Incidence Of Any Adverse Events Research Articles

PO-04-108 THE EFFICACY AND SAFETY OF ETRIPAMIL NASAL SPRAY FOR THE TREATMENT OF ACUTE PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Paroxysmal Supraventricular Tachycardia (PSVT) treatment requires medically supervised intervention. This is derived from the lack of effective and safe self-administrated treatment for PSVT. Etripamil is a novel short-acting calcium channel blocker with a rapid intranasal spray and shows promising potential for the unsupervised treatment of PSVT, especially in the dosage of 70 mg. We aim to evaluate the efficacy and safety of Etripamil for the acute conversion of PSVT. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through December 1st, 2022. RevMan version 5.4 software was used to pool dichotomous outcomes using risk ratio (RR) presented with the corresponding confidence interval (CI) while using the fixed-effects model. Three RCTs with a total of 496 patients (296 in the etripamil group and 200 in the placebo group) were included in our analysis. Etripamil was effective for PSVT conversion at 15 minutes (RR: 1.84 with 95% CI [1.37, 2.48]), 30 minutes (RR: 1.86 with 95% CI [1.42, 2.44]), and at 60 minutes after the drug administration (RR: 1.25 with 95% CI [1.05, 1.50]); decreasing medical intervention seeking (RR: 0.58 with 95% CI [0.37, 0.90]); and decreasing emergency (ER) visits (RR: 0.61 with 95% CI [0.38, 0.97]). However, there was no difference at 300 minutes (RR: 1.10 with 95% CI [0.97, 1.25]). Also, Etripamil was associated with higher rates of the incidence of any adverse events (AEs) (RR: 3.17 with 95% CI [2.15, 4.69]), nasal discomfort (RR: 3.82 with 95% CI [2.01, 7.24]), nasal congestion (RR: 5.89 with 95% CI [1.93, 17.97]), epistaxis (RR: 4.74 with 95% CI [1.21, 18.50]), and rhinorrhea (RR: 3.53 with 95% CI [1.22, 10.26]) with no difference regarding any serious adverse events (SAEs) incidence (RR: 0.30 with 95% CI [0.01, 7.21]). Etripamil was effective in inducing PSVT termination for up to 60 minutes and reduced medical treatment seeking and ER visits. Also, Etripamil was associated with higher rates of AEs, including epistaxis, nasal congestion, and rhinorrhea; however, it was not associated with SAEs. Therefore, Etripamil constitutes a promising strategy for PSVT self-termination without medical supervision; however, further RCTs are required before endorsement in clinical practice.

Review of the Trace Amine-Associated Receptor 1 (TAAR1) Agonist Ulotaront: Part II—Summary of Initial Clinical Efficacy/Safety Results

AbstractIntroductionUlotaront is a trace amine-associated receptor 1 (TAAR1) agonist with serotonin 5-HT1A agonist activity that has received FDA Breakthrough Therapy Designation for the treatment of schizophrenia. Here we summarize ongoing clinical research characterizing the efficacy and safety of ulotaront as a member of the novel trace amine-associated receptor 1 (TAAR1) agonist class.MethodsSummarized are results from a double-blind, placebo-controlled study to evaluate the efficacy and safety of ulotaront (50 mg or 75 mg) in an acute exacerbation of schizophrenia, and a 6-month, open-label follow-up study. Also summarized are post-hoc analyses evaluating negative symptom efficacy, and key safety and adverse event (AE) outcomes.ResultsIn the short-term study, treatment with ulotaront was associated with significant (p<0.001) endpoint improvement in the PANSS total score (effect size [ES]: 0.45), the CGI-Severity score (ES: 0.52) and the Brief Negative Symptom Scale total score (ES: 0.48). The incidence of any AE was lower on ulotaront versus placebo (45.8% vs. 50.4%), and the number needed to harm (NNH) for individual AEs on ulotaront were all >40. Ulotaront was associated with lower risk for antipsychotic class-related AEs (extrapyramidal symptoms, akathisia, somnolence, nausea/vomiting, increased weight/metabolic labs, prolactinemia). The 6-month study demonstrated further improvement, with a completion rate (67%) that was higher than reported for current dopamine D2 antipsychotics.ConclusionsThe emerging profile of ulotaront is characterized by significant improvement in positive and negative symptoms of schizophrenia. The safety and tolerability profile of ulotaront is markedly different with respect to antipsychotic class-related AEs. The benefit-risk profile of ulotaront, as a member of a novel TAAR1 agonist class, is distinguished from antipsychotics by lack of AEs related to D2 and serotonin 5-HT2A receptor blockade.FundingSunovion Pharmaceuticals, Inc., and Otsuka Pharmaceutical Development & Commercialization, Inc.

