Clinical Outcomes In Adult Patients Research Articles

Impact of Sulfonamide Allergy Label on Clinical Outcomes in Patients with Pneumocystis jirovecii Pneumonia.

The presence of antibiotic allergy labels can have harmful impacts on clinical outcomes, particularly among immunosuppressed patients, in whom there have been associations with increased complications, readmission rates, and mortality. We explore the effects of a sulfonamide allergy label (SAL) on clinical outcomes in adult patients with Pneumocystis jirovecii pneumonia (PJP). In this retrospective matched cohort study, we utilized TriNetX, a multicenter national database, to match 535 adult patients with PJP and SAL to an equal number of controls. We identified cases indexed between 01/01/2010 and 01/01/2023 utilizing ICD-10 codes for PJP and allergy status to sulfonamides and through detection of P. jirovecii antigen with immunofluorescence or PCR. Propensity score matching was performed in a 1:1 fashion for demographics and comorbidities, and our analysis included clinical outcomes that occurred within 30days after the occurrence of the index event. While hospitalization risk tended to be lower among patients with SAL as compared to controls (RR: 0.90; 95% CI 0.81-1.01), there were no major differences in the risk of respiratory failure (RR: 0.94; 95% CI 0.84-1.05), prednisone use (RR: 1; 95% CI 0.91-1.10), intensive level of care requirement (RR: 0.85; 95% CI 0.69-1.06), intubation (RR: 0.85; 95% CI 0.61-1.19), or mortality (RR: 0.98; 95% CI 0.68-1.42). The presence of SAL did however impact antibiotic prescription patterns, with an underutilization of trimethoprim (RR: 0.50; 95% CI 0.43-0.59) and sulfamethoxazole (RR, 0.47; 95% CI 0.40-0.56) and overuse of alternative agents by patients with SAL as compared to controls. Yet, there was no difference in the occurrence of adverse outcomes such as hepatotoxicity (RR: 1.09; 95% CI 0.49-2.45) or acute kidney injury (RR: 0.94; 95% CI 0.78-1.14) between patients with SAL and controls. The presence of SAL alters antibiotic prescription patterns among adults with Pneumocystis infection but has no clinically significant impact on outcomes.

Clinical impact of a cardiac intensivist in an adult cardiac care unit from the RESCUE registry

Abstract Funding Acknowledgements None. Purpose Dedicated intensive care unit (ICU) physician staffing is assocated with a reduction in ICU mortality rates in general medical and surgical ICUs. However, limited data area available on the role of cardiac intensivist in the cardiac intensive care unit (CICU). We investigated the association of cardiac intensivist-directed care with clinical outcomes in adult patients admitted to the CICU. Methods The SMART-RESCUE study is a multicenter, retrospective and prosective registry of patients that presented witth cardiogenic shock (CS). Between January 2014 and December 2018, 1,247 patients with CS were enrolled from 12 major centers in Korea. The study population was divided into 2 groups, according to the presence of a cardiac intensivist. The primary outcome was in-hospital mortality. Results THe analysis with SMART-RESCUE registry included 1,247 patients with CS (n=552 in the group with cardiac intensivist and n=695 in the group without cardiac intensivist) (Table 1). The in-hospital survival rate was significant higher in the group with intensivist than that in the group without intensivist (72.1% vs 59.2%, p < 0.001) (Figure 1). Cardiac intensive care with cardiac intensivist was associated with a reduction in risk-adjusted in-hospital mortality (adjusted odds ratio for in hospital death, 0.53; 95% confidence interval: 0.401 to 0.704; p < 0.001). Survival analysis also revealed significantly higher death free survival in te group with intensitivst. In multivariable analysis, cardiac intensivist, chronic kidney disease, ECMO-cardiopulmonary resuscitation, ST elevation myocardial infarction presentation and vasotrope-inotrope score were selected to be significant prognostic predictors for death in the CICU. Concluison: The presence of a dedicated cardiac intensivist was associated with a reduction in hospital mortality rates in patients with cardiovascular disease who required critical care.

Effect of Phenobarbital-Based Alcohol Withdrawal Protocol on Provider Practice and Patient Outcomes—A Quality Improvement Study

