Association of frailty with short-term outcomes,organ support and resource use in critically ill patients

Purpose

Frail patients are known to experience poor outcomes. Nevertheless, we know less about how frailty manifests itself in patients’ physiology during critical illness and how it affects resource use in intensive care units (ICU). We aimed to assess the association of frailty with short-term outcomes and organ support used by critically ill patients.

Methods

Retrospective analysis of prospective collected data from 93 ICUs in Brazil from 2014 to 2015. We assessed frailty using the modified frailty index (MFI). The primary outcome was in-hospital mortality. Secondary outcomes were discharge home without need for nursing care, ICU and hospital length of stay (LOS), and utilization of ICU organ support and transfusion. We used mixed logistic regression and competing risk models accounting for relevant confounders in outcome analyses.

Results

The analysis consisted of 129,680 eligible patients. There were 40,779 (31.4%) non-frail (MFI?=?0), 64,407 (49.7%) pre-frail (MFI?=?1–2) and 24,494 (18.9%) frail (MFI?≥?3) patients. After adjusted analysis, frailty was associated with higher in-hospital mortality (OR 2.42, 95% CI 1.89–3.08), particularly in patients admitted with lower SOFA scores. Frail patients were less likely to be discharged home (OR 0.36, 95% CI 0.54–0.79) and had higher hospital and ICU LOS than non-frail patients. Use of all forms of organ support (mechanical ventilation, non-invasive ventilation, vasopressors, dialysis and transfusions) were more common in frail patients and increased as MFI increased.

Conclusions

Frailty, as assessed by MFI, was associated with several patient-centered endpoints including not only survival, but also ICU LOS and organ support.

     

Spontaneous rupture of the spleen in chronic calcifying pancreatitis: report of three cases

Spontaneous rupture of the spleen is a rare complication of chronic calcifying pancreatitis. Anemia and hemorrhagic shock may not occur, making diagnosis more difficult. Favourable response to conservative treatment does not prevent the need for splenectomy, as calcifiying chronic pancreatitis may progress locally. We report three cases of spontaneous rupture of the spleen. In two cases, splenic rupture revealed calcifying chronic pancreatitis and both patients underwent urgent splenectomy. In the third case, the patient was known to have calcifying chronic pancreatitis, and splenectomy was performed because of unsuccessful conservative treatment. We discuss the role of distal pancreatectomy during splenectomy to reduce the rate of postoperative complications and additional surgery. We also discuss the role of arterial embolisation and laparoscopy in the management of this rare condition.     

Medical marijuana laws and adolescent marijuana use in the United States: a systematic review and meta‐analysis

Aims

To conduct a systematic review and meta‐analysis of studies in order to estimate the effect of US medical marijuana laws (MMLs) on past‐month marijuana use prevalence among adolescents.

Methods

A total of 2999 papers from 17 literature sources were screened systematically. Eleven studies, developed from four ongoing large national surveys, were meta‐analyzed. Estimates of MML effects on any past‐month marijuana use prevalence from included studies were obtained from comparisons of pre–post MML changes in MML states to changes in non‐MML states over comparable time‐periods. These estimates were standardized and entered into a meta‐analysis model with fixed‐effects for each study. Heterogeneity among the study estimates by national data survey was tested with an omnibus F‐test. Estimates of effects on additional marijuana outcomes, of MML provisions (e.g. dispensaries) and among demographic subgroups were abstracted and summarized. Key methodological and modeling characteristics were also described. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed.

Results

None of the 11 studies found significant estimates of pre–post MML changes compared with contemporaneous changes in non‐MML states for marijuana use prevalence among adolescents. The meta‐analysis yielded a non‐significant pooled estimate (standardized mean difference) of ?0.003 (95% confidence interval = ?0.012, +0.007). Four studies compared MML with non‐MML states on pre‐MML differences and all found higher rates of past‐month marijuana use in MML states pre‐MML passage. Additional tests of specific MML provisions, of MML effects on additional marijuana outcomes and among subgroups generally yielded non‐significant results, although limited heterogeneity may warrant further study.

Conclusions

Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. Limited heterogeneity exists among estimates of effects of MMLs on other patterns of marijuana use, of effects within particular population subgroups and of effects of specific MML provisions.

     

Brain structure in asymptomatic FMR1 premutation carriers at risk for fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.     

Association of Type D personality with the autonomic and hemodynamic response to the cold pressor test

Mechanisms relating Type D personality to poor health are largely unknown, with autonomic nervous system function being a candidate. This study examined the physiologic response to cold stress. Undergraduates (N = 101, 84% female) underwent a cold pressor test. An electrocardiogram, impedance cardiogram, and blood pressure were recorded. Type D personality was assessed by self‐report questionnaire. Type D was associated with increased systolic and diastolic blood pressure reactivity. Exploratory analyses showed Type D men to respond with increased respiratory sinus arrhythmia (i.e., higher parasympathetic activity), and decreased pre‐ejection period (i.e., larger sympathetic activity), while Type D women showed a reciprocal response pattern. In conclusion, Type D personality was associated with an exaggerated hemodynamic response to cold stress, which may contribute to an increased risk of hypertension in Type D individuals.     

Positive affect dimensions and their association with inflammatory biomarkers in patients with chronic heart failure

Background

In cardiac patients positive affect has found to be associated with improved clinical outcomes, with reduced inflammation being one of the potential mechanisms responsible.

Methods

Positive affect was assessed using The Global Mood Scale (GMS), Positive and Negative Affect Schedule (PANAS), and Hospital Anxiety and Depression Scale (HADS) in patient with chronic heart failure (N = 210; 67 ± 9 years, 79% men). Markers of inflammation (TNFα, sTNFr1, sTNFr2, IL-6 and CRP) were measured and averaged at three consecutive time points.

Results

The positive affect dimensions of the GMS and PANAS were significantly associated with lower averaged levels of sTNFr2, TNFα and IL-6 (p < .1), even after adjustment for clinical and lifestyle confounders. Positive affect of the HADS was significantly associated with lower averaged levels of hsCRP (p < .1), but was no longer significant after correction for lifestyle confounders and depressive symptoms.

Conclusion

Positive affect is associated with reduced inflammation in patients with heart failure.     

PDC expressing CD36, CD61 and IL-10 may contribute to propagation of immune tolerance

Human plasmacytoid dendritic cells (PDC) are blood dendritic cell antigen 2 (BDCA2) and blood dendritic cell antigen 4 (BDCA4) positive leukocytes that do not express common lineage markers. They have been described as proinflammatory innate immune cells and are the major source of αIFN in the human body. PDC-derived secretion of type I IFNs upon triggering of nucleic acid-sensing toll-like receptors (TLR) primes immune cells to rapidly respond to microbial stimuli and promotes a Th1 response. Here, we report that human PDC express CD36 and CD61 (β3 integrin), both involved in uptake of apoptotic cells and in induction of tolerance. Freshly isolated PDC and PDC within human blood leukocytes constitutively express IL-10. Thus, PDC may possess a so far neglected role in propagation of immune tolerance.