Effect of risk status for severe COVID-19 on individual contact behaviour during the SARS-CoV-2 pandemic in 2020/2021-an analysis based on the German COVIMOD study.

BACKGROUND: One of the primary aims of contact restriction measures during the SARS-CoV-2 pandemic has been to protect people at increased risk of severe disease from the virus. Knowledge about the uptake of contact restriction measures in this group is critical for public health decision-making. We analysed data from the German contact survey COVIMOD to assess differences in contact patterns based on risk status, and compared this to pre-pandemic data to establish whether there was a differential response to contact reduction measures. METHODS: We quantified differences in contact patterns according to risk status by fitting a generalised linear model accounting for within-participant clustering to contact data from 31 COVIMOD survey waves (April 2020-December 2021), and estimated the population-averaged ratio of mean contacts of persons with high risk for a severe COVID-19 outcome due to age or underlying health conditions, to those without. We then compared the results to pre-pandemic data from the contact surveys HaBIDS and POLYMOD. RESULTS: Averaged across all analysed waves, COVIMOD participants reported a mean of 3.21 (95% confidence interval (95%CI) 3.14,3.28) daily contacts (truncated at 100), compared to 18.10 (95%CI 17.12,19.06) in POLYMOD and 28.27 (95%CI 26.49,30.15) in HaBIDS. After adjusting for confounders, COVIMOD participants aged 65 or above had 0.83 times (95%CI 0.79,0.87) the number of contacts as younger age groups. In POLYMOD, this ratio was 0.36 (95%CI 0.30,0.43). There was no clear difference in contact patterns due to increased risk from underlying health conditions in either HaBIDS or COVIMOD. We also found that persons in COVIMOD at high risk due to old age increased their non-household contacts less than those not at such risk after strict restriction measures were lifted. CONCLUSIONS: Over the course of the SARS-CoV-2 pandemic, there was a general reduction in contact numbers in the German population and also a differential response to contact restriction measures based on risk status for severe COVID-19. This differential response needs to be taken into account for parametrisations of mathematical models in a pandemic setting.

Trade-off between benefits, harms and economic efficiency of low-dose CT lung cancer screening: a microsimulation analysis of nodule management strategies in a population-based setting.

BACKGROUND: In lung cancer screening, a nodule management protocol describes nodule assessment and thresholds for nodule size and growth rate to identify patients who require immediate diagnostic evaluation or additional imaging exams. The Netherlands-Leuvens Screening Trial and the National Lung Screening Trial used different selection criteria and nodule management protocols. Several modelling studies have reported variations in screening outcomes and cost-effectiveness across selection criteria and screening intervals; however, the effect of variations in the nodule management protocol remains uncertain. This study evaluated the effects of the eligibility criteria and nodule management protocols on the benefits, harms and cost-effectiveness of lung screening scenarios in a population-based setting in Germany. METHODS: We developed a modular microsimulation model: a biological module simulated individual histories of lung cancer development from carcinogenesis onset to death; a screening module simulated patient selection, screening-detection, nodule management protocols, diagnostic evaluation and screening outcomes. Benefits included mortality reduction, life years gained and averted lung cancer deaths. Harms were costs, false positives and overdiagnosis. The comparator was no screening. The evaluated 76 screening scenarios included variations in selection criteria and thresholds for nodule size and growth rate. RESULTS: Five years of annual screening resulted in a 9.7-12.8% lung cancer mortality reduction in the screened population. The efficient scenarios included volumetric assessment of nodule size, a threshold for a volume of 300 mm3 and a threshold for a volume doubling time of 400 days. Assessment of volume doubling time is essential for reducing overdiagnosis and false positives. Incremental cost-effectiveness ratios of the efficient scenarios were 16,754-23,847 euro per life year gained and 155,287-285,630 euro per averted lung cancer death. CONCLUSIONS: Lung cancer screening can be cost-effective in Germany. Along with the eligibility criteria, the nodule management protocol influences screening performance and cost-effectiveness. Definition of the thresholds for nodule size and nodule growth in the nodule management protocol should be considered in detail when defining optimal screening strategies.

