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1.
J Psychiatry Neurosci ; 44(6): 1-8, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509363

RESUMO

Background: Multiple lines of evidence suggest that the onset and course of bipolar disorder is influenced by environmental light conditions. Increased suppression of melatonin by light (supersensitivity) in patients with bipolar disorder has been postulated as an endophenotype by several studies. However, due to methodological shortcomings, the results of these studies remain inconclusive. This study investigated melatonin suppression in euthymic patients with bipolar I disorder using evening blue light specifically targeting the melanopsin system. Methods: Melatonin suppression was assessed in euthymic patients with bipolar I disorder and healthy controls by exposure to monochromatic blue light (λmax = 475 nm; photon density = 1.6 × 1013 photons/cm2/s) for 30 minutes at 2300 h, administered via a ganzfeld dome for highly uniform light exposure. Serum melatonin concentrations were determined from serial blood sampling via radioimmunoassay. All participants received mydriatic eye drops and were genotyped for the PER3 VNTR polymorphism to avoid or adjust for potential confounding. As secondary outcomes, serum melatonin concentrations during dark conditions and after monochromatic red light exposure (λmax = 624 nm; photon density = 1.6 × 1013 photons/cm2/s) were also investigated. Changes in subjective alertness were investigated for all 3 lighting conditions. Results: A total of 90 participants (57 controls, 33 bipolar I disorder) completed the study. Melatonin suppression by monochromatic blue light did not differ between groups (F1,80 = 0.56; p = 0.46). Moreover, there were no differences in melatonin suppression by monochromatic red light (F1,82 = 1.80; p = 0.18) or differences in melatonin concentrations during dark conditions (F1,74 = 1.16; p = 0.29). Healthy controls displayed a stronger increase in subjective alertness during exposure to blue light than patients with bipolar I disorder (t85 = 2.28; p = 0.027). Limitations: Large interindividual differences in melatonin kinetics may have masked a true difference. Conclusion: Despite using a large cohort and highly controlled laboratory conditions, we found no differences in melatonin suppression between euthymic patients with bipolar I disorder and healthy controls. These findings do not support the notion that supersensitivity is a valid endophenotype in bipolar I disorder.

2.
Z Orthop Unfall ; 2019 Sep 09.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-31499573

RESUMO

In spring 2016, an updated sepsis definition (Sepsis-3) introduced a new explanation for the clinical picture of sepsis. Until then, sepsis had been understood as a "systemic inflammatory response syndrome (SIRS)" resulting from infection. An improved understanding of the molecular mechanisms and broad epidemiological studies of the clinical appearance shifted the focus from the inflammatory response to the multicausal tissue damage resulting in organ dysfunction. This paradigm shift highlights organ failure as a result of a dysregulated response of an organism to infection. Central to the new definition is the understanding that sepsis patients form a heterogeneous group and that the clinical picture requires alternative explanation patterns: e.g. sepsis is insufficiently explained by an overwhelming inflammatory response, it also comprises "immune paralysis" as another important pattern. Furthermore, severity of sepsis reflects the capacity of an organism to adapt and to mitigate the tissue damage through metabolic changes and repair mechanisms. Consistent with the paradigm of the new sepsis definition, adaptation in the presence of infections is crucial for the organism. Seriously injured or multiple trauma patients represent a patient group at particular risk, as sepsis often complicates the courses of these patients due to nosocomial infections. Along with comorbidities, past infections and age, leakage of skin and intestinal barriers as well as impaired defence and repair mechanism predispose trauma patients for a septic course. New pathophysiological insights suggest that the control of extracellular haem is of paramount significance. Haemolysis, transfusion and the consecutive expression of haem binding (such as haemopexin) or haem catabolic pathways (such as haem oxygenase) impair the ability of an organism to adapt, correlate with the prognosis and/or are strongly influenced by the surgical treatment concepts. Established treatment concepts of early causal and supportive therapy (damage control, antibiotic and fluid therapy) contribute to the reduction of mortality, depending on stringent implementation as part of Standard Operating Procedures (SOPs) and quality management. The paradigm shift in sepsis research offers an improved understanding of the underlying pathogenic factors within complex and heterogeneous patient groups, such as nosocomial sepsis following trauma. These novel approaches will allow developing new treatment strategies potentially contributing to a significant reduction in morbidity and mortality of trauma patients.Key messages1) According to the new paradigm, the ability to adapt to the pathogenic load associated with trauma and infection is crucial for an organism.2) Seriously injured or multiple trauma patients are predisposed for septic courses due to impaired adaptation mechanisms.3) Established treatment concepts of early causal and supportive therapy (damage control, antibiotic treatment, restrictive transfusion, and volume resuscitation) reduce mortality, in particular as part of SOPs and quality management strategies.4) Newly emerging treatment concepts that focus on the control of extracellular haem are promising, but require more evidence for translation into clinical practice.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31563506

