Papers by Edward Goldstein
BMC Infectious Diseases, 2020
Background: Antibiotic use contributes to the rates of sepsis and the associated mortality, parti... more Background: Antibiotic use contributes to the rates of sepsis and the associated mortality, particularly through lack of clearance of resistant infections following antibiotic treatment. At the same time, there is limited information on the effects of prescribing of some antibiotics vs. others on subsequent sepsis and sepsis-related mortality.
Methods: We used a multivariable mixed-effects model to relate state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2014 and 2015 to state-specific rates of mortality with sepsis (ICD-10 codes A40-41 present as either underlying or contributing causes of death on a death certificate) in different age groups of US adults between 2014 and 2015, adjusting for additional covariates and random effects associated with the ten US Health and Human Services (HHS) regions.
Results: Increase in the rate of prescribing of oral penicillins by 1 annual dose per 1000 state residents was associated with increases in annual rates of mortality with sepsis of 0.95 (95% CI (0.02,1.88)) per 100,000 persons aged 75-84y, and of 2.97 (0.72,5.22) per 100,000 persons aged 85 + y. Additionally, the percent of individuals aged 50-64y lacking health insurance, as well as the percent of individuals aged 65-84y who are African-American were associated with rates of mortality with sepsis in the corresponding age groups.
Conclusions: Our results suggest that prescribing of penicillins is associated with rates of mortality with sepsis in older US adults. Those results, as well as the related epidemiological data suggest that replacement of certain antibiotics, particularly penicillins in the treatment of different syndromes should be considered with the aim of reducing the rates of severe outcomes, including mortality related to bacterial infections.
Background: Information on influenza-associated mortality in Russia is limited and largely relate... more Background: Information on influenza-associated mortality in Russia is limited and largely related to deaths with influenza in the diagnosis that represent a small fraction of all influenza-associated deaths.
Methods: Using previously developed methodology (Goldstein et al., Epidemiology 2012), we regressed the monthly rates of mortality for respiratory causes, as well as circulatory causes (available from the Russian Federal State Statistics Service (Rosstat)) during the 2013/14 through the 2018/19 influenza seasons linearly against the monthly proxies for the incidence of influenza A/H3N2, A/H1N1 and B (obtained using data from the Smorodintsev Research Institute of Influenza (RII) on influenza/ARI consultations, testing of respiratory specimens and genetic/antigenic characterization of influenza viruses), adjusting for the baseline rates of mortality not associated with influenza circulation and temporal trends.
Results: For the 2013/14 through the 2018/19 seasons, influenza circulation was associated with an average annual 17636 (95% CI (9482,25790)) deaths for circulatory causes and 4179 (3250,5109) deaths for respiratory causes, with the largest number of deaths (32298 (18071,46525) for circulatory causes and 6689 (5019,8359) for respiratory causes) estimated during the 2014/15 influenza season. Influenza A/H3N2 was responsible for 51.8% of all circulatory influenza-associated deaths and 37.2% of all respiratory influenza-associated deaths. Influenza A/H1N1 was responsible for 23.4% of all circulatory influenza-associated deaths and 29.5% of all respiratory influenza-associated deaths. Influenza B was responsible for 24.9% of all circulatory influenza-associated deaths and 33.3% of all respiratory influenza-associated deaths, with the overwhelming majority of those deaths being caused by the B/Yamagata viruses. Compared to the 2013/14 through the 2015/16 seasons, during the 2016/17 through the 2018/19 seasons (when levels of influenza vaccination were significantly higher), the volume of influenza-associated mortality declined by about 16.1%, or 3809 annual respiratory and circulatory deaths.
Conclusions: Influenza circulation is associated with a substantial mortality burden in Russia, particularly for circulatory deaths, with some reduction in mortality rates observed following the major increase in influenza vaccination coverage. Those results support the potential utility of further extending the levels of influenza vaccination, the use of quadrivalent influenza vaccines, and extra efforts for protecting individuals with circulatory disease in Russia, including vaccination and the use of antiviral medications.
Epidemiology, 2019
Background: There is uncertainty about the burden of hospitalization associated with respiratory ... more Background: There is uncertainty about the burden of hospitalization associated with respiratory syncytial virus (RSV) and influenza in children, including those with underlying medical conditions.
Methods: We applied previously developed methodology to HealthCare Cost and Utilization Project (HCUP) hospitalization data and additional data related to asthma diagnosis/previous history in hospitalized children to estimate RSV and influenza-associated hospitalization rates in different subpopulations of US children between 2003-2010.
Results: The estimated average annual rates (per 100,000 children) of RSV-associated hospitalization with a respiratory cause (ICD-9 codes 460-519) present anywhere in the discharge diagnosis were 2381 (95% CI(2252,2515)) in children less than a year of age; 710.6(609.1,809.2) (age 1y); 395(327.7,462.4) (age 2y); 211.3(154.6,266.8) (age 3y); 111.1(62.4,160.1) (age 4y); 72.3(29.3,116.4) (ages 5-6y); 35.6(9.9,62.2) (ages 7-11y); and 39(17.5,60.6) (ages 12-17y). The corresponding rates of influenza-associated hospitalization were lower, ranging from 181(142.5,220.3) in age <1y to 17.9(11.7,24.2) in ages 12-17y. The relative risks for RSV-related hospitalization associated with a prior diagnosis of asthma in age groups under 5y ranged between 3.1(2.1,4.7) (age <1y) to 6.7(4.2,11.8) (age 2y); the corresponding risks for influenza-related hospitalization ranged from 2.8(2.1,4) (age <1y) to 4.9(3.8,6.4) (age 3y).