Decision-support tools to build climate resilience against emerging infectious diseases in Europe and beyond.

Climate change is one of several drivers of recurrent outbreaks and geographical range expansion of infectious diseases in Europe. We propose a framework for the co-production of policy-relevant indicators and decision-support tools that track past, present, and future climate-induced disease risks across hazard, exposure, and vulnerability domains at the animal, human, and environmental interface. This entails the co-development of early warning and response systems and tools to assess the costs and benefits of climate change adaptation and mitigation measures across sectors, to increase health system resilience at regional and local levels and reveal novel policy entry points and opportunities. Our approach involves multi-level engagement, innovative methodologies, and novel data streams. We take advantage of intelligence generated locally and empirically to quantify effects in areas experiencing rapid urban transformation and heterogeneous climate-induced disease threats. Our goal is to reduce the knowledge-to-action gap by developing an integrated One Health-Climate Risk framework.

Occurrence of Antimicrobial Resistance in the Environment in Germany, Austria, and Switzerland: A Narrative Review of Existing Evidence.

(1) Background: This study summarizes the current research on antibiotic resistance (AR) in the environment conducted in Austria, Germany, and Switzerland; (2) Methods: A narrative systematic literature review of epidemiological studies based on searches in EMBASE and CAB abstracts (up to 16 June2021) was conducted. Environmental reservoirs included water sources, wastewater, animal husbandry, wildlife, soil, and sediment; (3) Results: Four hundred and four records were screened, and 52 studies were included. Thirteen studies examined aquatic environments, and eleven investigated wastewater. Eight studies investigated both wildlife and animal husbandry. Less evidence was available for sediments, soil, and air. Considerable heterogeneity in research focus, study design, sampling, and measurement of resistance was observed. Resistance to all categories of antimicrobials in the WHO CIA list was identified. Resistance to critically important and highly important substances was reported most frequently; (4) Conclusions: The current research scope presents data-gathering efforts. Usage of a unified protocol for isolate collection, selecting sampling sites, and susceptibility testing is required to provide results that can be compared between the studies and reservoirs. Epidemiological, environmental, and ecological factors should be considered in surveys of the environmental dissemination of AR. Systematic epidemiological studies investigating AR at the interface of human, animal, and environmental health are needed.

Facing the Omicron variant-how well do vaccines protect against mild and severe COVID-19? Third interim analysis of a living systematic review.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is currently the dominant variant globally. This third interim analysis of a living systematic review summarizes evidence on the effectiveness of the coronavirus disease 2019 (COVID-19) vaccine (vaccine effectiveness, VE) and duration of protection against Omicron. Methods: We systematically searched literature on COVID-19 for controlled studies, evaluating the effectiveness of COVID-19 vaccines approved in the European Union up to 14/01/2022, complemented by hand searches of websites and metasearch engines up to 11/02/2022. We considered the following comparisons: full primary immunization vs. no vaccination, booster immunization vs. no vaccination, and booster vs. full primary immunization. VE against any confirmed SARS-CoV-2 infection, symptomatic, and severe COVID-19 (i.e., COVID-19-related hospitalization, ICU admission, or death) was indicated, providing estimate ranges. Meta-analysis was not performed due to high study heterogeneity. The risk of bias was assessed with ROBINS-I, and the certainty of the evidence was evaluated using GRADE. Results: We identified 26 studies, including 430 to 2.2 million participants, which evaluated VE estimates against infections with the SARS-CoV-2 Omicron variant. VE against any confirmed SARS-CoV-2 infection ranged between 0-62% after full primary immunization and between 34-66% after a booster dose compared to no vaccination. VE range for booster vs. full primary immunization was 34-54.6%. After full primary immunization VE against symptomatic COVID-19 ranged between 6-76%. After booster immunization VE ranged between 3-84% compared to no vaccination and between 56-69% compared to full primary immunization. VE against severe COVID-19 ranged between 3-84% after full primary immunization and between 12-100% after booster immunization compared to no vaccination, and 100% (95% CI 71.4-100) compared to full primary immunization (data from only one study). VE was characterized by a moderate to strong decline within 3-6 months for SARS-CoV-2 infections and symptomatic COVID-19. Against severe COVID-19, protection remained robust for at least up to 6 months. Waning immunity was more profound after primary than booster immunization. The risk of bias was moderate to critical across studies and outcomes. GRADE certainty was very low for all outcomes. Conclusions: Under the Omicron variant, the effectiveness of EU-licensed COVID-19 vaccines in preventing any SARS-CoV-2 infection is low and only short-lasting after full primary immunization, but can be improved by booster vaccination. VE against severe COVID-19 remains high and is long-lasting, especially after receiving the booster vaccination.

