| 1. |
- Chew, Michelle S., et al.
(författare)
-
Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index
- 2022
-
Ingår i: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 128:1, s. 26-36
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality.METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE.RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds.CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE.CLINICAL TRIAL REGISTRATION: NCT03436238.
|
|
| 2. |
- Strittmatter, Frank, et al.
(författare)
-
Thromboxane A2 induces contraction of human prostate smooth muscle by Rho kinase- and calmodulin-dependent mechanisms
- 2011
-
Ingår i: European Journal of Pharmacology. - : Elsevier. - 0014-2999 .- 1879-0712. ; 650:2-3, s. 650-655
-
Tidskriftsartikel (refereegranskat)abstract
- Thromboxane A(2) (TXA(2)) induces contraction in different smooth muscle types via its receptor (TXA(2) receptor). However, any motoric role of TXA(2) in prostate smooth muscle tone has not been studied to date. Here, we investigated whether TXA(2) induces contraction of human prostate tissue. After ethical approval, prostate tissue was obtained from 47 patients undergoing radical prostatectomy. Effects of the TXA(2) analogue U46619 ((5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptonic acid) in isolated human prostate strips were studied in organ bath experiments with or without the Rho kinase inhibitor, Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride), or the calmodulin antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride). Expression of TXA(2) synthase and TXA(2) receptors were examined by Western blot analysis and immunohistochemistry. Endogenous TXA(2) was quantified by enzyme immunoassay. U46619 induced concentration-dependent contractions of human prostate strips, with a maximum contraction at 3 μM. U46619-induced prostate contraction was significantly inhibited by Y27632 (30 μM) and by W7 (100 μM). TXA(2) synthase and TXA(2) receptors were detected by Western blot analysis. Immunohistochemical stainings showed that expression of TXA(2) synthase in prostate tissue was located to glandular cells, while prostate TXA(2) receptors were located to smooth muscle and glandular cells. The stable TXA(2) metabolite TXB(2) was detected by enzyme immunoassay in the prostate. TXA(2) induces contraction of isolated human prostate tissue by TXA(2) receptor activation. Prostate smooth muscle TXA(2) receptors are coupled to Rho kinase and Ca(2+)-dependent mechanisms. The distribution of TXA(2) synthase and TXA(2) receptors in the human prostate suggests TXA(2)-mediated paracrine epithelial-stromal interactions.
|
|
| 3. |
- Andersson, Christian X, 1973, et al.
(författare)
-
Shedding and gamma-Secretase mediated intramembrane proteolysis of the mucin-type molecule CD43
- 2005
-
Ingår i: Biochem J.. ; 387:2, s. 377-384
-
Tidskriftsartikel (refereegranskat)abstract
- CD43 is a transmembrane molecule that contains a 123-aminoacids-long cytoplasmic tail and a highly O-glycosylated extracellular domain of mucin type. Endogenous CD43 expressed in COLO 205, K562 and Jurkat cells revealed a membrane-associated, 20 kDa CD43-specific cytoplasmic tail fragment (CD43-CTF) upon inhibition of gamma-secretase. This fragment was formed by an extracellular cleavage, as it was not accumulated after treating cells with 1,10-phenanthroline, a metalloprotease inhibitor. When CD43 was transfected into HEK-293 cells expressing dominant-negative PS1 (presenilin-1), the CD43-CTF was accumulated, but not in cells with wild-type PS1. Owing to its accumulation in the presence of a non-functional PS variant, it may thus be a novel gamma-secretase substrate. This CTF is formed by an extracellular cleavage close to the membrane, is a fragment that can be concluded to be a substrate for gamma-secretase. However, the intracellular gamma-secretase product has not been possible to detect, suggesting a quick processing of this product. During normal growth the CTF was not found without gamma-secretase inhibition, but when the cells (COLO 205) were very confluent the fragment could be detected. The intracellular domain of CD43 has previously been shown to contain a functional nuclear localization signal, and has been suggested to be involved in gene activation. From this and the present results, a novel way to explain how mucin-type molecules may transduce intracellular signals can be proposed.
|
|
| 4. |
- Andersson, Erik, et al.
