Vasovagal reactions after COVID-19 vaccination in Japan

Coronavirus disease 2019 (COVID-19) vaccine administration started in February 2021 in Japan. As of December 2021, approximately 75% of the population aged ≥12 years had received two doses of vaccine. We conducted a study to investigate vasovagal reactions (VVR) after COVID-19 vaccination using data on adverse events following immunization. The crude reporting rate of VVR (cases/1,000,000 doses) after vaccination was 9.6 in all age groups combined, and was more frequent in the younger age groups: 28.6 and 37.2 in individuals aged 10–19 years and 20–29 years, respectively. In individuals aged 10–29 years, the rate was similar in males and females (33.0 and 34.2, respectively, p = 0.53); but was higher after dose 1 than after dose 2 (57.4 and 8.8, respectively, p < 0.001). Based on these results, caution needs to be exercised when vaccinating adolescents and young adults, especially with dose 1 of COVID-19 vaccines.     

Associations of HLA and drug-metabolizing enzyme genes in co-trimoxazole-induced severe cutaneous adverse reactions

Co-trimoxazole is mainly used as a first-line drug for treatment and prophylaxis against Pneumocystis jiroveci pneumonia. This drug, however, has been reported as the most common causative drug for severe cutaneous adverse reactions (SCARs). This study aimed to extensively elucidate the associations between genetic polymorphisms of HLA class I and genes involved in bioactivation and detoxification of co-trimoxazole on co-trimoxazole-induced SCARS in a large sample size and well-defined Thai SCARs patients. A total of 67 patients with co-trimoxazole-induced SCARs, consisting of 51 SJS/TEN patients and 16 DRESS patients, and 91 co-trimoxazole tolerant controls were enrolled in the study. The results clearly demonstrated that the HLA-B¹13:01 allele was significantly associated with co-trimoxazole-induced SCARs, especially with DRESS (OR = 8.44, 95% CI = 2.66–26.77, P = 2.94 × 10⁻⁴, Pc = 0.0126). Moreover, the HLA-C¹08:01 allele was significantly associated with co-trimoxazole-induced SJS/TEN in the HIV/AIDS patients with an OR of 8.51 (95% CI = 2.18–33.14, P = 8.60 × 10⁻⁴, Pc = 0.0241). None of the genes involved in the bioactivation and detoxification of co-trimoxazole investigated in this study play any major role in the development of all phenotypes of SCARs.     

Clinical Outcomes and Patency after Transjugular Intrahepatic Portosystemic Shunt Reduction for Overshunting Adverse Events

PurposeTo assess clinical outcomes and patency after transjugular intrahepatic portosystemic shunt (TIPS) reduction for overshunting adverse events.Materials and MethodsThis multicenter, retrospective observational study included 33 patients (male-to-female ratio, 20:13; mean age, 59 years; mean Model for End-Stage Liver Disease [MELD] score, 15) who underwent TIPS reduction between 2007 and 2020. Procedure indications included medically refractory hepatic encephalopathy (HE) (85%), post-TIPS hepatic insufficiency (HI) (12%), and heart failure (3%). The measured outcomes included improvement in HE (classified using the West Haven system) and HI, patency of reduced TIPS, and transplant-free survival (TFS).ResultsTIPS reductions were successfully performed using parallel stent (94%) or other (6%) techniques at a median of 120 days after TIPS creation (HE, median, 164 days; HI, median, 5 days). The portosystemic pressure gradient increased from a mean of 10 to 17 mm Hg (P < .001). The overall HE rate after TIPS reduction was 54%; HE was persistent, improved, and resolved in 21%, 32%, and 46% cases, respectively. In patients with HI, the MELD score increased from a mean of 22 before TIPS to 34 after TIPS (P = .061), but without improvement (0%) in HI after TIPS reduction (mean MELD score, 30; P = .266). Recurrent ascites occurred in 14% of the patients. The median shunt patency was 961 days (95% confidence interval, 476–1,447). The 30-day, 6-month, 1-year, and 3-year shunt patency rates were 92%, 81%, 74%, and 37%, respectively. The median TFS was not reached. The 30-day, 6-month, 1-year, and 3-year survival rates were 97%, 90%, 81%, and 60%, respectively.ConclusionsAlthough TIPS reduction may be an effective and durable approach to treat post-TIPS medically refractory HE, shunt reduction may not achieve meaningful benefit for HI.     

