Mortality associated with Omicron and influenza infections in France before and during the COVID-19 pandemic.

For many deaths associated with influenza and Omicron infections, those viruses are not detected. We applied previously developed methodology to estimate the contribution of influenza and Omicron infections to all-cause mortality in France for the 2014-2015 through the 2018-2019 influenza seasons, and the period between week 33, 2022 and week 12, 2023. For the 2014-2015 through the 2018-2019 seasons, influenza was associated with annual average of 15,654 (95% CI (13,013, 18,340)) deaths, while between week 33, 2022 and week 12, 2023, we estimated 7,851 (5,213, 10,463) influenza-associated deaths and 32,607 (20,794, 44,496) SARS-CoV-2 associated deaths. For many Omicron-associated deaths for cardiac disease, mental&behavioural disorders, and other causes, Omicron infections are not characterised as a contributing cause of death - for example, between weeks 33-52 in 2022, we estimated 23,983 (15,307, 32,620) SARS-CoV-2-associated deaths in France, compared with 12,811 deaths with COVID-19 listed on death certificate. Our results suggest the need for boosting influenza vaccination coverage in different population groups in France, and for wider detection of influenza infections in respiratory illness episodes (including pneumonia) in combination with the use of antiviral medications. For Omicron epidemics, wider detection of Omicron infections in persons with underlying health conditions is needed.

Prescribing for different antibiotic classes across age groups in the Kaiser Permanente Northern California population in association with influenza incidence, 2010-2018.

There is limited information on the volume of antibiotic prescribing that is influenza-associated, resulting from influenza infections and their complications (such as streptococcal pharyngitis). We estimated that for the Kaiser Permanente Northern California population during 2010-2018, 3.4% (2.8%-4%) of all macrolide prescriptions (fills), 2.7% (2.3%-3.2%) of all aminopenicillin prescriptions, 3.1% (2.4%-3.9%) of all 3rd generation cephalosporins prescriptions, 2.2% (1.8%-2.6%) of all protected aminopenicillin prescriptions and 1.3% (1%-1.6%) of all quinolone prescriptions were influenza-associated. The corresponding proportions were higher for select age groups, e.g. 4.3% of macrolide prescribing in ages over 50 years, 5.1% (3.3%-6.8%) of aminopenicillin prescribing in ages 5-17 years and 3.3% (1.9%-4.6%) in ages <5 years was influenza-associated. The relative contribution of influenza to antibiotic prescribing for respiratory diagnoses without a bacterial indication in ages over 5 years was higher than the corresponding relative contribution to prescribing for all diagnoses. Our results suggest a modest benefit of increasing influenza vaccination coverage for reducing prescribing for the five studied antibiotic classes, particularly for macrolides in ages over 50 years and aminopenicillins in ages <18 years, and the potential benefit of other measures to reduce unnecessary antibiotic prescribing for respiratory diagnoses with no bacterial indication, both of which may contribute to the mitigation of antimicrobial resistance.

Antibiotic prescribing across age groups in the Kaiser Permanente Northern California population in association with different diagnoses, and with influenza incidence, 2010-2018.

There is limited information on the volume of antibiotic prescribing that is influenza-associated, resulting from influenza infections and their complications (such as streptococcal pharyngitis and otitis media). Here, we estimated age/diagnosis-specific proportions of antibiotic prescriptions (fills) for the Kaiser Permanente Northern California population during 2010-2018 that were influenza-associated. The proportion of influenza-associated antibiotic prescribing among all antibiotic prescribing was higher in children aged 5-17 years compared to children aged under 5 years, ranging from 1.4% [95% CI (0.7-2.1)] in aged <1 year to 2.7% (1.9-3.4) in aged 15-17 years. For adults aged over 20 years, the proportion of influenza-associated antibiotic prescribing among all antibiotic prescribing was lower, ranging from 0.7% (0.5-1) for aged 25-29 years to 1.6% (1.2-1.9) for aged 60-64 years. Most of the influenza-associated antibiotic prescribing in children aged under 10 years was for ear infections, while for age groups over 25 years, 45-84% of influenza-associated antibiotic prescribing was for respiratory diagnoses without a bacterial indication. This suggests a modest benefit of increasing influenza vaccination coverage for reducing antibiotic prescribing, as well as the potential benefit of other measures to reduce unnecessary antibiotic prescribing for respiratory diagnoses with no bacterial indication in persons aged over 25 years, both of which may further contribute to the mitigation of antimicrobial resistance.