RESUMO

BACKGROUND: Shoulder joint aspirations are frequently performed to rule out infection. In case of unsuccessful aspiration, physicians often augment the aspiration liquid by injecting saline solution. METHODS: We performed shoulder joint aspirations by fluoroscopic assistance and analyzed the value of an additional saline solution irrigation in patients undergoing revision shoulder surgery. Native joints and post-fracture repair, post-arthroscopy, and post-arthroplasty shoulders were included. A minimum of 3 deep intraoperative tissue samples served as the microbiological gold standard. RESULTS: We performed 106 aspirations occurring between 0 and 179 days before revision surgery. Among them, we could sample intra-articular liquid directly in 60 cases and after saline solution injection in 43 cases, whereas 3 cases remained unsuccessful. According to intraoperative samples, 24 shoulders were infected but only 10 of 24 (42%) yielded pathogens in the aspirate. Moreover, of the 43 saline solution-enforced irrigations, none revealed bacteria but 8 (17%) confirmed infection in intraoperative samples. Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of presurgical aspirations were 33%, 98%, 80%, and 83%, respectively. CONCLUSION: When surgical revision is planned, presurgical shoulder joint aspiration is not reliable to sufficiently exclude shoulder joint infection. Nevertheless, a positive aspiration finding can guide clinical decision making, so we propose to perform aspiration only if there is a clinically high index of suspicion for an infection. Irrigation after unsuccessful primary aspiration is futile.

4.
Intensive Care Med ; 45(10): 1433-1435, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31375864
5.
Pharmacopsychiatry ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434140

RESUMO

The treatment of depressive episodes remains complicated by the long latency of antidepressant efficacy, insufficient response, and high risk of suicide. Ketamine and esketamine have been proposed as fast-acting substances able to overcome these impediments.Since the first randomized controlled trial in the year 2000, numerous studies have explored the antidepressant efficacy of ketamine and esketamine. Clear evidence has emerged that a single infusion exerts a significant antidepressant and antisuicidal effect in both unipolar and bipolar depression. A few studies suggest that antidepressant response can be improved and maintained by repeated administration. Although intravenous application has been most common, subcutaneous, intramuscular, and intranasal application has also been successful. There is some evidence that ketamine may accelerate the response to electroconvulsive therapy without improving the overall response rate.The precise position of ketamine and esketamine within treatment algorithms have yet to be defined, and issues surrounding potential toxicity need to be resolved.

6.
Arch Biochem Biophys ; 672: 108075, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412260

RESUMO

Sepsis is a life-threatening clinical syndrome defined as a deregulated host response to infection associated with organ dysfunction. Mechanisms underlying the pathophysiology of septic liver dysfunction are incompletely understood. Among others, the iron containing tetrapyrrole heme inflicts hepatic damage when released into the circulation during systemic inflammation and sepsis. Accordingly, hemolysis and decreased concentrations of heme-scavenging proteins coincide with an unfavorable outcome of critically ill patients. As the liver is a key organ in heme metabolism and host response to infection, we investigated the impact of labile heme on sinusoidal microcirculation and hepatocellular integrity. We here provide experimental evidence that heme increases portal pressure via a mechanism that involves hepatic stellate cell-mediated sinusoidal constriction, a hallmark of microcirculatory failure under stress conditions. Moreover, heme exerts direct cytotoxicity in vitro and aggravates tissue damage in a model of polymicrobial sepsis. Heme binding by albumin, a low-affinity but high-capacity heme scavenger, attenuates heme-mediated vasoconstriction in vivo and prevents heme-mediated cytotoxicity in vitro. We demonstrate that fractions of serum albumin-bound labile heme are increased in septic patients. We propose that heme scavenging might be used therapeutically to maintain hepatic microcirculation and organ function in sepsis.

