First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden: A Population-based Real-world Study with Focus on Immunotherapy.

BACKGROUND AND PURPOSE: The treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) has evolved significantly since the introduction of immunotherapies. We here describe PD-L1 testing rates, treatment patterns, and real-world outcomes for PD-(L)1 inhibitors in Sweden. MATERIALS AND METHODS: Data were obtained from the Swedish National Lung Cancer Registry for patients with advanced NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 who initiated first-line -systemic treatment from 01 April 2017 to 30 June 2020. PD-L1 testing was available in the registry from 01 January 2018. Kaplan-Meier was used for overall survival (OS) by type treatment and histology. RESULTS: A total of 2,204 patients with pathologically confirmed unresectable stage IIIB/C or IV NSCLC initiated first-line treatment, 1,807 (82%) with nonsquamous (NSQ) and 397 (18%) with SQ. Eighty-six per cent (NSQ) or 85% (SQ) had been tested for PD-L1 expression, a proportion that increased over time. The use of platinum-based therapy as first-line treatment decreased substantially over time while there was an upward trend for PD-(L)1-based therapy. Among patients with PS 0-1 initiating a first-line PD-(L)1 inhibitor monotherapy, the median OS was 18.6 and 13.3 months for NSQ and SQ NSCLC patients, respectively, while for the PD-(L)1 inhibitor and chemotherapy combination regimen, the median OS was 24.0 months for NSQ and not evaluable for SQ patients. INTERPRETATION: The majority of advanced NSCLCs in Sweden were tested for PD-L1 expression. Real-world OS in patients with PS 0-1 receiving first-line PD-(L)1 inhibitor-based regimens was similar to what has been reported in pivotal clinical trials on PD-(L)1 inhibitors.

Assessing the use of antibiotics and the burden of varicella in Belgium using a retrospective GP database analysis.

BACKGROUND: Varicella is a highly contagious infection that typically occurs in childhood. While most cases have a generally benign outcome, infection results in a considerable healthcare burden and serious complications may occur. OBJECTIVES: The objective of this study was to characterize the burden of varicella in a real-world primary care setting in Belgium, including the rate of varicella-related complications, medication management and general practitioner (GP) visits. METHODS: The study was a retrospective observational study using data from a longitudinal patient database in a primary care setting in Belgium. Patients with a GP visit and a varicella diagnosis between January 2016 and June 2019 were eligible and data one month prior and three months after the diagnosis were included. Outcomes included varicella-related complications, antibiotic use, antiviral use, and GP follow-up visits. Antibiotic use could be specified by class of antibiotic and linked to a diagnosis. Complications were identified based on concomitant diagnosis with varicella during the study period. RESULTS: 3,847 patients with diagnosis of varicella were included, with a mean age of 8.4 years and a comparable distribution of gender. 12.6% of patients with varicella had a concomitant diagnosis of a varicella-related complication. During the follow-up period, 27.3% of patients with varicella were prescribed antibiotics, either systemic (19.8%) and/or topical (10.3%). The highest rate of antibiotic prescriptions was observed in patients with complications (63.5%) and in patients younger than 1 year (41.8%). Nevertheless, 5.3% of the patients were prescribed antibiotics without a concomitant diagnosis of another infection. The most commonly prescribed systemic antibiotics were amoxicillin alone or combined with beta-lactamase inhibitor, and thiamphenicol. Fusidic acid and tobramycin were the most prescribed topical antibiotics. Antivirals were prescribed for 2.7% of the study population. 4.7% of the patients needed a follow-up visit with their GP. CONCLUSIONS: This study reports a substantial burden of varicella in a primary care setting in Belgium, with high rates of complications and antibiotic use.

Economic burden of varicella in Europe in the absence of universal varicella vaccination.