(författare)
-
A Randomized Controlled Trial of Guided Internet-delivered Cognitive Behavioral Therapy for Erectile Dysfunction
- 2011
-
Ingår i: Journal of Sexual Medicine. - : Wiley-Blackwell. - 1743-6095 .- 1743-6109. ; 8:10, s. 2800-2809
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction. Men with erectile dysfunction are often worried about their condition, have interpersonal difficulties, and have a reduced quality of life. Internet-delivered cognitive behavior therapy (ICBT) has been shown effective for a number of health problems but evidence is limited concerning the treatment of erectile dysfunction. less thanbrgreater than less thanbrgreater thanAim. The study investigated the effects of ICBT for erectile dysfunction. less thanbrgreater than less thanbrgreater thanMethods. Seventy-eight men were included in the study and randomized to either ICBT or to a control group, which was an online discussion group. Treatment consisted of a 7-week Web-based program with e-mail-based therapist support. Each therapist spent an average of 55 minutes per participant. less thanbrgreater than less thanbrgreater thanMain Outcome Measure. The International Index of Erectile Functioning five-item version was administered via the telephone at pretreatment, post-treatment, and 6 months after receiving ICBT. less thanbrgreater than less thanbrgreater thanResults. At post-treatment, the treatment group had significantly greater improvements with regard to erectile performance compared with the control group. Between-group differences at post-treatment were small (d = 0.1), but increased at the 6-month follow-up (d = 0.88). less thanbrgreater than less thanbrgreater thanConclusions. This study provides support for the use of ICBT as a possible treatment format for erectile dysfunction.
|
|
| 5. |
- Andersson, Erik, et al.
(författare)
-
Cost-effectiveness of an internet-based booster program for patients with obsessive-compulsive disorder : Results from a randomized controlled trial
- 2015
-
Ingår i: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier. - 2211-3649 .- 2211-3657. ; 4, s. 14-19
-
Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavior therapy (CBT) is an effective treatment for OCD when delivered face-to-face, in group-format and also via the internet. However, despite overall large effect sizes, a considerable amount of the patients relapse. One intervention that has the potential to reduce these relapse rates is booster programs, but if booster program is a cost-effective method of preventing relapse is still unknown. We used health economical data from a recent randomized controlled trial, where patients who had undergone an internet-based CBT were randomly allocated to receive an additional booster program. Assessment points were 4-, 7-, 12- and 24-month. Health economical data were primarily analyzed using a societal perspective. Results showed that the booster program was effective in preventing relapse, and the cost of one avoided relapse was estimated to $1066-1489. Cost-effectiveness acceptability curves showed that the booster program had a 90% probability of being cost-effective given a willingness to pay of $1000-1050 the first year, but this figure grew considerably after two years ($2500-5500). We conclude that internet-based booster programs are probably a cost-effective alternative within one-year time frame and that more treatment may be needed to maintain adequate cost-effectiveness up to two years. (C) 2014 Elsevier Inc. All rights reserved.
|
|
| 6. |
- Andersson, Erik, et al.
(författare)
-
Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial
- 2011
-
Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 11:215
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Irritable Bowel Syndrome (IBS) is highly prevalent and is associated with a substantial economic burden. Cognitive behavior therapy (CBT) has been shown to be effective in treating IBS. The aim of this study was to evaluate the cost-effectiveness of a new treatment alternative, internet-delivered CBT based on exposure and mindfulness exercises. Methods: Participants (N = 85) with IBS were recruited through self-referral and were assessed via a telephone interview and self-report measures on the internet. Participants were randomized to internet-delivered CBT or to a discussion forum. Economic data was assessed at pre-, post- and at 3-month and 1 year follow-up. Results: Significant cost reductions were found for the treatment group at $16,806 per successfully treated case. The cost reductions were mainly driven by reduced work loss in the treatment group. Results were sustained at 3-month and 1 year follow-up. Conclusions: Internet-delivered CBT appears to generate health gains in IBS treatment and is associated with cost-savings from a societal perspective.
|
|
| 7. |
- Andersson, Erik, et al.