Introduction: Alcohol is the most common substance use disorder in the United States. Despite this prevalence, there remains significant heterogeneity in medical management of alcohol withdrawal syndrome (AWS). While the 2020 American Society of Addition Medicine continues to recommend the use of benzodiazepines as first-line therapy for AWS, there is increasing use of phenobarbital in patients at high risk of severe AWS. Despite phenobarbital’s favorable pharmacologic profile, historically, clinical utilization on general medicine services has been low and often restricted. In this project, we have examined practice patterns and associated clinical outcomes in adult patients experiencing AWS on the general medicine service pre and post implementation of a phenobarbital-based protocol for the treatment of severe AWS at our institution. Methods: This quality improvement study evaluated changes in management of AWS on general medicine units associated with implementation of a phenobarbital-based protocol and order set in the electronic medical record (EMR). Our primary outcome measures were receipt of a phenobarbital loading dose, concomitant benzodiazepine administration, and total benzodiazepine dose. Safety outcomes were also explored to assess clinical impacts of this protocol implementation. The project was determined “not research” by our Institutional Review Board. Results: Phenobarbital-protocol implementation was associated with increased frequency of receiving a phenobarbital loading dose (49.5% vs 9.4%; P < .001), decreased use of concomitant benzodiazepine/phenobarbital (4.3% vs 28.9%; P < .001), and decreased total benzodiazepine dose (7.8 vs 15.5 mg; P < .001). Regarding safety, there was no significant pre/post difference in the rate of ICU transfer, but among those transferred there was a trend toward decreased mechanical ventilation rate (100% vs 28.6%; P = .051), and a significantly reduced ICU length of stay (median 11 vs 3 days; P = .04). There were no pre/post differences in seizures, delirium or use of adjunct medications. Conclusions: This quality improvement study demonstrates a marked change in provider prescribing practices for treating AWS after implementation of an institutional phenobarbital-based protocol. We observed no difference in overall clinical outcomes after protocol implementation, although a larger follow-up study is needed to confirm this and to further explore the shorter ICU length of stay for patients with AWS postimplementation.

Clinical Impact of Vancomycin MIC on Outcomes in Patients With Coagulase-negative Staphylococcal Bacteremia

Coagulase-negative staphylococci (CoNS) are Gram-positive organisms that are a known component of normal skin flora and the most common cause of nosocomial bacteremia. For CoNS species, the vancomycin MIC breakpoint for susceptibility set by the Clinical and Laboratory Standards Institute is ≤4 µg/mL. There has been published reports of vancomycin heteroresistance in CoNS with vancomycin MICs of 2 to 4 µg/mL. The aim of this retrospective cohort analysis was to assess the clinical impact of vancomycin MICs <2 µg/mL versus ≥2 µg/mL in adult patients with CoNS bloodstream infections. Adult patients admitted to University Medical Center New Orleans with a blood culture positive for CoNS were assessed. The primary outcome was difference in 30-day mortality. Secondary outcomes were in-hospital, all-cause mortality; duration of bacteremia; hospital length of stay; and percentage of oxacillin-resistant CoNS. There was no difference in mortality in the vancomycin MIC <2 µg/mL group versus the vancomycin MIC ≥2 µg/mL group at 30 days (15.4% vs 17.4%; P = 1). In-hospital, all-cause mortality was also not different between groups (11.5% vs 13%; P = 1). Hospital length of stay between groups was 28.2 days versus 21 days (P = 0.692). Median duration of bacteremia was 1 day in both groups (P = 0.975), and median scheduled duration of antibiotic therapy was 14.9 days and 19.5 days (P = 0.385). The source and mode of acquisition of CoNS were similar between groups. Of all CoNS isolates, 58.7% (44 of 75) were oxacillin resistant. Staphylococcus epidermidis was the most common CoNS species at 66.7% (50 of 75). Of all isolates, 30.7% (23 of 75) had a vancomycin MIC ≥2 µg/mL, and 87% (20 of 23) of these were S. epidermidis. There was a higher percentage of S. epidermidis in the vancomycin MIC ≥2 µg/mL group than in the MIC <2 µg/mL group (87% vs 57.7%; P = 0.012). CoNS with a vancomycin MIC ≥2 µg/mL were also more likely to be oxacillin resistant (78.3% vs 50%; P = 0.005). There was no difference in clinical outcomes in adult patients with a CoNS bloodstream infection with a vancomycin MIC <2 µg/mL versus ≥2 µg/mL. At present, vancomycin remains appropriate empiric therapy for CoNS bloodstream infection. Further research is needed to determine if there is a true clinical impact of a vancomycin MIC ≥2 µg/mL in CoNS infections.

Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis

PurposeMultidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection.MethodsFrom the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality.ResultsIn total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality.ConclusionsMDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.

Survival Outcomes of APA as a Starting treatment: Impact in real-world patients with mCSPC (OASIS).

