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1.
Sci Rep ; 14(1): 1430, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38228695

ABSTRACT

During the Covid-19 pandemic, accurate PCR tests were augmented by the cheap, rapid, and logistically convenient, yet less sensitive antigen tests. In Israel, a testing policy shift was implemented due to limited availability of PCR tests during the Omicron surge. Thus, both PCR and antigen tests were used, as this was the only alternative for mass testing and surveillance at the time. Yet, evidence-based surveillance requires a robust understanding of the expected consequences of changing the testing policy. Using 41,065 paired tests performed by trained staff between January and April 2022 in Israel, we estimate how the sensitivity of antigen tests changes as a function of Ct value and other key covariates. The results reveal a logarithmic relationship between antigen detection probability and viral load, as quantified by Ct-values of the PCR tests. Further analysis shows a statistically significant association with an odds ratio of approximately 0.76 with each unit of Ct-value. The analysis suggests that in spite of their compromised sensitivity, antigen tests are a natural solution for routine use, while PCR tests should be considered in situations where a false negative result could have serious consequences. These findings are the foundations of policies that will utilize the strengths of the different tests, and achieve enhanced hybrid surveillance.


Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , COVID-19/epidemiology , Pandemics , Public Health , Israel/epidemiology , Polymerase Chain Reaction , Sensitivity and Specificity , COVID-19 Testing
2.
J Clin Epidemiol ; 163: 111-116, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37774957

ABSTRACT

OBJECTIVES: This study aims to address limitations in assessing vaccine protection using the classical vaccine effectiveness (VE) measure, especially in contexts where a significant portion of the population is already vaccinated or infected. STUDY DESIGN AND SETTING: We propose using the adjusted number of cases (ANC) as a building block for deriving vaccine effectiveness measures. This approach accounts for biases arising from small and unrepresentative unvaccinated reference groups with incomplete data. We demonstrate the use of these measures for assessing the protection conferred by a booster dose against severe COVID-19 using data from Israel. RESULTS: The use of ANC and the derived measures reveals a more comprehensive understanding of the complex immunity landscape compared to traditional VE measures. This approach enables meaningful comparisons between different vaccination categories and provides insights to inform policy decisions. CONCLUSION: In situations with widespread vaccination and prior infections, traditional VE measures can be limited in their informative value. Using the ANC offers a more robust and insightful assessment of vaccine effectiveness. A demonstration of the evaluation of booster dose protection against severe COVID-19 in Israel underscores the importance of adopting complementary measures to guide public health strategies.


Subject(s)
COVID-19 , Vaccines , Humans , Vaccination , COVID-19/epidemiology , COVID-19/prevention & control , Israel/epidemiology , Public Health
4.
Commun Biol ; 6(1): 315, 2023 03 23.
Article in English | MEDLINE | ID: mdl-36959496

ABSTRACT

Following evidence of waning immunity against both infection and severe disease after 2 doses of the BNT162b2 vaccine, Israel began administering a 3rd BNT162b2 dose (booster) in July 2021. Recent studies showed that the 3rd dose provides a much lower protection against infection with the Omicron variant compared to the Delta variant and that this protection wanes quickly. However, there is little evidence regarding the protection of the 3rd dose against Omicron (BA.1/BA.2) severe disease. In this study, we estimate the preservation of immunity from severe disease up to 7 months after receiving the booster dose. We calculate rates of severe SARS-CoV-2 disease between groups of individuals aged 60 and above, comparing those who received two doses at least 4 months previously to those who received the 3rd dose (stratified by the time from vaccination), and to those who received a 4th dose. The analysis shows that protection conferred by the 3rd dose against Omicron severe disease did not wane over a 7-month period. Moreover, a 4th dose further improved protection, with a severe disease rate approximately 3-fold lower than in the 3-dose cohorts.