A Meta-Analysis Evaluating the Effectiveness and Safety of Upadacitinib in Treating Rheumatoid Arthritis in Patients With Inadequate Response to Disease-Modifying Anti-Rheumatic Drugs.

Upadacitinib, an oralJanus kinase(JAK)inhibitor, is used to manage rheumatoid arthritis. The objective was to generate statistical evidence from the existing data for upadacitinibefficacy and safety in various treatment regimens with different dosages in active rheumatoid arthritis patients. We searched PubMed, Cochrane, and ClinicalTrials.gov using PRISMA guidelines, providing data on the efficacy and safety of upadacitinibversus placebo in rheumatoid arthritis. 20% improvement in the American College of Rheumatology (ACR20) score response at 12 weeks was the primary outcome measure. Safety in adverse events, infections, or hepatic dysfunction was considered. The Mantel-Haenszel formula with random effect was used for the pooled odds ratio (OR) at a 95% confidence interval (CI) for dichotomous data. Meta-analysis was performed using RevMan version 5.4. Statistical heterogeneity was reported using I2 statistics; I2 > 75% was considered significant heterogeneity. A P value of less than 0.05 was considered significant. Data from 3233 patients were included in the analysis. The use of upadacitinib was associated with increased rates of achieving an ACR20 response compared with placebo (pooled OR 3.71; 95% CI 3.26-4.23; p-value <0.00001). Compared to a placebo, a 12 mg twice daily dose had the greatest effect, followed by a 15 mg once daily dose. Compared to the placebo, the incidence of any adverse event (pooled OR 1.66; 95% CI 1.36-2.02; p-value 0.0001) and infection (pooled OR 1.46; 95% CI 1.23-1.74; p-value 0.001) was found to be significantly higher in upadacitinib. Other adverse events, such as hepatic disorders and herpes zoster infections, were not statistically significant (p-value> 0.05). Maximum adverse events were seen at 12 mg twice daily. Upadacitinib, 15 mg once daily in combination with Methotrexate, was the most efficacious treatment regimen and was not associated with a significant risk for treatment-related adverse events in rheumatoid arthritis patients.

Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new ICI combination therapy, and its efficacy has been reported in various types of cancer. However, the safety profile of DT remains unclear, especially considering rare adverse events (AEs). We aimed to assess the frequency of AEs associated with DT. This study type is a systematic review and meta-analysis. Four databases were searched for articles. Randomized trials, single-arm trials, and prospective and retrospective observational studies were included. The type of cancer, previous treatment, and performance status were not questioned. Major AE indicators such as any AE and the pooled frequency of each specific AE were used as outcomes. As a subgroup analysis, we also compared cases in which DT was performed as first-line treatment with those in which it was performed as second-line or later treatment. The protocol for this systematic review was registered on the University Hospital Medical Information Network (UMIN) Center website (ID: UMIN000046751). Forty-one populations including 3099 patients were selected from 30 articles. Pooled frequencies of key AE indicators are shown below: any AEs, 77.8% [95% confidence interval (CI): 67.9-87.6]; grade ⩾ 3 AEs, 29.3% (95% CI: 24.2-34.4); serious AEs, 34.9% (95% CI: 28.1-41.7); AE leading to discontinuation, 13.3% (95% CI: 9.3-17.4); treatment-related deaths, 0.98% (95% CI: 0.5-1.5). AEs with a frequency exceeding 15% are shown below: fatigue, 30.1% (95% CI: 23.8-36.3); diarrhea, 21.7% (95% CI: 17.8-25.6); pruritus 17.9% (95% CI: 14.4-21.3); decreased appetite, 17.7% (95% CI: 13.7-22.0); nausea, 15.6% (95% CI: 12.1-19.6). There were no significant differences in these pooled frequencies between subgroups. The incidence of any AE in DT therapy was approximately 78%, and the incidence of grade 3 or higher AEs was approximately 30%, which was independent of prior therapy.