Rise in the prevalence of resistance to extended-spectrum cephalosporins in the USA, nursing homes and antibiotic prescribing in outpatient and inpatient settings.

The prevalence of resistance to extended-spectrum (ES) cephalosporins for multiple types of infections treated in US hospitals and the incidence of hospitalization with ESBL-producing Enterobacteriaceae (many of which are detected in nursing home residents) have grown markedly in recent years. Here, I review these developments, as well as evidence for their adverse consequences, including the increase in the overall burden of bacterial infections due to proliferation of ESBL-producing/ES cephalosporin-resistant bacteria, the contribution of ESBL-producing/ES cephalosporin-resistant bacteria to the increase in the burden of mortality associated with bacterial infections and the contribution of the proliferation of ESBL-producing bacteria to the prevalence of carbapenem resistance. I argue that in order to mitigate the escalation of these phenomena, a reduction in outpatient prescribing of cephalosporins, especially to older adults, mitigation of transmission of ESBL-producing organisms in nursing homes and a reduction in inpatient prescribing of ES cephalosporins (which has seen a major increase in recent years) are needed.

On the increasing incidence of SARSCoV-2 in older adolescents and younger adults during the epidemic in Mexico / Sobre la incidencia creciente de SARS-CoV-2 en adolescentes mayores y adultos jóvenes durante la epidemia en México

Abstract Objective: To estimate temporary changes in the incidence of SARS-CoV-2-confirmed hospitalizations (by date of symptom onset) by age group during and after the national lockdown. Materials and methods: For each age group g, we computed the proportion E(g) of individuals in that age group among all cases aged 10-59y during the early lockdown period (April 20-May 3, 2020), and the corresponding proportion L(g) during the late lockdown (May 18-31, 2020) and post-lockdown (June 15-28, 2020) periods and computed the prevalence ratio: PR(g)=L(g)/E(g). Results: For the late lockdown and post-lockdown periods, the highest PR values were found in age groups 15-19y (late: PR=1.69, 95%CI 1.05,2.72; post-lockdown: PR=2.05, 1.30,3.24) and 20-24y (late: PR=1.43, 1.10,1.86; post-lockdown: PR=1.49, 1.15,1.93). These estimates were higher in individuals 15-24y compared to those ≥30y. Conclusions: Adolescents and younger adults had an increased relative incidence of SARS-CoV-2 during late lockdown and post-lockdown periods. The role of these age groups should be considered when implementing future pandemic response efforts.

Resumen Objetivo: Estimar los cambios temporales en la incidencia de hospitalizaciones confirmadas por SARS-CoV-2 (por fecha de inicio de los síntomas) por grupo de edad durante y después del cierre nacional. Material y métodos: Para cada grupo de edad g, calculamos la proporción E(g) de individuos en ese grupo de edad entre todos los casos de 10 a 59 años durante el periodo de cierre temprano (del 20 de abril al 3 de mayo de 2020) y la proporción correspondiente L(g) durante los periodos de cierre tardío (18-31 de mayo de 2020) y posterior al cierre (15-28 de junio de 2020), y se calculó la razón de prevalencia: RP(g)=L(g)/E(g). Resultados: Para los periodos de cierre tardío y posterior al cierre, los valores de RP más altos se dieron en los grupos de edad de 15 a 19 años (tardío: RP=1.69, IC95% 1.05,2.72; después del cierre: RP=2.05, 1.30,3.24) y 20-24 años (tardío: RP=1.43, 1.10,1.86; después del cierre: RP=1.49, 1.15,1.93). Estas estimaciones fueron más altas en personas de 15 a 24 años en comparación con las de ≥ 30 años Conclusiones: Los adolescentes y los adultos jóvenes tuvieron una mayor incidencia relativa de SARS-CoV-2 durante los periodos de cierre tardío y posteriores al cierre. El papel de estos grupos de edad en la transmisión de la enfermedad debe tenerse en cuenta al implementar futuros esfuerzos de respuesta a una pandemia.

On the increasing incidence of SARS-CoV- 2 in older adolescents and younger adults during the epidemic in Mexico.

