Trajectories of post-traumatic stress in sepsis survivors two years after ICU discharge: a secondary analysis of a randomized controlled trial.

BACKGROUND: Post-traumatic stress has been identified as a frequent long-term complication in survivors of critical illnesses after sepsis. Little is known about long-term trajectories of post-traumatic stress and potentially modifiable risk factors following the ICU stay. Study objective was to explore and compare different clinical trajectories of post-traumatic stress symptoms in sepsis survivors up to two years after discharge from ICU. METHODS: Data on post-traumatic stress symptoms by means of the Post-traumatic Symptom Scale (PTSS-10) were collected in sepsis survivors at one, six, 12 and 24 months after discharge from ICU. Data on chronic psychiatric diagnoses prior ICU were derived from the primary care provider's health records, and data on intensive care treatment from ICU documentation. Trajectories of post-traumatic symptoms were identified ex post, discriminating patterns of change and k-means clustering. Assignment to the trajectories was predicted in multinomial log-linear models. RESULTS: At 24 months, all follow-up measurements of the PTSS-10 were completed in N = 175 patients. Three clusters could be identified regarding clinical trajectories of PTSS levels: stable low symptoms (N = 104 patients [59%]), increasing symptoms (N = 45 patients [26%]), and recovering from symptoms (N = 26 patients [15%]). Patients with initially high post-traumatic symptoms were more likely to show a decrease (OR with 95% CI: 1.1 [1.05, 1.16]). Females (OR = 2.45 [1.11, 5.41]) and patients reporting early traumatic memories of the ICU (OR = 4.04 [1.63, 10]) were at higher risk for increasing PTSS levels. CONCLUSION: Post-traumatic stress is a relevant long-term burden for sepsis patients after ICU stay. Identification of three different trajectories within two years after ICU discharge highlights the importance of long-term observation, as a quarter of patients reports few symptoms at discharge yet an increase in symptoms in the two years following. Regular screening of ICU survivors on post-traumatic stress should be considered even in patients with few symptoms and in particular in females and patients reporting traumatic memories of the ICU.

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).

First Direct Measurement Constraining the

The rate of the final step in the astrophysical αp process, the ^{34}Ar(α,p)^{37}K reaction, suffers from large uncertainties due to a lack of experimental data, despite having a considerable impact on the observable light curves of x-ray bursts and the composition of the ashes of hydrogen and helium burning on accreting neutron stars. We present the first direct measurement constraining the ^{34}Ar(α,p)^{37}K reaction cross section, using the Jet Experiments in Nuclear Structure and Astrophysics gas jet target. The combined cross section for the ^{34}Ar,Cl(α,p)^{37}K,Ar reaction is found to agree well with Hauser-Feshbach predictions. The ^{34}Ar(α,2p)^{36}Ar cross section, which can be exclusively attributed to the ^{34}Ar beam component, also agrees to within the typical uncertainties quoted for statistical models. This indicates the applicability of the statistical model for predicting astrophysical (α,p) reaction rates in this part of the αp process, in contrast to earlier findings from indirect reaction studies indicating orders-of-magnitude discrepancies. This removes a significant uncertainty in models of hydrogen and helium burning on accreting neutron stars.

Piloting an ICU follow-up clinic to improve health-related quality of life in ICU survivors after a prolonged intensive care stay (PINA): feasibility of a pragmatic randomised controlled trial.