7.
Immunohorizons ; 3(2): 45-60, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-31356153

RESUMO

T lymphocytes (T cells) are highly specialized members of the adaptive immune system and hold the key to the understanding the hosts' response toward invading pathogen or pathogen-associated molecular patterns such as LPS. In this study, noninvasive Raman spectroscopy is presented as a label-free method to follow LPS-induced changes in splenic T cells during acute and postacute inflammatory phases (1, 4, 10, and 30 d) with a special focus on CD4+ and CD8+ T cells of endotoxemic C57BL/6 mice. Raman spectral analysis reveals highest chemical differences between CD4+ and CD8+ T cells originating from the control and LPS-treated mice during acute inflammation, and the differences are visible up to 10 d after the LPS insult. In the postacute phase, CD4+ and CD8+ T cells from treated and untreated mice could not be differentiated anymore, suggesting that T cells largely regained their original status. In sum, the biological information obtained from Raman spectra agrees with immunological readouts demonstrating that Raman spectroscopy is a well-suited, label-free method for following splenic T cell activation in systemic inflammation from acute to postacute phases. The method can also be applied to directly study tissue sections as is demonstrated for spleen tissue one day after LPS insult.

8.
J Affect Disord ; 257: 518-526, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31323593

RESUMO

INTRODUCTION: Suicide belongs to the leading causes of maternal perinatal mortality and suicidal ideation is one of the strongest predictors for suicide attempt and completion and thus represents an opportunity for early intervention prior to self and infant harm. This post-hoc analysis aims to investigate predictors of peripartum suicidality (PS) and potential maternal and infant outcomes of PS. METHODS: In the prospective-longitudinal Maternal Anxiety in Relation to Infant Development (MARI) study, n = 306 women were repeatedly examined from early pregnancy until 16 months postpartum using interviews (Composite International Diagnostic Interview for Women) and questionnaires (Edinburgh Postnatal Depression Scale, Brief Symptom Inventory) to obtain sociodemographic, gynecological and offspring characteristics as well as information about PS (thoughts of death/self-harm, suicide plans, suicide attempt). RESULTS: PS was indicated by n = 15 women. A stepwise multivariate logistic regression revealed a history of suicide attempt (OR = 17.84, 95%CI: 4.61-69.05), living together with the partner (OR = 0.14, 95%CI: 0.03-0.63), and social support (OR = 0.35, 95%CI: 0.13-0.91) as significant predictors for PS (model fit: AUC = 0.7926). As compared to women with no PS, infants of women with PS presented lower scores in neuropsychological development (p = 0.020). LIMITATIONS: This post-hoc analysis was conducted with the aim of generating hypotheses for future research. The small number of women who indicated PS limits the statistical power. CONCLUSION: PS is an important perinatal complication that requires clinical attention. Larger prospective studies are warranted to verify the findings. This will lead to improved preventive and therapeutic approaches and a better understanding of the motives behind maternal suicide and infanticide.

9.
Br J Gen Pract ; 69(686): e647-e656, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31308002

RESUMO

BACKGROUND: Multimorbidity is a complex issue in modern medicine and a more nuanced understanding of how this phenomenon occurs over time is needed. AIM: To determine the prevalence, characteristics, and patterns of patients living with multimorbidity, specifically the unique combinations (unordered patterns) and unique permutations (ordered patterns) of multimorbidity in primary care. DESIGN AND SETTING: A retrospective cohort analysis of the prospectively collected data from 1990 to 2013 from the Canadian Primary Care Sentinel Surveillance Network electronic medical record database. METHOD: Adult primary care patients who were aged ≥18 years at their first recorded encounter were followed over time. A list of 20 chronic condition categories was used to detect multimorbidity. Computational analyses were conducted using the Multimorbidity Cluster Analysis Tool to identify all combinations and permutations. RESULTS: Multimorbidity, defined as two or more and three or more chronic conditions, was prevalent among adult primary care patients and most of these patients were aged <65 years. Among female patients with two or more chronic conditions, 6075 combinations and 14 891 permutations were detected. Among male patients with three or more chronic conditions, 4296 combinations and 9716 permutations were detected. While specific patterns were identified, combinations and permutations became increasingly rare as the total number of chronic conditions and patient age increased. CONCLUSION: This research confirms that multimorbidity is common in primary care and provides empirical evidence that clinical management requires a tailored, patient-centred approach. While the prevalence of multimorbidity was found to increase with increasing patient age, the largest proportion of patients with multimorbidity in this study were aged <65 years.

