Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunisation Stress-related Responses with COVID-19 mRNA Vaccine

Background: With the implementation of mass vaccination campaigns against COVID 19, the safety of vaccine needs to be evaluated. Objective: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunisation stress related responses (ISRR) with the Moderna COVID 19 vaccine. Methods: This nested case control study included recipients who received the Moderna vaccine at a mass vaccination centre, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1:4) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. Results: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2,478 recipients (cases 2) showed 318 events of IHSR and 2,558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2,129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and history of allergy; for ISRR, they were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. Conclusion: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should beware of the occurrence of ISRR. Risk factor identification may contribute to the stratification of high risk recipients for IHSR and ISRR.

Rapid Classification and Treatment Algorithm of Cardiogenic Shock Complicating Acute Coronary Syndromes: The SAVE ACS Classification

Introduction. We aimed to identify the independent “frontline” predictors of 30-day mortality in patients with acute coronary syndromes (ACS) and propose a rapid cardiogenic shock (CS) classification and management pathway. Materials and Methods. From 2011 to 2019, a total of 11439 incident ACS patients were treated in our institution. Forward conditional logistic regression analysis was performed to determine the “frontline” predictors of 30 day mortality. The C-statistic assessed the discriminatory power of the model. As a validation cohort, we used 431 incident ACS patients admitted from January 1, 2020, to July 20, 2020. Results. Independent predictors of 30-day mortality included age (OR 1.05; 95% CI 1.04 to 1.07, p < 0.001 ), intubation (OR 7.4; 95% CI 4.3 to 12.74, p < 0.001 ), LV systolic impairment (OR severe_vs_normal 1.98; 95% CI 1.14 to 3.42, p = 0.015 , OR moderate_vs_normal 1.84; 95% CI 1.09 to 3.1, p = 0.022 ), serum lactate (OR 1.25; 95% CI 1.12 to 1.41, p < 0.001 ), base excess (OR 1.1; 95% CI 1.04 to 1.07, p < 0.001 ), and systolic blood pressure (OR 0.99; 95% CI 0.982 to 0.999, p = 0.024 ). The model discrimination was excellent with an area under the curve (AUC) of 0.879 (0.851 to 0.908) ( p < 0.001 ). Based on these predictors, we created the SAVE (SBP, Arterial blood gas, and left Ventricular Ejection fraction) ACS classification, which showed good discrimination for 30-day AUC 0.814 (0.782 to 0.845) and long-term mortality p log − rank < 0.001 . A similar AUC was demonstrated in the validation cohort (AUC 0.815). Conclusions. In the current study, we introduce a rapid way of classifying CS using frontline parameters. The SAVE ACS classification could allow for future randomized studies to explore the benefit of mechanical circulatory support in different CS stages in ACS patients.

Colours, capsules and concept flavour names on cigarette packs appeal to youth in Mexico

BackgroundFlavoured cigarettes are popular in Mexico. We examined how cigarette packaging design features used to communicate flavour influence perceptions of appeal, harm, perceived interest and pack preference among Mexico City residents.MethodsWe conducted an experimental survey. Participants aged 13–34 years were randomly assigned to one of three conditions, viewed packs with systematically manipulated design features (colour, capsule image and flavour name) and answered questions on appeal, perceived harm, perceived interest and pack preference. Data were analysed using mixed effects and conditional logistic regression.Results1500 adolescents and 950 adults participated. Regardless of flavour, cigarette packs with a background colour and capsule image were more appealing to adolescents (OR=13.19, 95% CI 11.53 to 15.10; OR=1.68, 95% CI 1.45 to 1.88) and adults (OR=4.18, 95% CI 3.73 to 4.69; OR=1.66, 95% CI 1.49 to 1.85) than packs without. Among adolescents, ‘Tropical Burst’ named packs were more appealing (OR=1.43, 95% CI 1.20 to 1.72) than packs without a flavour name and among adults, ‘Arctic Air’ named packs were more appealing (OR=1.20, 95% CI 1.02 to 1.14). Adolescents and adults reported a preference for trying packs that displayed a flavour name, background colour or capsule image (b=0.104, b=0.702, b=1.316, p<0.001 and b=0.126, b=0.619, b=0.775, p<0.001).ConclusionsColours and flavour capsule images appeal to adolescents and adults in Mexico. Mexico should consider adopting plain packaging to reduce appeal and interest.

Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants

Background The recently emerged SARS-CoV-2 omicron variant raised concerns around potential escape from vaccine-elicited immunity. Limited data are available on real-world vaccine effectiveness (VE) of mRNA-1273 against omicron. Here, we report VE of 2 or 3 mRNA-1273 doses against infection and hospitalization with omicron and delta, including among immunocompromised individuals. Methods This test negative study was conducted at Kaiser Permanente Southern California. Cases were individuals aged ≥18 years testing positive by RT-PCR with specimens collected between 12/6/2021 and 12/23/2021 with variant determined by spike gene status. Randomly sampled test negative controls were 5:1 matched to cases by age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression models were used to evaluate adjusted odds ratio (aOR) of vaccination with mRNA-1273 doses between cases and controls. VE(%) was calculated as (1-aOR)x100. Results 6657 test positive cases (44% delta, 56% omicron) were included. The 2-dose VE against omicron infection was 30.4% (95% CI, 5.0%-49.0%) at 14-90 days after vaccination and declined quickly thereafter. The 3-dose VE was 95.2% (93.4%-96.4%) against delta infection and 62.5% (56.2%-67.9%) against omicron infection. The 3-dose VE against omicron infection was low among immunocompromised individuals (11.5%; 0.0%-66.5%). None of the cases (delta or omicron) vaccinated with 3 doses were hospitalized compared to 53 delta and 2 omicron unvaccinated cases. Conclusions VE of 3 mRNA-1273 doses against infection with delta was high and durable, but VE against omicron infection was lower. VE against omicron infection was particularly low among immunocompromised individuals. No 3-dose recipients were hospitalized for COVID-19.

US lesion visibility predicts clinically significant upgrade of prostate cancer by systematic biopsy

Purpose To identify predictors of when systematic biopsy leads to a higher overall prostate cancer grade compared to targeted biopsy. Methods and materials 918 consecutive patients who underwent prostate MRI followed by MRI/US fusion biopsy and systematic biopsies from January 2015 to November 2019 at a single academic medical center were retrospectively identified. The outcome was upgrade of PCa by systematic biopsy, defined as cases when systematic biopsy led to a Gleason Grade (GG) ≥ 2 and greater than the maximum GG detected by targeted biopsy. Generalized linear regression and conditional logistic regression were used to analyze predictors of upgrade. Results At the gland level, the presence of an US-visible lesion was associated with decreased upgrade (OR 0.64, 95% CI 0.44–0.93, p = 0.02). At the sextant level, upgrade was more likely to occur through the biopsy of sextants with MRI-visible lesions (OR 2.58, 95% CI 1.87–3.63, p < 0.001), US-visible lesions (OR 1.83, 95% CI 1.14–2.93, p = 0.01), and ipsilateral lesions (OR 3.89, 95% CI 2.36–6.42, p < 0.001). Conclusion Systematic biopsy is less valuable in patients with an US-visible lesion, and more likely to detect upgrades in sextants with imaging abnormalities. An approach that takes additional samples from regions with imaging abnormalities may provide analogous information to systematic biopsy.

Association between glycemic control and risk of venous thromboembolism in diabetic patients: a nested case–control study

Background Previous studies suggested an elevated risk of venous thromboembolism (VTE) among patients with type 2 diabetes mellitus (T2DM), with a possible sex difference. The impact of glycemic control on the risk of VTE is unclear. Our objective was to analyze the association between glycemic control and the risk of unprovoked (idiopathic) VTE in men and women with T2DM. Methods We conducted a nested case–control analysis (1:4 matching) within a cohort of patients with incident T2DM between 1995 and 2019 using data from the CPRD GOLD. We excluded patients with known risk factors for VTE prior to onset of DM. Cases were T2DM patients with an unprovoked treated VTE. The exposure of interest was glycemic control measured as HbA1c levels. We conducted conditional logistic regression analyses adjusted for several confounders. Results We identified 2′653 VTE cases and 10′612 controls (53.1% females). We found no association between the HbA1c level and the risk of VTE in our analyses. However, when the most recent HbA1c value was recorded within 90 days before the index date, women with HbA1c levels > 7.0% had a 36–55% increased relative risk of VTE when compared to women with HbA1c > 6.5–7.0%. Conclusions Our study raises the possibility that female T2DM patients with HbA1c levels > 7% may have a slightly higher risk for unprovoked VTE compared to women with HbA1c levels > 6.5–7.0%. This increase may not be causal and may reflect differences in life style or other characteristics. We observed no effect of glycemic control on the risk of VTE in men.

The association of zonulin-related proteins with prevalent and incident inflammatory bowel disease

Background Current evidence regarding the association of serum zonulin-related proteins (ZRP) levels with prevalent inflammatory bowel disease (IBD) is contradictory. Moreover, the association with the subsequent risk of incident IBD is still unexplored. This study aimed to investigate the association of serum ZRP levels with both prevalent and incident IBD. Method The study included a total of 130 women (51–61 years) from the Women’s Health in Lund Area (WHILA) study, which included 18 prevalent IBD (diagnosed before baseline) and 47 incident IBD diagnosed during the 17 years (median) follow-up and age- and sampling time-matched controls. Serum ZRP was tested in all participants by ELISA. Results The serum ZRP levels were significantly higher in prevalent IBD compared to their matched controls (63.2 ng/ml vs 57.0 ng/ml, p = 0.02), however, no evidence of a difference in ZRP levels was found between the women who developed IBD during the follow-up period and their matched controls (61.2 ng/ml vs 59.7 ng/ml, p = 0.34). Using linear mixed models, we found that the association between serum ZRP levels and prevalent IBD (β = 6.2, p = 0.01), remained after adjusting for potential confounders. Conditional logistic regression models showed no evidence of an association between ZRP level and incident IBD (OR 1.03, p = 0.34). Conclusion Higher serum ZRP levels were associated with prevalent IBD, but not with incident IBD in our study samples.