65 Background: Over the last decade,androgen receptor signaling inhibitors (ARSIs; apalutamide [APA], enzalutamide [ENZ], abiraterone acetate + prednisone [AAP]) in combination with androgen-deprivation therapy (ADT) have emerged as more effective life-prolonging treatment options for mCSPC. We examined the impact of ARSI starting therapy in mCSPC on long-term clinical outcomes in real-world clinical practice in the US. Methods: This retrospective, observational cohort study evaluated clinical outcomes in adult patients with mCSPC using the ConcertAI RWD 360 prostate cancer dataset. All patients with newly diagnosed mCSPC from 1 Jan 2018 to 30 Sept 2022 were enrolled and followed up until 31 Mar 2023. Among other outcomes, PSA50 and PSA90 (PSA response defined as a ≥50% and ≥90% decline from baseline, respectively) and undetectable PSA (PSA ≤0.2 ng/mL) were assessed using the Kaplan-Meier method. Relative risks of onset of castration resistance (CR) and death were estimated using multivariate Cox proportional hazard models adjusted for potential confounding factors (age, comorbidities, BMI, baseline PSA). Results: 165 patients with mCSPC started on APA + ADT, 643 started on ENZ + ADT, 1064 on AAP +ADT, 293 on docetaxel (DTX) + ADT, and 543 on ADT alone (Table). A higher proportion of patients initiating APA achieved PSA50, PSA90, or undetectable PSA compared with other treatments. CR-free survival was significantly longer in patients first treated with an ARSI + ADT than those treated with DTX + ADT or ADT alone. Reduced risk of developing CR was observed in patients starting with APA + ADT compared with ADT alone (adjusted hazard ratio [aHR] 0.36, 95% CI 0.19, 0.67; p=0.0016). OS was longer in patients started on ARSIs compared to ADT alone. Patients starting with APA + ADT were observed to have a lower risk of death compared with ENZ + ADT (aHR 0.48, 95% CI 0.23, 0.99; p&lt;0.05) or AAP + ADT (aHR 0.43, 95% CI 0.21, 0.90; p&lt;0.05). Conclusions: ADT alone continues to be used widely despite the availability of newer and more effective life prolonging therapies. Use of APA + ADT as starting treatment for mCSPC demonstrated significantly better clinical outcomes than other ARSIs, DXT + ADT, or ADT alone in real-world clinical practice in the US. [Table: see text]

Impact of Empirical Antibiotics Therapy on the Clinical Outcomes of Adult Patients Admitted to the Intensive Care Units with Sepsis in Sudan Impact of emperical antibiotics on the clincal outcomes of adult patients admitted to the intensive care unit with sepsis

Introduction: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Early recognition and administration of appropriate empirical antibiotic therapy are associated with lower mortality rate and shorter length of stay. This study aims to identify the risk factors for developing sepsis, the common sites of infection, the isolated microorganisms, and to evaluate the impact of appropriate empiric antibiotic on the mortality rate and length of stay the in two tertiary care hospitals in Sudan. Methodology: A prospective hospital-based study was done on 30 patients who were admitted to the intensive care unit (ICU) during a four-month study period. Data were retrieved from patients’ records. Data were analyzed using SPSS Version 20. Results: Out of the 30 study patients, 43% were females. The median age of the group was 68 years and 57% of the patients were above 65 years. The most common risk factor for developing sepsis was diabetes mellitus (23.33%), followed by malignancy (16.67%). The most common site of infection was the chest (33.33%). In total, 19 different regimens of empirical antibiotics were prescribed, where 43.4% were appropriate and 56.6% were inappropriate. Among the studied population, 18 patients died and the overall mortality was 60%. The study found that in patients who received appropriate empiric antibiotics, mortality significantly decreased (p = 0.006). Patients who received appropriate treatment were also found to have a numerically 4-days shorter length of ICU stay but this did not reach statistical significance due to small sample size. Conclusions: The study concluded that diabetes mellitus is the most common risk factor for developing sepsis, followed by malignancy. Gram-negative organisms are the most common isolated microorganisms. Respiratory infection is the most common source of infections. The prescribed empirical antibiotics were mostly inappropriate. Moreover, patients with appropriate empirical antibiotics had shorter ICU stays and increased survival when compared with those who had inappropriate treatment.

Clinical Surveillance vs Anticoagulation Therapy for Isolated Subsegmental Pulmonary Embolism: A Systematic Review of Clinical Outcomes.

This systematic review aims to evaluate and compare differences in clinical outcomes for adult patients diagnosed with ISSPE who were managed with anticoagulation vs clinical surveillance. PubMed, Embase, ProQuest, Cochrane, and Google Scholar were searched to identify studies evaluating the use of anticoagulation and/or clinical surveillance in patients diagnosed with ISSPE. The search included studies published up to August 3, 2023. Outcomes of interest included 90-day recurrent venous thromboembolism (VTE), major bleeding, and all-cause mortality rates. Ten studies were included with a total of 1224 patients. Of these patients, 791 were treated with anticoagulation and 433 underwent surveillance. Studies found no difference in recurrent VTE rates, with the majority of studies reporting no recurrence. Of the studies that reported VTE recurrence, rates were .5% to 1.4% for the anticoagulation groups and 3.1% to 3.2% for the surveillance groups. Major bleeding rates were also similar. In anticoagulated patients, major bleeding rates ranged from 1% to 10%. In clinical surveillance patients, the majority found no rate of major bleeding, with 2 studies reporting rates of .8% to 3.2%. Mortality rates ranged widely with no significant differences reported. Clinical surveillance appears to be a safe and effective alternative to anticoagulation in patients with ISSPE. Ninety-day rates of recurrent VTE, major bleeding, and mortality were comparable between groups. These findings highlight the need for updated practice management guidelines to improve patient outcomes.

