Understanding health care pathways of patients with sepsis: protocol of a mixed-methods analysis of health care utilization, experiences, and needs of patients with and after sepsis.

BACKGROUND: Sepsis is associated with about 20% of deaths worldwide. It often presents with non-specific initial symptoms, making its emergency treatment an interdisciplinary and cross-sectoral challenge. Three in four sepsis survivors suffers from new cognitive, psychological, or physical sequelae for which specific treatment concepts are scarce. The AVENIR project aims to improve the understanding of patient pathways, and subjective care experiences and needs along the entire healthcare pathway before, with and after sepsis. Based on this, concrete recommendations for the organization of care and patient information materials will be developed with close patient participation. METHODS: Mixed-methods study including (1) analysis of anonymized nationwide health claims data from Germany, (2) linkage of health claims data with patient care reports (PCR) of emergency medical services from study regions in two federal states within Germany, and (3) qualitative exploration of the patient, relative, and care provider perspective on sepsis care. In (1), we analyze inpatient and outpatient health care utilization until 30 days pre-sepsis; clinical sepsis care including intra- and inter-hospital transfers; and rehabilitation, inpatient and outpatient aftercare of sepsis survivors as well as costs for health care utilization until 24 months post-sepsis. We attempt to identify survivor classes with similar health care utilization by Latent Class Analyses. In (2), PCR are linked with health claims data to establish a comprehensive database outlining care pathways for sepsis patients from pre-hospital to follow-up. We investigate e.g., whether correct initial assessment is associated with acute (e.g., same-day lethality) and long-term (e.g., new need for care, long-term mortality) outcomes of patients. We compare the performance of sepsis-specific screening tools such as qSOFA, NEWS-2 or PRESEP in the pre-clinical setting. In (3), semi-structured interviews as well as synchronous and asynchronous online focus groups are conducted and analyzed using qualitative content analyses techniques. DISCUSSION: The results of the AVENIR study will contribute to a deeper understanding of sepsis care pathways in Germany. They may serve as a base for improvements and innovations in sepsis care, that in the long-term can contribute to reduce the personal, medical, and societal burden of sepsis and its sepsis sequelae. TRIAL REGISTRATION: Registered at German Clinical Trial Register (ID: DRKS00031302, date of registration: 5th May 2023).

Association between hospital onset of infection and outcomes in sepsis patients - A propensity score matched cohort study based on health claims data in Germany.

BACKGROUND: Hospital-acquired infections are a common source of sepsis. Hospital onset of sepsis was found to be associated with higher acute mortality and hospital costs, yet its impact on long-term patient-relevant outcomes and costs is unknown. OBJECTIVE: We aimed to assess the association between sepsis origin and acute and long-term outcomes based on a nationwide population-based cohort of sepsis patients in Germany. METHODS: This retrospective cohort study used nationwide health claims data from 23 million health insurance beneficiaries. Sepsis patients with hospital-acquired infections (HAI) were identified by ICD-10-codes in a cohort of adult patients with hospital-treated sepsis between 2013 and 2014. Cases without these ICD-10-codes were considered as sepsis cases with community-acquired infection (CAI) and were matched with HAI sepsis patients by propensity score matching. Outcomes included in-hospital/12-month mortality and costs, as well as readmissions and nursing care dependency until 12 months postsepsis. RESULTS: We matched 33,110 HAI sepsis patients with 28,614 CAI sepsis patients and 22,234 HAI sepsis hospital survivors with 19,364 CAI sepsis hospital survivors. HAI sepsis patients had a higher hospital mortality than CAI sepsis patients (32.8% vs. 25.4%, RR 1.3, p < .001). Similarly, 12-months postacute mortality was higher (37.2% vs. 30.1%, RR=1.2, p < .001). Hospital and 12-month health care costs were 178% and 22% higher in HAI patients than in CAI patients, respectively. Twelve months postsepsis, HAI sepsis survivors were more often newly dependent on nursing care (33.4% vs. 24.0%, RR=1.4, p < .001) and experienced 5% more hospital readmissions (mean number of readmissions: 2.1 vs. 2.0, p < .001). CONCLUSIONS: HAI sepsis patients face an increased risk of adverse outcomes both during the acute sepsis episode and in the long-term. Measures to prevent HAI and its progression into sepsis may be an opportunity to mitigate the burden of long-term impairments and costs of sepsis, e.g., by early detection of HAI progressing into sepsis, particularly in normal wards; adequate sepsis management and adherence to sepsis bundles in hospital-acquired sepsis; and an improved infection prevention and control.

