Mixed Patient Population Research Articles

Assessment of the accuracy of estimated free phenytoin concentrations in a mixed patient population

ObjectivesPhenytoin is an anti-epileptic drug that has a narrow therapeutic index, and therefore requires therapeutic drug monitoring. Only the free fraction is pharmacologically active, and in some cases, accurate determination...

Diagnostic accuracy of cerebral [18F]FDG PET in atypical parkinsonism

BackgroundAtypical parkinsonism (AP) often presents with Parkinson’s symptoms but has a much worse long-term prognosis. The diagnosis is presently based on clinical criteria, but a cerebral positron emission tomography (PET) scan with [18F]fluoro-2-deoxy-2-d-glucose ([18F]FDG) may assist in the diagnosis of AP such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Lewy body dementia (DLB). Only few studies have evaluated the sensitivity and specificity of [18F]FDG PET for separating the diseases in a mixed patient population, which we aim to assess in a retrospective material.ResultsWe identified 156 patients referred for a cerebral [18F]FDG PET for suspicion of AP during 2017–2019. The [18F]FDG PET was analysed by a nuclear medicine specialist blinded to clinical information but with access to dopamine transporter imaging. The reference standard was the follow-up clinical diagnosis (follow-up: 6–72 months). The overall accuracy for correct classification was 74%. Classification sensitivity (95% confidence interval, CI) and specificity (95% CI) for MSA (n = 20) were 1.00 (0.83–1.00) and 0.91 (0.85–0.95), for DLB/Parkinson with dementia (PDD) (n = 26) were 0.81 (0.61–0.93) and 0.97 (0.92–0.99) and for CBD/PSP (n = 68) were 0.62 (0.49–0.73) and 0.97 (0.90–0.99).ConclusionsOur results support the additional use of [18F]FDG PET for the clinical diagnosis of AP with moderate to high sensitivity and specificity. Use of [18F]FDG PET may be beneficial for prognosis and supportive treatment of the patients and useful for future clinical treatment trials.

Diagnostic accuracy of the Dutch version of the 4AT for delirium detection in a mixed patient population and setting

BackgroundDelirium is an acute disturbance in attention, awareness and cognition. Immediate detection in older adults is recommended because delirium is associated with adverse outcomes. The 4 ‘A’s Test (4AT) is a short screening instrument for delirium. The aim of this study is to evaluate diagnostic accuracy of the Dutch version of the screening tool 4AT for delirium detection in different settings.MethodsProspective observational study conducted in two hospitals in patients aged ≥ 65 years in geriatric wards and the Emergency Department (ED). Each participant underwent two assessments; the index test 4AT, followed by the reference standard for delirium performed by a geriatric care specialist. The reference standard delirium is according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria.ResultsA total of 71 geriatric inpatients and 49 older ED patients were included. The prevalence of delirium was 11.6% in the acute geriatric ward and 6.1% in the ED. The sensitivity and specificity of the 4AT in the acute geriatric ward were 0.88 and 0.69, respectively. In the ED, the sensitivity and specificity were 0.67 and 0.83, respectively. The area under the receiver operating characteristic curve was 0.80 for the acute geriatric ward setting and 0.74 for the ED setting.ConclusionThe Dutch version of the 4AT is a reliable screening tool for delirium detection in both acute geriatric wards and ED. Due to its brevity and practicality (i.e., no special training is required to administer the tool), it is useful in clinical practice.

Abstract P1-02-01: Comparing the efficacy of aromatase inhibitors vs tamoxifen in hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer: a systematic review and trial-level meta-analysis