Growth factor concentrate therapy for management of hair loss: a prospective, real-world study

&lt;p class="abstract"&gt;The present pilot study was conducted to determine the role of growth factor concentrate (GFC) therapy, a modified platelet-rich plasma (PRP) technique for the management of androgenetic alopecia. In this study, patients diagnosed with androgenic alopecia were treated with subcutaneous injections of GFC in the scalp. A total of 3 injections were administered 4 weeks apart, and the patients were followed up for 24 weeks. The treatment outcomes were assessed by taking global macroscopic photographs, trichoscopic photomicrographs, and by performing a hair pull test after 24 weeks of therapy and compared to the baseline. To determine the safety of the treatment, the incidence of any adverse event was recorded throughout the study period. The patient’s self-satisfaction was assessed using a survey-based questionnaire at the end of the study period. The global macroscopic photographs showed a significant improvement in hair growth post-GFC therapy in all 5 patients. These findings were supported by trichoscopic photomicrographs, in which a pronounced improvement in hair density along with a decrease in the shaft diameter variability and number of yellow dots were observed. Hair pull test was found to be negative in 100% of patients 4 months post-therapy. The therapy was found to be well tolerated with high patient satisfaction (80%). GFC therapy was found to have a promising role in the management of androgenetic alopecia in both male and female patients.&lt;/p&gt;

570 FRAILTY AND DISABILITY IN OLDER PATIENTS AND THE EFFECTS OF APIXABAN ON QUALITY OF LIFE AND DEPRESSIVE SYMPTOMS. THE EXPERIENCE OF THE APULEIO STUDY

Abstract Introduction The APULEIO study was designed to describe the psychological effects of apixaban in Italian elderly patients with non-valvular atrial fibrillation (NVAF), deep vein thrombosis (DVT) or pulmonary embolism (PE). The existence of implications of treatment on health-related quality of life (HRQL) and mood is among the most important knowledge gaps in cardiovascular care of older subjects. Real-world data on these issues, essential to improve therapy adherence, are lacking. Aim of the present analysis was to evaluate the presence of a different response to oral anticoagulation in the disabled, frail and robust subjects enrolled in the study. Methods APULEIO was a multicenter, prospective, observational study including apixaban eligible patients. The 12-Item Short Form Health Survey (SF-12), the Beck Depression Inventory-II (BDI-II) and the Frail non-Disabled (FiND) questionnaire were used to evaluate, respectively, HRQL, depressive symptoms and the presence of disability and frailty. The findings of the baseline and the 6-month evaluation - end of the study - will be presented. Results Overall, 376 patients had complete data. Of these, 163 (43.4%), 111 (29.5%) and 102 (27.1%) subjects were, respectively, defined disabled, frail and robust. No differences for reason to anticoagulate were observed by FiND category (p=0.797; overall, AF: 77.1%; DVT/PE: 22.9%). Patients with disability were older (Disabled – D: 79±11; Frail - F: 72±12; Robust – R: 72±12 years; p&amp;lt;0.0001), more frequently women (D: 66.9; F: 43.2; R: 24.5%; p&amp;lt;0.0001), with a greater clinical complexity, as expressed by the CHA2DS2-VASc score (D: 4.3±1.5; F: 3.2±1.5; R: 2.9±1.6; p&amp;lt;0.0001), and showed a higher heart rate (D: 82±17; F: 77±14; R: 77±15 bpm; p=0.0414). BMI (overall, 27.5±4.7 Kg/m2; p=0.328), left ventricular ejection fraction (overall, 53±10%; p=0.453), and systolic (overall, 129±15 mmHg; p=0.219) and diastolic (overall, 76±10 mmHg; p=0.285) arterial pressure were similar among groups. The incidence of any adverse event was higher in those with disability (D: 14.1; F: 8.1; R: 3.9%; p=0.0190), but the proportion of those with serious adverse events was similar among categories (overall, 6.9%; p=0.105). When studying HRQL, at enrollment, the Physical Health composite score of the SF-12 was significantly different among groups (D: 32.7±7.9; F: 42.4±9.3; R: 45.6±8.0; p&amp;lt;0.0001). At the 6-month evaluation (D: 37.0±10.1; F: 43.9±8.8; R: 47.2±7.3; p&amp;lt;0.0001), only the improvement for disabled subjects was significant (p=0.0020). At Baseline, the Mental Health composite score of the SF-12 was lower in disabled and frail patients, when compared to robust ones (D: 46.8±9.8; F: 47.7±9.2; R: 51.4±8.6; p&amp;lt;0.0001). After 6 months, once again, only the improvement for disabled subjects (D: 37.0±10.1; F: 43.9±8.8; R: 47.2±7.3; p=0.0004) was significant (p&amp;lt;0.0001) and statistically greater than that observed for frail and robust patients. Regarding depressive symptoms, at enrollment, the BDI-II score was worse in the disabled and frail groups (D: 14.7±9.8; F: 9.0±8.1; R: 4.7±4.5; p&amp;lt;0.0001). At the 6-month assessment, it was possible to observe an improvement (D: 10.5±8.5; F: 6.8±7.8; R: 4.2±4.5; p&amp;lt;0.0001) in disabled (p&amp;lt;0.0001) and frail subjects (p=0.0112), but not in robust ones (p=0.1705). Conclusions The APULEIO study demonstrates that disability and frailty are common conditions in older subjects anticoagulated for AF and DVT/PE. Disabled patients present a higher clinical complexity than frail and robust ones. After 6 months of therapy, the use of apixaban is associated with a significant improvement of HRQL in disabled individuals and of depressive symptoms in disabled and frail ones. No changes were found in robust subjects. No differences by group were observed in the incidence of serious adverse events. These findings confirm the efficacy and safety of apixaban also when applying a multidimensional approach to high-risk geriatric populations.