Assessment of the Effects of Active Immunisation against Respiratory Syncytial Virus (RSV) using Decision-Analytic Models: A Systematic Review with a Focus on Vaccination Strategies, Modelling Methods and Input Data.

BACKGROUND: Several vaccine and antibody candidates are currently in development for the prevention of lower respiratory tract infections caused by the respiratory syncytial virus (RSV). METHODS: We searched MEDLINE, Embase, and SCOPUS and included model-based evaluations of RSV vaccinations. Two reviewers performed the selection, data extraction, and quality evaluation with EVIDEM. Cost-effectiveness (CE) estimates were converted to $US purchasing power parity (PPP), year 2018 values. Potential economic and epidemiological outcomes were summarised for maternal, infant, children, and elderly vaccinations. The PROSPERO identifier is CRD42019122570. RESULTS: In total, 22 model-based studies were reviewed. On average, a potential 27% reduction in RSV hospitalisations in infants was projected for maternal vaccination and 50% for direct infant immunisation. The CE of maternal vaccination was $US1766-5857 PPP 2018/disability-adjusted life-years (DALYs) for Global Alliance for Vaccines and Immunisation (Gavi)-eligible countries. For England, the maximum cost-effective price of maternal vaccination was estimated at $US81.5 PPP 2018. Infant vaccination was associated with higher CE ratios in low- and high-income settings. Vaccination of neonates born before the RSV season was the most cost effective in high-income settings. Higher values for vaccine effectiveness, duration of protection, and vaccine uptake increased the benefits. Due to indirect effects, the vaccination of school-age children and a cocooning strategy were effective alternatives to protect infants, and the vaccination of children aged < 5 years had a beneficial impact on the elderly. CONCLUSION: RSV vaccines with anticipated characteristics may reduce a sizeable proportion of the RSV burden. The results are subject to uncertainty because of the limited epidemiological and clinical data. Data on RSV incidence and hospitalisation risk for granular age strata should be prioritised to facilitate the evaluation of RSV interventions and decision making.

Cost Effectiveness of Elderly Pneumococcal Vaccination in Presence of Higher-Valent Pneumococcal Conjugate Childhood Vaccination: Systematic Literature Review with Focus on Methods and Assumptions.

