Sudden sensorineural hearing loss (SSNHL), a rare audiological condition that accounts for 1% of all cases of sensorineural hearing loss, can cause permanent hearing damage. Soon after the launch of global COVID-19 vaccination campaigns, the World Health Organization released a signal detection about SSNHL cases following administration of various COVID-19 vaccines. Post-marketing studies have been conducted in different countries using either pharmacovigilance or medico-administrative databases to investigate SSNHL as a potential adverse effect of COVID-19 vaccines. Here, we examine the advantages and limitations of each type of post-marketing study available. While pharmacoepidemiological studies highlight the potential association between drug exposure and the event, pharmacovigilance approaches enable causality assessment. The latter objective can only be achieved if an expert evaluation is provided using internationally validated diagnostic criteria. For a rare adverse event such as SSNHL, case information and quantification of hearing loss are mandatory for assessing seriousness, severity, delay onset, differential diagnoses, corrective treatment, recovery, as well as functional sequelae. Appropriate methodology should be adopted depending on whether the target objective is to assess a global or individual risk.

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The helicase-primase inhibitor amenamevir (AMNV) was approved for herpes zoster in Japan in 2017. The authors conducted a 1-month postmarketing observational study to evaluate the real-world safety and efficacy (cutaneous improvement and pain resolution) of AMNV in patients with herpes zoster. Of the 3453 patients registered between March 2018 and December 2020, 3110 were included in the safety analyses. The mean age (±standard deviation) was 63.7 ± 17.5 years, with 57.9% of patients aged ≥65 years. Most patients had mild (53.3%) or moderate (41.0%) cutaneous lesions. Regarding pain, 43.9%, 25.6%, and 12.5% of patients had pain at the levels of 1-3, 4-6, and 7-10 on the numerical rating scale. In total, 30.0%, 27.2%, and 16.1% of patients were concomitantly treated with analgesics: acetaminophen, nonsteroidal anti-inflammatory drugs, and Ca2+ channel α 2δ ligands, respectively, and 10.6% were treated with topical antiherpetic drugs. Adverse drug reactions occurred in 0.77% of patients, including four serious adverse drug reactions in four patients (hyponatremia, thrombocytopenia, rash, and rhabdomyolysis). Regarding important potential risks, renal disorder, cardiovascular events, and decreased platelets were observed in one, one, and two patients, respectively. Concerning efficacy, the cutaneous improvement rate (significantly improved or improved) was 95.5%, with significantly higher improvement rates in patients treated with AMNV for 7 days and in patients with less severe cutaneous lesions or less pain. Factors affecting the time to pain resolution were the severity of cutaneous lesions and pain at the start of AMNV treatment and older age. This study demonstrated that the AMNV is safe and effective in patients with herpes zoster in a real-world clinical setting.