OBJECTIVE: To estimate temporary changes in the inciden-ce of SARS-CoV-2-confirmed hospitalizations (by date of symptom onset) by age group during and after the national lockdown. MATERIALS AND METHODS: For each age group g, we computed the proportion E(g) of individuals in that age group among all cases aged 10-59y during the early lock-down period (April 20-May 3, 2020), and the corresponding proportion L(g) during the late lockdown (May 18-31, 2020) and post-lockdown (June 15-28, 2020) periods and computed the prevalence ratio: PR(g)=L(g)/E(g). RESULTS: For the late lockdown and post-lockdown periods, the highest PR values were found in age groups 15-19y (late: PR=1.69, 95%CI 1.05,2.72; post-lockdown: PR=2.05, 1.30,3.24) and 20-24y (late: PR=1.43, 1.10,1.86; post-lockdown: PR=1.49, 1.15,1.93). These estimates were higher in individuals 15-24y compared to those ≥30y. CONCLUSIONS: Adolescents and younger adults had an increased relative incidence of SARS-CoV-2 during late lockdown and post-lockdown periods. The role of these age groups should be considered when implementing future pandemic response efforts.

How to detect and reduce potential sources of biases in studies of SARS-CoV-2 and COVID-19.

In response to the coronavirus disease (COVID-19) pandemic, public health scientists have produced a large and rapidly expanding body of literature that aims to answer critical questions, such as the proportion of the population in a geographic area that has been infected; the transmissibility of the virus and factors associated with high infectiousness or susceptibility to infection; which groups are the most at risk of infection, morbidity and mortality; and the degree to which antibodies confer protection to re-infection. Observational studies are subject to a number of different biases, including confounding, selection bias, and measurement error, that may threaten their validity or influence the interpretation of their results. To assist in the critical evaluation of a vast body of literature and contribute to future study design, we outline and propose solutions to biases that can occur across different categories of observational studies of COVID-19. We consider potential biases that could occur in five categories of studies: (1) cross-sectional seroprevalence, (2) longitudinal seroprotection, (3) risk factor studies to inform interventions, (4) studies to estimate the secondary attack rate, and (5) studies that use secondary attack rates to make inferences about infectiousness and susceptibility.

On the Effect of Age on the Transmission of SARS-CoV-2 in Households, Schools, and the Community.

BACKGROUND: There is limited information on the effect of age on the transmission of SARS-CoV-2 infection in different settings. METHODS: We reviewed published studies/data on detection of SARS-CoV-2 infection in contacts of COVID-19 cases, serological studies, and studies of infections in schools. RESULTS: Compared to younger/middle-aged adults, susceptibility to infection for children younger than 10 years is estimated to be significantly lower, while estimated susceptibility to infection in adults older than 60 years is higher. Serological studies suggest that younger adults (particularly those younger than 35 years) often have high cumulative incidence of SARS-CoV-2 infection in the community. There is some evidence that given limited control measures, SARS-CoV-2 may spread robustly in secondary/high schools, and to a lesser degree in primary schools, with class size possibly affecting that spread. There is also evidence of more limited spread in schools when some mitigation measures are implemented. Several potential biases that may affect these studies are discussed. CONCLUSIONS: Mitigation measures should be implemented when opening schools, particularly secondary/high schools. Efforts should be undertaken to diminish mixing in younger adults, particularly individuals aged 18-35 years, to mitigate the spread of the epidemic in the community.

On the increasing role of older adolescents and younger adults during the SARS-CoV-2 epidemic in Mexico.

Background: During the first months of the SARS-CoV-2 pandemic, Mexico implemented a national lockdown followed by post-lockdown mitigation. Methods: We used daily number of SARS-CoV-2-confirmed hospitalizations (by date of symptom onset) to assess the changes in the incidence of individuals between the age of 10-59 years during the epidemic in Mexico. For each age group g, we computed the proportion E(g) of individuals in that age group among all cases aged 10-59y during the early lockdown period (April 20-May 3, 2020), and the corresponding proportion L(g) during the late lockdown period (May 18-31, 2020) and post-lockdown mitigation (June 15-28, 2020). For each later period (late lockdown or post-lockdown), we computed the proportion ratios relative to the early lockdown period PR(g)=L(g)/E(g). For each pair of age groups g1,g2, PR(g1)> PR(g2) is interpreted as a relative increase in SARS-CoV-2 infections in the age group g1 compared to g2 for the late lockdown and post-lockdown periods vs. the early lockdown period. Results: For the late lockdown period, the highest PR estimates belong to persons aged 15-19y (PR=1.69(95%CI(1.05, 2.72))) and 20-24y (PR=1.43(1.10,1.86)). For the post-lockdown period, the highest PR estimates were also in age groups 15-19y (PR=2.05(1.30, 3.24)) and 20-24y (PR=1.49(1.15,1.93)). These estimates were higher in persons 15-24y compared to those ≥30y. Conclusions: Our results suggest that adolescents and younger adults had an increased relative incidence during late lockdown and the post-lockdown mitigation periods. The role of these age groups during the epidemic should be considered when implementing future pandemic response efforts.

