with less neurologic disability and lower pain scores had higher MoCA scores (95% CI 0.24-0.65 and 95% CI 0.09-0.42, respectively). Patients with at least high school education scored higher on the MoCA (95% CI 2.2-5). When comparing patients dichotomized for CD, patients never on rituximab scored higher than patients only treated with rituximab (p < 0.029). There was no significant association between annualized relapse rate, age, sex, disease duration, AQP4 serostatus or brain lesions, and CD. CD was more pronounced among Black than White patients (95% CI -2.7 to -0.7). Multivariable analysis of serial MoCA did not indicate change (p = 0.715). Descriptive analysis of serial MoCA showed 30% (45/150) of patients with worsening MoCA performance had impaired language and verbal recall. DISCUSSION: To our knowledge, this is the largest study of diverse cohort to investigate CD in patients with NMOSD. Our findings demonstrate 34% of patients with NMOSD experience mild-to-moderate CD, while 30% of patients demonstrated decline on serial testing. The substantial prevalence of CD in this pilot report highlights the need for improved and validated screening tools and comprehensive measures to investigate CD in NMOSD.

Return visit rates after an emergency department discharge for children with sickle cell pain episodes.

BACKGROUND: High return visit rates after hospitalization for people with sickle cell disease (SCD) have been previously established. Due to a lack of multicenter emergency department (ED) return visit rate data, the return visit rate following ED discharge for pediatric SCD pain treatment is currently unknown. PROCEDURE: A seven-site retrospective cohort study of discharged ED visits for pain by children with SCD was conducted using the Pediatric Emergency Care Applied Research Network Registry. Visits between January 2017 and November 2021 were identified using previously validated criteria. The primary outcome was the 14-day return visit rate, with 3- and 7-day rates also calculated. Modified Poisson regression was used to analyze associations for age, sex, initial hospitalization rate, and a visit during the COVID-19 pandemic with return visit rates. RESULTS: Of 2548 eligible ED visits, approximately 52% were patients less than 12 years old, 50% were female, and over 95% were non-Hispanic Black. The overall 14-day return visit rate was 29.1% (95% confidence interval [CI]: 27.4%-30.9%; site range 22.7%-31.7%); the 7- and 3-day return visit rates were 23.0% (95% CI: 21.3%-24.6%) and 16.7% (95% CI: 15.3%-18.2%), respectively. Younger children had slightly lower 14-day return visit rates (27.3% vs. 31.1%); there were no associations for site hospitalization rate, sex, and a visit occurring during the pandemic with 14-day returns. CONCLUSION: Nearly 30% of ED discharged visits after SCD pain treatment had a return visit within 14 days. Increased efforts are needed to identify causes for high ED return visit rates and ensure optimal ED and post-ED care.

Clinical and epidemiological correlates of treatment change in patients with NMOSD: insights from the CIRCLES cohort.

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) represent rare autoimmune diseases of the central nervous system largely targeting optic nerve(s) and spinal cord. The present analysis used real-world data to identify clinical and epidemiological correlates of treatment change in patients with NMOSD. METHODS: CIRCLES is a longitudinal, observational study of NMOSD conducted at 15 centers across North America. Patients with ≥ 60 days of follow-up and receiving on-study maintenance treatment were evaluated. The mean annual relapse rate (ARR) was estimated using negative binomial models; the likelihood of treatment change was estimated using Cox proportional hazards models. Relapses were included as time-varying covariates to estimate the relationship to treatment change. RESULTS: Of 542 patients included, 171 (31.5%) experienced ≥ 1 relapse on the study and 133 patients (24.5%) had ≥ 1 change in the treatment regimen. Two categories of variables significantly correlated with the likelihood of treatment change: (1) relapse: any on-study relapse (hazard ratio [HR] = 2.91; p < 0.001), relapse phenotypes (HR range = 2.15-5.49; p < 0.001), and pre-study ARR > 0.75 (HR 2.28; p < 0.001); 2) disease phenotype: brain syndrome only vs transverse myelitis involvement at onset (HR 2.44; p = 0.008), disease duration < 1 vs > 5 years (HR 1.66; p = 0.028), or autoimmune comorbidity (HR 1.55; p = 0.015). A subset of these factors significantly correlated with shorter time to first rituximab discontinuation. CONCLUSIONS: In CIRCLES, relapse patterns and disease phenotype significantly correlated with changes in the maintenance treatment regimen. Such findings may facilitate the identification of patients with NMOSD who are likely to benefit from treatment change to reduce relapse risk or disease burden and enhance the quality of life.