TBI-Containing with T-Cell Replete Full Haplotype Mismatched Hematopoietic Stem Cell Transplantation in Adult Patients with De Novo Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the 2nd most frequent developing hematologic malignancy with deep heterogeneity, but unfortunately the majority of patients relapse even after allogeneic hematopoietic stem cell transplantation (HSCT) in complete remission (CR). We have developed allogeneic HSCT from familial mismatched/haploidentical donors (FMT) in adult patients with a single disease entity of AML lacking of both HLA-identical siblings and well-matched unrelated donors (WMUD) from the mid 1990s. Previously, several pilot studies of FMT performed with various total body irradiation (TBI)-based conditioning regimens (2~12 gray) with or without post-transplant cyclophosphamide (PT-Cy) as a graft-versus-host disease (GvHD) prophylaxis were reported. Here, we demonstrate about the encouraging outcomes of FMT using unmanipulated peripheral blood donor stem cells (PBSCs) and de-escalated dose of TBI (4~8 gray) containing conditioning regimen without T-cell depletion manner. Although PT-Cy as a specific GvHD prophylaxis regimen is increasingly used for both adult and pediatric FMT, our group investigated the clinical outcomes in adult patients with de novo AML who received full haplotype mismatched HSCT after TBI containing preparation regimen consisted of fractionated TBI (total 4 gray for elderly and 8 gray for &amp;lt;60 years old), fludarabine (150 mg/m 2/day), busulfex (6.4mg/kg/day), and anti-thymocyte globulin (ATG). For GvHD prophylaxis, rabbit ATG (thymoglobulin, Genzyme, 1.25mg/kg/day for 4 days at D-4 to D-1) and a combination of tacrolimus and short-term methotrexate was used. G-CSF mobilized unmanipulated PBSCs were used with a median CD34+ dose of 6.5 x 10 6/kg (1~25.6). From 2008 to the end of 2022, total 429 adult patients were enrolled, and data demonstrated that our trial of intermediate-dose of ATG and reduced toxicity of TBI-containing conditioning regimen to reduce graft-failure even for high levels of donor-specific antibody titer, early transplant-related mortality, critical cytomegalovirus (CMV) disease, and emerging post-transplant lymphoproliferative disease with rapid immune recovery has shown very successful outcomes. Briefly, the median absolute neutrophil count recovery was 12 days (10~26) and the platelet of 14 days (5~38). There was no either primary or secondary graft-failures at all. With a median follow-up of 36.5 months (2~242) for survivors, overall survival rate (OS) and relapse-free survival (RFS) for patients in any CR (n=338) and relapse/refractory status (n=91) were 62.9% vs. 34.3% and 59.5% vs. 32.2%, respectively. Although there was no significant difference in the subgroup analysis, de novo and young aged patients in any CR showed the best OS 73% (Figure 1). Cumulative incidences of acute GvHD and chronic GvHD were 66% (59-73), 70% (63-76), respectively. The incidences of moderate to severe acute GvHD and chronic GvHD were 16.1%, 30.5%, respectively. By univariate and multivariate analyses, patient's age &amp;lt;54 (p=0.043), pre-HSCT CR1 (p &amp;lt;0.001), absence of mod to severe chronic GvHD (p &amp;lt;0.001), and use of post-transplant iron-chelating agent (p=0.001) were the statistically significant in the study. The GvHD-free and relapse-free survival rate in CR1 was 62.4% for younger patients (age &amp;lt;54) and 47.9% for older patients (p=ns). The non-relapse mortality rate was 27.2% for all enrolled patients and 16% for CR patients. The rapidity of immune recovery was also compared with our old control cohort when we performed T-cell depletion using the CliniMACS system, and it showed a significant reconstitution of CD4+ cells (&amp;gt;300/ul) at 3 months post-FMT compared to the much delayed T-cell depleted FMT. Of note, CMV DNAemia was relatively higher (76.9%) than reported in other studies, likely due to the use of ATG and the endemic region of our country. Therefore, we suggest that the strategic reduction of fractionated TBI 4~8 gray-based conditioning with unmanipulated PBSCs graft without PT-Cy seems feasible with favorable outcomes for adult patients with de novo AML undergoing FMT in CR, especially even in a certain subgroup of elderly patients with AML.

