Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been ...established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear.
The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up.
The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio HR 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors.
Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.
Aims Three randomized trials of implantable cardioverter defibrillator (ICD) therapy vs medical treatment for the prevention of death in survivors of ventricular fibrillation or sustained ventricular ...tachycardia have been reported with what might appear to be different results. The present analysis was performed to obtain the most precise estimate of the efficacy of the ICD, compared to amiodarone, for prolonging survival in patients with malignant ventricular arrhythmia. Methods and Results Individual patient data from the Antiarrhythmics vs Implantable Defibrillator (AVID) study, the Cardiac Arrest Study Hamburg (CASH) and the Canadian Implantable Defibrillator Study (CIDS) were merged into a master database according to a pre-specified protocol. Proportional hazard modelling of individual patient data was used to estimate hazard ratios and to investigate subgroup interactions. Fixed effect meta-analysis techniques were also used to evaluate treatment effects and to assess heterogeneity across studies. The classic fixed effects meta-analysis showed that the estimates of ICD benefit from the three studies were consistent with each other (P heterogeneity=0·306). It also showed a significant reduction in death from any cause with the ICD; with a summary hazard ratio (ICD:amiodarone) of 0·72 (95% confidence interval 0·60, 0·87;P=0·0006). For the outcome of arrhythmic death, the hazard ratio was 0·50 (95% confidence interval 0·37, 0·67;P<0·0001). Survival was extended by a mean of 4·4 months by the ICD over a follow-up period of 6 years. Patients with left ventricular ejection fraction ≤35% derived significantly more benefit from ICD therapy than those with better preserved left ventricular function. Patients treated before the availability of non-thoracotomy ICD implants derived significantly less benefit from ICD therapy than those treated in the non-thoracotomy era. Conclusion Results from the three trials of the ICD vs amiodarone are consistent with each other. There is a 28% reduction in the relative risk of death with the ICD that is due almost entirely to a 50% reduction in arrhythmic death.
Background
Irritable bowel syndrome (IBS) is a common and often debilitating chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Pharmacological treatments are ...often ineffective, leading to the development of a variety of behavioral interventions. Mindfulness‐based stress reduction (MBSR) is one such program that has shown efficacy in reducing gastrointestinal (GI) symptoms and improving quality of life (QOL). This single‐arm intervention study examines the association of clinical outcomes with changes in specific aspects of mindfulness.
Methods
Adults with IBS (53 women, 15 men) participated in an 8‐week MBSR class. Primary outcomes of GI symptom severity, quality of life, and GI‐specific anxiety, as well as specific aspects of mindfulness using the Five Factor Mindfulness Questionnaire (FFMQ), were assessed at baseline, post‐treatment, and 6‐month follow‐up.
Key Results
Gastrointestinal symptom responder rate was 71%, and there was a significant pre‐post treatment change for three of the five FFMQ scales. Regression analysis indicated that change in the Act with Awareness (P = .02) facet of mindfulness was the strongest predictor of GI symptom and QOL improvement.
Conclusions & Inferences
Mindfulness‐based stress reduction training was associated with robust improvements in GI symptoms and associated problems in participants with IBS. Although significant increases in 3 of the 5 measured facets of mindfulness were found, regression analyses suggest that increases in the ability to retain present moment focus and act with awareness may be particularly important for improving outcomes in individuals with IBS. These results may inform the refinement of mindfulness‐based protocols specifically for treatment of IBS.
MBSR led to a GI symptom responder rate of 71% and a significant pre‐post treatment change for three of five facets of mindfulness (FFMQ scales). Regression analysis indicated that change in the Act with Awareness (p = .02) facet of mindfulness was the strongest predictor of GI symptom and QOL improvement. Increases in the ability to retain present‐moment focus and act with awareness may be particularly important for improving outcomes in individuals with IBS
Abstract
Background
Telemedicine is a strategy for overcoming barriers to access evidence-based psychotherapy. Digital modalities that operate outside session-based treatment formats, such as ongoing ...two-way messaging, may further address these challenges. However, no study to date has established suitability criteria for this medium.
Methods
A large outpatient sample (
n
= 10,718) engaged in daily messaging with licensed clinicians from a telemedicine provider. Patients consisted of individuals from urban and rural settings in all 50 states of the US, who signed up to the telemedicine provider. Using a longitudinal design, symptoms changes were observed during a 12 week treatment course. Symptoms were assessed from baseline every three weeks using the Patient Health Questionnaire (PHQ-9) for depression, and the Generalized Anxiety Disorder (GAD-7) for anxiety. Demographics and engagement metrics, such as word count for both patients and therapists, were also assessed. Growth mixture modeling was used to tease apart symptoms trajectories, and identify predictors of treatment response.