BACKGROUND: Though the disease burden of varicella in Europe has been reported previously, the economic burden is still unknown. This study estimated the economic burden of varicella in Europe in the absence of Universal Varicella Vaccination (UVV) in 2018 Euros from both payer (direct costs) and societal (direct and indirect costs) perspectives. METHODS: We estimated the country specific and overall annual costs of varicella in absence of UVV in 31 European countries (27 EU countries, plus Iceland, Norway, Switzerland and the United Kingdom). To obtain country specific unit costs and associated healthcare utilization, we conducted a systematic literature review, searching in PubMed, EMBASE, NEED, DARE, REPEC, Open Grey, and public heath websites (1/1/1999-10/15/2019). The number of annual varicella cases, deaths, outpatient visits and hospitalizations were calculated (without UVV) based on age-specific incidence rates (Riera-Montes et al. 2017) and 2018 population data by country. Unit cost per varicella case and disease burden data were combined using stochastic modeling to estimate 2018 costs stratified by country, age and healthcare resource. RESULTS: Overall annual total costs associated with varicella were estimated to be €662,592,061 (Range: €309,552,363 to €1,015,631,760) in Europe in absence of UVV. Direct and indirect costs were estimated at €229,076,206 (Range €144,809,557 to €313,342,856) and €433,515,855 (Range €164,742,806 to €702,288,904), respectively. Total cost per case was €121.45 (direct: €41.99; indirect: €79.46). Almost half of the costs were attributed to cases in children under 5 years, owing mainly to caregiver work loss. The distribution of costs by healthcare resource was similar across countries. France and Germany accounted for 49.28% of total annual costs, most likely due to a combination of high numbers of cases and unit costs in these countries. CONCLUSIONS: The economic burden of varicella across Europe in the absence of UVV is substantial (over 600 M€), primarily driven by caregiver burden including work productivity losses.

Fiscal analysis of the pediatric immunization program in Belgium applying a lifetime government perspective framework.

OBJECTIVES: A public economic framework was used to explore lifetime government costs and benefits in relation to the Pediatric Immunization Program (PIP) in Belgium based on cases and deaths averted. METHODS: To estimate changes in net government revenue, we developed a decision-analytic model that quantifies lifetime tax revenues and transfers based on changes in morbidity and mortality arising from Belgium's Pediatric Immunization Program (PIP). The model considered differences in incidence rates with vaccines included in Belgium's PIP: compared with the pre-vaccine era. Changes in deaths and comorbid conditions attributed to PIP on the Belgium 2020 birth cohort were used to estimate gross lifetime earnings changes, tax revenue gains attributed to averted morbidity and mortality avoidance, disability transfer cost savings, and averted special education costs associated with each vaccine. RESULTS: Vaccinating a single birth cohort according to the PIP gives rise to fiscal gains of €56 million in averted tax revenue loss, €8 million disability savings, and €6 million special education cost-savings. Based on the costs of implementing the PIP, we estimate the fiscal benefit-cost ratio (fBCR) of €2.2 investment return for the government from every €1 invested excluding longevity costs. CONCLUSIONS: Reducing vaccine-preventable conditions generates tax revenue for the government, providing fiscal justification for sustained immunization investments.

Clinical and economic burden of acute otitis media caused by Streptococcus pneumoniae in European children, after widespread use of PCVs-A systematic literature review of published evidence.

BACKGROUND: Acute otitis media (AOM) is a common childhood disease frequently caused by Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV7, PCV10, PCV13) can reduce the risk of AOM but may also shift AOM etiology and serotype distribution. The aim of this study was to review estimates from published literature of the burden of AOM in Europe after widespread use of PCVs over the past 10 years, focusing on incidence, etiology, serotype distribution and antibiotic resistance of Streptococcus pneumoniae, and economic burden. METHODS: This systematic review included published literature from 31 European countries, for children aged ≤5 years, published after 2011. Searches were conducted using PubMed, Embase, Google, and three disease conference websites. Risk of bias was assessed with ISPOR-AMCP-NPC, ECOBIAS or ROBIS, depending on the type of study. RESULTS: In total, 107 relevant records were identified, which revealed wide variation in study methodology and reporting, thus limiting comparisons across outcomes. No homogenous trends were identified in incidence rates across countries, or in detection of S. pneumoniae as a cause of AOM over time. There were indications of a reduction in hospitalization rates (decreases between 24.5-38.8% points, depending on country, PCV type and time since PCV introduction) and antibiotic resistance (decreases between 14-24%, depending on country), following the widespread use of PCVs over time. The last two trends imply a potential decrease in economic burden, though this was not possible to confirm with the identified cost data. There was also evidence of an increase in serotype distributions towards non-vaccine serotypes in all of the countries where non-PCV serotype data were available, as well as limited data of increased antibiotic resistance within non-vaccine serotypes. CONCLUSIONS: Though some factors point to a reduction in AOM burden in Europe, the burden still remains high, residual burden from uncovered serotypes is present and it is difficult to provide comprehensive, accurate and up-to-date estimates of said burden from the published literature. This could be improved by standardised methodology, reporting and wider use of surveillance systems.

