title
stringlengths 1
1.19k
| keywords
stringlengths 0
668
| concept
stringlengths 0
909
| paragraph
stringlengths 0
61.8k
| PMID
stringlengths 10
11
|
|---|---|---|---|---|
Appearance-based rejection sensitivity (ARS-D) | As hypothesized, the ARS-D decreased between pretreatment and posttreatment by | PMC10683190 |
||
Preliminary findings on acceptance | PMC10683190 |
|||
Dropout rates | PHYSICAL ILLNESS | Of the 24 patients enrolled at pretreatment assessment, 11 patients (45.8%) terminated the BEAT program prematurely (dropouts): Of these, one (9.1%) dropped out after the pretreatment assessment in the waiting-time period, seven (63.6%) during the nine treatment sessions of the active treatment, and three (27.3%) during the follow-up period. Considering dropout reasons, for three patient (27.3%) the BEAT program was too demanding, especially the email-guided self-help sessions, two patients (18.2%) cancelled the first workshop due to time issues or illness, two patients (18.2%) had developed a physical illness that needed prior treatment and for four patients (36.4%) dropout reasons were unknown as they didn’t reply to emails and phone calls. Compared to patients who remained in the study, those who terminated BEAT prematurely did not differ with respect to pretreatment values of age, ARS-D, BDI-FS, EDE-Q global score, BMI-SDS, and WBQ ( | PMC10683190 |
|
Patient’s subjective evaluation of the BEAT program | Mean treatment satisfaction of the completers (Treatment satisfaction with different aspects of BEAT | PMC10683190 |
||
Limitations | There are limitations with respect to the findings of the current pilot study. First of all, the sample size was small and our findings need to be reevaluated in larger samples. In order to prevent the risk of early dropout due to lack of motivation, we further kept the waiting period short (two weeks), which contrasts with waiting periods for psychotherapy of up to two months in Switzerland [ | PMC10683190 |
||
Conclusion | eating disorder, eating disorders, depressive symptoms | PATHOLOGY | The present pilot study documents initial evidence of the effects of a blended treatment program (BEAT) for youth aged 14 to 24 suffering from LOC, including elements of CBT for eating disorders and interventions to improve interpersonal emotion regulation. Large preliminary treatment effects were found for LOC psychopathology, co-occurring depressive symptoms, appearance-based rejection sensitivity and general eating disorder pathology. Patients who completed treatment with BEAT expressed high treatment satisfaction, but a considerable dropout rate calls for more detailed analyses in attrition to blended and online treatments in this age group. Larger, randomized between-group control designs are needed to more thoroughly test the specific effects of BEAT. | PMC10683190 |
Acknowledgements | RECRUITMENT | We would like to thank the participating patients and postgraduate psychologist in psychotherapy training for trusting us with the scientific analysis of their work. We thank Master and Bachelor students at the University of Fribourg who helped with recruitment and study procedures. | PMC10683190 |
|
Authors’ contributions | SM, FF, and AHM contributed to the conception and conduction of the study. SM designed and supervised the study, including data collection and safety of included patients. FF carried out the data collection, study organization and administration. AHM carried out data analysis and interpretations were discussed with SM, FF and MR. FF wrote the first draft of the manuscript, which was reviewed and edited by SM, AHM and MR. All authors read and approved the final manuscript. | PMC10683190 |
||
Funding | This study was funded by the Research Pool of the University of Fribourg, Switzerland (no project number available). The funder was not involved in any part of this study. | PMC10683190 |
||
Availability of data and materials | The datasets generated and/or analyzed during the current study are not publicly available due to sensible data but are available from the last author ([email protected]) on reasonable request. | PMC10683190 |
||
Declarations | PMC10683190 |
|||
