Patient Outcome Variables Research Articles

Complement factor D as a predictor of Achilles tendon healing and long‐term patient outcomes

Dense connective tissue healing, such as tendon, is protracted leading to highly variable and unsatisfactory patient outcomes. Biomarkers prognostic of long-term clinical outcomes is, however, unknown. The present study was designed to investigate the proteomic profile of healing, identify potential biomarkers, and assess their association with the patient's long-term outcomes after ATR. Quantitative mass spectrometry analysis demonstrated 1423 proteins in healing and contralateral healthy Achilles tendons of 28 ATR patients. Comparing healing at 2weeks and healthy protein profiles, we identified 821 overlapping, 390 upregulated, and 17 downregulated proteins. Upregulated proteins are related mainly to extracellular matrix organization and metabolism, while downregulated pathways were associated with exocytosis in immune modulation and thrombosis formation. Further proteomic profiling in relation to validated patient outcomes revealed the downregulated pro-inflammatory complement factor D (CFD) as the most reliable predictive biomarker of successful tendon healing. Our finding showed a comprehensive proteomic landscape and bioinformatics on human connective tissue, indicating subtype-specific and shared biological processes and proteins in healing and healthy Achilles tendons, as well as in tendons related to good and poor patient outcomes. Inflammatory protein CFD and serpin family B member 1 were finally identified as potential predictive biomarkers of effective healing outcomes when combined the proteomic profiles with a validated clinical database. Following the future elucidation of the mechanisms associated with the identified biomarkers as predictors of good outcomes, our findings could lead to improved prognostic accuracy and development of targeted treatments, thus improving the long-term healing outcomes for all patients.

Center Variability in Patient Outcomes Following HeartMate 3 Implantation: An Analysis of the MOMENTUM 3 Trial

BackgroundAs left ventricular assist device (LVAD) survival rates continue to improve, evaluating site-specific variability in outcomes can facilitate identifying targets for quality-improvement initiative opportunities in the field. MethodsDeidentified center-specific outcomes were analyzed for HeartMate 3 (HM3) patients enrolled in the MOMENTUM 3 pivotal and continued access protocol trials. Centers < 25th percentile for HM3 volumes were excluded. Variability in risk-adjusted center mortality was assessed at 90 days and 2 years (conditional upon 90-day survival). Adverse event (AE) rates were compared across centers. ResultsIn the 48 included centers (1958 patients), study-implant volumes ranged between 17 and 106 HM3s. Despite similar trial-inclusion criteria, patient demographics varied across sites, including age quartile ((Q)1–Q3:57–62 years), sex (73%–85% male), destination therapy intent (60%–84%), and INTERMACS profile 1–2 (16%–48%). Center mortality was highly variable, nadiring at ≤ 3.6% (≤ 25th percentile) and peaking at ≥ 10.4% (≥ 75th percentile) at 90 days and ≤ 10.2% and ≥ 18.7%, respectively, at 2 years. Centers with low mortality rates tended to have lower 2-year AE rates, but no center was a top performer for all AEs studied. ConclusionsMortality and AEs were highly variable across MOMENTUM 3 centers. Studies are needed to improve our understanding of the drivers of outcome variability and to ascertain best practices associated with high-performing centers across the continuum of intraoperative to chronic stages of LVAD support.

"Delayed-Immediate" Hernia Repairs in Infected Wounds: Clinical and Economic Outcomes.

Wound class in hernia repairs impacts surgical technique and outcomes. Hernia recurrence and complications are high when dirty wounds are treated in one stage. We hypothesize patients who undergo intentionally staged repairs are less likely to have adverse outcomes and associated costs. Patients were identified by retrospective chart review. Patient characteristics and outcome variables were collected. An economic analysis of cost variables was performed using medical records and published meta-analyses. There were 8 patients in the staged repairs group and 10 patients in the control group. Length of stay was 14.9days (±8.8), and 8.7 days (±6.4), respectively. Rate of hernia recurrence within 1year was 14.3% and 37.5%. Rate of mesh infection at 30days was 0% and 10%. Compared to controls, delayed-immediate repairs had a nearly 2-fold index surgical cost. Although there is an increased cost associated with delayed-immediate repairs, this cost may be offset by the decreased infection, seroma, dehiscence, enterocutaneous fistula formation, and hernia recurrence rate that necessitates future interventions. Further data collection is required to determine if clinical and economic benefit is seen long-term.

