Addressing psychosocial needs in patients with Long-COVID (PsyLoCo-Study): study protocol of a pilot-study of a specialized modular intervention.

Introduction: After an acute infection with the corona virus 10-20% of those affected suffer from ongoing or new symptoms. A causal therapy for the phenomenon known as Long/Post-COVID is still lacking and specific therapies addressing psychosocial needs of these patients are imperatively needed. The aim of the PsyLoCo-study is developing and piloting a psychotherapeutic manual, which addresses Long/Post-COVID-related psychosocial needs and supports in coping with persistent bodily symptoms as well as depressive or anxiety symptoms. Methods and analysis: This pilot trial implements a multi-centre, 2-arm (N=120; allocation ratio: 1:1), parallel group, randomised controlled design. The pilot trial is designed to test the feasibility and estimate the effect of 1) a 12-session psychotherapeutic intervention compared to 2) a wait-list control condition on psychosocial needs as well as bodily and affective symptoms in patients suffering from Long/Post-COVID. The intervention uses an integrative, manualized, psychotherapeutic approach. The primary study outcome is health-related quality of life. Outcome variables will be assessed at three timepoints, pre-intervention (t1), post-intervention (t2) and three months after completed intervention (t3). To determine the primary outcome, changes from t1 to t2 are examined. The analysis will be used for the planning of the RCT to test the efficacy of the developed intervention. Discussion: The pilot study will evaluate a 12-session treatment manual for Long/Post-COVID sufferers and the therapy components it contains. The analysis will provide insights into the extent to which psychotherapeutic treatment approaches improve the symptoms of Long/Post-COVID sufferers. The treatment manual is designed to be carried out by psychotherapists as well as people with basic training in psychotherapeutic techniques. This approach was chosen to enable a larger number of practitioners to provide therapeutic support for Long/Post-COVID patients. After completion of the pilot study, it is planned to follow up with a randomized controlled study and to develop a treatment guideline for general practitioners and interested specialists. Trial registration: The pilot trial has been registered with the German Clinical Trials Register (Deutsches Register Klinischer Studien; Trial-ID: DRKS00030866; URL: https://drks.de/search/de/trial/DRKS00030866) on March 7, 2023.

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.

Return to work after sepsis-a German population-based health claims study.

Background: Long-term impairments after sepsis can impede the return to work in survivors. We aimed to describe rates of return to work 6 and 12 months postsepsis. Methods: This retrospective, population-based cohort study was based on health claims data of the German AOK health insurance of 23.0 million beneficiaries. We included 12-months survivors after hospital-treated sepsis in 2013/2014, who were ≤60 years at the time of the admission and were working in the year presepsis. We assessed the prevalence of return to work (RTW), persistent inability to work and early retirement. Results: Among 7,370 working age sepsis survivors, 69.2% returned to work at 6 months postsepsis, while 22.8% were on sick leave and 8.0% retired early. At 12 months postsepsis, the RTW rate increased to 76.9%, whereas 9.8% were still on sick leave and 13.3% retired early. Survivors who returned to work had a mean of 70 (SD 93) sick leave days in the 12 months presepsis (median 28 days, IQR 108 days). Conclusion: One out of four working age sepsis survivors does not resume work in the year postsepsis. Specific rehabilitation and targeted aftercare may be opportunities to reduce barriers to RTW after sepsis.

Effect of a regular consumption of traditional and roasted oat and barley flakes on blood lipids and glucose metabolism-A randomized crossover trial.

Background: Regular consumption of the soluble dietary fiber ß-glucan is associated with decreased total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and blood glucose. Barley and oat flakes as natural sources of ß-glucan were roasted to improve sensory quality. The aim of this study was to investigate whether roasting of barley and oat flakes changes the physiological impact of the ß-glucan-rich flakes on glucose and lipid metabolism. Method: A five-armed randomized crossover trial design was used. The intervention study was conducted from May 2018 to May 2019 and included 32 healthy subjects with moderately increased LDL cholesterol (≥2.5 mmol/L). During the 3-week intervention periods, 80 g of roasted or traditional barley or oat flakes, or four slices of white toast bread per day were consumed for breakfast. At the start and the end of each intervention, fasting and postprandial blood was taken. The intervention periods were separated by 3-week wash-out periods. Results: During the interventions with the cereal flakes, TC and LDL cholesterol concentrations were significantly reduced compared to baseline values by mean differences of 0.27-0.33 mmol/L and 0.21-0.30 mmol/L, respectively (p < 0.05), while high-density lipoprotein (HDL) cholesterol was only reduced after the intervention with barley flakes (p < 0.05). After the intervention period with toast, TC and HDL cholesterol increased (p < 0.05). The fasting levels of triglycerides, fasting blood glucose and insulin did not change in any group. The effects of traditional and roasted varieties on blood lipids did not differ between the groups. Conclusion: The regular consumption of traditional or roasted barley and oat flakes contributes to the management of cardiovascular diseases by improving TC and LDL cholesterol. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03648112, identifier NCT03648112.