[Once vaccinated, always vaccinated? A claims data analysis on repeated influenza vaccinations among individuals aged ≥ 60 years]. / Einmal geimpft, immer geimpft? Routinedatenanalyse zur wiederholten Influenzaimpfung von ≥ 60-Jährigen.

BACKGROUND: The Standing Committee on Vaccination recommends the seasonal influenza vaccination as a standard vaccination for individuals aged ≥ 60 years and as an indication vaccination independent of age. Empirical data on repeated vaccination are not available for Germany. The aim of this study was therefore to investigate the frequency and influencing factors of repeated vaccinations. METHODS: We conducted a longitudinal retrospective observational study with claims data from ≥ 60­year-olds insured with the statutory health insurance AOK Plus in Thuringia between 2012 and 2018. The number of seasons with influenza vaccination was described and the association with various individual characteristics was analysed in a regression model. RESULTS: Included were 103,163 individuals with at least one influenza vaccination in the 2014/2015 season, of whom 75.3% had been vaccinated in ≥ 6 of 7 seasons. We found repeated vaccinations more frequently among nursing home residents (rate ratio (RR) 1.27), individuals with increased health risk due to underlying diseases (RR 1.21) and higher age groups (vs. 60-69 years: RR 1.17-1.25). With each additional year of participating in a disease management program, the number of vaccinations increased (RR 1.03). Women (RR 0.91), individuals with nursing care level 1 (vs. no nursing care level: RR 0.90) and people with a comorbidity (vs. no comorbidity: RR 0.97) were less likely to receive repeated vaccinations. DISCUSSION: A large proportion of individuals aged ≥ 60 years who have been vaccinated against influenza once is likely to repeatedly receive vaccinations. In accordance with vaccination recommendations, nursing home residents and in particular individuals with an increased health risk are vaccinated repeatedly. General practitioners play a central role: non-acute patient contacts should be used to offer vaccinations, especially to women and individuals in need of care who are living at home.

The Effects of Postacute Rehabilitation on Mortality, Chronic Care Dependency, Health Care Use, and Costs in Sepsis Survivors.

Rationale: Sepsis often leads to long-term functional deficits and increased mortality in survivors. Postacute rehabilitation can decrease long-term sepsis mortality, but its impact on nursing care dependency, health care use, and costs is insufficiently understood. Objectives: To assess the short-term (7-12 months postdischarge) and long-term (13-36 months postdischarge) effect of inpatient rehabilitation within 6 months after hospitalization on mortality, nursing care dependency, health care use, and costs. Methods: An observational cohort study used health claims data from the health insurer AOK (Allgemeine Ortskrankenkasse). Among 23.0 million AOK beneficiaries, adult beneficiaries hospitalized with sepsis in 2013-2014 were identified by explicit codes from the International Classification of Diseases, Tenth Revision. The study included patients who were nonemployed presepsis, for whom rehabilitation is reimbursed by the AOK and thus included in the dataset, and who survived at least 6 months postdischarge. The effect of rehabilitation was estimated by statistical comparisons of patients with rehabilitation (treatment group) and those without (reference group). Possible differential effects were investigated for the subgroup of ICU-treated sepsis survivors. The study used inverse probability of treatment weighting based on propensity scores to adjust for differences in relevant covariates. Costs for rehabilitation in the 6 months postsepsis were not included in the cost analysis. Results: Among 41,918 6-month sepsis survivors, 17.2% (n = 7,224) received rehabilitation. There was no significant difference in short-term survival between survivors with and without rehabilitation. Long-term survival rates were significantly higher in the rehabilitation group (90.4% vs. 88.7%; odds ratio [OR] = 1.2; 95% confidence interval [95% CI] = 1.1-1.3; P = 0.003). Survivors with rehabilitation had a higher mean number of hospital readmissions (7-12 months after sepsis: 0.82 vs. 0.76; P = 0.014) and were more frequently dependent on nursing care (7-12 months after sepsis: 47.8% vs. 42.3%; OR = 1.2; 95% CI = 1.2-1.3; P < 0.001; 13-36 months after sepsis: 52.5% vs. 47.5%; OR = 1.2; 95% CI = 1.1-1.3; P < 0.001) compared with those without rehabilitation, whereas total health care costs at 7-36 months after sepsis did not differ between groups. ICU-treated sepsis patients with rehabilitation had higher short- and long-term survival rates (short-term: 93.5% vs. 90.9%; OR = 1.5; 95% CI = 1.2-1.7; P < 0.001; long-term: 89.1% vs. 86.3%; OR = 1.3; 95% CI = 1.1-1.5; P < 0.001) than ICU-treated sepsis patients without rehabilitation. Conclusions: Rehabilitation within the first 6 months after ICU- and non-ICU-treated sepsis is associated with increased long-term survival within 3 years after sepsis without added total health care costs. Future work should aim to confirm and explain these exploratory findings.

