Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 ...vaccine. The time course of natural and hybrid immunity is unknown.
Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event.
The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously.
Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.
Recent reports have asserted that, because of energy underreporting, dietary self-report data suffer from measurement error so great that findings that rely on them are of no value. This commentary ...considers the amassed evidence that shows that self-report dietary intake data can successfully be used to inform dietary guidance and public health policy. Topics discussed include what is known and what can be done about the measurement error inherent in data collected by using self-report dietary assessment instruments and the extent and magnitude of underreporting energy compared with other nutrients and food groups. Also discussed is the overall impact of energy underreporting on dietary surveillance and nutritional epidemiology. In conclusion, 7 specific recommendations for collecting, analyzing, and interpreting self-report dietary data are provided: (1) continue to collect self-report dietary intake data because they contain valuable, rich, and critical information about foods and beverages consumed by populations that can be used to inform nutrition policy and assess diet-disease associations; (2) do not use self-reported energy intake as a measure of true energy intake; (3) do use self-reported energy intake for energy adjustment of other self-reported dietary constituents to improve risk estimation in studies of diet-health associations; (4) acknowledge the limitations of self-report dietary data and analyze and interpret them appropriately; (5) design studies and conduct analyses that allow adjustment for measurement error; (6) design new epidemiologic studies to collect dietary data from both short-term (recalls or food records) and long-term (food-frequency questionnaires) instruments on the entire study population to allow for maximizing the strengths of each instrument; and (7) continue to develop, evaluate, and further expand methods of dietary assessment, including dietary biomarkers and methods using new technologies.
Dietary measurement error creates serious challenges to reliably discovering new diet-disease associations in nutritional cohort studies. Such error causes substantial underestimation of relative ...risks and reduction of statistical power for detecting associations. On the basis of data from the Observing Protein and Energy Nutrition Study, we recommend the following approaches to deal with these problems. Regarding data analysis of cohort studies using food-frequency questionnaires, we recommend 1) using energy adjustment for relative risk estimation; 2) reporting estimates adjusted for measurement error along with the usual relative risk estimates, whenever possible (this requires data from a relevant, preferably internal, validation study in which participants report intakes using both the main instrument and a more detailed reference instrument such as a 24-hour recall or multiple-day food record); 3) performing statistical adjustment of relative risks, based on such validation data, if they exist, using univariate (only for energy-adjusted intakes such as densities or residuals) or multivariate regression calibration. We note that whereas unadjusted relative risk estimates are biased toward the null value, statistical significance tests of unadjusted relative risk estimates are approximately valid. Regarding study design, we recommend increasing the sample size to remedy loss of power; however, it is important to understand that this will often be an incomplete solution because the attenuated signal may be too small to distinguish from unmeasured confounding in the model relating disease to reported intake. Future work should be devoted to alleviating the problem of signal attenuation, possibly through the use of improved self-report instruments or by combining dietary biomarkers with self-report instruments.
Booster doses for the ongoing COVID-19 pandemic are under consideration in many countries. We report a three-month follow-up of 700 participants in a fourth vaccine dose study, comparing BNT162b2 and ...mRNA1273, administered four months after a third BNT162b2 dose. The primary outcomes are the levels of IgG, neutralizing antibodies, and microneutralization and the secondary outcomes are the levels of IgA and T cell activation, and clinical outcomes of SARS-CoV-2 infection and substantial symptomatic disease. Waning of the immune response is evident during follow-up, with an 11% (β = 0.89, 95% CI, 0.88-0.9) and 21% (β = 0.79, 95% CI, 0.76-0.82) multiplicative decay per week of IgG and neutralizing antibodies, respectively, in the mRNA1273 group, and of 14% (β = 0.86, 95% CI, 0.86-0.87) and 26% (β = 0.74, 95% CI, 0.72-0.76), respectively, in the BNT162b2 group. Direct neutralization of Omicron variants is low relative to ancestral strains. Cumulatively over the study period, both vaccines show little efficacy against infection but were highly efficacious against substantial symptomatic disease 89% (IRR 0.11, 95% CI, 0.02-0.37) and 71% (IRR 0.29, 95% CI, 0.13-0.57) for mRNA1273 and BNT162b2, respectively. These results are informative for further boosting policy-making. Trial registration numbers (clinicaltrials.gov): NCT05231005 and NCT05230953.
