Understanding which factors predict the outcome of internet-based cognitive behavioral therapy for insomnia (iCBT-I) may help to tailor this intervention to the patient's needs. We have conducted a ...secondary analysis of a randomized, controlled trial comparing a multicomponent iCBT-I (MCT) and an online sleep restriction therapy (SRT) for 83 chronic insomnia patients. The difference in the Insomnia Severity Index from pre- to post-treatment and from pre-treatment to follow-up at 6 months after treatment was the dependent variable. Prognostic and treatment-predictive factors assessed at baseline were analyzed with multiple linear regression. The shorter duration of insomnia, female gender, high health-related quality of life, and the higher total number of clicks had prognostic value for a better outcome. Other factors were found to be prognostic for outcome at the follow-up assessment: treatment with benzodiazepines, sleep quality, and personal significance of sleep problems. A high level of dysfunctional beliefs and attitudes about sleep (DBAS) was a moderator for better effects in the MCT at post-treatment assessment. Various prognostic factors (e.g., duration of insomnia, gender, or quality of life) may influence the success of treatment. The DBAS scale may be recommended to select patients for MCT rather than SRT.
Sleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the ...possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain.
eSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI < 5/h). Patients with significant SDB are randomized to treatment (ASV+ group) or no treatment (ASV- group) from the second night after stroke. In all patients, clinical, physiological and magnetic resonance imaging studies are performed between day 1 (visit 1) and days 4-7 (visit 4) and repeated at day 90 ± 7 (visit 6) after stroke.
The trial will give information on the feasibility and efficacy of ASV treatment in patients with acute stroke and SDB and allows assessing the impact of SDB on stroke outcome. Diagnosing and treating SDB during the acute phase of stroke is not yet current medical practice. Evidence in favour of ASV treatment from a randomized multicentre trial may lead to a change in stroke care and to improved outcomes.
ClinicalTrials.gov NCT02554487 , retrospectively registered on 16 September 2015 (actual study start date, 13 August 2015), and www.kofam.ch (SNCTP000001521).
Sleep-disordered breathing (SDB) is frequent in patients with acute stroke. Little is known, however about the evolution of SDB after stroke. Most of our knowledge stems from smaller cohort studies ...applying limited cardiopulmonary sleep recordings or from cross-sectional data collected in different populations.
This study aims to determine prevalence, type and intra-individual evolution of SDB based on full-night polysomnography (PSG) in acute stroke and 3 months thereafter. Furthermore, we aimed to identify predictors of SDB in the acute and chronic phase and to evaluate associations between SDB and functional outcome at 3 months (M3).
A total of 166 patients with acute cerebrovascular events were evaluated by full PSG at baseline and 105 again at M3. The baseline prevalence of SDB (apnoea–hypopnoea index (AHI)>5·h
−1
) was 80.5% and 25.4% of the patients had severe SDB (AHI>30·h
−1
). Obstructive sleep apnoea was more prevalent than central sleep apnoea (83.8%
versus
13%). Mean±SD AHI was 21.4±17.6·h
−1
and decreased significantly at M3 (18±16.4·h
−1
; p=0.018). At M3, 91% of all patients with baseline SDB still had an AHI>5·h
−1
and in 68.1% the predominant type of SDB remained unchanged (78.9% in obstructive sleep apnoea and 44.4% in central sleep apnoea). The only predictors of SDB at baseline were higher age and body mass index and in the chronic phase additionally baseline AHI. Baseline AHI was associated with functional outcome (modified Rankin score >3) at M3.
The high prevalence of SDB in acute stroke, its persistence after 3 months, and the association with functional outcome supports the recommendation for a rapid SDB screening in stroke patients.
Introduction
Cardiovascular parameters characterizing blood pressure (BP), heart rate (HR), endothelial function and arterial stiffness predict cerebro-cardiovascular events (CCVE) in the general ...population. Considering the paucity of data in stroke patients, we assessed these parameters as potential predictors of recurrent CCVE at acute stroke stroke.