Conclusions: RSV-associated hospitalization rates in young children are high and decline rapidly with age. There are additional risks for both RSV and influenza hospitalization associated with a prior diagnosis of asthma, with the rates of RSV-related hospitalization in the youngest children diagnosed with asthma being particularly high.
BMC Public Health, 2019
Background: Rates of sepsis/septicemia hospitalization in the US have risen significantly during ... more Background: Rates of sepsis/septicemia hospitalization in the US have risen significantly during recent years. Antibiotic resistance and use may contribute to those rates through various mechanisms, including lack of clearance of resistant infections following antibiotic treatment, with some of those infections subsequently devolving into sepsis. At the same time, there is limited information on the effect of prescribing of certain antibiotics vs. others on the rates of septicemia and sepsis-related hospitalizations and mortality.
Methods: We used multivariable linear regression to relate state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2011 and 2012 to state-specific rates of septicemia hospitalization (ICD-9 codes 038.xx present anywhere on a discharge diagnosis) in each of the following age groups of adults: (18-49y, 50-64y, 65-74y, 75-84y, 85 + y) reported to the Healthcare Cost and Utilization Project (HCUP) between 2011 and 2012, adjusting for additional covariates, and random effects associated with the ten US Health and Human Services (HHS) regions.
Results: Increase in the rate of prescribing of oral penicillins by 1 annual dose per 1000 state residents was associated with increases in annual septicemia hospitalization rates of 0.19 (95% CI (0.02,0.37)) per 10,000 persons aged 50-64y, of 0.48(0.12,0.84) per 10,000 persons aged 65-74y, and of 0.81(0.17,1.40) per 10,000 persons aged 74-84y. Increase by 1 in the percent of African Americans among state residents in a given age group was associated with increases in annual septicemia hospitalization rates of 2.3(0.32,4.2) per 10,000 persons aged 75-84y, and of 5.3(1.1,9.5) per 10,000 persons aged over 85y. Average minimal daily temperature was positively associated with septicemia hospitalization rates in persons aged 18-49y, 50-64y, 75-84y and over 85y.
Conclusions: Our results suggest positive associations between the rates of prescribing for penicillins and the rates of hospitalization with septicemia in US adults aged 50-84y. Further studies are needed to better understand the potential effect of antibiotic replacement in the treatment of various syndromes, including the potential impact of
the recent US FDA guidelines on restriction of fluoroquinolone use, as well as the potential effect of changes in the practices for prescribing of penicillins on the rates of sepsis-related hospitalization and mortality.
Background: Rates of hospitalization with sepsis and septicemia in the US have risen significantl... more Background: Rates of hospitalization with sepsis and septicemia in the US have risen significantly during the last two decades, and changes in diagnostic practices don’t fully explain that rise. Antibiotic resistance may contribute to the rates of sepsis/septicemia hospitalization through lack of clearance of bacterial infections following antibiotic treatment during different stages of infection. At the same time, there is limited information about the relation between prevalence of resistance to various antibiotics in different bacteria and rates of hospitalizations with sepsis and septicemia.
Methods: For different age groups of adults (18-49y,50-64y,65-74y,75-84y,85+y) and combinations of antibiotics/bacteria, we evaluated associations between state-specific average annual rates of hospitalizations with septicemia (ICD-9 codes 038.xx present on the discharge diagnosis) in a given age group reported to the Healthcare Cost and Utilization Project (HCUP) between 2011-2012, and state-specific prevalence (percentage) of resistant samples for a given combination of antibiotics/bacteria among catheter-associated urinary tract infections in the CDC Antibiotic Resistance Patient Safety Atlas data between 2011-2014.
Results: Prevalence of resistance to fluoroquinolones in E. coli had the strongest association with septicemia hospitalization rates for adults aged over 50y. A number of positive correlations between prevalence of resistance for different combinations of antibiotics/bacteria and septicemia hospitalization rates in adults were also found.
Conclusions: Our findings about the relation between prevalence of resistance to commonly prescribed antibiotics, particularly fluoroquinolones, and rates of septicemia hospitalization in US adults stress the need for enhancing antibiotic stewardship in different settings, especially for fluoroquinolones, preventing acquisition of antibiotic-resistant bacteria, and new antibiotics.
Background: While circulation of respiratory syncytial virus (RSV) results in high rates of hospi... more Background: While circulation of respiratory syncytial virus (RSV) results in high rates of hospitalization, particularly among young children and the elderly, little is known about the role of different age groups in propagating annual RSV epidemics.
Methods: We evaluate the roles played by individuals in different age groups during RSV epidemics in the US between 2001-2012 using the previously defined relative risk (RR) statistic estimated for hospitalization data from the Healthcare Cost and Utilization Project (HCUP). Transmission modeling was used to examine the robustness of our inference method.
Results: Children aged 3-4y and 5-6y each had the highest RR estimate for 5/11 seasons in the data, with RSV hospitalization rates in infants being generally higher during seasons when children aged 5-6y had the highest RR estimate. Children aged 2y had the highest RR estimate during one season. RR estimates in infants and individuals aged 11y and older were mostly lower than in children aged 1-10y. Peak RR values aligned with high-transmitter groups in most model simulations.
Conclusions: Our estimates suggest the prominent relative roles of children aged under 10y (particularly those aged 3-6y) in propagating RSV epidemics. These results, combined with further modeling work should help inform RSV vaccination policies.
Background: There is limited information on the roles of different age groups in propagating pert... more Background: There is limited information on the roles of different age groups in propagating pertussis outbreaks, and the temporal changes in those roles since the introduction of acellular pertussis vaccines.
Methods: The relative roles of different age groups in propagating the 2010 and the 2014 pertussis epidemics in California were evaluated using the RR statistic that measures the change in the group’s proportion among all detected cases before-vs.-after the epidemic peak.
