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

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.Peer Reviewe

Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences and Countermeasures.

Circadian (∼ 24 hour) timing systems pervade all kingdoms of life, and temporally optimize behaviour and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behaviour and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these too are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally-driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioural and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Date of Service Provision and Date of Payment in Claims Data: Dealing with Time Differences

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

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

Digital Interventions for Mental Disorders:Key Features, Efficacy, and Potential for Artificial Intelligence Applications

Mental disorders are highly prevalent and often remain untreated. Many limitations of conventional face-to-face psychological interventions could potentially be overcome through Internet-based and mobile-based interventions (IMIs). This chapter introduces core features of IMIs, describes areas of application, presents evidence on the efficacy of IMIs as well as potential effect mechanisms, and delineates how Artificial Intelligence combined with IMIs may improve current practices in the prevention and treatment of mental disorders in adults. Meta-analyses of randomized controlled trials clearly show that therapist-guided IMIs can be highly effective for a broad range of mental health problems. Whether the effects of unguided IMIs are also clinically relevant, particularly under routine care conditions, is less clear. First studies on IMIs for the prevention of mental disorders have shown promising results. Despite limitations and challenges, IMIs are increasingly implemented into routine care worldwide. IMIs are also well suited for applications of Artificial Intelligence and Machine Learning, which provides ample opportunities to improve the identification and treatment of mental disorders. Together with methodological innovations, these approaches may also deepen our understanding of how psychological interventions work, and why. Ethical and professional restraints as well as potential contraindications of IMIs, however, should also be considered. In sum, IMIs have a high potential for improving the prevention and treatment of mental health disorders across various indications, settings, and populations. Therefore, implementing IMIs into routine care as both adjunct and alternative to face-to-face treatment is highly desirable. Technological advancements may further enhance the variability and flexibility of IMIs, and thus even further increase their impact in people’s lives in the future

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field