Ethics approval and consent to participate | All participants provided written informed consent before participating. The study complied with the Declaration of Helsinki and was reviewed and approved by the Ethics Committee of the Canton Bern, Switzerland (ID: 2018–00230).In Switzerland, young people even under the age of 14 have the right of non-information of their legal guardians with respect to a participation in a psychotherapeutic treatment. The capacity to judge is deemed to exist from around the age of 14. Therefore, young people under the age of 16 have the right to receive therapeutic services without the consent of their legal representatives (Swiss Civil Code: Art. 305 Abs. 1 and Art. 19c ZGB; Federal Constitution of the Swiss Confederation: Art. 11 Abs. 2 BV). In accordance with Swiss law, we therefore examined at the end of the information session, whether youth did fully understand the study procedure and their rights. If this was approved, we did no longer have the right to inform the parents, unless the person was either suicidal or a threat to others (Swiss Criminal Code: Art. 321 StGB). Based on this right, we forewent not to obtain parental consent and adolescents under the age of 18 years were not obliged to inform legal guardians about their participation. However, adolescents were motivated to inform their parents/ legal representatives about the study and a legal representative study information was provided if adolescents agreed to inform their representatives. Therefore, informed consents were signed either by participating youth alone or together with their legal guardians.This procedure has been submitted and approved by the cantonal ethics committee. The Journal examined and approved the legal basis of this procedure as well (Munsch et al. 2021). | PMC10683190 |
||
Consent for publication | Not applicable. | PMC10683190 |
||
Competing interests | The authors declare no competing interests. | PMC10683190 |
||
References | PMC10683190 |
|||
Materials and methods | IUT, depression | RECRUITMENT | 64 patients with GAD at a large primary health care center in Stockholm, Sweden, were randomized to IUT or MCT. Feasibility outcomes included participant recruitment and retention, willingness to receive psychological treatment, and therapists’ competence in and adherence to treatment protocols. Self-reported scales were used to assess treatment outcomes, including worry, depression, functional impairment, and quality of life. | PMC10266649 |
Results | IUT | RECRUITMENT | Recruitment was satisfactory, and dropout was low. On a scale from 0 to 6, participants were satisfied with participating in the study (M = 5.17, SD = 1.09). Following brief training, therapists’ competence was rated as moderate, and adherence was rated as weak to moderate. From pre- to post-treatment, reductions on the primary treatment outcome measure of worry were of a large effect size and statistically significant in both the IUT and MCT conditions (Cohen’s | PMC10266649 |
Conclusion | IUT, GAD in primary health care. | It is feasible to carry out a full-scale RCT to compare the effects of IUT to MCT for patients with GAD in primary health care. Both protocols seem effective, and MCT seems superior to IUT, but a full-scale RCT is needed to confirm these conclusions. | PMC10266649 |
|
Trial registration | ClinicalTrials.gov (no. | PMC10266649 |
||
Data Availability | Data cannot be shared publicly because of Swedish legal and ethical restrictions related to sensitive patient information. Data are available from Region Stockholm (contact via data protection officer Camilla Heise Löwgren, | PMC10266649 |
||
Introduction | anxiety disorders, IUT, psychiatric, depression, somatic complaints | SECONDARY, RECRUITMENT, DISORDERS | Across the world, primary health care is the setting where most people with common mental disorders receive diagnosis and treatment [Cognitive behavioral therapy (CBT) is an effective treatment for several anxiety disorders [Although CBT is not recommended as the first-hand treatment for GAD, previous meta-analyses suggest that it is an effective treatment [One of the main CBT protocols used for GAD in Sweden is intolerance-of-uncertainty therapy (IUT) [Another protocol for treating GAD is metacognitive therapy (MCT) [Although both IUT and MCT are well-established protocols, only one previous study has compared the effectiveness of IUT and MCT in the treatment of GAD [A full-scale randomized controlled trial (RCT) designed to evaluate effects of CBT and MCT in primary health care patients with GAD could investigate whether CBT and/or MCT is as effective in this setting as in psychiatric care. People with GAD who seek primary care for their symptoms typically present with somatic complaints [However, to the best of our knowledge, neither protocol has been evaluated in a primary health care setting. There are therefore several uncertainties about the feasibility of performing a full-scale RCT designed to compare the effectiveness of the two protocols for patients with GAD in primary health care, including recruiting and retaining participants [Thus, the primary aim of the present randomized controlled pilot trial was to investigate the feasibility of a future full-scale RCT designed to compare the effects of IUT and MCT in primary health care patients with GAD. Feasibility outcomes included participant recruitment and retention, willingness to receive psychological treatment, and therapists’ competence in and adherence to treatment protocols. A secondary aim was to explore the preliminary effects of the two treatments on measures of worry, depression, functional impairment, and quality of life. | PMC10266649 |
