Clinician experiences of healthy lifestyle promotion and perceptions of digital interventions as complementary tools for lifestyle behavior change in primary care.

BACKGROUND: Evidence-based practice for healthy lifestyle promotion in primary health care is supported internationally by national policies and guidelines but implementation in routine primary health care has been slow. Referral to digital interventions could lead to a larger proportion of patients accessing structured interventions for healthy lifestyle promotion, but such referral might have unknown implications for clinicians with patients accessing such interventions. This qualitative study aimed to explore the perceptions of clinicians in primary care on healthy lifestyle promotion with or without digital screening and intervention. METHODS: Focus group interviews were conducted at 10 primary care clinics in Sweden with clinicians from different health professions. Transcribed interviews were analyzed using content analysis, with inspiration from a phenomenological-hermeneutic method involving naïve understanding, structural analysis and comprehensive understanding. RESULTS: Two major themes captured clinicians' perceptions on healthy lifestyle promotion: 1) the need for structured professional practice and 2) deficient professional practice as a hinder for implementation. Sub-themes in theme 1 were striving towards professionalism, which for participants meant working in a standardized fashion, with replicable routines regardless of clinic, as well as being able to monitor statistics on individual patient and group levels; and embracing the future with critical optimism, meaning expecting to develop professionally but also being concerned about the consequences of integrating digital tools into primary care, particularly regarding the importance of personal interaction between patient and provider. For theme 2, sub-themes were being in an unmanageable situation, meaning not being able to do what is perceived as best for the patient due to lack of time and resources; and following one's perception, meaning working from a gut feeling, which for our participants also meant deviating from clinical routines. CONCLUSIONS: In efforts to increase evidence-based practice and lighten the burden of clinicians in primary care, decision- and policy-makers planning the introduction of digital tools for healthy lifestyle promotion will need to explicitly define their role as complements to face-to-face encounters. Our overriding hope is that this study will contribute to maintaining meaningfulness in the patient-clinician encounter, when digital tools are added to facilitate patient behavior change of unhealthy lifestyle behaviors.

Internet-Delivered Cognitive Behavior Therapy for Adolescents With Irritable Bowel Syndrome: A Randomized Controlled Trial.

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.

Exposure-based cognitive-behavioural therapy via the internet and as bibliotherapy for somatic symptom disorder and illness anxiety disorder: randomised controlled trial.

BACKGROUND: In DSM-5 two new diagnoses, somatic symptom disorder (SSD) and illness anxiety disorder (IAD), have replaced DSM-IV hypochondriasis. There are no previous treatment studies for these disorders. Cognitive-behavioural therapy (CBT) delivered as therapist-guided or unguided internet treatment or as unguided bibliotherapy could be used to increase treatment accessibility. AIMS: To investigate the effect of CBT delivered as guided internet treatment (ICBT), unguided internet treatment (U-ICBT) and as unguided bibliotherapy. METHOD: A randomised controlled trial (RCT) where participants (n = 132) with a diagnosis of SSD or IAD were randomised to ICBT, U-ICBT, bibliotherapy or to a control condition on a waiting list (trial registration: Clinicaltrials.gov identifier NCT01966705). RESULTS: Compared with the control condition, all three treatment groups made large and significant improvements on the primary outcome Health Anxiety Inventory (between-group d at post-treatment was 0.80-1.27). CONCLUSIONS: ICBT, U-ICBT and bibliotherapy can be highly effective in the treatment of SSD and IAD. This is the first study showing that these new DSM-5 disorders can be effectively treated.

The health preoccupation diagnostic interview: inter-rater reliability of a structured interview for diagnostic assessment of DSM-5 somatic symptom disorder and illness anxiety disorder.

Somatic symptom disorder (SSD) and illness anxiety disorder (IAD) are two new diagnoses introduced in the DSM-5. There is a need for reliable instruments to facilitate the assessment of these disorders. We therefore developed a structured diagnostic interview, the Health Preoccupation Diagnostic Interview (HPDI), which we hypothesized would reliably differentiate between SSD, IAD, and no diagnosis. Persons with clinically significant health anxiety (n = 52) and healthy controls (n = 52) were interviewed using the HPDI. Diagnoses were then compared with those made by an independent assessor, who listened to audio recordings of the interviews. Ratings generally indicated moderate to almost perfect inter-rater agreement, as illustrated by an overall Cohen's κ of .85. Disagreements primarily concerned (a) the severity of somatic symptoms, (b) the differential diagnosis of panic disorder, and (c) SSD specifiers. We conclude that the HPDI can be used to reliably diagnose DSM-5 SSD and IAD.