Results: For the 2010-11 epidemic, evidence for a predominant transmission age group was weak, with the largest RR estimates being 1.26(95%CI (1.08,1.46)) (aged 11-13y); 1.19(1.01,1.4) (aged 9-10y); 1.17(0.86,1.59) (aged 14-15y); 1.12(0.86,1.46) (aged 16-19y); and 1.1(0.89,1.36) (aged 7-8y). The 2014 epidemic showed a strong signal of the role of older adolescents, with the highest RR estimate being in those aged 14-15y (RR=1.83(1.61,2.07)), followed by adolescents aged 16-19y (RR=1.41(1.24,1.61)) and 11-13y (RR=1.26(1.12,1.41)), with lower RR estimates in other age groups.
Conclusions: As the time following introduction of acellular pertussis vaccines in California progressed, older adolescents played an increasing role in transmission during the major pertussis outbreaks. Pertussis vaccination for older adolescents with vaccines effective against pertussis transmission should be considered with the aim of mitigating future pertussis epidemics in the community.
Epidemiology, 2012
Background-Existing methods for estimation of mortality attributable to influenza are limited by ... more Background-Existing methods for estimation of mortality attributable to influenza are limited by methodological and data uncertainty. We have used proxies for disease incidence of the three influenza co-circulating subtypes (A/H3N2, A/H1N1 and B) that combine data on influenza-like illness consultations and respiratory specimen testing to estimate influenza-associated mortality in the US between 1997 and 2007.
Background: There is limited information on the roles of different age groups in propagating pert... more Background: There is limited information on the roles of different age groups in propagating pertussis outbreaks, and on the impact of vaccination on pertussis transmission in the community.
Methods: The relative roles of different age groups in propagating the 2012 pertussis outbreak in Wisconsin were evaluated using the RR statistic that measures the change in the group’s proportion among all detected cases before-vs.-after the epidemic peak. The impact of vaccination in different age groups against infection (that is potentially different from the protective effect against detectable disease) was evaluated using the odds ratios (OR), within each age group, for being vaccinated vs. under-vaccinated before vs. after the outbreak’s peak.
Results: The RR statistic suggests that children aged 13-14y played the largest relative role during the outbreak’s ascent (with estimates consistent across the three regions in Wisconsin that were studied), followed by children aged 11-12y, 7-8y, and 9-10y. Young children and older teenagers and adults played more limited relative roles during the outbreak. Results of the vaccination status analysis for the 5th dose of DTaP (OR=0.44 (0.23,0.86) for children aged 7-8y, OR=0.51 (0.27,0.95) for children aged 9-10y) and of Tdap for children aged 13-14y (OR=0.38 (0.16,0.89)) are consistent with protective effect against infection.
Conclusions: While our epidemiological findings for the 5th dose of DTaP and for Tdap are consistent with protective effect against infection, further studies, including those estimating vaccine effectiveness against infection/transmission to others are needed to evaluate the impact of vaccination on the spread of pertussis in the community.
Epidemics, 2015
Please cite this article as: Worby, C.J., Chaves, S.S., Wallinga, J., Lipsitch, M., Finelli, L., ... more Please cite this article as: Worby, C.J., Chaves, S.S., Wallinga, J., Lipsitch, M., Finelli, L., Goldstein, E.,On the relative role of different age groups in influenza epidemics, Epidemics (2015), http://dx.
American Journal of Epidemiology, 2014
Limited information on age-and sex-specific estimates of influenza-associated death with differen... more Limited information on age-and sex-specific estimates of influenza-associated death with different underlying causes is currently available. We regressed weekly age-and sex-specific US mortality outcomes underlying several causes between 1997 and 2007 to incidence proxies for influenza A/H3N2, A/H1N1, and B that combine data on influenzalike illness consultations and respiratory specimen testing, adjusting for seasonal baselines and time trends. Adults older than 75 years of age had the highest average annual rate of influenza-associated mortality, with 141.15 deaths per 100,000 people (95% confidence interval (CI): 118.3, 163.9), whereas children under 18 had the lowest average mortality rate, with 0.41 deaths per 100,000 people (95% CI: 0.23, 0.60). In addition to respiratory and circulatory causes, mortality with underlying cancer, diabetes, renal disease, and Alzheimer disease had a contribution from influenza in adult age groups, whereas mortality with underlying septicemia had a contribution from influenza in children. For adults, within several age groups and for several underlying causes, the rate of influenza-associated mortality was somewhat higher in men than in women. Of note, in men 50-64 years of age, our estimate for the average annual rate of influenza-associated cancer mortality per 100,000 persons (1.90, 95% CI: 1.20, 2.62) is similar to the corresponding rate of influenza-associated respiratory deaths (1.81, 95% CI: 1.42, 2.21). Age, sex, and underlying health conditions should be considered when planning influenza vaccination and treatment strategies.
American Journal of Epidemiology, 2011
Experimental and epidemiologic evidence indicates that variations of absolute humidity account fo... more Experimental and epidemiologic evidence indicates that variations of absolute humidity account for the onset and seasonal cycle of epidemic influenza in temperate regions. A role for absolute humidity in the transmission of pandemic influenza, such as 2009 A/H1N1, has yet to be demonstrated and, indeed, outbreaks of pandemic influenza during more humid spring, summer, and autumn months might appear to constitute evidence against an effect of humidity. However, here the authors show that variations of the basic and effective reproductive numbers for influenza, caused by seasonal changes in absolute humidity, are consistent with the general timing of pandemic influenza outbreaks observed for 2009 A/H1N1 in temperate regions, as well as wintertime transmission of epidemic influenza. Indeed, absolute humidity conditions correctly identify the region of the United States vulnerable to a third, wintertime wave of pandemic influenza. These findings suggest that the timing of pandemic influenza outbreaks is controlled by a combination of absolute humidity conditions, levels of susceptibility, and changes in population-mixing and contact rates. disease outbreaks; disease susceptibility; disease transmission, infectious; humidity; influenza, human Abbreviation: CDC, Centers for Disease Control and Prevention.
