The COVID-19 pandemic's impact on rheumatic disease patients' satisfaction with access to medical services.

The COVID-19 hurt various lifestyle aspects, especially the treatment and follow-up of patients with chronic diseases such as autoimmune inflammatory rheumatic diseases (RD). The new circumstances changed the frequency of medical examinations and the way patients with rheumatic diseases are followed up. The objective is to study the impact of COVID-19 on RD patients' satisfaction with access to medical services. A national multicenter observational cross-sectional anonymous online survey was conducted on patients with RD using a specially developed web-based platform and structured questionnaire https://rheumatologycovid19.bg/ . The study was carried out with the support of intra-university project №6/2022 MU-Plovdiv. 1288 patients participated, with an average age of 47.03 (SD ± 12.80 years), of whom 992 (81.6%) were women. The questionnaire contained 41 questions grouped into 5 panels. Descriptive statistics were used-mean, alternative analysis, logistic regression and Decision Tree using the CRT (classification and regression trees) method. The study found that RD patients' satisfaction with access to medical services was influenced by communication type and the frequency of visits to the rheumatologist, difficulties in prescribing and finding medicines and the presence of comorbidities. The likelihood of patients' satisfaction with their rheumatologist was 5.5 and 3 times higher for in-person and other means of communication, respectively, compared to those without any communication. The relative share of patients who communicated by phone was larger (59%) compared to pre-pandemic (41%), where direct contact with the physician prevailed (80%). The results of the study confirmed the need to optimize remote access to medical care for patients with RD during the pandemic.

Reporting rates for VAERS death reports following COVID-19 vaccination, December 14, 2020-November 17, 2021.

PURPOSE: Despite widely available safety information for the COVID-19 vaccines, vaccine hesitancy remains a challenge. In some cases, vaccine hesitancy may be related to concerns about the number of reports of death to the Vaccine Adverse Event Reporting System (VAERS). We aimed to provide information and context about reports of death to VAERS following COVID-19 vaccination. METHODS: This is a descriptive study evaluating reporting rates for VAERS death reports for COVID-19 vaccine recipients in the United States between December 14, 2020, and November 17, 2021. Reporting rates were calculated as death events per million persons vaccinated and compared to expected all-cause (background) death rates. RESULTS: 9201 death events were reported for COVID-19 vaccine recipients aged 5 years and older (or age unknown). Reporting rates for death events increased with increasing age, and males generally had higher reporting rates than females. For death events within 7 days and 42 days of vaccination, respectively, observed reporting rates were lower than the expected all-cause death rates. Reporting rates for Ad26.COV2.S vaccine were generally higher than for mRNA COVID-19 vaccines, but still lower than the expected all-cause death rates. Limitations of VAERS data include potential reporting bias, missing or inaccurate information, lack of a control group, and reported diagnoses, including deaths, are not causally verified diagnoses. CONCLUSIONS: Reporting rates for death events were lower than the all-cause death rates expected in the general population. Trends in reporting rates reflected known trends in background death rates. These findings do not suggest an association between vaccination and overall increased mortality.

Prophylactic Central Neck Lymph Node Dissection Adds No Short-Term Benefit to Total Thyroidectomy for Differentiated Thyroid Cancer.

Background and Objectives: To answer the research question: "Is prophylactic central neck lymph node dissection (pCNLD) beneficial among differentiated thyroid carcinoma (DTC) patients?" Materials and Methods: This was a retrospective cohort study enrolling DTC patients treated at the University Hospital Kaspela, Bulgaria, from 30 January 2019 to October 2021. The predictor variable was presence of pCNLD (total thyroidectomy with vs. without pCNLD). The main outcome variables were postoperative complications (i.e., vocal cord paralysis, hypoparathyroidism, postoperative bleeding, and adjacent organ injury) and recurrence parameters. Appropriate statistics were computed with the significant level at p ≤ 0.05. Results: During the study period, 300 DTC patients (59.7% with pCNLD; 79.3% females) with an average age of 52 ± 2.8 years were treated. The mean follow-up period of the entire cohort was 45.8 ± 19.1 months. On bivariate analyses, TT with pCNLD, when compared to TT alone, required longer surgical time (mean difference: 9.4 min), caused nearly similar complications (except transient hypothyroidism: p = 0.04; relative risk, 1.32; 95% confidence interval, 1.0 to 1.73), and no significantly different recurrence events, time to recurrence, and recurrent sites. The benefit-risk analyses using the number needed to treat and to harm (NNT; NNH) also confirmed that TT plus pCNLD was not very beneficial in DTC management. Conclusion: The results of this study refute the benefit of pCNLD in DTC patient care with TT. Further well-designed studies in a larger cohort with a longer follow-up period are required to confirm this conclusion.