10.
Transl Psychiatry ; 9(1): 162, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175283

RESUMO

Prospective monitoring of mood was started by Kraepelin who made and recorded frequent observations of his patients. During the last decade, the number of research studies using remotely collected electronic mood data has increased markedly. However, standardized measures and methods to collect, analyze and report electronic mood data are lacking. To get better understanding of the nature, correlates and implications of mood and mood instability, and to standardize this process, we propose guidelines for reporting of electronic mood data (eMOOD). This paper provides an overview of remotely collected electronic mood data in mood disorders and discusses why standardized reporting is necessary to evaluate and inform mood research in Psychiatry. Adherence to these guidelines will improve interpretation, reproducibility and future meta-analyses of mood monitoring in mood disorder research.

11.
Rev Sci Instrum ; 90(5): 053704, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31153234

RESUMO

We present an advanced experimental setup for time-resolved photoemission electron microscopy (PEEM) with sub-20 fs resolution, which allows for normal incidence and highly local sample excitation with ultrashort laser pulses. The scheme makes use of a sample rear side illumination geometry that enables us to confine the sample illumination spot to a diameter as small as 6 µm. We demonstrate an operation mode in which the spatiotemporal dynamics following a highly local excitation of the sample is globally probed with a laser pulse illuminating the sample from the front side. Furthermore, we show that the scheme can also be operated in a time-resolved normal incidence two-photon PEEM mode with interferometric resolution, a technique providing a direct and intuitive real-time view onto the propagation of surface plasmon polaritons.

12.
Haematologica ; 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221783

RESUMO

MYC is a widely acting transcription factor and its deregulation is a crucial event in many human cancers. MYC is important biologically and clinically in multiple myeloma, but the mechanisms underlying its dysregulation are poorly understood. We show that MYC rearrangements are present in 36.0% of newly diagnosed myeloma patients, as detected in the largest set of next generation sequencing data to date (n=1267). Rearrangements were complex and associated with increased expression of MYC and PVT1, but not other genes at 8q24. The highest effect on gene expression was detected in cases where the MYC locus is juxtaposed next to super-enhancers associated with genes such as IGH, IGK, IGL, TXNDC5/BMP6, FAM46C and FOXO3. We identified three hotspots of recombination at 8q24, one of which is enriched for IGH-MYC translocations. Breakpoint analysis indicates primary myeloma rearrangements involving the IGH locus occur through non-homologous end joining, whereas secondary MYC rearrangements occur through microhomology-mediated end joining. This mechanism is different to lymphomas, where non-homologous end joining generates MYC rearrangements. Rearrangements resulted in over-expression of key genes and ChIP-seq identified that HK2, a member of the glucose metabolism pathway, is directly over-expressed through binding of MYC at its promoter.

13.
Nat Genet ; 51(5): 793-803, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31043756

RESUMO

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.


Assuntos
Transtorno Bipolar/genética , Loci Gênicos , Transtorno Bipolar/classificação , Estudos de Casos e Controles , Transtorno Depressivo Maior/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/genética , Esquizofrenia/genética , Biologia de Sistemas
14.
Schizophr Res ; 209: 185-192, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31138482

RESUMO

BACKGROUND: Despite being recommended for use in clinical trials, the consensus remission criteria were found to leave patients with persisting symptoms, relevant areas of functional impairment and a decreased sense of wellbeing. Therefore, to evaluate the appropriateness of the schizophrenia consensus criteria, a definition of remission based on the Clinical Global Impression Scale (CGI) was developed and remitter subgroups were compared. METHODS: 239 patients with a schizophrenia spectrum disorder were evaluated regarding their remission status after inpatient treatment. Remission in schizophrenia was defined according to the symptom-severity component of the consensus criteria by Andreasen et al. and a CGI based definition was calculated using sensitivity and specificity using receiver operating curves (asymptomatic remitter). Both remitter groups (schizophrenia consensus versus asymptomatic remitters) were compared regarding different clinical variables at discharge as well as the likelihood to relapse within a 1-year follow-up period. Both schizophrenia remitter subgroups were compared to remitters in major depression as a reference value. RESULTS: Following the consensus criteria, 63% of the schizophrenia patients were in remission compared to only 18% following the asymptomatic criterion. The schizophrenia consensus remitters were less likely to be concurrent treatment responders (p < 0.0001), had a significantly greater illness severity (p < 0.0001) and less functioning (p = 0.0358) as well as a significantly greater risk to relapse (p = 0.0174) compared to the schizophrenia asymptomatic remitters as well as the depressed remitters. CONCLUSION: It should be critically re-evaluated if the currently proposed consensus criteria are adequate to measure what is traditionally understood to be remission.