Stop of proton-pump inhibitor treatment in patients with liver cirrhosis (STOPPIT): study protocol for a prospective, multicentre, controlled, randomized, double-blind trial

BackgroundProton-pump inhibitors (PPI) are liberally prescribed in patients with liver cirrhosis. Observational studies link PPI therapy in cirrhotic patients with an increased risk for infectious complications, hepatic encephalopathy and an increased risk for hospitalization and mortality. However, patients with liver cirrhosis are also considered to be at risk for peptic ulcer bleeding. The STOPPIT trial evaluates if discontinuation of a pre-existing PPI treatment delays a composite endpoint of re-hospitalization and/or death in patients (recently) hospitalized with liver cirrhosis compared to patients on continued PPI medication.MethodsThe STOPPIT-trial is a prospective, multicentre, randomized, double-blinded, placebo-controlled, parallel-group trial. In total, 476 patients with complicated liver cirrhosis who already receive long-term PPI therapy without evidence-based indication are 1:1 randomized to receive either esomeprazole 20 mg (control group) or placebo (intervention group) for 360 days. Patients with an indication for PPI therapy (such as a recent diagnosis of peptic ulcers, severe reflux esophagitis, severe hemorrhagic gastritis, recent endoscopic therapy for oesophageal varices) are excluded. The primary composite endpoint is the time-to re-hospitalization and/or death. Secondary endpoints include rates of re-hospitalization, mortality, occurrence of infections, hepatic decompensation and acute-on-chronic liver failure. The safety endpoint is defined as manifestation of an evidence-based indication for PPI re-therapy. The impact of PPI continuation or discontinuation on the intestinal microbiota will be studied. The recruitment will take place at 18 study sites throughout Germany. Recruitment has started in April 2021.DiscussionThe STOPPIT trial is the first clinical trial to study the effects of PPI withdrawal on relevant outcome variables in patients with complicated liver cirrhosis. If the hypothesis that PPI withdrawal improves clinical outcomes of cirrhosis patients is confirmed, this would argue for a strong restriction of the currently liberal prescription practice of PPIs in this population. If, on the other hand, the trial demonstrates an increased risk of gastrointestinal bleeding events in patients after PPI withdrawal, this could create a rationale for a more liberal, prophylactic PPI treatment in patients with liver cirrhosis.Trial registrationEU clinical trials register EudraCT 2019-005008-16 (registered December 27, 2019). ClinicalTrials.gov NCT04448028 (registered June 25, 2020). German Clinical Trials Register DRKS00021290 (registered March 10, 2021).

Head and neck cancer organoids as a promising tool for personalized cancer therapy: A literature review.

Background and AimChemotherapy and targeted therapy are used in treating head and neck cancers (HNCs) either alone or in combination with surgery, especially in advanced tumors but these treatments have resulted in variable outcomes in different patients. This, along with the introduction of new therapies to improve the survival of patients makes it necessary to search for models that can predict the response to treatment among different patients. Organoids, as three‐dimensional culture models, have been studied more widely in non‐HNCs and to a lesser extent in HNCs as tools to predict treatment outcomes. We aimed to conduct a review to validate the use of organoids as a preclinical tool for the treatment of HNCs patients.MethodsA comprehensive literature search was separately performed by both authors in PubMed and google scholar databases, using the following keywords: “organoid,” “head and neck cancer,” “personalized medicine,” “chemotherapy,” and “targeted therapy.” The articles published up to September 2021 were included in this review and selected according to a quality appraisal method.ResultsExamination of HNC‐derived organoids made in various studies showed that these organoids had the ability to recapitulate original tumor features, including histopathological properties, functional characteristics, and expression of molecular markers in almost all of the studies. Differential sensitivity to chemotherapy drugs similar to in vivo was observed in sensitivity testing. Epidermal growth factor receptor (EGFR) expression levels were different between organoids from different patients and EGFR expression level was found to correlate with the response to anti‐EGFR targeted therapy. A similar result was reported for organoids derived from salivary adenoid cystic carcinoma.ConclusionSince HNC‐derived organoids seem to recapitulate characteristics of original tumors and to show differential responses to different chemotherapy and targeted therapy agents, these organoids might have the potential to be used as preclinical prediction tools for the treatment of HNC patients.

Variable susceptibility of intestinal organoid-derived monolayers to SARS-CoV-2 infection.

Gastrointestinal effects associated with Coronavirus Disease 2019 (COVID-19) are highly variable for reasons that are not understood. In this study, we used intestinal organoid-derived cultures differentiated from primary human specimens as a model to examine interindividual variability. Infection of intestinal organoids derived from different donors with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) resulted in orders of magnitude differences in virus replication in small intestinal and colonic organoid-derived monolayers. Susceptibility to infection correlated with angiotensin I converting enzyme 2 (ACE2) expression level and was independent of donor demographic or clinical features. ACE2 transcript levels in cell culture matched the amount of ACE2 in primary tissue, indicating that this feature of the intestinal epithelium is retained in the organoids. Longitudinal transcriptomics of organoid-derived monolayers identified a delayed yet robust interferon signature, the magnitude of which corresponded to the degree of SARS-CoV-2 infection. Interestingly, virus with the Omicron variant spike (S) protein infected the organoids with the highest infectivity, suggesting increased tropism of the virus for intestinal tissue. These results suggest that heterogeneity in SARS-CoV-2 replication in intestinal tissues results from differences in ACE2 levels, which may underlie variable patient outcomes.