Extracorporeal membrane oxygenation and paediatric palliative care in an ICU.

OBJECTIVES: Compare rates, clinical characteristics, and outcomes of paediatric palliative care consultation in children supported on extracorporeal membrane oxygenation admitted to a single-centre 16-bed cardiac or a 28-bed paediatric ICU. METHODS: Retrospective review of clinical characteristics and outcomes of children (aged 0-21 years) supported on extracorporeal membrane oxygenation between January, 2017 and December, 2019 compared by palliative care consultation. MEASUREMENTS AND RESULTS: One hundred children (N = 100) were supported with extracorporeal membrane oxygenation; 19% received a palliative care consult. Compared to non-consulted children, consulted children had higher disease severity measured by higher complex chronic conditions at the end of extracorporeal membrane oxygenation hospitalisation (5 versus. 3; p < 0.001), longer hospital length of stay (92 days versus 19 days; p < 0.001), and higher use of life-sustaining therapies after decannulation (79% versus 23%; p < 0.001). Consultations occurred mainly for longitudinal psychosocial-spiritual support after patient survived device deployment with a median of 27 days after cannulation. Most children died in the ICU after withdrawal of life-sustaining therapies regardless of consultation status. Over two-thirds of the 44 deaths (84%; n = 37) occurred during extracorporeal membrane oxygenation hospitalisation. CONCLUSIONS: Palliative care consultation was rare showing that palliative care consultation was not viewed as an acute need and only considered when the clinical course became protracted. As a result, there are missed opportunities to involve palliative care earlier and more frequently in the care of extracorporeal membrane survivors and non-survivors and their families.

An Automatic Pediatric Palliative Care Consultation for Children Supported on Extracorporeal Membrane Oxygenation: A Survey of Perceived Benefits and Barriers.

Background: Pediatric palliative care (PPC) consultation is infrequent among children on extracorporeal membrane oxygenation (ECMO). Objective: Investigate intensive care unit (ICU) team members' perceptions of automatic PPC consultation for children on ECMO in an ICU in the United States. Methods: Cross-sectional survey assessing benefits, barriers to PPC, and consultation processes. Results: Of 291 eligible respondents, 48% (n = 140) completed the survey and 16% (n = 47) answered an open-ended question. Benefits included support in decision-making (n = 98; 70%) and identification of goals of care (n = 89; 64%). Barriers included perception of giving up on families (n = 59; 42%) and poor acceptability by other team members (n = 58; 41%). Respondents endorsed communication with the primary ICU team before (n = 122; 87%) and after (n = 129; 92%) consultation. Open-ended responses showed more positive (79% vs. 13%) than negative statements. Positive statements reflected on expanding PPC to other critically-ill children where negative statements revealed unrecognized value in PPC. Conclusions: Results demonstrate opportunities for education about the scope of PPC and improvements in PPC delivery.

Prevalence of specialised palliative care consultation for eligible children within a paediatric cardiac ICU.