The Brunnsviken Brief Quality of Life Scale (BBQ): Development and Psychometric Evaluation.

Measurements of subjective quality of life (QoL) are an important complement to symptom ratings in clinical research and practice. Despite there being several established QoL self-rating scales, we identified a need for a freely accessible, easy-to-use inventory, validated for use with both clinical and non-clinical samples, based on the overall life satisfaction conceptualization of QoL. The Brunnsviken Brief Quality of life scale (BBQ) was designed to meet these requirements. Items were selected by performing a factor analysis on a large data-set of QoL ratings collected previously. Six life areas (Leisure time, View on life, Creativity, Learning, Friends and Friendship, and View of self) were identified as important for overall QoL and were included in the BBQ. A psychometric evaluation was performed using two independent samples: healthy undergraduate students (n = 163), and a sample seeking treatment for social anxiety disorder (n = 568). Results suggested a unifactorial structure, with good concurrent and convergent validity, high internal and test-retest reliability, and accurate classification ability. We conclude that the BBQ is a valid and reliable measure of subjective QoL for use in clinical and research settings. The BBQ is presently available in 31 languages and can be freely downloaded from www.bbqscale.com .

Testing the Mediating Effects of Obsessive Beliefs in Internet-Based Cognitive Behaviour Therapy for Obsessive-Compulsive Disorder: Results from a Randomized Controlled Trial.

UNLABELLED: Although cognitive interventions for obsessive-compulsive disorder (OCD) have been tested in randomized trials, there are few trials that have tested the specific mechanisms of cognitive interventions, i.e. how they achieve their effects. In this study, we aimed to investigate the mediating effects of a short cognitive intervention in the treatment of OCD and used data from a recently conducted randomized controlled trial where 101 participants were allocated to either Internet-based CBT (ICBT) or to a control condition. Obsessive beliefs were measured at pre-treatment, at the time they had received the cognitive intervention, and also at post-treatment. Weekly OCD symptoms were measured throughout the 10 weeks of treatment. We hypothesized that (1) the ICBT group would have greater reductions in obsessive beliefs (controlling for change in OCD symptoms) after completing the cognitive intervention, and that (2) this reduction would, in turn, predict greater OCD symptom reduction throughout the rest of the treatment period. Contrary to our expectations, the longitudinal mediation analysis indicated that (1) being randomized to ICBT actually increased the degree of obsessive beliefs after receiving the cognitive intervention at weeks 1-3, and (2) increase in obsessive beliefs predicted better outcome later in treatment. However, when repeating the analysis using cross-sectional data at post-treatment, the results were in line with the initial hypotheses. Results were replicated when the control condition received ICBT. We conclude that, although obsessive beliefs were significantly reduced at post-treatment for the ICBT group, early increase rather than decrease in obsessive beliefs predicted favourable outcome. KEY PRACTITIONER MESSAGE: This study investigated the impact of cognitive interventions on obsessive beliefs for patients with obsessive-compulsive disorder. Results showed that a sudden increase in obsessive beliefs is not an indicator of worse treatment response. On the contrary, it is more likely that the patient is better off when having this sudden increase. Clinicians should not be alarmed if the patient has a sudden increase in obsessive beliefs, but we do recommend the clinician to investigate the reasons for this further.

Internet-delivered exposure-based cognitive-behavioural therapy and behavioural stress management for severe health anxiety: randomised controlled trial.

BACKGROUND: Exposure-based cognitive-behavioural therapy (CBT) delivered via the internet has been shown to be effective for severe health anxiety (hypochondriasis) but has not been compared with an active, effective and credible psychological treatment, such as behavioural stress management (BSM). AIMS: To investigate two internet-delivered treatments - exposure-based CBT v. BSM - for severe health anxiety in a randomised controlled trial (trial registration: NCT01673035). METHOD: Participants (n = 158) with a principal diagnosis of severe health anxiety were allocated to 12 weeks of exposure-based CBT (n = 79) or BSM (n = 79) delivered via the internet. The Health Anxiety Inventory (HAI) was the primary outcome. RESULTS: Internet-delivered exposure-based CBT led to a significantly greater improvement on the HAI compared with BSM. However, both treatment groups made large improvements on the HAI (pre-to-post-treatment Cohen's d: exposure-based CBT, 1.78; BSM, 1.22). CONCLUSIONS: Exposure-based CBT delivered via the internet is an efficacious treatment for severe health anxiety.