Boosters reduce in-hospital mortality in patients with COVID-19: An observational cohort analysis

BackgroundReal-world data on the effectiveness of boosters against COVID-19, especially as new variants continue to emerge, is limited. Our objective was to assess demographic, clinical, and outcome variables of patients requiring hospitalization for severe SARS-CoV-2 infection comparing fully vaccinated and boosted (FV&B), fully vaccinated (FV), and unvaccinated (UV) patients.MethodsThis multicenter observational cohort analysis compared demographic, clinical, and outcome variables in FV&B, FV, and UV adults hospitalized for COVID-19. Partially vaccinated (PV) and individuals still hospitalized beyond the designated follow-up date of February 1, 2022 were excluded. The primary endpoint was in-hospital mortality. Secondary endpoints included characteristics and outcomes in subpopulations of intensive care and geriatric (age >65) patients.FindingsBetween August 12th, 2021 and January 20th, 2022, 8232 patient encounters had a primary diagnosis of COVID-19 and required inpatient treatment. Of the 8232 encounters requiring hospitalization, 448 (5.8%) were FV&B, 2257 (29.2%) were FV, and 5023 (65.0%) were UV; 357 PV and 147 still hospitalized were excluded. The median age of FV&B cohort was 73 (IQR 62, 82) compared to 70 (IQR 59, 80) for FV and 59 (IQR 45, 71) for UV (0.001). Most patients were female in both the FB&V and UV groups with 51.1% and 51.8%, respectively, while the FV group had a majority of males (51.3%). The median Elixhauser weighted score was 12 (IQR 3, 22) for FV&B, 10 (IQR 2, 20) for FV, and 9 (IQR 0, 17) for UV groups (p < 0.001). In-hospital mortality was 7.1% in the FV&B, 10.3% in the FV group, and 12.8% in the UV group (p < 0.001). The FV&B group had lower in-hospital mortality than both FV and UV groups (p = 0.045 and p = 0.001, respectively). The FV group had lower in-hospital mortality than the UV group (p = 0.004).InterpretationFully vaccinated and boosted patients requiring hospital-level care for breakthrough COVID-19 have lower in-hospital mortality than fully vaccinated and unvaccinated patients despite being older and higher risk at baseline. Boosters offer added protection beyond full vaccination in preventing death. As COVID-19 continues to spread, larger expansive trials are needed to further identify risk factors for severe outcomes among the FV&B population.FundingThis research received no specific grant from any funding agency in public, commercial, or not-for-profit sectors.

Role of muscle-targeted nutritional therapy: new data.

To provide an updated overview of recent efficacy data on the use of muscle-targeted nutritional therapy, which should consider the optimization of protein and essential amino acids intakes, possibly in combination with supplementation with vitamin D (correction of deficiency/insufficiency status) and v-3 fatty acids. Intervention studies conducted in the last years in different healthcare settings and heterogeneous patient populations support the use of muscle-targeted oral nutritional supplementation to improve muscle mass, function and physical performance in patients with sarcopenia. Higher efficacy is likely to be achieved in combination with individually tailored resistance exercise training programs and when nutritional therapy and the provision of specific nutrients result in an adequate protein-calorie balance. However, not only a reactive but also a pro-active application of this therapy could be proposed as evidence exists on the maintenance of or improvement in the same outcome variables in patients at risk of losing skeletal muscle mass. Based on available efficacy data, both a reactive and pro-active use of muscle-targeted nutritional therapy are promising and should be proposed. However, future research should be directed toward the management of patient populations characterized by substantial muscle wasting, as these have been frequently excluded from previous trials, perhaps to avoid confounding.