Number needed to immunize to prevent RSV with extended half-life monoclonal antibody.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the most important respiratory pathogens in young children. Infants <6 months of age and infants and young children with extreme pre-term birth, and cardiac and pulmonary co-morbidities experience the highest incidence of severe RSV disease. There are no licensed vaccines; immunoprophylaxis is recommended for the highest risk children. Extended half-life RSV monoclonal antibodies (EHL-mAbs) are under development intended for immunization of all infants and high-risk children <2 years of age. We modeled the anticipated public health benefits of RSV EHL-mAb immunization using the number needed to immunize (NNI). METHODS: We combined RSV hospitalization, outpatient and outpatient lower respiratory tract infection (LRI) incidence estimates and a range of immunization efficacies to estimate the annual NNI. We calculated the absolute incidence rate reduction (ARR) by multiplying the incidence rates by immunization efficacy. NNI was calculated as the reciprocal of the ARR. RESULTS: For an RSV EHL-mAb with 70% efficacy, 6-18 infants would need to be immunized to prevent one RSV-associated outpatient visit, and 13-33 infants would need to be immunized to prevent one RSV-associated LRI outpatient visit. To prevent one RSV-associated hospitalization, 37-85 infants 0-5 months of age, and 107-280 infants 6-11 months of age would need to be immunized. CONCLUSIONS: Public health benefits, such as disease cases averted due to immunization, are essential elements in consideration of candidate vaccines for a national immunization program. An RSV EHL-mAb of moderate efficacy could have high impact. These data provide an additional perspective for public health decision making.

Temporal rise in the proportion of both younger adults and older adolescents among COVID-19 cases in Germany: evidence of lesser adherence to social distancing practices?

Background: There is uncertainty about the role of different age groups in propagating the SARS-CoV-2 epidemics in different countries, particularly under current social distancing practices. Methods: We used the Robert Koch Institute data on weekly COVID-19 cases in different age groups in Germany. To minimize the effect of changes in healthcare seeking behavior (e.g. for older adults) and testing practices, we included the following eight 5-year age groups in the analyses: 10-14y through 45-49y. For each age group g, we considered the proportion PL(g) of individuals in age group g among all detected cases aged 10-49y during weeks 13-14, 2020 (later period), as well as corresponding proportion PE(g) for weeks 10-11, 2020 (early period), and defined the relative risk RR(g) for the age group g to be the ratio RR(g) = PL(g)/PE(g). For each pair of age groups g1, g2, a higher value of RR(g1) compared to RR(g2), or, alternatively, a value above 1 for the odds ratio OR(g1, g2) = RR(g1)/RR(g2) for a COVID-19 case to be in group g1 vs. g2 for the later vs. early periods is interpreted as the relative increase in the population incidence of SARS-Cov-2 in the age group g1 compared to g2 for the later vs. early period. Results: The relative risk RR(g) was highest for individuals aged 20-24y (RR=1.4(95% CI (1.27,1.55))), followed by individuals aged 15-19y (RR=1.14(0.99,1.32)), aged 30-34y (RR=1.07(0.99,1.16)), aged 25-29y (RR= 1.06(0.98,1.15)), aged 35-39y (RR=0.95(0.87,1.03)), aged 40-44y (RR=0.9(0.83,0.98)), aged 45-49y (RR=0.83(0.77,0.89)) and aged 10-14y (RR=0.78(0.64,0.95)). For the age group 20-24y, the odds ratio relative to any other age group for a case to be during the later vs. early period was significantly above 1. For the age group 15-19y, the odds ratio relative to any other age group either above 35y or 10-14y for a case to be during the later vs. early period was significantly above 1. Conclusions: The observed relative increase with time in the prevalence of individuals aged 15-34y (particularly those aged 20-24y) among detected COVID-19 cases in Germany is unlikely to be explained by increases in the likelihood of seeking medical care or the likelihood of being tested for individuals in those age groups compared to individuals aged 35-49y or 10-14y, and should be indicative of the actual increase in the prevalence of individuals aged 15-34y among SARS-CoV-2 infections in the German population. That increase likely reflects elevated mixing among individuals aged 15-34y (particularly those aged 20-24y) compared to other age groups, possibly due to lesser adherence to social distancing practices.