Abstract Background: Five years of adjuvant endocrine therapy (ET) including aromatase inhibitors (AIs) and tamoxifen (TAM) is considered the standard of care in hormone receptor–positive, human epidermal growth factor–negative (HR+/HER2−) early breast cancer (eBC). Clinical practice guidelines recommend the use of an AI or TAM depending on menopausal status and clinical risk stratification. Although TAM is generally recommended and more commonly used in premenopausal women, there is mixed evidence for different clinical outcomes. Patient-level meta-analyses conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) showed significantly lower rates of BC recurrence with AIs vs TAM. However, this was not specific to patients with HR+/HER2− eBC. This trial-level meta-analysis was conducted to compare AIs ± ovarian function suppression (OFS) vs TAM ± OFS in HR+/HER2−, pre- and postmenopausal patients with eBC. Methods: A systematic literature review (SLR) was conducted using key literature databases, ie, Embase, PubMed, and MEDLINE In-Process (from database inception to March 2022) and key conferences (2019-2021). Studies selected for the SLR were those that included either ≥80% of patients with HR+/HER2− eBC in the mixed patient population or subgroup data provided specifically for patients with HR+/HER2− eBC. Of these, randomized controlled trials (RCTs) investigating AI ± OFS vs TAM ± OFS and assessing disease-free survival (DFS) were included in the trial-level meta-analysis. This meta-analysis was conducted using the generic invariance method to obtain a pooled effect estimate (hazard ratio [HR]) together with its CI for DFS. This pooled estimate was calculated as a weighted average of the intervention effects estimated in the individual trials. Both fixed- and random-effect models (FEM, REM) were used to estimate the effect size. A base-case analysis was performed including all eligible trials. Three other scenario analyses were conducted: trials investigating only nonsteroidal AIs (NSAIs), assessing only premenopausal women, and assessing only postmenopausal women. Heterogeneity across the trials was assessed using I2 statistic. Results: A total of 5 RCTs comparing AI ± OFS vs TAM ± OFS were eligible for the meta-analysis (SOFT, HOBOE, BIG 1-98, N-SAS BC 03, Li 2019; additional information on rationale for exclusion of specific trials will be reported). Two studies assessing NSAI vs TAM included postmenopausal women, while 3 studies assessing AIs + OFS vs TAM ± OFS included premenopausal women. A total of 6623 patients were followed up for 34-97.2 months across these five trials. Heterogeneity was found to be low (I2 < 40%) across all scenarios. The base-case results (including all studies) using FEM significantly favored AIs ± OFS over TAM ± OFS, with a 29% reduction in risk of recurrence or death (pooled HR, 0.71 [95%CI, 0.64-0.80]). Similar results were observed with NSAIs ± OFS vs TAM ± OFS (HR, 0.73 [95% CI, 0.64-0.83]). Among premenopausal patients, the pooled HR for AIs + OFS vs TAM ± OFS was 0.66 (95% CI, 0.54-0.79). For postmenopausal women, the HR was 0.75 (95% CI, 0.65-0.87), favoring AIs over TAM. The findings for the base-case and different scenarios remained consistent when REM was used. Conclusions: This trial-level meta-analysis suggests significantly greater benefit with AIs than with TAM for HR+/HER2− eBC. Notably, AIs in combination with OFS are associated with a 34% reduction in risk of recurrence or death vs TAM ± OFS in premenopausal women; these results are aligned with the patient-level data findings of the EBCTCG. The findings indicate that AIs ± OFS are associated with a better DFS in the HR+/HER2− population, especially premenopausal women, than TAM ± OFS. Citation Format: Wolfgang Janni, Michael Untch, Nadia Harbeck, Joseph Gilgorov, William Jacot, Stephen K. Chia, Jean-Francois Boileau, Sina Haftchenary, Rhea Gupta, Namita Mishra, Purnima Pathak, Giuseppe Curigliano. Comparing the efficacy of aromatase inhibitors vs tamoxifen in hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer: a systematic review and trial-level meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-02-01.

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

Comparison of weight loss outcomes between Roux-en-Y gastric bypass and sleeve gastrectomy in a racially mixed urban patient population.

National data show a trend favoring laparoscopic sleeve gastrectomy (SG) over Roux-en-Y gastric bypass (RYGB). Published data demonstrating the differences in weight loss between the two procedures are mixed. In this retrospective study using clinical data from 2010 to 2020, we compared the clinical and demographic characteristics of patients undergoing either SG or RYGB to evaluate their long-term weight loss outcomes. University hospital in the United States. A total of 3329 patients were identified in our institutional Metabolic and Bariatric Surgery Accreditation and Quality Improvement database using Current Procedural Terminology codes for either RYGB or SG. A general linear model was used for baseline characteristics. Logistic regression was used for factors favoring RYGB versus SG. A multivariable linear mixed model was used for weight-trajectory analysis. Cox regression was used for a cumulative hazard ratio of 10% weight regained from nadir. Factors favoring RYGB were diagnoses of type 2 diabetes and gastroesophageal reflux disease, Hispanic ethnicity, and surgeon's preference. SG was favored among Black patients and smokers. RYGB was associated with more weight loss at all time points. The risk of weight regain was significantly higher after SG versus RYGB. The bariatric procedure choice is significantly influenced by race, medical history, and surgeon's experience. RYGB results in a significantly more durable weight loss compared with SG regardless of race or other stratification factors.