Abstract TP94: Stroke Severity Scales Do Not Predict Adverse Hospital Outcome Variables In Young Stroke Patients: Results From A Regional Stroke Center Of Excellence

Introduction: Acute ischemic stroke (AIS) among young patients is increasing in the US. This study sought to describe the risk factors, clinical characteristics, and hospital outcomes of young AIS patients who were treated in intensive care units (ICU). Methods: The current study was retrospective analysis of electronic healthcare data from a Regional Comprehensive Stroke Center of Excellence. The data was collected from admitted patients between Oct 2016 and Feb 2021 and included AIS patients between 18 and 45 years of age. Correlation and regression analysis were performed in order to understand the relation between risk predictors such as Acute Physiology and Chronic Health Evaluation (APACHE) IV score, Acute Physiology Score (APS), National Institute of Health Stroke Score (NIHSS), and Intensive Care after Thrombolytic (ICAT) and hospital outcomes. Results: There were 217 young AIS patients and 50.2% were males. More than half of the patients were white Hispanic (54%), followed by African American (24%), and whites (13%). Nearly 8% patients received intravenous thrombolysis, 2% endovascular reperfusion therapy, and 6% both treatments. Nearly 16% were smokers, 46% were hypertensive, 31% were dyslipidemic, 18% had previous stoke, 49% were obese or overweight, 18% were diabetic, 2% had carotid stenosis, 6% had CAD, and 1% had dysrhythmia. The mean (standard deviation) of APACHE, APS, NIHSS and ICAT scores were 5.0 (3.8), 33.8 (17.5), 5.5 (8.5), and 1.5 (1.5) respectively. Severity adjusted mean (SD) length of stay in hospital and ICU were 1.2 (0.9) and 1.2 (1.2) days, respectively. Severity adjusted ventilator days were 1.7 (2.1) days. Mean severity (SD) adjusted ICU and in-hospital mortality rates were 0.05 (0.54) and 0.60 (2.8) respectively. Analysis showed no association between risk predictors and adverse hospital outcome variables. Conclusion: Risk predictor scores did not predict adverse hospital outcomes in our AIS patients. Significant number of young AIS patients had chronic conditions which could have increased their stroke risk. Considering that majority of stroke risk factors are modifiable, strategies to decrease these risk factors to lower stroke rates should be prioritized among all these patients, independent of their risk scores.

Patient Factors Associated With Increased Risk for Complications After the Latarjet Procedure.

Background:The open Latarjet has become the most common method of addressing significant glenoid bone loss in patients with recurrent glenohumeral instability.Purpose:To describe national trends in Latarjet procedures and risk factors for complications associated with this procedure.Study Design:Cohort study; Level of evidence, 3.Methods:Eligible patients were identified through the National Surgical Quality Improvement Program (NSQIP) data set over the years 2014 to 2018 by using the Current Procedural Terminology (CPT) code for “capsulorrhaphy anterior with coracoid process transfer” (CPT 23462). Patient and surgical outcome variables were extracted and analyzed from the NSQIP database. Logistic regression analysis and odds ratios (ORs) were performed to evaluate the relative risk of complications.Results:The authors identified 458 patients (399 men and 59 women) from the data set. The mean body mass index was 27.4 kg/m2, and mean operative time was 130.2 minutes. Statistically significant variables included smoking status and sex, which were further stratified. Smokers were 2.19 times more likely to experience at least 1 adverse outcome, including deep vein thrombosis (DVT), pulmonary embolism, reoperation, wound infection, unplanned readmission, or readmission (95% CI, 0.62-7.82). Specifically, smokers were 7.8 times more likely to have a DVT (95% CI, 0.58-105.96), 1.4 times more likely to undergo reoperation (95% CI, 0.14-5.73), and 2.4 times more likely to have an unplanned readmission (95% CI, 0.19-28.68). Women were 2.2 times more likely to experience at least 1 adverse outcome. Specifically, women were found to be 6.4 times more likely to have a DVT (95% CI, 0.76-54.87), 4.1 times more likely to have an unplanned readmission (95% CI, 0.00-106.21), and 4.7 times more likely to have a readmission (95% CI, 0.00-13.92).Conclusion:The results indicate that smokers and female patients are at a higher risk of experiencing adverse outcomes and may require additional pre- and postprocedural precautions when undergoing the Latarjet procedure. With the increase in frequency, providers should be aware of patient-related factors that may lead to adverse outcomes.

Between-Center Variation in Outcome After Endovascular Treatment of Acute Stroke: Analysis of Two Nationwide Registries.

Insight in differences in patient outcomes between endovascular thrombectomy (EVT) centers can help to improve stroke care. We assessed between-center variation in functional outcome of patients with acute ischemic stroke who were treated with EVT. We analyzed to what extent this variation may be explained by modifiable center characteristics. We used nationwide registry data of patients with stroke treated with EVT in the Netherlands and in the Czech Republic. Primary outcome was modified Rankin Scale score at 90 days as an indicator of disability. We used multilevel ordinal logistic regression to quantify the between-center variation in outcomes and the impact of patient and center characteristics. Between-center variation was expressed as the relative difference in odds of a more favorable modified Rankin Scale score between a relatively better performing center (75th percentile) and a relatively worse performing center (25th percentile). We included a total of 4518 patients treated in 33 centers. Adjusted for patient characteristics, the odds of a more favorable outcome in a center at the 75th percentile of the outcome distribution were 1.46 times higher (95% CI, 1.31-1.70) than the odds in a center at the 25th percentile. Adjustment for center characteristics, including the median time between stroke onset and reperfusion per center, decreased this relative difference in odds to 1.30 (95% CI, 1.18-1.50, P=0.01). This translates into an absolute difference in likelihood of good functional outcome of 8% after adjustment for patient characteristics and to 5% after further adjustment for modifiable center characteristics. The considerable between-center variation in patient outcomes after EVT for acute ischemic stroke could be largely explained by center-specific characteristics, such as time to reperfusion. Improvement of these parameters may likely result in a decrease in center-specific differences, and an overall improvement in outcome of patients with acute ischemic stroke.