(författare)
-
Cost-effectiveness of internet-based cognitive behavior therapy for obsessive-compulsive disorder : results from a randomized controlled trial
- 2015
-
Ingår i: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier. - 2211-3649 .- 2211-3657. ; 4, s. 47-53
-
Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder (OCD) is a common and disabling disorder. Although evidence-based psychological treatments exists, such as cognitive behavior therapy (CBT), the cost-effectiveness of CBT has not been properly investigated. In this trial, we used health economic data from a recently conducted randomized controlled trial, where 101 OCD patients were allocated to either internet-based CBT (ICBT) or control condition (online support therapy). We analyzed treatment effectiveness in relation to costs, using both a societal- (including all direct and indirect costs) and a health care unit perspective (including only the direct treatment costs). Bootstrapped net benefit regression analyses were also conducted, comparing the difference in costs and effects between ICBT and control condition, with different willingness-to-pay scenarios. Results showed that ICBT produced one additional remission for an average societal cost of $931 and this figure was even lower ($672) when narrowing the perspective to treatment costs only. The cost-utility analysis also showed that ICBT generated one additional QALY to an average price of $7186 from a societal perspective and $4800 when just analyzing the treatment costs. We conclude that ICBT is a cost-effective treatment and the next step in this line of research is to compare the cost-effectiveness of ICBT with face-to-face CBT. (C) 2014 Elsevier Inc. All rights reserved.
|
|
| 8. |
- Andersson, Erik, et al.
(författare)
-
d-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants A Randomized Clinical Trial
- 2015
-
Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 72:7, s. 659-667
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE It is unclear whether D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist that enhances fear extinction, can augment the effects of exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). OBJECTIVES To examine whether DCS augments the effects of CBT for OCD and to explore (post hoc) whether concomitant antidepressant medication moderates the effects of DCS. DESIGN, SETTING, AND PARTICIPANTS A 12-week, double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4, 2012, and September 26, 2013. Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial. The main analysis was by intention-to-treat population. INTERVENTIONS All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo, administered 1 hour before each of 5 exposure and response prevention tasks. MAIN OUTCOMES AND MEASURES Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up. Remission was defined as a score of 12 or lower on the Y-BOCS. RESULTS In the primary intention-to-treat analyses, DCS did not augment the effects of CBT compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50] at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week 12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction with antidepressants (clinician-rated Y-BOCS, B = -1.08; Z = -2.79; P = .005). Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group, at both posttreatment and follow-up (clinician-rated Y-BOCS: t(62) = -3.00; P = .004; and t(61) = -3.49; P < .001, respectively). In the DCS group, a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up (60% [95% CI, 45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P = .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%] remission rate in both groups). CONCLUSIONS AND RELEVANCE The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction. Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD.
|
|
| 9. |
- Andersson, Evelyn, et al.
(författare)
-
Genetic Polymorphisms in Monoamine Systems and Outcome of Cognitive Behavior Therapy for Social Anxiety Disorder
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703Tpolymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients.MethodParticipants were recruited from two separate randomized controlled CBT trials (trial 1: n = 112, trial 2: n = 202). Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment) for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report.ResultsAt long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials.ConclusionsNone of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD.
|
|
| 10. |
- Andersson, Erik, et al.
(författare)
-
Internet-based cognitive behavior therapy for obsessive compulsive disorder: A pilot study
- 2011
-
Ingår i: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 11:125
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive behavior therapy (CBT) is widely regarded as an effective treatment for obsessive compulsive disorder (OCD), but access to CBT therapists is limited. Internet-based CBT (ICBT) with therapist support is a way to increase access to CBT but has not been developed or tested for OCD. The aim of this study was to evaluate ICBT for OCD. less thanbrgreater than less thanbrgreater thanMethod: An open trial where patients (N = 23) received a 15-week ICBT program with therapist support consisting of psychoeducation, cognitive restructuring and exposure with response prevention. The primary outcome was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), which was assessed by a psychiatrist before and immediately after treatment. Secondary outcomes were self-rated measures of OCD symptoms, depressive symptoms, general functioning, anxiety and quality of life. All assessments were made at baseline and post-treatment. less thanbrgreater than less thanbrgreater thanResults: All participants completed the primary outcome measure at all assessment points. There were reductions in OCD symptoms with a large within-group effect size (Cohens d = 1.56). At post-treatment, 61% of participants had a clinically significant improvement and 43% no longer fulfilled the diagnostic criteria of OCD. The treatment also resulted in statistically significant improvements in self-rated OCD symptoms, general functioning and depression. less thanbrgreater than less thanbrgreater thanConclusions: ICBT with therapist support reduces OCD symptoms, depressive symptoms and improves general functioning. Randomized trials are needed to confirm the effectiveness of this new treatment format.
|
|
