Association of Receipt of the Ad26.COV2.S COVID-19 Vaccine With Presumptive Guillain-Barré Syndrome, February-July 2021.

Importance: As part of postauthorization safety surveillance, the US Food and Drug Administration (FDA) has identified a potential safety concern for Guillain-Barré syndrome (GBS) following receipt of the Ad26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccine. Objective: To assess reports of GBS received in the Vaccine Adverse Event Reporting System (VAERS) following Ad26.COV2.S vaccination. Design, Setting, and Participants: Reports of presumptive GBS were identified in a US passive reporting system (VAERS) February-July 2021 and characterized, including demographics, clinical characteristics, and relevant medical history. Exposures: Receipt of the Ad26.COV2.S vaccine; the comparator was the background rate of GBS in the general (unvaccinated) population that had been estimated and published based on a standardized case definition. Main Outcomes and Measures: Presumptive GBS; the reporting rate was analyzed, including calculation of the observed to expected ratio based on background rates and vaccine administration data. Because of limited availability of medical records, cases were not assessed according to the Brighton Collaboration criteria for GBS. Results: As of July 24, 2021, 130 reports of presumptive GBS were identified in VAERS following Ad26.COV2.S vaccination (median age, 56 years; IQR, 45-62 years; 111 individuals [86.0%] were < 65 years; 77 men [59.7%]). The median time to onset of GBS following vaccination was 13 days (IQR, 10-18 days), with 105 cases (81.4%) beginning within 21 days and 123 (95.3%) within 42 days. One hundred twenty-one reports (93.1%) were serious, including 1 death. With approximately 13 209 858 doses of vaccine administered to adults in the US, the estimated crude reporting rate was 1 case of GBS per 100 000 doses administered. The overall estimated observed to expected rate ratio was 4.18 (95% CI, 3.47-4.98) for the 42-day window, and in the worst-case scenario analysis for adults 18 years or older, corresponded to an estimated absolute rate increase of 6.36 per 100 000 person-years (based on a rate of approximately 8.36 cases per 100 000 person-years [123 cases per 1 472 162 person-years] compared with a background rate of approximately 2 cases per 100 000 person-years). For both risk windows, the observed to expected rate ratio was elevated in all age groups except individuals aged 18 through 29 years. Conclusions and Relevance: These findings suggest a potential small but statistically significant safety concern for Guillain-Barré syndrome following receipt of the Ad26.COV2.S vaccine. However, the findings are subject to the limitations of passive reporting systems and presumptive case definition, and they must be considered preliminary pending analysis of medical records to establish a definitive diagnosis.

Assessment of tissue allograft safety monitoring with administrative healthcare databases: a pilot project using Medicare data.

Assess whether Medicare data are useful for monitoring tissue allograft safety and utilization. We used health care claims (billing) data from 2007 for 35 million fee-for-service Medicare beneficiaries, a predominantly elderly population. Using search terms for transplant-related procedures, we generated lists of ICD-9-CM and CPT(®) codes and assessed the frequency of selected allograft procedures. Step 1 used inpatient data and ICD-9-CM procedure codes. Step 2 added non-institutional provider (e.g., physician) claims, outpatient institutional claims, and CPT codes. We assembled preliminary lists of diagnosis codes for infections after selected allograft procedures. Many ICD-9-CM codes were ambiguous as to whether the procedure involved an allograft. Among 1.3 million persons with a procedure ascertained using the list of ICD-9-CM codes, only 1,886 claims clearly involved an allograft. CPT codes enabled better ascertainment of some allograft procedures (over 17,000 persons had corneal transplants and over 2,700 had allograft skin transplants). For spinal fusion procedures, CPT codes improved specificity for allografts; of nearly 100,000 patients with ICD-9-CM codes for spinal fusions, more than 34,000 had CPT codes indicating allograft use. Monitoring infrequent events (infections) after infrequent exposures (tissue allografts) requires large study populations. A strength of the large Medicare databases is the substantial number of certain allograft procedures. Limitations include lack of clinical detail and donor information. Medicare data can potentially augment passive reporting systems and may be useful for monitoring tissue allograft safety and utilization where codes clearly identify allograft use and coding algorithms can effectively screen for infections.

Incidence of endophthalmitis after corneal transplant or cataract surgery in a medicare population.