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.

Age- and risk factor-based serologic screening for Hepatitis C virus among an Urban, high-risk population.

Hepatitis C virus (HCV) screening among individuals born between 1945 and 1965 (ie birth cohort) may augment risk factor-based screening. We assessed HCV seropositivity among injection drug users (IDUs) and birth cohort members from New York City. We assessed HCV risk factors and seropositivity in 7722 participants from community health, HIV prevention, syringe exchange and drug treatment programmes. A total of 26.6% were HCV seropositive, 55.8% were born between 1945 and 1965, and 82.2% had ever injected drugs. Among all participants, HCV seropositivity was higher among IDUs compared to non-IDUs (60.5% versus 7.7%, odds ratio (OR) = 18.5, 95% confidence interval (CI) [16.2, 21.1], P < .0001) and among birth cohort members compared to non-birth cohort members (31.3% versus 22.3%, OR = 1.6, 95%CI [1.4, 1.8], P < .0001). Within the birth cohort, HCV seroprevalence among IDUs was 68.5% versus 11.8%, OR = 16.2, 95%CI [13.7, 19.3]. After adjustment, HCV seroprevalence was higher in IDUs, previously incarcerated, whites (<42 years) and 'other races' (versus blacks), HIV-infected, those who snorted heroin, those with liver disease history, and those who had sex with an HCV-seropositive partner. HCV seroprevalence among IDU, birth cohort members, was considerably higher than among the general population. In this high-risk, urban population, the association between IDU and HCV seropositivity was approximately ten times that between birth cohort membership and HCV seropositivity.

Psychometric properties of the Bulgarian version of Hospital Survey on Patient Safety Culture.

OBJECTIVE: To explore the psychometrics of the Bulgarian version of the Hospital Survey on Patient Safety Culture (B-HSOPSC) and its suitability for use in Bulgaria. DESIGN: A national web-based cross-sectional survey of the safety patient culture. SETTING: The hospitals' staffs from 28 administrative areas in the country. INTERVENTIONS: Web-based self-administered questionnaire. PARTICIPANTS: Physicians and non-physicians such as nurses, midwifes, etc., working at hospitals. MAIN OUTCOME MEASURES: Confirmatory factor analysis (CFA) was performed to assess the psychometric properties of the original US structure. Assessment of construct validity included convergent validity, discriminant validity, and nomological validity of constructs. RESULTS: A total of 525 valid cases were included in the analysis. The results of CFA revealed acceptable values for absolute indices and lower for the incremental index, comparative fit index. Due to the very low convergence validity, the dimension 'staffing' was removed from the model. Additionally, one item was removed from another dimension. The B-HSOPSC included 11 dimensions and 37 items. CONCLUSIONS: The B-HSOPSC had acceptable levels of global and local fits. Its safety culture dimensions were sufficiently distinguishable and correlated with outcome variables.

Involvement of general practitioners in colorectal cancer voluntary screening campaign: a mixed-methods study.

PURPOSE: To investigate the attitudes and willingness of the general practitioners (GPs) as well as their actual participation in the voluntary colorectal cancer (CRC) screening campaign without additional financial incentives for them, combining quantitative and qualitative approaches. METHODS: A multiple-case practice based study was designed using a mixed method, triangulation techniques and a sequential explanatory design strategy. The study included all 41 GPs practices in the Municipality of Asenovgrad. A questionnaire, face-to-face semi-structured interviews, nonparticipant direct structured observations and documentation review were used to collect data. Variation analysis, alternative analysis for percentage calculation and Mann-Whitney U test to compare two independent groups and Fisher's Exact Test were used. Statistical significance of the null hypothesis was assumed at p<0.05. RESULTS: Older GPs (p=0.015) and those working with a practice nurse (p=0.000) were more inclined to participate in the CRC screening campaign. GPs more knowledgeable of the importance of CRC screening with iFOBT (immunochemical faecal occult blood test), (p=0.002) and those trusting its quality (p=0.007) were more willing and ready to take part in the screening campaign. Among barriers that GPs encountered in the present screening campaign were lack of knowledge and experience about iFOBT, lack of materials and insufficient incentives. CONCLUSION: Some limitations influence the voluntary participation of GPs in CRC screening campaign that have to be considered before decisions can be made on the implementation of population-based CRC screening programme in Bulgaria in accordance with European guidelines on best practice.