Epidemiology, 2014
Background-There is limited information on differences in the dynamics of influenza transmission ... more Background-There is limited information on differences in the dynamics of influenza transmission during time periods when schools are open compared with periods when they are closed.
Some past epidemics of different influenza subtypes (particularly A/H3N2) in the US saw co-circul... more Some past epidemics of different influenza subtypes (particularly A/H3N2) in the US saw co-circulation of vaccine-type and variant strains. There is evidence that natural infection with one influenza subtype offers short-term protection against infection with another influenza subtype (henceforth, cross-immunity). This suggests that such cross-immunity for strains within a subtype is expected to be strong. Therefore, while vaccination effective against one strain may reduce transmission of that strain, this may also lead to a reduction of the vaccine-type strain's ability to suppress spread of a variant strain. It remains unclear what the joint effect of vaccination and cross-immunity is for co-circulating influenza strains within a subtype, and what is the potential benefit of a bivalent vaccine that protects against both strains. We simulated co-circulation of vaccine-type and variant strains under a variety of scenarios. In each scenario, we considered the case when the vaccine efficacy against the variant strain is lower than the efficacy against the vaccine-type strain (monovalent vaccine), as well the case when vaccine is equally efficacious against both strains (bivalent vaccine). Administration of a bivalent vaccine results in a significant reduction in the overall incidence of infection compared to administration of a monovalent vaccine, even with lower coverage by the bivalent vaccine. Additionally, we found that with greater cross-immunity, increasing coverage levels for the monovalent vaccine becomes less beneficial, while introducing the bivalent vaccine becomes more beneficial. Our work exhibits the limitations of influenza vaccines that have low efficacy against non-vaccine strains, and demonstrates the benefits of vaccines that offer good protection against multiple influenza strains. The results elucidate the need for guarding against the potential co-circulation of non-vaccine strains for an influenza subtype, at least during select seasons, possibly through inclusion of multiple strains within a subtype (particularly A/H3N2) in a vaccine.
Background: The epidemic sizes of influenza A/H3N2, A/H1N1, and B infections vary from year to ye... more Background: The epidemic sizes of influenza A/H3N2, A/H1N1, and B infections vary from year to year in the United States. We use publicly available US Centers for Disease Control (CDC) influenza surveillance data between 1997 and 2009 to study the temporal dynamics of influenza over this period.
The availability of weekly Web-based participatory surveillance data on self-reported influenza-l... more The availability of weekly Web-based participatory surveillance data on self-reported influenza-like illness (ILI), defined here as self-reported fever and cough/sore throat, over several influenza seasons allows for estimation of the incidence of influenza infection in population cohorts. We demonstrate this using syndromic data reported through the Influenzanet surveillance platform in the Netherlands. We used the 2011-2012 influenza season, a low-incidence season that began late, to assess the baseline rates of self-reported ILI during periods of low influenza circulation, and we used ILI rates above that baseline level from the 2012-1013 season, a major influenza season, to estimate influenza attack rates for that period. The latter conversion required estimates of age-specific probabilities of self-reported ILI given influenza (Flu) infection (P(ILI | Flu)), which were obtained from separate data (extracted from Hong Kong, China, household studies). For the 2012-2013 influenza season in the Netherlands, we estimated combined influenza A/B attack rates of 29.2% (95% credible interval (CI): 21.6, 37.9) among survey participants aged 20-49 years, 28.3% (95% CI: 20.7, 36.8) among participants aged 50-60 years, and 5.9% (95% CI: 0.4, 11.8) among participants aged ≥61 years. Estimates of influenza attack rates can be obtained in other settings using analogous, multiseason surveillance data on self-reported ILI together with separate, context-specific estimates of P(ILI | Flu).
Journal of Infectious Diseases, 2012
Background. Although deaths associated with laboratory-confirmed influenza virus infections are r... more Background. Although deaths associated with laboratory-confirmed influenza virus infections are rare, the excess mortality burden of influenza estimated from statistical models may more reliably quantify the impact of influenza in a population.
The Lancet Infectious Diseases, 2014
Background The emergence of Neisseria gonorrhoeae with decreased susceptibility to extended spect... more Background The emergence of Neisseria gonorrhoeae with decreased susceptibility to extended spectrum cephalosporins raises the prospect of untreatable gonorrhoea. In the absence of new treatments, eff orts to slow the increasing incidence of resistant gonococcus require insight into the factors that contribute to its emergence and spread. We assessed the relatedness between isolates in the USA and reconstructed likely spread of lineages through diff erent sexual networks.
Emerging Infectious Diseases, 2012
Mathematical Biosciences, 2009
Many of the studies on emerging epidemics (such as SARS and pandemic flu) use mass action models ... more Many of the studies on emerging epidemics (such as SARS and pandemic flu) use mass action models to estimate reproductive numbers and the needed control measures. In reality, transmission patterns are more complex due to the presence of various social networks. One level of complexity can be accommodated by considering a community of households. Our study of transmission dynamics in a community of households emphasizes five types of reproductive numbers for the epidemic spread: household-to-household reproductive number, leaky vaccine-associated reproductive numbers, perfect vaccine reproductive number, growth rate reproductive number, and the individual reproductive number. Each of those carries different information about the transmission dynamics and the required control measures, and often some of those can be estimated from the data while others cannot. Simulations have shown that under certain scenarios there is an ordering for those reproductive numbers. We have proven a number of ordering inequalities under general assumptions about the individual infectiousness profiles. Those inequalities allow, for instance, to estimate the needed vaccine coverage and other control measures without knowing the various transmission parameters in the models. Along the way, we have also shown that in choosing between increasing vaccine efficacy and increasing coverage levels by the same factor, preference should go to efficacy.