Results
Two subpopulations had GAD-7 and PHQ-9 remission outcomes (
Recovery
and
Acute Recovery
, 30.7% of patients), while two others showed amelioration of symptoms (
Depression
and
Anxiety Improvement
, 36.9% of patients). Two subpopulations experienced no changes in symptoms (
Chronic and Elevated Chronic
, 32.4% of patients). Higher use of written communication, patient characteristics, and engagement metrics reliably distinguished patients with the greatest level of remission (
Recovery
and
Acute Recovery
groups).
Conclusions
Remission of depression and anxiety symptoms was observed during delivery of psychotherapy through messaging. Improvement rates were consistent with face-to-face therapy, suggesting the suitability of two-way messaging psychotherapy delivery. Characteristics of improving patients were identified and could be used for treatment recommendation. These findings suggest the opportunity for further research, to directly compare messaging delivery with a control group of treatment as usual.
Trial registration
Clinicaltrials.gov
Identifier:
NCT03699488
, Retrospectively Registered October 8, 2018.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are ...missing.
Objectives
The goal of these evidence‐ and consensus‐based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus‐based recommendations for the histopathological definition, diagnosis and the assessment of patients.
Methods
The guidelines development followed a pre‐defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies.
Results
Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately.
Conclusions
International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).
We present long-term (months–years) X-ray spectral variability of the Seyfert 1.8 galaxy NGC 1365 as observed by Swift, which provides well-sampled observations over a much longer time-scale (six ...years) and a much larger flux range than is afforded by other observatories. At very low luminosities, the spectrum is very soft, becoming rapidly harder as the luminosity increases and then, above a particular luminosity, softening again. At a given flux level, the scatter in hardness ratio is not very large, meaning that the spectral shape is largely determined by the luminosity. The spectra were therefore summed in luminosity bins and fitted with a variety of models. The best-fitting model consists of two power laws, one unabsorbed and another, more luminous, which is absorbed. In this model, we find a range of intrinsic 0.5–10.0 keV luminosities of approximately 1.1–3.5 erg s−1, and a very large range of absorbing columns, of approximately 1022–1024 cm−2. Interestingly, we find that the absorbing column decreases with increasing luminosity, but that this result is not due to changes in ionization. We suggest that these observations might be interpreted in terms of a wind model in which the launch radius varies as a function of ionizing flux and disc temperature and therefore moves out with increasing accretion rate, i.e. increasing X-ray luminosity. Thus, depending on the inclination angle of the disc relative to the observer, the absorbing column may decrease as the accretion rate goes up. The weaker, unabsorbed, component may be a scattered component from the wind.
Bleaching in corals due to environmental stress represents a loss of energy intake often leading to an increase in mortality risk. Successful coral recovery from severe bleaching events may depend on ...the rate of replenishment of algal symbiont populations following the period of thermal stress, the supply of an alternative food source, or both. Here, we explore the role of food availability in promoting the survival and recovery of a common coral (
Acropora intermedia
) following acute experimentally induced thermal stress. Fed corals were provided with live rotifers daily, to maintain densities of zooplankton in tanks that are typical of coral reefs. After a 6-week acclimation phase, heated corals were subjected to a +4 °C thermal anomaly for a 7-day period (bleaching phase) then temperatures were returned to normal for a further 2 weeks (recovery phase). Results demonstrated that heated corals had higher survival when they were provided with heterotrophic food. Fed corals experienced reduced loss of chlorophyll
a
, relative to unfed corals. During the recovery phase, both fed and unfed corals recovered within a few days; however, fed corals recovered to pre-bleaching phase levels of chlorophyll
a
, whereas unfed corals stabilized approximately one-third below this level. Protein levels of fed corals declined markedly during the bleaching phase, but recovered all of their losses by the end of the recovery phase. In contrast, unfed corals had low protein levels that were maintained throughout the experiment. To the extent that these results are representative of corals’ responses to thermal anomalies in nature, the findings imply that availability of particulate food matter has the potential to increase corals’ capacity to survive thermally induced bleaching and to ameliorate its sub-lethal effects. They also support the hypothesis that different rates of heterotrophy are an important determinant of variation in resilience to thermal stress among reef environments.