Safety and Immunogenicity of mRNA Vaccines Against Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Lung Cancer Receiving Immune Checkpoint Inhibitors: A Multicenter Observational Study in Japan

IntroductionPatients with cancer have been prioritized for vaccination against severe acute respiratory syndrome coronavirus 2. Nevertheless, there are limited data regarding the safety, efficacy, and risk of developing immune-related adverse events (irAEs) associated with mRNA vaccines in patients with lung cancer, especially those being actively treated with immune checkpoint inhibitors.MethodsThis multicenter observational study was conducted at nine hospitals in Japan. Patients with lung cancer (≥20 y) actively treated with immune checkpoint inhibitors between 4 weeks prefirst vaccination and 4 weeks postsecond vaccination were enrolled. The primary end point was the incidence of irAEs of any grade on the basis of an assumed incidence without vaccination rate of 35%. Immunogenicity was assessed by measuring anti–spike (S)-IgG antibody levels against severe acute respiratory syndrome coronavirus 2.ResultsA total of 126 patients with lung cancer (median age, 71 y; interquartile range, 65–74) were enrolled from May to November 2021 and followed up until December 2021. There were 26 patients (20.6%, 95% confidence interval: 13.9%–28.8%) and seven patients (5.6%, 95% confidence interval: 2.3%–11.1%) who developed irAEs of any grade pre- and postvaccination, respectively, which was lower than the predicted incidence without vaccination. None of the patients experienced exacerbation of preexisting irAE postvaccination. S-IgG antibodies were seroconverted in 96.7% and 100% of the patients with lung cancer and controls, respectively, but antibody levels were significantly lower in patients with lung cancer (p < 0.001).ConclusionsPatients with lung cancer who were actively treated with ICIs were safely vaccinated without an increased incidence of irAEs; however, their vaccine immunogenicity was lower. This requires further evaluation.     

COVID-19 vaccine induced interstitial lung disease

A 60-year-old man presented with dyspnea four days after the second dose of the coronavirus disease (COVID-19) vaccine. Imaging revealed extensive ground-glass opacification. Blood tests were notable for elevated KL-6 levels. Bronchoalveolar lavage fluid analysis showed increased lymphocyte-dominant inflammatory cells and decreased CD4/CD8 ratio. These findings were consistent with the diagnosis of drug-induced interstitial lung disease (DIILD). To the best of our knowledge, this has never been reported in previous literature. Treatment with glucocorticoids relieved his symptoms. This paper highlights that although extremely rare, COVID-19 vaccine could cause DIILD, and early diagnosis and treatment are crucial to improve patient outcomes.     

Preventing Adverse Drug Reactions After Hospital Discharge (PADR-AD): Protocol for a randomised-controlled trial in older people

BackgroundAdverse drug reactions (ADRs) and adverse drug events (ADEs) in older people contribute to a significant proportion of hospital admissions and are common following discharge. Effective interventions are therefore required to combat the growing burden of preventable ADRs. The Prediction of Hospitalisation due to Adverse Drug Reactions in Elderly Community Dwelling Patients (PADR-EC) score is a validated risk score developed to assess the risk of ADRs in people aged 65 years and older and has the potential to be utilised as part of an intervention to reduce ADRs.ObjectivesThis trial was designed to investigate the effectiveness of an intervention to reduce ADR incidence in older people and to obtain further information about ADRs and ADEs in the 12–24 months following hospital discharge.MethodsThe study is an open-label randomised-controlled trial to be conducted at the Royal Hobart Hospital, a 500-bed public hospital in Tasmania, Australia. Community-dwelling patients aged 65 years and older with an unplanned overnight admission to a general medical ward will be recruited. Following admission, the PADR-EC ADR score will be calculated by a research pharmacist, with the risk communicated to clinicians and discussed with participants. Following discharge, nominated general practitioners and community pharmacists will receive the risk score and related medication management advice to guide their ongoing care of the patient. Follow-up with participants will occur at 3 and 12 and 18 and 24 months to identify ADRs and ADEs. The primary outcome is moderate-severe ADRs at 12 months post-discharge, and will be analysed using the cumulative incidence proportion, survival analysis and Poisson regression.SummaryIt is hypothesised that the trial will reduce ADRs and ADEs in the intervention population. The study will also provide valuable data on post-discharge ADRs and ADEs up to 24 months post-discharge.     

童年期不良经历对个体健康影响的研究进展

童年期不良经历(ACEs)作为一项全球性的严峻公共卫生挑战,其对全生命周期的健康影响不容小觑。因此本文从心理健康、生理健康、性传播疾病及危险性行为、健康危险行为4个方面对ACEs的健康影响进行综述,为ACEs及其可能健康结局提供参考。