Use of a Victorian statewide surveillance programme to evaluate the burden of healthcare-associated Staphylococcus aureus bacteraemia and Clostridioides difficile infection in patients with cancer.

Patients with cancer are at high risk for infection, but the epidemiology of healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB) and Clostridioides difficile infection (HA-CDI) in Australian cancer patients has not previously been reported. To compare the cumulative aggregate incidence and time trends of HA-SAB and HA-CDI in a predefined cancer cohort with a mixed statewide patient population in Victoria, Australia. All SAB and CDI events in patients admitted to Victorian healthcare facilities between 1 July 2010 and 31 December 2018 were submitted to the Victorian Healthcare Associated Infection Surveillance System Coordinating Centre. Descriptive analyses and multilevel mixed-effects Poisson regression modelling were applied to a standardised data extract. In total, 10 608 and 13 118 SAB and CDI events were reported across 139 Victorian healthcare facilities, respectively. Of these, 89 (85%) and 279 (88%) were healthcare-associated in the cancer cohort compared with 34% (3561/10 503) and 66% (8403/12 802) in the statewide cohort. The aggregate incidence was more than twofold higher in the cancer cohort compared with the statewide cohort for HA-SAB (2.25 (95% confidence interval (CI): 1.74-2.77) vs 1.11 (95% CI: 1.07-1.15) HA-SAB/10 000 occupied bed-days) and threefold higher for HA-CDI (6.26 (95% CI: 5.12-7.41) vs 2.31 (95% CI: 2.21-2.42) HA-CDI/10 000 occupied bed-days). Higher quarterly diminishing rates were observed in the cancer cohort than the statewide data for both infections. Our findings demonstrate a higher burden of HA-SAB and HA-CDI in a cancer cohort when compared with state data and highlight the need for cancer-specific targets and benchmarks to meaningfully support quality improvement.

Study on Acalculous Cholecystitis in Critically Ill Patients

Introduction: Acute acalculous cholecystitis (AAC) may be a serious complication of critical illness. We evaluated the underlying diseases, clinical and diagnostic features, the severity of associated organ failures, and the outcome of operatively treated AAC during a mixed ICU patient population.
 Aim: To study acalculous cholecystitis in critically ill patients with given data.
 Methods: The data of all ICU patients who had operatively confirmed AAC during their ICU stay between 1 January 2021 and 31 July 2021 were collected from the hospital records and the intensive care unit's data management system for further analysis.
 Results: Two hundred and eighteen cases of acute cholecystitis with complete charts were available for analysis. The study group included 67 critically ill patients with ASA 3 and 4, while the control group included 150 fit patients with ASA 1 and 2. Both groups were comparable with regard to preoperative data. Histopathology confirmed severe cholecystitis in a significant number of cases in the study group compared to the control group. Significantly higher rates of morbidity and mortality were recorded in the study group. Equally, significantly more patients from the study group were managed in the ICU.
 Conclusion: Acute acalculous cholecystitis was associated with severe illness, infection, long ICU stay, and multiple organ failure. Mortality was related to the degree of organ failure. Prompt diagnosis and active treatment of AAC are often life-saving in these patients.

The Effects of COVID-19 Pandemic on Trauma Registry and Performance Improvement Operations and Workforce Nationwide: A Survey of Trauma Center Association of America Members.

BackgroundTrauma Centers integrate Trauma Registrars and Performance Improvement Nurses to drive quality care. Delays in their duties could have negative impacts on outcomes and performance. We aim to investigate the impact of COVID-19 pandemic on Trauma Center operations by assessing performance of trauma registry and performance improvement processes across the United States.MethodsA cross-sectional study was performed utilizing data from two anonymous questionnaires distributed to Trauma Center Association of America members. Descriptive statistics, Fisher's Exact Test, and multivariable logistic regression were performed with statistical significance defined as P < 0.05.ResultsOf 90.2% (83) of Trauma Registrars and 85.9% (67) of Performance Improvement personnel reported that their Trauma Centers have treated COVID-19 patients. Among trauma registrars, respondents did not significantly differ in the current status of completing registry cases (P> 0.05), during COVID-19 compared to prior (P> 0.05), or adjusted odds of COVID-19 delaying completion of entries (P> 0.05). Having >2 Performance Improvement Nurses was significantly associated with improved performance during the COVID-19 pandemic (P= 0.03) whereas working at a Trauma Center which treats adults-only or mixed patient population (adult and pediatric) was associated with being 1-3 months behind in closing of performance improvement cases (P= 0.02).ConclusionsThe negative impact of COVID-19 on Trauma Registrars and Performance Improvement Nurses has been minimal. Adequate staffing/experience seem to mitigate delays and decreased performance. Implementation of expanded staffing, improved training, and evidenced-based revision of Trauma Center logistics may help mitigate future disruptions relating to COVID-19 and allow Trauma Centers to recover and improve their operations.