Occurrence and Risk Factors for New Dependency on Chronic Care, Respiratory Support, Dialysis and Mortality in the First Year After Sepsis.

Sepsis survival is associated with adverse outcomes. Knowledge about risk factors for adverse outcomes is lacking. We performed a population-based cohort study of 116,507 survivors of hospital-treated sepsis identified in health claims data of a German health insurance provider. We determined the development and risk factors for long-term adverse events: new dependency on chronic care, chronic dialysis, long-term respiratory support, and 12-month mortality. At-risk patients were defined by absence of these conditions prior to sepsis. Risk factors were identified using simple and multivariable logistic regression analyses. In the first year post-sepsis, 48.9% (56,957) of survivors had one or more adverse outcome, including new dependency on chronic care (31.9%), dialysis (2.8%) or respiratory support (1.6%), and death (30.7%). While pre-existing comorbidities adversely affected all studied outcomes (>4 comorbidities: OR 3.2 for chronic care, OR 4.9 for dialysis, OR 2.7 for respiratory support, OR 4.7 for 12-month mortality), increased age increased the odds for chronic care dependency and 12-month mortality, but not for dialysis or respiratory support. Hospital-acquired and multi-resistant infections were associated with increased risk of chronic care dependency, dialysis, and 12-month mortality. Multi-resistant infections also increased the odds of respiratory support. Urinary or respiratory infections or organ dysfunction increased the odds of new dialysis or respiratory support, respectively. Central nervous system infection and organ dysfunction had the highest OR for chronic care dependency among all infections and organ dysfunctions. Our results imply that patient- and infection-related factors have a differential impact on adverse life changing outcomes after sepsis. There is an urgent need for targeted interventions to reduce the risk.

[White Paper - Improving the care of patients with impairments following sepsis and infections]. / White Paper ­ Verbesserung der Versorgungs- und Behandlungsangebote für Menschen mit Sepsis- und Infektionsfolgen.

Hundreds of thousands of individuals who experience lasting sequelae after sepsis and infections in Germany do not receive optimal care. In this White Paper we present measures for improvement, which were developed by a multidisciplinary expect panel as part of the SEPFROK project. Improved care rests on four pillars: 1. cross-sectoral assessment of sequelae and a structured discharge and transition management, 2. interdisciplinary rehabilitation and aftercare with structural support, 3. strengthening the specific health literacy of patients and families, and 4. increased research into causes, prevention and treatment of sequelae. To achieve this, appropriate cross-sectoral care structures and legal frameworks must be created.

The effect of influenza and pneumococcal vaccination in the elderly on health service utilisation and costs: a claims data-based cohort study.