The role of pharmacogenetics in Efficacy and safety of protease inhibitor based therapy in human immunodeficiency virus type (HIV) infection.

Antiretroviral therapy has markedly reduced morbidity and mortality for persons living with human immunodeficiency virus (HIV). HIV can now be classified as a chronic disease; until a cure is found, patients are likely to require life-long therapy. However, despite these undoubted advances, there are many issues that need to be resolved, including the problems associated with long-term efficacy and toxicity. Moreover, pharmacotherapy of patients infected with HIV is challenging because a great number of comorbidities increase polypharmacy and the risk for drug-drug interactions. There is considerable interindividual variability in patient outcomes in terms of drug disposition, drug efficacy and adverse events. The basis of these differences is multifactorial, but host genetics are believed to play a significant part. HIV-infected population consists of ethnically diverse individuals on complex and potentially toxic antiretroviral regimens on a long-term basis. These individuals would benefit greatly from predictive tests that identify the most durable regimens. Pharmacogenetics holds that promise. Thus, detailed understanding of the metabolism and transport of antiretrovirals and the influence of genetics on these pathways is important. To this end, this review provides an up-to-date overview of the metabolism of antiHIV therapeutics of the protease inhibitors Lopinavir and Ritonavir and the impact of genetic variation in drug metabolism and transport on the treatment of HIV.

Competitive Endogenous RNA Network Involving miRNA and lncRNA in Non-Hodgkin Lymphoma: Current Advances and Clinical Perspectives.

Non-Hodgkin lymphoma (NHL) is a heterogeneous malignancy with variable patient outcomes. There is still a lack of understanding about the different players involved in lymphomagenesis, and the identification of new diagnostic and prognostic biomarkers is urgent. MicroRNAs and long non-coding RNAs emerged as master regulators of B-cell development, and their deregulation has been associated with the initiation and progression of lymphomagenesis. They can function by acting alone or, as recently proposed, by creating competing endogenous RNA (ceRNA) networks. Most studies have focused on individual miRNAs/lncRNAs function in lymphoma, and there is still limited data regarding their interactions in lymphoma progression. The study of miRNAs’ and lncRNAs’ deregulation in NHL, either alone or as ceRNAs networks, offers new insights into the molecular mechanisms underlying lymphoma pathogenesis and opens a window of opportunity to identify potential diagnostic and prognostic biomarkers. In this review, we summarized the current knowledge regarding the role of miRNAs and lncRNAs in B-cell lymphoma, including their interactions and regulatory networks. Finally, we summarized the studies investigating the potential of miRNAs and lncRNAs as clinical biomarkers, with a special focus on the circulating profiles, to be applied as a non-invasive, easy-to-obtain, and reproducible liquid biopsy for dynamic management of NHL patients.

Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited cardiac arrhythmia condition, triggered by physical or acute emotional stress, that predominantly expresses early in life. Gain-of-function mutations in the cardiac ryanodine receptor gene (RYR2) account for the majority of CPVT cases, causing substantial disruption of intracellular calcium (Ca2+ ) homeostasis particularly during the periods of β-adrenergic receptor stimulation. However, the highly variable penetrance, patient outcomes, and drug responses observed in clinical practice remain unexplained, even for patients with well-established founder RyR2 mutations. Therefore, investigation of the electrophysiological consequences of CPVT-causing RyR2 mutations is crucial to better understand the pathophysiology of the disease. The development of strategies for reprogramming human somatic cells to human induced pluripotent stem cells (hiPSCs) has provided a unique opportunity to study inherited arrhythmias, due to the ability of hiPSCs to differentiate down a cardiac lineage. Employment of genome editing enables generation of disease-specific cell lines from healthy and diseased patient-derived hiPSCs, which subsequently can be differentiated into cardiomyocytes. This paper describes the means for establishing an hiPSC-based model of CPVT in order to recapitulate the disease phenotype in vitro and investigate underlying pathophysiological mechanisms. The framework of this approach has the potential to contribute to disease modeling and personalized medicine using hiPSC-derived cardiomyocytes. © 2021 Wiley Periodicals LLC.