Iron Overload and Treatment Outcome in an Adult Sickle Cell Disease Cohort

Objective. Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD) and has a compounded effect on iron overload, especially when simple top-off transfusions are given. Adults with sickle cell anemia (SCA: HbSS or HbSβ 0-thalassemia), often require episodic blood transfusions on a chronic basis and, hence, are at risk of developing transfusional iron overload. We monitored 83 adult SCD patients with a diagnosis of iron overload during routine treatment and follow up at our clinical center. The aim of this study was to observe and describe treatment outcomes for individuals with iron overload seen at the University of Illinois adult sickle cell center between 2010 and 2023. Method. Patients eligible for the study were aged 18 years or above at the time of their initial visit. Patients were identified from our institutional clinical and translational research informatics data warehouse using computable phenotype algorithms as well as SCD outpatient encounter information to improve accuracy of abstracted data. Results of our queries were abstracted in the form of identified patient data and subsequently reviewed in Epic electronic health record (Epic, Verona, WI). We retrospectively studied adult subjects with SCD seen during routine clinical care between 2010 and 2023. Selected subjects had a diagnosis of iron overload, determined by 2 consecutive ferritin levels &amp;gt;1000ng/ml in steady state plus a significant transfusion history. We extracted data on clinical laboratory markers, abdominal imaging, use of iron chelation at baseline and in the final year of follow up, whether patients were receiving chronic erythrapheresis treatment at baseline and at end of follow up, and if alive at the end of the follow up period. Subjects have variable start date and follow up period, beginning at the start of diagnosis of iron overload and ending in June 2023 or last identifiable follow up visit, or mortality. Result. Baseline characteristics of 83 adult patients included in our study are summarized in table 1. Seventy percent of the patients were female and just about everyone had HbSS disease. The females had older median age (39.5year; IQR 32-50 years) than males. The mean ferritin value was significantly higher than the initial measure after a median follows up period of 5.3 years. During the follow up period, 40% of male patients discontinued iron chelation therapy whereas only 5.6% of females did the same. Multivariable analyses were performed for association between change in ferritin measure (between follow up period) with demographic data and other covariates presented in Table 1. Covariates were eliminated by backward selection. Predictors retained in the final model include follow-up period, initial ferritin value, gender, ALT, AST, and albumin. Females had a higher drop in their follow up ferritin, but this was not significant. Neither use of iron chelation therapy at baseline nor erythrapheresis at baseline predicted a change in ferritin value, however we did not collect information on compliance or duration of therapy. Patients followed up for longer duration, or who have higher ALT, had subsequent higher measure for follow up ferritin. Higher albumin predicted a lower ferritin at follow up. The effects of liver markers on ferritin are likely correlative only. After a median follow up period of 5.3years, about 22% of the patients were confirmed to be deceased. Some patients lost to follow up have an indeterminate alive status. Predictors of mortality in multivariate analysis include follow up ferritin value, albumin, and HCV status. Positive HCV status had a strong association with cirrhosis (p=0.001) as 71% of HCV positive individuals had cirrhosis. In turn 53% of the cirrhotic patients died in the follow up period. Conclusion. Here we present an overview of the clinical outcomes of adult patients with SCD and iron overload during a median follow up period of 5.3 years. Despite limitations of a typical retrospective study, our study illustrates the difficulty associated with the management of transfusional iron overload during routine treatment follow up, especially in patients continuing to undergo episodic transfusion treatment. We also continue to underline the low adherence with chelation therapy in adult populations with SCD and iron overload, and the high mortality associated with the condition.

Real-World Patient Characteristics, Treatment Patterns, and Outcomes in Patients with Lower-Risk Myelodysplastic Syndromes Who Have Been Treated with Luspatercept

Background: Myelodysplastic syndromes (MDS) are a group of rare, clonal bone marrow malignancies characterized by ineffective erythropoiesis. Erythropoiesis-stimulating agents (ESAs) are a treatment option for anemia in patients with lower-risk MDS (LR-MDS); however as only one in three patients respond to ESAs, there is a need for additional treatment options. In April 2020, luspatercept was approved for the treatment of anemia in adult patients with LR-MDS who failed to respond to ESAs. The aim of this study was to investigate real-world treatment patterns and early clinical outcomes in adult patients in the United States with LR-MDS receiving luspatercept. Methods: This was a retrospective observational cohort study of adult patients (aged ≥ 18 years at initial MDS diagnosis) with an International Prognostic Scoring System/Revised IPSS (IPSS-R/IPSS) classification of Very Low-, Low-, or Intermediate-risk MDS on or before the initial MDS diagnosis date +30 days, who were actively treated with a therapy of interest (including ESAs, hypomethylating agents [HMAs], erythroid maturation agents [EMAs], iron chelation therapy [ICT], white blood cells [WBCs], growth factors, chemotherapy, immunomodulating drugs [IMiDs], and platelet growth factors), and who received at least one dose of luspatercept between initial MDS diagnosis and November 1, 2022 in the COTA Vantage database which contains longitudinal, HIPAA-compliant data pertaining to the diagnosis, clinical management, and outcomes of patients with cancer from a mix of academic and community settings. The index date was the date of luspatercept initiation. Patients were required to have at least 2 months of medical data post-index unless they died during this period. All analyses were descriptive. Results: A total of 86 patients who were treated with luspatercept (median age 78.0 years, 79.1% White, 52.3% male, 80.2% ECOG 0-1) were included. Median baseline hemoglobin level was 7.8 g/dL (range: 5.3-11.4 g/dL). Median time from MDS diagnosis to luspatercept initiation was 35.4 months and the median follow-up time was 13.4 months. The majority of patients (89.5%) were previously treated with ESAs for a median duration of 9.0 months. The two most used ESAs were darbepoetin alfa (54.5%) and epoetin alfa (44.2%). In addition, 40.7% of patients had previously received a non-ESA treatment, most commonly azacitidine (62.9%) or lenalidomide (31.4%). The median duration of treatment (DoT) with luspatercept was 9.9 months. Around a quarter of patients who received luspatercept (25.6%, n = 22) received a further treatment, such as an ESA or an HMA for a median of 2.8 months. Overall, 51/76 (67.1%) patients with a baseline hemoglobin test who received luspatercept had an increase in hemoglobin of ≥1 g/dL compared with baseline (i.e. the closest hemoglobin test within 6 months prior to index date). Of these, 56.9% maintained the ≥1 g/dL hemoglobin level for ≥8 weeks and 45.1% maintained it for ≥16 weeks. Further, 44/76 (57.9%) patients with a baseline hemoglobin test who received luspatercept had an increase in hemoglobin ≥1.5 g/dL compared with baseline. Of these, 50.0% maintained the ≥1.5 g/dL hemoglobin level for ≥8 weeks and 25.0% maintained it for ≥16 weeks. Conclusion: This real-world study described treatment patterns and outcomes in patients with LR-MDS receiving luspatercept. An improvement in hemoglobin levels was observed in more than half of patients. In a quarter of patients who had a ≥1.5 g/dL increase compared to baseline, these improvements were maintained for ≥16 weeks. As this was a relatively small and descriptive study, future analyses are required to further elucidate these findings.