Subject(s)
BNT162 Vaccine , COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2 , Israel/epidemiology
5.
Ann Allergy Asthma Immunol ; 130(2): 233-239.e4, 2023 02.
Article in English | MEDLINE | ID: mdl-36441058

ABSTRACT

BACKGROUND: Cow's milk allergy (CMA) is a common food allergy among infants. Information regarding the best timing for first exposure to cow's milk formula (CMF) is controversial and more evidence is required. Few randomized control trials have tried to accurately assess the timing and preventive effect of exposure to CMF on small cohorts. OBJECTIVE: This study assessed the association between early, continuing exposure to CMF on the basis of the parents' preferences and the development of immunoglobulin E (IgE)-mediated CMA in a large birth cohort. METHODS: Newborns were prospectively recruited shortly before birth and divided into 2 groups according to parental feeding preference for the first 2 months of life: (1) exclusive breastfeeding (EBF); or (2) at least 1 meal of CMF (with or without breastfeeding) daily. Infants were followed up monthly until the age of 12 months. RESULTS: Among 1992 infants participating in the study, 1073 (53.86%) were in the EBF group until 2 months of age. IgE-mediated CMA was confirmed in 0.85% (n = 17); all were in the EBF group. Within this group, the prevalence of IgE-mediated CMA was 1.58% compared with 0 in the other groups (relative risk, 29.98; P < .001). Post hoc analysis revealed IgE-mediated CMA prevalence of 0.7% in the per-protocol EBF group vs 3.27% among breastfed infants who were exposed to a small amount of CMF during the first 2 months of life. A family atopic background did not affect the results. CONCLUSION: Early, continuing exposure to CMF from birth has the potential to prevent the development of IgE-mediated CMA and should be encouraged. However, the exposure needs to be consistent because occasional exposure increases the risk of developing IgE-mediated CMA and should be avoided.


Subject(s)
Food Hypersensitivity , Infant Formula , Milk Hypersensitivity , Animals , Cattle , Female , Food Hypersensitivity/prevention & control , Immunoglobulin E , Milk , Milk Hypersensitivity/epidemiology , Milk Hypersensitivity/prevention & control , Prospective Studies , Humans , Infant, Newborn , Infant
6.
Lancet Infect Dis ; 23(1): 67-73, 2023 01.
Article in English | MEDLINE | ID: mdl-36096146

ABSTRACT

BACKGROUND: The BNT162b2 (Pfizer-BioNTech) two-dose vaccine regiment for children and the BNT162b2 third dose for adolescents were approved shortly before the SARS-CoV-2 omicron (B.1.1.529) outbreak in Israel. We aimed to estimate the effects of these vaccines on the rates of confirmed infection against the omicron variant in children and adolescents. METHODS: In this observational cohort study, we extracted data for the omicron-dominated (sublineage BA.1) period. We compared rates of confirmed SARS-CoV-2 infection between children aged 5-10 years 14-35 days after receiving the second vaccine dose with an internal control group of children 3-7 days after receiving the first dose (when the vaccine is not yet effective). Similarly, we compared confirmed infection rates in adolescents aged 12-15 years 14-60 days after receiving a booster dose with an internal control group of adolescents 3-7 days after receiving the booster dose. We used Poisson regression, adjusting for age, sex, socioeconomic status, calendar week, and exposure. FINDINGS: Between Dec 26, 2021, and Jan 8, 2022, we included 1 158 289 participants. In children aged 5-10 years, the adjusted rate of confirmed infection was 2·3 times (95% CI 2·0-2·5) lower in children who received a second dose than in the internal control group. The adjusted infection rate in children who received a second dose was 102 infections per 100 000 risk-days (94-110) compared with 231 infections per 100 000 risk-days (215-248) in the corresponding internal control cohort. In adolescents aged 12-15 years, the booster dose decreased confirmed infection rates by 3·3 times (2·8-4·0) compared with in the internal control group. The adjusted infection rate of the booster cohort was 70 per 100 000 risk-days (60-81) compared with 232 per 100 000 risk-days (212-254) in the internal control cohort. INTERPRETATION: A recent two-dose vaccination regimen with BNT162b2 and a recent booster dose in adolescents substantially reduced the rate of confirmed infection compared with the internal control groups. Future studies are needed to assess the duration of this protection and protection against other outcomes such as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 and long-COVID. FUNDING: None.