Temporal rise in the proportion of younger adults and older adolescents among coronavirus disease (COVID-19) cases following the introduction of physical distancing measures, Germany, March to April 2020.

Using data on coronavirus disease (COVID-19) cases in Germany from the Robert Koch Institute, we found a relative increase with time in the prevalence in 15-34 year-olds (particularly 20-24-year-olds) compared with 35-49- and 10-14-year-olds (we excluded older and younger ages because of different healthcare seeking behaviour). This suggests an elevated role for that age group in propagating the epidemic following the introduction of physical distancing measures.

Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period.

It is urgent to understand the future of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1 using time-series data from the United States to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained because a resurgence in contagion could be possible as late as 2024.

The relation between prescribing of different antibiotics and rates of mortality with sepsis in US adults.

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.

Hospitalizations Associated with Respiratory Syncytial Virus and Influenza in Children, Including Children Diagnosed with Asthma.

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 Health Care Cost and Utilization Project 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 and 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 2,381 (95% CI(2252,2515)) in children <1 year of age; 710.6 (609.1, 809.2) (1 y old); 395 (327.7, 462.4) (2 y old); 211.3 (154.6, 266.8) (3 y old); 111.1 (62.4, 160.1) (4 y old); 72.3 (29.3, 116.4) (5-6 y of age); 35.6 (9.9,62.2) (7-11 y of age); and 39 (17.5, 60.6) (12-17 y of age). The corresponding rates of influenza-associated hospitalization were lower, ranging from 181 (142.5, 220.3) in <1 year old to 17.9 (11.7, 24.2) in 12-17 years of age. The relative risks for RSV-related hospitalization associated with a prior diagnosis of asthma in age groups <5 y ranged between 3.1 (2.1, 4.7) (<1 y old) and 6.7 (4.2, 11.8) (2 y old; the corresponding risks for influenza-related hospitalization ranged from 2.8 (2.1, 4) (<1y old) to 4.9 (3.8, 6.4) (3 y old). CONCLUSION: 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.

Real-time estimation of the influenza-associated excess mortality in Hong Kong.

Statistical models are commonly employed in the estimation of influenza-associated excess mortality that, due to various reasons, is often underestimated by laboratory-confirmed influenza deaths reported by healthcare facilities. However, methodology for timely and reliable estimation of that impact remains limited because of the delay in mortality data reporting. We explored real-time estimation of influenza-associated excess mortality by types/subtypes in each year between 2012 and 2018 in Hong Kong using linear regression models fitted to historical mortality and influenza surveillance data. We could predict that during the winter of 2017/2018, there were ~634 (95% confidence interval (CI): (190, 1033)) influenza-associated excess all-cause deaths in Hong Kong in population ⩾18 years, compared to 259 reported laboratory-confirmed deaths. We estimated that influenza was associated with substantial excess deaths in older adults, suggesting the implementation of control measures, such as administration of antivirals and vaccination, in that age group. The approach that we developed appears to provide robust real-time estimates of the impact of influenza circulation and complement surveillance data on laboratory-confirmed deaths. These results improve our understanding of the impact of influenza epidemics and provide a practical approach for a timely estimation of the mortality burden of influenza circulation during an ongoing epidemic.

Levels of outpatient prescribing for four major antibiotic classes and rates of septicemia hospitalization in adults in different US states - a statistical analysis.

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.

Rise in mortality involving poisoning by medicaments other than narcotics, including poisoning by psychotropic drugs in different age/racial groups in the US.

