Safety Surveillance of Varicella Vaccines in the Vaccine Adverse Event Reporting System, United States, 2006-2020.

BACKGROUND: . The Vaccine Adverse Event Reporting System (VAERS) is the United States national passive vaccine safety surveillance system. We updated the data on the safety of single-antigen varicella vaccine (VAR) and assessed the safety of combination measles, mumps, rubella, and varicella vaccine (MMRV) licensed in the United States using VAERS data. METHODS: US VAERS reports received after administration of VAR and MMRV during 2006-2020 were identified. Reports were analyzed by vaccine type, age, seriousness, most common adverse events (AEs), and concomitant vaccines. We reviewed medical records of selected reports of AEs of special interest and conducted empirical Bayesian data mining to identify disproportionally reported AEs. RESULTS: During 2006-2020, approximately 132.8 million VAR doses were distributed; 40 684 reports were received in VAERS (30.6/100 000 doses distributed), with 4.1% classified as serious (1.3/100 000 doses distributed). Approximately 35.5 million MMRV doses were distributed; 13 325 reports were received (37.6/100 000 doses distributed) with 3.3% classified as serious (1.3/100 000 doses distributed). The most common adverse health events after both VAR and MMRV were injection site reactions (31% and 27%), rash (28% and 20%), and fever (12% and 14%), respectively. Vaccination errors accounted for 23% of reports after VAR administration and 41% after MMRV administration, but ≥95% of them did not describe an adverse health event. AEs associated with evidence of vaccine strain varicella-zoster virus (vVZV) infection included meningitis, encephalitis, herpes zoster, and 6 deaths (all in immunocompromised persons with contraindications for vaccination). No new or unexpected AE was disproportionally reported. CONCLUSIONS: No new or unexpected safety findings were detected for VAR and MMRV given as recommended, reinforcing the favorable safety profiles of these vaccines. Providers should obtain specimens for viral testing and strain-typing for serious AEs if they consider vVZV as the possible causative agent.

Thromboembolic events after Ad.26.COV2.S COVID-19 vaccine: Reports to the Vaccine Adverse Event Reporting System.

PURPOSE: The Food and Drug Administration (FDA) has identified a potential safety concern for thromboembolic events (TEEs) after Ad.26.COV2.S COVID-19 Vaccine. We sought to characterize the frequency, severity, type, and anatomic location of TEEs reported to the Vaccine Adverse Event Reporting System (VAERS) following Ad.26.COV2.S. METHODS: Reports of TEEs after Ad.26.COV2.S were identified in VAERS, and demographics, clinical characteristics, and relevant medical history were summarized. For a subset of reports, physicians reviewed available medical records and evaluated clinical presentation, diagnostic evaluation, risk factors, and treatment. The crude reporting rate of TEEs was estimated based on case counts in VAERS and vaccine administration data. RESULTS: Through February 28, 2022, FDA identified 3790 reports of TEEs after Ad.26.COV2.S. Median age was 56 years, and 1938 individuals (51.1%) were female. Most reports, 2892 (76.3%), were serious, including 421 deaths. Median time to onset was 12 days post-vaccination. Obesity and ischemia were among the most commonly documented risk factors. Thrombocytopenia (platelet count less than 150 000/µl) was documented in 63 records (11.5%) and anti-platelet 4 antibodies in 25 (4.6%). Medical review identified cases of severe clot burden (e.g., bilateral, saddle, or other massive pulmonary embolism with or without cor pulmonale; lower extremity thrombus involving the external iliac, common femoral, popliteal, posterior tibial, peroneal, and gastrocnemius veins). The crude reporting rate was ~20.7 cases of TEE per 100 000 doses of Ad.26.COV2.S administered. CONCLUSIONS: Life-threatening or fatal TEEs have been reported after Ad.26.COV2.S, including bilateral massive pulmonary embolism or other severe clot burden.

Red blood cell alloantibodies are associated with increased alloimmunization against human leukocyte antigens.