UNASSIGNED: Between 2012 and 2017, the U.S. Food and Drug Administration (FDA) approved 10 antidiabetic indicated therapies. Due to the limited literature on voluntarily reported safety outcomes for recently approved antidiabetic drugs, this study investigated adverse drug reactions (ADRs) reported in the FDA Adverse Event Reporting System (FAERS).
UNASSIGNED: A disproportionality analysis of spontaneously reported ADRs was conducted. FAERS reports from January 1, 2012 to March 31, 2022 were compiled, allowing a 5-year buffer following drug approval in 2017. Reporting odds ratios were calculated for the top 10 ADRs, comparing new diabetic agents to the other approved drugs in their therapeutic class.
UNASSIGNED: 127,525 reports were identified for newly approved antidiabetic medications listed as the primary suspect (PS). For sodium-glucose co-transporter-2 (SGLT-2) inhibitors, the odds of blood glucose increased, nausea, and dizziness being reported was greater for empagliflozin. Dapagliflozin was associated with greater reports of weight decreased. Canagliflozin was found to have a disproportionally higher number of reports for diabetic ketoacidosis, toe amputation, acute kidney injury, fungal infections, and osteomyelitis. Assessing glucagon-like peptide-1 (GLP-1) receptor agonists, dulaglutide and semaglutide were associated with greater reports of gastrointestinal adverse drug reactions. Exenatide was disproportionally associated with injection site reactions and pancreatic carcinoma reports.
UNASSIGNED: Pharmacovigilance studies utilizing a large publicly available dataset allow an essential opportunity to evaluate the safety profile of antidiabetic drugs utilized in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved antidiabetic medications to determine causality.
Adverse drug reactions reported for antidiabetic medications Introduction: This study investigated the trends in voluntary reporting of adverse drug reactions for recently approved antidiabetic medications. Methods: Data from the FDA Adverse Events Reporting System were evaluated. The top 10 adverse drug reactions were compared between antidiabetic medications in the same therapeutic class. Results: We identified 127,525 adverse drug reaction reports for the newer approved antidiabetic medications. For SGLT-2 inhibitors, empagliflozin was associated with greater reports of blood glucose increase, nausea, and dizziness; weight decreased was reported more often for dapagliflozin; and diabetic ketoacidosis, toe amputation, acute kidney injury, fungal infections, and osteomyelitis were reported more commonly for canagliflozin. Assessing GLP-1 receptor agonists, the odds of gastrointestinal adverse drug reactions being reported was greater for dulaglutide and semaglutide. Exenatide was disproportionally associated with injection site reactions and pancreatic carcinoma reports. Conclusion: Medication safety studies using a large publicly available dataset allows an essential opportunity to evaluate the safety profile of antidiabetic drugs in the real-world setting. Additional research is needed to determine if the reported safety concerns for recently approved antidiabetic medications to determine causality.

UNASSIGNED: Sodium-glucose co-transporter-2 (SGLT2) inhibitors such as empagliflozin are increasingly prescribed as initial glucose-lowering drugs for type 2 diabetes (T2D), based on their cardiorenal benefits. However, information regarding the safety and the effectiveness of monotherapy with SGLT2 inhibitors in routine clinical practice is limited.
UNASSIGNED: We analyzed data from a prospective, 3-year, post-marketing surveillance study of empagliflozin in Japan. We evaluated adverse drug reactions (ADRs) (the primary endpoint) and glycemic effectiveness with or without other glucose-lowering drugs.
UNASSIGNED: 7931 T2D patients were treated with empagliflozin. At baseline, mean age was 58.7 years, 63.0% were male, and 1835 (23.14%) were not receiving other glucose-lowering drugs. ADRs occurred in 141 (7.68%) and 875 (14.62%) patients initiating empagliflozin as monotherapy or combination therapy, respectively. The most frequent ADRs of special interest with empagliflozin as monotherapy or combination therapy were urinary tract infections (0.82% and 1.14% of patients, respectively) and excessive/frequent urination (0.65%, 1.50%). At last observation, glycated hemoglobin level was reduced by a mean of 0.78% with empagliflozin monotherapy (from baseline mean of 7.55%) and 0.74% with combination therapy (baseline 8.16%).
UNASSIGNED: Empagliflozin is well tolerated and effective in clinical practice in Japan when initiated as monotherapy or combination therapy.

