Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity ...and can be affected by changing diagnosis and coding practices over time.
To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals.
Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014.
Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance.
Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews.
A total of 173 690 sepsis cases (mean age, 66.5 SD, 15.5 y; 77 660 42.4% women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y 95% CI, -2.3% to 3.5%, P = .67) whereas incidence per claims increased (+10.3%/y 95% CI, 7.2% to 13.3%, P < .001). In-hospital mortality using clinical criteria declined (-3.3%/y 95% CI, -5.6% to -1.0%, P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (-1.3%/y 95% CI, -3.2% to 0.6%, P = .19). In contrast, mortality using claims declined significantly (-7.0%/y 95% CI, -8.8% to -5.2%, P < .001), as did death or discharge to hospice (-4.5%/y 95% CI, -6.1% to -2.8%, P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% 95% CI, 52.9% to 92.0% vs 32.3% 95% CI, 24.4% to 43.0%, P < .001), with comparable positive predictive value (70.4% 95% CI, 64.0% to 76.8% vs 75.2% 95% CI, 69.8% to 80.6%, P = .23).
In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.
Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of ...action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.
GWAS have emerged as popular tools for identifying genetic variants that are associated with disease risk. Standard analysis of a case-control GWAS involves assessing the association between each ...individual genotyped SNP and disease risk. However, this approach suffers from limited reproducibility and difficulties in detecting multi-SNP and epistatic effects. As an alternative analytical strategy, we propose grouping SNPs together into SNP sets on the basis of proximity to genomic features such as genes or haplotype blocks, then testing the joint effect of each SNP set. Testing of each SNP set proceeds via the logistic kernel-machine-based test, which is based on a statistical framework that allows for flexible modeling of epistatic and nonlinear SNP effects. This flexibility and the ability to naturally adjust for covariate effects are important features of our test that make it appealing in comparison to individual SNP tests and existing multimarker tests. Using simulated data based on the International HapMap Project, we show that SNP-set testing can have improved power over standard individual-SNP analysis under a wide range of settings. In particular, we find that our approach has higher power than individual-SNP analysis when the median correlation between the disease-susceptibility variant and the genotyped SNPs is moderate to high. When the correlation is low, both individual-SNP analysis and the SNP-set analysis tend to have low power. We apply SNP-set analysis to analyze the Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer GWAS discovery-phase data.
Fever is a common manifestation of both infectious and noninfectious processes in recipients of hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy. ...Understanding the diverse causes of fever in these settings allows for accurate diagnosis and optimal use of antibiotics.
Herein we review common noninfectious syndromes seen in HCT and CAR-T recipients and discuss best practices in the management of these complex clinical scenarios regarding diagnosis and antibiotic use. In recent years, adverse effects of antimicrobials have highlighted the importance of antimicrobial stewardship in HCT and CAR-T patients, and an antibiotic de-escalation strategy is a safe and important tool in mitigating these adverse events, even in patients with ongoing neutropenia who become afebrile without a known infection. Common adverse events associated with antibiotics include an increased risk of Clostridiodes difficile infection (CDI), a higher incidence of multidrug-resistant organisms (MDROs), and microbiome dysbiosis.
Clinicians should be aware of noninfectious causes of fever in these immunocompromised patients and utilize best antibiotic practices while managing these patients.
COVID-19 and cardiac arrhythmias Bhatla, Anjali; Mayer, Michael M; Adusumalli, Srinath ...
Heart rhythm,
09/2020, Volume:
17, Issue:
9
Journal Article
Peer reviewed
Open access
Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. Severe acute respiratory syndrome coronavirus 2 infection may cause injury ...to cardiac myocytes and increase arrhythmia risk.
The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality.
We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.
Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred in patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (odds ratio OR 4.68; 95% confidence interval CI 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment. Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated. Only cardiac arrests were associated with acute in-hospital mortality.
Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.
Treatment strategies to prevent ventricular tachycardia (VT) in patients with an implantable cardioverter-defibrillator (ICD) include antiarrhythmic drugs (AADs) and catheter ablation (CA).
The ...purpose of this study was to systematically compare the efficacy of AADs and CA for the prevention of VT in patients with ICDs.
Major databases were searched (October 2015) for randomized trials evaluating AADs or CA vs standard medical therapy to prevent VT in ICD patients. Primary outcome was the number of VT episodes leading to appropriate ICD interventions.
Eight trials (n = 2268, follow-up 15 ± 6 months) evaluated AADs, and 6 trials (n = 427, follow-up 14 ± 8 months) evaluated CA. A significant reduction in appropriate ICD interventions was found with both CA (odds ratio OR 0.45, 95% confidence interval CI 0.28-0.71, P = .001) and AADs (OR 0.66, 95% CI 0.44-0.97, P = .037), with no significant difference between the 2 treatment strategies. The benefit of AADs was driven by amiodarone and not confirmed with other AADs. A reduction of inappropriate ICD interventions was found with AADs (OR 0.30, P = .001) but not with CA. Both CA and AADs were not associated with decreased mortality over follow-up. Amiodarone appeared to increase the risk of death (OR 3.36, 95% CI 1.36-8.30, P = .009).
In patients with an ICD, both AADs (amiodarone) and CA reduce the risk of recurrent VT compared to control medical therapy, with no significant difference between the 2 treatments. AADs are also associated with a reduction of inappropriate ICD therapies. The significant reduction of recurrent VT episodes does not appear to result in a mortality benefit, with a potential for increased mortality with amiodarone.