Subject(s)
COVID-19 , Humans , Adolescent , Child , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Israel/epidemiology , Post-Acute COVID-19 Syndrome , BNT162 Vaccine
7.
J Forensic Sci ; 67(5): 1801-1809, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35855550

ABSTRACT

Footwear comparison is used to link between a suspect's shoe and a shoeprint found at a crime scene. Forensic examiners compare the two items, and the conclusion reached is based on class characteristics and randomly acquired characteristics (RACs), such as scratches or holes. An important question concerns the distribution of the location of RACs on shoe soles, which can serve as a benchmark for comparison. This study examines the probability of observing RACs in different areas of a shoe sole using a database of approximately 13,000 RACs observed on 386 outsoles. The analysis is somewhat complicated as the shoes are differentiated by shape and contact surface, and the RACs' locations are subject to measurement errors. A method that takes into account these challenges is presented. All impressions are normalized to a standardized axis to allow for inter-comparison of RACs on outsoles of different sizes and contact areas, and RACs are localized to one of 14 subareas of the shoe sole. Expected frequencies in each region are assumed to be Poisson distributed with rate parameters that depend on the subarea and the contact surface. Three different estimation approaches are studied: a naive crude approach, a shoe-specific random effects model, and an estimate that is based on conditional maximum likelihood. It is shown that the rate is not uniform across the shoe sole and that RACs are approximately twice as likely to appear at certain locations, corresponding to the foot's morphology. The results can guide investigators in determining a shoeprint's evidential value.


Subject(s)
Forensic Medicine , Shoes , Crime , Databases, Factual , Probability
8.
N Engl J Med ; 386(23): 2201-2212, 2022 06 09.
Article in English | MEDLINE | ID: mdl-35613036

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
COVID-19 , BNT162 Vaccine/immunology , BNT162 Vaccine/therapeutic use , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Humans , Immunity, Innate , Reinfection/immunology , Reinfection/prevention & control , SARS-CoV-2 , Time Factors , Viral Vaccines/immunology , Viral Vaccines/therapeutic use
9.
N Engl J Med ; 386(18): 1712-1720, 2022 05 05.
Article in English | MEDLINE | ID: mdl-35381126

ABSTRACT

BACKGROUND: On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19). METHODS: Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day. RESULTS: The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks. CONCLUSIONS: Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.


Subject(s)
COVID-19 , SARS-CoV-2 , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Israel/epidemiology
10.
Nat Commun ; 13(1): 1971, 2022 04 13.
Article in English | MEDLINE | ID: mdl-35418201

ABSTRACT

Israel began administering a BNT162b2 booster dose to restore protection following the waning of the 2-dose vaccine. Biological studies have shown that a "fresh" booster dose leads to increased antibody levels compared to a fresh 2-dose vaccine, which may suggest increased effectiveness. To compare the real-world effectiveness of a fresh (up to 60 days) booster dose with that of a fresh 2-dose vaccine, we took advantage of a quasi-experimental study that compares populations that were eligible to receive the vaccine at different times due to age-dependent policies. Specifically, we compared the confirmed infection rates in adolescents aged 12-14 (215,653 individuals) who received the 2-dose vaccine and in adolescents aged 16-18 (103,454 individuals) who received the booster dose. Our analysis shows that the confirmed infection rate was lower by a factor of 3.7 (95% CI: 2.7 to 5.2) in the booster group.


Subject(s)
BNT162 Vaccine , COVID-19 , Adolescent , COVID-19/prevention & control , Humans , Immunization, Secondary , Israel , SARS-CoV-2
11.
Am J Epidemiol ; 191(8): 1420-1428, 2022 07 23.
Article in English | MEDLINE | ID: mdl-35355048

ABSTRACT

The worldwide shortage of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while the pandemic still remains uncontrolled has led many countries to the dilemma of whether or not to vaccinate previously infected persons. Understanding the level of protection conferred by previous infection compared with that of vaccination is important for policy-making. We analyzed an updated individual-level database of the entire population of Israel to assess the protection provided by both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with coronavirus disease 2019 (COVID-19), severe disease, and death due to COVID-19. Outcome data were collected from December 20, 2020, to March 20, 2021. Vaccination was highly protective, with overall estimated effectiveness of 94.5% (95% confidence interval (CI): 94.3, 94.7) for documented infection, 95.8% (95% CI: 95.2, 96.2) for hospitalization, 96.3% (95% CI: 95.7, 96.9) for severe illness, and 96.0% (95% CI: 94.9, 96.9) for death. Similarly, the overall estimated level of protection provided by prior SARS-CoV-2 infection was 94.8% (95% CI: 94.4, 95.1) for documented infection, 94.1% (95% CI: 91.9, 95.7) for hospitalization, and 96.4% (95% CI: 92.5, 98.3) for severe illness. Our results should be considered by policy-makers when deciding whether or not to prioritize vaccination of previously infected adults.