The EUROPEP questionnaire for patient's evaluation of general practice care: Bulgarian experience.

AIM: To validate the Bulgarian EUROPEP-questionnaire and its implementation to measure patient evaluation of general practice care in Bulgarian population. METHODS: A multicenter cross-sectional study was conducted at twenty five primary care practices from South-Central Region of Bulgaria. A total of 1000 adult patients aged over 18 years and visiting the practice for more than a year were approached consecutively to take part in the study. The internal consistency and test-retest reliability of the EUROPEP questionnaire were evaluated. To confirm the construct validity of the questionniare, еxplanatory factor analysis was performed. RESULTS: Cronbach'alpha for "clinical behaviour" is 0.95 and for "organisation of care" 0.81. Factor analysis identifed two factors, which accounted for 77.0% of the total variation in these items. On average, 58.7% of respondents rated the level of care received as excellent. The waiting time in the waiting room was the item most poorly rated (33.8%). The item "keeping patients' records and data confidential" was the most highly rated (88.8%). Patients were less satisfied with "providing quick services for urgent health problems" (78.5% excellent or good) and "getting an appropriate for them appointment" (76.2% excellent or good). CONCLUSION: Two scales with satisfactory psychometric properties were established in the Bulgarian version of the EUROPEP-questionnaire. The study identified areas requiring improvement in general practice, such as reduction in waiting times and obtaining patient's convenience appointment.

Fibrosis Progression in Patients With Chronic Hepatitis C Virus Infection.

BACKGROUND: Fibrosis progression varies markedly in hepatitis C virus (HCV)-infected individuals. We investigated factors that influence fibrosis progression in chronic HCV infection. METHODS: HCV-infected patients who underwent at least 2 liver biopsies were included in this study. Associations between fibrosis progression and epidemiologic, virologic, and disease-associated factors were analyzed using logistic regression and multistate Markov modeling. RESULTS: We analyzed 936 biopsy specimens obtained from 378 individuals. Mean age (±SD) at first biopsy was 48.3 ± 9.3 years, 59.3% of patients were male, 59.9% were white, and 86.7% were infected with HCV genotype 1. Fibrosis progression and cirrhosis occurred in 57.4% and 5.8%, respectively. Fibrosis progression between the first and last biopsies was associated with lower fibrosis in the first biopsy specimen (P < .001) and with the occurrence of at least 1 flare in the alanine aminotransferase (ALT) level (>200 U/L; P = .007). We found the highest fibrosis progression rate between stages 0 and 1 and the lowest between stages 2 and 3. Increased necroinflammation and higher ALT level were associated with faster progression. HCV genotype 3-infected patients were more likely to progress to cirrhosis (P < .001). CONCLUSIONS: Fibrosis progression in HCV is not linear but varies according to stage, with the highest progression in patients with the lowest fibrosis severity. Patients who experience flares in the ALT level are also more likely to progress.

Inappropriate statistical method in a parallel-group randomized controlled trial results in unsubstantiated conclusions.

The conclusions of Cassani et al. in the January 2015 issue of Nutrition Journal (doi: 10.1186/1475-2891-14-5 ) cannot be substantiated by the analysis reported nor by the data themselves. The authors ascribed the observed decrease in inflammatory markers to the components of flaxseed and based their conclusions on within-group comparisons made between the final and the baseline measurements separately in each arm of the randomized controlled trial. However, this is an improper approach and the conclusions of the paper are invalid. A correct analysis of the data shows no such effects.

Intrahepatic and Peripheral CXCL10 Expression in Hepatitis C Virus-Infected Patients Treated With Telaprevir, Pegylated Interferon, and Ribavirin.