Efficacy, immunogenicity and safety of COVID-19 vaccines in older adults: a systematic review and meta-analysis.

BackgroundOlder adults are more susceptible to severe health outcomes for coronavirus disease 2019 (COVID-19). Universal vaccination has become a trend, but there are still doubts and research gaps regarding the COVID-19 vaccination in the elderly. This study aimed to investigate the efficacy, immunogenicity, and safety of COVID-19 vaccines in older people aged ≥ 55 years and their influencing factors.MethodsRandomized controlled trials from inception to April 9, 2022, were systematically searched in PubMed, EMBASE, the Cochrane Library, and Web of Science. We estimated summary relative risk (RR), rates, or standardized mean difference (SMD) with 95% confidence interval (CI) using random-effects meta-analysis. This study was registered with PROSPERO (CRD42022314456).ResultsOf the 32 eligible studies, 9, 21, and 25 were analyzed for efficacy, immunogenicity, and safety, respectively. In older adults, vaccination was efficacious against COVID-19 (79.49%, 95% CI: 60.55−89.34), with excellent seroconversion rate (92.64%, 95% CI: 86.77−96.91) and geometric mean titer (GMT) (SMD 3.56, 95% CI: 2.80−4.31) of neutralizing antibodies, and provided a significant protection rate against severe disease (87.01%, 50.80−96.57). Subgroup and meta-regression analyses consistently found vaccine types and the number of doses to be primary influencing factors for efficacy and immunogenicity. Specifically, mRNA vaccines showed the best efficacy (90.72%, 95% CI: 86.82−93.46), consistent with its highest seroconversion rate (98.52%, 95% CI: 93.45−99.98) and GMT (SMD 6.20, 95% CI: 2.02−10.39). Compared to the control groups, vaccination significantly increased the incidence of total adverse events (AEs) (RR 1.59, 95% CI: 1.38−1.83), including most local and systemic AEs, such as pain, fever, chill, etc. For inactivated and DNA vaccines, the incidence of any AEs was similar between vaccination and control groups (p > 0.1), while mRNA vaccines had the highest risk of most AEs (RR range from 1.74 to 7.22).ConclusionCOVID-19 vaccines showed acceptable efficacy, immunogenicity and safety in older people, especially providing a high protection rate against severe disease. The mRNA vaccine was the most efficacious, but it is worth surveillance for some AEs it caused. Increased booster coverage in older adults is warranted, and additional studies are urgently required for longer follow-up periods and variant strains.

Efficacy and Safety of Botulinum Toxin Type A for Treatment of Glabellar Lines: A Network Meta-Analysis of Randomized Controlled Trials.