Cold Weather and Cardiac Arrest in 4 Seasons: Helsinki, Finland, 1997‒2018

Objectives. To test the a priori hypothesis that out-of-hospital cardiac arrest (OHCA) is associated with cold weather during all seasons, not only during the winter. Methods. We applied a case‒crossover design to all cases of nontraumatic OHCA in Helsinki, Finland, over 22 years: 1997 to 2018. We statistically defined cold weather for each case and season, and applied conditional logistic regression with 2 complementary models a priori according to the season of death. Results. There was an association between cold weather and OHCA during all seasons, not only during the winter. Each additional cold day increased the odds of OHCA by 7% (95% confidence interval [CI] = 4%, 10%), with similar strength of association during the autumn (6%; 95% CI = 0%, 12%), winter (6%; 95% CI = 1%, 12%), spring (8%; 95% CI = 2%, 14%), and summer (7%; 95% CI = 0%, 15%). Conclusions. Cold weather, defined according to season, increased the odds of OHCA during all seasons in similar quantity. Public Health Implications. Early warning systems and cold weather plans focus implicitly on the winter season. This may lead to incomplete measures in reducing excess mortality related to cold weather. (Am J Public Health. 2022;112(1):107–115. https://doi.org/10.2105/AJPH.2021.306549 )

Individual and joint effects of trehalose and glutamate on diabetic retinopathy: a propensity score-matched case-control study

Although previous studies demonstrate that trehalose can help maintain glucose homeostasis in healthy humans, its role and joint effect with glutamate on diabetic retinopathy (DR) remain unclear. We aimed to comprehensively quantify the associations of trehalose and glutamate with DR. This study included 69 pairs of DR and matched type 2 diabetic (T2D) patients. Serum trehalose and glutamate were determined via ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry system. Covariates were collected by a standardized questionnaire, clinical examinations and laboratory assessments. Individual and joint association of trehalose and glutamate with DR were quantified by multiple conditional logistic regression models. The adjusted odds of DR averagely decreased by 86% [odds ratio (OR): 0.14; 95% confidence interval (CI): 0.06,0.33] with per interquartile range increase of trehalose. Comparing with the lowest quartile, adjusted OR (95% CI) were 0.20 (0.05,0.83), 0.14 (0.03,0.63) and 0.01 (<0.01,0.05) for participants in the 2nd, 3rd and 4th quartiles of trehalose, respectively. In addition, as compared to their counterparts, T2D patients with lower trehalose (<median) and higher glutamate (≥ median) had the highest odds of DR (OR: 36.81; 95% CI: 6.75, 200.61). Apparent super-multiplicative effect of trehalose and glutamate on DR was observed, whereas relative excess risk due to interaction (RERI) was not significant. The study suggests that trehalose is beneficial to inhibit the occurrence of DR and synergistically decreases the risk of DR with reduced glutamate. Our findings also provide new insights into the mechanisms of DR and further longitudinal studies are required to confirm these findings.

Associations of FGF21 and GDF15 with mitochondrial dysfunction in children living with perinatally-acquired HIV: A cross-sectional evaluation of pediatric AIDS clinical trials group 219/219C

Background In persons living with HIV, mitochondrial disease (MD) is difficult to diagnose, as clinical signs are non-specific with inconsistent patterns. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are mitokines elevated in MD patients without HIV, and associated with cardiometabolic comorbidities in adults living with HIV. We assessed relationships of these biomarkers with MD in children living with perinatally-acquired HIV infection (CPHIV). Setting Cross-sectional study of CPHIV from Pediatric ACTG 219/219C classified by Mitochondrial Disease Criteria (MDC) that defines scores 2–4 as “possible” MD. Methods Each case with MDC equaling 4 (MDC4; n = 23) was matched to one randomly selected control displaying no MDC (MDC0; n = 23) based on calendar date. Unmatched cases with MDC equaling 3 (MDC3; n = 71) were also assessed. Plasma samples proximal to diagnoses were assayed by ELISA. Mitokine distributions were compared using Wilcoxon tests, Spearman correlations were calculated, and associations with MD status were assessed by conditional logistic regression. Results Median FGF21 and GDF15 concentrations, respectively, were highest in MDC4 (143.9 and 1441.1 pg/mL), then MDC3 (104.0 and 726.5 pg/mL), and lowest in controls (89.4 and 484.7 pg/mL). Distributions of FGF21 (paired Wilcoxon rank sum p = 0.002) and GDF15 (paired Wilcoxon rank sum p<0.001) differed in MDC4 vs MDC0. Mitokine concentrations were correlated across all participants (r = 0.33; p<0.001). Unadjusted odds ratios of being MDC4 vs MDC0 were 5.2 [95% confidence interval (CI): 1.06–25.92] for FGF21 and 3.5 (95%CI: 1.19–10.25) for GDF15. Relationships persisted after covariate adjustments. Conclusion FGF21 and GDF15 levels may be useful biomarkers to screen for CPHIV with mitochondrial dysfunction.