Kidney Dysfunction in the Setting of Liver Failure: Core Curriculum 2024.

Individuals with liver disease are susceptible to pathophysiological derangements that lead to kidney dysfunction. Patients with advanced cirrhosis and acute liver failure (ALF) are at risk of developing acute kidney injury (AKI). Hepatorenal syndrome type 1 (HRS-1, also called HRS-AKI) constitutes a form of AKI unique to the state of cirrhosis and portal hypertension. Although HRS-1 is a condition primarily characterized by marked renal vasoconstriction and kidney hypoperfusion, other pathogenic processes, such as acute tubular injury and renal vein congestion, can overlap and further complicate the course of HRS-1. ALF can lead to AKI through mechanisms that involve systemic inflammation, direct drug toxicity, or bile acid-induced tubulopathy. In addition, the growing prevalence of nonalcoholic steatohepatitis is changing the spectrum of chronic kidney disease in cirrhosis. In this installment of AJKD's Core Curriculum in Nephrology, we explore the underpinnings of how cirrhosis, ALF, acute cholestasis, and post-liver transplantation can be associated with various forms of acute, subacute, or chronic kidney diseases. We navigate through the recommended therapies for each condition, including supportive care, pharmacological interventions, kidney replacement therapy, and organ transplantation. Finally, key acid-base and electrolyte disorders associated with hepatobiliary disease are also summarized.

Microbial lipopeptides: their pharmaceutical and biotechnological potential, applications, and way forward.

As lead molecules, cyclic lipopeptides with antibacterial, antifungal, and antiviral properties have garnered a lot of attention in recent years. Because of their potential, cyclic lipopeptides have earned recognition as a significant class of antimicrobial compounds with applications in pharmacology and biotechnology. These lipopeptides, often with biosurfactant properties, are amphiphilic, consisting of a hydrophilic moiety, like a carboxyl group, peptide backbone, or carbohydrates, and a hydrophobic moiety, mostly a fatty acid. Besides, several lipopeptides also have cationic groups that play an important role in biological activities. Antimicrobial lipopeptides can be considered as possible substitutes for antibiotics that are conventional to address the current drug-resistant issues as pharmaceutical industries modify the parent antibiotic molecules to render them more effective against antibiotic-resistant bacteria and fungi, leading to the development of more resistant microbial strains. Bacillus species produce lipopeptides, which are secondary metabolites that are amphiphilic and are typically synthesized by non-ribosomal peptide synthetases (NRPSs). They have been identified as potential biocontrol agents as they exhibit a broad spectrum of antimicrobial activity. A further benefit of lipopeptides is that they can be produced and purified biotechnologically or biochemically in a sustainable manner using readily available, affordable, renewable sources without harming the environment. In this review, we discuss the biochemical and functional characterization of antifungal lipopeptides, as well as their various modes of action, method of production and purification (in brief), and potential applications as novel antibiotic agents.

Add-on tiotropium versus step-up inhaled corticosteroid plus long-acting beta-2-agonist in real-world patients with asthma.