Botulinum toxin type A (BoNT/A) has been used in aesthetic applications worldwide, including glabellar lines. Currently, four BoNT/A preparations were approved for the improvement of moderate-to-severe glabellar lines: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and prabotulinumtoxinA. DaxibotulinumtoxinA is a new form of BoNT/A drug that is developed in clinical application. We performed this network meta-analysis (NMA) to assess the efficacy and safety of all these different BoNT/A formulations for treating glabellar lines. The investigators searched randomized controlled trials (RCTs) using the Medical Subject Headings (MeSH) terms "botulinum toxin" and "glabellar lines." We searched the relevant studies in electronic databases as following: PubMed, Elsevier, EMBASE and the Cochrane Library. The end points included the percentage of subjects with a glabellar line severity (GLS) score of none (0) or mild (1), and the percentage of subjects achieving ≥ 1-point and 2-point improvement in glabellar line severity at maximum frown at approximately month 1 by the investigators' assessment. All formulations of BoNT/A were far superior to placebo in efficacy. DaxibotulinumtoxinA was the only treatment that significantly increased the proportion of subjects achieving ≥ 1 point improvement in GLS score compared with other BoNT/A formulations. Moreover, daxibotulinumtoxinA was ranked the highest for the proportion of subjects achieving ≥ 2-point improvement in GLS score. No significant differences were revealed for the incidence of any adverse events (AEs) that related to treatment or drug among all BoNT/A preparations. The overall results of this NMA suggested that daxibotulinumtoxinA is a new BoNT/A preparation that may be not only more effective but also well-tolerated for the treatment of glabellar lines. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial.

SummaryBackgroundThe enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration.MethodsWe conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345).FindingsBetween June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%–100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%–99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%–100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%–2.86%) and -0.34% (95%CI: -2.78%–2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00–3.00) and 1.00 (95%CI: 0.75–1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines.InterpretationEV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated.FundingHubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd.

O18-6 Safety of encorafenib, binimetinib, plus cetuximab for Japanese patients with BRAF V600E metastatic colorectal cancer

The encorafenib, binimetinib, and cetuximab (triplet) regimen showed a similar incidence of any adverse events (AEs) and grade 3 or higher AEs compared to the control regimen in the global phase III BEACON trial. However, safety profile of the triplet regimen in Japanese patients (pts) is limited due to a small number of pts enrolled to the BEACON trial. The expanded access program (EAP) was conducted to evaluate the safety and efficacy of this regimen in Japan. Herein we report safety in details and treatment status.

Safety of an inactivated, whole-virion COVID-19 vaccine (CoronaVac) in people aged 60 years or older in Hong Kong: a modified self-controlled case series

BackgroundBecause evidence on the safety of COVID-19 vaccines in older adults is scarce, we aimed to evaluate the incidence and risk of adverse events after CoronaVac (Sinovac Biotech) vaccination in adults aged 60 years or older.MethodsIn this modified self-controlled case series, we enrolled adults aged 60 years or older who had received at least one dose of CoronaVac in Hong Kong between Feb 23, 2021, and Jan 31, 2022. We extracted population-based, electronic health record data from the clinical management system of the Hospital Authority on adverse events of special interest (from Jan 1, 2005, to Feb 23, 2022) and patients' demographic information (from Jan 1, 2018, to Jan 31, 2022), previous diagnoses (from Jan 1, 2018, to Jan 31, 2022), medication history (from Jan 1, 2018, to Jan 31, 2022), and laboratory tests, including those for SARS-CoV-2 infection (from Jan 1, 2018, to Jan 31, 2022). Details of vaccination status were provided by the Department of Health of the Hong Kong Government and were linked to data from the Hospital Authority with identity card numbers or passport numbers. Our outcomes were the overall incidence of any adverse event of special interest and the incidence rates of 30 adverse events of special interest, as suggested by the WHO Global Advisory Committee on Vaccine Safety, in the inpatient setting within 21 days (2 days for anaphylaxis) of either the first, second, or third CoronaVac dose compared with a baseline period. Individuals who had a history of a particular event between Jan 1, 2005, and Feb 23, 2021, were excluded from the corresponding analysis. We evaluated the risk of an adverse event of special interest using conditional Poisson regression, adjusting for seasonal effects.FindingsOf 1 253 497 individuals who received at least one dose of CoronaVac during the study period, 622 317 (49·6%) were aged at least 60 years and were included in the analysis. Our analysis sample received 1 229 423 doses of CoronaVac and had a mean age of 70·40 years (SD 8·10). 293 086 (47·1%) of 622 317 participants were men and 329 231 (52·9%) were women. The incidence of individual adverse events of interest ranged from 0·00 per 100 000 people to 57·49 per 100 000 people (thromboembolism). The first and third doses of CoronaVac were not associated with a significant excess risk of an adverse event of special interest within 21 days (or 2 days for anaphylaxis) of vaccination. After the second dose, the only significantly increased risk was for anaphylaxis (adjusted incidence rate ratio 2·61, 95% CI 1·08–6·31; risk difference per 100 000 people 0·61, 95% CI 0·03–1·81).InterpretationBecause older age is associated with poor outcomes after SARS-CoV-2 infection, the benefits of CoronaVac vaccination in older adults outweigh the risks in regions where COVID-19 is prevalent. Ongoing monitoring of vaccine safety is warranted.FundingThe Food and Health Bureau of the Government, Hong Kong Special Administrative Region, China and AIR@InnoHK, administered by the Innovation and Technology Commission.TranslationFor the Chinese translation of the abstract see Supplementary Materials section.

