Thomas Harder

Bio: Thomas Harder is an academic researcher from Robert Koch Institute. The author has contributed to research in topics: Vaccination & Systematic review. The author has an hindex of 20, co-authored 69 publications receiving 1369 citations.

Burden of Six Healthcare-Associated Infections on European Population Health: Estimating Incidence-Based Disability-Adjusted Life Years through a Population Prevalence-Based Modelling Study

Abstract: Background Estimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011–2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs. Methods and Findings The included HAIs were healthcare-associated pneumonia (HAP), healthcare-associated urinary tract infection (HA UTI), surgical site infection (SSI), healthcare-associated Clostridium difficile infection (HA CDI), healthcare-associated neonatal sepsis, and healthcare-associated primary bloodstream infection (HA primary BSI). The burden of these HAIs was measured in disability-adjusted life years (DALYs). Evidence relating to the disease progression pathway of each type of HAI was collected through systematic literature reviews, in order to estimate the risks attributable to HAIs. For each of the six HAIs, gender and age group prevalence from the ECDC PPS was converted into incidence rates by applying the Rhame and Sudderth formula. We adjusted for reduced life expectancy within the hospital population using three severity groups based on McCabe score data from the ECDC PPS. We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per 100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of burden of disease. HAP and HA primary BSI were associated with the highest burden because of their high severity. The cumulative burden of the six HAIs was higher than the total burden of all other 32 communicable diseases included in the BCoDE 2009–2013 study. The main limitations of the study are the variability in the parameter estimates, in particular the disease models’ case fatalities, and the use of the Rhame and Sudderth formula for estimating incident number of cases from prevalence data. Conclusions We estimated the EU/EEA burden of HAIs in DALYs in 2011–2012 using a transparent and evidence-based approach that allows for combining estimates of morbidity and of mortality in order to compare with other diseases and to inform a comprehensive ranking suitable for prioritization. Our results highlight the high burden of HAIs and the need for increased efforts for their prevention and control. Furthermore, our model should allow for estimations of the potential benefit of preventive measures on the burden of HAIs in the EU/EEA.

Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis

Abstract: Background Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries. Methods We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias. Results We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10–92%) in four clinical trials, 45% (95%CI: 15–65%) in three cohort studies, and 59% (95%CI: 35–74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35–80%) in two clinical trials and 48% (95%CI: 25–63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity. Conclusions Our meta-analysis revealed significant VE of PPV23 against both IPD and pneumococcal pneumonia by any serotype in the elderly, comparable to the efficacy of PCV13 against vaccine-serotype disease in a recent clinical trial in elderly people. Due to its broader serotype coverage and the decrease of PCV13 serotypes among adults resulting from routine infant immunization with PCV13, PPV23 continues to play an important role for protecting adults against IPD and pneumococcal pneumonia.

Epidemiology and burden of sepsis acquired in hospitals and intensive care units: a systematic review and meta-analysis

Abstract: Sepsis is recognized as a global public health problem, but the proportion due to hospital-acquired infections remains unclear We aimed to summarize the epidemiological evidence related to the burden of hospital-acquired (HA) and ICU-acquired (ICU-A) sepsis We searched MEDLINE, Embase and the Global Index Medicus from 01/2000 to 03/2018 We included studies conducted hospital-wide or in intensive care units (ICUs), including neonatal units (NICUs), with data on the incidence/prevalence of HA and ICU-A sepsis and the proportion of community and hospital/ICU origin We did random-effects meta-analyses to obtain pooled estimates; inter-study heterogeneity and risk of bias were assessed Of the 13,239 studies identified, 51 met the inclusion criteria; 22 were from low- and middle-income countries Twenty-eight studies were conducted in ICUs, 13 in NICUs, and ten hospital-wide The proportion of HA sepsis among all hospital-treated sepsis cases was 236% (95% CI 17–318%, range 16–364%) In the ICU, 244% (95% CI 167–342%, range 103–425%) of cases of sepsis with organ dysfunction were acquired during ICU stay and 487% (95% CI 383–593%, range 187–694%) had a hospital origin The pooled hospital incidence of HA sepsis with organ dysfunction per 1000 patients was 93 (95% CI 73–119, range 2–206)) In the ICU, the pooled incidence of HA sepsis with organ dysfunction per 1000 patients was 565 (95% CI 35–902, range 92–2544) and it was particularly high in NICUs Mortality of ICU patients with HA sepsis with organ dysfunction was 523% (95% CI 434–611%, range 301–646%) There was a significant inter-study heterogeneity Risk of bias was low to moderate in ICU-based studies and moderate to high in hospital-wide and NICU studies HA sepsis is of major public health importance, and the burden is particularly high in ICUs There is an urgent need to improve the implementation of global and local infection prevention and management strategies to reduce its high burden among hospitalized patients

Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021.