BACKGROUND: The World Health Organization recently described sudden sensorineural hearing loss (SSNHL) as a possible adverse effect of COVID-19 vaccines. Recent discordant pharmacoepidemiologic studies invite robust clinical investigations of SSNHL after COVID-19 messenger RNA (mRNA) vaccines. This postmarketing surveillance study, overseen by French public health authorities, is the first to clinically document postvaccination SSNHL and examine the role of potential risk factors.
OBJECTIVE: This nationwide study aimed to assess the relationship between SSNHL and exposure to mRNA COVID-19 vaccines and estimate the reporting rate (Rr) of SSNHL after mRNA vaccination per 1 million doses (primary outcome).
METHODS: We performed a retrospective review of all suspected cases of SSNHL after mRNA COVID-19 vaccination spontaneously reported in France between January 2021 and February 2022 based on a comprehensive medical evaluation, including the evaluation of patient medical history, side and range of hearing loss, and hearing recovery outcomes after a minimum period of 3 months. The quantification of hearing loss and assessment of hearing recovery outcomes were performed according to a grading system modified from the Siegel criteria. A cutoff of 21 days was used for the delay onset of SSNHL. The primary outcome was estimated using the total number of doses of each vaccine administered during the study period in France as the denominator.
RESULTS: From 400 extracted cases for tozinameran and elasomeran, 345 (86.3%) spontaneous reports were selected. After reviewing complementary data, 49.6% (171/345) of documented cases of SSNHL were identified. Of these, 83% (142/171) of SSNHL cases occurred after tozinameran vaccination: Rr=1.45/1,000,000 injections; no difference for the rank of injections; complete recovery in 22.5% (32/142) of cases; median delay onset before day 21=4 days (median age 51, IQR 13-83 years); and no effects of sex. A total of 16.9% (29/171) of SSNHL cases occurred after elasomeran vaccination: Rr=1.67/1,000,000 injections; rank effect in favor of the first injection (P=.03); complete recovery in 24% (7/29) of cases; median delay onset before day 21=8 days (median age 47, IQR 33-81 years); and no effects of sex. Autoimmune, cardiovascular, or audiovestibular risk factors were present in approximately 29.8% (51/171) of the cases. SSNHL was more often unilateral than bilateral for both mRNA vaccines (P<.001 for tozinameran; P<.003 for elasomeran). There were 13.5% (23/142) of cases of profound hearing loss, among which 74% (17/23) did not recover a serviceable ear. A positive rechallenge was documented for 8 cases.
CONCLUSIONS: SSNHL after COVID-19 mRNA vaccines are very rare adverse events that do not call into question the benefits of mRNA vaccines but deserve to be known given the potentially disabling impact of sudden deafness. Therefore, it is essential to properly characterize postinjection SSNHL, especially in the case of a positive rechallenge, to provide appropriate individualized recommendations.

Case investigation and contact tracing are core public health activities used to interrupt disease transmission. These activities are traditionally conducted manually. During periods of high COVID-19 incidence, US health departments were unable to scale up case management staff to deliver effective and timely contact-tracing services. In response, digital contact tracing (DCT) apps for mobile phones were introduced to automate these activities. DCT apps detect when other DCT users are close enough to transmit COVID-19 and enable alerts to notify users of potential disease exposure. These apps were deployed quickly during the pandemic without an opportunity to conduct experiments to determine effectiveness. However, it is unclear whether these apps can effectively supplement understaffed manual contact tracers.
The aims of this study were to (1) evaluate the effectiveness of COVID-19 DCT apps deployed in the United States during the COVID-19 pandemic and (2) determine if there is sufficient DCT adoption and interest in adoption to meet a minimum population use rate to be effective (56%). To assess uptake, interest and safe use covariates were derived from evaluating DCTs using the American Psychological Association App Evaluation Model (AEM) framework.
We analyzed data from a nationally representative survey of US adults about their COVID-19-related behaviors and experiences. Survey respondents were divided into three segments: those who adopted a DCT app, those who are interested but did not adopt, and those not interested. Descriptive statistics were used to characterize factors of the three groups. Multivariable logistic regression models were used to analyze the characteristics of segments adopting and interested in DCT apps against AEM framework covariates.
An insufficient percentage of the population adopted or was interested in DCTs to achieve our minimum national target effectiveness rate (56%). A total of 17.4% (n=490) of the study population reported adopting a DCT app, 24.7% (n=697) reported interest, and 58.0% (n=1637) were not interested. Younger, high-income, and uninsured individuals were more likely to adopt a DCT app. In contrast, people in fair to poor health were interested in DCT apps but did not adopt them. App adoption was positively associated with visiting friends and family outside the home (odds ratio [OR] 1.63, 95% CI 1.28-2.09), not wearing masks (OR 0.52, 95% CI 0.38-0.71), and adopters thinking they have or had COVID-19 (OR 1.60, 95% CI 1.21-2.12).
Overall, a small percentage of the population adopted DCT apps. These apps may not be effective in protecting adopters\' friends and family from their maskless contacts outside the home given low adoption rates. The public health community should account for safe use behavioral factors in future public health contact-tracing app design. The AEM framework was useful in developing a study design to evaluate DCT effectiveness and safety.