BACKGROUND: To date, cost-effectiveness of influenza and pneumococcal vaccinations was assumed in several health economic modelling studies, but confirmation by real-world data is sparse. The aim of this study is to assess the effects on health care utilisation and costs in the elderly using real-world data on both, outpatient and inpatient care. METHODS: Retrospective community-based cohort study with 138,877 individuals aged ≥ 60 years, insured in a large health insurance fund in Thuringia (Germany). We assessed health care utilisation and costs due to influenza- or pneumococcal-associated diseases, respiratory infections, and sepsis in 2015 and 2016. Individuals were classified into four groups according to their vaccination status from 2008 to 2016 (none, both, or either only influenza or pneumococcal vaccination). Inverse probability weighting based on 236 pre-treatment covariates was used to adjust for potential indication and healthy vaccinee bias. RESULTS: Influenza vaccination appeared as cost-saving in 2016, with lower disease-related health care costs of - €178.87 [95% CI - €240.03;- €117.17] per individual (2015: - €50.02 [95% CI - €115.48;€15.44]). Cost-savings mainly resulted from hospital inpatient care, whereas higher costs occurred for outpatient care. Overall cost savings of pneumococcal vaccination were not statistically significant in both years, but disease-related outpatient care costs were lower in pneumococci-vaccinated individuals in 2015 [- €9.43; 95% CI - €17.56;- €1.30] and 2016 [- €12.93; 95% CI - €25.37;- €0.48]. Although we used complex adjustment, residual bias cannot be completely ruled out. CONCLUSION: Influenza and pneumococcal vaccination in the elderly can be cost-saving in selective seasons and health care divisions. As cost effects vary, interpretation of findings is partly challenging.

Epidemiology and Costs of Postsepsis Morbidity, Nursing Care Dependency, and Mortality in Germany, 2013 to 2017.

Importance: Sepsis survivorship is associated with postsepsis morbidity, but epidemiological data from population-based cohorts are lacking. Objective: To quantify the frequency and co-occurrence of new diagnoses consistent with postsepsis morbidity and mortality as well as new nursing care dependency and total health care costs after sepsis. Design, Setting, and Participants: This retrospective cohort study based on nationwide health claims data included a population-based cohort of 23.0 million beneficiaries of a large German health insurance provider. Patients aged 15 years and older with incident hospital-treated sepsis in 2013 to 2014 were included. Data were analyzed from January 2009 to December 2017. Exposures: Sepsis, identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) hospital discharge codes. Main Outcomes and Measures: New medical, psychological, and cognitive diagnoses; long-term mortality; dependency on nursing care; and overall health care costs in survivors at 1 to 12, 13 to 24, and 25 to 36 months after hospital discharge. Results: Among 23.0 million eligible individuals, we identified 159 684 patients hospitalized with sepsis in 2013 to 2014. The mean (SD) age was 73.8 (12.8) years, and 75 809 (47.5%; 95% CI, 47.2%-47.7%) were female patients. In-hospital mortality was 27.0% (43 177 patients; 95% CI, 26.8%-27.3%). Among 116 507 hospital survivors, 86 578 (74.3%; 95% CI, 74.1%-74.6%) had a new diagnosis in the first year post sepsis; 28 405 (24.4%; 95% CI, 24.1%-24.6%) had diagnoses co-occurring in medical, psychological, or cognitive domains; and 23 572 of 74 878 survivors (31.5%; 95% CI, 31.1%-31.8%) without prior nursing care dependency were newly dependent on nursing care. In total, 35 765 survivors (30.7%; 95% CI, 30.4%-31.0%) died within the first year. In the second and third year, 53 089 (65.8%; 95% CI, 65.4%-66.1%) and 40 959 (59.4%; 95% CI, 59.0%-59.8%) had new diagnoses, respectively. Health care costs for sepsis hospital survivors for 3 years post sepsis totaled a mean of €29 088/patient ($32 868/patient) (SD, €44 195 [$49 938]). New postsepsis morbidity (>1 new diagnosis) was more common in survivors of severe sepsis (75.6% [95% CI, 75.1%-76.0%]) than nonsevere sepsis (73.7% [95% CI, 73.4%-74.0%]; P < .001) and more common in survivors treated in the intensive care unit (78.3% [95% CI, 77.8%-78.7%]) than in those not treated in the intensive care unit (72.8% [95% CI, 72.5%-73.1%]; P < .001). Postsepsis morbidity was 68.5% (95% CI, 67.5%-69.5%) among survivors without prior morbidity and 56.1% (95% CI, 54.2%-57.9%) in survivors younger than 40 years. Conclusions and Relevance: In this study, new medical, psychological, and cognitive diagnoses consistent with postsepsis morbidity were common after sepsis, including among patients with less severe sepsis, no prior diagnoses, and younger age. This calls for more efforts to elucidate the underlying mechanisms, define optimal screening for common new diagnoses, and test interventions to prevent and treat postsepsis morbidity.