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Papers by Edward Goldstein
Methods: We used a multivariable mixed-effects model to relate state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2014 and 2015 to state-specific rates of mortality with sepsis (ICD-10 codes A40-41 present as either underlying or contributing causes of death on a death certificate) in different age groups of US adults between 2014 and 2015, adjusting for additional covariates and random effects associated with the ten US Health and Human Services (HHS) regions.
Results: Increase in the rate of prescribing of oral penicillins by 1 annual dose per 1000 state residents was associated with increases in annual rates of mortality with sepsis of 0.95 (95% CI (0.02,1.88)) per 100,000 persons aged 75-84y, and of 2.97 (0.72,5.22) per 100,000 persons aged 85 + y. Additionally, the percent of individuals aged 50-64y lacking health insurance, as well as the percent of individuals aged 65-84y who are African-American were associated with rates of mortality with sepsis in the corresponding age groups.
Conclusions: Our results suggest that prescribing of penicillins is associated with rates of mortality with sepsis in older US adults. Those results, as well as the related epidemiological data suggest that replacement of certain antibiotics, particularly penicillins in the treatment of different syndromes should be considered with the aim of reducing the rates of severe outcomes, including mortality related to bacterial infections.
Methods: Using previously developed methodology (Goldstein et al., Epidemiology 2012), we regressed the monthly rates of mortality for respiratory causes, as well as circulatory causes (available from the Russian Federal State Statistics Service (Rosstat)) during the 2013/14 through the 2018/19 influenza seasons linearly against the monthly proxies for the incidence of influenza A/H3N2, A/H1N1 and B (obtained using data from the Smorodintsev Research Institute of Influenza (RII) on influenza/ARI consultations, testing of respiratory specimens and genetic/antigenic characterization of influenza viruses), adjusting for the baseline rates of mortality not associated with influenza circulation and temporal trends.
Results: For the 2013/14 through the 2018/19 seasons, influenza circulation was associated with an average annual 17636 (95% CI (9482,25790)) deaths for circulatory causes and 4179 (3250,5109) deaths for respiratory causes, with the largest number of deaths (32298 (18071,46525) for circulatory causes and 6689 (5019,8359) for respiratory causes) estimated during the 2014/15 influenza season. Influenza A/H3N2 was responsible for 51.8% of all circulatory influenza-associated deaths and 37.2% of all respiratory influenza-associated deaths. Influenza A/H1N1 was responsible for 23.4% of all circulatory influenza-associated deaths and 29.5% of all respiratory influenza-associated deaths. Influenza B was responsible for 24.9% of all circulatory influenza-associated deaths and 33.3% of all respiratory influenza-associated deaths, with the overwhelming majority of those deaths being caused by the B/Yamagata viruses. Compared to the 2013/14 through the 2015/16 seasons, during the 2016/17 through the 2018/19 seasons (when levels of influenza vaccination were significantly higher), the volume of influenza-associated mortality declined by about 16.1%, or 3809 annual respiratory and circulatory deaths.
Conclusions: Influenza circulation is associated with a substantial mortality burden in Russia, particularly for circulatory deaths, with some reduction in mortality rates observed following the major increase in influenza vaccination coverage. Those results support the potential utility of further extending the levels of influenza vaccination, the use of quadrivalent influenza vaccines, and extra efforts for protecting individuals with circulatory disease in Russia, including vaccination and the use of antiviral medications.
Methods: We applied previously developed methodology to HealthCare Cost and Utilization Project (HCUP) hospitalization data and additional data related to asthma diagnosis/previous history in hospitalized children to estimate RSV and influenza-associated hospitalization rates in different subpopulations of US children between 2003-2010.
Results: The estimated average annual rates (per 100,000 children) of RSV-associated hospitalization with a respiratory cause (ICD-9 codes 460-519) present anywhere in the discharge diagnosis were 2381 (95% CI(2252,2515)) in children less than a year of age; 710.6(609.1,809.2) (age 1y); 395(327.7,462.4) (age 2y); 211.3(154.6,266.8) (age 3y); 111.1(62.4,160.1) (age 4y); 72.3(29.3,116.4) (ages 5-6y); 35.6(9.9,62.2) (ages 7-11y); and 39(17.5,60.6) (ages 12-17y). The corresponding rates of influenza-associated hospitalization were lower, ranging from 181(142.5,220.3) in age <1y to 17.9(11.7,24.2) in ages 12-17y. The relative risks for RSV-related hospitalization associated with a prior diagnosis of asthma in age groups under 5y ranged between 3.1(2.1,4.7) (age <1y) to 6.7(4.2,11.8) (age 2y); the corresponding risks for influenza-related hospitalization ranged from 2.8(2.1,4) (age <1y) to 4.9(3.8,6.4) (age 3y).
Conclusions: RSV-associated hospitalization rates in young children are high and decline rapidly with age. There are additional risks for both RSV and influenza hospitalization associated with a prior diagnosis of asthma, with the rates of RSV-related hospitalization in the youngest children diagnosed with asthma being particularly high.
Methods: We used multivariable linear regression to relate state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2011 and 2012 to state-specific rates of septicemia hospitalization (ICD-9 codes 038.xx present anywhere on a discharge diagnosis) in each of the following age groups of adults: (18-49y, 50-64y, 65-74y, 75-84y, 85 + y) reported to the Healthcare Cost and Utilization Project (HCUP) between 2011 and 2012, adjusting for additional covariates, and random effects associated with the ten US Health and Human Services (HHS) regions.