Self-Reported adverse events among Chinese healthcare workers immunized with COVID-19 vaccines composed of inactivated SARS-CoV-2

ABSTRACT Mass vaccination is critical to control the pandemic of coronavirus disease 2019 (COVID-19). Fear of adverse events (AEs) after COVID-19 vaccination is a main factor associated with vaccination hesitancy. We aimed to analyze AEs in healthcare workers (HCWs) vaccinated with COVID-19 vaccines (Aikewei or CoronaVac) composed of inactivated virus. We used a structured self-administered questionnaire to conduct two surveys on COVID-19 vaccination among HCWs in perinatal medicine and obstetrics/gynecology from April 5 to April 21, 2021. In total, 1392 HCWs who had received at least one vaccine dose were included. Of them, 1264 (90.8%) were females and 1047 (75.2%) received two doses. The overall incidence of any AEs after the first and second dose was 38.2% (532/1392) and 31.0% (325/1047) respectively (χ2 = 13.506, P = .0002). Female and HCWs aged 18–30 y were more likely to report AEs. The most common AEs were local reaction, accounting for 48.1% and 67.4% of all AEs after the first and second dose respectively. The systemic AEs were mainly neurological (9.8% and 4.8% after the first and second injection respectively) and flu-like symptoms (6.3% and 3.2%). Overall, most of AEs were mild, only 5.1% (after the first dose) and 2.8% (after the second dose) of individuals with AEs received symptomatic treatment or sick leaves, and none of them required hospitalization. Our data added more evidence that inactivated COVID-19 vaccines are highly safe. The data are valuable to overcome vaccine hesitancy associated with concerns about the safety of COVID-19 vaccines.

Immune Checkpoint Inhibitor Combination Therapy versus Sunitinib as First-Line Treatment for Favorable-IMDC-Risk Advanced Renal Cell Carcinoma Patients: A Meta-Analysis of Randomized Clinical Trials.

Background: Novel combination therapies have been shown to improve the outcomes of treatment-naive patients with locally advanced or metastatic renal cell carcinoma (aRCC). However, the optimal systemic therapy for aRCC of favorable risk has yet to be clarified. We aimed to evaluate the efficacy and safety of different immunotherapy (IO) combinations, either with another IO (IO–IO) or with an antiangiogenic (IO–TKI), versus sunitinib in the first-line setting in aRCC patients with favorable IMDC risk. Methods: We conducted a systematic search for evidence in PubMed, Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials published up to February 2021. The GRADE approach was used to assess the quality of evidence. Survival hazard ratios were extracted for analysis in the favorable-risk aRCC subgroup (IMDC). A sensitivity analysis was performed excluding trials of combination therapy without TKI. Results: Five randomized controlled phase III trials with a total of 1088 patients were included in the analysis. The studies compared different combinations versus sunitinib monotherapy. All clinical trials reported overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) data. Four out of five trials reported complete response (CR). There was no difference in OS nor PFS between treatment arms in the IMDC favorable-risk subgroup analysis (OS: HR = 1.07, 95% CI = 0.81–1.41; PFS: HR = 0.74, 95% CI = 0.46–1.19). A benefit in ORR and CR was found for combination therapy vs. sunitinib (ORR: HR = 1.89, 95% CI = 1.29–2.76; CR: HR = 3.58, 95% CI = 2.04–6.28). In the sensitivity analysis, including only IO–TKI vs. sunitinib, no difference in OS was found; however, an advantage in PFS was observed (OS: HR = 0.99, 95% CI 0.69–1.43; PFS: HR = 0.60 (0.45–0.81). The safety profile reported is consistent with previous reports. We did not find differences in the incidence of any adverse event (AE) or of grade ≥3 AEs. Conclusion: This meta-analysis shows that combinations of IO–KI as first-line treatment in favorable-IMDC-risk aRCC improve PFS, ORR, and CR, but not OS, versus sunitinib.

Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis.