Comprehensive Genetic Analysis Results of TSC1/TSC2 Genes in Patients with Clinical Suspicion of Tuberous Sclerosis Complex and Definition of 3 Novel Variants.

Background Tuberous Sclerosis Complex is an autosomal dominant multi-system disorder with an incidence of about 1 in 6000 live births. Defects in either TSC1 (* 605284) or TSC2 (* 191092) genes encoding the components of the Tuberous Sclerosis Complex are responsible for the disease. Therefore, consideration of TSC1/TSC2 pathogenic variations is recommended in the updated diagnostic criteria of Tuberous Sclerosis Complex.Aims To present the TSC1/TSC2 screening results of a mixed patient population as well as possible new variants in 23 cases from 20 different families who were referred to our Genetic Diseases Diagnosis Center with the signs and symptoms of Tuberous Sclerosis Complex.Study designRetrospective, cross-sectional study.Methods Germline TSC1/TSC2 variants were screened in DNA samples extracted from peripheral blood samples of 23 patients from 20 unrelated families using targeted high-throughput sequencing and multiplex ligation-dependent probe amplification methods. The variants identified were classified according to ACMG 2015 guidelines.Results In total, 5 different pathogenic/likely pathogenic changes have been defined. All these pathogenic/likely pathogenic variants were located in the TSC2 gene. Three of the pathogenic/likely pathogenic variants were novel. Two patients who are twin sisters were found to have TSC2/PKD1 contiguous deletion syndrome. One of the 3 novel variants was a mosaic in-frame deletion. We did not identify any pathogenic variants of the TSC1 gene.Conclusion The novelty of most of the variants found, including a mosaic likely pathogenic variant, and the presence of a large genomic rearrangement, supports the importance of a comprehensive approach in analyzing TSC1/TSC2 genes. Genetic diagnosis should be performed with caution, considering the possibility of mosaic variants with low allelic fractions.

Diagnostic accuracy and clinical applicability of the Swedish version of the 4AT assessment test for delirium detection, in a mixed patient population and setting

BackgroundDelirium is common in older hospitalized patients. It has serious consequences e.g., poor health outcomes, mortality and increased costs. Despite that, many cases are undetected. Early detection of delirium is important in improving outcomes and use of assessment tools improves detection rates. The 4AT is a brief screening tool for delirium detection, which has not previously been translated into Swedish. The study aim was to evaluate diagnostic accuracy and clinical applicability of a Swedish version of the screening tool 4AT for delirium detection.MethodThis diagnostic test accuracy study used a quantitative and a qualitative approach and evaluated the patients’ and the health care professionals’ experiences of the tool. Study included 200 patients ≥65 years from a university hospital and a county hospital in two Swedish regions. Medical specialties were geriatric stroke/neurology, geriatric multimorbidity, severe cognitive impairment, orthopaedic, and urology. The translated 4AT was tested against the reference standard DSM-IV-TR criteria, based on the Organic Brain Syndrome scale and patient records. The 4AT was assessed simultaneously and independently by two assessors. Additionally, data was collected through patient record reviews, and questions about applicability to the patients (n = 200) and the assessors (n = 37). Statistical analyses, and qualitative content analyses were conducted.ResultsBy reference standard 18% had delirium, and by 4AT 19%. The overall percent agreement was 88%, AUROC 0.808, sensitivity 0.70 (95% CI 0.51–0.84) and specificity 0.92 (95% CI 0.87–0.96). In the ward for severe cognitive impairment (n = 63) the 4AT was less sensitive and less specific. In the other wards (n = 132) sensitivity was 0.77 (95% CI 0.50–0.93), specificity 0.93 (95% CI 0.87–0.97), and AUROC 0.848. Interrater reliability (Kappa) was 0.918, p = < 0.001 (n = 144). The 4AT was well tolerated by patients, easy to use for health care professionals, and took a few minutes to conduct.ConclusionThe Swedish version of 4AT is an accurate and applicable tool to use in clinical practice for detecting delirium in hospitalized patients across different medical specialities, and to use by different professionals and levels of seniority. To improve patient outcomes, we recommend the 4AT to be incorporated in clinical practice in health care settings in Sweden.