Materials and methods | PMC10266649 |
|||
Setting | DISORDERS | The study was conducted between 2018 and 2020 at Liljeholmen Primary Health Care Center, Stockholm, Sweden, which is one of the country’s largest primary health care centers and serves 31,000 patients. The center has a team of therapists who assess and treat patients with mild to moderate common mental disorders in accordance with national clinical guidelines [ | PMC10266649 |
|
Participants | psychiatric disorder, bipolar disorder, cognitive impairment, psychosis | DISORDER | Patients at Liljeholmen Primary Health Care Center with a primary diagnosis of GAD were invited to participate. Patients were excluded from the study if they were younger than 18 years; unable to speak Swedish; or had a severe psychiatric disorder (e.g., psychosis, bipolar disorder), cognitive impairment, substance use disorder, or other ongoing psychological treatment. Patients who had initiated or altered a psychopharmaceutical prescription less than six weeks prior to study inclusion were also excluded.Because assessing treatment effectiveness was not a primary aim, a power calculation was not conducted, but a goal of recruiting at least 50 participants was set to enable us to assess feasibility and preliminary effectiveness. | PMC10266649 |
Treatments | Both treatments were protocol-based. The protocols ( | PMC10266649 |
||
Therapists | IUT | RECRUITMENT | Therapists were recruited from the team that provides psychological treatment at Liljeholmen Primary Health Care Center. The mean age of the ten therapists was 43.9 years (SD = 7.9), nine were women, six were clinical psychologists, and four were social workers. The therapists had a mean of 10.1 years (SD = 5.8) of clinical experience, and 4.5 years (SD = 7.0) of experience working with patients with GAD. Four therapists self-selected to provide IUT and six self-selected to provide MCT. Therapists provided either IUT or MCT throughout the whole trial. All therapists had completed basic training in CBT, and one had completed advanced training to become a psychotherapist. Before recruitment and not as part of the present study, three therapists had participated in specific training in treating GAD: a one-day workshop on MCT (one IUT therapist), a one-day workshop on applied relaxation (one IUT therapist), and a two-day workshop on applied relaxation (one MCT therapist). | PMC10266649 |
Training and supervision | Although therapists already used the Mini International Neuropsychiatric Interview (M.I.N.I.) [ | PMC10266649 |
||
Assessments | PMC10266649 |
|||
Feasibility | IUT, worry, anxiety | SESSION, RECRUITMENT | Feasibility was assessed with several measures, including flow of recruitment, retention, participants willingness to receive psychological treatment, and therapist competence in and adherence to the treatment protocols. Participants completed an evaluation form post-treatment. It included items on perceptions of the number of self-report measures, the procedure of audio-recording the sessions, the pace of treatment, the extent to which participants believed that their problems with worry and anxiety had predominantly psychological causes, and overall satisfaction with treatment. Responses were made on a scale that ranged from 0 to 6, where 0 was the lowest and 6 the highest rating, and 3 represented “lagom,” a Swedish term that generally has a positive connotation and means “just right” or “just enough.” The evaluation form included a free-text item where participants could provide additional comments about the study or treatment.All treatment sessions were audio-recorded so that therapists would not know which sessions would be selected to assess their competence in the treatment that they provided and their adherence to the protocol. For each therapist, three recordings of session five were randomly selected for assessment of both competence and adherence. Session five was chosen to ensure that a treatment session was selected. As competence and adherence are somewhat overlapping constructs [Competence in IUT was assessed with the Cognitive Therapy Scale-Revised (CTS-R) [ | PMC10266649 |