UNLABELLED: We assessed peripheral and liver CXCL10 levels in 15 patients treated with telaprevir/pegylated interferon/ribavirin. Induction of peripheral CXCL10 messenger RNA (mRNA) peaked (mean fold-induction [±SD], 3.1 ± 1.9) between treatment hour 6 and day 2, while induction of intrahepatic CXCL10 mRNA peaked (mean fold-induction [±SD], 1.3 ± 0.54) at hour 10 or day 4. Peripheral CXCL10 levels were higher at treatment hour 10 (P = .032) and day 2 (P = .009) in patients with undetectable virus 2 weeks after treatment initiation. Treatment hour 10 (P = .023) and peak (P = .034) intrahepatic CXCL10 levels were also higher in these patients. CXCL10 did not distinguish treatment responders from nonresponders. In conclusion, CXCL10 identified very rapid virological response in patients treated with a direct-acting antiviral. CLINICAL TRIALS REGISTRATION: NCT00892697.

Telaprevir-based treatment effects on hepatitis C virus in liver and blood.

UNLABELLED: Understanding hepatitis C virus (HCV) replication has been limited by access to serial samples of liver, the primary site of viral replication. Our understanding of how HCV replicates and develops drug-resistant variants in the liver is limited. We studied 15 patients chronically infected with genotype 1 HCV treated with telaprevir (TVR)/pegylated-interferon alpha/ribavirin. Hepatic fine needle aspiration was performed before treatment and at hour 10, days 4 and 15, and week 8 after initiation of antiviral therapy. We measured viral kinetics, resistance patterns, TVR concentrations, and host transcription profiles. All patients completed all protocol-defined procedures that were generally well tolerated. First-phase HCV decline (baseline/treatment day 4) was significantly slower in liver than in plasma (slope plasma: -0.29; liver, -0.009; P < 0.001), whereas second-phase decline (posttreatment days 4-15) did not differ between the two body compartments (-0.11 and -0.15, respectively; P = 0.1). TVR-resistant variants were detected in plasma, but not in liver (where only wild-type virus was detected). Based upon nonstructural protein 3 sequence analysis, no compartmentalization of viral populations was observed between plasma and liver compartments. Gene expression profiling revealed strong tissue-specific expression signatures. Human intrahepatic TVR concentration, measured for the first time, was lower, compared to plasma, on a gram per milliliter basis. We found moderate heterogeneity between HCV RNA levels from different intrahepatic sites, indicating differences in hepatic microenvironments. CONCLUSION: These data support an integrated model for HCV replication wherein the host hepatic milieu and innate immunity control the level of viral replication, and the early antiviral response observed in the plasma is predominantly driven by inhibition of hepatic high-level HCV replication sites.

Feasibility of immunochemical faecal occult blood testing for colorectal cancer screening in Bulgaria.

PURPOSE: Colorectal carcinoma (CRC) is the second most common cancer in Europe. Screening guidelines recommend a range of screening options that include faecal occult blood tests (FOBTs). The efficacy of FOBT-based CRC screening is dependent on the participation rate, thus emphasizing the importance of the latter. This study aimed at analysing the feasibility of CRC screening with immunochemical FOBT (iFOBT). METHODS: A cross-sectional study of 600 asymptomatic persons at average risk, aged ≥45years from urban and rural municipalities was performed. An educational brochure, iFOBT kit with translated colored leaflet, informed consent form and questionnaire were administered to participants by 30 general practitioners. Faecal samples were analysed for occult blood using point-of-care rapid iFOBT (cut off 10 ng(GPs)Hb/ml) by the patients themselves at home. The questionnaire aimed to establish if they encountered difficulties in self-testing and self-analysing. Direct and indirect measures of test feasibility were used difficulties for reported study participation rate. RESULTS: The participation rate was 78.8% (473 participants). Patients < 65 years (x² =70.8, Р<0.001), those with lower education level (x² =82.1, p<0.001), and patients living in villages (x² =4.3, p<0.05) reported difficulties more frequently and they needed help for self-testing by iFOBT. Positive test was found in 8.5% of all participants. Of them 19 persons (48.7%) had haemorrhoids, 8 (20.0%) benign neoplasms, and 3 (7.5%) had CRC. CONCLUSIONS: CRC screening study by means of iFOBT as a point-of-care test proved to be feasible, since a high participation rate was obtained.

FibroSURE as a noninvasive marker of liver fibrosis and inflammation in chronic hepatitis B.