Patients and methods
This is a secondary outcome analysis of a prospective observational longitudinal Sleep Deficiency & Stroke Outcome Study (ClinicalTrials.gov Identifier: NCT02559739). The study consecutively recruited acute ischemic stroke patients. Cardiovascular parameters (blood pressure variability BPV, heart rate variability HRV, endothelial function, and arterial stiffness) were assessed within the first week post-stroke. Future CCVE were recorded over a 3-year follow-up. Multivariate Cox regression analysis was used to investigate the prognostic value of 48 cardiovascular parameters regarding CCVE risk.
Results
Out of 447 recruited patients, 359 were included in this analysis. 20% of patients developed a future CCVE. A high variability of systolic BP (
n
= 333) and nocturnal HR (non-linear parameters;
n
= 187) at acute stroke predicted CCVE risk after adjustment for demographic parameters, cardiovascular risk factors and mean BP or HR, respectively. Endothelial dysfunction (
n
= 105) at acute stroke predicted CCVE risk after adjustment for age and sex, but not after adjustment for cardiovascular risk factors. Diurnal HR and arterial stiffness at acute stroke were not associated with CCVE risk.
Conclusion
High blood pressure variability, high nocturnal HRV and endothelial function contribute to the risk for future CCVE after stroke.
Behavioral changes are common in patients with multiple sclerosis (MS), however not as readily recognized as cognitive impairments.
The aim of this study was to analyze behavioral changes and its ...relation to disease characteristics, disability, and cognitive impairments in patients with MS.
This is a single-center cross-sectional study. A detailed neuropsychological examination, including the Frontal Systems Behavior Scale (FrSBe), the Beck depression inventory (BDI), and the Wuerzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS) test, was performed. FrSBe results were correlated with disease characteristics, disability, and cognitive assessments.
66 patients were enrolled (mean age: 43.4 years; disease duration: 9.3 years; Expanded Disability Status Scale: 3.0). Up to one third of patients showed behavioral changes in at least one domain or the total score of the FrSBe. Patients were mildly affected with regard to cognitive functioning. Consistent correlation was found between behavioral changes and fatigue (WEIMuS) and depressive symptoms (BDI), but not with disease characteristics, disability, or cognitive functions. There was an increase of behavioral changes on all FrSBe scales in the current status compared to the retrospectively rated status before disease onset. Self- and family ratings with regard to current behavioral changes were similar.
Behavioral changes are common in otherwise mildly affected MS patients with up to one third being affected. In this patient cohort, behavioral changes occur largely independent of disease characteristics, physical disability, and cognitive functioning but correlate with both fatigue and depressive symptoms. Therefore, they should be tested specifically.
Different specimen types are used for influenza diagnosis but comparative data for viral loads from different swab types are limited. We compared influenza viral loads (determined by quantitative ...reverse transcription polymerase chain reaction RT‐PCR) in 93 paired midturbinate and nasopharyngeal swab aliquots from influenza infected patients enrolled in a phase 3 randomized‐controlled study with the objective of maximizing the number of swabs available for sequence analysis. Midturbinate swabs yielded a 53% lower viral load versus nasopharyngeal swabs, and this difference was similar for influenza A and B. These data suggest that nasopharyngeal swabs might be preferred in diagnostic settings when obtaining higher viral load is important.
To investigate the directionality of neural interactions as assessed by electrophysiology, we adapted methods of structural analysis from the field of econometrics. In particular, within the ...framework of autoregressive modelling of the data, we considered quantitative measures of linear relationship between multiple time series adopting the Wiener-Granger concept of causality. The techniques were evaluated with local field potential measurements from the cat visual system. Here, several issues had to be addressed. First, out of several statistical tests of the stationarity of local field potentials considered, those based on the Kolmogorov-Smirnov and on the reverse arrangement statistics proved to be most powerful. The application of those tests to the experimental data showed that the large part of the local field potentials can be considered stationary on a time scale of 1 s. Second, out of the several investigated methods for the determination of an optimal order of the autoregressive model, the Akaike Information Criterion had the most suitable properties. The identified order of the model, across different repetitions of the trials, was consistently 5-8. Third, although the individual segments of field potentials used for the analysis were relatively short, the methods of structural analysis applied produced reliable results, confirming findings of simulations of data with similar properties. Furthermore the features of the estimated models were consistent among trials, so that the analysis of average measures of interaction appears to be a viable approach to investigate the relationship between the recording sites. In summary, the statistical methods considered have proved to be suitable for the study of the directionality of neuronal interactions.