Treatment effects | depression, worry, anxiety | Severity of worry was assessed with the 16-item Penn State Worry Questionnaire (PSWQ) [Severity of worry and depression was assessed pre-treatment, mid-treatment (following the fifth session), post-treatment, and at follow-up six months after the end of treatment. Functional impairment and quality of life were assessed pre-treatment, post-treatment, and at follow-up. At the follow-up assessment, participants completed a survey about any additional psychological, psychopharmaceutical, or other treatment for anxiety or depression that they had received following treatment completion. Data on medication and sick leave during the study period (from inclusion to follow-up) were collected from participants’ medical records. | PMC10266649 |
|
Procedure | RECRUITMENT | Recruitment started in spring 2018 and ended in autumn 2019. Treatments were completed in January 2020. The last 6-month follow-up, via regular mail and online forms, finished in August 2020.Patients who visited their general practitioner at Liljeholmen Primary Health Care Center for mental health problems and/or medically unexplained symptoms were referred to the therapist team for diagnostic assessment with the M.I.N.I. [ | PMC10266649 |
|
Flow of participants in the study. | To allocate each participant, a research nurse phoned an independent assistant who had access to a randomization list generated by another independent assistant using an online service (At inclusion, the research nurse collected information in a survey format on the background characteristics of participants ( | PMC10266649 |
||
Baseline characteristics of participants. | IUT, anxiety disorder | Abbreviations: IUT = intolerance-of-uncertainty therapy; MCT = metacognitive therapy; GAD = generalized anxiety disorder; CBT = cognitive behavioral therapy. | PMC10266649 |
|
Statistical analyses | IUT | DER | Statistical analyses were performed with SPSS (Version 27, SPSS Inc., Chicago, IL). Proportions, means, and standard deviations (SDs) were calculated for feasibility measures. Differences in session attendance between the IUT and MCT groups were investigated with an independent t-test and differences in dropout with a Fisher’s exact test. A descriptive analysis investigating the normality of continuous outcome variables was performed. In the preliminary evaluation of treatment effects, multilevel modeling was used to estimate the effects of time and of time by group on continuous outcome measures from the pre-treatment to the post-treatment assessment and from the post-treatment to the follow-up assessment. The maximum likelihood method was used to estimate model parameters. A first-order autoregressive structure with homogenous variances provided the best fit and was thus used as the covariance structure. We started with a basic model with a fixed intercept, we then built models adding random intercept and slope, and finally an interaction term. Allowing intercepts to vary (i.e., random intercepts model) means that the outcome variable is at different levels prior to treatment (i.e., the symptom level varies across participants). Similarly, allowing slopes to vary means that the change trajectory may vary across participants. Finally, to investigate whether treatment condition moderated the effect, an interaction term of time (fixed effect; treatment period) and treatment condition (fixed effect; IUT or MCT) was added to the model with random intercept and slope. Each model’s fit to observed data was evaluated with the likelihood ratio test. Models with significantly better fit than previous models were retained. Standardized effect sizes for between-group effects at mid-treatment, post-treatment, and follow-up were calculated as Cohen’s Treatment response was assessed with the reliable change index [To assess recovery rates, two procedures were employed that combine statistically reliable change with clinically meaningful change. First, an RCI of 7 points and a cut-off of 53 points on the PSWQ as used in the study by van der Heiden and colleagues [ | PMC10266649 |
Ethical approval and consent to participate | Ethical approval for this study was obtained from the Regional Ethical Review Board in Stockholm, Sweden (2018/505-31). The research was conducted in accordance with the World Medical Association Declaration of Helsinki, and all patients and therapists provided written informed consent. | PMC10266649 |
||
Results | PMC10266649 |
|||