BACKGROUND: Alloantibodies recognizing human leukocyte antigens (HLA) can cause immune-mediated refractoriness to platelet transfusion. An association between HLA alloimmunization and red blood cell (RBC) alloimmunization has been suggested but remains uncertain. STUDY DESIGN AND METHODS: We tested for HLA alloantibodies in 660 patients with and without RBC alloantibodies. Calculated panel reactive antibody (cPRA) values were determined for HLA alloimmunized patients. Current and historical diagnoses and blood product exposure were catalogued. Variables associated with high-level HLA alloimmunization (cPRA ≥ 90%) were evaluated. RESULTS: The cohort included 366 women and 294 men with median age of 66 years (interquartile range [IQR], 53-76). The number of patients with and without RBC alloantibodies was 447 and 213, respectively. Among patients with and without RBC alloantibodies, 20.6% and 8.5% had a cPRA ≥ 90%, respectively (p < 0.0001). In univariate analyses of men and nulliparous women and previously pregnant women, the median number of RBC alloantibodies was significantly higher in patients with a cPRA ≥ 90% (p < 0.0001). The number of RBC alloantibodies remained an independent predictor of a cPRA ≥ 90% in multivariate analysis (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.22-1.85). Other independent predictors of a cPRA ≥ 90% were parity (OR 1.26, 95% CI 1.08-1.47), age (OR 0.98, 95% CI 0.97-1.00), history of renal disease (OR 1.88, 95% CI 1.02-3.48), and number of non-leukoreduced products transfused (OR 1.02, 95% CI 1.00-1.04). CONCLUSIONS: RBC alloimmunization was significantly associated with HLA alloimmunization with a cPRA ≥ 90%. RBC alloimmunization status combined with specific components of the clinical history may estimate the risk of high-level HLA alloimmunization.

Provision of KEL1-negative blood to obstetric patients: a 3-year single-institution retrospective review.

BACKGROUND: KEL1 alloimmunization is a major cause of hemolytic disease of the fetus and newborn (HDFN). While select countries have guidelines for preventing transfusion-associated KEL1 alloimmunization, the United States does not. Beth Israel Deaconess Medical Center instituted a policy in April 2009 whereby women not more than 50 years of age on the obstetric service were transfused KEL1-negative red blood cells (RBCs). We sought to determine compliance and impact for prevention of KEL1 alloimmunization and HDFN. STUDY DESIGN AND METHODS: All women not more than 50 years of age without anti-K transfused RBCs during an obstetric admission from April 9, 2009, to April 9, 2012, were identified (227). Adherence to policy, factors contributing to nonadherence, and subsequent impact were evaluated. For comparison, all cases of anti-K detection in women not more than 50 years of age admitted to nonobstetric services and all cases of transfusion-associated KEL1 alloimmunization in women not more than 50 years of age during the 10 years prior were identified. RESULTS: Eighty-four percent received only KEL1-negative units. Three (1.3%) women not more than 50 years of age on the obstetric service were identified with anti-K, while 17 (1.5%) women not more than 50 years of age on nonobstetric services had anti-K detected; only five of 20 had a prior RBC transfusion. In the 10 years prior, there were 27 cases of transfusion-associated KEL1 alloimmunization in women not more than 50 years of age. There were no cases of KEL1 HDFN in either period. CONCLUSION: Although the findings demonstrate feasibility of providing KEL1-negative RBCs to women of childbearing potential, evidence for clinical benefit is lacking. The low prevalence of KEL1 in blood donors, the lack of significant differences in alloimmunization rates, and no cases of HDFN during the study period questions the clinical benefit of such a policy.

Interdependence of social-ecological-technological systems in Phoenix, Arizona: consequences of an extreme precipitation event.