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.

Nonunions and Their Operative Treatment­a DRG-Based Epidemiological Analysis for the Years 2007-2019 in Germany

BACKGROUND: Nonunions, which arise as a complication of fractures, are an impor - tant medical and socio-economic problem. The goal of this study was to analyze nonunions in Germany with respect to the patients' age and sex, the anatomical site of the lesions, and their operative treatment. METHODS: The study was performed on the basis of DRG (diagnosis-related group) data acquired for billing purposes and collected by the German Federal Statistical Office. The administrative frequencies of nonunions and fractures treated in the inpatient setting, broken down by sex and age group, were calculated from the documentation of ICD codes. An investigation was also made of surgical treatments for nonunion, as they were categorized by the German procedure classification (Operationen- und Prozedurenschlüssel, OPS). RESULTS: The administrative frequency of nonunion was 14.84 per 100 000 persons per year, with a 2% decline in case numbers over the period 2007-2019. Nonunions develop in 2% of fractures. Nonunions affect men more often than women (58% vs. 42%). In men, their incidence as a function of age is highest under age 30; in women, it rises steadily with increasing age. The most common type of surgical treatment is a combination of resection, bone transplantation, and osteosynthesis. CONCLUSION: This is the first detailed nationwide study of diagnoses of nonunions in Germany and their surgical treatment. Despite a slow decline in their incidence, nonunions remain an important problem in the inpatient setting. The risk profile for nonunions is sex-, age-, and site-specific.

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.

Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID-19.

BACKGROUND: Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID-19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA). This approach is potentially associated with both advantages (e.g. a preserved diaphragmatic motility and an optimised ventilation-perfusion ratio of the ventilated lung), as well as risks (e.g. a higher rate of ventilator-induced lung injury or a worsening of pulmonary oedema due to increases in transpulmonary pressure). As a consequence, spontaneous breathing in people with COVID-19-ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists. OBJECTIVES: To assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID-19 with ARDS compared to ventilation strategies that avoid spontaneous breathing. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, Clinical Trials.gov WHO ICTRP, and medRxiv) and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies from their inception to 2 March 2022. SELECTION CRITERIA: Eligible study designs comprised randomised controlled trials (RCTs) that evaluated spontaneous breathing in participants with COVID-19-related ARDS compared to ventilation strategies that avoided spontaneous breathing (e.g. using NMBA or deep sedation levels). Additionally, we considered controlled before-after studies, interrupted time series with comparison group, prospective cohort studies and retrospective cohort studies. For these non-RCT studies, we considered a minimum total number of 50 participants to be compared as necessary for inclusion. Prioritised outcomes were all-cause mortality, clinical improvement or worsening, quality of life, rate of (serious) adverse events and rate of pneumothorax. Additional outcomes were need for tracheostomy, duration of ICU length of stay and duration of hospitalisation. DATA COLLECTION AND ANALYSIS: We followed the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently screened all studies at the title/abstract and full-text screening stage. We also planned to conduct data extraction and risk of bias assessment in duplicate. We planned to conduct meta-analysis for each prioritised outcome, as well as subgroup analyses of mortality regarding severity of oxygenation impairment and duration of ARDS. In addition, we planned to perform sensitivity analyses for studies at high risk of bias, studies using NMBA in addition to deep sedation level to avoid spontaneous breathing and a comparison of preprints versus peer-reviewed articles. We planned to assess the certainty of evidence using the GRADE approach. MAIN RESULTS: We identified no eligible studies for this review. AUTHORS' CONCLUSIONS: We found no direct evidence on whether early spontaneous breathing in SARS-CoV-2-induced ARDS is beneficial or detrimental to this particular group of patients.  RCTs comparing early spontaneous breathing with ventilatory strategies not allowing for spontaneous breathing in SARS-CoV-2-induced ARDS are necessary to determine its value within the treatment of severely ill people with COVID-19. Additionally, studies should aim to clarify whether treatment effects differ between people with SARS-CoV-2-induced ARDS and people with non-SARS-CoV-2-induced ARDS.

[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.

Development and validation of risk-adjusted quality indicators for the long-term outcome of acute sepsis care in German hospitals based on health claims data.

