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AbstractObjectivesIn this study we aimed to describe and compare groups formed by a rules‐based algorithm to prospectively identify clients at risk of poor outcomes in order to guide tailored public health nursing (PHN) intervention approaches.DesignData‐driven methods using standardized Omaha System PHN documentation.SampleClients ages 13–40 who received PHN home visiting services for both the Caretaking/parenting and Mental health problems (N = 4109).MeasurementWe applied a theory‐based algorithm consisting of six rules using existing Omaha System data. We examined the groups formed by the algorithm using standard descriptive, inferential statistics, and Latent Class Analysis.ResultsClients (N = 4109) were 25.1 (SD = 5.9) years old and had an average of 7.3 (SD = 3.2) problems, 250 (SD = 319) total interventions, and 32 (SD = 44) Mental health interventions. Overall outcomes improved after PHN interventions (p < .001 for all) and having more Mental health signs/symptoms was negatively associated with outcome scores (p < .001 for all).ConclusionsThis algorithm may be helpful in identifying high‐risk clients during a baseline assessment who may benefit from more intensive mental health interventions. Findings show there is value using the Omaha System for PHN documentation and algorithm clinical decision support development. Future research should focus on algorithm implementation in PHN clinical practice.

Abstract Background Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Recent studies have proposed prognostic meningioma classification systems using DNA methylation profiling, copy number variants, DNA sequencing, RNA sequencing, histology, or integrated models based on multiple combined features. Targeted gene expression profiling has generated robust biomarkers integrating multiple molecular features for other cancers, but is understudied for meningiomas. Methods Targeted gene expression profiling was performed on 173 meningiomas and an optimized gene expression biomarker (34 genes) and risk score (0 to 1) was developed to predict clinical outcomes. Clinical and analytical validation was performed on independent meningiomas from 12 institutions across 3 continents (N = 1856), including 103 meningiomas from a prospective clinical trial. Gene expression biomarker performance was compared to 9 other classification systems. Results The gene expression biomarker improved discrimination of postoperative meningioma outcomes compared to all other classification systems tested in the independent clinical validation cohort for local recurrence (5-year area under the curve [AUC] 0.81) and overall survival (5-year AUC 0.80). The increase in area under the curve compared to the current standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval [CI] 0.07–0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% CI 0.37–0.78, P = 0.0001) and re-classified up to 52.0% meningiomas compared to conventional clinical criteria, suggesting postoperative management could be refined for 29.8% of patients. Conclusions A targeted gene expression biomarker improves discrimination of meningioma outcomes compared to recent classification systems and predicts postoperative radiotherapy responses.

We conducted a retrospective/prospective worldwide study on patients with neuroendocrine neoplasms (NENs) and a molecularly proven SARS-CoV-2 positivity. Preliminary results regarding 85 patients of the INTENSIVE study have been published in 2021. Now we are reporting the 2-year analysis.Here, we are reporting data from consecutive patients enrolled between 1 June 2020, and 31 May 2022. Among the 118 contacted centers, 25 were active to enroll and 19 actively recruiting at the time of data cut-off for a total of 280 patients enrolled. SARS-CoV-2 positivity occurred in 47.5% of patients in 2020, 35.1% in 2021, and 17.4% in 2022. The median age for COVID-19 diagnosis was 60 years. Well-differentiated tumors, non-functioning, metastatic stage, and gastroenteropancreatic (GEP) primary sites represented most of the NENs. COVID-19-related pneumonia occurred in 22.8% of the total, with 61.3% of them requiring hospitalization; 11 patients (3.9%) needed sub-intensive or intensive care unit therapies and 14 patients died (5%), in 11 cases (3.9%) directly related to COVID-19. Diabetes mellitus and age at COVID-19 diagnosis > 70 years were significantly associated with COVID-19 mortality, whereas thoracic primary site with COVID-19 morbidity. A significant decrease in both hospitalization and pneumonia occurred in 2022 vs 2020. In our largest series of NEN patients with COVID-19, the NEN population is similar to the general population of patients with NEN regardless of COVID-19. However, older age, non-GEP primary sites and diabetes mellitus should be carefully considered for increased COVID-19 morbidity and mortality. Relevant information could be derived by integrating our results with NENs patients included in other cancer patients with COVID-19 registries.

