Clash of the pandemics – At least 150’000 adults in Switzerland suffer from obesity grades 2 or 3 and are thus at elevated risk for severe COVID-19

Background: Grade 2 and 3 obesity, alongside with other relevant risk factors, are substantially and independently associated with adverse outcomes of coronavirus disease 2019 (COVID-19). However, for Switzerland, due to the lack of synthesis studies, it is currently unknown how many people are affected by obesity at all. This knowledge may help to better estimate the relevance and size of this group at elevated risk, which could be incorporated into strategies to protect risk groups during the still unfolding COVID-19 pandemic. This study aimed to provide a first overall estimation of how many people in Switzerland are currently affected by grade 2 or 3 obesity. Methods: Five representative national population-based studies were accessed which were conducted between 2012 and 2017 and which include data on height and weight of adult men and women in Switzerland. Results: In Switzerland in 2012-2017, among the 11.20% adults who were obese (body mass index (BMI) ≥30.0kg/m2), 1.76% (95% CI 1.50-2.02) suffered from grade 2 obesity (BMI 35.0-39.9 kg/m2), and 0.58% (95% CI 0.50-0.66) from grade severe 3 obesity (BMI ≥40.0 kg/m2). Converted into estimated absolute population numbers, this corresponds to a total of approximately n=154,515 people who suffer from grade 2 or 3 obesity (n=116,216 and n=38,298, respectively). Conclusions: This risk group includes many younger people in Switzerland. The number of people with obesity-related risk becomes 3.8 to 13.6 times higher if grade 1 obesity and overweight people are also included in this risk group, for which there are arguments arising in the latest literature. In general, this large group at risk for severe COVID-19 should be given more attention and support. If it is confirmed that obesity plays a major role in severe COVID-19 courses, then every kilo of body weight that is not gained or that is lost in lockdown counts.

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The Risk of Invasive Pneumococcal Disease Differs between Risk Groups in Norway Following Widespread Use of the 13-Valent Pneumococcal Vaccine in Children

Microorganisms ◽

10.3390/microorganisms9081774 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1774

Author(s):

Brita Askeland Winje ◽

Didrik Frimann Vestrheim ◽

Richard Aubrey White ◽

Anneke Steens

Keyword(s):

Invasive Pneumococcal Disease ◽

Pneumococcal Disease ◽

Risk Group ◽

Population Data ◽

Risk Groups ◽

The Elderly ◽

Population Based ◽

Childhood Vaccination ◽

Medical Risk ◽

Icd 10

The elderly and adults with medical risk conditions remain at high risk of invasive pneumococcal disease (IPD), highlighting the importance of adequate preventive efforts. In an observational population-based study in Norway (pop ≥ 5 years, 2009–2017) covering six years post-PCV13 implementation, we explored the incidence and risk of IPD associated with age and comorbidities. We obtained the data on 5535 IPD cases from the Norwegian Surveillance System for Communicable Diseases and the population data from Statistics Norway. To define comorbidities, we obtained ICD-10 codes from the Norwegian Patient Registry for the cases and the Norwegian population. The average annual decrease in PCV13 IPD incidence was significant in all risk groups and decreased post-PCV13 introduction by 16–20% per risk group, implying a nondifferential indirect protection from the childhood vaccination. The IPD incidence remained high in the medical risk groups. The relative importance of medical risk conditions was 2.8 to 6 times higher in those aged 5–64 versus ≥65 years for all types of IPD, since age itself is a risk factor for IPD. In groups without medical risk, the risk of IPD was eight times higher in those aged ≥65 compared to those 5–64 years (RR 8.3 (95% CI 7.3–9.5)). Our results underscore the need for age- and risk-group-based prevention strategies.

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Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.646982 ◽

2021 ◽

Vol 9 ◽

Author(s):

Pengju Li ◽

Shihui Hao ◽

Yongkang Ye ◽

Jinhuan Wei ◽

Yiming Tang ◽

...