Assessing the fiscal consequences of novel and existing treatments for triple negative breast cancer in Switzerland by applying a government perspective framework.

BACKGROUND: Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer that can impact patients' employment and workforce participation. This study estimates how the employment effects of TNBC impact government tax revenue and public benefits expenditure in Switzerland, representing the fiscal burden of disease (FBoD), and likely consequences of introducing new treatment options. METHODS: A four-state cohort model was used to calculate fiscal effects for two treatments: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab monotherapy (P + C→P) and neoadjuvant chemotherapy alone (C). Lifetime present values of tax revenue, social benefit payments, and healthcare costs were calculated for the average population and those undergoing treatment to assess the FBoD. RESULTS: An average TNBC patient treated with C and P + C→P is expected to generate CHF128,999 and CHF97,008 less tax than the average population, respectively, and require increased social benefit payments. Compared to C, 75% of the incremental healthcare costs of P + C→P are estimated to be offset through tax revenue gains. CONCLUSIONS: This analysis demonstrates that 75% of the additional costs of a new TNBC treatment option can be offset by gains in tax revenue. Fiscal analysis can be a useful tool to complement existing methods for evaluating new treatments.

Global burden and economic impact of vaccine-preventable cancer mortality.

BACKGROUND: Infections are responsible for approximately 13% of cancer cases worldwide and many of these infections can be prevented by vaccination. Human papillomavirus (HPV) and hepatitis B virus (HBV) are among the most common infections that cause cancer deaths globally, despite effective prophylactic vaccines being available. This analysis aims to estimate the global burden and economic impact of vaccine-preventable cancer mortality across World Health Organization (WHO) regions. METHODS: The number of deaths and years of life lost (YLL) due to five different vaccine-preventable cancer forms (oral cavity, liver, laryngeal, cervical, and oropharyngeal cancer) in each of the WHO regions (African, Eastern Mediterranean, European, the Americas, South-East Asia Pacific, and Western Pacific) were obtained from the Institute for Health Metrics Evaluation global burden of disease dataset. Vaccine-preventable mortality was estimated considering the fraction attributable to infection, to estimate the number of deaths and YLL potentially preventable through vaccination. Data from the World Bank on GDP per capita were used to estimate the value of YLL (VYLL). The robustness of these results was explored with sensitivity analysis. Given that several Epstein-Barr virus (EBV) vaccines are in development, but not yet available, the impact of a potential vaccine for EBV was evaluated in a scenario analysis. RESULTS: In 2019, there were 465,740 potentially vaccine-preventable cancer deaths and 14,171,397 YLL across all WHO regions. The estimated economic impact due to this mortality was $106.3 billion globally. The sensitivity analysis calculated a range of 403,025-582,773 deaths and a range in productivity cost of $78.8-129.0 billion. In the scenario analysis EBV-related cancer mortality increased the global burden by 159,723 deaths and $32.4 billion. CONCLUSION: Overall, the findings from this analysis illustrate the high economic impact of premature cancer mortality that could be potentially preventable by vaccination which may assist decision-makers in allocating limited resources among competing priorities. Improved implementation and increased vaccination coverage of HPV and HBV should be prioritized to decrease this burden.

Increased Risk of Long-Term Disabilities Following Childhood Bacterial Meningitis in Sweden.

Importance: Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort. Objective: To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden. Design, Setting, and Participants: This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023. Exposure: A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021. Main Outcomes and Measures: Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood. Results: The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median. Conclusions and Relevance: The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.

Productivity costs due to human papillomavirus-related cancer mortality in the United Kingdom.