Subject(s)
COVID-19 , Viral Vaccines , Adult , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Israel/epidemiology , SARS-CoV-2
12.
Proc Natl Acad Sci U S A ; 119(10): e2112010119, 2022 03 08.
Article in English | MEDLINE | ID: mdl-35235460

ABSTRACT

Eutrophication is a major driver of species loss in plant communities worldwide. However, the underlying mechanisms of this phenomenon are controversial. Previous studies have raised three main explanations: 1) High levels of soil resources increase standing biomass, thereby intensifying competitive interactions (the "biomass-driven competition hypothesis"). 2) High levels of soil resources reduce the potential for resource-based niche partitioning (the "niche dimension hypothesis"). 3) Increasing soil nitrogen causes stress by changing the abiotic or biotic conditions (the "nitrogen detriment hypothesis"). Despite several syntheses of resource addition experiments, so far, no study has tested all of the hypotheses together. This is a major shortcoming, since the mechanisms underlying the three hypotheses are not independent. Here, we conduct a simultaneous test of the three hypotheses by integrating data from 630 resource addition experiments located in 99 sites worldwide. Our results provide strong support for the nitrogen detriment hypothesis, weaker support for the biomass-driven competition hypothesis, and negligible support for the niche dimension hypothesis. The results further show that the indirect effect of nitrogen through its effect on biomass is minor compared to its direct effect and is much larger than that of all other resources (phosphorus, potassium, and water). Thus, we conclude that nitrogen-specific mechanisms are more important than biomass or niche dimensionality as drivers of species loss under high levels of soil resources. This conclusion is highly relevant for future attempts to reduce biodiversity loss caused by global eutrophication.


Subject(s)
Biodiversity , Biomass , Fertilizers , Grassland , Nitrogen
13.
Prev Med ; 155: 106947, 2022 02.
Article in English | MEDLINE | ID: mdl-34974072

ABSTRACT

Development of an effective vaccine against Covid-19 is crucial to reducing infection. mRNA BNT162b2, developed and manufactured by Pfizer-BioNTech, was one of the first FDA-approved vaccinations reporting high efficacy (95%) and minimal side effects. Evaluating effectiveness of BNT162b2 in a general population has been made possible after the implementation of a nation-wide vaccination program in Israel. This retrospective cohort study was carried out in Maccabi HealthCare services, Israel among 1.6 million members aged 16 and over. The population was divided into those who were at least seven days post- second vaccination and those who had not been vaccinated. Number of days till the end of the study or Covid-19 infection, Covid-19-related hospitalization and mortality was calculated for each participant between 18.1.2021 to 25.4.2021. Participants who had reached day eight after second vaccination during the study period could contribute days to both groups. Vaccine efficacy (VE) was calculated using a conditional Poisson model, controlling for age group, gender, hypertension, diabetes and obesity, fitted within clusters defined by geographical statistical area and calendar week. BNT162b2 was found effective for the total population group for infection, hospitalization and mortality, with adjusted VE of 93·0% (CI:92·6-93·4%), 93·4% (CI:91·9-94·7%) and 91·1% (CI:86·5-94·1%) respectively. VE for infection was lower for participants aged 75 and over, and for those with hypertension, diabetes and obesity. This study strengthens the evidence that the Pfizer-BioNTech vaccination is effective in preventing infection, hospitalization and mortality.


Subject(s)
COVID-19 , Adolescent , Aged , BNT162 Vaccine , COVID-19 Vaccines , Humans , Israel , Retrospective Studies , SARS-CoV-2 , Vaccine Efficacy
14.
N Engl J Med ; 385(26): 2421-2430, 2021 12 23.
Article in English | MEDLINE | ID: mdl-34879188