The prospect of universal influenza vaccines is generating much interest and research at the intersection of immunology, epidemiology, and viral evolution. While the current focus is on developing a ...vaccine that elicits a broadly cross-reactive immune response in clinical trials, there are important downstream questions about global deployment of a universal influenza vaccine that should be explored to minimize unintended consequences and maximize benefits. Here, we review and synthesize the questions most relevant to predicting the population benefits of universal influenza vaccines and discuss how existing information could be mined to begin to address these questions. We review three research topics where computational modeling could bring valuable evidence: immune imprinting, viral evolution, and transmission. We address the positive and negative consequences of imprinting, in which early childhood exposure to influenza shapes and limits immune responses to future infections via memory of conserved influenza antigens. However, the mechanisms at play, their effectiveness, breadth of protection, and the ability to "reprogram" already imprinted individuals, remains heavily debated. We describe instances of rapid influenza evolution that illustrate the plasticity of the influenza virus in the face of drug pressure and discuss how novel vaccines could introduce new selective pressures on the evolution of the virus. We examine the possible unintended consequences of broadly protective (but infection-permissive) vaccines on the dynamics of epidemic and pandemic influenza, compared to conventional vaccines that have been shown to provide herd immunity benefits. In conclusion, computational modeling offers a valuable tool to anticipate the benefits of ambitious universal influenza vaccine programs, while balancing the risks from endemic influenza strains and unpredictable pandemic viruses. Moving forward, it will be important to mine the vast amount of data generated in clinical studies of universal influenza vaccines to ensure that the benefits and consequences of these vaccine programs have been carefully modeled and explored.
To evaluate the efficacy of intraocular injections with bevacizumab in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).
Prospective, randomized, sham ...injection-controlled, double-masked clinical trial.
Sixty patients with ME secondary to CRVO.
At baseline, patients were randomized 1:1 to receive intraocular injections of bevacizumab or sham injections every 6 weeks for 6 months.
The primary outcome measure was the proportion of patients gaining at least 15 letters at 6 months. Secondary outcome measures included mean change from baseline best-corrected visual acuity (BCVA), foveal thickness, and neovascular glaucoma.
At the end of follow-up, 18 of 30 patients (60.0%) in the study group had gained ≥15 letters compared with 6 of 30 patients (20.0%) in the control group (P=0.003). The BCVA improved by 14.1 letters at 24 weeks compared with a decrease of 2.0 letters in the control group (P < 0.003). The mean decrease in central retinal thickness (CRT) was significantly greater in the study group (426 μm) than in the control group (102 μm) at all time points up to week 24 (P < 0.001). No residual edema, defined as CRT <300 μm at 24 weeks, was found in 26 of 30 patients (86.7%) in the treatment group compared with 6 of 30 patients (20%) in the control group (P < 0.001). In the sham group, 5 of 30 patients (16.7%) had developed iris rubeosis at week 24. No patients in the study group had rubeosis at week 24 (P=0.052). There were no events of endophthalmitis, retinal tear, or retinal detachment during the 24-week treatment period. No serious non-ocular adverse events were reported.
Intraocular injections of bevacizumab given every 6 weeks for 6 months improve visual acuity (VA) and reduce ME significantly compared with sham.
Proprietary or commercial disclosure may be found after the references.
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term ...course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count <200 cells per μL by 18 months postinfusion. Patients with durable responses to axi-cel had significantly longer durations of B-cell aplasia, and this duration correlated strongly with the recovery of CD4+ T-cell counts. There were significantly more infections within the first 28 days compared with any other period of follow-up, with the majority being mild-moderate in severity. Receipt of corticosteroids was the only factor that predicted risk of infection in a multivariate analysis (hazard ratio, 3.69; 95% confidence interval, 1.18-16.5). Opportunistic infections due to Pneumocystis jirovecii and varicella-zoster virus occurred up to 18 months postinfusion in patients who prematurely discontinued prophylaxis. These results support the use of comprehensive supportive care, including long-term monitoring and antimicrobial prophylaxis, beyond 12 months after axi-cel treatment.
•Delayed CD4+ T-cell recovery leads to a risk for opportunistic infections for ≥1 year after CD19-directed CAR T-cell therapy.•Antimicrobial prophylaxis, immunoglobulin replacement, and growth factor use may minimize nonrelapse morbidity and mortality after axi-cel.
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Class IC antiarrhythmic drugs (IC-AADs) can effectively suppress premature ventricular contractions (PVCs). However, IC-AADs increase mortality in patients with PVCs and left ventricular dysfunction ...after myocardial infarction. Whether IC-AADs can be safely used to treat premature ventricular contraction-induced cardiomyopathy (PVC-CM) remains to be established.
The purpose of this study was to determine the safety and efficacy of IC-AADs in patients suspected of having PVC-CM.
The electronic medical records at the Hospital of the University of Pennsylvania were screened to identify all patients suspected of having PVC-CM treated with flecainide or propafenone. Clinical, electrocardiographic, and imaging studies were reviewed.
Twenty patients suspected of having PVC-CM were treated with IC-AADs. Patients had undergone an average of 1.3 ± 0.2 previous unsuccessful ablations. Six had an implantable or wearable defibrillator. With IC-AAD treatment, mean PVC burden decreased from 36.2% ± 3.5% to 10.0% ± 2.4% (P <.001). Mean left ventricular ejection fraction (LVEF) increased from 37.4% ± 2.0% to 49.0% ± 1.9% (P <.001). Seven patients with myocardial delayed enhancement on cardiac magnetic resonance imaging (all <5% of the total myocardium) experienced similar improvement in LVEF (from 36.8% ± 4.3% before IC-AAD to 51.7% ± 3.7% afterward; P <.01). Over an average 3.8 ± 0.9 treatment-years, no sustained ventricular arrhythmias or sudden cardiac deaths occurred.
In patients suspected of having PVC-CM, IC-AADs effectively suppressed PVCs, leading to LVEF recovery in the majority. No adverse events occurred in this small cohort.
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