BACKGROUND: Noninvasive markers of liver fibrosis have not been extensively studied in patients with chronic hepatitis B virus (HBV) infection. Our aim was to evaluate the capacity of FibroSURE, one of the two noninvasive fibrosis indices commercially available in the United States, to identify HBV infected patients with moderate to severe fibrosis. METHODS: Forty-five patients who underwent liver biopsy at a single tertiary care center were prospectively enrolled and had FibroSURE performed within an average interval of 11 days of the biopsy. RESULTS: Of the 45 patients, 40% were Asian, 40% were African American, and 13% were Caucasian; 27% were co-infected with HIV and 67% had no or mild fibrosis. We found FibroSURE to have moderate capacity to discriminate between patients with moderate to high fibrosis and those with no to mild fibrosis (area under receiver operating characteristic [AUROC] curve = 0.77; 95% confidence interval [CI] [0.61, 0.92]). When we combined the fibrosis score determined by FibroSURE with aspartate aminotransferase (AST) measurements and HIV co-infection status, the discriminatory ability significantly improved reaching an AUROC of 0.90 (95% CI [0.80, 1.00]). FibroSURE also had a good ability to differentiate patients with no or mild from those with moderate to high inflammation (AUROC = 0.83; 95% CI [0.71, 0.95]). CONCLUSIONS: FibroSURE in combination with AST levels has an excellent capacity to identify moderate to high fibrosis stages in chronic HBV-infected patients. These data suggest that FibroSURE may be a useful substitute for liver biopsy in chronic HBV infection.

Predictors of a severe course and mortality in patients with COVID-19-associated pneumonia.

INTRODUCTION: Severe and critical forms of SARS-CoV-2 pneumonia are associated with high morbidity and mortality. Numerous research studies have been conducted around the world to investigate various variables (demographic, clinical, laboratory, etc.) in an attempt to understand the relationships between them and the course and outcome of patients with COVID-19 infection and pneumonia.

Determinants of hepatitis C virus treatment completion and efficacy in drug users assessed by meta-analysis.

BACKGROUND: Hepatitis C virus (HCV)-infected drug users (DUs) have largely been excluded from HCV care. We conducted a systematic review and meta-analysis of the literature on treatment completion and sustained virologic response (SVR) rates in DUs. We assessed the effects of different treatment approaches and services to promote HCV care among DUs as well as demographic and viral characteristics. METHODS: Studies of at least 10 DUs treated with pegylated interferon/ribavirin that reported SVR were analyzed. Heterogeneity was assessed (Cochran test) and investigated (meta-regression), and pooled rates were estimated (random effects). RESULTS: Thirty-six studies comprising 2866 patients were retrieved. The treatment completion rate among DUs was 83.4% (95% confidence interval [CI], 77.1%-88.9%). Among studies that included addiction-treated and untreated patients during HCV therapy, the higher the proportion of addiction-treated patients, the higher the HCV treatment completion rate (P < .0001). After adjusting for human immunodeficiency virus (HIV)/HCV coinfection, sex, and treatment of addiction, support services during antiviral therapy increased treatment completion (P < .0001). The pooled SVR rate was 55.5% (95% CI, 50.6%-60.3%). Genotype 1/4 (P = .0012) and the proportion of HIV-coinfected DUs (P = .0173) influenced the SVR rate. After adjusting for HCV genotype 1/4 and HIV/HCV coinfection, the SVR rate was positively correlated with involvement of a multidisciplinary team (P < .0001). CONCLUSIONS: Treatment of addiction during HCV therapy results in higher treatment completion. Our pooled SVR rate is similar to that obtained in registration trials in the general population. Treatment of addiction during HCV therapy will likely be important for HCV-infected DUs undergoing treatment with more complex regimens including direct-acting antivirals.

Laparoscopic exploration of bile ducts in patients with calculosis. Indications, methods and first results.