15.
Int J Nurs Stud ; 96: 99-118, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31060734

RESUMO

BACKGROUND: Dementia is one of the most prevalent conditions in older adults in residential aged care. Dementia has a significant impact on a person's ability to eat, drink and participate in mealtime activities. Dementia impacts memory, appetite, gross and fine motor skills, communication skills, mood and social behaviours, all of which can decrease the person's ability to engage in a meal. OBJECTIVES: The objective was to review the literature on strategies to promote mealtime function in people with dementia living in residential aged care and assess their effectiveness. The review considered studies reporting outcome measures that related to nutritional status, communication, behaviour and eating skills and ability. DESIGN: Systematic review using the Joanna Briggs Institute review methods. DATA SOURCES: Seven databases (MEDLINE, CINAHL, Cochrane Database of Systematic Reviews, EMBASE, Current Contents, PsycINFO and Allied and Complementary Medicine Database) were searched for research published 2000-2017 in English. Eligible studies included quantitative studies reporting a mealtime intervention delivered to people with dementia in residential aged care compared with standard care reporting nutritional, behavioural or functional outcomes, including observation studies with no comparator. REVIEW METHODS: Studies were screened and independently appraised by two reviewers using Joanna Briggs Institute (JBI) critical appraisal tools based on study design. Data was extracted from eligible studies using JBI extraction tables that assess study design, population characteristics, intervention and comparator, outcome measures and findings. Results related to mealtime function were tabulated and reported in narrative format. RESULTS: 136 studies were identified, of which 20 were eligible for inclusion. Studies reported strategies related to: food presentation; meal styles; environment adaptations; skills training; music therapy and animal-assisted therapy. Outcomes included measures of nutritional status, communication and behavioural and psychological symptoms of dementia. Low quality evidence suggested that playing music and introducing fish to the dining room may improve the food intake of people with dementia by a small amount. Montessori and spaced retrieval programs also demonstrated some positive impact on eating skills and nutritional intake. Animal-assisted therapy also demonstrated small statistically significant improvements in weight and body mass index. CONCLUSION: There is insufficient evidence to highly recommend any specific intervention to improve mealtime functional ability in people with dementia. Further research is required through robust study designs using valid and reliable outcome measures to demonstrate clinically significant effects for mealtime interventions.

16.
J Am Heart Assoc ; 8(10): e012260, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31112430

RESUMO

Background Sepsis is the overwhelming host response to infection leading to shock and multiple organ dysfunction. Cardiovascular complications greatly increase sepsis-associated mortality. Although murine models are routinely used for preclinical studies, the benefit of using genetically engineered mice in sepsis is countered by discrepancies between human and mouse sepsis pathophysiology. Therefore, recent guidelines have called for standardization of preclinical methods to document organ dysfunction. We investigated the course of cardiac dysfunction and myocardial load in different mouse models of sepsis to identify the optimal measurements for early systolic and diastolic dysfunction. Methods and Results We performed speckle-tracking echocardiography and assessed blood pressure, plasma inflammatory cytokines, lactate, B-type natriuretic peptide, and survival in mouse models of endotoxemia or polymicrobial infection (cecal ligation and puncture, [ CLP ]) of moderate and high severity. We observed that myocardial strain and cardiac output were consistently impaired early in both sepsis models. Suppression of cardiac output was associated with systolic dysfunction in endotoxemia or combined systolic dysfunction and reduced preload in the CLP model. We found that cardiac output at 2 hours post- CLP is a negative prognostic indicator with high sensitivity and specificity that predicts mortality at 48 hours. Using a known antibiotic (ertapenem) treatment, we confirmed that this approach can document recovery. Conclusions We propose a non-invasive approach for assessment of cardiac function in sepsis and myocardial strain and strain rate as preferable measures for monitoring cardiovascular function in sepsis mouse models. We further show that the magnitude of cardiac output suppression 2 hours post- CLP can be used to predict mortality.