Introduction Maintaining fluid intake sufficient to reduce arginine vasopressin (AVP) secretion has been hypothesised to slow kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). However, evidence to support this as a clinical practice recommendation is of poor quality. The aim of the present study is to determine the long-term efficacy and safety of prescribed water intake to prevent the progression of height-adjusted total kidney volume (ht-TKV) in patients with chronic kidney disease (stages 1–3) due to ADPKD. Methods and analysis A multicentre, prospective, parallel-group, open-label, randomised controlled trial will be conducted. Patients with ADPKD (n=180; age ≤65 years, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m 2 ) will be randomised (1:1) to either the control (standard treatment+usual fluid intake) or intervention (standard treatment+prescribed fluid intake) group. Participants in the intervention arm will be prescribed an individualised daily fluid intake to reduce urine osmolality to ≤270 mOsmol/kg, and supported with structured clinic and telephonic dietetic review, self-monitoring of urine-specific gravity, short message service text reminders and internet-based tools. All participants will have 6-monthly follow-up visits, and ht-TKV will be measured by MRI at 0, 18 and 36 months. The primary end point is the annual rate of change in ht-TKV as determined by serial renal MRI in control vs intervention groups, from baseline to 3 years. The secondary end points are differences between the two groups in systemic AVP activity, renal disease (eGFR, blood pressure, renal pain), patient adherence, acceptability and safety. Ethics and dissemination The trial was approved by the Human Research Ethics Committee, Western Sydney Local Health District. The results will inform clinicians, patients and policy-makers regarding the long-term safety, efficacy and feasibility of prescribed fluid intake as an approach to reduce kidney cyst growth in patients with ADPKD. Trial registration number ANZCTR12614001216606.

Objectives: Administrative criteria are often used to define COVID-19 outcomes despite challenges in differentiating hospitalization “for” vs “with” COVID-19 and unknown reliability for identifying COVID-related cardiopulmonary complications. We implemented a protocol to adjudicate COVID-related events across 14 studies participating in C4R. Methods: C4R cohorts ascertained COVID-related hospitalizations and deaths via questionnaires or ongoing surveillance. Medical records were reviewed by C4R physicians using a standardized protocol to assign COVID-related diagnoses as definite or probable. C4R diagnoses were compared against ICD codes assigned to the events. This report includes data from events centrally adjudicated by C4R as of September 2022. Results: Among 144 events ascertained across 7 cohorts as potentially COVID-related, SARS-CoV-2 infection was confirmed in 107/117 (91%) non-fatal hospitalizations and 26/27 (96%) deaths. Of confirmed infections, COVID-19 illness was diagnosed as the cause of 101/107 (94%) hospitalizations and 24/26 (92%) deaths ( Table ). Of non-fatal hospitalizations with infection, 72% were diagnosed with severe or critical COVID-19, 78% with COVID-associated pneumonia, and 29% with renal failure; other complications were less common. C4R review did not validate diagnoses indicated by ICD codes for 1 COVID-19 infection, 5 pneumonias, 1 stroke, and 7 renal failure cases. C4R review did identify diagnoses that were not ICD-coded for 13 infections, 31 pneumonias, 6 myocardial infarctions, 5 venous thromboses, and 21 renal failure cases. Conclusions: Protocolized medical records review by C4R confirmed COVID-19 as the cause of hospitalization or death in 87% of events ascertained as potentially COVID-related and 94% of those in which SARS-CoV-2 infection was confirmed. Both false-positive and false-negative misclassification by ICD criteria was observed. Protocolized review may be useful to identify and validate COVID-related events for epidemiologic research.

Introduction: Over 6 million people in the U.S. have heart failure (HF), less than half are expected to survive beyond 5 years. The need to better stratify mortality risk in HF is recognized. Frailty is associated with mortality in HF but not routinely measured clinically. As frailty is linked to inflammation and malnutrition, we hypothesized that the Metabolic Vulnerability Index (MVX) a multimarker score of systemic inflammation (small HDL particles, GlycA) and malnutrition (leucine, valine, isoleucine, citrate), could serve as a biomarker of frailty to predict mortality risk. Methods: Clinical data and plasma were collected from 1,389 patients from a HF community cohort between 2003-2012. We measured frailty using the Rockwood Index as the proportion of deficits present out of 32 physical limitations and comorbidities. MVX was calculated from the nuclear magnetic resonance LipoProfile® test. Patients were categorized by frailty (0-0.15; 0.16-0.27; 0.28-0.78) and MVX (33.4-50, 50-60, 60-70, 70-85.8) cutpoints. Cox models estimated the association of frailty and MVX assignment with mortality, adjusted for Meta-Analysis Global Group in Chronic HF (MAGGIC) score, a validated clinical risk score for HF mortality. Results: Frailty and MVX scores were available in 985 patients (median age 77, IQR: 67-84; 48% women). Higher frailty was associated with higher MVX (p-trend < 0.001). The highest frailty and MVX groups experienced large increases in risk of death, after adjustment for MAGGIC score (HR=3.3, 95% CI=2.6-4.2) and (HR=2.7, 95% CI=2.1-3.5), respectively. When adjusted for one another and MAGGIC score, MVX and frailty associations with death were only minimally attenuated: frailty (HR=3.2, 95% CI=2.5-4.0) and MVX (HR=2.4, 95% CI=1.9-3.2) (Figure 1). Conclusion: In this community cohort of patients with HF, frailty and MVX are positively associated with one another. However, both indicators are independently associated with an increased risk of death and can contribute to risk stratification.