Keyword(s):

High Risk ◽

Urothelial Cancer ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

The Cancer Genome Atlas ◽

Data Set ◽

Related Risk ◽

Metastatic Urothelial Cancer

Immune checkpoint inhibitor (ICI) treatment has been used to treat advanced urothelial cancer. Molecular markers might improve risk stratification and prediction of ICI benefit for urothelial cancer patients. We analyzed 406 cases of bladder urothelial cancer from The Cancer Genome Atlas (TCGA) data set and identified 161 messenger RNAs (mRNAs) as differentially expressed immunity genes (DEIGs). Using the LASSO Cox regression model, an eight-mRNA-based risk signature was built. We validated the prognostic and predictive accuracy of this immune-related risk signature in 348 metastatic urothelial cancer (mUC) samples treated with anti-PD-L1 (atezolizumab) from IMvigor210. We built an immune-related risk signature based on the eight mRNAs: ANXA1, IL22, IL9R, KLRK1, LRP1, NRG3, SEMA6D, and STAP2. The eight-mRNA-based risk signature successfully categorizes patients into high-risk and low-risk groups. Overall survival was significantly different between these groups, regardless if the initial TCGA training set, the internal TCGA testing set, all TCGA set, or the ICI treatment set. The hazard ratio (HR) of the high-risk group to the low-risk group was 3.65 (p < 0.0001), 2.56 (p < 0.0001), 3.36 (p < 0.0001), and 2.42 (p = 0.0009). The risk signature was an independent prognostic factor for prediction survival. Moreover, the risk signature was related to immunity characteristics. In different tumor mutational burden (TMB) subgroups, it successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome. Our eight-mRNA-based risk signature is a stable biomarker for urothelial cancer and might be able to predict which patients benefit from ICI treatment. It might play a role in precision individualized immunotherapy.

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Three Separate Clinical Entities of Infective Endocarditis—A Population-Based Study From Southern Finland 2013–2017

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa334 ◽

2020 ◽

Vol 7 (9) ◽

Author(s):

Mika Halavaara ◽

Timi Martelius ◽

Veli-Jukka Anttila ◽

Asko Järvinen

Keyword(s):

Infective Endocarditis ◽

Drug Use ◽

Prosthetic Valve ◽

Risk Group ◽

Case Fatality ◽

Risk Groups ◽

Population Based ◽

Intravenous Drug Use ◽

Population Based Study ◽

Population Based Survey

Abstract Background Health care–associated infective endocarditis (HAIE) and intravenous drug use–related IE (IDUIE) have emerged as major groups in infective endocarditis (IE). We studied their role and clinical picture in a population-based survey. Methods A population-based retrospective study including all adult patients diagnosed with definite or possible IE in Southern Finland in 2013–2017. IE episodes were classified according to the mode of acquisition into 3 groups: community-acquired IE (CAIE), HAIE, and IDUIE. Results Total of 313 episodes arising from 291 patients were included. Incidence of IE was 6.48/100 000 person-years. CAIE accounted for 38%, HAIE 31%, and IDUIE 31% of IE episodes. Patients in the IDUIE group were younger, and they more frequently had right-sided IE (56.7% vs 5.0%; P < .001) and S. aureus as etiology (74.2% vs 17.6%; P < .001) compared with the CAIE group. In-hospital (15.1% vs 9.3%; P = .200) and cumulative 1-year case fatality rates (18.5% vs 17.5%; P = .855) were similar in CAIE and IDUIE. Patients with HAIE had more comorbidities, prosthetic valve involvement (29.9% vs 10.9%; P = .001), enterococcal etiology (20.6% vs 5.9%; P = .002), and higher in-hospital (27.8% vs 15.1%; P = .024) and cumulative 1-year case fatality rates (43.3% vs 18.5%; P < .001) than patients with CAIE. Staphylococcus aureus caused one-fifth of IE episodes in both groups. Conclusions Our study indicates that in areas where injection drug use is common IDUIE should be regarded as a major risk group for IE, along with HAIE, and not seen as part of CAIE. Three different risk groups, CAIE, HAIE, and IDUIE, with variable characteristics and outcome should be recognized in IE.