BACKGROUND: Human papillomavirus (HPV) causes several cancers such as cervical cancer and some head and neck (oral cavity, pharynx, and larynx), vulval, vaginal, anal, and penile cancers. As HPV vaccination is available, there is potential to prevent these cancers attributed to HPV and consequently the burden associated with them. The aim of this analysis was to estimate the number of HPV-related cancer deaths and the productivity costs due to years of life lost (YLL) in the United Kingdom (UK). METHOD: A model was developed utilizing UK 2019 mortality data sourced from country-specific databases for England, Scotland, Wales, and Northern Ireland for the following HPV-related cancers: head and neck (ICD-10 C00-14 and C32), cervix uteri (C53), vaginal (C51), vulval (C52), anal (C21), and penile (C60). The proportion of deaths and years of life lost (YLL) due to HPV were estimated using HPV attributable fractions for each anatomic location from the published literature. Labor force participation, retirement ages, and mean annual earnings, discounted at 3.5% annually, were applied to YLL to calculate the present value of future lost productivity (PVFLP). RESULTS: A total of 1817 deaths due to HPV-related cancers were reported in the UK in 2019 resulting in 31,804 YLL. Restricting to only YLL that occurred prior to retirement age yielded a total YPLL of 11,765 and a total PVFLP of £187,764,978. CONCLUSIONS: There is a high disease burden in the UK for HPV-related cancers, with a large economic impact on the wider economy due to productivity losses. Implementing and reinforcing public health measures to maintain high HPV vaccination coverage in both males and females may further facilitate reduction of this burden.

Burden and indirect cost of vaccine-preventable cancer mortality in Europe.

BACKGROUND: The economic and mortality burden of cancer is high worldwide. In Europe, cancer was responsible for 1.3 million deaths in 2020 and incurred an estimated cost of €50 billion from premature mortality. Human papillomavirus (HPV) and hepatitis B virus (HBV) are among the leading causes of infection-related cancers despite the availability of effective vaccines against these infections. This analysis estimated the mortality and productivity loss of HBV- and HPV-associated cancers that could be preventable through vaccination across European regions. MATERIALS AND METHODS: Institute for Health Metrics Evaluation (IHME) data were used to estimate mortality, years of life lost (YLL), and the value of years of life lost (VYLL) from five HBV- and HPV-related cancers (oral cavity, oropharynx, larynx, cervical, and liver cancers) across 40 European countries in 2019. Preventable deaths and YLL were estimated based on fractions attributable to infections. Data from the World Bank on GDP per capita were used to estimate the VYLL. The robustness of these results was explored with sensitivity and scenario analyses. RESULTS: In 2019, 31,906 cancer deaths resulted in an economic burden of €18,521,614,725 due to productivity losses across Europe. HPV-related cervical cancer had the highest mortality (19,473 deaths) and economic burden (€10,706,253,185). HBV-related liver cancer and HPV-related larynx, oral cavity, and oropharynx cancers also had a substantial burden, particularly in males. Eastern Europe had the highest YLL (308,179; 39%) and Western Europe was responsible for the greatest VYLL (€8,281,306,504; 45%), although the highest VYLL per death was in Northern Europe (€923,638). HPV-related oropharynx cancer had the highest VYLL per death (€656,607). CONCLUSION: HPV- and HBV-related cancer deaths are associated with substantial mortality and productivity losses in Europe, which could be reduced by the continued prioritization and implementation of prophylactic public health measures including systematic awareness, vaccination, and screening efforts.

The indirect costs of human papillomavirus-related cancer in Central and Eastern Europe: years of life lost and productivity costs.

