The past few decades saw considerable advances in research and dissemination of evidence-based psychotherapies, yet available treatment resources are not able to meet the high need for care for ...individuals suffering from depression or anxiety. Blended care psychotherapy, which combines the strengths of therapist-led and internet interventions, can narrow this gap and be clinically effective and efficient, but has rarely been evaluated outside of controlled research settings.
This study evaluated the effectiveness of a blended care intervention (video-based cognitive behavior therapy and internet intervention) under real-world conditions.
This is a pragmatic retrospective cohort analysis of 385 participants with clinical range depression and/or anxiety symptoms at baseline, measured using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), who enrolled in blended care psychotherapy treatment. Participants resided in the United States and had access to the blended care intervention as a mental health benefit offered through their employers. Levels of depression and anxiety were tracked throughout treatment. Hierarchical linear modeling was used to examine the change in symptoms over time. The effects of age, gender, and providers on participants' symptom change trajectories were also evaluated. Paired sample t-tests were also conducted, and rates of positive clinical change and clinically significant improvement were calculated.
The average depression and anxiety symptoms at 6 weeks after the start of treatment were 5.94 and 6.57, respectively. There were significant linear effects of time on both symptoms of depression and anxiety (β=-.49, P<.001 and β=-.64, P<.001). The quadratic effect was also significant for both symptoms of depression and anxiety (β=.04, P<.001 for both), suggesting a decelerated decrease in symptoms over time. Approximately 73% (n=283) of all 385 participants demonstrated reliable improvement, and 83% (n=319) recovered on either the PHQ-9 or GAD-7 measures. Large effect sizes were observed on both symptoms of depression (Cohen d=1.08) and of anxiety (d=1.33).
Video blended care cognitive behavioral therapy interventions can be effective and efficient in treating symptoms of depression and anxiety in real-world conditions. Future research should investigate the differential and interactive contribution of the therapist-led and digital components of care to patient outcomes to optimize care.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In tall core-wall buildings with concrete unbonded post-tensioned flat-plate gravity framing, modeling the behavior of the slab-wall-column framing under earthquake loading can be crucial to ...determining structural response quantities for the design of the flat-plate framing. The outrigger action of the gravity system also affects the overall dynamic properties of the building and may affect wall moment and shear demands. The outrigger effect can be modeled using a slab-beam model, which uses linear-elastic frame elements with concentrated nonlinear hinges at each end. In this study, the slab-beam model is calibrated using results from a slab-wall-column laboratory test. Recommendations suitable for design-office practice are presented. Keywords: earthquake engineering; flat plate; gravity framing; nonlinear modeling; outrigger action; plastic hinge; post-tensioned slab; slab-column joint; slab-wall connection.
Objective
Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster (HZ), and the risk appears to be increased in patients treated with tofacitinib. The aim of this study was to ...evaluate whether concomitant treatment with conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) or glucocorticoids (GCs) contributes to the increased risk of HZ in RA patients treated with tofacitinib.
Methods
HZ cases were identified from the databases of 2 phase I, 9 phase II, 6 phase III, and 2 long‐term extension studies of tofacitinib in RA patients. Crude incidence rates (IRs) of all HZ events (serious and nonserious) per 100 patient‐years (with 95% confidence intervals 95% CIs) were calculated for unique patients. Within phase III studies, we described HZ rates according to concomitant csDMARD treatment and baseline GC use. A multivariable Cox proportional hazards regression model was used to evaluate HZ risk factors across studies.
Results
Across all studies (6,192 patients; 16,839 patient‐years), HZ was reported in 636 tofacitinib‐treated patients (IR 4.0, 95% CI 3.7–4.4). In most cases (93%), HZ was classified as nonserious, and the majority of patients (94%) had involvement of only 1 dermatome. HZ IRs varied across regions, from 2.4 (95% CI 2.0–2.9) in Eastern Europe to 8.0 (95% CI 6.6–9.6) in Japan and 8.4 (95% CI 6.4–10.9) in Korea. Within phase III studies, HZ IRs varied according to tofacitinib dose, background csDMARD treatment, and baseline use of GCs. The IRs were numerically lowest for monotherapy with tofacitinib 5 mg twice daily without GCs (IR 0.56 95% CI 0.07–2.01) and highest for tofacitinib 10 mg twice daily with csDMARDs and GCs (IR 5.44 95% CI 3.72–7.68). Age, GC use, tofacitinib dose, and enrollment within Asia were independent risk factors for HZ.
