Test negative case-control study of COVID-19 vaccine effectiveness for symptomatic SARS-CoV-2 infection among healthcare workers: Zambia, 2021-2022

Objectives
The study aim was to evaluate vaccine effectiveness (VE) of COVID-19 vaccines in preventing symptomatic COVID-19 among healthcare workers (HCWs) in Zambia. We sought to answer the question, ‘What is the vaccine effectiveness of a complete schedule of the SARS-CoV-2 vaccine in preventing symptomatic COVID-19 among HCWs in Zambia?’

Design/setting
We conducted a test-negative case–control study among HCWs across different levels of health facilities in Zambia offering point of care testing for COVID-19 from May 2021 to March 2022.

Participants
1767 participants entered the study and completed it. Cases were HCWs with laboratory-confirmed SARS-CoV-2 and controls were HCWs who tested SARS-CoV-2 negative. Consented HCWs with documented history of vaccination for COVID-19 (vaccinated HCWs only) were included in the study. HCWs with unknown test results and unknown vaccination status, were excluded.

Primary and secondary outcome measures
The primary outcome was VE among symptomatic HCWs. Secondary outcomes were VE by: SARS-CoV-2 variant strains based on the predominant variant circulating in Zambia (Delta during May 2021 to November 2021 and Omicron during December 2021 to March 2022), duration since vaccination and vaccine product.

Results
We recruited 1145 symptomatic HCWs. The median age was 30 years (IQR: 26–38) and 789 (68.9%) were women. Two hundred and eighty-two (24.6%) were fully vaccinated. The median time to full vaccination was 102 days (IQR: 56–144). VE against symptomatic SARS-CoV-2 infection was 72.7% (95% CI: 61.9% to 80.7%) for fully vaccinated participants. VE was 79.4% (95% CI: 58.2% to 90.7%) during the Delta period and 37.5% (95% CI: –7.0% to 63.3%) during the Omicron period.

Conclusions
COVID-19 vaccines were effective in reducing symptomatic SARS-CoV-2 among Zambian HCWs when the Delta variant was circulating but not when Omicron was circulating. This could be related to immune evasive characteristics and/or waning immunity. These findings support accelerating COVID-19 booster dosing with bivalent vaccines as part of the vaccination programme to reduce COVID-19 in Zambia.

Leggi
Dicembre 2023

Optimal measurement of gastric emptying of solids in gastroparesis or functional dyspepsia: evidence to establish standard test

Objective
Symptoms in gastroparesis (Gp) and functional dyspepsia (FD) overlap; using egg protein substitute to measure gastric emptying of solids (GES), ~40% of patients are reclassified from Gp to FD, and vice versa. Our aim was to assess inter-individual and intra-individual coefficients of variation (COV) in GES in symptomatic patients with Gp or FD with documented slow or normal GES, respectively.

Design
Scintigraphic GES (T1/2 and GE% at 2 and 4 hours) using a 320 kcal real egg meal (30% fat) was tested in the following: single measurements in 20 patients with diabetes mellitus (10 each type 1 and type 2); repeat GES to estimate COVintra measured: 3 days apart in 9 Gp, 4 weeks apart in 21 Gp and 18 with FD with normal GE assigned to placebo and in 70 patients at 94.3 weeks (median) apart.

Results
COVinter for GE% at 4 hours and GE T1/2 were respectively 14.2% and 23.5% in FD and 27.5% and 33% in Gp; COVintra for GE% at 4 hours and GE T1/2 up to 4 weeks apart were 23.4% and 37.9% in FD and 20.1% and 33% in Gp. GE% at 2 hours showed less consistent results. However, >85% retained original diagnosis as normal or delayed. From clinical GES to baseline research for Gp group, repeat GES (after treatment) showed the COVintra for GE% at 4 hours was 37.3% at median 94.3 weeks, with 26/70 changed diagnoses.

Conclusion
The 320 kcal (30% fat) GES scintigraphic test provides consistent diagnosis in >85% and should be the standard test for suspected gastric emptying disorders.

Leggi
Novembre 2023

WHY STOP? A prospective observational vignette-based study to determine the cognitive-behavioural effects of rapid diagnostic PCR-based point-of-care test results on antibiotic cessation in ICU infections

Objectives
Point-of-care tests (POCTs) for infection offer accurate rapid diagnostics but do not consistently improve antibiotic stewardship (ASP) of suspected ventilator-associated pneumonia. We aimed to measure the effect of a negative PCR-POCT result on intensive care unit (ICU) clinicians’ antibiotic decisions and the additional effects of patient trajectory and cognitive-behavioural factors (clinician intuition, dis/interest in POCT, risk averseness).

Design
Observational cohort simulation study.

Setting
ICU.

Participants
70 ICU consultants/trainees working in UK-based teaching hospitals.