Preventive effects of influenza and pneumococcal vaccination in the elderly - results from a population-based retrospective cohort study.

Influenza and pneumococcal vaccinations are recommended in the elderly to reduce life-threatening complications like sepsis. Protection may be reduced with increasing age. We aimed to assess the effectiveness of both vaccines in the elderly by performing a retrospective cohort study of 138,877 individuals aged ≥60 y in Germany, who were insured in a large statutory health insurance (AOK PLUS). We used longitudinal claims data to classify individuals according to vaccination status 2008-2014, and assessed vaccine effectiveness (VE) in 2015 and 2016. Inverse probability weighting based on generalized propensity scores was used to adjust for systematic between-group differences. Influenza vaccination was associated with a reduction of hospital treatment in laboratory-confirmed influenza in 2015 (VE = 41.32 [95%CI 0.85, 65.26]), but had no significant impact on the overall influenza incidence. Complications of influenza (pneumonia and sepsis) were reduced in 2016. We found a rise in influenza-like illness and acute respiratory infections in both years and an increased 90-d mortality after hospital-treated pneumonia in vaccinees in 2015. Pneumococcal vaccination was effective in preventing hospital-treated pneumonia within the first and second year after vaccination (VE = 52.45 [13.31, 73.92] and 46.04 [5.46, 69.21], respectively), but had no impact on sepsis incidence or pneumonia mortality. Influenza and pneumococcal vaccination can prevent severe complications from influenza and hospital-treated pneumonia in the elderly, respectively. Vaccine effects differ between years and seasons and are partly difficult to interpret. Despite extensive efforts to adjust for between-group differences, residual bias cannot be ruled out, possibly explaining signals like increased ILI or pneumonia mortality.

[Date of Service Provision and Date of Payment in Claims Data: Dealing with Time Differences]. / Leistungs- und Abrechnungsdatum in GKV-Routinedaten: Umgang mit zeitlichen Abweichungen.

AIM: The paper quantifies discrepancies between date of payment and date of service provision when doing analyses in relation to date of death and also in relation to the end of a calendar year. In analyses of this type, time differences between service provision and payment can lead to both under- and overestimation of service use. We aim to capture these phenomena in claims data from different sectors (primary care, medication prescription, prescription of remedies and medical aids, hospital care). METHOD: We have used pre-structured claims data from a scientific data warehouse of a large German statutory health insurance covering people that died in 2016. We investigated the discrepancies in time between date of service provision and date of payment for different outpatient and inpatient services based on data from 2015 to 2017. An exact date (dd/mm/yyyy) was only available for data covering prescriptions of remedies and medical aids. Data covering medication prescriptions were only exact to the month of payment (mm/yyyy), whereas data covering outpatient physician care were only exact to the quarter of payment (q/yyyy). RESULTS: For both outpatient physician care and hospital care, less than 1% had a payment date after the date of death. The share is considerably higher (28-31%) for prescriptions of remedies and medical aids. The majority of payments occurred within 3 months after death (93% for prescriptions of remedies and medical aids, 67% for primary care services). Less than 1% of outpatient physician care and about 18% of remedies had been paid after the end of the calender year 2015. Here too, the majority of payments were made within the first 3 months of 2016 (100% of prescriptions of remedies and medical aids, 65% of primary care services). CONCLUSIONS: Discrepancies in time between date of service provision and date of payment pose a challenge and are a potential source of under-/overestimation of health service utilization when doing analyses in relation to date of death or the end of a calendar year. This needs to be taken into account when requesting the data, but also in preparing and analysing them. The primary recommendation is to ensure that services with a payment date after death are included explicitly.