Conclusion
Patients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The transcription factor SRY (sex-determining region)-box 2 (SOX2) is an important functional marker of neural precursor cells (NPCs) and plays a critical role in self-renewal and neuronal ...differentiation; however, the molecular mechanisms underlying its functions are poorly understood. Using human embryonic stem cell-derived NPCs to model neurogenesis, we found that SOX2 is required to maintain optimal levels of LIN28, a well-characterized suppressor of let-7 microRNA biogenesis. Exogenous LIN28 expression rescued the NPC proliferation deficit, as well as the early but not the late stages of the neurogenic deficit associated with the loss of SOX2. We found that SOX2 binds to a proximal site in the LIN28 promoter region and regulates LIN28 promoter acetylation, likely through interactions with the histone acetyltransferase complex. Misexpression of let-7 microRNAs in NPCs reduced proliferation and inhibited neuronal differentiation, phenocopying the loss of SOX2. In particular, we identified let-7i as a novel and potent inhibitor of neuronal differentiation that targets MASH1 and NGN1, two well-characterized proneural genes. In conclusion, we discovered the SOX2–LIN28/let-7 pathway as a unique molecular mechanism governing NPC proliferation and neurogenic potential.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Summary Background In previous clinical trials of patients with metastatic renal-cell carcinoma, patients treated with axitinib as second-line therapy had longer median progression-free survival than ...those treated with sorafenib. We therefore undertook a phase 3 trial comparing axitinib with sorafenib in patients with treatment-naive metastatic renal-cell carcinoma. Methods In this randomised, open-label, phase 3 trial, patients with treatment-naive, measurable, clear-cell metastatic renal-cell carcinoma from 13 countries were stratified by Eastern Cooperative Oncology Group performance status, and then randomly assigned (2:1) by a centralised registration system to receive axitinib 5 mg twice daily, or sorafenib 400 mg twice daily. The primary endpoint was progression-free survival, assessed by masked independent review committee in the intention-to-treat population. This ongoing trial is registered at ClinicalTrials.gov , NCT00920816. Findings Between June 14, 2010, and April 21, 2011, we randomly assigned 192 patients to receive axitinib, and 96 patients to receive sorafenib. The cutoff date for this analysis was July 27, 2012, when 171 (59%) of 288 patients died or had disease progression, as assessed by the independent review committee. There was no significant difference in median progression-free survival between patients treated with axitinib or sorafenib (10·1 months 95% CI 7·2–12·1 vs 6·5 months 4·7–8·3, respectively; stratified hazard ratio 0·77, 95% CI 0·56–1·05). Any-grade adverse events that were more common (≥10% difference) with axitinib than with sorafenib were diarrhoea (94 50% of 189 patients vs 38 40% of 96 patients), hypertension (92 49% vs 28 29%), weight decrease (69 37% vs 23 24%), decreased appetite (54 29% vs 18 19%), dysphonia (44 23% vs ten 10%), hypothyroidism (39 21% vs seven 7%), and upper abdominal pain (31 16% vs six 6%); those more common with sorafenib than with axitinib included palmar-plantar erythrodysaesthesia (PPE; 37 39% of 96 patients vs 50 26% of 189), rash (19 20% vs 18 10%), alopecia (18 19% vs eight 4%), and erythema (18 19% vs five 3%). The most common grade 3 or 4 adverse events in patients treated with axitinib included hypertension (26 14% of 189 patients), diarrhoea (17 9%), asthenia (16 8%), weight decrease (16 8%), and PPE (14 7%); common grade 3 or 4 adverse events in patients treated with sorafenib included PPE (15 16% of 96 patients), diarrhoea (five 5%), and asthenia (five 5%). Serious adverse events were reported in 64 (34%) of 189 patients receiving axitinib, and 24 (25%) of 96 patients receiving sorafenib. Interpretation Axitinib did not significantly increase progression-free survival in patients with treatment-naive metastatic renal-cell carcinoma compared with those treated with sorafenib, but did demonstrate clinical activity and an acceptable safety profile. Funding Pfizer Inc.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Background In a phase 3 trial comparing the efficacy and safety of axitinib versus sorafenib as second-line treatment for metastatic renal cell carcinoma, patients given axitinib had a longer ...progression-free survival (PFS). Here, we report overall survival and updated efficacy, quality of life, and safety results. Methods Eligible patients had clear cell metastatic renal cell carcinoma, progressive disease after one approved systemic treatment, and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1. 723 patients were stratified by ECOG PS and previous treatment and randomly allocated (1:1) to receive axitinib (5 mg twice daily; n=361) or sorafenib (400 mg twice daily; n=362). The primary endpoint was PFS assessed by a masked, independent radiology review committee. We assessed patient-reported outcomes using validated questionnaires. Baseline characteristics and development of hypertension on treatment were studied as prognostic factors. Efficacy was assessed in the intention-to-treat population, and safety was assessed in patients who received at least one dose of the study drug. This ongoing trial is registered on ClinicalTrials.gov , number NCT00678392. Findings Median overall survival was 20·1 months (95% CI 16·7–23·4) with axitinib and 19·2 months (17·5–22·3) with sorafenib (hazard ratio HR 0·969, 95% CI 0·800–1·174; one-sided p=0·3744). Median investigator-assessed PFS was 8·3 months (95% CI 6·7–9·2) with axitinib and 5·7 months (4·7–6·5) with sorafenib (HR 0·656, 95% CI 0·552–0·779; one-sided p<0·0001). Patient-reported outcomes scores were similar in the treatment groups at baseline, were maintained during treatment, but decreased at end-of-treatment. Common grade 3 or higher treatment-related adverse events were hypertension (60 17%), diarrhoea (40 11%), and fatigue (37 10%) in 359 axitinib-treated patients and hand–foot syndrome (61 17%), hypertension (43 12%), and diarrhoea (27 8%) in 355 sorafenib-treated patients. In a post-hoc 12-week landmark analysis, median overall survival was longer in patients with a diastolic blood pressure of 90 mm Hg or greater than in those with a diastolic blood pressure of less than 90 mm Hg: 20·7 months (95% CI 18·4–24·6) versus 12·9 months (10·1–20·4) in the axitinib group (p=0·0116), and 20·2 months (17·1–32·0) versus 14·8 months (12·0–17·7) in the sorafenib group (one-sided p=0·0020). Interpretation Although overall survival, a secondary endpoint for the study, did not differ between the two groups, investigator-assessed PFS remained longer in the axitinib group compared with the sorafenib group. These results establish axitinib as a second-line treatment option for patients with metastatic renal cell carcinoma. Funding Pfizer Inc.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Introduction:
Access to quality mental health medication management (MM) in the United States is limited, even among those with employment-based health insurance. This implementation, feasibility, ...and outcome study sought to design and evaluate an evidence-based telemental health MM service using a collaborative care model (CoCM).