OBJECTIVE: Retrospectively apply criteria from Center to Advance Palliative Care to a cohort of children treated in a cardiac ICU and compare children who received a palliative care consultation to those who were eligible for but did not receive one. METHODS: Medical records of children admitted to a cardiac ICU between January 2014 and June 2017 were reviewed. Selected criteria include cardiac ICU length of stay >14 days and/or ≥ 3 hospitalisations within a 6-month period. MEASUREMENTS AND RESULTS: A consultation occurred in 17% (n = 48) of 288 eligible children. Children who received a consult had longer cardiac ICU (27 days versus 17 days; p < 0.001) and hospital (91 days versus 35 days; p < 0.001) lengths of stay, more complex chronic conditions at the end of first hospitalisation (3 versus1; p < 0.001) and the end of the study (4 vs.2; p < 0.001), and higher mortality (42% versus 7%; p < 0.001) when compared with the non-consulted group. Of the 142 pre-natally diagnosed children, only one received a pre-natal consult and 23 received it post-natally. Children who received a consultation (n = 48) were almost 2 months of age at the time of the consult. CONCLUSIONS: Less than a quarter of eligible children received a consultation. The consultation usually occurred in the context of medical complexity, high risk of mortality, and at an older age, suggesting potential opportunities for more and earlier paediatric palliative care involvement in the cardiac ICU. Screening criteria to identify patients for a consultation may increase the use of palliative care services in the cardiac ICU.

Palliative Care in Children With Heart Disease Treated in an ICU.

OBJECTIVES: Describe pediatric palliative care consult in children with heart disease; retrospectively apply Center to Advance Palliative Care criteria for pediatric palliative care consults; determine the impact of pediatric palliative care on end of life. DESIGN: A retrospective single-center study. SETTING: A 16-bed cardiac ICU in a university-affiliated tertiary care children's hospital. PATIENTS: Children (0-21 yr old) with heart disease admitted to the cardiac ICU from January 2014 to June 2017. MEASUREMENTS AND MAIN RESULTS: Over 1,000 patients (n = 1, 389) were admitted to the cardiac ICU with 112 (8%) receiving a pediatric palliative care consultation. Patients who received a consult were different from those who did not. Patients who received pediatric palliative care were younger at first hospital admission (median 63 vs 239 d; p = 0.003), had a higher median number of complex chronic conditions at the end of first hospitalization (3 vs 1; p < 0.001), longer cumulative length of stay in the cardiac ICU (11 vs 2 d; p < 0.001) and hospital (60 vs 7 d; p < 0.001), and higher mortality rates (38% vs 3%; p < 0.001). When comparing location and modes of death, patients who received pediatric palliative care were more likely to die at home (24% vs 2%; p = 0.02) and had more comfort care at the end of life (36% vs 2%; p = 0.002) compared to those who did not. The Center to Advance Palliative Care guidelines identified 158 patients who were eligible for pediatric palliative care consultation; however, only 30 patients (19%) in our sample received a consult. CONCLUSIONS: Pediatric palliative care consult rarely occurred in the cardiac ICU. Patients who received a consult were medically complex and experienced high mortality. Comfort care at the end of life and death at home was more common when pediatric palliative care was consulted. Missed referrals were apparent when Center to Advance Palliative Care criteria were retrospectively applied.

Management of children with solid organ injuries after blunt torso trauma.

BACKGROUND: Management of children with intra-abdominal solid organ injuries has evolved markedly. We describe the current management of children with intra-abdominal solid organ injuries after blunt trauma in a large multicenter network. METHODS: We performed a planned secondary analysis of a prospective, multicenter observational study of children (<18 years) with blunt torso trauma. We included children with spleen, liver, or kidney injuries identified by computed tomography, laparotomy/laparoscopy, or autopsy. Outcomes included disposition and interventions (blood transfusion for intra-abdominal hemorrhage, angiography, laparotomy/laparoscopy). We performed subanalyses of children with isolated injuries. RESULTS: A total of 12,044 children were enrolled; 605 (5.0%) had intra-abdominal solid organ injuries. The mean (SD) age was 10.7 (5.1) years, and injured organs included spleen 299 (49.4%), liver 282 (46.6%), and kidney 147 (24.3%). Intraperitoneal fluid was identified on computed tomography in 461 (76%; 95% confidence interval [CI], 73-80%), and isolated solid organ injuries were present in 418 (69%; 95% CI, 65-73%). Treatment included therapeutic laparotomy in 17 (4.1%), angiographic embolization in 6 (1.4%), and blood transfusion in 46 (11%) patients. Laparotomy rates for isolated injury were 11 (5.4%) of 205 (95% CI, 2.7-9.4%) at non-freestanding children's hospitals and 6 (2.8%) of 213 (95% CI, 1.0-6.0%) at freestanding children's hospitals (difference, 2.6%; 95% CI, -7.1% to 12.2%). Dispositions of the 212 children with isolated Grade I or II organ injuries were home in 6 (3%), emergency department observation in 9 (4%), ward in 114 (54%), intensive care unit in 73 (34%), operating suite in 7 (3%), and transferred in 3 (1%) patients. Intensive care unit admission for isolated Grade I or II injuries varied by center from 9% to 73%. CONCLUSION: Most children with solid organ injuries are managed with observation. Blood transfusion, while uncommon, is the most frequent therapeutic intervention; angiographic embolization and laparotomy are uncommon. Emergency department disposition of children with isolated Grade I to II solid organ injuries is highly variable and often differs from published guidelines. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III; therapeutic study, level IV.