Feasibility | IUT | RECRUITMENT | Of the 69 patients who met the study criteria, 64 provided written informed consent and were included in the study. The flow of recruitment, an important measure of future RCT feasibility, was good, with an average of 4.6 (SD = 2.7, range = 1–10) patients consenting to participate and being included in the study per month from July 2018 to August 2019. The majority (81%) of participants were women, and the mean duration of GAD was 14 years (Participants in the IUT group attended a mean of 10.5 (SD = 2.0) sessions, and participants in the MCT group attended a mean of 8.5 (SD = 3.1) sessions. An independent sample t-test showed that participants in the IUT group attended significantly more sessions (t = 3.15, p = .003, d = 0.78). Seven participants (10.9%) dropped out during the treatment period (In the total sample, participants believed that the number of measures was “lagom” (just right) (M = 3.25, SD = 0.88). They viewed being recorded during the sessions neither positively nor negatively (M = 3.53, SD = 1.25) and thought the pace of treatment was “lagom” (M = 3.29, SD = 0.70). Furthermore, participants believed to some extent that their problems had predominantly psychological causes (M = 4.69, SD = 1.22). Overall, they were satisfied with participating in the study (M = 5.17, SD = 1.09). There were non-significant between-group differences in means (ts = -0.79–1.75, ps = .085-.735, ds = 0.09–0.46), except for the number of measures. Participants in the MCT group believed to a larger extent that there were too many measures than participants in the IUT group (On average, the four IUT therapists treated eight participants each (range = 4–12), and the six MCT therapists five participants each (range = 2–10). For IUT therapists, the CTS-R item mean was 2.9 (SD = 0.4), representing a level of competence between “advanced beginner” and “competent”, and close to the corresponding widely adopted competence threshold mean item score of 3 [ | PMC10266649 |
Treatment effects | PMC10266649 |
|||
Changes in symptoms of worry | IUT, worry | Within-group analyses showed that both IUT and MCT resulted in statistically significant reductions in the severity of worry as assessed with the PSWQ ( | PMC10266649 |
|
Estimated marginal means and standard deviations for the PSWQ, PHQ-9, WHODAS, and the SWLS from pretreatment to 6-month follow-up. | IUT | Abbreviations: PSWQ: Penn State Worry Questionnaire; PHQ-9: Patient Health Questionnaire 9; WHODAS: World Health Organization Disability Assessment Schedule 2.0; SWLS: Satisfaction with Life Scale; IUT: intolerance-of-uncertainty therapy; MCT: metacognitive therapy.We observed large within-group effect sizes from pre-treatment to mid-treatment (IUT: F(60.09) = 13.39, p = .001; MCT: F(55.46) = 21.83, p < .001) and from pre-treatment to post-treatment (IUT: F(58.82) = 32.54, p < .001; MCT: F(66.84) = 71.85, p < .001) ( | PMC10266649 |
|
Within-group and between-group effect sizes with 95% confidence intervals for the PSWQ, PHQ-9, WHODAS, and the SWLS from pre-treatment to 6-month follow-up. | IUT | Abbreviations: PSWQ: Penn State Worry Questionnaire; PHQ-9: Patient Health Questionnaire 9; WHODAS: World Health Organization Disability Assessment Schedule 2.0; SWLS: Satisfaction with Life Scale; IUT: intolerance-of-uncertainty therapy; MCT: metacognitive therapy; d = model-based Cohen’s d effect sizeBetween post-treatment and the 6-month follow-up, worry scores remained stable in the IUT group (F(57.81) = 0.01, p = .980) and the MCT group (F(46.39) = 1.18, p = .283) (At post-treatment, 71.9% of the participants in the IUT group and 96.3% in the MCT group met the criteria for reliable improvement (≥7 point decrease in PSWQ score). One participant in the IUT group and none in the MCT group met the criteria for reliable deterioration (≥7 point increase in PSWQ score). At the 6-month follow-up, 67.9% of the participants in the IUT group and 82.6% in the MCT group met the criteria for reliable improvement. At follow-up, one participant in each group met the criteria for reliable deterioration. Significantly more participants in the MCT group than in the IUT group met the criteria for reliable improvement at post-treatment (χRegardless of whether we used a PSWQ cut-off score of 47 points, as in the Nordahl study [ | PMC10266649 |
|
Changes in depressive symptoms | IUT, depressive symptoms | Between pre-treatment and mid-treatment, IUT and MCT both statistically significantly reduced depressive symptoms as measured by the PHQ-9 (IUT: F(61.54) = 5.32, p = .024; MCT: F(57.00) = 12.97, p = .001) ( | PMC10266649 |
|
Changes in functional impairment | IUT, MCT reduced functional impairment | Between pre-treatment and post-treatment, only MCT reduced functional impairment statistically significant as measured by the WHODAS (IUT: F(63.51) = 3.72, p = .058; MCT: F(58) = 51.29, p < .001) ( | PMC10266649 |
|