BACKGROUND: Previous systematic reviews concluded that pneumococcal vaccination in the elderly was cost effective. However, recently published economic evaluations state that it may not be cost effective when children are vaccinated with higher-valent pneumococcal conjugate vaccines. The literature suggests that the outcomes of vaccination in the elderly are strongly influenced by the vaccine effectiveness (VE) against the vaccine-type pneumococcal diseases (PD) and the impact of childhood vaccination on the vaccine-type PD incidence in the elderly, but the extent remains unclear. METHODS: We conducted a systematic literature search of cost-effectiveness studies on vaccination in the elderly in the PubMed database starting from 2006. We included studies that consider the presence of a childhood vaccination with pneumococcal conjugate vaccine (PCV) 10 and PCV13. We focus on methods and assumptions used in modeling VE and epidemiology of PD over time. RESULTS: Twenty-eight economic evaluations underwent full-text review and data extraction. Thirteen were selected for quality assessment. The studies with a higher quality score provide evidence that vaccinating the elderly with PCV13 is not cost effective, when an ongoing rapid decline in the incidence of PCV13-type PD is modeled. A moderate persistence of PCV13 serotypes, in particular due to PCV10 childhood vaccination, makes vaccination of the elderly with PCV13 more attractive. There is no agreement that combining PCV13 with polysaccharide vaccine PPSV23 is cost effective. PPSV23 is attractive when it is effective against non-invasive PD. CONCLUSION: Methodological approaches and assumptions in modeling VE and the indirect effects of childhood vaccination have a major impact on outcomes of decision-analytic models and cost-effectiveness estimates. Considering recently observed trends in the epidemiology of pneumococcal serotypes, there is currently inconclusive evidence regarding the cost effectiveness of pneumococcal vaccination of the elderly due to lack of studies that model key serotypes such as serotype 3 separately from other groups of serotypes.

Analysis of contemporary HIV/AIDS health care costs in Germany: Driving factors and distribution across antiretroviral therapy lines.

To analyze contemporary costs of HIV health care and the cost distribution across lines of combination antiretroviral therapy (cART). To identify variations in expenditures with patient characteristics and to identify main cost determinants. To compute cost ratios between patients with varying characteristics.Empirical data on costs are collected in Germany within a 2-year prospective observational noninterventional multicenter study. The database contains information for 1154 HIV-infected patients from 8 medical centers.Means and standard deviations of the total costs are estimated for each cost fraction and across cART lines and regimens. The costs are regressed against various patient characteristics using a generalized linear model. Relative costs are calculated using the resultant coefficients.The average annual total costs (SD) per patient are &OV0556;22,231.03 (8786.13) with a maximum of &OV0556;83,970. cART medication is the major cost fraction (83.8%) with a mean of &OV0556;18,688.62 (5289.48). The major cost-driving factors are cART regimen, CD4-T cell count, cART drug resistance, and concomitant diseases. Viral load, pathology tests, and demographics have no significant impact. Standard non-nucleoside reverse transcriptase inhibitor-based regimens induce 28% lower total costs compared with standard PI/r regimens. Resistance to 3 or more antiretroviral classes induces a significant increase in costs.HIV treatment in Germany continues to be expensive. Majority of costs are attributable to cART. Main cost determinants are CD4-T cells count, comorbidity, genotypic antiviral resistance, and therapy regimen. Combinations of characteristics associated with higher expenditures enhance the increasing effect on the costs and induce high cost cases.

The Role of decision-analytic modelling in German health technology assessments.

BACKGROUND: Decision-analytic modelling (DAM) has become a widespread method in health technology assessments (HTA), but the extent to which modelling is used differs among international HTA institutions. In Germany, the use of DAM is optional within HTAs of the German Institute of Medical Documentation and Information (DIMDI). Our study examines the use of DAM in DIMDI HTA reports and its effect on the quality of information provided for health policies. METHODS: A review of all DIMDI HTA reports (from 1998 to September 2012) incorporating an economic assessment was performed. All included reports were divided into two groups: HTAs with DAM and HTAs without DAM. In both groups, reports were categorized according to the quality of information provided for healthcare decision making. RESULTS: Of the sample of 107 DIMDI HTA reports, 17 (15.9%) used DAM for economic assessment. In the group without DAM, conclusions were limited by the quality of economic information in 51.1% of the reports, whereas we did not find limited conclusions in the group with DAM. Furthermore, 24 reports without DAM (26.7%) stated that using DAM would likely improve the quality of information of the economic assessment. CONCLUSION: The use of DAM techniques can improve the quality of HTAs in Germany. When, after a systematic review of existing literature within a HTA, it is clear that DAM is likely to positively affect the quality of the economic assessment DAM should be used.