Mental Health Among Patients with Non-Hodgkin Lymphoma: A Danish Nationwide Study of Psychotropic Drug Use in 7,201 Patients and 36,005 Matched Comparators

Introduction: A cancer diagnosis is associated with profound psychological distress that potentially can lead to mental health problems such as depression and anxiety. Non-Hodgkin lymphomas (NHLs) are a heterogenous group of indolent and aggressive cancer diseases with high variability in treatment selections and patient outcomes. Some patients are chronically ill with recurrent need for mild chemotherapy whereas others face immediately life-threatening, yet curable disease. To gain valuable insights into the psychological distress associated with NHLs, the present study investigated the incident psychotropic drug (PD - antidepressants, anxiolytics, and antipsychotics) use, contact patterns to psychiatric departments, and intentional self-harm (including suicide) in Danish NHL patients relative to sex- and age matched individuals from the background population.Methods: The study was carried out as a nationwide population-based matched cohort study based on prospectively collected data from several Danish registries. All adult NHL patients (≥18 years) diagnosed between 2005 and 2015 were identified in the Danish Lymphoma Registry and included if they had not been treated with any kind of PD within the last 10 years prior to date of NHL diagnosis (index date). NHL patients were matched on age and sex with five random comparators from the Danish background population on the index date. Comparators had to be alive and without PD use 10 years prior to the index date. Incident PD use was defined as first redeemed prescription of PD after index date. Prescriptions were captured in the National Prescription Registry and described by cumulative incidences using the Aalen-Johansen estimator with death and NHL relapse as competing risk. Contacts with psychiatric departments and registration of intentional self-harm or completed suicide were captured in the Danish National Patient Registry. Patients were subcategorized according to type of lymphoma (Table 1).Results: In total, 7,201 NHL patients and 36,005 matched comparators were included (median follow-up 7.1 years). Follicular lymphoma (FL, 44.4%) and diffuse large B-cell lymphoma (DLBCL, 41.0%) were the most common subtypes (Table 2). Two-year cumulative incidence of PD use was higher in NHL patients overall (16.2%, 95%CI 15.4-17.0%) compared to matched comparators (5.7%, 95%CI 5.5-5.9%). Patients with aggressive NHL subtypes tended to have the highest incidence of PD use (Figure 1). Antidepressants (two-year cumulative incidence, 9.0%, 95%CI 8.4-9.6) and anxiolytics (8.2%, 95%CI 7.6-8.8) were the most used PDs in all NHL subtypes. The risk of PD use was higher in the first years following diagnosis, but except for patients with indolent NHL subtypes, the risk of PD use normalized over time to that of the background population. As for the risk of any psychiatric department contacts, there was no difference in two-year cumulative incidences between NHL patients (range 0.6-0.9%) and the matched comparators (range 0.6%-0.9%), whereas the two-year cumulative incidence of intentional self-harm and suicide was slightly higher for NHL patients (0.3%) compared to the matched comparators (0.2%, p=0.01).Conclusion: This study suggests that NHL patients have a significantly higher risk of mental health problems compared to the Danish background population, (when) using PD prescriptions as a proxy measure. The risk of intentional self-harm and completed suicide was also higher, but numerical differences were very small. Overall, the results emphasize the need for directing clinical attention on mental health in newly diagnosed NHL patients and screening for relevant symptoms during follow-up to provide best possible support to patients suffering from anxiety and depression. [Display omitted] DisclosuresØvlisen: Abbvie: Other: Travel expenses. Kragholm: Novartis: Honoraria. Nielsen: Lundbeck: Honoraria, Other: Investigator, Research Funding; Otsuka Pharmaceuticals: Honoraria, Other: Prior Advisor, Research Funding; Bristol-Myers Squibb: Honoraria; Astra Zeneca: Honoraria, Other: Prior advisor; Janssen & Cilag: Honoraria, Other: Investigator; Servier: Honoraria; Teva A/S: Honoraria; Eli Lilly: Honoraria, Other: Prior Advisor; Takeda: Other: Prior advisor; Medivir: Other; Boehringer: Other: Investigator. Brown: BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartys: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Dahl-Soerensen: Takeda: Other: Travel grant. Frederiksen: Novartis: Research Funding; Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding. Mannering: Novartis: Research Funding; Swedish Orphan Biovitrum (SOBI): Membership on an entity's Board of Directors or advisory committees. Jørgensen: Gilead: Consultancy; Roche: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Clausen: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expences ASH 2019; Gilead: Consultancy, Other: Travel expences 15th ICML . El-Galaly: ROCHE Ltd: Ended employment in the past 24 months; Abbvie: Other: Speakers fee.