Agreement between the GLIM criteria and PG-SGA in a mixed patient population at a nutrition outpatient clinic

The Global Leadership Initiative on Malnutrition (GLIM) criteria is a step-wise process including a screening tool of choice for risk assessment of malnutrition before assessment of diagnosis and grading of malnutrition severity. The agreement between GLIM and the established malnutrition assessment method Patient Generated-Subjective Global Assessment (PG-SGA) is uncertain. Also, several aspects of GLIM remain to be clearly defined. In this study, we compared diagnosis of malnutrition with the GLIM criteria to the PG-SGA, and explored the differences between the methods. This cross-sectional study was conducted at the Nutrition Outpatient Clinic at Oslo University Hospital, Norway. Patients were included from September-December 2019. Nutritional Risk Screening 2002 (NRS-2002) was used as the screening tool in the GLIM process before diagnosing and grading the severity of malnutrition. Results are presented with and without the initial risk screening. The diagnostic results from the GLIM process were compared to the malnutrition diagnosis using the PG-SGA. In total, 144 patients, median age 58 years, participated in the study. The full GLIM process identified 36% of the patients as malnourished, while the PG-SGA identified 69% of the patients as malnourished. Comparison of GLIM and PG-SGA showed fair agreement, however the agreement was better when the NRS-2002 screening was excluded. Considering the PG-SGA a gold standard, GLIM had a sensitivity of 51% and a specificity of 98%. The introduction of new cut-off values for fat-free mass did not considerably alter the diagnosis of malnutrition within GLIM. The GLIM criteria showed only fair agreement with the PG-SGA, however the agreement was better when the initial NRS-2002 screening was excluded. A joint consensus on how to perform the GLIM process is needed for comparisons of future studies, and before routine use in clinical practice.

High-power short-duration radiofrequency ablation for atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction In recent times, high-power short-duration (HPSD) radiofrequency ablation (RFA) has emerged as an alternative strategy for pulmonary vein isolation (PVI) in atrial fibrillation (AF). Purpose We aimed to compare HPSD approach and conventional, ablation-index (AI) guided PVI using contact force sensing ablation catheters in respect of efficacy, safety, procedural characteristics, and outcome. Methods A total of 184 consecutive AF patients with first PVI were enrolled (age: 60 ± 11 years, paroxysmal: 56.5%, persistent: 43.5%) between November 2016 and December 2019. An ablation protocol of 50W energy with 15-20 g contact force was used for a duration of 8-12 sec based on the loss of capture concept in the HPSD group (n = 91) meanwhile, PVI was achieved according to the conventional power settings (posterior wall 25W, AI: 400, anterior wall 35W, AI: 550 ) in the control group (n = 93). During 1-year follow-up, documented AF for more than 30 seconds was considered as recurrence. Results Radiofrequency time and procedural time were significantly shorter using HPSD ablation (26.0 ± 12.7 min vs. 42.9 ± 12.6 min, p &amp;lt; 0.001, and 91 ± 30.1 min vs. 105.3 ± 28 min, p &amp;lt; 0.001). The HPSD strategy significantly lowered fluoroscopy time and radiation dose (5.47 ± 4.07 min vs. 8.15 ± 10.04 min, p = 0.019, and 430.2 ± 534.06 cGycm2 vs. 604.2 ± 633.9 cGycm2, p = 0.046). The HPSD group showed significantly less arrhythmia recurrence during 1-year follow-up with 76.9% of patients free from AF compared to 66.7% in the control group (p = 0.037). No pericardial tamponade, periprocedural thromboembolic complication, or atrio-oesophageal fistula occurred in the HPSD group. We observed 2 pericardial tamponade and 1 periprocedural stroke in the control group. Conclusions HPSD RFA for AF was demonstrated to be safe, and lead to significantly improved 1-year outcome in our mixed patient population. HPSD protocol significantly shortened procedural and radiofrequency time with decreased fluoroscopy time and radiation exposure.

