In the Absence of Effects: An Individual Patient Data Meta-Analysis of Non-response and Its Predictors in Internet-Based Cognitive Behavior Therapy

Background: Negative effects of psychological treatments have recently received increased attention in both research and clinical practice. Most investigations have focused on determining the occurrence and characteristics of deterioration and other adverse and unwanted events, such as interpersonal issues, indicating that patients quite frequently experience such incidents in treatment. However, non-response is also negative if it might have prolonged an ongoing condition and caused unnecessary suffering. Yet few attempts have been made to directly explore non-response in psychological treatment or its plausible causes. Internet-based cognitive behavior therapy (ICBT) has been found effective for a number of diagnoses but has not yet been systematically explored with regard to those patients who do not respond.Methods: The current study collected and aggregated data from 2,866 patients in 29 clinical randomized trials of ICBT for three categories of diagnoses: anxiety disorders, depression, and other (erectile dysfunction, relationship problems, and gambling disorder). Raw scores from each patient variable were used in an individual patient data meta-analysis to determine the rate of non-response on the primary outcome measure for each clinical trial, while its potential predictors were examined using binomial logistic regression. The reliable change index (RCI) was used to classify patients as non-responders.Results: Of the 2,118 patients receiving treatment, and when applying a RCI of z ≥ 1.96, 567 (26.8%) were classified as non-responders. In terms of predictors, patients with higher symptom severity on the primary outcome measure at baseline, Odds Ratio (OR) = 2.04, having a primary anxiety disorder (OR = 5.75), and being of male gender (OR = 1.80), might have higher odds of not responding to treatment.Conclusion: Non-response seems to occur among approximately a quarter of all patients in ICBT, with predictors related to greater symptoms, anxiety disorders, and gender indicating increasing the odds of not responding. However, the results need to be replicated before establishing their clinical relevance, and the use of the RCI as a way of determining non-response needs to be validated by other means, such as by interviewing patients classified as non-responders

An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events

Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653). An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com

Cost-effectiveness of therapist-assisted internet-delivered psychological therapies for PTSD differing in trauma focus in England: an economic evaluation based on the STOP-PTSD trial

Background: Although there are effective psychological treatments for post-traumatic stress disorder (PTSD), they remain inaccessible for many people. Digitally enabled therapy is a way to overcome this problem; however, there is little evidence on which forms of these therapies are most cost effective in PTSD. We aimed to assess the cost-effectiveness of the STOP-PTSD trial, which evaluated two therapist-assisted, internet-delivered cognitive behavioural therapies: cognitive therapy for PTSD (iCT-PTSD) and a programme focusing on stress management (iStress-PTSD). Methods: In this health economic evaluation, we used data from the STOP-PTSD trial (n=217), a single-blind, randomised controlled trial, to compare iCT-PTSD and iStress-PTSD in terms of resource use and health outcomes. In the trial, participants (aged ≥18 years) who met DSM-5 criteria for PTSD were recruited from primary care therapy services in South East England. The interventions were delivered online with therapist support for the first 12 weeks, and three telephone calls over the next 3 months. Participants completed questionnaires on symptoms, wellbeing, quality of life, and resource use at baseline, 13 weeks, 26 weeks, and 39 weeks after randomisation. We used a cost-effectiveness analysis to assess cost per quality-adjusted life year (QALY) at 39 weeks post-randomisation, from the perspective of the English National Health Service (NHS) and personal social services and on the basis of intention-to-treat for complete cases. Treatment modules and the platform design were developed with extensive input from service users: service users also advised on the trial protocol and methods, including the health economic measures. This is a pre-planned analysis of the STOP-PTSD trial; the trial was registered prospectively on the ISRCTN Registry (ISRCTN16806208). Findings: NHS costs were similar across treatment groups, but clinical outcomes were superior for iCT-PTSD compared with iStress-PTSD. The incremental cost-effectiveness ratio for NHS costs and personal social services was estimated as £1921 per QALY. iCT-PTSD had an estimated 91·6% chance of being cost effective at the £20 000 per QALY threshold. From the societal perspective, iCT-PTSD was cost saving compared with iStress-PTSD. Interpretation: iCT-PTSD is a cost-effective form of therapist-assisted, internet-delivered psychological therapy relative to iStress-PTSD, and it could be considered for clinical implementation

On the measurement of procrastination : comparing two scales in six European countries

Peer reviewe

A randomised controlled trial of guided internet-based cognitive behavioural therapy for perfectionism: Effects on psychopathology and transdiagnostic processes