Outcome Differences Between Direct Admissions to the PICU From ED and Escalations From Floor.

To compare the outcomes (mortality and ICU length of stay) of patients with direct admissions to the PICU from the emergency department [ED]) versus as an escalation of care from the floor. A retrospective cohort study with a secondary analysis of registry data. Patient demographics and outcome variables collected from January 1, 2015, to December 31, 2019, were obtained from the Virtual Pediatric Systems database. Patients with a source of admission other than the hospital's ED or pediatric floor were excluded. Multivariable regression analysis controlling for age groups, sex, race, diagnostic categories, and severity of illness (Pediatric Index of Mortality III), with clustering for sites, was performed. A total of 209 695 patients from 121 sites were included in the analysis. A total of 154 716 (73.7%) were admitted directly from the ED, and 54 979 were admitted (26.2%) as an escalation of care from the floor. Two groups differed in age and race distribution, medical complexity, diagnostic categories, and severity of illness. After controlling for measured confounders, patients with floor escalations had higher mortality (2.78% vs 1.95%; P < .001), with an odds ratio of 1.71 (95% CI 1.5 to 1.9) and longer PICU length of stay (4.9 vs 3.6 days; P < .001). The rates of most of the common ICU procedures and their durations were also significantly higher in patients with an escalation of care. Compared with direct admissions to the PICU from the ED, patients who were initially triaged to the pediatric floor and then require escalation to the PICU have worse outcomes. Further research is needed to explore the potential causes of this difference.

EP.TH.208The need for speed: Reduced operative time in laparoscopic sleeve gastrectomy may reduce length of hospital stay

Abstract Introduction Length of stay (LOS) in laparoscopic sleeve gastrectomy (LSG) is affected by multiple factors, including gender, BMI &amp;gt;50, comorbidities, socioeconomic status and increased operative time (OT). This study aimed to evaluate the effect of reduced OT on LOS. Methods Analysis was conducted using a prospective database in patients who underwent LSG by a single surgeon at a single institution from January 2015 to December 2019. Patients receiving other operations (e.g. adhesiolysis, cholecystectomy, para-oesophageal hiatal hernia repair or ventral hernia repair) during LSG were excluded. All the patients were divided into two groups: OT ≤ 60 minutes and OT &amp;gt; 60 minutes. Patient demographics and outcome variables, including LOS, 30-day readmission, unexpected return to operating theatre, complications and mortality, were collected and analysed. Results A total of 1412 patients were included. In OT ≤ 60 minutes group (N = 804), the average LOS was 1.37 days and the average operative time was 51.31 minutes. In OT &amp;gt; 60 minutes group (N = 608), the average LOS was 1.66 days and the average operative time was 77.95 minutes. OT ≤ 60 minutes group showed a statistically significant decrease in LOS compared to OT &amp;gt; 60 minutes group (P-value &amp;lt;0.0001). The 30-day readmission rate was 0.97%. Complications included one gastric leak (0.07%), one postoperative bleeding requiring reoperation (0.07%), three (0.21%) portal vein thrombosis, and no mortality. Conclusion Our study demonstrated that reduced OT (≤60 minutes) in LSG was associated with reduced LOS but without increase in complication rates and mortality. This has implications for economic considerations for both hospitals and patients, especially in self-funded payer models.

Review of microbiological sampling in diabetic foot disease

Introduction: Diabetes mellitus is a significant cause of morbidity and mortality. Foot-related complications affect 2–2.5% of people with diabetes. There is significant variation in outcomes for patients with diabetic foot disease within the UK. The multidisciplinary approach to diabetic foot disease is well publicised and protocols, guidance and consensus approaches exist for most components of the management of diabetic foot disease. Antimicrobial therapy to treat diabetic foot infections based on microbiological sampling and culture is well documented, but no consensus exists on how these samples should be obtained, processed and reported. Methods: A literature review was undertaken to establish the reporting of techniques used in obtaining and processing microbiological samples in diabetic foot disease to establish if consensus exists in the methodologies used with a view to develop best practice guidelines. Results: Six out of 102 papers reported all processes in obtaining and processing microbiological samples. Conclusion: No gold standard consensus exists for microbiological sampling of diabetic foot infections, preventing optimisation of this aspect of management of diabetic foot disease and ultimately potentially adversely affecting the outcomes of this growing patient cohort.