Results: Increase in the rate of prescribing of oral penicillins by 1 annual dose per 1000 state residents was associated with increases in annual septicemia hospitalization rates of 0.19 (95% CI (0.02,0.37)) per 10,000 persons aged 50-64y, of 0.48(0.12,0.84) per 10,000 persons aged 65-74y, and of 0.81(0.17,1.40) per 10,000 persons aged 74-84y. Increase by 1 in the percent of African Americans among state residents in a given age group was associated with increases in annual septicemia hospitalization rates of 2.3(0.32,4.2) per 10,000 persons aged 75-84y, and of 5.3(1.1,9.5) per 10,000 persons aged over 85y. Average minimal daily temperature was positively associated with septicemia hospitalization rates in persons aged 18-49y, 50-64y, 75-84y and over 85y.
Conclusions: Our results suggest positive associations between the rates of prescribing for penicillins and the rates of hospitalization with septicemia in US adults aged 50-84y. Further studies are needed to better understand the potential effect of antibiotic replacement in the treatment of various syndromes, including the potential impact of
the recent US FDA guidelines on restriction of fluoroquinolone use, as well as the potential effect of changes in the practices for prescribing of penicillins on the rates of sepsis-related hospitalization and mortality.
Methods: For different age groups of adults (18-49y,50-64y,65-74y,75-84y,85+y) and combinations of antibiotics/bacteria, we evaluated associations between state-specific average annual rates of hospitalizations with septicemia (ICD-9 codes 038.xx present on the discharge diagnosis) in a given age group reported to the Healthcare Cost and Utilization Project (HCUP) between 2011-2012, and state-specific prevalence (percentage) of resistant samples for a given combination of antibiotics/bacteria among catheter-associated urinary tract infections in the CDC Antibiotic Resistance Patient Safety Atlas data between 2011-2014.
Results: Prevalence of resistance to fluoroquinolones in E. coli had the strongest association with septicemia hospitalization rates for adults aged over 50y. A number of positive correlations between prevalence of resistance for different combinations of antibiotics/bacteria and septicemia hospitalization rates in adults were also found.
Conclusions: Our findings about the relation between prevalence of resistance to commonly prescribed antibiotics, particularly fluoroquinolones, and rates of septicemia hospitalization in US adults stress the need for enhancing antibiotic stewardship in different settings, especially for fluoroquinolones, preventing acquisition of antibiotic-resistant bacteria, and new antibiotics.
Methods: We evaluate the roles played by individuals in different age groups during RSV epidemics in the US between 2001-2012 using the previously defined relative risk (RR) statistic estimated for hospitalization data from the Healthcare Cost and Utilization Project (HCUP). Transmission modeling was used to examine the robustness of our inference method.
Results: Children aged 3-4y and 5-6y each had the highest RR estimate for 5/11 seasons in the data, with RSV hospitalization rates in infants being generally higher during seasons when children aged 5-6y had the highest RR estimate. Children aged 2y had the highest RR estimate during one season. RR estimates in infants and individuals aged 11y and older were mostly lower than in children aged 1-10y. Peak RR values aligned with high-transmitter groups in most model simulations.
Conclusions: Our estimates suggest the prominent relative roles of children aged under 10y (particularly those aged 3-6y) in propagating RSV epidemics. These results, combined with further modeling work should help inform RSV vaccination policies.
Methods: The relative roles of different age groups in propagating the 2010 and the 2014 pertussis epidemics in California were evaluated using the RR statistic that measures the change in the group’s proportion among all detected cases before-vs.-after the epidemic peak.
Results: For the 2010-11 epidemic, evidence for a predominant transmission age group was weak, with the largest RR estimates being 1.26(95%CI (1.08,1.46)) (aged 11-13y); 1.19(1.01,1.4) (aged 9-10y); 1.17(0.86,1.59) (aged 14-15y); 1.12(0.86,1.46) (aged 16-19y); and 1.1(0.89,1.36) (aged 7-8y). The 2014 epidemic showed a strong signal of the role of older adolescents, with the highest RR estimate being in those aged 14-15y (RR=1.83(1.61,2.07)), followed by adolescents aged 16-19y (RR=1.41(1.24,1.61)) and 11-13y (RR=1.26(1.12,1.41)), with lower RR estimates in other age groups.
Conclusions: As the time following introduction of acellular pertussis vaccines in California progressed, older adolescents played an increasing role in transmission during the major pertussis outbreaks. Pertussis vaccination for older adolescents with vaccines effective against pertussis transmission should be considered with the aim of mitigating future pertussis epidemics in the community.
Methods: The relative roles of different age groups in propagating the 2012 pertussis outbreak in Wisconsin were evaluated using the RR statistic that measures the change in the group’s proportion among all detected cases before-vs.-after the epidemic peak. The impact of vaccination in different age groups against infection (that is potentially different from the protective effect against detectable disease) was evaluated using the odds ratios (OR), within each age group, for being vaccinated vs. under-vaccinated before vs. after the outbreak’s peak.
Results: The RR statistic suggests that children aged 13-14y played the largest relative role during the outbreak’s ascent (with estimates consistent across the three regions in Wisconsin that were studied), followed by children aged 11-12y, 7-8y, and 9-10y. Young children and older teenagers and adults played more limited relative roles during the outbreak. Results of the vaccination status analysis for the 5th dose of DTaP (OR=0.44 (0.23,0.86) for children aged 7-8y, OR=0.51 (0.27,0.95) for children aged 9-10y) and of Tdap for children aged 13-14y (OR=0.38 (0.16,0.89)) are consistent with protective effect against infection.