BACKGROUND: ICU survivors often suffer from prolonged physical and mental impairments resulting in the so called "Post-Intensive Care Syndrome" (PICS). The aftercare of former ICU patients affected by PICS in particular has not been addressed sufficiently in Germany so far. The aim of this study was to evaluate the feasibility of a pragmatic randomised trial (RCT) comparing an intensive care unit (ICU) follow-up clinic intervention to usual care. METHODS: This pilot study in a German university hospital evaluated the feasibility of a pragmatic RCT. Patients were assigned in a 1:1 ratio to an ICU follow-up clinic intervention or to usual care. The concept of this follow-up clinic was previously developed in a participatory process with patients, next of kin, health care professionals and researchers. We performed a process evaluation and determined acceptability, fidelity, completeness of measurement instruments and practicality as feasibility outcomes. The RCT's primary outcome (health-related quality of life) was assessed six months after ICU discharge by means of the physical component scale of the Short-Form-12 self-report questionnaire. RESULTS: The pilot study was conducted from June 2020 to May 2021 with 21 and 20 participants in the intervention and control group. Principal findings related to feasibility were 85% consent rate (N = 48), 62% fidelity rate, 34% attrition rate (N = 41) and 77% completeness of outcome measurements. The primary effectiveness outcome (health-related quality of life) could be measured in 93% of participants who completed the study (N = 27). The majority of participants (85%) needed assistance with follow-up questionnaires (practicality). Median length of ICU stay was 13 days and 85% (N = 41) received mechanical ventilation, median Sequential Organ Failure Assessment Score was nine. Six-month follow-up assessment was planned for all study participants and performed for 66% (N = 41) of the participants after 197 days (median). CONCLUSION: The participatory developed intervention of an ICU follow-up clinic and the pragmatic pilot RCT both seem to be feasible. We recommend to start a pragmatic RCT on the effectiveness of the ICU follow-up clinic. TRIAL REGISTRATION: ClinicalTrials.gov US NLM, NCT04186468, Submission: 02/12/2019, Registration: 04/12/2019, https://clinicaltrials.gov/ct2/show/NCT04186468.

[Attitudes of general practitioners and medical practice assistants towards the delegation of medical services: Results of a survey in Berlin, Brandenburg and Thuringia]. / Einstellungen von Hausärzt:innen und Medizinischen Fachangestellten zur Delegation ärztlicher Leistungen ­ Ergebnisse einer Befragung in Berlin, Brandenburg und Thüringen.

INTRODUCTION: The delegation of tasks and responsibilities from general practitioners (GPs) to medical practice assistants (MPAs) can contribute to ensuring primary care in Germany. The aim of the study was to collect and analyze attitudes and procedures of GPs and MPAs regarding the delegation of physician-related tasks and activities. METHODOLOGY: A self-designed, piloted questionnaire was sent to all GPs listed within the regional Associations of Statutory Health Insurance Physicians (KV) in Thuringia, Berlin, and Brandenburg (n=5,516) and their MPAs. Participants were asked to indicate which physician-related activities were already delegated and on which occasions further delegations could be considered. RESULTS: 890 GPs (response rate: 16.1%) and 566 MPAs participated in the written survey. The participants were predominantly female and most of them worked in urban areas. Numerous activities, such as medical history taking, triage, Disease Management Program (DMP) controls, vaccinations and home visits, have already been delegated. The willingness to delegate further tasks (e. g., follow-up prescriptions and referrals, independent takeover of simple consultations, assessing the necessity of physician consultation) was high. CONCLUSION: The survey showed a high level of willingness of both occupational groups to delegate physician-related activities to MFAs. An expansion seems possible under certain conditions. Many activities have already been delegated to MPAs in primary care practices. Our survey provides suggestions regarding further tasks suitable for delegation, some of which go beyond the delegation agreement valid in Germany.

Triage Accuracy of Symptom Checker Apps: 5-Year Follow-up Evaluation.

BACKGROUND: Symptom checkers are digital tools assisting laypersons in self-assessing the urgency and potential causes of their medical complaints. They are widely used but face concerns from both patients and health care professionals, especially regarding their accuracy. A 2015 landmark study substantiated these concerns using case vignettes to demonstrate that symptom checkers commonly err in their triage assessment. OBJECTIVE: This study aims to revisit the landmark index study to investigate whether and how symptom checkers' capabilities have evolved since 2015 and how they currently compare with laypersons' stand-alone triage appraisal. METHODS: In early 2020, we searched for smartphone and web-based applications providing triage advice. We evaluated these apps on the same 45 case vignettes as the index study. Using descriptive statistics, we compared our findings with those of the index study and with publicly available data on laypersons' triage capability. RESULTS: We retrieved 22 symptom checkers providing triage advice. The median triage accuracy in 2020 (55.8%, IQR 15.1%) was close to that in 2015 (59.1%, IQR 15.5%). The apps in 2020 were less risk averse (odds 1.11:1, the ratio of overtriage errors to undertriage errors) than those in 2015 (odds 2.82:1), missing >40% of emergencies. Few apps outperformed laypersons in either deciding whether emergency care was required or whether self-care was sufficient. No apps outperformed the laypersons on both decisions. CONCLUSIONS: Triage performance of symptom checkers has, on average, not improved over the course of 5 years. It decreased in 2 use cases (advice on when emergency care is required and when no health care is needed for the moment). However, triage capability varies widely within the sample of symptom checkers. Whether it is beneficial to seek advice from symptom checkers depends on the app chosen and on the specific question to be answered. Future research should develop resources (eg, case vignette repositories) to audit the capabilities of symptom checkers continuously and independently and provide guidance on when and to whom they should be recommended.