BACKGROUND: Human papilloma virus (HPV) is a common cause of several types of cancer, including head and neck (oral cavity, pharynx, oropharynx, hypopharynx, nasopharynx, and larynx), cervical, vulval, vaginal, anal, and penile cancers. As HPV vaccines are available, there is potential to prevent HPV-related disease burden and related costs. METHOD: A model was developed for nine Central Eastern European (CEE) countries (Bulgaria, Croatia, Czechia, Hungary, Poland, Romania, Serbia, Slovakia, Slovenia). This model considered cancer patients who died from 11 HPV-related cancers (oropharynx, oral cavity, nasopharynx, hypopharynx, pharynx, anal, larynx, vulval, vaginal, cervical, and penile) in 2019. Due to data limitations, Bulgaria only included four cancer types. The model estimated the number of HPV-related deaths and years of life lost (YLL) based on published HPV-attributable fractions. YLL was adjusted with labor force participation, retirement age and then multiplied by mean annual earnings, discounted at a 3% annual rate to calculate the present value of future lost productivity (PVFLP). RESULTS: In 2019, there were 6,832 deaths attributable to HPV cancers resulting in 107,846 YLL in the nine CEE countries. PVFLP related to HPV cancers was estimated to be €46 M in Romania, €37 M in Poland, €19 M in Hungary, €15 M in Czechia, €12 M in Croatia, €10 M in Serbia, €9 M in Slovakia, €7 M in Bulgaria and €4 M in Slovenia. CONCLUSIONS: There is a high disease burden of HPV-related cancer-related deaths in the CEE region, with a large economic impact to society due to substantial productivity losses. It is critical to implement and reinforce public health measures with the aim to reduce the incidence of HPV-related diseases, and the subsequent premature cancer deaths. Improving HPV screening and increasing vaccination programs, in both male and female populations, could help reduce this burden.

A systematic literature review of the human papillomavirus prevalence in locally and regionally advanced and recurrent/metastatic head and neck cancers through the last decade: The "ALARM" study.

AIMS: The aim of this systematic literature review was to provide updated information on human papillomavirus (HPV) prevalence in locally and regionally advanced (LA) and recurrent/metastatic (RM) head and neck cancer (HNC) worldwide. METHODS: Electronic searches were conducted on clinicaltrials.gov, MEDLINE/PubMed, Embase, and ASCO/ESMO journals of congresses for interventional studies (IS; Phase I-III trials) as well as MEDLINE and Embase for non-interventional studies (NIS) of LA/RM HNC published between January 01, 2010 and December 31, 2020. Criteria for study selection included: availability of HPV prevalence data for LA/RM HNC patients, patient enrollment from January 01, 2010 onward, and oropharyngeal cancer (OPC) included among HNC types. HPV prevalence per study was calculated as proportion of HPV+ over total number of enrolled patients. For overall HPV prevalence across studies, mean of reported HPV prevalence rates across studies and pooled estimate (sum of all HPV+ patients over sum of all patients enrolled) were assessed. RESULTS: Eighty-one studies (62 IS; 19 NIS) were included, representing 9607 LA/RM HNC cases, with an overall mean (pooled) HPV prevalence of 32.6% (25.1%). HPV prevalence was 44.7% (44.0%) in LA and 24.3% (18.6%) in RM. Among 2714 LA/RM OPC patients from 52 studies with available data, mean (pooled) value was 55.8% (50.7%). The majority of data were derived from Northern America and Europe, with overall HPV prevalence of 46.0% (42.1%) and 24.7% (25.3%) across studies conducted exclusively in these geographic regions, respectively (Northern Europe: 31.9% [63.1%]). A "p16-based" assay was the most frequently reported HPV detection methodology (58.0%). CONCLUSION: Over the last decade, at least one quarter of LA/RM HNC and half of OPC cases studied in IS and NIS were HPV+. This alarming burden is consistent with a potential implication of HPV in the pathogenesis of at least a subgroup of HNC, underscoring the relevance of HPV testing and prophylaxis to HNC prevention and management.

Assessing the impact of kidney cancer-related premature mortality and productivity loss in Greece and Portugal.

OBJECTIVE: In 2018, 371,750 people were diagnosed with kidney cancer globally, constituting 2.2% of all cancer diagnoses. Since 2010, the number of kidney cancer deaths in Europe have decreased in people under 65. However, this is not the case in Greece and Portugal. This study estimated the mortality and lost productivity due to premature mortality from kidney cancer in Greece and Portugal. METHODS: Years of life lost (YLL) and present value of future lost productivity (PVFLP) due to kidney cancer mortality (ICD-10 code: C64 - Malignant neoplasm of kidney, except renal pelvis) were calculated using the human capital approach. Age-specific mortality, mean earnings, and labor force participation rates were used in these calculations. RESULTS: In 2019, there were 564 and 454 kidney cancer deaths in Greece and Portugal, respectively, resulting in 5,871 (3,636 in males and 2,234 in females) and 5,397 (3,100 in males and 2,297 in females) YLL, respectively. YPLL and annual PVFLP were estimated to be 1,326 and €14.8 M in Greece and 1,278 and €11.8 M in Portugal, respectively. CONCLUSION: YLL and PVFLP due to kidney cancer mortality are substantial in Greece and Portugal. These results provide new evidence to assist decision-makers in allocating resources to reduce cancer burden.