INTRODUCTION: In the last few years there has been a resurgence of laparoscopic exploration of the common bile duct as an alternative to endoscopic retrograde cholangiopancreatography (ERCP), the primary method for diagnosis and treatment of biliary tract calculosis. AIM: The aim of this study was to clarify the indications and methods for performing laparoscopic bile duct exploration, based on our experience in the field and data from the literature. PATIENTS AND METHODS: We recruited 12 patients who underwent laparoscopic exploration and stone extraction from the common bile duct (CBD) in the surgical ward of Kaspela Hospital, Plovdiv over the period January 2011 to January 2012. The diagnostic and therapeutic modalities used in the study included laboratory tests, ultrasound study, CT, ERCP, digital cholangiography, clamp and balloon stone extraction, primary suture and choledochoduodenostomy. RESULTS: Stone extraction was successfully performed in 8 patients using the transcystic approach through an incision used in the cholangiography. The procedure failed in the remaining four patients and we used here 2-cm longitudinal choledochotomy. In two patients the control cholangiography following the extraction of stones demonstrated complete clearance of the biliary tree and free passage of contrast agent from bile duct to duodenum (patent ampulla of Vater). In these two patients we performed a primary closure of the choledochotomy with a single interrupted suture ("ideal choledochotomy"). In two patients from the choledochotomy group, the control cholangiography showed the presence of residual stones or fragments trapped above the sphincter of Oddi with no contrast medium in the duodenum. In these cases we completed this procedure with latero-lateral choledochoduodenostomy by Flërken. All patients had a smooth postoperative course with no recorded complications. The average hospital stay was 5 days. CONCLUSIONS: Laparoscopic exploration of the biliary ducts in calculosis is an efficient, safe and reliable method to manage this serious complication of gall-stone disease in the hands of an experienced laparoscopic surgeon. The results of its application are comparable and in some cases even better than those of ERCP used as a therapeutic procedure as regards clearance of the CBD and the complications involved in these two procedures.

Post-authorization safety surveillance of Ad.26.COV2.S vaccine: Reports to the Vaccine Adverse Event Reporting System and v-safe, February 2021-February 2022.

BACKGROUND: On 2/27/2021, FDA authorized Janssen COVID-19 Vaccine (Ad.26.COV2.S) for use in individuals 18 years of age and older. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system, and v-safe, a smartphone-based surveillance system. METHODS: VAERS and v-safe data from 2/27/2021 to 2/28/2022 were analyzed. Descriptive analyses included sex, age, race/ethnicity, seriousness, AEs of special interest (AESIs), and cause of death. For prespecified AESIs, reporting rates were calculated using the total number of doses of Ad26.COV2.S administered. For myopericarditis, observed-to-expected (O/E) analysis was performed based on the number verified cases, vaccine administration data, and published background rates. Proportions of v-safe participants reporting local and systemic reactions, as well as health impacts, were calculated. RESULTS: During the analytic period, 17,018,042 doses of Ad26.COV2.S were administered in the United States, and VAERS received 67,995 reports of AEs after Ad26.COV2.S vaccination. Most AEs (59,750; 87.9 %) were non-serious and were similar to those observed during clinical trials. Serious AEs included COVID-19 disease, coagulopathy (including thrombosis with thrombocytopenia syndrome; TTS), myocardial infarction, Bell's Palsy, and Guillain-Barré syndrome (GBS). Among AESIs, reporting rates per million doses of Ad26.COV2.S administered ranged from 0.06 for multisystem inflammatory syndrome in children to 263.43 for COVID-19 disease. O/E analysis revealed elevated reporting rate ratios (RRs) for myopericarditis; among adults ages 18-64 years, the RR was 3.19 (95 % CI 2.00, 4.83) within 7 days and 1.79 (95 % CI 1.26, 2.46) within 21 days of vaccination. Of 416,384 Ad26.COV2.S recipients enrolled into v-safe, 60.9 % reported local symptoms (e.g. injection site pain) and 75.9 % reported systemic symptoms (e.g., fatigue, headache). One-third of participants (141,334; 33.9 %) reported a health impact, but only 1.4 % sought medical care. CONCLUSION: Our review confirmed previously established safety risks for TTS and GBS and identified a potential safety concern for myocarditis.

Surveillance of COVID-19 vaccine safety among elderly persons aged 65 years and older.

BACKGROUND: Monitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public. METHODS: We evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. FINDINGS: Four outcomes met the threshold for a statistical signal following BNT162b2 vaccination including pulmonary embolism (PE; RR = 1.54), acute myocardial infarction (AMI; RR = 1.42), disseminated intravascular coagulation (DIC; RR = 1.91), and immune thrombocytopenia (ITP; RR = 1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the mRNA-1273 or Ad26 COV2.S vaccines. INTERPRETATION: This early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following BNT162b2 vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.