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P3398Cystatin C based eGFR estimation compared to crea-based estimation equation for assessing risk of cardiovascular and total mortality in population-based studies and patients with manifest CVD

European Heart Journal ◽

10.1093/eurheartj/ehz745.0274 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

D Rothenbacher ◽

M Rehm ◽

L Iacoviello ◽

H Tunstall-Pedoe ◽

S Soederberg ◽

...

Keyword(s):

Smoking Status ◽

Adult Population ◽

Specific Treatment ◽

Total Mortality ◽

Public Health Problem ◽

Risk Groups ◽

Population Based ◽

Adverse Outcomes ◽

Ckd Stage ◽

History Of

Abstract Introduction Chronic kidney disease (CKD) represents a global public health problem and affects a large proportion of the adult population worldwide. Early detection, adequate risk stratification and specific treatment can prevent or delay the adverse effects of CKD. Purpose To assess cardiovascular risk and total mortality of subjects with CKD using cystatin C based and Crea-based estimated glomerular filtration rate (eGFR) equations (CKDEpi) in the general population, in diseased cohorts, and in specific subgroups. Methods The present study has been conducted within the BiomarCaRE project, with harmonized data from 21 population-based cohorts from 6 European countries and 3 cardiovascular disease (CVD) cohorts from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for age, sex, cohort, smoking status, body mass index, history of diabetes, history of hypertension, and total cholesterol. Results 21 population-based cohorts (n=76,954, median age 51 years, 52.2% men, 4.4% diabetic) and 3 diseased cohorts (n=4,982, median age 63 years, 75.6% men, 18.7% diabetic) with an average follow-up between 2.8 and 23.5 years and between 0.5 and 9.4 years, respectively, were included in the analysis. Prevalence of CKD-stage 3–5 by CKD-EPIcrea and CKD-EPIcys eGFR respectively, was 3.4% and 7.3% in the population-based cohorts and 13.9% and 14.4% in the diseased cohorts. In the population-based cohorts the incidence (per 1000 person years) of a non-fatal or fatal CVD event and total mortality respectively, was 10.0 and 11.8, whereas it was 21.2 and 17.8 in the diseased cohorts. In the population-based cohorts the HR for a CVD-event was 1.32 (95% CI 1.21–1.44) for the population with CKD-EPIcrea stage 3–5 and it was 1.47 (95% CI 1.35–1.60) based on CKD-EPIcys after adjustment for covariates. The HR for total mortality for those with CKD-EPIcrea stage 3–5 was 1.31 (1.21–1.41) and for CKD-EPIcys it was 1.86 (95% CI 1.73–2.00). Discrepancies between CKD-EPIcrea and CKD-EPIcys were even more striking across subgroups with and without diabetes or across specific age groups. Conclusion CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of CKD-EPIcrea and CKD-EPIcys eGFR differ considerably between specific risk groups. Therefore, the clinical utility of both equations in different risk groups has to be considered and should be evaluated further. Acknowledgement/Funding 7th framework programme collaborative project, grant agreement no. HEALTH-F2-2011-278913

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Characterization of Exosome-Related Gene Risk Model to Evaluate the Tumor Immune Microenvironment and Predict Prognosis in Triple-Negative Breast Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2021.736030 ◽

2021 ◽

Vol 12 ◽

Author(s):

Pengjun Qiu ◽

Qiaonan Guo ◽

Qingzhi Yao ◽

Jianpeng Chen ◽

Jianqing Lin

Keyword(s):

Triple Negative ◽

Immune Cell ◽

Risk Model ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Expression Levels ◽