Background: A step-up approach (increasing inhaled corticosteroid [ICS] dose and/or add-on treatment) is recommended for asthma that is uncontrolled despite ICS plus long-acting beta-2-agonist (LABA) combination treatment. Understanding the impact of different treatment options on health outcomes can help guide treatment decision-making. Objective: To compare the effectiveness of add-on tiotropium 1.25 µg (two puffs once daily) versus an increased ICS plus LABA dose in a real-world cohort of patients with asthma initiated on ICS plus LABA. Methods: De-identified data from patients ages ≥12 years and with asthma who were initiated on ICS plus LABA, and then had tiotropium added (Tio group; index date) or an ICS plus LABA dose increased (inc-ICS group; index date) were collected from two medical and pharmacy claims data bases (2014-2018). To account for population/group differences, propensity score matching was performed. The primary end point was the exacerbation risk after the index date. Secondary end points included exacerbation rates 6 and 12 months postindex, health-care resource utilization, costs, and short-acting beta-2-agonist (SABA) refills 12 months postindex. Results: Overall, 7857 patients (Tio group, 2619; inc-ICS group, 5238) were included. The exacerbation risk was 35% lower in the Tio group than in the inc-ICS group (hazard ratio 0.65 [95% confidence interval, 0.43-0.99]; p = 0.044). Exacerbation rates in the Tio group also were significantly lower within 6 and 12 months postindex (64% and 73%, respectively). All-cause and asthma-related emergency department (ED) visits were 47% and 74% lower, respectively (p < 0.0001 for both), and all-cause and asthma-related hospitalizations were 48% (p < 0.01) and 76% (p < 0.001) lower, respectively, in the Tio group. Also, significantly fewer patients in the Tio group versus the inc-ICS group required SABA refills (56% versus 67%, p < 0.0001). Conclusion: Add-on tiotropium significantly decreased the risk and rate of exacerbations, decreased all-cause and asthma-related ED visits and hospitalizations, and reduced SABA refills compared with increasing the ICS plus LABA dose. The findings supported the use of add-on tiotropium for patients with uncontrolled asthma taking ICS plus LABA.

Incidence and impact of acute kidney injury on patients with implantable left ventricular assist devices: a Meta-analysis.

Background: We aimed to evaluate the acute kidney injury (AKI) incidence and its associated risk of mortality in patients with implantable left ventricular assist devices (LVAD).Methods: A systematic literature search in Ovid MEDLINE, EMBASE, and Cochrane Databases was conducted through January 2020 to identify studies that provided data on the AKI incidence and AKI-associated mortality risk in adult patients with implantable LVADs. Pooled effect estimates were examined using random-effects, generic inverse variance method of DerSimonian-Laird.Results: Fifty-six cohort studies with 63,663 LVAD patients were enrolled in this meta-analysis. The pooled incidence of reported AKI was 24.9% (95%CI: 20.1%-30.4%) but rose to 36.9% (95%CI: 31.1%-43.1%) when applying the standard definition of AKI per RIFLE, AKIN, and KDIGO criteria. The pooled incidence of severe AKI requiring renal replacement therapy (RRT) was 12.6% (95%CI: 10.5%-15.0%). AKI incidence did not differ significantly between types of LVAD (p = .35) or indication for LVAD use (p = .62). While meta-regression analysis did not demonstrate a significant association between study year and overall AKI incidence (p = .55), the study year was negatively correlated with the incidence of severe AKI requiring RRT (slope = -0.068, p < .001). The pooled odds ratios (ORs) of mortality at 30 days and one year in AKI patients were 3.66 (95% CI, 2.00-6.70) and 2.22 (95% CI, 1.62-3.04), respectively. The pooled ORs of mortality at 30 days and one year in severe AKI patients requiring RRT were 7.52 (95% CI, 4.58-12.33) and 5.41 (95% CI, 3.63-8.06), respectively.Conclusion: We found that more than one-third of LVAD patients develop AKI based on standard definitions, and 13% develop severe AKI requiring RRT. There has been a potential improvement in the incidence of severe AKI requiring RRT for LVAD patients. AKI in LVAD patients was associated with increased 30-day and 1 year mortality.

Impact of ANCA-Associated Vasculitis on Outcomes of Hospitalizations for Goodpasture's Syndrome in the United States: Nationwide Inpatient Sample 2003-2014.