Trajectories of depression in sepsis survivors: an observational cohort study.

BACKGROUND: Advances in critical care medicine have led to a growing number of critical illness survivors. A considerable part of them suffers from long-term sequelae, also known as post-intensive care syndrome. Among these, depressive symptoms are frequently observed. Depressive symptom trajectories and associated factors of critical illness survivors have rarely been investigated. Study objective was to explore and compare different trajectories of depressive symptoms in sepsis survivors over 1 year after discharge from ICU. METHODS: Data of a randomized controlled trial on long-term post-sepsis care were analyzed post hoc. Depressive symptoms were collected at 1, 6 and 12 months post-ICU discharge using the Major Depression Inventory (MDI), among others. Statistical analyses comprised descriptive analysis, univariate and multivariate, linear and logistic regression models and Growth Mixture Modeling. RESULTS: A total of 224 patients were included into this analysis. We identified three latent classes of depressive symptom trajectories: Over the course of 1 year, 152 patients recovered from mild symptoms, 27 patients showed severe persistent symptoms, and 45 patients recovered from severe symptoms. MDI sum scores significantly differed between the three classes of depressive symptom trajectories at 1 and 6 months after ICU discharge (p < 0.024 and p < 0.001, respectively). Compared with other classes, patients with the mild recovered trajectory showed lower levels of chronic pain (median sum score of 43.3 vs. 60.0/53.3 on the Graded Chronic Pain Scale, p < 0.010) and posttraumatic stress (4.6% with a sum score of ≥ 35 on the Posttraumatic Stress Scale 10 vs. 48.1%/33.3%, p < 0.003); and higher levels of health-related quality of life (HRQOL) using the Short Form-36 scale within 1 month after ICU discharge (p < 0.035). CONCLUSIONS: In the first year after discharge from ICU, sepsis survivors showed three different trajectories of depressive symptoms. Course and severity of depressive symptoms were associated with chronic pain, posttraumatic stress and reduced HRQOL at discharge from ICU. Regular screening of sepsis survivors on symptoms of depression, chronic pain and posttraumatic stress within 1 year after ICU may be considered. Trial registration ISRCTN, ISRCTN 61744782. Registered April 19, 2011-Retrospectively registered, http://www.isrctn.com/ISRCTN61744782 .

Implications for post critical illness trial design: sub-phenotyping trajectories of functional recovery among sepsis survivors.

BACKGROUND: Patients who survive critical illness suffer from a significant physical disability. The impact of rehabilitation strategies on health-related quality of life is inconsistent, with population heterogeneity cited as one potential confounder. This secondary analysis aimed to (1) examine trajectories of functional recovery in critically ill patients to delineate sub-phenotypes and (2) to assess differences between these cohorts in both clinical characteristics and clinimetric properties of physical function assessment tools. METHODS: Two hundred ninety-one adult sepsis survivors were followed-up for 24 months by telephone interviews. Physical function was assessed using the Physical Component Score (PCS) of the Short Form-36 Questionnaire (SF-36) and Activities of Daily Living and the Extra Short Musculoskeletal Function Assessment (XSFMA-F/B). Longitudinal trajectories were clustered by factor analysis. Logistical regression analyses were applied to patient characteristics potentially determining cluster allocation. Responsiveness, floor and ceiling effects and concurrent validity were assessed within clusters. RESULTS: One hundred fifty-nine patients completed 24 months of follow-up, presenting overall low PCS scores. Two distinct sub-cohorts were identified, exhibiting complete recovery or persistent impairment. A third sub-cohort could not be classified into either trajectory. Age, education level and number of co-morbidities were independent determinants of poor recovery (AUROC 0.743 ((95%CI 0.659-0.826), p < 0.001). Those with complete recovery trajectories demonstrated high levels of ceiling effects in physical function (PF) (15%), role physical (RP) (45%) and body pain (BP) (57%) domains of the SF-36. Those with persistent impairment demonstrated high levels of floor effects in the same domains: PF (21%), RP (71%) and BP (12%). The PF domain demonstrated high responsiveness between ICU discharge and at 6 months and was predictive of a persistent impairment trajectory (AUROC 0.859 (95%CI 0.804-0.914), p < 0.001). CONCLUSIONS: Within sepsis survivors, two distinct recovery trajectories of physical recovery were demonstrated. Older patients with more co-morbidities and lower educational achievements were more likely to have a persistent physical impairment trajectory. In regard to trajectory prediction, the PF score of the SF-36 was more responsive than the PCS and could be considered for primary outcomes. Future trials should consider adaptive trial designs that can deal with non-responders or sub-cohort specific outcome measures more effectively.

