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- Bulman, Zackery P., et al.
(författare)
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Research priorities towards precision antibiotic therapy to improve patient care
- 2022
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Ingår i: LANCET MICROBE. - : Elsevier. - 2666-5247. ; 3:10, s. e795-e802
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance presents an incessant threat to our drug armamentarium that necessitates novel approaches to therapy. Over the past several decades, investigation of pharmacokinetic and pharmacodynamic (PKPD) principles has substantially improved our understanding of the relationships between the antibiotic, pathogen, and infected patient. However, crucial gaps in our understanding of the pharmacology of antibacterials and their optimal use in the care of patients continue to exist; simply attaining antibiotic exposures that are considered adequate based on traditional targets can still result in treatment being unsuccessful and resistance proliferation for some infections. It is this salient paradox that points to key future directions for research in antibiotic therapeutics. This Personal View discusses six priority areas for antibiotic pharmacology research: (1) antibiotic-pathogen interactions, (2) antibiotic targets for combination therapy, (3) mechanistic models that describe the time-course of treatment response, (4) understanding and modelling of host response to infection, (5) personalised medicine through therapeutic drug management, and (6) application of these principles to support development of novel therapies. Innovative approaches that enhance our understanding of antibiotic pharmacology and facilitate more accurate predictions of treatment success, coupled with traditional pharmacology research, can be applied at the population level and to individual patients to improve outcomes.
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- Jensen, S., et al.
(författare)
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Quality of life in pediatric patients with obsessive-compulsive disorder during and 3 years after stepped-care treatment
- 2022
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Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 31:9, s. 1377-1389
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to investigate the long-term quality of life (QoL) in a large sample of pediatric obsessive-compulsive disorder (OCD) patients. The study included 220 pediatric OCD patients from the Nordic Long-term OCD Treatment Study (NordLOTS) who were evaluated at seven time points before, during, and after stepped-care treatment over a 3-year follow-up period. Data from three symptom severity trajectory classes formed the basis of the QoL evaluation: acute (n = 127, N = 147), slow (n = 46, N = 63), and limited responders (n = 47, N = 59). Patients' QoL was assessed using parent and child ratings of the revised Questionnaire for Measuring Health-related Quality of Life in Children and Adolescents (KINDL-R). QoL was analyzed by trajectory class using a random mixed effects model. The association between pre-treatment factors and long-term QoL was investigated across classes in a multivariate model. Three years after treatment, the acute responder class had reached QoL levels from a general population, whereas the limited responder class had not. The slow responder class reached norm levels for the child-rated QoL only. Higher levels of co-occurring externalizing symptoms before treatment were associated with lower parent-rated QoL during follow-up, while adolescence and higher levels of co-occurring internalizing symptoms were associated with lower child-rated QoL during follow-up. For some patients, residual OCD symptoms in the years after treatment, even at levels below assumed clinical significance, are associated with compromised QoL. Co-occurring symptoms could be part of the explanation. Assessing QoL after OCD treatment, beyond the clinician-rated symptom severity, could detect patients in need of further treatment and/or assessment. Trial registry: Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; ; ISRCTN66385119.
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- Bonnert, M., et al.
(författare)
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Internet-Delivered Cognitive Behavior Therapy for Adolescents With Irritable Bowel Syndrome: A Randomized Controlled Trial
- 2017
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Ingår i: Am J Gastroenterol. - Stockholm : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 112:1, s. 152-162
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Few treatments have been able to effectively manage pediatric irritable bowel syndrome (IBS). Internet-delivered cognitive behavior therapy (Internet-CBT) based on exposure for abdominal symptoms is effective for adult IBS. The objective of this study was to evaluate the efficacy of Internet-CBT based on behavioral exposure for adolescents with IBS. METHODS: Adolescents with IBS fulfilling the Rome III criteria were randomized to either Internet-CBT or a wait-list control. The Internet-CBT was a 10-week intervention where the main component was exposure to IBS symptoms by reduction of avoidance of abdominal symptoms and instead stepwise provocation of symptoms. The primary outcome was total score on Gastrointestinal Symptoms Rating Scale for IBS (GSRS-IBS). Secondary outcomes included adolescent- and parent-rated quality of life and parent-rated gastrointestinal symptoms. Difference between groups was assessed from pretreatment to posttreatment and the Internet-CBT group was also evaluated at 6 months after treatment completion. RESULTS: A total of 101 adolescents with IBS (13-17 years of age) were included in this study. Dropout rates were low (6%) and all randomized patients were included in intent-to-treat analyses based on mixed effects models. Analyses showed a significant larger pretreatment to posttreatment change on the primary outcome GSRS-IBS (B=-6.42, P=0.006, effect size Cohen's d=0.45, 95% confidence interval (0.12, 0.77)) and on almost all secondary outcomes for the Internet-CBT group compared with the control group. After 6 months, the results were stable or significantly improved. CONCLUSIONS: Internet-CBT based on exposure exercises for adolescents with IBS can effectively improve gastrointestinal symptoms and quality of life.
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- Sampaio, Filipa, PhD, 1985-, et al.
(författare)
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Cost-effectiveness of internet-delivered cognitive-behavioural therapy for adolescents with irritable bowel syndrome
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:1, s. e023881-
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Tidskriftsartikel (refereegranskat)abstract
- To assess whether exposure-based internet-delivered cognitive–behavioural therapy (internet-CBT) is a cost-effective treatment for adolescents with irritable bowel syndrome (IBS) compared with a waitlist control, from a societal perspective, based on data from a randomised trial.DesignWithin-trial cost-effectiveness analysis.SettingParticipants were recruited from the whole of Sweden via primary, secondary and tertiary care clinics reached through news media and advertising.ParticipantsAdolescents (aged 13–17) with a diagnosis of IBS.InterventionsParticipants were randomised to either an exposure-based internet-CBT, including 10 weekly modules for adolescents and five modules for parents, or a waitlist.Outcome measuresThe main health outcome was the quality-adjusted life-year (QALY) estimated by mapping Pediatric Quality-of-Life Inventory (PedsQL) scores onto EQ-5D-3L utilities. The secondary outcome was the point improvement on the PedsQL scale. Data on health outcomes and resource use were collected at baseline and 10 weeks post-treatment. Resource use was measured using the Trimbos and Institute of Medical Technology Assessment Cost Questionnaire for Psychiatry (TIC-P) . Incremental cost-effectiveness ratios (ICER) were calculated as the difference in average costs by the difference in average outcomes between groups.ResultsThe base-case results showed that internet-CBT costs were on average US$170.24 (95% CI 63.14 to 315.04) more per participant than the waitlist. Adolescents in the internet-CBT group showed small QALY gains (0.0031; 95% CI 0.0003 to 0.0061), and an average improvement of 5.647 points (95% CI 1.82 to 9.46) on the PedsQL compared with the waitlist. Internet-CBT yielded an ICER of $54 916/QALY gained and a probability of cost-effectiveness of 74% given the Swedish willingness-to-pay threshold. The ICER for the outcome PedsQL was US$85.29/point improvement.ConclusionsOffering internet-CBT to adolescents with IBS improves health-related quality of life and generates small QALY gains at a higher cost than a waitlist control. Internet-CBT is thus likely to be cost-effective given the strong efficacy evidence, small QALY gains and low cost.Trial registration numberNCT02306369; Results.
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