Background and objectives: Goodpasture's syndrome (GS) is a rare, life-threatening autoimmune disease. Although the coexistence of anti-neutrophil cytoplasmic antibody (ANCA) with Goodpasture's syndrome has been recognized, the impacts of ANCA vasculitis on mortality and resource utilization among patients with GS are unclear. Materials and Methods: We used the National Inpatient Sample to identify hospitalized patients with a principal diagnosis of GS from 2003 to 2014 in the database. The predictor of interest was the presence of ANCA-associated vasculitis. We tested the differences concerning in-hospital treatment and outcomes between GS patients with and without ANCA-associated vasculitis using logistic regression analysis with adjustment for other clinical characteristics. Results: A total of 964 patients were primarily admitted to hospital for GS. Of these, 84 (8.7%) had a concurrent diagnosis of ANCA-associated vasculitis. Hemoptysis was more prevalent in GS patients with ANCA-associated vasculitis. During hospitalization, GS patients with ANCA-associated required non-significantly more mechanical ventilation and non-invasive ventilation support, but non-significantly less renal replacement therapy and plasmapheresis than those with GS alone. There was no significant difference in in-hospital outcomes, including organ failure and mortality, between GS patients with and without ANCA-associated vasculitis. Conclusions: Our study demonstrated no significant differences between resource utilization and in-hospital mortality among hospitalized patients with coexistence of ANCA vasculitis and GS, compared to those with GS alone.

Liver Disease-Associated Glomerulopathies.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect a significant number of individuals globally and their extra-hepatic manifestations, including glomerular disease, are well established. Additionally, liver disease-associated IgA nephropathy is the leading cause of secondary IgA nephropathy with disease course varying from asymptomatic urinary abnormalities to progressive kidney injury. Herein we provide an updated review on the epidemiology, pathogenesis, clinical manifestations, and treatment of HBV- and HCV-related glomerulonephritis as well as IgA nephropathy in patients with liver disease. The most common HBV-related glomerulonephritis is membranous nephropathy, although membranoproliferative glomerulonephritis and podocytopathies have been described. The best described HCV-related glomerulonephritis is cryoglobulinemic glomerulonephritis occurring in about 30% of patients with mixed cryoglobulinemic vasculitis. The mainstay of treatment for HBV-GN and HCV-GN is antiviral therapy, with significant improvement in outcomes since the emergence of the direct-acting antivirals. However, cases with severe pathology and/or a more aggressive disease trajectory can be offered a course of immunosuppression, commonly anti-CD20 therapy, particularly in the case of cryoglobulinemic glomerulonephritis.

AI Can Improve the Economics of Blindness Prevention in Canada.

Diabetic retinopathy is a leading cause of vision loss in Canada and creates significant economic and social burden on patients. Diabetic retinopathy is largely a preventable complication of diabetes mellitus. Yet, hundreds of thousands of Canadians continue to be at risk and thousands go on to develop vision loss and disability. Blindness has a significant impact on the Canadian economy, on families and the quality of life of affected individuals. This paper provides an economic analysis on two potential interventions for preventing blindness and concludes that use of AI to identify high-risk individuals could significantly decrease the costs of identifying, recalling, and screening patients at risk of vision loss, while achieving similar results as a full-fledged screening and recall program. We propose that minimal data interoperability between optometrists and family physicians combined with artificial intelligence to identify and screen those at highest risk of vision loss can lower the costs and increase the feasibility of screening and treating large numbers of patients at risk of going blind in Canada.

Prevalence and Predictors of Adverse Events Associated With Dipeptidyl Peptidase-4 (DPP-4) Inhibitors in Type 2 Diabetic Patients: A Cross-sectional Study.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral hypoglycemic agents widely prescribed in India despite safety concerns. However, studies focused on their safety profile are scarce, especially in South India. Objective: To evaluate the prevalence and predictors of adverse events (AEs) with DPP-4 inhibitors in patients with type 2 diabetes mellitus (T2DM). Research design and methods: This retrospective cross-sectional study analyzed data from medical records of T2DM patients prescribed DPP-4 inhibitors admitted to the medicine department from 2019 to 2021 at a South Indian tertiary care hospital. The causality of AEs was assessed using the WHO-Uppsala Monitoring Centre (WHO-UMC) criteria and the Naranjo scale, and severity using the Modified Hartwig and Seigel scale. We applied a Generalized model with a binary response and logit-link function to understand the factors that best explain the AE. The best-fit models were chosen based on least Akaike's information criterion and highest PseudoR 2 and presented the odds ratio (OR) with a 95% confidence interval. The analyses were performed in R software version 4.2.1. Results: Among the 796 patients included in the study, 26% experienced AEs. A total of 212 AEs were observed, and Saxagliptin-associated AEs were the most prevalent (66.6%). Hepatic AEs were predominant (37.7%), followed by gastrointestinal events (16.5%) and electrolyte imbalances (12.3%). Most AEs were possible based on WHO-UMC criteria (78.7%) and the Naranjo scale (86.7%), with 58% being of moderate severity and 42% mild. In the multivariate analysis, aspartate transaminase [OR: 1.013 (0.006-1.020)], alkaline phosphatase [OR: 1.004 (1.001-1.007)] and patients already on DPP-4 inhibitors [OR 1.191(1.012-1.366)] were significant predictors for AEs with DPP-4 inhibitors. Conclusion: The study highlighted a high prevalence of AEs with DPP-4 inhibitors and identified significant predictors of these AEs. These findings underscore the necessity of vigilant monitoring and risk assessment while prescribing DPP-4 inhibitors to the Indian population.