Background/Aims: Parathyroid hormone (PTH) derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and ...pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. Methods: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 µg PTH-1-37, 20 µg PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. Results: PTH was absorbed rapidly from the subcutaneous tissue with a median tmax of 30 minutes for 20 and 40 µg of PTH-1-37. tmax was 45 minutes for 20 µg PTH-1-34. Elimination half-lives were estimated as 76 ± 34 min and 70 ± 13 min for 20 µg and 40 µg PTH-1-37 (mean ± SD), and 78 ± 34 for 20 µg PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34) increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. Conclusions: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism.
Protocol-mandated, outcome-driven treatment adaptations are common in many types of clinical trials, and a prominent feature of so-called treat-to-target trials. Successive treatment escalation ...(dosage increase or addition of a drug) if disease activity targets are not reached is a typical design element in these studies. Focusing on the first treatment escalation step, here we address ways of estimating the effect of this outcome-based intervention as well some issues pertaining to the design of such treatment changes in randomized trials.
Estimating escalation effects requires to disentangle them from concurrent effects, including persisting effects of the randomized treatment and regression to the mean. A regression-based method and a likelihood ratio test were adapted and assessed in simulations and in data from a recent treat-to-target study in rheumatoid arthritis. In simulations, the procedures were satisfactory in terms of bias and sensitivity with some advantage for the likelihood ratio test. They were able to identify evidence for the escalation effect in the examined study. In summary, both analysis methods are useful, but are sensitive to key assumptions and rely on compliance to the protocol as well as frequent and complete assessments.
Furthermore, we examined different treatment escalation designs, including escalation at multiple time points (early escalation). If a longitudinal model for the disease activity is available, we describe how early escalation strategies can decrease the overall disease burden. We provide recommendations for the design of treatment escalation procedures in typical settings.
Objective
To compare clinical effectiveness between tocilizumab and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional ...synthetic disease‐modifying antirheumatic drugs initiating biologic therapy.
Methods
Patients prescribed tocilizumab (intravenous) or TNFi were prospectively observed in routine clinical practice for 52 weeks across 158 sites in 26 countries. The primary observation was the change from baseline in Disease Activity Score based on 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) at week 24 using analysis of covariance for between‐groups comparison. Secondary end points included Clinical Disease Activity Index (CDAI) and patient‐reported outcomes at weeks 24 and 52.
Results
Of 1,216 patients, 35% initiated tocilizumab and 65% initiated TNFi. RA duration was shorter, and disease activity and corticosteroid use were higher in tocilizumab patients. Tocilizumab‐treated patients had greater improvement in DAS28‐ESR at weeks 24 and 52 (week 24 difference 95% confidence interval in adjusted means: −0.831 −1.086, −0.576; P < 0.001). Change from baseline in CDAI was also greater with tocilizumab (adjusted means difference: week 24, −3.48; week 52, −4.60; both P < 0.001). Tocilizumab‐treated patients had more improvement in the Health Assessment Questionnaire disability index than TNFi‐treated patients (P < 0.05). The cumulative probability of drug discontinuation at week 52 was lower with tocilizumab (15%) than TNFi (27%; P < 0.001, unadjusted analysis). Unadjusted frequencies (events per 100 patient‐years) for tocilizumab and TNFi were 6.44 and 11.99 for serious adverse events, 1.98 and 5.03 for serious infections, and 0.74 and 0.77 for deaths, respectively.
Conclusion
Patients initiating tocilizumab experienced greater effectiveness and drug survival than those initiating TNFi in an observational setting.
PDF