Tony Johnson—memories and a tribute Freedman, Laurence S.; Colton, Theodore
Statistics in medicine,
28 February 2023, Letnik:
42, Številka:
5
Journal Article
We pooled data from 5 large validation studies of dietary self-report instruments that used recovery biomarkers as references to clarify the measurement properties of food frequency questionnaires ...(FFQs) and 24-hour recalls. The studies were conducted in widely differing US adult populations from 1999 to 2009. We report on total energy, protein, and protein density intakes. Results were similar across sexes, but there was heterogeneity across studies. Using a FFQ, the average correlation coefficients for reported versus true intakes for energy, protein, and protein density were 0.21, 0.29, and 0.41, respectively. Using a single 24-hour recall, the coefficients were 0.26, 0.40, and 0.36, respectively, for the same nutrients and rose to 0.31, 0.49, and 0.46 when three 24-hour recalls were averaged. The average rate of under-reporting of energy intake was 28% with a FFQ and 15% with a single 24-hour recall, but the percentages were lower for protein. Personal characteristics related to under-reporting were body mass index, educational level, and age. Calibration equations for true intake that included personal characteristics provided improved prediction. This project establishes that FFQs have stronger correlations with truth for protein density than for absolute protein intake, that the use of multiple 24-hour recalls substantially increases the correlations when compared with a single 24-hour recall, and that body mass index strongly predicts under-reporting of energy and protein intakes.
To examine the effects of reverse causation on estimates from the weighted cumulative exposure (WCE) model that is used in pharmacoepidemiology to explore drug-health outcome associations, and to ...identify sensitivity analyses for revealing such effects.
314,099 patients with diabetes under Clalit Health Services, Israel, were followed over 2002-2012. The association between metformin and pancreatic cancer (PC) was explored using a WCE model within the framework of discrete-time Cox regression. We used computer simulations to explore the effects of reverse causation on estimates of a WCE model and to examine sensitivity analyses for revealing and adjusting for reverse causation. We then applied those sensitivity analyses to our data.
Simulation demonstrated bias in the weighted cumulative exposure model and showed that sensitivity analysis could reveal and adjust for these biases. In our data, a positive association was observed (hazard ratio (HR) = 3.24, 95% confidence interval (CI): 2.24-4.73) with metformin exposure in the previous 2 years. After applying sensitivity analysis, assuming reverse causation operated up to 4 years before cancer diagnosis, the association between metformin and PC was no longer apparent.
Reverse causation can cause substantial bias in the WCE model. When suspected, sensitivity analyses based on causal analysis are advocated.
Omidubicel is an ex vivo expanded hematopoietic progenitor cell and nonexpanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We report results of a phase 3 trial ...to evaluate the efficacy of omidubicel compared with standard umbilical cord blood transplantation (UCBT). Between January 2017 and January 2020, 125 patients age 13 to 65 years with hematologic malignancies were randomly assigned to omidubicel vs standard UCBT. Patients received myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil for graft-versus-host disease (GVHD). The primary end point was time to neutrophil engraftment. The treatment arms were well balanced and racially diverse. Median time to neutrophil engraftment was 12 days (95% confidence interval CI, 10-14 days) for the omidubicel arm and 22 days (95% CI, 19-25 days) for the control arm (P < .001). The cumulative incidence of neutrophil engraftment was 96% for patients receiving omidubicel and 89% for patients receiving control transplants. The omidubicel arm had faster platelet recovery (55% vs 35% recovery by 42 days; P = .028), had a lower incidence of first grade 2 to 3 bacterial or invasive fungal infection (37% vs 57%; P = .027), and spent more time out of hospital during the first 100 days after transplant (median, 61 vs 48 days; P = .005) than controls. Differences in GVHD and survival between the 2 arms were not statistically significant. Transplantation with omidubicel results in faster hematopoietic recovery and reduces early transplant-related complications compared with standard UCBT. The results suggest that omidubicel may be considered as a new standard of care for adult patients eligible for UCBT. The trial was registered at www.clinicaltrials.gov as #NCT02730299.
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