Intravenous Iron Replacement in Patients with Left Ventricular Assist Devices

<h3>Purpose</h3> In patients supported by LVADs, iron deficiency is a common cause of anemia (IDA) and its associated morbidity. The clinical benefits of intravenous (IV) iron replacement in heart failure are well described, but there are fewer data supporting IDA treatment in LVAD patients. This study assessed the clinical and financial impact of IV ferric carboxymaltose (FCM) in an outpatient LVAD population through evaluation of anemia, blood transfusion requirements, readmissions, and insurance reimbursement. <h3>Methods</h3> This was a single-center prospective observational study of LVAD patients with IDA (ferritin <100 ng/mL or 100-300 ng/mL with Tsat <20%). Outpatients received FCM 750 mg x 2 doses given 1 week apart. The primary endpoint was the resolution of anemia at 1, 3, and 6 months. Blood transfusion requirements and readmissions were assessed pre- and post-FCM therapy. Financial analysis included the comparison of drug-specific reimbursement to drug acquisition cost. <h3>Results</h3> Eighty patients received FCM therapy. Baseline data are shown in Table 1. On average, patients were 19 months post-implant, 16% had experienced a gastrointestinal bleed within the last 3 months, and mean baseline Hgb was 9.9 g/dL. At 1 month, mean Hgb significantly improved (12.0±1.9 g/dL vs 9.9±1.4, p<0.0001), and this was maintained at 3 months (12.1±2.0, p<0.0001) and 6 months (12.2±2.1, p<0.0001) (Figure 1). When comparing the 3- and 6-month periods pre- and post-FCM, blood transfusion requirements and hospital admissions were both significantly reduced (Table 3). The majority of patients were covered by Medicare (67.5%) or a commercial payor (18.2%) with drug reimbursement to cost ratios of 0.81 and 1.97, respectively. <h3>Conclusion</h3> This prospective evaluation of IV iron replacement with 2 doses of FCM in a large cohort of LVAD patients demonstrated a resolution of anemia and subsequent reduction in blood transfusion and readmission requirements. In a mixed payor patient population, drug reimbursement supports utilization of FCM for this indication.

Predictors of outcome in children with disorders of mitochondrial metabolism in the pediatric intensive care unit.

BackgroundThe aim of this study was to identify factors predicting outcome in patients with mitochondrial disease admitted to pediatric intensive care units (PICU).MethodsRetrospective study of 2434 patients (age <21 years) admitted to a PICU from 1 January 2006 through 31 March 2016 and captured in the Virtual Pediatric Systems database with ICD9 diagnosis 277.87, disorders of mitochondrial metabolism. Factors influencing mortality and prolonged length of stay (≥14 days) were analyzed using logistic regression.ResultsPredictors independently affecting mortality (adjusted odds ratios and 95% confidence intervals, p < 0.05): age 1–23 months 3.4 (1.7–6.6) and mechanical ventilation 4.7 (2.6–8.6) were risk factors; post-operative 0.2 (0.1–0.6), readmission 0.5 (0.3–0.9), and neurologic reason for admittance 0.3 (0.1–0.9) were factors reducing risk. Predictors affecting prolonged length of stay: mechanical ventilation 7.4 (5.2–10.3) and infectious reason for admittance 2.0 (1.3–3.2) were risk factors, post-operative patients 0.3 (0.2–0.5) had lower risk. The utility of PRISM and PIM2 scores in this patient group was evaluated.ConclusionsThe single most predictive factor for both mortality and prolonged length of stay is the presence of mechanical ventilation. Age 1–23 months is a risk factor for mortality, and infectious reason for admittance indicates risk for prolonged length of stay.Impact Presence of mechanical ventilation is the factor most strongly associated with negative outcome in patients with mitochondrial disease in pediatric intensive care.Age 1–23 months is a risk factor for mortality, and infectious reason for admittance indicates risk for prolonged length of stayPRISM3 and PIM2 are not as accurate in patients with mitochondrial disease as in a mixed patient population

Elevated plasma factor VIII levels in a mixed patient population on anticoagulation and past venous thrombosis