Changes in quality of life | IUT | Between pre-treatment and post-treatment, MCT resulted in a significant improvement in quality of life as measured by the SWLS (F(55) = 13.01, p = .001), whereas IUT did not (F(63.84) = 1.58, p = .213) ( | PMC10266649 |
|
Changes in pharmaceutical treatment | IUT | Consistent with the study protocol, pharmaceutical treatment for mental health problems remained stable during the treatment period for most participants. However, four participants in the IUT group initiated pharmaceutical treatment during the study of which three ceased pharmaceutical treatment prior to post-treatment. At post-treatment, 29 participants received pharmaceutical treatment for mental health problems. Nine of these 29 ceased pharmaceutical treatment by follow-up (three from the IUT group and six from the MCT group). Two participants in the IUT group reduced their dosage. One participant in the IUT group started pharmaceutical treatment at the follow-up assessment. Seven participants ceased all use of pharmaceuticals for mental health problems between post-treatment and follow-up; six of them were in the MCT group. | PMC10266649 |
|
Changes in sick leave | IUT, depression, stress disorders, stress disorder | At pre-treatment, six participants (two in the IUT group, four in the MCT group) were on sick leave between 25% of full time and full time: three for stress disorders, two for depression, and one for GAD. Of these participants, one in the IUT group remained on full-time sick leave for depression at post-treatment and follow-up. In addition, one participant in the MCT group who had not been on sick leave at pre-treatment was on 50% sick leave for a stress disorder at post-treatment. At follow-up, one participant in the IUT group was on 50% sick leave for GAD, and one participant in the MCT group was on full-time sick leave for a stress disorder. | PMC10266649 |
|
Additional treatment received at follow-up | IUT, depression, anxiety | At 6-month follow-up, four of the 48 participants who responded to the follow-up questionnaire (8.3%) had received additional CBT since the end of the study, two in each group. Twelve participants (25.0%) had received pharmaceutical treatment for anxiety or depression, seven in the IUT group and five in the MCT group. One participant had received other treatment for anxiety due to intimate partner violence. | PMC10266649 |
|
Discussion | PMC10266649 |
|||
Main findings | IUT, depressive symptoms | RECRUITMENT, RECRUITMENT, SECONDARY | The primary aim of the present pilot study was to investigate the feasibility of a future RCT designed to compare the effectiveness of IUT and MCT in primary health care patients with GAD. There were several uncertainties about feasibility because, to the best of our knowledge, neither treatment had previously been evaluated in a primary health care setting. These included participant recruitment and retention, willingness to receive psychological treatment, and therapists’ competence in and adherence to treatment protocols. The results showed that patients with GAD were willing to participate. Recruitment was good, and the dropout rate was low. Participants reported that they were satisfied with taking part in the study and with the treatment they received. They believed to some extent that their symptoms had predominantly psychological causes, which suggests that it is feasible to provide psychological treatment to these patients in primary health care. Following brief training in the protocols, therapists in both groups showed some competence in the treatment they delivered. MCT therapists’ adherence was rated significantly lower than that of IUT therapists.The secondary aim of the present pilot study was to conduct a preliminary evaluation of the effects of the two treatments. Both IUT and MCT significantly reduced worry from pre-treatment to post-treatment, and the effect sizes were large. Similarly, depressive symptoms decreased significantly in both treatment groups; effect sizes were moderate for IUT and large for MCT. However, functional impairment declined significantly only in the MCT group. Similarly, quality of life increased significantly from pre-treatment to post-treatment in the MCT group only. From post-treatment to the 6-month follow-up, effects on outcome measures were maintained. MCT was the superior treatment for all outcomes from pre-treatment to post-treatment, and the between-group effect sizes were large, except for quality of life, which did not differ between treatment groups. From post-treatment to follow-up, the only significant difference between groups was in functional impairment, which improved in the IUT group. At post-treatment and follow-up, more MCT than IUT participants had a reliable reduction in worry and had recovered from worry. Moreover, not only was MCT the more effective treatment, but on average, it was two sessions shorter than IUT. If the RCT replicates these findings, it would mean that MCT is more effective than IUT and can be delivered in a shorter course of therapy, which would make it useful in primary health care. | PMC10266649 |