Abstract: The Delta variant has become the dominant strain of SARS-CoV-2. We summarised the evidence on COVID-19 vaccine effectiveness (VE) identified in 17 studies that investigated VE against different endpoints. Pooled VE was 63.1% (95% confidence interval (CI): 40.9-76.9) against asymptomatic infection, 75.7% (95% CI: 69.3-80.8) against symptomatic infection and 90.9% (95% CI: 84.5-94.7) against hospitalisation. Compared with the Alpha variant, VE against mild outcomes was reduced by 10-20%, but fully maintained against severe COVID-19.

Frequency and impact of confounding by indication and healthy vaccinee bias in observational studies assessing influenza vaccine effectiveness: a systematic review

Abstract: Evidence on influenza vaccine effectiveness (VE) is commonly derived from observational studies. However, these studies are prone to confounding by indication and healthy vaccinee bias. We aimed to systematically investigate these two forms of confounding/bias. Systematic review of observational studies reporting influenza VE and indicators for bias and confounding. We assessed risk of confounding by indication and healthy vaccinee bias for each study and calculated ratios of odds ratios (crude/adjusted) to quantify the effect of confounder adjustment. VE-estimates during and outside influenza seasons were compared to assess residual confounding by healthy vaccinee effects. We identified 23 studies reporting on 11 outcomes. Of these, 19 (83 %) showed high risk of bias: Fourteen due to confounding by indication, two for healthy vaccinee bias, and three studies showed both forms of confounding/bias. Adjustment for confounders increased VE on average by 12 % (95 % CI: 7–17 %; all-cause mortality), 9 % (95 % CI: 4–14 %; all-cause hospitalization) and 7 % (95 % CI: 4–10 %; influenza-like illness). Despite adjustment, nine studies showed residual confounding as indicated by significant off-season VE-estimates. These were observed for five outcomes, but more frequently for all-cause mortality as compared to other outcomes (p = 0.03) and in studies which indicated healthy vaccinee bias at baseline (p = 0.01). Both confounding by indication and healthy vaccinee bias are likely to operate simultaneously in observational studies on influenza VE. Although adjustment can correct for confounding by indication to some extent, the resulting estimates are still prone to healthy vaccinee bias, at least as long as unspecific outcomes like all-cause mortality are used. Therefore, cohort studies using administrative data bases with unspecific outcomes should no longer be used to measure the effects of influenza vaccination.

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Abstract: Summary Background Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged Interpretation Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases. Funding European Centre for Disease Prevention and Control.

Nosocomial Bloodstream Infection in Critically Ill Adults: Excess Length of Stay, Extra Costs, and Attributable Mortality

Abstract: OBJECTIVE To determine the excess length of stay, extra costs, and mortality attributable to nosocomial bloodstream infection in critically ill patients. DESIGN Pairwise-matched (1:1) case-control study. SETTING Surgical intensive care unit (SICU) in a tertiary health care institution. PATIENTS All patients admitted in the SICU between July 1, 1988, and June 30, 1990, were eligible. Cases were defined as patients with nosocomial bloodstream infection; controls were selected according to matching variables in a stepwise fashion. METHODS Matching variables were primary diagnosis for admission, age, sex, length of stay before the day of infection in cases, and total number of discharge diagnoses. Matching was successful for 89% of the cohort; 86 matched case-control pairs were studied. MAIN OUTCOME MEASURES Crude and attributable mortality, excess length of hospital and SICU stay, and overall costs. RESULTS Nosocomial bloodstream infection complicated 2.67 per 100 admissions to the SICU during the study period. The crude mortality rates from cases and controls were 50% and 15%, respectively (P < .01); thus, the estimated attributable mortality rate was 35% (95% confidence interval, 25% to 45%). The median length of hospital stay significantly differed between cases and controls (40 vs 26 days, respectively; P < .01). When only matched pairs who survived bloodstream infection were considered (n = 41), cases stayed in the hospital a median of 54 days vs 30 days for controls (P < .01), and cases stayed in the SICU a median of 15 days vs 7 days for controls (P < .01). Thus, extra hospital and SICU length of stay attributable to bloodstream infection was 24 and 8 days, respectively. Extra costs attributable to the infection averaged $40,000 per survivor. CONCLUSIONS The attributable mortality from nosocomial bloodstream infection is high in critically ill patients. The infection is associated with a doubling of the SICU stay, an excess length of hospital stay of 24 days in survivors, and a significant economic burden.

Meta-analysis of prevalence

Abstract: Meta-analysis is a method to obtain a weighted average of results from various studies. In addition to pooling effect sizes, meta-analysis can also be used to estimate disease frequencies, such as incidence and prevalence. In this article we present methods for the meta-analysis of prevalence. We discuss the logit and double arcsine transformations to stabilise the variance. We note the special situation of multiple category prevalence, and propose solutions to the problems that arise. We describe the implementation of these methods in the MetaXL software, and present a simulation study and the example of multiple sclerosis from the Global Burden of Disease 2010 project. We conclude that the double arcsine transformation is preferred over the logit, and that the MetaXL implementation of multiple category prevalence is an improvement in the methodology of the meta-analysis of prevalence.