OBJECTIVE: To estimate the incidence of infectious endophthalmitis after corneal transplant or cataract surgery, to evaluate the trend of endophthalmitis during the study period, and to assess demographic risk factors for endophthalmitis after surgeries. DESIGN: A retrospective population-based cohort study. PARTICIPANTS AND CONTROLS: Study cohorts were derived from the Medicare claims databases, 2006 to 2011. Patients were continuously enrolled in Medicare Part A, Part B, and Part D. Patients undergoing corneal transplant or cataract surgery were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes. METHODS: Endophthalmitis was defined in 3 different ways: (1) using ICD-9-CM codes (sensitive definition), (2) combining ICD-9-CM codes with Current Procedural Terminology, Fourth Edition (CPT-4) codes (specific definition), or (3) combining ICD-9-CM codes with antifungal prescriptions for endophthalmitis caused by fungal infection. Demographic risk factors for endophthalmitis were examined using multivariate Cox models. MAIN OUTCOME MEASURES: Incidence rates of endophthalmitis were calculated and compared for each definition of endophthalmitis at 6-week and 6-month intervals after corneal transplant or cataract surgery. RESULTS: The infectious endophthalmitis incidence rates ranged from 0.11% to 1.05% in the corneal transplant cohort, 0.06% to 0.20% in the cataract surgery cohort, and 0.16% to 0.68% in the concurrent surgery cohort, depending on the definition and time interval after surgery. Compared with the cataract surgery cohort, the corneal transplant cohort had a higher adjusted hazard ratio (HR) of endophthalmitis within the 6-week postoperative interval (HR, 2.744; 95% confidence interval [CI], 1.544-4.880 in the sensitive definition and HR, 2.792; 95% CI, 1.146-6.802 in the specific definition) and within the 6-month postoperative interval (HR, 4.607; 95% CI, 3.144-6.752 for the sensitive definition and HR, 4.385; 95% CI, 2.245-8.566 for the specific definition). CONCLUSIONS: It is possible to monitor the trend of infectious endophthalmitis after corneal transplant or cataract surgery through examining Medicare claims databases as long as a consistent definition of endophthalmitis is used. The annual incidence of endophthalmitis was stable over time during the study period for both corneal transplant and cataract surgery procedures; however, there was a wider year-to-year variation for the corneal transplant cohort.

The US Food and Drug Administration review of the safety and effectiveness of nonstandardized allergen extracts.

BACKGROUND: Nonstandardized allergen extracts have been used for a century. Until 1972, these products were regulated by the National Institutes of Health, and products were not required to have an individualized showing of effectiveness. Jurisdiction was then transferred to the US Food and Drug Administration (FDA), which established external review panels to make recommendations regarding safety and effectiveness. Two external panels deliberated, the first from 1974-1979 and the second from 1982-1983. OBJECTIVE: We sought to review external panels' recommendations and assess the safety and effectiveness of nonstandardized allergen extracts, FDA-reviewed available literature, and databases since 1972. METHODS: Currently licensed nonstandardized allergen extracts were reviewed according to extract type. Available data were collected from medical and nonscientific search engines. Nomenclature was ascertained by consulting www.itis.gov or www.atcc.org. The FDA's Adverse Event Reporting System was probed for events associated with extract use. Provisional threshold levels of safety and effectiveness were established, and extracts were sorted according to whether they met the thresholds. RESULTS: In the Adverse Event Reporting System, there were 178 adverse event reports, including 13 deaths, associated with allergen extract use over 23 years. No single group of extracts predominated. Among 1269 allergen extracts reviewed, there were 480 for which use in the diagnosis and treatment of allergic disease were addressed in the literature, 207 for which only diagnostic use was addressed, 565 for which minimal or no supportive literature was identified, and 17 for which potential safety concerns were found. CONCLUSIONS: When used according to professional guidelines, almost all nonstandardized allergen extracts for diagnosis and therapy appear to be safe. Provisional thresholds of effectiveness were met by 54% of extracts reviewed.

Reported infections after human tissue transplantation before and after new Food and Drug Administration (FDA) regulations, United States, 2001 through June, 2010.