Background
Intracranial pressure waveform morphology reflects compliance, which can be decreased by ventriculitis. We investigated whether morphologic analysis of intracranial pressure dynamics ...predicts the onset of ventriculitis.
Methods
Ventriculitis was defined as culture or Gram stain positive cerebrospinal fluid, warranting treatment. We developed a pipeline to automatically isolate segments of intracranial pressure waveforms from extraventricular catheters, extract dominant pulses, and obtain morphologically similar groupings. We used a previously validated clinician-supervised active learning paradigm to identify metaclusters of triphasic, single-peak, or artifactual peaks. Metacluster distributions were concatenated with temperature and routine blood laboratory values to create feature vectors. A L2-regularized logistic regression classifier was trained to distinguish patients with ventriculitis from matched controls, and the discriminative performance using area under receiver operating characteristic curve with bootstrapping cross-validation was reported.
Results
Fifty-eight patients were included for analysis. Twenty-seven patients with ventriculitis from two centers were identified. Thirty-one patients with catheters but without ventriculitis were selected as matched controls based on age, sex, and primary diagnosis. There were 1590 h of segmented data, including 396,130 dominant pulses in patients with ventriculitis and 557,435 pulses in patients without ventriculitis. There were significant differences in metacluster distribution comparing before culture-positivity versus during culture-positivity (
p
< 0.001) and after culture-positivity (
p
< 0.001). The classifier demonstrated good discrimination with median area under receiver operating characteristic 0.70 (interquartile range 0.55–0.80). There were 1.5 true alerts (ventriculitis detected) for every false alert.
Conclusions
Intracranial pressure waveform morphology analysis can classify ventriculitis without cerebrospinal fluid sampling.
Abstract Background Anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent strokes. Vitamin K antagonists, such as warfarin, are associated with numerous practical ...limitations – frequent anticoagulation monitoring, lifestyle and dietary restrictions – that complicate patient management and may impact health-related quality of life (HRQoL). This study derived HRQoL estimates for AF patients receiving warfarin or dabigatran etexilate (dabigatran), a new oral anticoagulant not requiring anticoagulation monitoring, during one year of stable treatment, i.e. in the absence of outcome events, such as strokes or major bleedings. Methods Changes in HRQoL over time and between treatments were assessed using the EQ-5D (utility and Visual Analogue Scale (VAS) scores) at baseline, 3 and 12 months in a sub-group of 1435 patients participating in the RE-LY trial. RE-LY was a phase III study that compared the safety and efficacy of warfarin, dabigatran 150 mg bid and dabigatran 110 mg bid for stroke prevention in patients with AF. Results Utilities ranged from 0.805 (dabigatran 150 mg bid) to 0.811 (dabigatran 110 mg bid) at baseline, and did not change over the one year observation period. No differences between the dabigatran groups and warfarin were statistically significant except for the dabigatran 150 mg bid group at 3 months. Similarly, none of the within-group or between-group differences in VAS scores were statistically significant. Conclusions Over the course of one year, all anticoagulated patients without outcome events (e.g. strokes or major bleedings) had stable HRQoL. Scores between dabigatran and warfarin were comparable, which was unexpected given the known complexities of warfarin treatment.
Neutrophils are implicated in the pathogenesis of many diseases involving inflammation. Neutrophils are also critical to host defence and have a key role in the innate immune response to infection. ...Despite their efficiencies against a wide range of pathogens however, their ability to contain and combat
Mycobacterium tuberculosis
(Mtb) in the lung remains uncertain and contentious. The host response to Mtb infection is very complex, involving the secretion of various cytokines and chemokines from a wide variety of immune cells, including neutrophils, macrophages, monocytes, T cells, B cells, NK cells and dendritic cells. Considering the contributing role neutrophils play in the advancement of many diseases, understanding how an inflammatory microenvironment affects neutrophils, and how neutrophils interact with other immune cells, particularly in the context of the infected lung, may aid the design of immunomodulatory therapies. In the current review, we provide a brief overview of the mechanisms that underpin pathogen clearance by neutrophils and discuss their role in the context of Mtb and non-Mtb infection. Next, we examine the current evidence demonstrating how neutrophils interact with a range of human and non-human immune cells and how these interactions can differentially prime, activate and alter a repertoire of neutrophil effector functions. Furthermore, we discuss the metabolic pathways employed by neutrophils in modulating their response to activation, pathogen stimulation and infection. To conclude, we highlight knowledge gaps in the field and discuss plausible novel drug treatments that target host neutrophil metabolism and function which could hold therapeutic potential for people suffering from respiratory infections.