The anti-thymic stromal lymphopoietin antibody (tezepelumab) has therapeutical potential for inadequately controlled asthma. However, evidence comparing tezepelumab with other biologics is scarce. To address this issue, we performed a network meta-analysis to compare and rank the efficacy of five treatments (tezepelumab, dupilumab, benralizumab, mepolizumab, and placebo) in overall participants and in subgroups stratified by the thresholds of type 2 inflammatory biomarkers, including peripheral blood eosinophil count (PBEC) and fractional exhaled nitric oxide (FeNO). The primary endpoints were annualized exacerbation rate (AER) and any adverse events (AAEs). In the ranking assessment using surface under the cumulative ranking curve (SUCRA) of AER, tezepelumab ranked the highest overall and across subgroups (based on PBEC and FeNO level thresholds). A significant difference was observed between tezepelumab and dupilumab in the patient subgroup with PBEC < 150, and between tezepelumab and benralizumab in overall participants and the patient subgroup with PBEC ≥ 300 and ≥150, respectively. There was no significant difference in the incidence of AAEs in the overall participants between each pair of five treatment arms. These results provide a basis for the development of treatment strategies for asthma and may guide basic, clinical, or translational research.

Long-term follow-up of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: post-marketing surveillance in Japan.

All Japanese patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab were enrolled in post-marketing surveillance (PMS) between June 2010 and August 2019 to assess the long-term effectiveness and safety of eculizumab. The reduction in intravascular hemolysis, the change in hemoglobin (Hb) level, and the change in renal function were assessed to determine the effectiveness of eculizumab. The types and frequencies of adverse events (AEs) were assessed to determine its safety. A total of 632 patients were enrolled and the median treatment duration was 3.6years. Treatment with eculizumab significantly reduced lactate dehydrogenase (LDH) levels and significantly increased Hb levels. These changes were maintained for up to 5years of treatment. An estimated glomerular filtration rate ≥ 60ml/min/1.73m2 and higher LDH level at baseline were associated with increases in Hb levels during eculizumab treatment. The overall incidence of any AE was 69.92/100 patient-years. Hemolysis was the most common AE (6.43/100 patient-years). The incidence of infection-related AEs was 20.57/100 patient-years, and included meningococcal infection in three patients (0.12/100 patient-years). This long-term follow-up of patients with PNH demonstrated the sustained effectiveness of eculizumab and supports its well-established safety profile.

Bilateral lumbar ultrasound-guided erector spinae plane block versus local anesthetic infiltration for perioperative analgesia in lumbar spine surgery: a randomized controlled trial.

Lumbar spinal surgery is associated with severe postoperative pain. We examined the analgesic efficacy of bilateral lumbar ultrasound-guided erector spinae plane block (ESPB) with ropivacaine compared with local infiltration. Patients undergoing elective lumbar arthrodesis were randomly divided into two groups. Control group received 0.375% ropivacaine 40 mL through the wound, and ESPB group received preoperative bilateral ESPB with 0.375% ropivacaine 40 mL. Primary outcome was postoperative pain intensity at rest using a Numeric Rating Scale (NRS). Secondary outcomes included difference in pain intensity between preintervention and defined timepoints, total amount of opioid analgesic requested by the patients at the same timepoints, the incidence of any adverse event, and the length of hospital stay (LOS) after surgery. Sixty patients were enrolled in the study. After surgery we detected a NRS value of 1.9±1.5 in ESPB group and 5.9±1.6 in control group (P<0.001). About the opioid consumption we found a total sufentanil tablets consumption of 17±6 and 10±3 at 48 hours for control group and ESPB group, respectively (P<0.001). Concerning LOS, 30 (100%) patients in the control group and 22 (73.3%) in ESPB group were discharged after 72 hours (P=0.005). Bilateral ultrasound-guided ESPB offers improved postoperative analgesia compared with local infiltration in patients undergoing lumbar spinal surgery.

Interleukin-1 blocking agents for treating COVID-19.

Interleukin-1 blocking agents for treating COVID-19.