Related Risk ◽

The Relationship

BackgroundAs a kind of small membrane vesicles, exosomes are secreted by most cell types from multivesicular endosomes, including tumor cells. The relationship between exosomes and immune response plays a vital role in the occurrence and development of tumors. Nevertheless, the interaction between exosomes and the microenvironment of tumors remains unclear. Therefore, we set out to study the influence of exosomes on the triple-negative breast cancer (TNBC) microenvironment.MethodOne hundred twenty-one exosome-related genes were downloaded from ExoBCD database, and IVL, CXCL13, and AP2S1 were final selected because of the association with TNBC prognosis. Based on the sum of the expression levels of these three genes, provided by The Cancer Genome Atlas (TCGA), and the regression coefficients, an exosome risk score model was established. With the median risk score value, the patients in the two databases were divided into high- and low-risk groups. R clusterProfiler package was employed to compare the different enrichment ways between the two groups. The ESTIMATE and CIBERSORT methods were employed to analyze ESTIMATE Score and immune cell infiltration. Finally, the correlation between the immune checkpoint-related gene expression levels and exosome-related risk was analyzed. The relationship between selected gene expression and drug sensitivity was also detected.ResultsDifferent risk groups exhibited distinct result of TNBC prognosis, with a higher survival rate in the low-risk group than in the high-risk group. The two groups were enriched by immune response and biological process pathways. A better overall survival (OS) was demonstrated in patients with high scores of immune and ESTIMATE rather than ones with low scores. Subsequently, we found that CD4+-activated memory T cells and M1 macrophages were both upregulated in the low-risk group, whereas M2 macrophages and activated mast cell were downregulated in the low-risk group in patients from the TCGA and GEO databases, respectively. Eventually, four genes previously proposed to be targets of immune checkpoint inhibitors were evaluated, resulting in the expression levels of CD274, CTLA4, LAG3, and TIM3 being higher in the low-risk group than high-risk group.ConclusionThe results of our study suggest that exosome-related risk model was related to the prognosis and ratio of immune cell infiltration in patients with TNBC. This discovery may make contributions to improve immunotherapy for TNBC.

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Prognostic Risk Assessment and Prediction of Radiotherapy Benefit for Women with Ductal Carcinoma In Situ (DCIS) of the Breast, in a Randomized Clinical Trial (SweDCIS)

Cancers ◽

10.3390/cancers13236103 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6103

Author(s):

Fredrik Wärnberg ◽

Per Karlsson ◽

Erik Holmberg ◽

Kerstin Sandelin ◽

Pat W. Whitworth ◽

...

Keyword(s):

Statistical Power ◽

Ductal Carcinoma ◽

Risk Group ◽

Treatment Strategies ◽

Significant Risk ◽

Risk Groups ◽

Breast Conserving Surgery ◽

Elevated Risk ◽

Dcis Treatment

Prediction of radiotherapy (RT) benefit after breast-conserving surgery (BCS) for DCIS is crucial. The aim was to validate a biosignature, DCISionRT®, in the SweDCIS randomized trial. Women were randomly assigned to RT or not after BCS, between 1987 and 2000. Tumor blocks were collected, and slides were sent to PreludeDxTM for testing. In 504 women with complete data and negative margins, DCISionRT divided 52% women into Elevated (DS > 3) and 48% in Low (DS ≤ 3) Risk groups. In the Elevated Risk group, RT significantly decreased relative 10-year ipsilateral total recurrence (TotBE) and 10-year ipsilateral invasive recurrence (InvBE) rates, HR 0.32 and HR 0.24, with absolute decreases of 15.5% and 9.3%. In the Low Risk group, there were no significant risk differences observed with radiotherapy. Using a cutoff of DS > 3.0, the test was not predictive for RT benefit (p = 0.093); however, above DS > 2.8 RT benefit was greater for InvBE (interaction p = 0.038). Recurrences at 10 years without radiotherapy increased significantly per 5 DS units (TotBE HR:1.5 and InvBE HR:1.5). Continuous DS was prognostic for TotBE risk although categorical DS did not reach significance. Absolute 10-year TotBE and InvBE risks appear sufficiently different to indicate that DCISionRT can aid physicians in selecting individualized adjuvant DCIS treatment strategies. Further analyses are planned in combined cohorts to increase statistical power.