Complex adaptive systems - such as critical infrastructures (CI) - are defined by their vast, multi-level interactions and emergent behaviors, but this elaborate web of interactions often conceals relationships. For instance, CI is often reduced to technological components, ignoring that social and ecological components are also embedded, leading to unintentional consequences from disturbance events. Analysis of CI as social-ecological-technological systems (SETS) can support integrated decision-making and increase infrastructure's capacity for resilience to climate change. We assess the impacts of an extreme precipitation event in Phoenix, AZ to identify pathways of disruption and feedback loops across SETS as presented in an illustrative causal loop diagram, developed through semi-structured interviews with researchers and practitioners and cross-validated with a literature review. The causal loop diagram consists of 19 components resulting in hundreds of feedback loops and cascading failures, with surface runoff, infiltration, and water bodies as well as power, water, and transportation infrastructures appearing to have critical roles in maintaining system services. We found that pathways of disruptions highlight potential weak spots within the system that could benefit from climate adaptation, and feedback loops may serve as potential tools to divert failure at the root cause. This method of convergence research shows potential as a useful tool to illustrate a broader perspective of urban systems and address the increasing complexity and uncertainty of the Anthropocene. Supplementary Information: The online version contains supplementary material available at 10.1186/s43065-023-00085-6.

Detection of fetomaternal hemorrhage.

The prevention of Rhesus D alloimmunization through Rh immune globulin (RhIg) administration is the major indication for the accurate detection and quantification of fetomaternal hemorrhage (FMH). In the setting of D incompatibility, D-positive fetal cells can sensitize the D-negative mother, resulting in maternal anti-D alloantibody production. These anti-D alloantibodies may lead to undesirable sequelae such as hemolytic disease of the newborn (HDN). Since the widespread adoption of FMH screening and RhIg immunoprophylaxis, the overall risk of Rh alloimmunization and infant mortality from HDN has substantially decreased. The rosette screen, the initial test of choice, is highly sensitive in qualitatively detecting 10 mL of fetal whole blood in the maternal circulation. As the screen is reliant on the presence of the D antigen to distinguish fetal from maternal cells, it cannot be used to detect FMH in D-positive mothers or in D-negative mothers carrying a D-negative fetus. The Kleihauer-Betke acid-elution test, the most widely used confirmatory test for quantifying FMH, relies on the principle that fetal RBCs contain mostly fetal hemoglobin (HbF), which is resistant to acid-elution whereas adult hemoglobin is acid-sensitive. Although the Kleihauer-Betke test is inexpensive and requires no special equipment, it lacks standardization and precision, and may not be accurate in conditions with elevated F-cells. Anti-HbF flow cytometry is a promising alternative, although its use is limited by equipment and staffing costs. Hematology analyzers with flow cytometry capabilities may be adapted for fetal cell detection, thus giving clinical laboratories a potentially attractive automated alternative for quantifying FMH.

Two-tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a whole-cell sonicate enzyme immunoassay followed by a VlsE C6 peptide enzyme immunoassay.

BACKGROUND: Lyme disease (LD) antibody testing currently involves a 2-tiered algorithm with a whole-cell sonicate (WCS) enzyme immunoassay (EIA), followed by IgM/IgG Western immunoblots. A single EIA using the C6 peptide of the Borrelia burgdorferi variable-major protein-like sequence expressed lipoprotein provides similar or better sensitivity but less specificity, compared with standard 2-tiered testing. Here, we investigated an alternative 2-tiered strategy, in which the first step remained a WCS EIA, but immunoblotting was replaced by a C6 EIA. METHODS: We determined the sensitivity of the 3 testing strategies with use of 91 serum samples from research study patients with LD and 78 serum samples from patients with LD whose samples were submitted to our hospital's clinical laboratory. Specificity was measured using 54 patients with other illnesses and 1246 healthy subjects from areas where the infection is endemic and nonendemic. RESULTS: The 2-EIA algorithm in early LD had similar sensitivity as C6 testing alone, and both strategies had better sensitivity than did standard 2-tiered testing (61% and 64%, respectively, vs 48%; P = .03 and P = .008). For late disease, all 3 strategies had 100% sensitivity. The specificity of the 2-EIA algorithm was equal to that of standard 2-tiered testing, and both 2-tiered strategies were more specific than C6 testing alone (for both, 99.5% vs 98.4%; P = .01). The positive predictive value of the 2-EIA algorithm was 70%, compared with 66% for standard 2-tiered testing and 43% for the C6 EIA alone. CONCLUSIONS: The 2-EIA strategy matched the individual strengths of the C6 EIA and Western blotting, without the drawbacks. The 2 EIAs provided sensitivity comparable to that of the C6 EIA but maintained the specificity of standard 2-tiered testing.