Methods
Clinicians saw four case vignettes describing patients who had completed a course of antibiotics for respiratory infection. Vignettes comprised clinical and biological data (ie, white cell count, C reactive protein), varied to create four trajectories: clinico-biological improvement (the ‘improvement’ case), clinico-biological worsening (‘worsening’), clinical improvement/biological worsening (‘discordant clin better’), clinical worsening/biological improvement (‘discordant clin worse’). Based on this, clinicians made an initial antibiotics decision (stop/continue) and rated confidence (6-point Likert scale). A PCR-based POCT was then offered, which clinicians could accept or decline. All clinicians (including those who declined) were shown the result, which was negative. Clinicians updated their antibiotics decision and confidence.

Measures
Antibiotics decisions and confidence were compared pre-POCT versus post-POCT, per vignette.

Results
A negative POCT result increased the proportion of stop decisions (54% pre-POCT vs 70% post-POCT, 2(1)=25.82, p

Leggi
Novembre 2023

Abstract 13902: Using a Proteomics-Based Cardiovascular Risk Test to Identify Systemic Changes in a Clinical Trial of Nonalcoholic Fatty Liver Disease

Circulation, Volume 148, Issue Suppl_1, Page A13902-A13902, November 6, 2023. Background:Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular outcomes. Assessment of the impact of NASH therapy on cardiovascular risk is an important element of NASH drug development but is challenging particularly in early phase trials. Aptamer-based proteomic profiles (Somalogic®) in serum have been used to develop and validate a risk score as a surrogate for cardiovascular (CV) risk.Hypothesis:Improvement in NASH histology will result in improved proteomic cardiovascular risk scores.Methods:A post-hoc analysis of proteomic profiles of serum samples, using the Somalogic® platform, from the Pioglitazone vs. Vitamin E vs. Placebo for Treatment of Nonalcoholic Fatty Liver Disease (PIVENS) trial was conducted. PIVENS was a 96-week trial of nondiabetic participants with (NASH). We applied the proteomic CV risk scores to samples from baseline, on therapy and end of treatment visits (n=7) visits and received liver histology results at baseline and 96 weeks on N = 209 (84.6%) study participants. Generalized linear and mixed models were used to assess the association between CV risk score, treatment arm and change in liver biopsy results.Results:Baseline scores were similar across groups (mean 0.19, SD 0.14). There was no association between treatment arms and changes in scores during therapy and end of treatment. However, improvement in histological markers of activity (lobular inflammation and NAFLD activity score) and fibrosis were associated with improved cv risk scores (Figure) (p< 0.05 for all).Conclusions:Improvement in hepatic inflammation, NAFLD activity score and fibrosis were associated with improved proteomic CV risk scores regardless of treatment provided. Additional prospective validation of these findings is warranted. Proteomic profiling can potentially be used to track changes in cardiovascular risk profile changes in response to therapy in the short term NASH treatment trials.

Leggi
Novembre 2023

Abstract 16196: E/e' Predicts Exercise Capacity in Participants Undergoing Exercise Stress Test

Circulation, Volume 148, Issue Suppl_1, Page A16196-A16196, November 6, 2023. Introduction:The ratio of early transmitral flow velocity (E) to early diastolic mitral annular velocity (e’) is a surrogate for left ventricular (LV) filling pressure. Post-stress E/e’ has been shown to predict exercise capacity, but few studies have investigated this correlation with baseline E/e’. Our aim was to evaluate the relationship between baseline E/e’ and exercise capacity during stress test.Methods:All patients undergoing exercise stress testing at University of Virginia from 1/2015 through 9/2015 with the required echo data were included in this study. E/e’ was categorized into quartiles. ANOVA was used to evaluate the relationship between quartiles of E/e’ and exercise duration or METS. Multivariate linear regression was used to adjust for the variables: age, sex, ejection fraction, systolic blood pressure, heart rate, and regional wall motion abnormalities.Results:Baseline characteristics of the 312 participants based on E/e’ quartiles are shown in Table 1; those with higher E/e’, on average, had higher baseline SBP, were older, and had a higher percentage of females. There was a significant difference in exercise duration and METS between E/e’ quartiles (Table 2A) [p < 0.001]. There was an inverse correlation between E/e’ and exercise capacity; the significance was more pronounced with increasing E/e’ (Table 2A) and was present even after adjusting for multiple covariates (Table 2B).Conclusions:Baseline E/e’ correlates with exercise capacity (both duration of exercise and total METS achieved). This suggests that elevated LV filling pressures at rest can predict exercise capacity and may be targeted in future studies to improve exercise tolerance.