BackgroundThrombophilia conditions are associated with an increased risk of venous thromboembolism. Elevated plasma levels of factor VIII (>150 IU/dL) increase the risk of venous thrombosis. The aim of this report is to analyze a subset of patients in whom plasma factor VIII levels were investigated as part of a thrombophilia panel at a specialty venous clinic at a tertiary care hospital. MethodsFrom January 2019 to December 2019, records of all patients (n = 306) who had a plasma factor VIII level assay performed as part of a thrombophilia panel were retrospectively analyzed. Group 1 (n = 92) had normal factor VIII levels (≤150 IU/dL), whereas group 2 (n = 214) had elevated factor VIII levels (>150 IU/dL). Venous thromboembolic events were classified as provoked if there was an association with surgery, trauma, immobilization, orthopedic fracture, peripartum period, or use of hormones. If there was no associated factor identifiable in the patient's history, the event was considered unprovoked. ResultsThe median age for patients in groups 1 and 2 was 55 and 65 years, respectively. Family history of deep venous thrombosis (DVT) was noted in 6 patients in group 1 (6.5%) vs 77 patients in group 2 (36%), P value: .0001. Unprovoked DVT was more commonly noted in group 2 patients (66%) compared with group 1 patients (5%), P value: .0001. In addition, venous ulceration was more commonly encountered in group 2 (23%) than group 1 (11%), P value: .008. Factor VIII level >150 IU/dL was a significant predictor of DVT occurrence itself (odds ratio: 3.3, P value <.005). Factor VIII level >200 IU/dL was a significant predictor of occurrence of two or more episodes of DVT (odds ratio: 12.3, P value < .005). ConclusionsFactor VIII levels were found to be elevated in a significant proportion of patients in whom thrombophilia testing was performed at a specialty venous clinic. This elevation was more common in patients with venous ulceration, a positive family history of DVT, and a personal history of an unprovoked DVT. Levels above 200 IU/dL were associated with DVT recurrence. This has important implications for secondary prophylactic strategies for DVT.

Quality of care in dysphagia patients: adaptation and validation of the Swedish SWAL-CARE questionnaire

BackgroundThe aim of this study was to adapt the instrument and evaluate the psychometric properties of the Swedish version of the Swallowing Quality of Care questionnaire (S-SWAL-CARE) in patients with oropharyngeal dysphagia.MethodsTranslation and adaptation of the original SWAL-CARE into Swedish was performed according to established international guidelines. Field testing was performed using 100 patients with oropharyngeal dysphagia due to multiple reasons such as head and neck cancer and neurologic/neuromuscular disease, who had undergone swallowing evaluation within 6 months prior to the study. The patients answered the S-SWAL-CARE, the Quality from the Patient’s Perspective (QPP) and the Swallowing Quality of Life (SWAL-QOL). Test–retest was performed in 20% of the participants. The reliability and validity of the S-SWAL-CARE were assessed by Pearson correlation coefficient and Cronbach’s alpha as well as convergent and discriminative validity, respectively.ResultsThe field testing of the S-SWAL-CARE resulted in sufficient reliability, with Cronbach’s alpha values exceeding 0.90 for all domains. All items correlated strongly to their own domain, with weaker correlations to the other domains, indicating proper scale structure. Results also indicate sufficient convergent and discriminant validity when tested for association to the QPP domains and the SWAL-QOL Total score. The test–retest reliability of the S-SWAL-CARE demonstrated sufficient intraclass correlation coefficient (ICC) for the General advice domain (0.73) and Clinical advice domain (0.82). The ICC for the Patient satisfaction domain was lower (0.44).ConclusionThe S-SWAL-CARE can be considered a reliable and valid tool to assess the dysphagia-related quality of care in a mixed Swedish dysphagia patient population.

Development and validation of the delirium risk assessment score (DRAS).

Development and validation of a delirium risk assessment score. Predisposing risk factors for delirium were used, which are easily assessed at hospital admission without additional clinical or laboratory testing. A systematic literature search identified ten risk factors: acute admission, alcohol use > 4 units/day, cognitive impairment, ADL impairment, age > 75years, earlier delirium, hearing/vision problems, number of medication ≥ 5, number of morbidities > 2 and male. The DRAS was developed in a mixed patient population (N = 842) by the use of univariate and multivariate analyses and -2 log-likelihood calculation to weigh the risk factors. Based on the sensitivity and specificity, a cutoff score was calculated. The validation was performed in 3 cohorts (N = 408, N = 186, N = 365). In cohort 3, the DRAS was compared (AUC, sensitivity and specificity) to 3 instruments (Inouye, Kalisvaart, VMS rules). The delirium incidence was 31.8%, 20.3%, 15.6% and 15.1%. All risk factors were independently predictive for delirium, except male. The multivariate analyses excluded morbidities. The final DRAS consists of 8 items; acute admission, cognitive impairment, alcohol use (3 points), ADLimpairment/mobilityproblems (2 points), higher age, earlier delirium, hearing/vision problems, and medication (1 point). The total score is 15 points and at a cut-of score of 5 or higher the patient is at risk of developing a delirium. The cutoff was at 5 or more points, AUC: 0.76 (95% CI 0.72-0.79), sensitivity 0.77, specificity 0.60. Validation cohorts AUC was 0.75 (95% CI 0.96-0.81), 0.76 (95% CI 0.70-0.83) and 0.78 (95% CI 0.70-0.87), sensitivity 0.71, 0.67 and 0.89 and specificity 0.70, 0.72 and 0.60. The comparison revealed the highest AUC for the DRAS. Based on an admission interview, the delirium risk can be easily evaluated using the DRAS shortlist score of predisposing risk factors for delirium in older inpatients.