Effect of Indocyanine Green and Infrared Diode Laser to Streptococcus mutans Biofilms.

Objective: The aim of this study was to quantitatively and qualitatively evaluate the effects of the indocyanine green (ICG)-near-infrared (NIR) photoreaction on Streptococcus mutans biofilms. Background: ICG recently emerged as a photosensitive agent for photodynamic therapy. Although the effects of ICG-NIR on S. mutans inhibition are documented, little is known about its influence on biofilms, which are resistant to antimicrobial treatment and a major cause of plaque that leads to dental caries. Methods: ICG was used as a photosensitizer with a diode laser irradiated in a rectangular shape (810 nm, 300 mW) as a light source on S. mutans ATCC 25175 biofilms. Viability was determined by the colony forming unit (CFU) count and confocal laser-scanning microscopy. The biofilm surface temperature was measured with a one-channel thermocouple thermometer. Results: ICG and NIR diode laser significantly decreased the CFU count of S. mutans compared with the control group in a time-dependent manner. When irradiated with light after ICG application, temperature changes of 8.4°C, 12.4°C, and 14.9°C were observed with 10, 30, and 60 sec of irradiation, respectively. Conclusions: The ICG-NIR diode laser photoreaction can inhibit S. mutans biofilms, especially at 60 sec. An optimized protocol is needed for clinical application of ICG-NIR diode laser treatment.

The effects of transport temperature and time on routine and specialized coagulation assays.

: Coagulation laboratories have largely stopped transporting whole blood specimens on ice, due to adverse effects on factor VIII, von Willebrand factor, and the prothrombin time. However, it is unknown whether ice should be required or avoided for other coagulation assays. Furthermore, the amount of time that specimens remain stable during transportation at room temperature (RT) is also largely unknown for many coagulation tests. Therefore, this study investigated specimen stability on ice and RT for a comprehensive panel of coagulation tests. One tube of whole blood from each volunteer (n = 22) was centrifuged immediately (time 0), one was stored for 4 h on ice, and one was stored for 4 h at RT before centrifugation. Among time 0, 4 h on ice, and 4 h at RT samples, no statistically significant differences were found for fibrinogen, activated protein C resistance, thrombin time, reptilase time, antithrombin activity, chromogenic protein C, factor XII, and antiplasmin activity. Prothrombin time, activated partial thromboplastin time, factors IX, XI, protein S activity, and plasminogen activity showed statistically, but not clinically, significant differences. On ice, the only analytes that showed clinically significant changes (≥6.0% from time 0) were factors VII, VIII, von Willebrand factor antigen, and ristocetin cofactor, which were 14.0% higher, and 19.2, 9.5, and 18.8% lower than time 0, respectively. At RT, all analytes were stable except factor VIII was 9.4% lower than time 0. Only factors II, V, X, and PTT-LA lupus anticoagulant showed a possible slight benefit from ice, but the statistically significant differences were not clinically significant. Ice did not substantially benefit any of the coagulation assays. All tests were stable at RT, except more study is needed regarding factor VIII.

Pediatric therapeutic apheresis: rationale and indications for plasmapheresis, cytapheresis, extracorporeal photopheresis, and LDL apheresis.