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A novel biosignature identifies DCIS patients with a poor biologic subtype with an unacceptably high rate of local recurrence after breast conserving surgery and radiotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.513 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 513-513

Author(s):

Frank Vicini ◽

Chirag Shah ◽

Pat W. Whitworth ◽

Steven C Shivers ◽

Fredrik Warnberg ◽

...

Keyword(s):

Risk Group ◽

Poor Response ◽

Risk Groups ◽

Recurrence Risk ◽

Breast Conserving Surgery ◽

Elevated Risk ◽

Ffpe Tissue ◽

Low Risk ◽

Recurrence Rates ◽

Significant Difference

513 Background: There is an unmet need to identify women diagnosed with DCIS who have a low recurrence risk and could omit radiotherapy (RT) after breast conserving surgery (BCS), or an elevated recurrence risk after treatment with BCS plus RT. DCISionRT and its response subtype (Rst) biosignature were evaluated in a contemporary cohort treated with BCS with or without RT to identify these risk groups. Methods: Pathology, clinical data, and FFPE tissue samples were evaluable for 485 women diagnosed with DCIS at centers in Sweden (1996-2004), the USA (1999-2008), and Australia (2006-2011). Patients were treated with BCS (negative margins) with or without whole breast RT. Ipsilateral breast tumor recurrence (IBTR) included DCIS or invasive breast cancer (IBC) that was local, regional, or metastatic. The patients were classified into Low and Elevated risk groups to assess IBTR and IBC rates. Patients in the Elevated risk group were categorized by two subtypes: a good response subtype (good Rst) or a poor response subtype (poor Rst) after BCS plus RT. Biosignatures were calculated using biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2) assayed using IHC on FFPE tissue. Hazard ratios and 10-year risks were calculated using Cox proportional hazards (CPH) and Kaplan-Meier analyses. Results: In the DCISionRT Elevated risk group, RT was associated with significantly reduced recurrence rates, but only for those patients with a good Rst (Table, IBTR HR=0.18, p<0.001, IBC HR=0.15, p=0.003, n=241). For Elevated risk group patients with a poor Rst, no benefit to RT was noted (Table). Additionally, irrespective of RT, patients with a poor Rst had 10-year IBTR/IBC rates of 25%/16%, which were much higher than good Rst rates of 6.6%/4.5% (IBE HR=3.6, p=0.02, IBC HR=4.4, p=0.04, n=190). For patients in the Low risk group, there was no significant difference in 10-year IBTR/IBC rates with and without RT (Table, IBTR p=0.4, IBC p=0.9, n=177). The distribution of clinicopathologic risk factors (age <50 years, grade 3, size >2.5 cm) did not identify poor vs. good response subtypes, and multivariable analysis (n=485) indicated these traditional clinicopathologic factors and endocrine therapy were not significantly associated with IBTR (p≥0.22) or IBC (p≥0.34). Conclusions: Biosignatures identified a Low risk patient group with low 10-year recurrence rates with or without RT who may be candidates for omitting adjuvant RT. Biosignatures also identified an Elevated risk group receiving BCS plus RT with a poor response subtype that had unacceptably high recurrence rates, warranting potential intensified or alternate therapy.[Table: see text]

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A prognostic nomogram based on LASSO Cox regression in patients with alpha-fetoprotein-negative hepatocellular carcinoma following non-surgical therapy

BMC Cancer ◽

10.1186/s12885-021-07916-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dongdong Zhou ◽

Xiaoli Liu ◽

Xinhui Wang ◽

Fengna Yan ◽

Peng Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Surgical Therapy ◽

Calibration Curve ◽

Cox Regression ◽

Validation Cohort ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Alpha Fetoprotein ◽

Clinicopathologic Characteristics

Abstract Background Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. Methods A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. Results The C-index of nomogram1was 0.708 (95%CI: 0.673–0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606–0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690–0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691–0.813; AUC: 0.784, 95%CI: 0.709–0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. Conclusions Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.

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Quantitative proteomic analysis of aberrant expressed lysine acetylation in gastrointestinal stromal tumors

Clinical Proteomics ◽

10.1186/s12014-021-09322-0 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Bo Wang ◽

Long Zhao ◽

Zhidong Gao ◽

Jianyuan Luo ◽

Haoran Zhang ◽

...