Leggi
Novembre 2023

Abstract 13988: Post Stress Test High-Sensitivity Cardiac Troponin I in the Evaluation of Patients With Acute Chest Pain for Enhanced Ischemic Risk Assessment: A Pilot Study

Circulation, Volume 148, Issue Suppl_1, Page A13988-A13988, November 6, 2023. Introduction:High-sensitivity cardiac troponin I (hs-cTnI) assays provide comparable diagnostic information that allow for better detection of myocardial injury. However, hs-cTnI release after cardiac stress testing and its potential utility for identifying inducible myocardial ischemia and risk-stratification are unclear.Aim:This pilot study examined integrating hs-cTnI biomarker testing into cardiac imaging stress testing to improve detection of inducible ischemia and aid in risk-stratification in patients with chest pain being evaluated for acute coronary syndrome (ACS).Methods:We prospectively enrolled 200 consecutive adult patients referred by the Emergency Room for cardiac stress testing for evaluation of possible ACS. A venous blood sample was collected between 0.5 and 2 hours post stress testing; cTnI concentrations were measured in-house by high sensitivity methods. Changes from pre-stress test hs-cTnI concentrations were calculated and association with outcome was explored using a logistic regression model.Results:Patient median age was 62 years, IQR 54-70; 49% were women. ACS known risk factors included hypertension 81.5%, cigarette smoking 49.5% and diabetes 33.5%. Median BMI was 31.63 kg/m2, IQR 27.24-35.84. Pre-stress test hs-cTnI median levels were 6 ng/L, IQR 5-9, for women (URL

Leggi
Novembre 2023

Abstract 11520: Safety and Efficacy of Botulinum Toxin Type A for Prevention of Postoperative Atrial Fibrillation in Cardiac Surgery Patients: Pulmonary Function Test Results From the Phase 2 NOVA Study

Circulation, Volume 148, Issue Suppl_1, Page A11520-A11520, November 6, 2023. Background:Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Autonomic neuromodulation, including injection of botulinum toxin into epicardial fat pads, may suppress and/or attenuate atrial fibrillation. The respiratory safety of a potential preventative treatment for AF is critical.Aim:To assess efficacy and pulmonary safety of botulinum toxin type A (BoNT/A; AGN-151607) 125U and 250U vs placebo for prevention of POAF after coronary artery bypass graft and/or valve surgery.Methods:NeurOtoxin for the PreVention of post-operative Atrial fibrillation (NOVA; NCT03779841) was a phase 2, international, multicenter, randomized, placebo-controlled trial. The primary endpoint was proportion of patients with continuous AF ≥30 seconds within the first 30 days. Respiratory function was assessed via pulmonary function tests (PFTs) performed at baseline and day 30 after treatment. Adverse events (AEs), serious adverse events (SAEs), and time to extubation were recorded.Results:A total of 323 patients were randomized: BoNT/A 125U (n=106), 250U (n=109), placebo (n=108). The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125U group (relative risk [RR] vs placebo, 0.80 [95% CI: 0.58, 1.10];P=0.16), and 47.2% of the 250U group (RR vs placebo, 1.04 [95% CI: 0.79, 1.37];P=0.78). Baseline, day 30, and change from baseline PFT results were similar for active treatment vs placebo (Table). Median time to extubation was 9.7, 9.6, and 9.6 h in the placebo, 125U, and 250U groups, respectively. Respiratory AEs were reported in 42.9%, 38.1%, and 50.5% of patients, and respiratory SAEs in 11.4%, 6.7%, and 5.5% of patients in the placebo, 125U, and 250U groups, respectively.Conclusion:In this analysis of respiratory function, there appeared to be no detrimental effect of AGN-151607 compared with placebo, as evidenced by similar outcomes in PFT parameters and respiratory AE/SAE incidences among treatment arms.

Leggi
Novembre 2023

Abstract 15645: Budget Impact Analysis of PrecisionCHD, an Artificial Intelligence Guided, Integrated Genetic-Epigenetic Test for Assessing CHD, Demonstrates Extensive Cost Savings Compared to Conventional Methods

Circulation, Volume 148, Issue Suppl_1, Page A15645-A15645, November 6, 2023. Coronary heart disease (CHD) costs the United States healthcare system at least $216 Billion in treatment cost and $147 billion in lost productivity annually. Therefore, there is an urgent need for cost-effective solutions to reduce both the human and economic burden of CHD. Because the initial CHD diagnostic approach has a large impact on subsequent costs and healthcare outcomes, risk bearing entities are keen to determine the optimal algorithmic approach for guiding the use of CHD diagnostic tools. In order to better understand the economic and clinical impact of a newly developed Precision Epigenetic test for assessing CHD status, PrecisionCHD, we conducted a budget impact analysis comparing the use of PrecisionCHD to the use of conventional exercise ECG and coronary computed tomographic angiography (CCTA) (in a 75:25 ratio) as the initial diagnostic assessment of CHD using nationally published cost estimates, generally accepted side effects, sensitivity and specificity metrics for each test, with all positive tests resulting in the initiation of moderate to high dose statin therapy as per treatment guidelines. Our analysis showed that for an insurance plan with 1 million covered individuals, a $20 co-pay for office visits and 10% co-insurance, the use of PrecisionCHD over exercise ECG and CCTA would result in $92 million in annual cost savings with a significant portion of those savings being secondary to the inferior performance of exercise ECG. Increasing the number of CCTA test performed increases the number of CHD cases detected, but also results in greater costs including costs secondary to contrast dye induced kidney damage. We conclude that the use of PrecisionCHD for CHD detection can improve healthcare outcomes and decrease CHD related costs. Given current trends in the developments in epigenetics-based approaches, it is likely that this advantage will increase further.

Leggi
Novembre 2023