Studies of rare side effects of new drugs with limited exposure may require pooling of multiple data sources. Federated Analyses (FA) allow real-time, interactive, centralized statistical processing of individual-level data from different data sets without transfer of sensitive personal data.
We review IT-architecture, legal considerations, and statistical methods in FA, based on a Swedish Medical Products Agency methodological development project.
In a review of all post-authorisation safety studies assessed by the EMA during 2019, 74% (20/27 studies) reported issues with lack of precision in spite of mean study periods of 9.3 years. FA could potentially improve precision in such studies. Depending on the statistical model, the federated approach can generate identical results to a standard analysis. FA may be particularly attractive for repeated collaborative projects where data is regularly updated. There are also important limitations. Detailed agreements between involved parties are strongly recommended to anticipate potential issues and conflicts, document a shared understanding of the project, and fully comply with legal obligations regarding ethics and data protection. FA do not remove the data harmonisation step, which remains essential and often cumbersome. Reliable support for technical integration with the local server architecture and security solutions is required. Common statistical methods are available, but adaptations may be required.
Federated Analyses require competent and active involvement of all collaborating parties but have the potential to facilitate collaboration across institutional and national borders and improve the precision of postmarketing drug safety studies.

BACKGROUND: Umeclidinium/vilanterol (UMEC/VI; ANORO ELLIPTA, GSK) is a commonly used dual bronchodilator. This study evaluated the safety and effectiveness of UMEC/VI in Korean patients with chronic obstructive pulmonary disease (COPD) over a 6-year period.
METHODS: This was an open-label, multicentre, observational, post-marketing surveillance study. A total of 3,375 patients were enrolled consecutively in 52 hospitals, by 53 physicians, between July 2014 and July 2020. Patients who were administered UMEC/VI (fixed-dose 62.5 μg/25 μg) at least once and were monitored for safety and effectiveness were included in the analysis. Incidence and severity of adverse events (AEs) reported after administrating at least one dose of UMEC/VI were monitored, including unexpected adverse events (UAEs) and adverse drug reactions (ADRs). Effectiveness of UMEC/VI after 24 weeks of administration was also assessed using physician\'s evaluation (effective, ineffective/no change, worsening, indeterminable) and lung function improvement.
RESULTS: Of 3,375 patients, 3,086 were included in the safety assessment group (mean age±standard deviation: 69.76±8.80 years; 85.9% male [n=2,652]; 73.1% aged ≥65 years [n=2,255]). The overall incidence of AEs was 28.8% (n=890), of which 2.2% (n=67) were ADRs. Serious AEs and UAEs were reported in 181 (5.9%) and 665 (21.6%) patients, respectively, and two patients (<0.1%) reported unexpected severe ADR. Of the 903/3,086 patients analysed for effectiveness, most (82.8%, n=748) showed overall disease improvement after UMEC/VI treatment.
CONCLUSIONS: This study confirmed UMEC/VI administered to Korean patients according to the prescribing information was well-tolerated and can be considered an effective option for COPD treatment.

The meningococcal serogroups A, C, W, and Y tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix®; Pfizer Ltd, Sandwich, Kent, UK) is licensed in more than 80 countries worldwide for the prevention of meningococcal disease caused by serogroups A, C, W, and Y in individuals throughout their lifespans. This report summarizes safety data from the MenACWY-TT clinical development program and postmarketing experience.
Within the clinical study program, reactogenicity data were based on 3 primary studies, including a large pooled analysis across multiple age groups, and long-term safety data were derived from 3 studies evaluating long-term antibody persistence. Postmarketing safety data through April 19, 2021, were collected and analyzed in connection with the MenACWY-TT Periodic Safety Update Report.
Approximately 32 million doses of MenACWY-TT have been administered worldwide, with more than 21,530 additional individuals receiving MenACWY-TT as part of clinical trials. The safety profile of MenACWY-TT was consistent between the clinical study program and the postmarketing experience, as well as with other licensed meningococcal vaccines. The most commonly observed adverse events (AEs) were pyrexia/fever, headache, injection site pain/reactions, nausea/vomiting, and fatigue; serious AEs were rare relative to the number of doses administered. Several cases of serogroup replacement/lack of efficacy were observed in the 1-year postmarketing period but did not appear to be related to MenACWY-TT use.
Extensive data derived from clinical trials and postmarketing experience indicate a consistently favorable safety profile for MenACWY-TT across a wide range of age groups.