© 2019 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (March 2019) in accordance with the publisher’s archiving policyBackground and objectives Perfectionism is a transdiagnostic process that has been associated with a range of psychopathology and also with other transdiagnostic processes. We have previously shown that guided internet-based cognitive behavioural therapy (ICBT) can reduce symptoms of dysfunctional perfectionism, however, no impact was observed on symptoms of depression and anxiety. Here we explore the impact of guided ICBT for perfectionism on symptoms of other associated psychopathology, specifically obsessive-compulsive disorder (OCD) and eating disorders, and also on other associated transdiagnostic processes (self-esteem, intolerance of uncertainty, and self-compassion). Methods Participants who presented with clinical levels of perfectionism were randomised to an experimental group that received the intervention (n = 62), or a wait list control group (n = 58). Questionnaires assessing symptoms of OCD, eating disorders, self-esteem, intolerance of uncertainty, and fear of self-compassion were completed pre-intervention, post-intervention (12 weeks), and at follow-up (24 weeks). Between group effect sizes are reported. Results The intervention led to significant decreases in symptoms of OCD (d = −0.9; CI: -1.4, −0.4) and eating disorders (d = −0.6; CI: -1.0, −0.1), and had an impact on other transdiagnostic processes resulting in increased self-esteem (d = 0.7; CI: 0.2, 1.2), decreases in intolerance of uncertainty (d = −0.9; CI: -1.4, −0.4), and fear of self-compassion (d = −0.8; CI: -1.3, −0.3). At follow-up changes were maintained in symptoms of OCD (d = −1.3; CI: -1.8, −0.8), disordered eating (d = −0.7; CI: -1.2, −0.2), intolerance of uncertainty (d = −0.8; CI: -1.2, −0.3), and fear of self-compassion (d = −1.0; CI: -1.5, −0.5). Conclusions Guided ICBT for perfectionism improves associated psychopathology and transdiagnostic processes. ClinicalTrials.gov registration no. NCT02756871

The fundamental constants and their variation: observational status and theoretical motivations

This article describes the various experimental bounds on the variation of the fundamental constants of nature. After a discussion on the role of fundamental constants, of their definition and link with metrology, the various constraints on the variation of the fine structure constant, the gravitational, weak and strong interactions couplings and the electron to proton mass ratio are reviewed. This review aims (1) to provide the basics of each measurement, (2) to show as clearly as possible why it constrains a given constant and (3) to point out the underlying hypotheses. Such an investigation is of importance to compare the different results, particularly in view of understanding the recent claims of the detections of a variation of the fine structure constant and of the electron to proton mass ratio in quasar absorption spectra. The theoretical models leading to the prediction of such variation are also reviewed, including Kaluza-Klein theories, string theories and other alternative theories and cosmological implications of these results are discussed. The links with the tests of general relativity are emphasized.Comment: 56 pages, l7 figures, submitted to Rev. Mod. Phy

Negative effects of Internet-based cognitive behavior therapy : Monitoring and reporting deterioration and adverse and unwanted events