Internet-delivered acceptance and values-based exposure treatment for fibromyalgia: a pilot study.

BACKGROUND: Acceptance and commitment therapy (ACT) is a promising treatment option for fibromyalgia (FM). Studies have shown that many cognitive behavioral protocols can be transferred to the Internet with sustained efficacy. However, no study has investigated the effect on an Internet-delivered ACT-based protocol for FM. This study evaluated the efficacy, acceptability, and the health economic effects of an Internet-delivered acceptance and values-based exposure treatment for FM. METHODS: This open pilot trial included 41 self-referred women with a FM diagnosis. The 10-week Internet-delivered treatment included acceptance, mindfulness, work with life-values, and systematic exposure to FM symptoms and FM-related situations. Participants also had regular contact with an assigned online therapist. Assessments were made at pretreatment, post-treatment, and 6-month follow-up. RESULTS: The treatment was completed by 70% of the participants. Attrition rates were low, with 98% completing the post-treatment assessment and 90% completing the 6-month follow-up assessment. Multiple imputations were used to replace missing values. Pre- to post-treatment within-group effect sizes were in the moderate to large range (Cohen's d = 0.62-1.56) on measures of FM symptoms and impact, disability, quality of life, depression, anxiety, fatigue, and psychological flexibility. All improvements were maintained at follow-up. Economical analyses revealed significant societal cost reductions that offset the treatment costs within 2 months of treatment completion. CONCLUSIONS: An Internet-delivered psychological treatment based on acceptance and exposure principles seems to be an efficacious, acceptable, and cost-effective treatment for FM. Randomized controlled trials are needed to confirm these results.

Prediction of symptomatic improvement after exposure-based treatment for irritable bowel syndrome.

BACKGROUND: Several studies show that psychological treatments relieve symptoms for patients suffering from irritable bowel syndrome (IBS). However, there are no consistent findings that show what patient characteristics make a psychological treatment more or less likely to result in improvement. We have previously conducted a study of a newly developed internet-delivered cognitive behavioral therapy (ICBT) that emphasized exposure to IBS symptoms and IBS-related situations and reduced symptom-related avoidance. The study showed that the treatment led to improvement in IBS symptoms compared to a waiting list and that treatment gains were maintained over a 15-18 month follow-up period. The aim of the present study was to investigate several possible predictors of short- and long-term treatment outcome in terms of symptom improvement, based on data collected in the previously conducted treatment trial. METHODS: Demographics, comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability were investigated as predictors of treatment outcome in the sample consisting of 79 participants diagnosed with IBS who had undergone 10 weeks of ICBT. Predictors that were significantly correlated with symptom levels at post-treatment and follow-up were entered into multiple regression analyses that controlled for pre-treatment symptom levels. RESULTS: There were measures within each domain, i.e., comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability, with the exception of demographic data, that were correlated with the symptom levels at post-treatment and follow-up. However, when these were entered into a multiple regression analyses that controlled for pre-treatment levels, none remained a significant predictor of the post-treatment and follow-up symptomatic status. CONCLUSIONS: The study did not find any individual characteristics that made patients more or less likely to respond to the exposure-based ICBT. The finding that comorbid psychological distress did not predict outcome is in accordance with previous studies. Reliable predictors for response to any type of psychological treatment for IBS remain to be established.

Further characterization of human glucocorticoid receptor mutants, R477H and G679S, associated with primary generalized glucocorticoid resistance.