Background: Methods for assessing long-term outcome quality of acute care for sepsis are lacking. We investigated a method for measuring long-term outcome quality based on health claims data in Germany. Materials and methods: Analyses were based on data of the largest German health insurer, covering 32% of the population. Cases (aged 15 years and older) with ICD-10-codes for severe sepsis or septic shock according to sepsis-1-definitions hospitalized in 2014 were included. Short-term outcome was assessed by 90-day mortality; long-term outcome was assessed by a composite endpoint defined by 1-year mortality or increased dependency on chronic care. Risk factors were identified by logistic regressions with backward selection. Hierarchical generalized linear models were used to correct for clustering of cases in hospitals. Predictive validity of the models was assessed by internal validation using bootstrap-sampling. Risk-standardized mortality rates (RSMR) were calculated with and without reliability adjustment and their univariate and bivariate distributions were described. Results: Among 35,552 included patients, 53.2% died within 90 days after admission; 39.8% of 90-day survivors died within the first year or had an increased dependency on chronic care. Both risk-models showed a sufficient predictive validity regarding discrimination [AUC = 0.748 (95% CI: 0.742; 0.752) for 90-day mortality; AUC = 0.675 (95% CI: 0.665; 0.685) for the 1-year composite outcome, respectively], calibration (Brier Score of 0.203 and 0.220; calibration slope of 1.094 and 0.978), and explained variance (R 2 = 0.242 and R 2 = 0.111). Because of a small case-volume per hospital, applying reliability adjustment to the RSMR led to a great decrease in variability across hospitals [from median (1st quartile, 3rd quartile) 54.2% (44.3%, 65.5%) to 53.2% (50.7%, 55.9%) for 90-day mortality; from 39.2% (27.8%, 51.1%) to 39.9% (39.5%, 40.4%) for the 1-year composite endpoint]. There was no substantial correlation between the two endpoints at hospital level (observed rates: ρ = 0, p = 0.99; RSMR: ρ = 0.017, p = 0.56; reliability-adjusted RSMR: ρ = 0.067; p = 0.026). Conclusion: Quality assurance and epidemiological surveillance of sepsis care should include indicators of long-term mortality and morbidity. Claims-based risk-adjustment models for quality indicators of acute sepsis care showed satisfactory predictive validity. To increase reliability of measurement, data sources should cover the full population and hospitals need to improve ICD-10-coding of sepsis.

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.

Cognitive deficits including executive functioning in relation to clinical parameters in paediatric MS patients.

BACKGROUND: A number of studies have investigated cognitive impairment in paediatric patients with multiple sclerosis (MS) but deficits regarding executive functions have not been comprehensively assessed up to now. This study was meant to explore cognitive impairment in German paediatric MS patients with a focus on deficits in executive functions and relate these to clinical disease parameters. METHODS AND FINDINGS: Forty paediatric MS patients, which presented at the German centre for MS in childhood and adolescence, were assessed for cognitive deficits applying a very comprehensive battery of cognitive tests including the Wechsler Intelligence scale and subtests of the D-KEFS for executive functions. The performance of MS patients was compared with a group of age and sex matched healthy controls using between-subjects ANOVAs. Paediatric MS patients performed worse in tests assessing verbal comprehension and fluency, processing speed, memory, calculation skills and other executive functions. Arranged by the cognitive domain, group differences were most pronounced regarding verbal comprehension and fluency for the WISC subtests Comprehension (p = 0.000), Vocabulary (p = 0.003) and Information (p = 0.005); regarding processing speed for the written SDMT (p = 0.001) and the WISC subtest Coding (p = 0.005); regarding memory for the VLMT training (p = 0.007) and the BASIC MLT pattern learning training (p = 0.009); regarding executive functions including working memory for the WISC subtest Arithmetics (p = 0.002), the D-KEFS Design Fluency (p = 0.003) and the Corsi block tapping backward task (p = 0.003). Fluid reasoning was largely intact. Relations of cognitive performance and clinical parameters were assessed in MS patients. Disease duration was associated with a reduced performance in tests belonging to the domains verbal comprehension and fluency (WISC Vocabulary: p = 0.034, WISC Information: p = 0.015) and fluid reasoning (WISC Picture Completion: p = 0.003) as well as the WISC Working Memory Index (p = 0.047). Patients with a disease onset between 11 and 14 years performed better in fluid reasoning (WISC matrix reasoning: p = 0.024) than patients with a disease onset at an age above 14. The number of relapses negatively influenced the visual spatial memory performance (BASIC MLT pattern learning training: p = 0.009). CONCLUSIONS: The distribution of cognitive deficits in a representative group German of paediatric MS patients was similar to the pattern known from other European and North-American cohorts. Paediatric MS patients do have cognitive deficits in executive functions and key qualities necessary for successful school performance. Disease duration, age of onset and the number of relapses influence cognitive performance. Cognitive screenings should be implemented on a regular basis for paediatric MS patients, enabling early intervention.