Introduction: DPP-4 inhibitors are a class of drugs used to manage type 2 diabetes mellitus. These drugs are commonly prescribed regardless of their safety issues in the Indian population. The studies focusing on the side effects or adverse events associated with these drugs and the contributing factors are limited in India. Understanding how common these adverse events are is vital to providing better patient care and management. Aim: To assess the frequency of adverse events with DPP-4 inhibitors and the contributory factors to these events. Method: A retrospective study analyzing the medical records of diabetic patients on DPP-4 inhibitors admitted to a major hospital in South India between 2019 and 2021 was conducted. The frequency, severity and potential causes of adverse events were identified through descriptive analysis. Result: A total of 796 diabetic patients on DPP-4 inhibitors were included in the study, out of which 26% (212 adverse events) experienced adverse events. Most common adverse events were related to liver (37.7%) followed by gastrointestinal (16.5%) and electrolyte imbalance (12.3%). The severity of the events was moderate (58%) and mild (42%). Elevated liver enzymes aspartate transaminase and alkaline phosphatase, and patients already on DPP-4 inhibitors were at high odds of developing adverse events. Conclusion: The study identifies DPP-4 inhibitor-associated adverse events and contributory factors that should be addressed when prescribing these drugs to diabetic patients.

Frequency and factors associated with DPP-4 inhibitor-induced adverse events in diabetic patients.

Development of a machine learning-based model for the prediction and progression of diabetic kidney disease: A single centred retrospective study.

BACKGROUND: Diabetic kidney disease (DKD) is a diabetic microvascular complication often characterized by an unpredictable progression. Hence, early detection and recognition of patients vulnerable to progression is crucial. OBJECTIVE: To develop a prediction model to identify the stages of DKD and the factors contributing to progression to each stage using machine learning. METHODOLOGY: A retrospective study was conducted in a South Indian tertiary care hospital and collected the details of patients diagnosed with DKD from January 2017 to January 2022. Bayesian optimization-based machine learning techniques such as classification and regression were employed. The model was developed with the help of an optimization framework that effectively balances classification, prediction accuracy, and explainability. RESULTS: Of the 311 patients diagnosed with DKD, 227 were selected for the study. A system for predicting DKD has been created for a patient dataset utilizing a variety of machine-learning approaches. The eXtreme gradient (XG) Boost method excelled, achieving 88.75% accuracy, 88.57% precision, 91.4% sensitivity,100% specificity, and 89.49% F1-score. An interpretable data-driven method highlights significant features for early DKD diagnosis. The best explainable prediction model uses the XG Boost classifier, revealing serum uric acid, urea, phosphorous, red blood cells, calcium, and absolute eosinophil count as the major predictors influencing the progression of DKD. In the case of regression models, the gradient boost regressor performed the best, with an R2 score of 0.97. CONCLUSION: Machine learning algorithms can effectively predict the stages of DKD and thus help physicians in providing patients with personalized care at the right time.