Trends in Anaphylaxis Hospitalizations among Adults in Spain and Their Relationship with Asthma—Analysis of Hospital Discharge data from 2016 to 2021

(1) Background: Anaphylaxis is a rapid-onset, life-threatening hypersensitivity reaction. This study explores the epidemiological trends and clinical outcomes of adult patients with and without asthma hospitalized for anaphylaxis in Spain from 2016 to 2021. (2) Methods: Data from the Spanish National Hospital Discharge Database (RAE-CMBD) were analyzed. We stratified patients with anaphylaxis based on their asthma diagnosis and evaluated various comorbidities and clinical outcomes. Propensity score matching was used to match confounders. (3) Results: The total number of hospitalizations for anaphylaxis remained stable, with a decrease in 2020 probably due to the COVID-19 pandemic. Drug-induced anaphylaxis increased, in addition to being the main triggering factor. Asthma prevalence among those admitted for anaphylaxis emerged from 7.63% to 10.69%, with a higher frequency of respiratory failure and need for mechanical ventilation in this group; despite this, ICU admissions and in-hospital mortality did not differ significantly between asthmatics and non-asthmatics. Asthma was also not a risk factor for severe anaphylaxis. Multivariable analysis identified advanced age, ischemic heart disease, acute respiratory failure, and invasive mechanical ventilation as factors associated with severe anaphylaxis. (4) Conclusions: This study provides valuable information on the complexity of anaphylaxis, its relationship with asthma, and factors influencing its severity. Overall, clinical outcomes did not differ significantly in asthmatic patients compared to non-asthmatic patients, although asthmatic patients had more respiratory complications. Further research is necessary to delve deeper into the multifactorial nature of anaphylaxis and its implications in clinical practice.

Anti-diabetic medication adherence and cardiovascular outcomes in patients with cancer: a nationwide population-based cohort study

Abstract Background Diabetes is an important cause of morbidity, which predisposes patients to major cardiovascular (CV) events and mortality. However, clinical implications of anti-diabetic medication adherence for cancer patients have not been well studied in the real clinical practice. Purpose This study aimed to evaluate the association between anti-diabetic medication adherence and clinical outcomes in adult patients with cancer. Methods Using the prospective nationwide cohort (Korean NHIS-NSC), we extracted adult cancer patients treated with anti-diabetic medications. Based on the medication possession ratio (MPR) value, participants were divided into 3 groups: good (MPR ≥0.8), moderate (0.5 ≤ MPR &amp;lt; 0.8), and poor (MPR&amp;lt;0.5) adherence groups. The primary outcomes were overall and CV mortality. The secondary outcome was CV events requiring hospitalization due to major CV diseases. Results Among 8,052 cancer patients with concomitant diabetes, 59.4% were nonadherence group (21.5% were moderate and 37.9% were poor adherence group). Over a median of 8.4 years of follow-up, 1,475 deaths and 2,931 CV events occurred. Compared to the good adherence group, the moderate and poor adherence groups had a 1.61-fold and 2.00-fold increased risk for overall mortality; and 1.66-fold and 1.98-fold elevated risk for CV mortality, respectively, after adjustment for possible confounders. Furthermore, moderate and poor adherence groups had a 1.29-fold and 1.38-fold elevated risk for new-onset CV events. These trends were consistent across CV event subtypes. Conclusions Nonadherence to anti-diabetic medication is common in cancer patients and is associated with worse clinical outcomes in adult cancer patients with diabetes. More attention should be paid to improve adherence to anti-diabetic medication among patients with cancer.