ABSTRACT

BACKGROUND: After promising initial results from the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) to persons 60 years of age or older, the booster campaign in Israel was gradually expanded to persons in younger age groups who had received a second dose at least 5 months earlier. METHODS: We extracted data for the period from July 30 to October 10, 2021, from the Israel Ministry of Health database regarding 4,696,865 persons 16 years of age or older who had received two doses of BNT162b2 at least 5 months earlier. In the primary analysis, we compared the rates of confirmed coronavirus disease 2019 (Covid-19), severe illness, and death among those who had received a booster dose at least 12 days earlier (booster group) with the rates among those who had not received a booster (nonbooster group). In a secondary analysis, we compared the rates in the booster group with the rates among those who had received a booster 3 to 7 days earlier (early postbooster group). We used Poisson regression models to estimate rate ratios after adjusting for possible confounding factors. RESULTS: The rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of approximately 10 (range across five age groups, 9.0 to 17.2) and was lower in the booster group than in the early postbooster group by a factor of 4.9 to 10.8. The adjusted rate difference ranged from 57.0 to 89.5 infections per 100,000 person-days in the primary analysis and from 34.4 to 38.3 in the secondary analysis. The rates of severe illness in the primary and secondary analyses were lower in the booster group by a factor of 17.9 (95% confidence interval [CI], 15.1 to 21.2) and 6.5 (95% CI, 5.1 to 8.2), respectively, among those 60 years of age or older and by a factor of 21.7 (95% CI, 10.6 to 44.2) and 3.7 (95% CI, 1.3 to 10.2) among those 40 to 59 years of age. The adjusted rate difference in the primary and secondary analyses was 5.4 and 1.9 cases of severe illness per 100,000 person-days among those 60 years of age or older and 0.6 and 0.1 among those 40 to 59 years of age. Among those 60 years of age or older, mortality was lower by a factor of 14.7 (95% CI, 10.0 to 21.4) in the primary analysis and 4.9 (95% CI, 3.1 to 7.9) in the secondary analysis. The adjusted rate difference in the primary and secondary analyses was 2.1 and 0.8 deaths per 100,000 person-days. CONCLUSIONS: Across the age groups studied, rates of confirmed Covid-19 and severe illness were substantially lower among participants who received a booster dose of the BNT162b2 vaccine than among those who did not.


Subject(s)
BNT162 Vaccine , COVID-19/epidemiology , Immunization, Secondary , Patient Acuity , Vaccine Efficacy/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/prevention & control , Female , Humans , Israel/epidemiology , Male , Middle Aged , Young Adult
15.
N Engl J Med ; 385(24): e85, 2021 12 09.
Article in English | MEDLINE | ID: mdl-34706170

ABSTRACT

BACKGROUND: In December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear. METHODS: We used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors. RESULTS: Among persons 60 years of age or older, the rate of infection in the July 11-31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age. CONCLUSIONS: These findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.


Subject(s)
Antibodies, Neutralizing/blood , BNT162 Vaccine/immunology , COVID-19/epidemiology , Immunogenicity, Vaccine , SARS-CoV-2 , Vaccine Efficacy , Adolescent , Adult , Aged , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/prevention & control , Female , Humans , Immunization, Secondary , Israel/epidemiology , Male , Middle Aged , Patient Acuity , Poisson Distribution , Regression Analysis , Socioeconomic Factors , Time Factors
16.
N Engl J Med ; 385(15): 1393-1400, 2021 10 07.
Article in English | MEDLINE | ID: mdl-34525275

ABSTRACT

BACKGROUND: On July 30, 2021, the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) was approved in Israel for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. Data are needed regarding the effect of the booster dose on the rate of confirmed coronavirus 2019 disease (Covid-19) and the rate of severe illness. METHODS: We extracted data for the period from July 30 through August 31, 2021, from the Israeli Ministry of Health database regarding 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (i.e., had received two doses of BNT162b2) at least 5 months earlier. In the primary analysis, we compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster. In all the analyses, we used Poisson regression after adjusting for possible confounding factors. RESULTS: At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1). CONCLUSIONS: In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Immunization, Secondary , Aged , Aged, 80 and over , BNT162 Vaccine , COVID-19/epidemiology , Databases, Factual , Female , Humans , Israel/epidemiology , Male , Middle Aged , Patient Acuity , Poisson Distribution , SARS-CoV-2
17.
J Forensic Sci ; 65(4): 1114-1119, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32134504

ABSTRACT

Quantifying the strength of gunshot residue (GSR) evidence requires scientific knowledge about the number of particles expected to be found on individuals who were or were not involved in a shooting. However, controlled experiments demand expensive resources in terms of microscope time and labor, which restricts the data of most studies to only a small group of individuals. We suggest a novel method that exploits data collected routinely on suspects during the daily work of forensic laboratories. These observational data relate to both persons who were involved in a shooting and innocent individuals. We suggest a mixture approach with different models for the number of gunshot residue particles in each group and develop an iterative algorithm to estimate the probabilities of observing the evidence under the defense proposition that the suspect is innocent and under the prosecution assumption that he is not. The method is applied to data of more than 500 suspects collected by the Israel National Police Division of Identification and Forensic Science. The analysis shows that the probability of finding three or more GSR particles on the hands of innocent suspects is very small, less than 1.5 in 1000 cases. Our new method enables researchers to use data on real cases, possibly supplemented by experimental data, in order to estimate the probabilities of a given GSR finding under the defense and prosecution propositions.