OBJECTIVE: Primary generalized glucocorticoid resistance is a rare condition characterized by a generalized insensitivity to glucocorticoids, to some extent due to an impaired function of the glucocorticoid receptor. Our earlier genetic analysis of the human glucocorticoid receptor (hGR) in 12 unrelated patients with primary generalized glucocorticoid resistance revealed two new mutations, R477H in exon 4 and G679S in exon 8 in two patients. In order to further study the molecular mechanisms underlying the phenotype of these mutations we have investigated their effect on glucocorticoid signal transduction. METHODS: We have studied the DNA-binding ability of the R477H mutant with an electrophoretic mobility shift assay (EMSA). The ability of the R477H and the G679S mutants to affect TNFα induced NF-κB activity and wild-type GR signalling was studied in transient transfection assays. RESULTS: In EMSA the R477H mutation showed a reduced ability to bind to a glucocorticoid-response element compared to the wild-type GR. In transient transfection assays both the R477H mutant and the G679S mutant showed a dominant negative effect on co-transfected wild-type GR in Cos 7 cells. However, both mutants showed full capacity to repress TNFα-induced NF-κB activity. CONCLUSION: The impaired DNA-binding of the hGR, R477H mutant may explain the severe phenotype of cortisol resistance seen with this mutation. The dominant negative effects of both mutants on wild-type GR signalling probably contribute to the patients' cortisol resistance.

Telephone versus internet administration of self-report measures of social anxiety, depressive symptoms, and insomnia: psychometric evaluation of a method to reduce the impact of missing data.

BACKGROUND: Internet-administered self-report measures of social anxiety, depressive symptoms, and sleep difficulties are widely used in clinical trials and in clinical routine care, but data loss is a common problem that could render skewed estimates of symptom levels and treatment effects. One way of reducing the negative impact of missing data could be to use telephone administration of self-report measures as a means to complete the data missing from the online data collection. OBJECTIVE: The aim of the study was to compare the convergence of telephone and Internet administration of self-report measures of social anxiety, depressive symptoms, and sleep difficulties. METHODS: The Liebowitz Social Anxiety Scale-Self-Report (LSAS-SR), Montgomery-Åsberg Depression Rating Scale-Self-Rated (MADRS-S), and the Insomnia Severity Index (ISI) were administered over the telephone and via the Internet to a clinical sample (N=82) of psychiatric patients at a clinic specializing in Internet-delivered treatment. Shortened versions of the LSAS-SR and the ISI were used when administered via telephone. RESULTS: As predicted, the results showed that the estimates produced by the two administration formats were highly correlated (r=.82-.91; P<.001) and internal consistencies were high in both administration formats (telephone: Cronbach alpha=.76-.86 and Internet: Cronbach alpha=.79-.93). The correlation coefficients were similar across questionnaires and the shorter versions of the questionnaires used in the telephone administration of the LSAS-SR and ISI performed in general equally well compared to when the full scale was used, as was the case with the MADRS-S. CONCLUSIONS: Telephone administration of self-report questionnaires is a valid method that can be used to reduce data loss in routine psychiatric practice as well as in clinical trials, thereby contributing to more accurate symptom estimates.

Internet-delivered exposure-based treatment vs. stress management for irritable bowel syndrome: a randomized trial.

OBJECTIVES: Our research group has developed an internet-delivered cognitive behavioral treatment (ICBT) for irritable bowel syndrome (IBS). We compared ICBT with internet-delivered stress management (ISM) for IBS to assess whether the effects of ICBT are specific. METHODS: This was a randomized controlled trial, including 195 self-referred participants diagnosed with IBS. The treatment interventions lasted for 10 weeks and included an online therapist contact. The ICBT emphasized acceptance of symptoms through exposure to IBS symptoms and related negative feelings. The ICBT also included mindfulness training. The ISM emphasized symptom control through relaxation techniques, dietary adjustments, and problem-solving skills. Severity of IBS symptoms was measured with the gastrointestinal symptom rating scale-IBS version (GSRS-IBS). Credibility of the treatments and expectancy of improvement were assessed with the treatment credibility scale. The participants' perceived therapeutic alliance with their online therapist was measured with the working alliance inventory. RESULTS: At post-treatment and 6-month follow-up, 192 (99%) and 169 (87%) participants returned data, respectively. At post-treatment and 6-month follow-up, we found significant differences on the GSRS-IBS, favoring ICBT. The difference on GSRS-IBS scores was 4.8 (95% confidence interval (CI): 1.2-8.4) at post-treatment and 5.9 (95% CI: 1.9-9.9) at 6-month follow-up. There were no significant differences on the treatment credibility scale or the working alliance inventory between the groups. CONCLUSIONS: Internet-delivered CBT has specific effects that cannot be attributed only to treatment credibility, expectancy of improvement, therapeutic alliance, or attention. Furthermore, a treatment based on exposure exercises specifically tailored for IBS may be a better treatment option than general stress and symptom management for IBS patients. ICBT is a promising treatment modality for IBS as it can be offered to IBS patients in much larger scale than conventional psychological treatments.