Materials and Methods:
CoCM MM was available to adult employees/dependents through their employer benefits, in addition to therapy. Outcomes included Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) collected at baseline and throughout participation. This analysis was not deemed to be human subjects research by the Western Institutional Review Board.
Results:
Over 17 months, 212 people enrolled and completed >2 assessments; the enrollees were 58.96% female with average age of 32.00 years (standard deviation SD = 7.38). In people with moderate to severe depression or anxiety, PHQ-9 and GAD-7 scores reduced by an average of 7.27 (SD = 4.80) and 6.71 (SD = 5.18) points after at least 12 ± 4 weeks in the program. At 24 ± 4 weeks, the PHQ-9 and GAD-7 reductions were on average 7.17 (SD = 5.00) and 6.03 (SD = 5.37), respectively. Approximately 65.88% of participants with either baseline depression or anxiety had a response on either the PHQ-9 or GAD-7 at 12 ± 4 weeks and 44.71% of participants experienced remission; at 24 ± 4 weeks, 56.41% had response and 41.03% experienced remission.
Conclusions:
An evidence-based CoCM telemedicine service within an employee behavioral health benefit is feasible and effective in reducing anxiety and depression symptoms when using measurement-based care. Widespread implementation of a benefit like this could expand access to evidence-based mental health MM.
Background:
Many employees experience high levels of stress in the workplace, which negatively impact their productivity and well-being. Effective stress management interventions exist, but are ...inaccessible due to insufficient numbers of mental health providers, long waiting times to initiate care, high out-of-pocket cost of care, and stigma related to receiving psychotherapy.
Introduction:
The purpose of this study was to test the efficacy, in real-world circumstances, of a structured, cognitive behavioral coaching (CBC) program delivered through video or telephone.
Materials and Methods:
Retrospective data on 289 subjects who had sought support for emotional health through a behavioral health benefit offered through employers were examined. Changes in perceived stress and well-being over the course of the program were measured using the Perceived Stress Scale (PSS) and Warwick–Edinburgh Mental Well-being Scale (WEMWBS), respectively. Rates of reliable change and satisfaction with the coaching program were also assessed.
Results:
Scores on both the PSS and WEMWBS improved between baseline and follow-up. Approximately 61.9% (n = 289) of participants demonstrated reliable improvement on either measure.
Discussion:
CBC is a promising intervention that has the potential to significantly expand access to effective and more affordable interventions for emotional health care.
Conclusions:
Coaching, when delivered by accredited professionals trained in cognitive behavioral theory and interventions and working in real-world settings, can be efficacious in decreasing perceived stress and increasing well-being when delivered through video or telephone.
Adenosine triphosphate (ATP) is used as an intracellular energy source by all living organisms. It plays a central role in the respiration and metabolism, and is the most important energy supplier in ...many enzymatic reactions. Its critical role as the energy storage molecule makes it extremely valuable to all cells.
We report here the detection of extracellular ATP in the cultures of a variety of bacterial species. The levels of the extracellular ATP in bacterial cultures peaked around the end of the log phase and decreased in the stationary phase of growth. Extracellular ATP levels were dependent on the cellular respiration as bacterial mutants lacking cytochrome bo oxidase displayed lower extracellular ATP levels. We have also shown that Escherichia coli (E. coli) and Salmonella actively depleted extracellular ATP and an ATP supplement in culture media enhanced the stationary survival of E. coli and Salmonella. In addition to E. coli and Salmonella the presence of the extracellular ATP was observed in a variety of bacterial species that contain human pathogens such as Acinetobacter, Pseudomonas, Klebsiella and Staphylococcus.
Our results indicate that extracellular ATP is produced by many bacterial species during growth and extracellular ATP may serve a role in the bacterial physiology.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