Psychological interventions for posttraumatic stress disorder involving primary care physicians: systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Evidence-based psychological interventions for posttraumatic stress disorder (PTSD) are available in specialized settings, but adequate care in primary care is often lacking. The aim of this systematic review was to determine the effectiveness of psychological interventions for PTSD involving primary care physicians (PCPs) and to characterize these interventions as well as their providers. METHOD: A systematic review and meta-analyses of randomized controlled trials (RCTs). Primary outcome were symptoms of PTSD. RESULTS: Four RCTs with a total of 774 patients suffering from PTSD symptoms were included, all applying cognitive behavioural based interventions. Three studies with psychological interventions being conducted by case managers were pooled in a meta-analysis. Interventions were not effective in the short term (0-6 months; SMD, - 0.1; 95% CI, - 0.24-0.04; I2 = 0%). Only two studies contributed to the meta-analysis for long term (12-18 months) outcomes yielding a small effect (SMD, - 0.23; 95% CI, - 0.38- -0.08; I2 = 0%). CONCLUSIONS: Psychological interventions for PTSD in primary care settings may be effective in the long term but number and quality of included studies was limited so the results should be interpreted with caution.

A novel but frequent variant in LPA KIV-2 is associated with a pronounced Lp(a) and cardiovascular risk reduction.

AIMS: Lp(a) concentrations represent a major cardiovascular risk factor and are almost entirely controlled by one single locus (LPA). However, many genetic factors in LPA governing the enormous variance of Lp(a) levels are still unknown. Since up to 70% of the LPA coding sequence are located in a difficult to access hypervariable copy number variation named KIV-2, we hypothesized that it may contain novel functional variants with pronounced effects on Lp(a) concentrations. We performed a large scale mutation analysis in the KIV-2 using an extreme phenotype approach. METHODS AND RESULTS: We compiled an discovery set of 123 samples showing discordance between LPA isoform phenotype and Lp(a) concentrations and controls. Using ultra-deep sequencing, we identified a splice site variant (G4925A) in preferential association with the smaller LPA isoforms. Follow-up in a European general population (n = 2892) revealed an exceptionally high carrier frequency of 22.1% in the general population. The variant explains 20.6% of the Lp(a) variance in carriers of low molecular weight (LMW) apo(a) isoforms (P = 5.75e-38) and reduces Lp(a) concentrations by 31.3 mg/dL. Accordingly the odds ratio for cardiovascular disease was reduced from 1.39 [95% confidence interval (CI): 1.17-1.66, P = 1.89e-04] for wildtype LMW individuals to 1.19 [95%CI: 0.92; 1.56, P = 0.19] in LMW individuals who were additionally positive for G4925A. Functional studies point towards a reduction of splicing efficiency by this novel variant. CONCLUSION: A highly frequent but until now undetected variant in the LPA KIV-2 region is strongly associated with reduced Lp(a) concentrations and reduced cardiovascular risk in LMW individuals.

Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease: Prospective 5 Years of Follow-Up and Apolipoprotein(a) Characterization.