Efficacy and Safety of Ertugliflozin in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of ertugliflozin in patients with type 2 diabetes. Methods: MEDLINE, EMBASE, and Cochrane Library were searched (July 31, 2021) for phase II/III randomized clinical trials, which reported the efficacy and safety of ertugliflozin. Continuous variables were calculated as weighted mean difference (WMD) and associated 95% confidence intervals (CIs); dichotomous data were expressed as risk ratios (RRs) with 95% CIs. Results: Nine randomized clinical trials including 5638 type 2 diabetes patients were included. For efficacy, ertugliflozin significantly reduced HbA1c (%) (WMD −0.452%; 95% CI −0.774 to −0.129), fasting plasma glucose (FPG) (WMD −0.870 mmol/L; 95% CI −1.418 to −0.322), body weight (WMD −1.774 kg; 95% CI −2.601 to −0.946), and blood pressure levels (systolic blood pressure: WMD −2.572 mmHg; 95% CI −3.573 to −1.571 and diastolic blood pressure: WMD −1.152 mmHg; 95% CI −2.002 to −0.303) compared with placebo and other hypoglycaemic agents. Compared with placebo, ertugliflozin was superior in reducing HbA1c (%) (WMD −0.641%) and FPG (WMD −1.249 mmol/L). And compared with active agents, ertugliflozin also could decrease HbA1c by 0.215% and FPG by 0.266 mmol/L. The interactive effect between different controls was significant (P interaction of 0.039). For safety, similar to other sodium-glucose cotransporter type-2 inhibitors, ertugliflozin mainly increased the risk of genital mycotic infection (RR: 4.004; 95% CI 2.504–6.402). There was no significant difference in the incidence of any adverse events (AEs), AEs related to study drug, serious AEs, deaths, and discontinuations due to AEs. Results were consistent with the most primary outcomes in subgroups analysis and sensitivity analysis. Conclusion: Ertugliflozin was relatively effective and tolerated in patients with type 2 diabetes compared with placebo or other hypoglycaemic agents, except for a high risk of genital mycotic infection. Systematic Review Registration: (ClinicalTrials.gov), identifier (CRD42020206356).

Humoral Immunogenicity to SARS-CoV-2 Vaccination in Liver Transplant Recipients: A Systematic Review and Meta-Analysis.

Solid organ transplant recipients generally show reduced immunogenicity to various vaccines. We aimed to assess the immunogenicity of the immune response among orthotopic liver transplant (OLT) recipients after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. A systematic search was performed to evaluate immunogenicity or adverse events reported after SARS-CoV-2 vaccination. The pooled analysis of 20 studies showed a humoral immune response rate of 0.70 (95% confidence interval [CI], 0.63-0.77) after SARS-CoV-2 vaccination among OLT recipients. The immunogenicity among OLT recipients was significantly lower compared to the overall population and healthy controls, with odds ratios (ORs) of 0.80 and 0.69. However, it was significantly higher than that of patients receiving other organ transplants, especially kidneys, with an OR of 1.50. Male sex, old age, chronic kidney disease, obesity, and multiple or high immunosuppressant doses significantly increased the risk of unresponsiveness in patients with OLT. The overall incidence of any adverse event after vaccination was 0.68 (95% CI, 0.55-0.81), similar to that of control. OLT recipients had an overall humoral immune response rate of 70% after SARS-CoV-2 vaccination, which is lower than that of healthy controls but favourable compared to those of other solid organ transplant recipients.

Safety of Remdesivir for Patients 80 Years of Age or Older with Coronavirus Disease 2019 (COVID-19).

Background and ObjectiveAlthough older patients with coronavirus disease 2019 (COVID-19) are at the high risk of exacerbation that requires treatment with remdesivir, the safety of this medication is unclear in clinical practice, especially among older patients. We aimed to retrospectively evaluate the safety of remdesivir in older patients with COVID-19 who required hospitalization in our institute.MethodsWe reviewed patients with COVID-19 who were treated with remdesivir at our institute between July 2020 and May 2021. We defined older patients as those aged 80 years or older at admission; all other patients were defined as younger patients. We evaluated the safety of remdesivir by examining the incidence of discontinuation of remdesivir treatment because of adverse events and the incidence of any adverse events.ResultsA total of 80 patients were included in this study. Compared with younger patients, fewer older patients were treated with remdesivir for more than 5 days: 4 (15.4%) vs 23 (42.6%). Discontinuation of remdesivir because of adverse events occurred in one older patient (3.9%) and four younger patients (7.4%) [p > 0.99]. Remdesivir-induced liver dysfunction was the most frequent adverse event, which occurred in 29 (36.3%) patients. There were no significant differences in the incidence of remdesivir-induced liver dysfunction, renal dysfunction, and fatigue.ConclusionsThe safety of remdesivir was suggested to be comparable between patients older than 80 years of age and patients younger than 80 years of age. The results of this study may encourage the administration of remdesivir to this older patient group.