Conclusions: While our epidemiological findings for the 5th dose of DTaP and for Tdap are consistent with protective effect against infection, further studies, including those estimating vaccine effectiveness against infection/transmission to others are needed to evaluate the impact of vaccination on the spread of pertussis in the community.
Methods: We used a multivariable mixed-effects model to relate state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2014 and 2015 to state-specific rates of mortality with sepsis (ICD-10 codes A40-41 present as either underlying or contributing causes of death on a death certificate) in different age groups of US adults between 2014 and 2015, adjusting for additional covariates and random effects associated with the ten US Health and Human Services (HHS) regions.
Results: Increase in the rate of prescribing of oral penicillins by 1 annual dose per 1000 state residents was associated with increases in annual rates of mortality with sepsis of 0.95 (95% CI (0.02,1.88)) per 100,000 persons aged 75-84y, and of 2.97 (0.72,5.22) per 100,000 persons aged 85 + y. Additionally, the percent of individuals aged 50-64y lacking health insurance, as well as the percent of individuals aged 65-84y who are African-American were associated with rates of mortality with sepsis in the corresponding age groups.
Conclusions: Our results suggest that prescribing of penicillins is associated with rates of mortality with sepsis in older US adults. Those results, as well as the related epidemiological data suggest that replacement of certain antibiotics, particularly penicillins in the treatment of different syndromes should be considered with the aim of reducing the rates of severe outcomes, including mortality related to bacterial infections.
Methods: Using previously developed methodology (Goldstein et al., Epidemiology 2012), we regressed the monthly rates of mortality for respiratory causes, as well as circulatory causes (available from the Russian Federal State Statistics Service (Rosstat)) during the 2013/14 through the 2018/19 influenza seasons linearly against the monthly proxies for the incidence of influenza A/H3N2, A/H1N1 and B (obtained using data from the Smorodintsev Research Institute of Influenza (RII) on influenza/ARI consultations, testing of respiratory specimens and genetic/antigenic characterization of influenza viruses), adjusting for the baseline rates of mortality not associated with influenza circulation and temporal trends.
Results: For the 2013/14 through the 2018/19 seasons, influenza circulation was associated with an average annual 17636 (95% CI (9482,25790)) deaths for circulatory causes and 4179 (3250,5109) deaths for respiratory causes, with the largest number of deaths (32298 (18071,46525) for circulatory causes and 6689 (5019,8359) for respiratory causes) estimated during the 2014/15 influenza season. Influenza A/H3N2 was responsible for 51.8% of all circulatory influenza-associated deaths and 37.2% of all respiratory influenza-associated deaths. Influenza A/H1N1 was responsible for 23.4% of all circulatory influenza-associated deaths and 29.5% of all respiratory influenza-associated deaths. Influenza B was responsible for 24.9% of all circulatory influenza-associated deaths and 33.3% of all respiratory influenza-associated deaths, with the overwhelming majority of those deaths being caused by the B/Yamagata viruses. Compared to the 2013/14 through the 2015/16 seasons, during the 2016/17 through the 2018/19 seasons (when levels of influenza vaccination were significantly higher), the volume of influenza-associated mortality declined by about 16.1%, or 3809 annual respiratory and circulatory deaths.
Conclusions: Influenza circulation is associated with a substantial mortality burden in Russia, particularly for circulatory deaths, with some reduction in mortality rates observed following the major increase in influenza vaccination coverage. Those results support the potential utility of further extending the levels of influenza vaccination, the use of quadrivalent influenza vaccines, and extra efforts for protecting individuals with circulatory disease in Russia, including vaccination and the use of antiviral medications.
Methods: We applied previously developed methodology to HealthCare Cost and Utilization Project (HCUP) hospitalization data and additional data related to asthma diagnosis/previous history in hospitalized children to estimate RSV and influenza-associated hospitalization rates in different subpopulations of US children between 2003-2010.
Results: The estimated average annual rates (per 100,000 children) of RSV-associated hospitalization with a respiratory cause (ICD-9 codes 460-519) present anywhere in the discharge diagnosis were 2381 (95% CI(2252,2515)) in children less than a year of age; 710.6(609.1,809.2) (age 1y); 395(327.7,462.4) (age 2y); 211.3(154.6,266.8) (age 3y); 111.1(62.4,160.1) (age 4y); 72.3(29.3,116.4) (ages 5-6y); 35.6(9.9,62.2) (ages 7-11y); and 39(17.5,60.6) (ages 12-17y). The corresponding rates of influenza-associated hospitalization were lower, ranging from 181(142.5,220.3) in age <1y to 17.9(11.7,24.2) in ages 12-17y. The relative risks for RSV-related hospitalization associated with a prior diagnosis of asthma in age groups under 5y ranged between 3.1(2.1,4.7) (age <1y) to 6.7(4.2,11.8) (age 2y); the corresponding risks for influenza-related hospitalization ranged from 2.8(2.1,4) (age <1y) to 4.9(3.8,6.4) (age 3y).
Conclusions: RSV-associated hospitalization rates in young children are high and decline rapidly with age. There are additional risks for both RSV and influenza hospitalization associated with a prior diagnosis of asthma, with the rates of RSV-related hospitalization in the youngest children diagnosed with asthma being particularly high.
Methods: We used multivariable linear regression to relate state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2011 and 2012 to state-specific rates of septicemia hospitalization (ICD-9 codes 038.xx present anywhere on a discharge diagnosis) in each of the following age groups of adults: (18-49y, 50-64y, 65-74y, 75-84y, 85 + y) reported to the Healthcare Cost and Utilization Project (HCUP) between 2011 and 2012, adjusting for additional covariates, and random effects associated with the ten US Health and Human Services (HHS) regions.