Diagnostic Characteristics of 3-Parameter and 2-Parameter Equations for the Calculation of a Combined Indicator of Vitamin B12 Status to Predict Cobalamin Deficiency in a Large Mixed Patient Population

A combined indicator for the determination of vitamin B12 status (4cB12) that employs four markers of vitamin B12 status (i.e., holotranscobalamin, HoloTC; vitamin B12, B12; methyl malonic acid, MMA; and homocysteine, Hcy) has been proposed for the comprehensive assessment of B12 status. We aimed to compare recently published 2- (2cB12) and 3-parameter (3cB12) cB12 equations missing one or two markers of B12 status with the established four-parameter cB12 (4cB12). In 3,614 routine samples in which HoloTC, B12, MMA, Hcy and serum folate were measured, cB12 was assessed with 4cB12, as well as with four 3cB12 and six 2cB12 equations. Diagnostic accuracy (AUC) curves were calculated by receiver operating characteristic (ROC) curve analysis with the four-parameter equation (4cB12) as an index. Furthermore, we investigated whether calculating cB12 in addition to a 2-step algorithm employing the same parameters would add diagnostic value for the diagnosis of vitamin B12 deficiency. HoloTC showed the highest diagnostic accuracy among the single markers (AUC = 0.94). The cB12 equation using HoloTC and MMA (2cB12HoloTC/MMA) had the highest AUC among the 2-parameter equations (0.98). Among the 3-parameter equations, 3cB12HoloTC/MMA/Hcy and 3cB12HoloTC/B12/MMA revealed an AUC of 0.99, which was significantly higher than that of 2cB12HoloTC/MMA (p < 0.01). Calculating 2cB12HoloTC/MMA in addition to using a stepwise algorithm employing HoloTC and MMA for diagnosis of vitamin B12 deficiency increased the positive likelihood ratio from 12.1 to 42.6. cB12 calculated with two or three markers of B12 status provides a good approximation of the 4cB12 equation. A 2cB12 equation employing the same parameters improved diagnostic accuracy compared to the use of a 2-step diagnostic algorithm alone. Our results suggest, that laboratories should consider enriching their reports by additionally reporting a corresponding 2cB12 or 3cB12 to results obtained in stepwise diagnostic algorithms.

PCN308 REAL-WORLD UTILIZATION OF BRIGATINIB IN PATIENTS WITH NON–SMALL CELL LUNG CANCER (NSCLC)

To describe real-world treatment duration in anaplastic lymphoma kinase positive (ALK+) NSCLC patients receiving brigatinib. This retrospective study used United States (US) specialty pharmacy data to identify all patients receiving brigatinib between May 2017 and November 2018. During this data collection period, brigatinib was approved in the US for patients with crizotinib-resistant metastatic ALK+ NSCLC. The study outcome was time to discontinuation, which was evaluated using Kaplan-Meier survival analysis. Dosing information obtained through prescribers’ instructions was described. 455 patients received brigatinib through the specialty pharmacy database during the study period. Of these, 313 patients (68.8%) received 90 mg/d for 7 days and escalated to 180 mg/d; 89 patients (19.6%) only received 180 mg/d and 24 patients (5.3%) only received 90 mg/d during study follow-up; and 29 (6.4%) patients received other dose combinations including 60 mg, 90 mg, 120 mg, 150 mg, 180 mg, and 240 mg qd. These data may not reflect initiation of drug for all patients, as patients may have received drug prior to specialty pharmacy. Overall, 374 patients (82.2%) received brigatinib 180 mg/d as their most recent dose. The median time to discontinuation was 16.4 months (95% CI: 11.0, NE). Kaplan-Meier estimates of continued use of brigatinib for specialty pharmacy patients at months 1 through 6 and at 12 months of the study period were 91.5%, 86.6%, 80.8%, 75.7%, 69.8%, 67.9% and 54.9%. In the real world, despite a mixed patient population across all treatment lines, estimates for continued brigatinib use remained high over time. In the absence of reported clinical outcomes in the real-world setting, time to discontinuation may be used as a proxy for the tolerability and effectiveness of brigatinib.