Subject(s)
Antimony/analysis , Barium/analysis , Hand , Lead/analysis , Models, Statistical , Skin/chemistry , Algorithms , Forensic Ballistics/methods , Humans , Microscopy, Electron, Scanning , Spectrometry, X-Ray Emission , Wounds, Gunshot
18.
Biometrics ; 76(2): 484-495, 2020 06.
Article in English | MEDLINE | ID: mdl-31621059

ABSTRACT

Right-truncated data arise when observations are ascertained retrospectively, and only subjects who experience the event of interest by the time of sampling are selected. Such a selection scheme, without adjustment, leads to biased estimation of covariate effects in the Cox proportional hazards model. The existing methods for fitting the Cox model to right-truncated data, which are based on the maximization of the likelihood or solving estimating equations with respect to both the baseline hazard function and the covariate effects, are numerically challenging. We consider two alternative simple methods based on inverse probability weighting (IPW) estimating equations, which allow consistent estimation of covariate effects under a positivity assumption and avoid estimation of baseline hazards. We discuss problems of identifiability and consistency that arise when positivity does not hold and show that although the partial tests for null effects based on these IPW methods can be used in some settings even in the absence of positivity, they are not valid in general. We propose adjusted estimating equations that incorporate the probability of observation when it is known from external sources, which results in consistent estimation. We compare the methods in simulations and apply them to the analyses of human immunodeficiency virus latency.


Subject(s)
Models, Statistical , Proportional Hazards Models , Biometry , Computer Simulation , HIV/physiology , HIV Infections/transmission , HIV Infections/virology , Humans , Likelihood Functions , Probability , Regression Analysis , Retrospective Studies , Virus Latency
19.
J Forensic Sci ; 63(4): 1269-1274, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29964343

ABSTRACT

Classification of particles as gunshot residues (GSRs) is conducted using a semiautomatic approach in which the system first classifies particles based on an automatic elemental analysis, and then, examiners manually analyze particles having compositions which are characteristic of or consistent with GSRs. Analyzing all the particles in the second stage is time consuming with many particles classified by the initial automated system as being potentially GSRs excluded as such by the forensic examiner. In this paper, a new algorithm is developed to improve the initial classification step. The algorithm is based on a binary tree that was trained on almost 16,000 particles from 43 stubs used to sample hands of suspects. The classification algorithm was tested on 5,900 particles from 23 independent stubs and performed very well in terms of false positive and false negative rates. A routine use of the new algorithm can reduce significantly the analysis time of GSRs.

20.
Ann Epidemiol ; 28(7): 475-480.e1, 2018 07.
Article in English | MEDLINE | ID: mdl-29661679

ABSTRACT

PURPOSE: To explore the impact of length-biased sampling on the evaluation of risk factors of nosocomial infections (NIs) in point-prevalence studies. METHODS: We used cohort data with full information including the exact date of the NI and mimicked an artificial 1-day prevalence study by picking a sample from this cohort study. Based on the cohort data, we studied the underlying multistate model which accounts for NI as an intermediate and discharge/death as competing events. Simple formulas are derived to display relationships between risk, hazard, and prevalence odds ratios. RESULTS: Due to length-biased sampling, long stay and thus sicker patients are more likely to be sampled. In addition, patients with NIs usually stay longer in hospital. We explored mechanisms that are-due to the design-hidden in prevalence data. In our example, we showed that prevalence odds ratios were usually less pronounced than risk odds ratios but more pronounced than hazard ratios. CONCLUSIONS: Thus, to avoid misinterpretation, knowledge of the mechanisms from the underlying multistate model is essential for the interpretation of risk factors derived from point-prevalence data.


Subject(s)
Cross Infection/epidemiology , Models, Statistical , Models, Theoretical , Cohort Studies , Factor Analysis, Statistical , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Prevalence , Proportional Hazards Models , Risk Factors
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