OBJECTIVE: Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. APPROACH AND RESULTS: This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene (LPA) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter (P<0.0001); 95.3% of patients expressed at least 1 small apo(a) isoform. Small apo(a) isoform (35.2%) carrying phenotypes were not tagged by single-nucleotide polymorphisms rs10455872 or rs3798220. CONCLUSIONS: Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however.

Significant differentiation in the apolipoprotein(a)/lipoprotein(a) trait between chimpanzees from Western and Central Africa.

Elevated Lipoprotein(a) (Lp(a)) plasma concentrations are a risk factor for cardiovascular disease in humans, largely controlled by the LPA gene encoding apolipoprotein(a) (apo(a)). Lp(a) is composed of low-density lipoprotein (LDL) and apo(a) and restricted to Catarrhini. A variable number of kringle IV (KIV) domains in LPA lead to a size polymorphism of apo(a) that is inversely correlated with Lp(a) concentrations. Smaller apo(a) isoforms and higher Lp(a) levels in central chimpanzees (Pan troglodytes troglodytes [PTT]) compared to humans from Europe had been reported. We studied apo(a) isoforms and Lp(a) concentrations in 75 western (Pan troglodytes verus [PTV]) and 112 central chimpanzees, and 12 bonobos (Pan paniscus [PPA]), all wild born and living in sanctuaries in Sierra Leone, Republic of the Congo, and DR Congo, respectively, and 116 humans from Gabon. Lp(a) levels were severalfold higher in western than in central chimpanzees (181.0 ± 6.7 mg/dl vs. 56.5 ± 4.3 mg/dl), whereas bonobos showed intermediate levels (134.8 ± 33.4 mg/dl). Apo(a) isoform sizes differed significantly between subspecies (means 20.9 ± 2.2, 22.9 ± 4.4, and 23.8 ± 3.8 KIV repeats in PTV, PTT, and PPA, respectively). However, far higher isoform-associated Lp(a) concentrations for all isoform sizes in western chimpanzees offered the main explanation for the higher overall Lp(a) levels in this subspecies. Human Lp(a) concentrations (mean 47.9 ± 2.8 mg/dl) were similar to those in central chimpanzees despite larger isoforms (mean 27.1 ± 4.9 KIV). Lp(a) and LDL, apoB-100, and total cholesterol levels only correlated in PTV. This remarkable differentiation between chimpanzees from different African habitats and the trait's similarity in humans and chimpanzees from Central Africa poses the question of a possible impact of an environmental factor that has shaped the genetic architecture of LPA. Overall, studies on the cholesterol-containing particles of Lp(a) and LDL in chimpanzees should consider differentiation between subspecies.

Structure, function, and genetics of lipoprotein (a).

Lipoprotein (a) [Lp(a)] has attracted the interest of researchers and physicians due to its intriguing properties, including an intragenic multiallelic copy number variation in the LPA gene and the strong association with coronary heart disease (CHD). This review summarizes present knowledge of the structure, function, and genetics of Lp(a) with emphasis on the molecular and population genetics of the Lp(a)/LPA trait, as well as aspects of genetic epidemiology. It highlights the role of genetics in establishing Lp(a) as a risk factor for CHD, but also discusses uncertainties, controversies, and lack of knowledge on several aspects of the genetic Lp(a) trait, not least its function.

Effect of a Primary Care Management Intervention on Mental Health-Related Quality of Life Among Survivors of Sepsis: A Randomized Clinical Trial.