Extracorporeal Membrane Oxygenation Uses in Refractory Cardiogenic Shock After Open-Heart Surgery.

Extracorporeal membrane oxygenation (ECMO) is the first-line therapy for temporary mechanical circulatory support allowing cardiac and pulmonary recovery or as a bridge to further therapeutic alternatives. The aim of this study was to report clinical outcomes in adult patients with refractory cardiac failure after open-heart surgery undergoing ECMO in a single center with an ECMO unit in Chile. We retrospectively analyzed adults with refractory cardiac failure after open-heart surgery who required a venoarterial (VA) ECMO between 2016 and 2021. Of 16 patients with VA ECMO, 60% were men (n=10), 90% had hypertension (n=14), 69% had < 30% of left ventricular ejection fraction (n=11), and the mean European System for Cardiac Operative Risk Evaluation II score was 12 ± 11%. ECMO support with central cannulation accounts for 81% (n=13), and an intra-aortic balloon pump was used in nine patients (56%). The mean time of support was 4.7 ± 2.6 days (1.5 - 12 days). ECMO weaning was achieved in 88% of patients, and in-hospital mortality was 44% (n=7) after discharge. The freedom from all-cause mortality at one year of follow-up of the entire cohort was 38% (n=6). VA ECMO is now a well-known life-saving therapeutic option, but mortality and morbidity remain high. Implementation of an ECMO program with educational training is mandatory in order to find the proper balance between patient benefits, ethical considerations, and public health financial input in South America.

Treatments for Moderate-to-Severe Alopecia Areata: A Systematic Narrative Review.

Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition. Baricitinib is the first oral selective Janus kinase (JAK) inhibitor approved for the treatment of adults with severe AA. As a better understanding of the evidence supporting the management of AA in clinical practice is needed, we conducted a systematic literature review and subsequent narrative review to describe available evidence pertaining to the efficacy and tolerability of treatments currently recommended for adults with moderate-to-severe forms of AA. From 2557 identified records, a total of 53 records were retained for data extraction: 9 reported data from 7 randomized controlled trials (RCTs) versus placebo, and 44 reported data from unique RCTs with no placebo arm, non-randomized trials, or observational studies. Across drug classes, data were reported heterogeneously, with little consistency of data collection or clinical endpoints used. The most robust evidence was for the JAK inhibitor class, in particular the JAK1/JAK2 inhibitor baricitinib. Five RCTs (three for baricitinib) demonstrated a consistent benefit of JAK inhibitor therapy over placebo across various clinical outcomes in adult patients with at least 50% scalp hair loss. Overall, hair regrowth varied widely for the other drug classes and was generally low for patients with moderate-to-severe AA. Relapses were commonly observed during treatment and upon discontinuation. Adverse effects were generally consistent with the known safety profile of each intervention. The heterogeneity observed prevented the conduct of a network meta-analysis or an indirect comparison of different treatments. We found that the current management of patients with moderate-to-severe AA often relies on the use of treatments that have not been well evaluated in clinical trials. The most robust evidence identified supported the use of baricitinib, and other oral JAK inhibitors, in patients with severe AA.

Evaluation of risdiplam efficacy in 5q spinal muscular atrophy: A systematic comparison of electrophysiologic with clinical outcome measures.

To assess compound muscle action potential (CMAP) amplitudes as electrophysiologic markers in relation to clinical outcome in adult patients with 5q-linked spinal muscular atrophy (SMA) before and during treatment with risdiplam. In this monocentric longitudinal cohort study, CMAP of 18 adult patients with SMA type 2 or 3 were assessed at baseline (T0 ) and after 10 months (T10 ) of risdiplam treatment. CMAP amplitudes of the median, ulnar, peroneal, and tibial nerves were compared with established clinical outcome scores, and with the course of disease before start of treatment. During a pharmacotherapy-naive pre-treatment period of 328 ± 46 days, Revised Upper Limb Module (RULM) score and peroneal nerve CMAP amplitudes decreased, while CMAP of tibial and upper limb nerves remained unchanged. CMAP amplitudes positively correlated with clinical scores (Hammersmith Functional Motor Scale-Expanded [HFMSE], RULM) at T0 . During risdiplam treatment, HFMSE and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores increased, paralleled by marked increase of CMAP amplitudes in both median nerves (T10 -T0 ; right: Δ = 1.4 ± 1.4 mV, p = 0.0003; left: Δ = 1.3 ± 1.4 mV, p = 0.0007), but not in ulnar, peroneal, or tibial nerves. A robust increase of median nerve CMAP amplitudes correlated well with an increase in the HFMSE score (T10 -T0 ). Median nerve CMAP amplitudes at T0 were associated with subsequent risdiplam-related improvement of HFMSE and CHOP INTEND scores at T10 . Median nerve CMAP amplitudes increase with risdiplam treatment in adult SMA patients, and should be further evaluated as potential easy-to-use electrophysiologic markers in assessing and monitoring clinical response to therapy.