Impact assessment of immunization and the COVID-19 pandemic on varicella across Europe using digital epidemiology methods: A descriptive study.

BACKGROUND: Varicella is usually a mild disease in children but may be life-threatening, especially in adolescents and adults. Infection control measures implemented during the Coronavirus Disease 2019 (COVID-19) pandemic may have suppressed varicella transmission, potentially creating an 'immunity debt', particularly in countries without universal varicella vaccination. OBJECTIVES: To assess trends in Google search engine queries for varicella keywords as a proxy for varicella infection rates and to evaluate the effect of universal varicella vaccination on these trends. A further objective was to assess the impact of the COVID-19 pandemic on varicella keyword search query trends in countries with and without universal varicella vaccination. METHODS: This study used the keyword research tool, Google Trends, to evaluate trends in time series of the relative search query popularity of language-specific varicella keywords in 28 European countries from January 2015 through December 2021. The Google Ads Keyword Planner tool was used to evaluate absolute search volumes from March 2018 through December 2021. RESULTS: The relative search query popularity of varicella keywords displayed marked seasonal variation. In all 28 countries, the relative search query popularity of varicella keywords declined after the start of the COVID-19 pandemic (March 2020), compared with pre-pandemic levels (range, -18% to -70%). From April 2020 to July 2021, a period of intense COVID-19 transmission and infection control, absolute search volumes for varicella keywords were lower than pre-pandemic levels but rebounded after July 2021, when infection control measures were relaxed. CONCLUSION: This evaluation of search query trends demonstrated that search query data could be used as a proxy for trends in varicella infection rates and revealed that transmission of varicella may have been suppressed during the COVID-19 pandemic. Consideration should be given to using search query data to better understand the burden of varicella, particularly in countries where surveillance systems are inadequate.

Clinical, economic, and humanistic burden of community acquired pneumonia in Europe: a systematic literature review.

BACKGROUND: Community-acquired pneumonia (CAP) is an infectious lung inflammation contracted outside the hospital. CAP is a leading cause of death among young children, elderly, and immunocompromised persons. Incidence can reach 14 cases/1,000 adults. Up to 50% of cases require inpatient hospitalization. Mortality is 0.7/1,000 cases or 4 million deaths per year. We sought to summarize multi-dimensional burden of CAP for selected European countries. METHODS: We conducted a systematic literature review of literature published from 2011 to 2021 whereby we sought information pertaining to the epidemiologic, clinical, economic, and humanistic burden of CAP. Findings were summarized descriptively. RESULTS: CAP incidence in Europe is variable, with the highest burden among those of advanced age and with chronic comorbidities. Etiology is primarily bacterial infection with Streptococcus pneumoniae being the most frequently implicated. Direct medical costs are primarily attributable to inpatient stay, which is exacerbated among high-risk populations. Higher mortality rates are associated with increasing age, the need for inpatient hospitalization, and antibiotic resistance. CONCLUSIONS: A better understanding of CAP is needed, specifically the economic and quality of life burden on patients and caregivers. We recommend further assessments using population-level and real-world data employing consistent disease definitions.

Cost-effectiveness of pembrolizumab as an adjuvant treatment for patients with resected stage IIB or IIC melanoma in Switzerland.