IMPORTANCE: Survivors of sepsis face long-term sequelae that diminish health-related quality of life and result in increased care needs in the primary care setting, such as medication, physiotherapy, or mental health care. OBJECTIVE: To examine if a primary care-based intervention improves mental health-related quality of life. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted between February 2011 and December 2014, enrolling 291 patients 18 years or older who survived sepsis (including septic shock), recruited from 9 intensive care units (ICUs) across Germany. INTERVENTIONS: Participants were randomized to usual care (n = 143) or to a 12-month intervention (n = 148). Usual care was provided by their primary care physician (PCP) and included periodic contacts, referrals to specialists, and prescription of medication, other treatment, or both. The intervention additionally included PCP and patient training, case management provided by trained nurses, and clinical decision support for PCPs by consulting physicians. MAIN OUTCOMES AND MEASURES: The primary outcome was change in mental health-related quality of life between ICU discharge and 6 months after ICU discharge using the Mental Component Summary (MCS) of the 36-Item Short-Form Health Survey (SF-36 [range, 0-100; higher ratings indicate lower impairment; minimal clinically important difference, 5 score points]). RESULTS: The mean age of the 291 patients was 61.6 years (SD, 14.4); 66.2% (n = 192) were men, and 84.4% (n = 244) required mechanical ventilation during their ICU stay (median duration of ventilation, 12 days [range, 0-134]). At 6 and 12 months after ICU discharge, 75.3% (n = 219 [112 intervention, 107 control]) and 69.4% (n = 202 [107 intervention, 95 control]), respectively, completed follow-up. Overall mortality was 13.7% at 6 months (40 deaths [21 intervention, 19 control]) and 18.2% at 12 months (53 deaths [27 intervention, 26 control]). Among patients in the intervention group, 104 (70.3%) received the intervention at high levels of integrity. There was no significant difference in change of mean MCS scores (intervention group mean at baseline, 49.1; at 6 months, 52.9; change, 3.79 score points [95% CI, 1.05 to 6.54] vs control group mean at baseline, 49.3; at 6 months, 51.0; change, 1.64 score points [95% CI, -1.22 to 4.51]; mean treatment effect, 2.15 [95% CI, -1.79 to 6.09]; P = .28). CONCLUSIONS AND RELEVANCE: Among survivors of sepsis and septic shock, the use of a primary care-focused team-based intervention, compared with usual care, did not improve mental health-related quality of life 6 months after ICU discharge. Further research is needed to determine if modified approaches to primary care management may be more effective. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN61744782.

Rehabilitation interventions for postintensive care syndrome: a systematic review.

OBJECTIVE: An increasing number of ICU patients survive and develop mental, cognitive, or physical impairments. Various interventions support recovery from this postintensive care syndrome. Physicians in charge of post-ICU patients need to know which interventions are effective. DATA SOURCES: Systematic literature search in databases (MEDLINE, EMBASE, Cochrane CENTRAL, PsycInfo, CINAHL; 1991-2012), reference lists, and hand search. STUDY SELECTION: We included comparative studies of rehabilitation interventions in adult post-ICU patients if they considered health-related quality of life, frequency/severity of postintensive care syndrome symptoms, functional recovery, need for care, autonomy in activities of daily living, mortality, or hospital readmissions. DATA EXTRACTION: Two reviewers extracted data and assessed risk of bias independently. DATA SYNTHESIS: From 4,761 publications, 18 studies with 2,510 patients were included. Studies addressed 20 outcomes, using 45 measures, covering inpatient (n = 4 trials), outpatient (n = 9), and mixed (n = 5) healthcare settings. Eight controlled trials with moderate to high quality were considered for evaluation of effectiveness. They investigated inpatient geriatric rehabilitation, ICU follow-up clinic, outpatient rehabilitation, disease management, and ICU diaries. Five of these trials assessed posttraumatic stress disorder, with four trials showing positive effects: first, ICU diaries reduced new-onset posttraumatic stress disorder (5% vs 13%, p = 0.02) after 3 months and second showed a lower mean Impact of Event Scale-Revised score (21.0 vs 32.1, p = 0.03) after 12 months. Third, aftercare by ICU follow-up clinic reduced Impact of Event Scale for women (20 vs 31; p < 0.01). Fourth, a self-help manual led to fewer patients scoring high in the Impact of Event Scale after 8 weeks (p = 0.026) but not after 6 months. For none of the other outcomes did more than one study report positive impacts. CONCLUSION: Interventions which have substantial effects in post-ICU patients are rare. Positive effects were seen for ICU-diary interventions for posttraumatic stress disorder. More interventions for the growing number of ICU survivors are needed.

Professional development of medical students - piloting a longitudinal curriculum at Jena University Hospital (LongProf).