Factors contributing to the adverse drug reactions associated with the dipeptidyl peptidase-4 (DPP-4) inhibitors: A scoping review.

BACKGROUND AND AIM: Adverse drug reactions are one of the contributors to increased hospital admission and length of hospital stay. Among the various antidiabetic agents prescribed, dipeptidyl peptidase-4 (DPP-4) inhibitors have gained wide recognition and shown more persistence than other novel hypoglycemic agents. We performed a scoping review to identify the risk factors contributing to the adverse drug reactions with DPP-4 inhibitors. METHODOLOGY: We followed Preferred Reporting Items for Scoping Review (PRISMA-ScR) Guidelines for reporting the findings. Data sources such as PubMed/MEDLINE, Scopus, Embase, and Cochrane were assessed. We included studies that reported the risk factors contributing to the DPP-4 inhibitor-associated adverse drug reactions. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the methodological quality of the studies. RESULTS: Of the 6406 studies retrieved, 11 studies met our inclusion criteria. Of these 11 studies, seven were post-marketing surveillance studies, one nested case-control study, one comparator cohort study, one food and drug administration (FDA) adverse event reporting system (FAERS)-based observational study, and one questionnaire-based cross-sectional survey study. A total of eight factors were identified that contributed to the DPP-4 inhibitor-associated adverse drug reactions. CONCLUSION: The included studies suggested age >65 years, females, grade 4 and 5 renal impairment, concomitant drugs, disease and drug therapy duration, liver disease, non-smokers, and non-hypertension as risk factors. Further studies should be conducted to provide insight into these risk factors so that the appropriate use of DPP-4 inhibitors in the diabetic population can be encouraged to improve the health-related quality of life. PROSPERO REGISTRATION: CRD42022308764.

Real-world impact of empagliflozin on total cost of care in adults with type 2 diabetes: Results from an outcomes-based agreement.

BACKGROUND: Value-based health care is expanding through payment models such as outcomes-based agreements between manufacturers and payers. OBJECTIVE: To describe the total-cost-of-care outcomes of an outcomes-based agreement evaluating the real-world impact of empagliflozin vs other type 2 diabetes mellitus (T2DM) drugs among all patients with T2DM, with and without cardiovascular disease (within and beyond the requirement of the agreement). METHODS: In this prospective real-world analysis, members from the health plan of an integrated health care delivery system from the commercial and Medicare Advantage lines of business, who qualify under the confines of the contract, were included for analysis. Thus, members aged 18 years and older who were continuously enrolled in the identification (January 1, 2018, to December 31, 2018) and measurement periods (≤1 year post-index) with a T2DM diagnosis were retained. Patients using empagliflozin and empagliflozin-combination drugs constituted the empagliflozin group; those using all other antihyperglycemics, the nonempagliflozin group. Patients with type 1 diabetes, or those using metformin or insulin monotherapy, at index were excluded. Eligible members were followed for up to the earliest occurrence of disenrollment date, discontinuation (60-day medication fill gap allowed) of empagliflozin (or nonempagliflozin containing) medication, or the end of the measurement period. We compared, using Student's t-test and summary statistics (for reporting the outcomes agreement) and a propensity-matched difference-in-difference model (for the followup evaluation beyond the requirement of the agreement), the mean all-cause total cost of care (pharmacy plus medical) per patient per month (PPPM) between the 2 groups, including a subgroup of members with a baseline cardiovascular disease diagnosis. RESULTS: There were 4,577 (3,069 and 1,508 in the commercial and Medicare) and 33,712 (15,571 and 18,141 in the commercial and Medicare) in the empagliflozin and nonempagliflozin groups, respectively. The difference in mean total cost PPPM was $75 lower for empagliflozin vs nonempagliflozin groups, driven mainly by lower medical costs in the empagliflozin group (-$465 PPPM). However, the difference was not statistically significant in the propensity score-matched model. CONCLUSIONS: Although empagliflozin had higher pharmacy costs, the total cost of care for patients with T2DM and with established cardiovascular disease were comparable to the group of patients with all other T2DM, driven mainly by lower medical costs. DISCLOSURES: The authors report no conflicts of interest beyond being employees of the 2 organizations involved in this outcomes-based agreement. Ms. Palli is a former employee of Boehringer Ingelheim Pharmaceuticals, Inc., who was affiliated at the time of study conduct.