AIM: To assess the cost-effectiveness of adjuvant pembrolizumab versus observation for patients with resected stage IIB/IIC melanoma from a third-party payers' perspective in Switzerland over a lifetime horizon. MATERIALS AND METHODS: A Markov state transition model with four health states (recurrence-free [RF], locoregional recurrence, distant metastases [DM], and death) was developed to determine the cost-effectiveness of pembrolizumab versus observation as an adjuvant treatment in patients with stage IIB/IIC melanoma who have undergone complete resection. The model utilized data from the KEYNOTE-716 randomized controlled trial (ClinicalTrials.gov, NCT03553836). The incremental cost-effectiveness ratio (ICER) (Swiss Franc [CHF] per life year or quality-adjusted life years [QALYs] gained) was calculated. A probabilistic sensitivity analysis and deterministic sensitivity analysis were conducted to assess the robustness of the base case results. RESULTS: Model results demonstrated that pembrolizumab is highly cost-effective as an adjuvant treatment for resected stage IIB/IIC melanoma versus observation in Switzerland. Base case results showed an ICER of CHF 27,424/QALY (EUR 27,342/QALY; exchange rate: 1 CHF = 0.997 EUR) for pembrolizumab versus observation. Results were most sensitive to changes to transition probabilities from the RF state. Most sensitivity and scenario analyses resulted in ICERs below the willingness-to-pay threshold (WTP) of CHF 100,000. At this WTP, pembrolizumab had a 78.9% probability of being cost-effective versus observation. LIMITATIONS: Due to a limited follow-up period in the KEYNOTE-716 trial, data from other clinical trials in the advanced melanoma setting were synthesized in a network meta-analysis and used to inform transition probabilities from DM to death in the cost-effectiveness model, to overcome the absence of these data from the trial. CONCLUSION: The model demonstrated that pembrolizumab is highly cost-effective versus observation in patients with resected stage IIB/IIC melanoma in Switzerland. The ICER was below the WTP threshold of CHF 100,000, commonly used for cost-effectiveness models in Switzerland.

Indirect Costs Due to Lung Cancer-Related Premature Mortality in Four European Countries.

INTRODUCTION: Lung cancer accounts for approximately 20% of all cancer-related deaths and for the loss of 3.2 million disability-adjusted life years (DALYs) annually across Europe. The present study investigated the productivity losses resulting from premature deaths due to lung cancer in four European countries. METHODS: The human capital approach (HCA) was used to estimate indirect cost of productivity losses due to premature death due to lung cancer (ICD-10 codes C33-34 malignant neoplasm of trachea, bronchus, and lung) in Belgium, the Netherlands, Norway, and Poland. Years of productive life lost (YPLL) and present value of future lost productivity (PVFLP) were calculated using national age-specific mortality, wages, and employment rates. Data were sourced from the World Health Organization, Eurostat, and the World Bank. RESULTS: In 2019, there were 41,468 lung cancer deaths in the included countries resulting in 59,246 YPLL and more than €981 million in productivity losses due to premature mortality. From 2010 to 2015, the PVFLP of lung cancer decreased by 14% in Belgium, 13% in the Netherlands, 33% in Norway, and 19% in Poland. From 2015 to 2019, the PVFLP of lung cancer decreased by 26% in Belgium, 27% in the Netherlands, 14% in Norway, and 38% in Poland. CONCLUSION: The results from this study illustrate a decreasing trend in productivity costs of premature mortality due to lung cancer, as illustrated by the decreasing PVFLP between 2010 and 2019. This trend could be driven by a shift in the distribution of deaths towards older age groups due to advancements in the preventative and treatment landscape. These results provide an economic measure of the lung cancer burden which may assist decision-makers in allocating scarce resources amongst competing priorities in the included countries.

HTA and Reimbursement Status of Metastatic Hormone­Sensitive Prostate Cancer, Non-Metastatic Castration-Resistant Prostate Cancer, and Metastatic Castration-Resistant Prostate Cancer Treatments in Europe: A Patient Access Landscape Review.

Background: Prostate cancer is the second most common cancer in men, with up to one-third of men being diagnosed in their lifetime. Recently, novel therapies have received regulatory approval with significant improvement in overall survival for metastatic castration-resistant prostate cancer, metastatic hormone-sensitive prostate cancer, and nonmetastatic castration-resistant prostate cancer. To improve decision-making regarding the value of anticancer therapies and support standardized assessment for use by health technology assessment (HTA) agencies, the European Society for Medical Oncology (ESMO) has developed a Magnitude of Clinical Benefit Scale (MCBS). Objective: This review aimed to map HTA status, reimbursement restrictions, and patient access for 3 advanced prostate cancer indications across 23 European countries during 2011-2021. Methods: HTA, country reimbursement lists, and ESMO-MCBS scorecards were reviewed for evidence and data across 26 European countries. Results: The analysis demonstrated that only in Greece, Germany, and Sweden was there full access across all included prostate cancer treatments. Treatments available for metastatic castration-resistant prostate cancer were widely reimbursed, with both abiraterone and enzalutamide accessible in all countries. In 3 countries (Hungary, the Netherlands, and Switzerland), there was a statistically significant difference (P<.05) between status of reimbursement and ESMO-MCBS "substantial benefit" (score of 4 or 5) vs "no substantial benefit" (score <4). Conclusion: Overall, the impact of the ESMO-MCBS on reimbursement decisions in Europe is unclear, with significant variation across the countries included in this review.