Outcomes after out-of-hospital endotracheal intubation errors.

INTRODUCTION: We sought to evaluate the association between three key out-of-hospital endotracheal intubation (ETI) errors and patient outcomes. METHODS: We prospectively collected multicenter data on out-of-hospital ETI attempted by Emergency Medical Service (EMS) rescuers. We probabilistically linked these data to statewide EMS, death and hospital discharge data sets. The key ETI error events were (1) endotracheal tube misplacement or dislodgement, (2) multiple ETI attempts (> or =4 laryngoscopies) and (3) failed ETI. The primary outcomes were death (survival to hospital discharge) and secondary complications identified through ICD-9 discharge diagnoses. Using Cox regression with heavyside functions, we identified the associations between out-of-hospital ETI errors and early (in the field or emergency department) and later (on or after hospital admission) death. We censored non-linked cases, adjusted for important clinical covariates, and used a shared frailty regression model to account for clustering by EMS agency. We evaluated the associations between out-of-hospital ETI errors and secondary complications using univariable odds ratios with exact 95% confidence intervals. RESULTS: Of 1954 out-of-hospital ETI, 444 (22.7%) patients experienced one or more ETI errors, including tube misplacement or dislodgement in 61 (3%), multiple ETI attempts in 62 (3%) and failed ETI in 359 (15%). Of the 1196 (61%) cases linked to outcomes, 872 (73%) died and 323 (27%) survived to hospital discharge. ETI errors were not associated with early death (tube misplacement or dislodgement: Hazard Ratio 0.98, 95% CI 0.65-1.47; multiple ETI attempts: 1.22, 0.80-1.85; failed ETI: 1.10, 0.88-1.39) or later death (tube misplacement or dislodgement: 0.40, 0.10-1.62; multiple ETI attempts: 1.77, 0.23-13.30; failed ETI: 0.76, 0.47-1.25). Pneumonitis was associated with failed ETI (n=20, 19%; univariable OR 2.54; 95% CI 1.24-5.25). CONCLUSION: Out-of-hospital ETI errors are not associated with mortality. Failed out-of-hospital ETI increases the odds of pneumonitis.

Resource utilization and its management in splenic trauma.

BACKGROUND: This study compared resource utilization and its management for splenic injury at 2 level-I trauma centers and a pediatric referral center with other facilities in a state currently developing a trauma system. METHODS: Management strategy, length of stay, and total charges for children were compared among the pediatric referral center, trauma centers, and other facilities. Adult management, length of stay, and total charges were compared between trauma centers and other facilities. RESULTS: Nonoperative management was more frequent in children at the pediatric referral center than trauma centers or other facilities and was more common in adults at trauma centers than at other facilities. Mean length of stay and total charges for children were significantly greater at the pediatric referral center and trauma centers than at other facilities and for adults at trauma centers than at other facilities. Facility type was associated with length of stay and total charges when injury type and severity were controlled. CONCLUSIONS: Nonoperative management of splenic injury is more common at trauma centers, and splenic trauma management may be more costly at trauma centers.