Results: Increase in the rate of prescribing of oral penicillins by 1 annual dose per 1000 state residents was associated with increases in annual septicemia hospitalization rates of 0.19 (95% CI (0.02,0.37)) per 10,000 persons aged 50-64y, of 0.48(0.12,0.84) per 10,000 persons aged 65-74y, and of 0.81(0.17,1.40) per 10,000 persons aged 74-84y. Increase by 1 in the percent of African Americans among state residents in a given age group was associated with increases in annual septicemia hospitalization rates of 2.3(0.32,4.2) per 10,000 persons aged 75-84y, and of 5.3(1.1,9.5) per 10,000 persons aged over 85y. Average minimal daily temperature was positively associated with septicemia hospitalization rates in persons aged 18-49y, 50-64y, 75-84y and over 85y.
Conclusions: Our results suggest positive associations between the rates of prescribing for penicillins and the rates of hospitalization with septicemia in US adults aged 50-84y. Further studies are needed to better understand the potential effect of antibiotic replacement in the treatment of various syndromes, including the potential impact of
the recent US FDA guidelines on restriction of fluoroquinolone use, as well as the potential effect of changes in the practices for prescribing of penicillins on the rates of sepsis-related hospitalization and mortality.
Methods: For different age groups of adults (18-49y,50-64y,65-74y,75-84y,85+y) and combinations of antibiotics/bacteria, we evaluated associations between state-specific average annual rates of hospitalizations with septicemia (ICD-9 codes 038.xx present on the discharge diagnosis) in a given age group reported to the Healthcare Cost and Utilization Project (HCUP) between 2011-2012, and state-specific prevalence (percentage) of resistant samples for a given combination of antibiotics/bacteria among catheter-associated urinary tract infections in the CDC Antibiotic Resistance Patient Safety Atlas data between 2011-2014.
Results: Prevalence of resistance to fluoroquinolones in E. coli had the strongest association with septicemia hospitalization rates for adults aged over 50y. A number of positive correlations between prevalence of resistance for different combinations of antibiotics/bacteria and septicemia hospitalization rates in adults were also found.
Conclusions: Our findings about the relation between prevalence of resistance to commonly prescribed antibiotics, particularly fluoroquinolones, and rates of septicemia hospitalization in US adults stress the need for enhancing antibiotic stewardship in different settings, especially for fluoroquinolones, preventing acquisition of antibiotic-resistant bacteria, and new antibiotics.
Methods: We evaluate the roles played by individuals in different age groups during RSV epidemics in the US between 2001-2012 using the previously defined relative risk (RR) statistic estimated for hospitalization data from the Healthcare Cost and Utilization Project (HCUP). Transmission modeling was used to examine the robustness of our inference method.
Results: Children aged 3-4y and 5-6y each had the highest RR estimate for 5/11 seasons in the data, with RSV hospitalization rates in infants being generally higher during seasons when children aged 5-6y had the highest RR estimate. Children aged 2y had the highest RR estimate during one season. RR estimates in infants and individuals aged 11y and older were mostly lower than in children aged 1-10y. Peak RR values aligned with high-transmitter groups in most model simulations.
Conclusions: Our estimates suggest the prominent relative roles of children aged under 10y (particularly those aged 3-6y) in propagating RSV epidemics. These results, combined with further modeling work should help inform RSV vaccination policies.
Methods: The relative roles of different age groups in propagating the 2010 and the 2014 pertussis epidemics in California were evaluated using the RR statistic that measures the change in the group’s proportion among all detected cases before-vs.-after the epidemic peak.
Results: For the 2010-11 epidemic, evidence for a predominant transmission age group was weak, with the largest RR estimates being 1.26(95%CI (1.08,1.46)) (aged 11-13y); 1.19(1.01,1.4) (aged 9-10y); 1.17(0.86,1.59) (aged 14-15y); 1.12(0.86,1.46) (aged 16-19y); and 1.1(0.89,1.36) (aged 7-8y). The 2014 epidemic showed a strong signal of the role of older adolescents, with the highest RR estimate being in those aged 14-15y (RR=1.83(1.61,2.07)), followed by adolescents aged 16-19y (RR=1.41(1.24,1.61)) and 11-13y (RR=1.26(1.12,1.41)), with lower RR estimates in other age groups.
Conclusions: As the time following introduction of acellular pertussis vaccines in California progressed, older adolescents played an increasing role in transmission during the major pertussis outbreaks. Pertussis vaccination for older adolescents with vaccines effective against pertussis transmission should be considered with the aim of mitigating future pertussis epidemics in the community.
Methods: The relative roles of different age groups in propagating the 2012 pertussis outbreak in Wisconsin were evaluated using the RR statistic that measures the change in the group’s proportion among all detected cases before-vs.-after the epidemic peak. The impact of vaccination in different age groups against infection (that is potentially different from the protective effect against detectable disease) was evaluated using the odds ratios (OR), within each age group, for being vaccinated vs. under-vaccinated before vs. after the outbreak’s peak.
Results: The RR statistic suggests that children aged 13-14y played the largest relative role during the outbreak’s ascent (with estimates consistent across the three regions in Wisconsin that were studied), followed by children aged 11-12y, 7-8y, and 9-10y. Young children and older teenagers and adults played more limited relative roles during the outbreak. Results of the vaccination status analysis for the 5th dose of DTaP (OR=0.44 (0.23,0.86) for children aged 7-8y, OR=0.51 (0.27,0.95) for children aged 9-10y) and of Tdap for children aged 13-14y (OR=0.38 (0.16,0.89)) are consistent with protective effect against infection.
Conclusions: While our epidemiological findings for the 5th dose of DTaP and for Tdap are consistent with protective effect against infection, further studies, including those estimating vaccine effectiveness against infection/transmission to others are needed to evaluate the impact of vaccination on the spread of pertussis in the community.