Clinical and economic outcomes in patients with chronic obstructive pulmonary disease initiating maintenance therapy with tiotropium bromide/olodaterol or fluticasone furoate/umeclidinium/vilanterol.

BACKGROUND: Clinical practice guidelines recommend dual long-acting muscarinic antagonists (LAMAs)/long-acting ß2agonists (LABAs) as maintenance therapy in patients with chronic obstructive pulmonary disease (COPD) and dyspnea or exercise intolerance. Escalation to triple therapy (TT) (LAMA/LABA/inhaled corticosteroid) is conditionally recommended for patients with continued exacerbations on dual LAMA/LABA therapy. Despite this guidance, TT use is widespread across COPD severities, which could impact clinical and economic outcomes. OBJECTIVE: To compare COPD exacerbations, pneumonia events, and disease-related and all-cause health care resource utilization and costs (in 2020 US dollars) in patients initiating fixed-dose combinations of either LAMA/LABA (tiotropium/olodaterol [TIO + OLO]) or TT (fluticasone furoate/umeclidinium/vilanterol [FF + UMEC + VI]). METHODS: This retrospective observational study of administrative claims included patients with COPD aged 40 years or older initiating TIO + OLO or FF + UMEC + VI from June 2015 to November 2019. TIO + OLO and FF + UMEC + VI cohorts in the overall and maintenance-naive populations were 1:1 propensity score matched on baseline demographics, comorbidities, COPD medications, health care resource utilization, and costs. Multivariable regression compared clinical and economic outcomes up to 12 months in FF + UMEC + VI vs TIO + OLO postmatched cohorts. RESULTS: After matching, there were 5,658 and 3,025 pairs in the overall and maintenance-naive populations, respectively. In the overall population, the risk of any (moderate or severe) exacerbation was 7% lower in FF + UMEC + VI vs TIO + OLO initiators (adjusted hazard ratio [aHR] = 0.93; 95% CI = 0.86-1.0; P = 0.047). There was no difference in the adjusted risk of any exacerbation in the maintenance-naive population (aHR = 0.99; 95% CI = 0.88-1.10). Pneumonia risk was not statistically different between cohorts in the overall (aHR = 1.12; 95% CI = 0.98-1.27) and maintenance-naive (aHR = 1.13; 95% CI = 0.95-1.36) populations. COPD- and/or pneumonia-related adjusted total annualized costs (95% CI) were significantly greater for FF + UMEC + VI vs TIO + OLO in the overall ($17,633 [16,661-18,604] vs $14,558 [13,709-15,407]; P < 0.001; differences [% of relative increase] = $3,075 [21.1%]) and maintenancenaive ($19,032 [17,466-20,598] vs $15,004 [13,786-16,223]; P < 0.001; $4,028 [26.8%]) populations, with significantly higher pharmacy costs with FF + UMEC + VI (overall: $6,567 [6,503-6,632] vs $4,729 [4,676-4,783]; P < 0.001; $1,838 [38.9%]; maintenance-naive: $6,642 [6,560-6,724] vs $4,750 [4,676-4,825]; P < 0.001; $1,892 [39.8%]). CONCLUSIONS: A lower risk of exacerbation was observed with FF + UMEC + VI vs TIO + OLO in the overall population but not among the maintenance-naive population. Patients with COPD initiating TIO + OLO had lower annualized costs than FF + UMEC + VI initiators in the overall and maintenance-naive populations. Thus, in the maintenance-naive population, initiation with dual LAMA/LABA therapy per practice guidelines can improve real-world economic outcomes. Study registration number: ClinicalTrials.gov (identifier: NCT05127304). DISCLOSURES: The study was funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). To ensure independent interpretation of clinical study results and enable authors to fulfill their role and obligations under the ICMJE criteria, BIPI grants all external authors access to relevant clinical study data. In adherence with the BIPI Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data after publication of the primary manuscript in a peer-reviewed journal, regulatory activities are complete and other criteria are met. Dr Sethi has received honoraria/fees for consulting/speaking from Astra-Zeneca, BIPI, and GlaxoSmithKline. He has received consulting fees for serving on data safety monitoring boards from Nuvaira and Pulmotect. He has received consulting fees from Apellis and Aerogen. His institution has received research funds for his participation in clinical trials from Regeneron and AstraZeneca. Ms Palli was an employee of BIPI at the time the study was conducted. Drs Clark and Shaikh are employees of BIPI. Ms Buysman and Mr Sargent are employees and Dr Bengtson was an employee of Optum, which was contracted by BIPI to conduct this study. Dr Ferguson reports grants and personal fees from Boehringer Ingelheim during the conduct of the study; grants from Novartis, Altavant, and Knopp; grants and personal fees from AstraZeneca, Verona, Theravance, Teva, and GlaxoSmithKline; and personal fees from Galderma, Orpheris, Dev.Pro, Syneos, and Ionis outside the submitted work. He was a paid consultant for BIPI for this study. The authors received no direct compensation related to the development of the manuscript. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Prevalence and Overlap of Cardiac, Renal, and Metabolic Conditions in US Adults, 1999-2020.