Apheresis refers to the removal of a component of the blood and is performed using a group of medical technologies in which peripheral blood is processed by an instrument that separates the various components. The selected component is isolated while the remainder is returned to the patient. The rationale behind therapeutic apheresis is to remove the pathogenic components from the circulation. Apheresis is also used for peripheral hematopoietic progenitor cell collection. The procedure can be safely performed in most children with modifications to account for smaller pediatric blood volumes.

Evaluation of Leuconostoc citreum HO12 and Weissella koreensis HO20 isolated from kimchi as a starter culture for whole wheat sourdough.

Leuconostoc citreum HO12 and Weissella koreensis HO20 isolated from kimchi were evaluated as starter cultures in the making of whole wheat sourdough bread. After 24h of fermentation at 25 °C, both lactobacilli grew to the final cell numbers of ca. 10(9)cfu/g dough, and both doughs had similar pHs and total titratable acidities. In addition, the fermentation quotient of the dough with Lc. citreum HO12 was slightly lower than that of the dough with W. koreensis HO20 (1.6 versus 2.8). Sourdoughs and bread with 50% sourdough produced with the starter cultures exhibited consistent ability to retard the growth of bread spoilage fungi (Penicillium roqueforti and Aspergillus niger) and rope-forming bacterium (Bacillus subtilis). Sourdough breads underwent a significant reduction in bread firming during storage. It seems that both lactobacilli have the potential to improve the shelf-life of wheat bread. The results indicate that the selected lactobacilli have unique fermentation characteristics and produce sourdough breads with overall satisfactory quality.

Patient ethnicity and the identification of anxiety in elderly primary care patients.

OBJECTIVES: To examine the role of ethnicity and primary care physician (PCP) identification of anxiety in older adults. DESIGN: A cross-sectional survey conducted between 2001 and 2003. SETTING: Primary care offices in the Baltimore, Maryland, area. PARTICIPANTS: A sample of 330 adults aged 65 and older from Maryland primary care practices with complete information on psychological status and physician assessments. MEASUREMENTS: PCPs were asked to rate anxiety on a Likert scale. Patient interviews included measures of psychological status and patient use of psychotropic medications. RESULTS: Older black patients were less likely than older white patients to be identified as anxious (unadjusted odds ratio (OR)=0.34, 95% confidence interval (CI)=0.18-0.64) and less likely to be taking psychotropic medications (unadjusted OR=0.40, 95% CI=0.20-0.81). In multivariate models that controlled for potentially influential characteristics including depression and anxiety symptoms, the association between identification (OR=0.30, 95% CI=0.15-0.61) with patient ethnicity remained significantly unchanged. CONCLUSION: PCPs were less likely to identify older black Americans as anxious than white patients. An understanding of the role of ethnicity in the identification of anxiety is important for the screening and management of anxiety in elderly people.

Chronic medical conditions and wishes to die among older primary care patients.

OBJECTIVE: To determine the prevalence of wishes to die and the medical correlates of wishes to die among primary care patients aged 65 years and older. METHOD: Three-hundred and fifty-five adults with and without significant depressive symptoms who were screened in primary care offices and invited to participate completed a baseline in-home assessment. Participants were interviewed using standardized measures of medical conditions, functional status, and psychological status. Thoughts of death and wishes to die were assessed with standard questions from the Composite International Diagnostic Interview (CIDI) Depression Section. RESULTS: The weighted point prevalence of thoughts of death was 9.7% and 6.1% for the wish to die. Several medical conditions were associated with a wish to die, for example myocardial infarction (MI). In multivariate models that adjusted for potentially influential characteristics, the association between a history of MI and the wish to die remained statistically significant (odds ratio (OR) = 3.32, 95% confidence interval (CI) (1.26, 8.75). CONCLUSIONS: Thoughts of death and a wish to die are common in older primary care patients and were more likely among persons with chronic medical conditions. Persons with a history of myocardial infarction may be particularly vulnerable to a wish to die.