Processors distributed about 1.5 million human tissue allografts in the U.S. in 2007. The potential for transmitting infections through allografts concerns clinicians and patients. In 2005, FDA implemented Current Good Tissue Practice (CGTP) rules requiring tissue establishments to report to FDA certain serious infections after allograft transplantations. We describe infection reports following tissue transplants received by FDA from 2005 through June, 2010, and compare reporting before and after implementation of CGTP rules. We identified reports received by FDA from January 2001 through June, 2010, for infections in human tissue recipients, examining the reports by tissue type, organism, time to onset, severity, and reporter characteristics. Among 562 reports, 83 (20.8/year) were received from 2001-2004, before the CGTP rules, 43 in the 2005 transition year, and 436 (96.9/year) from 2006 through June, 2010, after the rules. Tissue processors accounted for 84.2% of reports submitted after the rules, compared to 26.5% previously. Bacterial infections were the most commonly reported organisms before (64.6%) and after (62.2%) the new rules. Afterward, 2.5% (11) of reports described deaths, and 33.7% (147) involved hospitalizations. Before the rules, 13% (11) described deaths, and another 72% involved hospitalizations. Reports received by the FDA quadrupled since 2005, suggesting that CGTP regulations have contributed to increased reporting and improved tissue safety surveillance. However, these data do not confirm that the reported infections were caused by suspect tissues; most reports may represent routine post-surgical infections not actually due to allografts.

Anaphylactoid reactions to Dextran 40 and 70: reports to the United States Food and Drug Administration, 1969 to 2004.

BACKGROUND: Clinical dextrans, such as Dextran 40 and Dextran 70, are associated with anaphylactoid reactions caused by dextran-reactive immunoglobulin G antibodies. When infused immediately before clinical dextrans, dextran 1 significantly reduces the incidence of severe anaphylactoid reactions. The objective of the study was to describe the frequency and characteristics of reports submitted to the United States Food and Drug Administration (FDA) for anaphylaxis or anaphylactoid events after clinical dextran administration. METHODS: We searched the FDA's Adverse Event Reporting System for reports associated with a clinical dextran and describing anaphylaxis/anaphylactoid reactions. Our case definition for a probable anaphylaxis/anaphylactoid event required signs or symptoms from at least two body systems, with at least one sign or symptom being hypotension, vasodilation, or respiratory difficulty, and onset within 60 minutes. Other reports were considered possible cases if the reporter specifically described the reaction as anaphylaxis or an anaphylactoid reaction. Premier RxMarket Advisor provided estimates of total US hospitalizations with clinical dextran or dextran 1 administration from 2000 to 2004, based on discharge billing data from a sample of US hospitals. The IMS National Sales Perspective provided estimates of total doses of dextrans sold in the United States from 1999 to 2004, based on volumes of dextrans sold in a sample of retail and nonretail outlets. RESULTS: The FDA received 366 clinical dextran adverse event reports from 1969 to 2004, of which 90 (24.6%) were anaphylaxis/anaphylactoid events. The ratio of hospitalizations where clinical dextran was administered to hospitalizations where dextran 1 was administered was 28.4:1. The expected ratio would be 1:1 if all clinical dextran patients had received dextran 1 pretreatment. The ratio of clinical dextran doses sold to dextran 1 doses sold in the United States was 38.6:1. CONCLUSIONS: A high proportion of adverse event reports for clinical dextrans described anaphylaxis or anaphylactoid reactions. Hospital discharge and product sales data suggest that dextran 1 has not been used consistently before clinical dextran administration in recent years. To reduce the risk of anaphylactoid reactions, physicians should consider routine administration of dextran 1 before the infusion of a clinical dextran.

Suspected meningococcal meningitis on an aircraft carrier.

A suspected case of meningococcal meningitis was diagnosed in a 24-year-old sailor onboard an aircraft carrier at sea in 2003. He was immediately confined to the ship's hospital ward under respiratory isolation precautions and was treated with intravenously administered antibiotics. His illness resolved without sequelae. A total of 99 close contacts from the ship were identified and given antibiotic prophylaxis, with directly observed therapy. British public health authorities were contacted to trace and treat persons identified as close contacts during a port call a few days before presentation. Managing a communicable disease such as meningococcal meningitis in the austere shipboard environment represents a unique challenge to military medical personnel. Successful management is possible through prompt treatment, respiratory isolation, and open communication between primary health care providers and public health officials. The identification of shipboard close contacts and other infection control procedures used by the ship's medical department are reviewed.

Community-acquired methicillin-resistant Staphylococcus aureus among military recruits.

We report an outbreak of 235 community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections among military recruits. In this unique environment, the close contact between recruits and the physical demands of training may have contributed to the spread of MRSA. Control measures included improved hygiene and aggressive clinical treatment.