Background: Heart failure (HF) is associated with metabolic alterations, including ketogenesis. However, determinants of ketogenesis and risk of mortality in HF is not defined. Total ketone bodies (KB) include β-hydroxybutyrate, acetoacetate, and acetone and can be measured in plasma by nuclear magnetic resonance (NMR). The aim of this study is to determine the relationship between KB and clinical characteristics in a community HF cohort and to assess the association between KB and all-cause mortality. Methods: A population-based cohort of 1,389 HF patients was prospectively enrolled between 2003 and 2012. Plasma KB was measured by LP4 NMR LipoProfile ® assay/test on the Vantera® NMR analyzer platform. A conditional inference tree method (ctree R Package) was used to determine optimal KB group cut points. Associations between clinical characteristics and KB were measured with Wilcoxon rank sum test and Pearson’s Chi-squared test. Kaplan-Meier method estimated survival. Cox regression analyses were used to estimate associations between KB concentrations and mortality. Results: Among the 1,382 HF patients with KB measurements, the median age was 78 years (IQR 68-84) and 52% were men. Median KB was 180 μM (IQR 134-308). Patients were divided into two groups with lower KB (≤471.5 μM) and higher KB (>471.5 μM). Patients with higher KB (N=210) had lower BMI, higher BNP, and were more likely to be in the New York Heart Association class III-IV; however, these patients were less likely to have hyperlipidemia, coronary disease, or diabetes mellitus (P < 0.05). Age, sex, creatinine, ejection fraction, or Meta-Analysis Global Group in Chronic HF (MAGGIC) score did not differ by KB group. Higher KB was associated with worse survival (figure). After adjustment for the MAGGIC score, higher KB was associated with increased risk of mortality (HR 1.3; 95% CI, 1.08-1.48). Conclusions: In this community HF cohort, higher KB was associated with increased mortality, independent of the MAGGIC score.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

AbstractBackgroundNimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH.MethodsThis was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling.ResultsA total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41–3.67, p‐value = 0.001, OR 2.76, 95% CI 1.37–5.55, p‐value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57–5.06, p‐value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48–12.74, p‐value <0.0001 and OR 3.92, 95% CI 2.05–7.52, p‐value <0.0001, respectively).ConclusionsOur findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

Abstract Aims Iron deficiency is common in pulmonary hypertension, but its clinical significance and optimal definition remain unclear. Methods and results Phenotypic data for 1028 patients enrolled in the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics study were analyzed. Iron deficiency was defined using the conventional heart failure definition and also based upon optimal cut-points associated with impaired peak oxygen consumption (peakVO2), 6-min walk test distance, and 36-Item Short Form Survey (SF-36) scores. The relationships between iron deficiency and cardiac and pulmonary vascular function and structure and outcomes were assessed. The heart failure definition of iron deficiency endorsed by pulmonary hypertension guidelines did not identify patients with reduced peakVO2, 6-min walk test, and SF-36 (P &gt; 0.208 for all), but defining iron deficiency as transferrin saturation (TSAT) &lt;21% did. Compared to those with TSAT ≥21%, patients with TSAT &lt;21% demonstrated lower peakVO2 [absolute difference: −1.89 (−2.73 to −1.04) mL/kg/min], 6-min walk test distance [absolute difference: −34 (−51 to −17) m], and SF-36 physical component score [absolute difference: −2.5 (−1.3 to −3.8)] after adjusting for age, sex, and hemoglobin (all P &lt; 0.001). Patients with a TSAT &lt;21% had more right ventricular remodeling on cardiac magnetic resonance but similar pulmonary vascular resistance on catheterization. Transferrin saturation &lt;21% was also associated with increased mortality risk (hazard ratio 1.63, 95% confidence interval 1.13–2.34; P = 0.009) after adjusting for sex, age, hemoglobin, and N-terminal pro-B-type natriuretic peptide. Conclusion The definition of iron deficiency in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines does not identify patients with lower exercise capacity or functional status, while a definition of TSAT &lt;21% identifies patients with lower exercise capacity, worse functional status, right heart remodeling, and adverse clinical outcomes.