Importance: Individually, cardiac, renal, and metabolic (CRM) conditions are common and leading causes of death, disability, and health care-associated costs. However, the frequency with which CRM conditions coexist has not been comprehensively characterized to date. Objective: To examine the prevalence and overlap of CRM conditions among US adults currently and over time. Design, Setting, and Participants: To establish prevalence of CRM conditions, nationally representative, serial cross-sectional data included in the January 2015 through March 2020 National Health and Nutrition Examination Survey (NHANES) were evaluated in this cohort study. To assess temporal trends in CRM overlap, NHANES data between 1999-2002 and 2015-2020 were compared. Data on 11 607 nonpregnant US adults (≥20 years) were included. Data analysis occurred between November 10, 2020, and November 23, 2022. Main Outcomes and Measures: Proportion of participants with CRM conditions, overall and stratified by age, defined as cardiovascular disease (CVD), chronic kidney disease (CKD), type 2 diabetes (T2D), or all 3. Results: From 2015 through March 2020, of 11 607 US adults included in the analysis (mean [SE] age, 48.5 [0.4] years; 51.0% women), 26.3% had at least 1 CRM condition, 8.0% had at least 2 CRM conditions, and 1.5% had 3 CRM conditions. Overall, CKD plus T2D was the most common CRM dyad (3.2%), followed by CVD plus T2D (1.7%) and CVD plus CKD (1.6%). Participants with higher CRM comorbidity burden were more likely to be older and male. Among participants aged 65 years or older, 33.6% had 1 CRM condition, 17.1% had 2 CRM conditions, and 5.0% had 3 CRM conditions. Within this subset, CKD plus T2D (7.3%) was most common, followed by CVD plus CKD (6.0%) and CVD plus T2D (3.8%). The CRM comorbidity burden was disproportionately high among participants reporting non-Hispanic Black race or ethnicity, unemployment, low socioeconomic status, and no high school degree. Among participants with 3 CRM conditions, nearly one-third (30.5%) did not report statin use, and only 4.8% and 3.0% used glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, respectively. Between 1999 and 2020, the proportion of US adults with multiple CRM conditions increased significantly (from 5.3% to 8.0%; P < .001 for trend), as did the proportion having all 3 CRM conditions (0.7% to 1.5%; P < .001 for trend). Conclusions and Relevance: This cohort study found that CRM multimorbidity is increasingly common and undertreated among US adults, highlighting the importance of collaborative and comprehensive management strategies.

Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of a Romiplostim Biosimilar in Chronic Refractory Immune Thrombocytopenic Purpura (ITP) Patients.

Romiplostim (Nplate®, Amgen Inc.) is an orphan drug approved for the treatment of chronic refractory immune thrombolytic purpura (ITP) in adult and pediatric patients. Limited availability of pharmacokinetic (PK) data and large inter- and intra-subject variability in PK and platelet response is a challenge in the clinical development of a romiplostim biosimilar. We compared pharmacokinetics (PK), pharmacodynamics (PD)/efficacy, and safety of a romiplostim biosimilar with Nplate in 24 patients with ITP following a single 3 µg/kg dose, and assessed efficacy of the romiplostim biosimilar at a titrated dose range of 1-5 µg/kg in 50 patients with ITP. The PK of the romiplostim biosimilar did not differ compared to the PK of Nplate, and PD/efficacy responses were similar between the products following the single dose. The romiplostim biosimilar showed historically comparable PD/efficacy with Nplate over 8 weeks when treated at the titrated dose range. It was well tolerated in both the studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12288-021-01431-y.

Flecainide-Induced Left Bundle Branch Block.

Flecainide is the first-line antiarrhythmic agent used in patients without structural heart disease. It is a class IC antiarrhythmic drug that inhibits inward sodium current through its dose-dependent blockade of voltage-gated calcium channels within the cardiac membrane. It has been shown to slow the conduction in the left bundle branch block. Unmonitored toxicity can cause ventricular dyssynchrony or fatal arrhythmia. We present a case in which flecainide use caused a new left bundle branch block (LBBB).

Ventriculitis Presenting as a Complication of Haemophilus Influenzae Mastoiditis and Meningitis.

Ventriculitis is a rare intracranial disease with potentially life-threatening consequences. Here, we present a case of acute mastoiditis that progressed to Haemophilus influenzae meningitis evolving to ventriculitis. This case was complicated by hydrocephalus that subsequently required the placement of a ventriculoperitoneal shunt. In patients presenting with mastoiditis, it is imperative to initiate early and appropriate treatment to prevent disease progression and devastating outcomes. We aim to increase recognition of potential complications and encourage childhood vaccination of Haemophilus influenzae.

Enhancing Communication and Patient Care: The Reverse Stethoscope Technique.

Patients with hearing loss have increased difficulties while navigating communication, especially complex conversations that take place in healthcare settings. Patients with hearing disabilities may often find themselves in noisy reception areas or busy emergency departments where their confidentiality is compromised for the sake of communication, resulting in suboptimal care. The reverse stethoscope technique is a tool that healthcare professionals can use to enhance communications to optimize patient care and maintain confidentiality. We describe a case of an 83-year-old male with bilateral hearing loss whose hearing disability became a major obstacle in his access to healthcare in the inpatient setting. With the help of the reverse stethoscope technique, the patient was able to understand his hospital course, diagnosis, and treatment options and was able to actively participate in making an informed decision.

Another Way to Break Hearts: Reverse Takotsubo Cardiomyopathy.

A 34-year-old female was found to be hypoxic shortly after intubation during elective eye surgery. The patient then went into ventricular fibrillation leading to cardiac arrest. Return of spontaneous circulation (ROSC) was achieved after several rounds of cardiopulmonary resuscitation with epinephrine. The patient was immediately taken for cardiac catherization which revealed angiographically normal coronary arteries. A computed tomography angiogram chest showed pulmonary embolism and unclear chronicity. Transthoracic echocardiogram (TTE) showed a reduced ejection fraction of 30%-35% with nearly akinetic basal walls, consistent with reverse Takotsubo cardiomyopathy. The patient was started on anticoagulation and was successfully extubated shortly afterward. Cardiac magnetic resonance imaging (MRI) one week later revealed a recovered left ventricular ejection fraction. Our case demonstrated variants of Takotsubo cardiomyopathy while highlighting the notion that cardiac function can be temporarily compromised by acute physiological stressors.