Breast cancer-related mortality in Central and Eastern Europe: years of life lost and productivity costs.

BACKGROUND: Breast cancer (BC) poses a public health challenge as the most commonly diagnosed cancer among women globally. While BC mortality has declined across Europe in the past three decades, an opposite trend has been reported in some transitional European countries. This analysis estimates the mortality burden and the cost of lost productivity due to BC deaths in nine Central and Eastern Europe (CEE) countries: Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia, that have defied the favorable cancer mortality trends. These estimates may provide relevant evidence to aid decision-makers in the prioritization of BC-targeted policies. METHODS: The human capital approach (HCA) was used to estimate years of life lost (YLL) and productivity losses due to premature death from BC (ICD-10 code: C50 Malignant neoplasm of breast). YLL and present value of future lost productivity (PVFLP) were calculated using age and gender-specific mortality, wages, and employment rates. Data were sourced from the World Health Organization (WHO), Eurostat, and the World Bank. RESULTS: In 2019, there were 19,726 BC deaths in the nine CEE countries. This study estimated BC deaths resulted in 267,184 YLL. Annual PVFLP was estimated to be €85 M in Poland, €46 M in Romania, €39 M in Hungary, €21 M in Slovakia, €18 M in Serbia, €16 M in Czech Republic, €15 M in Bulgaria, €13 M in Croatia, and €7 M in Slovenia. CONCLUSION: Premature death from BC leads to substantial YLL and productivity losses. Lost productivity costs due to premature BC-related mortality exceeded €259 million in 2019 alone. The data modeled provide important evidence toward resource allocation priorities for BC prevention, screening, and treatment that could potentially decrease productivity losses. Careful consideration should be given to BC-specific policies, such as surveillance programs and the availability of new treatments in CEE countries to decrease the medical and financial burden of the disease.

Clinical and economic burden of pneumococcal disease among adults in Sweden: A population-based register study.

Pneumococcal disease is a major cause of clinical and economic burden worldwide. This study investigated the burden of pneumococcal disease in Swedish adults. A retrospective population-based study was conducted using Swedish national registers, including all adults aged ≥18 years with a diagnosis of pneumococcal disease (defined as pneumococcal pneumonia, meningitis, or septicemia) in inpatient or outpatient specialist care between 2015-2019. Incidence and 30-day case fatality rates, healthcare resource utilization, and costs were estimated. Results were stratified by age (18-64, 65-74, and ≥75 years) and the presence of medical risk factors. A total of 10,391 infections among 9,619 adults were identified. Medical factors associated with higher risk for pneumococcal disease were present in 53% of patients. These factors were associated with increased pneumococcal disease incidence in the youngest cohort. In the cohort aged 65-74 years, having a very high risk for pneumococcal disease was not associated with an increased incidence. Pneumococcal disease incidence was estimated at 12.3 (18-64), 52.1 (64-74), and 85.3 (≥75) per 100,000 population. The 30-day case fatality rate increased with age (18-64: 2.2%, 65-74: 5.4%, ≥75: 11.7%), and was highest among septicemia patients aged ≥75 (21.4%). The 30-day average number of hospitalizations was 1.13 (18-64), 1.24 (64-74) and 1.31 (≥75). The average 30-day cost/infection was estimated at €4,467 (18-64), €5,278 (65-74), and €5,898 (≥75). The 30-day total direct cost of pneumococcal disease between 2015-2019 was €54.2 million, with 95% of costs from hospitalizations. The clinical and economic burden of pneumococcal disease in adults was found to increase with age, with nearly all costs associated with pneumococcal disease from hospitalizations. The 30-day case fatality rate was highest in the oldest age group, though not negligible in the younger age groups. The findings of this study can inform the prioritization of pneumococcal disease prevention in adult and elderly populations.