18.
Nervenarzt ; 2019 Apr 02.
Artigo em Alemão | MEDLINE | ID: mdl-30941458

RESUMO

Despite unlimited access to therapeutic drug monitoring lithium poisoning is still a common and potentially life-threatening but in most cases preventable complication of lithium treatment; however, it is still considered to be the gold standard in the treatment of affective disorders. The necessity of drug monitoring and potential lithium toxicity substantiate the skepticism of many therapists with respect to this often very effective treatment. This therefore limits the use of lithium although the unique therapeutic effects and high efficiency are well known. This retrospective data analysis of risk factors and etiology of lithium poisoning cases identified 58 cases of lithium poisoning, which were treated internally in this hospital between 2010 and 2014. Of the patients 67.2% were female and the majority were classified as chronic poisoning (66.1%). The most relevant patient-related risk factor seemed to be insufficient self-management as 26% of cases of lithium poisoning occurred during febrile infections or exsiccosis. Regarding practitioner-related risk factors, an insufficient consideration of drug interactions, insufficient therapeutic drug monitoring after dose increase and a paucity of experience and knowledge concerning lithium treatment were most relevant. This study illustrates the most important risk factors for lithium poisoning and their frequencies and contributes to raise awareness for this highly relevant topic. These data can help to prevent further cases of lithium poisoning. Furthermore, the results enable a comparison between the actual treatment reality and currently available evidence for the treatment of lithium poisoning.

19.
Crit Care ; 23(1): 110, 2019 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947753

RESUMO

BACKGROUND: CAP (Community acquired pneumonia) is frequent, with a high mortality rate and a high burden on health care systems. Development of predictive biomarkers, new therapeutic concepts, and epidemiologic research require a valid, reproducible, and quantitative measure describing CAP severity. METHODS: Using time series data of 1532 patients enrolled in the PROGRESS study, we compared putative measures of CAP severity for their utility as an operationalization. Comparison was based on ability to correctly identify patients with an objectively severe state of disease (death or need for intensive care with at least one of the following: substantial respiratory support, treatment with catecholamines, or dialysis). We considered IDSA/ATS minor criteria, CRB-65, CURB-65, Halm criteria, qSOFA, PSI, SCAP, SIRS-Score, SMART-COP, and SOFA. RESULTS: SOFA significantly outperformed other scores in correctly identifying a severe state of disease at the day of enrollment (AUC = 0.948), mainly caused by higher discriminative power at higher score values. Runners-up were the sum of IDSA/ATS minor criteria (AUC = 0.916) and SCAP (AUC = 0.868). SOFA performed similarly well on subsequent study days (all AUC > 0.9) and across age groups. In univariate and multivariate analysis, age, sex, and pack-years significantly contributed to higher SOFA values whereas antibiosis before hospitalization predicted lower SOFA. CONCLUSIONS: SOFA score can serve as an excellent operationalization of CAP severity and is proposed as endpoint for biomarker and therapeutic studies. TRIAL REGISTRATION: clinicaltrials.gov NCT02782013 , May 25, 2016, retrospectively registered.

20.
Artigo em Inglês | MEDLINE | ID: mdl-30991657

RESUMO

Rural areas of New York State (NYS) have higher rates of alcohol-related motor vehicle (MV) crash injury than metropolitan areas. While alcohol-related injury has declined across the three geographic regions of NYS, disparities persist with rural areas having smaller declines. Our study aim was to examine factors associated with alcohol-related MV crashes in Upstate and Long Island using multi-sourced county-level data that included the Crash Outcome Data Evaluation System (CODES) with emergency department visits and hospitalizations, traffic citations, demographic, economic, transportation, alcohol outlets, and Rural-Urban Continuum Codes (RUCCS). A cross-sectional study design employed zero-truncated negative binominal regression models to assess relative risks (RR) with 95% confidence interval (CI). Counties (n = 57, 56,000 alcohol-related crashes over the 3 year study timeframe) were categorized by mean annual alcohol-related MV injuries per 100,000 population: low (24.7 ± 3.9), medium (33.9 ± 1.7) and high (46.1 ± 8.0) (p < 0.0001). In multivariable analyses, alcohol-related MV injury was elevated for non-adjacent, non-metropolitan counties (RR 2.5, 95% CI: 1.6-3.9) with higher citations for impaired driving showing a small, but significant protective effect. Less metropolitan areas had higher alcohol-related MV injury with inconsistent alcohol-related enforcement measures. In summary, higher alcohol-related MV injury rates in non-metropolitan counties demonstrated a dose-response relationship with proximity to a metropolitan area. These findings suggest areas where intervention efforts might be targeted to lower alcohol-related MV injury.

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