Background: Professionalism is an important prerequisite for the quality of medical care with specific competencies anchored in the National Competence-Based Learning Objectives Catalogue Medicine 2.0. To date, there are hardly any explicit teaching formats at German universities to achieve these. A longitudinal curriculum for the development of medical professionalism (LongProf) has now been developed, implemented and evaluated at Jena University Hospital. Methods: The target group of the four-semester-curriculum were medical students from the fifth semester onwards. After a nine-month conception phase, a total of nine courses (6 teaching units each) took place from the winter semester 2021/22. Students also had the opportunity to interact with experienced doctors in mentoring sessions. The courses were evaluated by the participating students (n=23) in terms of acceptance and individually perceived professional development through quantitative surveys and qualitative focus group interviews. Results: The qualitative and quantitative evaluation revealed mostly positive feedback (mean >7/9). Students stated that the courses had provided them with lasting support in developing their own medical professionalism and in coping with the demands of their studies. The personal and long-term relationship building between students and teachers was considered particularly helpful. Discussion and conclusion: A multi-semester curriculum opens up ways for implementing the development of medical professionalism in medical studies. A trusting relationship between students and teachers, made possible by the longitudinal structure, is seen as conducive to the development of an individual medical identity. The curriculum is a useful complement to regular medical studies.

Patient perspective on task shifting from general practitioners to medical practice assistants - a quantitative survey in Germany.

INTRODUCTION: Various developments result in increasing workloads in general practices. New models of care and a restructuring of the division of tasks could provide relief. One approach is to extend the delegation of medical tasks from general practitioners (GPs) to medical practice assistants (MPAs). So far, there has been a lack of information about specific situations in which patients are willing to be treated exclusively by MPAs. METHODS: In three German federal states, patients who visited a general practice were surveyed exploratively and cross-sectionally with a self-designed, paper-based questionnaire. The data were analysed descriptively and multivariate. A mixed binary logistic regression model was calculated to account for cluster effects at practice level (random intercept model). The dependent variable was patients' acceptance of task delegation. RESULTS: A total of 1861 questionnaires from 61 general practices were included in the analysis. Regarding the current problem/request, a total of 30% of respondents could imagine being treated only by MPAs. Regarding theoretical reasons for consultation, more than half of the patients agreed to be treated by MPAs. According to the regression model, MPAs were preferred when patients were younger (10-year OR = 0.84, 95%-CI [0.75, 0.93]) or had a less complicated issue (OR = 0.44, 95%-CI [0.26, 0.8]). For four current problems/requests ("acute complaints" OR = 0.27, 95%-CI [0.17, 0.45], "routine health check" OR = 0.48, 95%-CI [0.3, 0.79], "new problem" OR = 0.13, 95%-CI [0.06, 0.28], "known problem" OR = 0.16, 95%-CI [0.1, 0.27]) patients prefer to be treated by GPs instead of MPAs. DISCUSSION: For the first time, statements could be made on patients' acceptance of task delegation in relation to current and theoretical reasons for treatment in general practices in Germany. The discrepancy in response behaviour on a theoretical and individual level could be explained by different contexts of questions and differences at practice level. Overall, patients seem to be open to increased delegation of medical tasks, depending on the reason for treatment. Selection and response biases should be considered in the interpretation. CONCLUSION: The results are not completely opposed to an extension of task delegation. Further interventional studies could provide information on the possible effects of expansion of delegable tasks.

Barriers and opportunities for implementation of a brief psychological intervention for post-ICU mental distress in the primary care setting - results from a qualitative sub-study of the PICTURE trial.

BACKGROUND: The results of critical illness and life-saving invasive measures during intensive care unit treatment can sometimes lead to lasting physical and psychological impairments. A multicentre randomized controlled trial from Germany (PICTURE) aims to test a brief psychological intervention, based on narrative exposure therapy, for post-traumatic stress disorder symptoms following intensive care unit treatment in the primary care setting. A qualitative analysis was conducted to understand feasibility and acceptance of the intervention beyond quantitative analysis of the main outcomes in the primary study. METHODS: Qualitative explorative sub-study of the main PICTURE trial, with eight patients from the intervention group recruited for semi-structured telephone interviews. Transcriptions were analysed according to Mayring's qualitative content analysis. Contents were coded and classified into emerging categories. RESULTS: The study population was 50% female and male, with a mean age of 60.9 years and transplantation surgery being the most frequent admission diagnosis. Four main factors were identified as conducive towards implementation of a short psychological intervention in a primary care setting: 1) long-term trustful relationship between patient and GP team; 2) intervention applied by a medical doctor; 3) professional emotional distance of the GP team; 4) brevity of the intervention. CONCLUSION: The primary setting has certain qualities such as a long-term doctor-patient relationship and low-threshold consultations that offer good opportunities for implementation of a brief psychological intervention for post-intensive care unit impairments. Structured follow-up guidelines for primary care following intensive care unit treatment are needed. Brief general practice-based interventions could be part of a stepped-care approach. TRIAL REGISTRATION: The main trial was registered at the DRKS (German Register of Clinical Trials: DRKS00012589) on 17/10/2017.