Applying Early Warning Score (EWS) in hospitals for adult mortality risk factors

The mortality rate among adult hospital patients is a significant indicator in assessing the quality of care and health services. High mortality rates can affect a hospital's reputation, reduce the credibility of medical personnel, and trigger public anxiety. Failure to recognize the worsening of a patient's condition can delay appropriate life support management. This scoping review aims to identify and analyze the Early Warning Score (EWS) application for adults with risk factors for death in regional general hospitals (RSUD). The scoping review was conducted by searching literature using electronic databases from January 2018-May 2023, such as PubMed, ScienceDirect, LibMed UGM, and hand searching. Relevant articles were selected based on inclusion criteria. The results contained two main themes: factors related to mortality in adult patients and the benefits of implementing EWS on the clinical outcomes of adult patients. Implementing EWS in adult patients with high-risk factors for mortality at Regional General Hospitals can help identify the worsening of the patient's condition early, reducing the risk of death. Increasing awareness of the importance of EWS, EWS training, and consistent use of EWS according to hospital protocols can help reduce mortality and improve overall patient clinical outcomes.

Achieving clinical outcomes with benralizumab in severe eosinophilic asthma patients in a real-world setting: ORBE II study

BackgroundThe ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain.MethodsORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables.ResultsA total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1–Q3) follow-up duration was 19.5 (14.2–24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes.ConclusionsThese data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP.Trial registrationNCT04648839.

Cyclosporine for omalizumab-refractory chronic urticaria: a report of five cases

BackgroundWhile both the AAAAI/ACAAI and the EAACI/GA2LEN/EuroGuiDerm/APAAACI guidelines recommend starting cyclosporine for patients with chronic urticaria who have had an inadequate response to omalizumab, many clinicians are hesitant to initiate cyclosporine due to paucity of clinical data. The objective of this study was to report real-life clinical outcomes in adult patients with chronic urticaria who had an inadequate response to omalizumab and were switched from omalizumab to cyclosporine. Medical records of adult patients with chronic urticaria who had an inadequate response with omalizumab and were later treated with cyclosporine were reviewed retrospectively. Data pertaining to treatment method, clinical response, and adverse effects were recorded.Results/presentation of casesFive patients with omalizumab-refractory chronic urticaria, three of whom also had angioedema and one with an inducible urticaria, were treated with low doses of oral cyclosporine (1–3 mg/kg/d). Four of five patients in this case series had complete resolution of symptoms with oral cyclosporine, while continuing other standard therapies. Systemic side effects occurred in three patients which prompted drug discontinuation in two patients.DiscussionCyclosporine alone was effective in inducing urticaria control in adult patients with chronic urticaria who had an inadequate response to omalizumab, though the impact of cyclosporine was limited by reversible adverse effects. Adverse effects were associated with pre-existing medical conditions. As novel chronic urticaria therapies are being investigated, this experience highlights the importance of uncovering chronic urticaria subtypes which tend to respond to cyclosporine, while providing alternative treatments with better tolerability.

Impact of Limiting Vancomycin Loading Doses in Patients With Methicillin-resistant Staphylococcus aureus Infections After Hospital Protocol Revision.

Background: Vancomycin loading doses are commonly used to quickly attain target serum concentrations; however, data supporting their effect on clinical patient outcomes is limited. In April 2020, our institution revised our pharmacist-driven vancomycin dosing protocol to reserve loading doses for hemodynamically unstable patients with suspected serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Prior to the protocol update, all patients treated with vancomycin at our institution received a weight-based loading dose. The purpose of this study is to assess clinical efficacy and safety outcomes related to the use of vancomycin loading doses. Methods: A retrospective, quasi-experimental study was performed to compare clinical outcomes in adult patients treated with vancomycin for laboratory-confirmed MRSA infections. Patients who received vancomycin therapy prior to our institution's vancomycin dosing protocol revisions (pre-intervention) were compared to patients who received vancomycin after the revisions (post-intervention). The primary outcome was all-cause, inpatient mortality. Secondary outcomes included persistent signs and symptoms of infection ≥5 days after vancomycin initiation, switch to alternative anti-MRSA therapy, and nephrotoxicity. Results: A total of 122 patients (63 pre-intervention patients and 59 post-intervention patients) were included. Receipt of a vancomycin loading dose did not impact the rate of inpatient mortality (4.76%vs 6.78%; OR 1.46, 95% CI [0.31, 6.79]). All secondary outcomes were similar between the two groups, including persistent signs and symptoms of infection, switch to alternative anti-MRSA therapy, and nephrotoxicity. Conclusions: Routine use of vancomycin loading doses is not associated with improved outcomes in hemodynamically stable patients with MRSA infections.