Severe dengue in adults and children, Ouagadougou (Burkina Faso), West Africa, October 2015–January 2017

Although dengue is the most common arbovirus infection worldwide, studies of severe dengue in Africa are lacking, and risk factors for severe dengue have been insufficiently described. This study was conducted in the context of the 2016 dengue epidemic in Burkina Faso to determine the prevalence of severe dengue, identify factors associated with severe dengue, and perform mapping of dengue cases in the country's capital, Ouagadougou. This cross-sectional study was conducted from November 2015 to January 2017. Data were collected in 15 public and private health centres, and included sociodemographic, clinical and patient outcome variables. Dengue was diagnosed using SD Bioline Dengue Duo rapid diagnostic tests. Data were analysed using Epi-Info Version 7. Logistic regression was used to identify predictors of severe dengue. P<0.05 was considered significant. Dengue case mapping was performed using Geographic Information System software (ArcGIS). Of the 811 patients who tested positive for dengue, 609 (75%) had early dengue (AgNS1 positive) and 272 (33.5%) had severe dengue. Patient age ranged from 1 to 83 years (median 30.5 years) and 393 (48.3%) were female. Renal failure (13.1%) and severe bleeding (10.6%) were the most common signs of severe dengue. Risk factors for severe dengue included age, male sex, haemoglobin S, diabetes, hypertension, and primary dengue.Dengue cases weremore concentratedin sectors located in the centre of the city and close to the health centres. Dengue is increasingly common in Africa and factors associated with severity should be sought systematically as soon as a patient tests positive. Additional studies are needed to determine if the factors found to be associated with severity can be used to identify patients at risk for dengue-related complications, and to provide early and specialized management to reduce morbidity and mortality related to dengue in Africa.

VENTILATOR-INDUCED DIAPHRAGMATIC DYSFUNCTION: MODIFIABLE CAUSES OF INJURY AND CORRELATED OUTCOMES

TOPIC: Critical Care TYPE: Late Breaking PURPOSE: The purposes of this study are to correlate the incidence of ventilator-induced diaphragmatic injury in the MICU to patient outcomes, and to assess for associations between diaphragmatic dysfunction and modifiable variables in mechanical ventilator management or sedation strategy. METHODS: Adult critically-ill patients admitted to Yale New Haven Hospital MICU were enrolled if intubated, mechanically ventilated, and qualified for a breathing trial. Diaphragm thickness, thickening fraction, and excursion were measured by bedside ultrasound, alongside an airway occlusion maneuver and maximum inspiratory pressure. These measurements were correlated with patient outcome variables, including duration of mechanical ventilation, re-intubation within 7 days of extubation, NIV following extubation, tracheostomy, and death during hospitalization, as well as modifiable ventilator settings and level of sedation. RESULTS: In an analysis of our first 13 patients, we found that there was a non-statistical difference in length of hospital stay between those with a reduced diaphragm thickening fraction (TF) ≤ 20% vs those with a normal TF (49.75 vs 32.22 days, p=0.087), although there was no difference in days on mechanical ventilation or length of ICU stay. When dividing patient subsets into categories of reduced or excessive effort (TF ≤ 20% or TF > 30%) vs normal effort (20% < TF ≤ 30%), we found that only those with abnormal effort had re-intubation within 7 days of extubation (3 vs 0) or required tracheostomy (3 vs 0). Those with a diaphragm thickening fraction ≤ 20% had near-statistically significant differences in admission APACHE II score (20.5 in low TF vs 15 in normal TF, p=0.063), as well as lower ventilatory pressure support (inspiratory pressure 17.78 cmH2O in low TF vs 22.39 cmH2O in normal TF, p=0.099). CONCLUSIONS: Although underpowered given a small initial dataset, our study may indicate that a reduced thickening fraction at time of breathing trial may correlate with a prolonged hospital stay, although is not a marker for prolonged mechanical ventilation. Reduced or increased effort may also suggest increased risk of re-intubation or need for tracheostomy. It is also important to note that those who had a higher severity of critical illness at time of intubation, and those who received less inspiratory support while on mechanical ventilation, had a reduced thickening fraction relative to those less ill or receiving greater pressure support. CLINICAL IMPLICATIONS: Only recently has diaphragmatic myotrauma been characterized as a potential mediator for prolonged mechanical ventilation and poor patient outcomes. However, the assessment of its presence by simple, reproducible, and non-invasive means has remained elusive, and its clinical utility dubious at best. This study illustrates the potential use of ultrasound-based diaphragmatic thickening fraction at time of spontaneous breathing trial as a measure of normal, decreased, or increased respiratory muscle effort, and how this may correlate to length of hospital stay, risk of re-intubation, and need for tracheostomy. It also suggests that the level of critical illness may correspond with a higher incidence of diaphragmatic injury, and that increased mechanical support, while maintaining lung protective strategy, may help maintain normal respiratory muscle function. Further studies will be necessary in the future to corroborate these results. DISCLOSURES: No relevant relationships by Jan Fouad, source=Web Response No relevant relationships by Lauren Killingsworth, source=Web Response No relevant relationships by Margaret Pisani, source=Web Response