Keyword(s):

Risk Group ◽

Risk Groups ◽

Quantitative Information ◽

Differentially Expressed ◽

High Rate ◽

Lysine Acetylation ◽

Kegg Pathways ◽

Tandem Mass Tag ◽

Cell Components ◽

Nih Classification

Abstract Background Gastrointestinal stromal tumor (GIST) is a common digestive tract tumor with high rate of metastasis and recurrence. Currently, we understand the genome, transcriptome and proteome in GIST. However, posttranscriptional modification features in GIST remain unclear. In the present study, we aimed to construct a complete profile of acetylome in GIST. Methods Five common protein modifications, including acetylation, succinylation, crotonylation, 2-hydroxyisobutyrylation, and malonylation were tested among GIST subgroups and significantly differentially- expressed lysine acetylation was found. The acetylated peptides labeled with Tandem Mass Tag (TMT)under high sensitive mass spectrometry, and some proteins with acetylation sites were identified. Subsequently, these proteins and peptides were classified into high/moderate (H/M) risk and low (L) risk groups according to the modified NIH classification standard. Furthermore, cell components, molecular function, biological processes, KEGG pathways and protein interaction networks were analyzed. Results A total of 2904 acetylation sites from 1319 proteins were identified, of which quantitative information of 2548 sites from 1169 proteins was obtained. Finally, the differentially-expressed lysine acetylation sites were assessed and we found that 42 acetylated sites of 38 proteins were upregulated in the H/M risk group compared with the L risk group, while 48 acetylated sites of 44 proteins were downregulated, of which Ki67 K1063Ac and FCHSD2 K24Ac were the two acetylated proteins that were most changed. Conclusions Our novel findings provide further understanding of acetylome in GIST and might demonstrate the possibility in the acetylation targeted diagnosis and therapy of GIST.

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Risk Factors for Pneumonia and Death in Adult Patients With Seasonal Influenza and Establishment of Prediction Scores: A Population-Based Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab068 ◽

2021 ◽

Vol 8 (3) ◽

Author(s):

Koichi Miyashita ◽

Eiji Nakatani ◽

Hironao Hozumi ◽

Yoko Sato ◽

Yoshiki Miyachi ◽

...

Keyword(s):

High Risk ◽

Seasonal Influenza ◽

Prediction Models ◽

Validation Cohort ◽

Risk Groups ◽

Population Based ◽

Limited Data ◽

Population Based Study ◽

Relative Risks ◽

Primary Care Settings

Abstract Background Seasonal influenza remains a global health problem; however, there are limited data on the specific relative risks for pneumonia and death among outpatients considered to be at high risk for influenza complications. This population-based study aimed to develop prediction models for determining the risk of influenza-related pneumonia and death. Methods We included patients diagnosed with laboratory-confirmed influenza between 2016 and 2017 (main cohort, n = 25 659), those diagnosed between 2015 and 2016 (validation cohort 1, n = 16 727), and those diagnosed between 2017 and 2018 (validation cohort 2, n = 34 219). Prediction scores were developed based on the incidence and independent predictors of pneumonia and death identified using multivariate analyses, and patients were categorized into low-, medium-, and high-risk groups based on total scores. Results In the main cohort, age, gender, and certain comorbidities (dementia, congestive heart failure, diabetes, and others) were independent predictors of pneumonia and death. The 28-day pneumonia incidence was 0.5%, 4.1%, and 10.8% in the low-, medium-, and high-risk groups, respectively (c-index, 0.75); the 28-day mortality was 0.05%, 0.7%, and 3.3% in the low-, medium-, and high-risk groups, respectively (c-index, 0.85). In validation cohort 1, c-indices for the models for pneumonia and death were 0.75 and 0.87, respectively. In validation cohort 2, c-indices for the models were 0.74 and 0.87, respectively. Conclusions We successfully developed and validated simple-to-use risk prediction models, which would promptly provide useful information for treatment decisions in primary care settings.

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