Internet-based cognitive-behavioural therapy for severe health anxiety: randomised controlled trial.

BACKGROUND: Hypochondriasis, characterised by severe health anxiety, is a common condition associated with functional disability. Cognitive-behavioural therapy (CBT) is an effective but not widely disseminated treatment for hypochondriasis. Internet-based CBT, including guidance in the form of minimal therapist contact via email, could be a more accessible treatment, but no study has investigated internet-based CBT for hypochondriasis. AIMS: To investigate the efficacy of internet-based CBT for hypochondriasis. METHOD: A randomised controlled superiority trial with masked assessment comparing internet-based CBT (n = 40) over 12 weeks with an attention control condition (n = 41) for people with hypochondriasis. The primary outcome measure was the Health Anxiety Inventory. This trial is registrated with ClinicalTrials.gov (NCT00828152). RESULTS: Participants receiving internet-based CBT made large and superior improvements compared with the control group on measures of health anxiety (between-group Cohen's d range 1.52-1.62). CONCLUSIONS: Internet-based CBT is an efficacious treatment for hypochondriasis that has the potential to increase accessibility and availability of CBT for hypochodriasis.

Acceptability, effectiveness, and cost-effectiveness of internet-based exposure treatment for irritable bowel syndrome in a clinical sample: a randomized controlled trial.

BACKGROUND: Internet-based cognitive behavior therapy (ICBT) has shown promising effects in the treatment of irritable bowel syndrome (IBS). However, to date no study has used a design where participants have been sampled solely from a clinical population. We aimed to investigate the acceptability, effectiveness, and cost-effectiveness of ICBT for IBS using a consecutively recruited sample from a gastroenterological clinic. METHODS: Sixty-one patients were randomized to 10 weeks of ICBT (n = 30) or a waiting list control (n = 31). The ICBT was guided by an online therapist and emphasized acceptance of symptoms through exposure and mindfulness training. Severity of IBS symptoms was measured with the Gastrointestinal symptom rating scale--IBS version (GSRS-IBS). Patients in both groups were assessed at pre- and post-treatment while only the ICBT group was assessed 12 months after treatment completion. Health economic data were also gathered at all assessment points and analyzed using bootstrap sampling. RESULTS: Fifty of 61 patients (82%) completed the post-treatment assessment and 20 of 30 patients (67%) in the ICBT group were assessed at 12-month follow-up. The ICBT group demonstrated significantly (p < .001) larger improvements on the IBS-related outcome scales than the waiting list group. The between group effect size on GSRS-IBS was Cohen's d = 0.77 (95% CI: 0.19-1.34). Similar effects were noted on measures of quality of life and IBS-related fear and avoidance behaviors. Improvements in the ICBT group were maintained at 12-month follow-up. The ICBT condition was found to be more cost-effective than the waiting list, with an 87% chance of leading to reduced societal costs combined with clinical effectiveness. The cost-effectiveness was sustained over the 12-month period. CONCLUSIONS: ICBT proved to be a cost-effective treatment when delivered to a sample recruited from a gastroenterological clinic. However, many of the included patients dropped out of the study and the overall treatment effects were smaller than previous studies with referred and self-referred samples. ICBT may therefore be acceptable and effective for only a subset of clinical patients. Study dropout seemed to be associated with severe symptoms and large impairment. Objective and empirically validated criteria to select which patients to offer ICBT should be developed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00844961.

Internet-based cognitive behavior therapy for obsessive compulsive disorder: a pilot study.

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. METHOD: 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. RESULTS: All participants completed the primary outcome measure at all assessment points. There were reductions in OCD symptoms with a large within-group effect size (Cohen's 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. CONCLUSIONS: 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.

Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial.

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.

A 5-Year follow-up of internet-based cognitive behavior therapy for social anxiety disorder.