BACKGROUND: Increase in mortality involving poisoning, particularly by narcotics, is known to have been one of the factors that affected life expectancy in the US during the last two decades, especially for white Americans and Native Americans. However, the contribution of medicaments other than narcotics to mortality in different racial/age groups is less studied. METHODS: We regressed annual rates of mortality involving poisoning by medicaments but not narcotics/psychodysleptics (ICD-10 codes T36-39.xx or T41-50.8 but not T40.xx present as either underlying or contributing causes of death), as well as annual rates of mortality for certain subcategories of the above, including mortality involving poisoning by psychotropic drugs but not narcotics/psychodysleptics (ICD-10 codes T43.xx but not T40.xx present as either underlying or contributing causes of death) in different age/racial groups for both the 2000-2011 period and the 2011-2017 period against calendar year. RESULTS: Annual numbers of deaths involving poisoning by medicaments but not narcotics/psychodysleptics grew from 4,332 between 2000-2001 to 11,401 between 2016-2017, with the growth in the rates of those deaths being higher for the 2011-2017 period compared to the 2000-2011 period. The largest increases in the rates of mortality involving poisoning by medicaments but not narcotics/psychodysleptics were in non-elderly Non-Hispanic Native Americans, followed by Non-Hispanic whites. Most of those increases came from increases in the rates of mortality involving poisoning by psychotropic medications; the latter rates grew for the period of 2015-2017 vs. 2000-2002 by factors ranging from 2.75 for ages 35-44y to 5.37 for ages 55-64y. CONCLUSIONS: There were major increases in mortality involving poisoning by non-narcotic, particularly psychotropic medicaments, especially in non-elderly non-Hispanic whites and Native Americans. Our results support the need for a comprehensive evaluation of the effect of psychotropic medications on health-related outcomes, including mortality for causes other than poisoning, and the impact of medication misuse.

Antimicrobial resistance prevalence, rates of hospitalization with septicemia and rates of mortality with sepsis in adults in different US states.

OBJECTIVES: Rates of hospitalization with sepsis/septicemia and associated mortality in the US have risen significantly during the last two decades. Antibiotic resistance may contribute to the rates of sepsis-related outcomes through lack of clearance of bacterial infections following antibiotic treatment during different stages of infection. However, there is limited information about the relationship between prevalence of resistance to various antibiotics in different bacteria and rates of sepsis-related outcomes. 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 prevalence (percentage) of resistant samples for a given combination of antibiotics/bacteria among catheter-associated urinary tract infections (CAUTIs) in the CDC Antibiotic Resistance Patient Safety Atlas data between 2011-2014, and rates of hospitalization with septicemia (ICD-9 codes 038.xx present on the discharge diagnosis) reported to the Healthcare Cost and Utilization Project (HCUP), as well as rates of mortality with sepsis (ICD-10 codes A40-41.xx present on death certificate). RESULTS: Among the different combinations of antibiotics/bacteria, prevalence of resistance to fluoroquinolones in Escherichia coli had the strongest association with septicemia hospitalization rates for individuals aged over 50y, and with sepsis mortality rates for individuals aged 18-84y. There were several positive correlations between prevalence of resistance for different combinations of antibiotics/bacteria and septicemia hospitalization/sepsis mortality rates in adults. CONCLUSIONS: These findings, and those from work on the relationship between antibiotic use and sepsis rates, support the association between use of/resistance to certain antibiotics and rates of sepsis-related outcomes, indicating the potential utility of antibiotic replacement.

On the Role of Different Age Groups and Pertussis Vaccines During the 2012 Outbreak in Wisconsin.

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 relative risk (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 (ORs), within each age group, for being vaccinated vs undervaccinated before vs after the outbreak's peak. RESULTS: The RR statistic suggests that children aged 13-14 years played the largest relative role during the outbreak's ascent (with estimates consistent across the 3 regions in Wisconsin that were studied), followed by children aged 7-8, 9-10, and 11-12 years. Young children and older teenagers and adults played more limited relative roles during the outbreak. Results of the vaccination status analysis for the fifth dose of DTaP (for children aged 7-8 years: OR, 0.44; 95% confidence interval [CI], 0.23-0.86; for children aged 9-10 years: OR, 0.51; 95% CI, 0.27-0.95); and for Tdap for children aged 13-14 years (OR, 0.38, 95% CI, 0.16-0.89) are consistent with protective effect against infection. CONCLUSIONS: While our epidemiological findings for the fifth 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 particularly for pertussis vaccines for adolescents, are needed to evaluate the impact of vaccination on the spread of pertussis in the community.