Examining the impact of a symptom assessment application on patient-physician interaction among self-referred walk-in patients in the emergency department (AKUSYM): study protocol for a multi-center, randomized controlled, parallel-group superiority trial.

BACKGROUND: Due to the increasing use of online health information, symptom checkers have been developed to provide an individualized assessment of health complaints and provide potential diagnoses and an urgency estimation. It is assumed that they support patient empowerment and have a positive impact on patient-physician interaction and satisfaction with care. Particularly in the emergency department (ED), symptom checkers could be integrated to bridge waiting times in the ED, and patients as well as physicians could take advantage of potential positive effects. Our study therefore aims to assess the impact of symptom assessment application (SAA) usage compared to no SAA usage on the patient-physician interaction in self-referred walk-in patients in the ED population. METHODS: In this multi-center, 1:1 randomized, controlled, parallel-group superiority trial, 440 self-referred adult walk-in patients with a non-urgent triage category will be recruited in three EDs in Berlin. Eligible participants in the intervention group will use a SAA directly after initial triage. The control group receives standard care without using a SAA. The primary endpoint is patients' satisfaction with the patient-physician interaction assessed by the Patient Satisfaction Questionnaire. DISCUSSION: The results of this trial could influence the implementation of SAA into acute care to improve the satisfaction with the patient-physician interaction. TRIAL REGISTRATION: German Clinical Trials Registry DRKS00028598 . Registered on 25.03.2022.

Healthcare Utilization and Costs in Sepsis Survivors in Germany-Secondary Analysis of a Prospective Cohort Study.

Background: Survivors of sepsis often face long-term sequelae after intensive care treatment. Compared to the period of hospitalization, little is known about the ambulatory healthcare utilization in sepsis patients. The study evaluated healthcare utilization and associated costs of sepsis care including allied health professions after initial hospitalization. Methods: Secondary analysis was performed on data in 210 sepsis patients prospectively enrolled from nine intensive care study centers across Germany. Data was collected via structured surveys among their Primary care (Family-) physicians (PCPs) within the first month after discharge from ICU (baseline) and again at 6, 12 and 24 months after discharge, each relating to the period following the last survey. Costs were assessed by standardized cost unit rates from a health care system's perspective. Changes in healthcare utilization and costs over time were calculated using the Wilcoxon rank-sum test. Results: Of the 210 patients enrolled, 146 (69.5%) patients completed the 24 months follow-up. In total, 109 patients were hospitalized within the first 6 months post-intensive care. Mean total direct costs per patient at 0-6 months were €17,531 (median: €6047), at 7-12 months €9029 (median: €3312), and at 13-24 months €18,703 (median: €12,828). The largest contributor to the total direct costs within the first 6 months was re-hospitalizations (€13,787 (median: €2965). After this first half year, we observed a significant decline in inpatient care costs for re-hospitalizations (p ≤ 0.001). PCPs were visited by more than 95% of patients over 24 months. Conclusions: Sepsis survivors have high health care utilization. Hospital readmissions are frequent and costly. Highest costs and hospitalizations were observed in more than half of patients within the first six months post-intensive care. Among all outpatient care providers, PCPs were consulted most frequently. Clinical impact: Sepsis survivors have a high healthcare utilization and related costs which persist after discharge from hospital. Within outpatient care, possible needs of sepsis survivors as physiotherapy or psychotherapy seem not to be met appropriately. Development of sepsis aftercare programs for early detection and treatment of complications should be prioritized.