BACKGROUND: Internet-based cognitive behavior therapy (CBT) has been shown to be a promising method to disseminate cognitive behavior therapy for social anxiety disorder (SAD). Several trials have demonstrated that Internet-based CBT can be effective for SAD in the shorter term. However, the long-term effects of Internet-based CBT for SAD are less well known. OBJECTIVE: Our objective was to investigate the effect of Internet-based CBT for SAD 5 years after completed treatment. METHOD: We conducted a 5-year follow-up study of 80 persons with SAD who had undergone Internet-based CBT. The assessment comprised a diagnostic interview and self-report questionnaires. The main outcome measure was the Liebowitz Social Anxiety Scale-Self-Report (LSAS-SR). Additional measures of social anxiety were the Social Interaction Anxiety Scale (SIAS) and the Social Phobia Scale (SPS). Attrition rates were low: 89% (71/80) of the participants completed the diagnostic interview and 80% (64/80) responded to the questionnaires. RESULTS: Mixed-effect models analysis showed a significant effect of time on the three social anxiety measures, LSAS-SR, SIAS, and SPS (F(3,98-102) = 16.05 - 29.20, P < .001) indicating improvement. From baseline to 5-year follow-up, participants' mean scores on the LSAS-SR were reduced from 71.3 (95% confidence interval [CI] 66.1-76.5) to 40.3 (95% CI 35.2 - 45.3). The effect sizes of the LSAS-SR were large (Cohen's d range 1.30 - 1.40, 95% CI 0.77 - 1.90). Improvements gained at the 1-year follow-up were sustained 5 years after completed treatment. CONCLUSIONS: Internet-based CBT for SAD is a treatment that can result in large and enduring effects. TRIAL REGISTRATION: Clinicaltrials.gov NCT01145690; http://clinicaltrials.gov/ct2/show/NCT01145690 (Archived by WebCite at http://www.webcitation.org/5ygRxDLfK).

Mitochondrial Coenzyme Q10 Determination Via Isotope Dilution Liquid Chromatography -Tandem Mass Spectrometry.

Coenzyme Q10 (CoQ10) is an essential part of the mitochondrial respiratory chain . Here, we describe an accurate and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determination of mitochondrial CoQ10 in isolated mitochondria . In the assay, mitochondrial suspensions are spiked with CoQ10-[2H9] internal standard (IS), extracted with organic solvents and CoQ10 quantified by LC-MS/MS using multiple reaction monitoring (MRM).

The one-carbon pool controls mitochondrial energy metabolism via complex I and iron-sulfur clusters.

Induction of the one-carbon cycle is an early hallmark of mitochondrial dysfunction and cancer metabolism. Vital intermediary steps are localized to mitochondria, but it remains unclear how one-carbon availability connects to mitochondrial function. Here, we show that the one-carbon metabolite and methyl group donor S-adenosylmethionine (SAM) is pivotal for energy metabolism. A gradual decline in mitochondrial SAM (mitoSAM) causes hierarchical defects in fly and mouse, comprising loss of mitoSAM-dependent metabolites and impaired assembly of the oxidative phosphorylation system. Complex I stability and iron-sulfur cluster biosynthesis are directly controlled by mitoSAM levels, while other protein targets are predominantly methylated outside of the organelle before import. The mitoSAM pool follows its cytosolic production, establishing mitochondria as responsive receivers of one-carbon units. Thus, we demonstrate that cellular methylation potential is required for energy metabolism, with direct relevance for pathophysiology, aging, and cancer.

Effectiveness and cost offset analysis of group CBT for hypochondriasis delivered in a psychiatric setting: an open trial.

Hypochondriasis is highly prevalent in medical settings, has detrimental effects for affected individuals, and is associated with high societal costs. Although cognitive behavior therapy (CBT) has been shown to be effective in the treatment of hypochondriasis, it is not widely available because of a lack of properly trained therapists. Therefore, it is essential to evaluate therapy forms that require less therapist time. The authors investigated the effect and economic impact of group CBT delivered in a psychiatric setting among 24 people with hypochondriasis. A within-group design with prolonged baseline was used, and all participants received 10 weeks of group-based treatment. The primary outcome measures were the Health Anxiety Inventory and the Illness Attitude Scales. Results indicate significant improvement on both measures at posttreatment and 6-month follow-up (Cohen's d = 1.03-1.72). Medical and nonmedical costs were substantially lowered. The authors conclude that group-based CBT delivered in a psychiatric setting is an effective and potentially highly cost-effective treatment for hypochondriasis.