Internet-based cognitive behavior therapy (ICBT) has the potential of providing many patients with an effective form of psychological treatment. However, despite helping to improve mental health and well-being, far from everyone seem to benefit. In some cases, negative effects may also emerge. The overall aim of the present thesis was to establish the occurrence and characteristics of such incidents in ICBT using a combination of quantitative and qualitative methods. Study I determined deterioration, non-response, and adverse and unwanted events in a sample of 133 patients undergoing ICBT for social anxiety disorder. The results indicated that up to 6.8% fared worse during the treatment period, depending on the self-report measure and time point, as determined using the Reliable Change Index (RCI), while the non-response rate was between 29.3 to 86.5% at post treatment assessment, and 12.9% experienced other negative effects. Study II investigated the responses to open-ended questions on adverse and unwanted events among 556 patients in four separate clinical trials of ICBT; social anxiety disorder, panic disorder, major depressive disorder, and procrastination. In total, 9.3% reported negative effects, with a qualitative content analysis revealing two categories and four subcategories; patient-related, i.e., gaining insight and experiencing new symptoms, and treatment-related, i.e., difficulties applying the treatment interventions and problems related to the treatment format. Study III explored the number of patients achieving reliable deterioration, as determined using the RCI on the individual raw scores of 2866 patients from 29 clinical trials of ICBT. The results showed that the deterioration rate was higher among patients in a control condition, 17.4%, in comparison to treatment, 5.8%. Predictors were related to decreased odds of deterioration for patients receiving treatment; clinical severity at pre treatment assessment, being in a relationship, having a university degree, and being older. As for the control condition, only clinical severity at pre treatment assessment was associated with decreased odds of deterioration. Study IV examined a newly developed self-report measure for monitoring and reporting adverse and unwanted events, the Negative Effects Questionnaire. The results suggested a six-factor solution with 32 items; symptoms, quality, dependency, stigma, hopelessness, and failure. One-third of the patients reported experiencing unpleasant memories, stress, and anxiety, with novel symptoms and a lack of quality in the treatment and therapeutic relationship having the greatest negative impact. The general finding of the present thesis is that negative effects do occur in ICBT and that they are characterized by deterioration, non-response, and adverse and unwanted events, similar to psychological treatments delivered face-to-face. Researchers and clinicians in ICBT are recommended to monitor and report negative effects to prevent a negative treatment trend and further the understanding of what might contribute to their incidents. Future research should investigate the relationship between negative effects and treatment outcome, especially at follow-up, to examine if they are transient or enduring. Also, interviews could be conducted with those achieving reliable deterioration to explore if and how it is experienced by the patients and to see if it is attributed to the treatment interventions or other circumstances.Internetbaserad kognitiv beteendeterapi (IKBT) har goda förutsättningar att kunna bli en form av psykologisk behandling som på ett effektivt sätt hjälper patienter med att hantera sin psykiska ohälsa och förbättra sitt välmående. Trots detta är det dock långtifrån alla som tycks bli bättre. För en del kan det till och med resultera i negativa effekter. Det övergripande syftet med denna avhandling har således varit att undersöka förekomsten av sådana fall och hur dessa uttrycks, såväl med kvantitativa som kvalitativa metoder. Studie I fastställde andelen försämrade, oförändrade samt andra ogynnsamma eller oönskade händelser bland 133 personer som behandlades med IKBT för social ångest. Resultatet visade att uppemot 6,8 % försämrades under sin behandlingsperiod beroende på vilket självskattningsformulär respektive tidpunkt som studerades, beräknat enligt metoden Reliable Change Index (RCI). Likaså var 29,3 % till 86,5 % oförändrade vid eftermätningen samt att 12,9 % rapporterade andra former av negativa effekter. Studie II undersökte svaren på öppna frågor som gällde ogynnsamma eller oönskade händelser bland 556 patienter i fyra olika kliniska studier med IKBT; social ångest, paniksyndrom, egentlig depressionsepisod och prokrastinering. Totalt sett rapporterade 9,3 % att de hade erfarit negativa effekter, vilka analyserades med hjälp av kvalitativ innehållsanalys. Två övergripande kategorier och fyra subkategorier framkom; patientrelaterade, som ökad insikt respektive nya symptom, samt behandlingsrelaterade, som svårigheter att implementera behandlingsinterventionerna respektive problem med behandlingsformatet. Studie III utrönte andelen patienter som försämrades i enlighet med RCI, baserat på insamlad rådata från 2866 personer i 29 olika kliniska studier med IKBT. Resultatet visade att försämring var mer förekommande hos de som var i en kontrollgrupp, 17,4 %, jämfört med de som fick behandling, 5,8 %. Bland de som genomgick behandling existerade det även ett par prediktorer som innebar lägre odds för försämring; större svårigheter vid förmätningen, att befinna sig i en relation, att ha en universitetsutbildning respektive att vara äldre. För de som var i en kontrollgrupp var enbart större svårigheter vid förmätningen relaterat till lägre odds för försämring. Studie IV testade ett nykonstruerat självskattningsformulär; Negative Effects Questionnaire. Resultatet visade på en faktorlösning med sex faktorer och 32 påståenden; symptom, kvalitet, beroende, stigma, hopplöshet respektive misslyckande. En tredjedel av personerna svarade att de hade upplevt obehagliga minnen, stress och ångest, samtidigt som nya symptom och bristande kvalitet i både behandlingen respektive den terapeutiska relationen hade haft störst negativ inverkan på dem. Den generella slutsatsen av denna avhandling är således att negativa effekter förekommer i IKBT och att de kännetecknas av försämring, ett oförändrat tillstånd samt andra ogynnsamma eller oönskade händelser, något som liknar tidigare forskning av psykologisk behandling som bedrivs ansikte-mot-ansikte. Forskare och behandlare i IKBT rekommenderas att övervaka och rapportera negativa effekter i syfte att förhindra en negativ utveckling i behandlingen samt för att öka kunskapen om vad som kan bidra till deras förekomst. Framtida forskning bör undersöka relationen mellan negativa effekter och behandlingsutfall utifrån längre tidsperspektiv för att se om dess påverkan är övergående eller ihållande. Vidare kan till exempel intervjuer utföras med de patienter som har försämrats för att ta reda på om och hur det uppfattas samt huruvida det har förorsakats av behandlingen eller andra omständigheter.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: In press.</p

Opportunities and restrictions – a discourse analysis on lesbian womens’ experiences of creating a family through assisted reproduction in Swedish public medical services

Syftet med studien är att utforska och förstå de resonemang lesbiska par begagnar sig av i beslutsfattandet om reproduktionsmetod. Här ingår även berättelser kring de erfarenheter paren har av möten med professionella inom svensk sjukvård och myndighetsutövning. Studien består av tio intervjuer med lesbiska par, vilka har fått barn inom den offentliga sjukvården sedan detta blev tillgängligt den 1 juli år 2005. Materialet har analyserats med hjälp av kvalitativ metod i det diskursanalytiska fältet. Resultatet visar att parens beslut har föregåtts av en process där alternativ har vägts mot varandra. Här återfinns två typer av tolkningsrepertoarer där svensk sjukvård har fått företräde på grundval av externa omständigheter. Den ena kretsar kring ett samhällsperspektiv där olika juridiska faktorer används retoriskt för att framhäva valet som rimligt. Den andra utgår ifrån ett familjeperspektiv, där det externa synliggörs genom konsekvenserna de får för den egna familjebilden.  Resultatet visar samtidigt på de erfarenheter paren har av att genomföra assisterad befruktning i Sverige. Dels beskrivs upplevelserna utifrån utsatthet, där rollen som vårdtagare och homosexuell framställs som en dubbel sårbarhet. Dels framkommer resonemang om acceptans, genom vilken paren hanterar och föregår bristande bemötande med olika argument som reducerar potentiella stressorer