Comparison to other studies | PMC10266649 |
|||
Feasibility | IUT, psychiatric | The only previous study comparing IUT and MCT was conducted in a psychiatric outpatient setting and did not aim to test feasibility [In the current study, following brief training in the protocols, the therapists from regular primary health care showed some competence in IUT and MCT, but the MCT therapists’ mean adherence was assessed as significantly lower than that of the IUT therapists. This may represent a real difference or reflect the fact that the response scale of the adherence measures was not calibrated, and the assessors may thus have interpreted it differently. Furthermore, only recordings of session 5 were assessed. We will therefore take steps to improve inter-rater reliability and include treatment integrity checks throughout the treatment period in the future RCT. At least two independent assessors will assess each measure, and more than one session will be assessed. In the previous study [ | PMC10266649 |
|
Treatment effects | IUT | As in the current study, in earlier studies that compared MCT to CBT for GAD, all treatments reduced worry, but MCT reduced worry significantly more [In this feasibility study, we did not assess potential mediators of effect, which could be of interest to include in the future RCT. However, one explanation for the better results in the MCT group may be that IUT only targets positive metacognitions about worry [ | PMC10266649 |
|
Strengths and limitations | sleep disturbance, fatigue, IUT, worry, depression, irritability | RECRUITMENT | This study had several strengths. Generalizability to other primary health care settings was strengthened by the recruitment of patients and therapists from regular primary health care and by keeping exclusion criteria to a minimum. In addition to measuring symptoms of worry and depression, the study also investigated functional impairment, quality of life, medication use, sick leave, and participants’ perceptions of the treatments and of study participation. Moreover, several therapists were involved in treatment, all sessions were audio-recorded, the therapists were blinded to which session would be assessed, and the therapists’ competence in and adherence to protocol were assessed by independent assessors.The study also had several limitations. First, only one large primary health care center in an urban area participated, which reduces the generalizability of the findings to other primary health care populations. Moreover, despite randomization, the distribution is uneven between the groups regarding married/cohabiting versus living alone, which may have affected the results. Second, therapists’ competence in and adherence to the protocols was assessed in only a small proportion of the sessions as one of several feasibility measures, and inter-rater reliability was not ascertained. Third, due to the lack of an inactive control group, no conclusive causal inferences of the effects of IUT and MCT can be made; however, because of the differential effects it is likely that the treatments were at least partly responsible. Fourth, therapists were not randomized or allocated to perform both IUT and MCT, but rather chose which treatment they wanted to provide. Thus, their prior interest and competence in the treatment they selected could have biased the findings.Finally, no sample size calculation was conducted, as the primary aim of the present study was to investigate feasibility. The mostly large effect sizes nevertheless suggest that the preliminary results regarding treatment effects are reliable. However, the lack of a sample size calculation constitutes a major limitation that may affect generalizability of the results.To obtain a fuller picture of how treatment may improve the complex symptoms of GAD, in addition to assessing worry, future studies could investigate the severity of other common symptoms in patients with GAD, such as fatigue, sleep disturbance, irritability, and muscle tension. Because patients with GAD visit primary health care frequently for a variety of symptoms, future studies should also consider use of care as an outcome. Furthermore, future studies should consider using clinician-assessed measures rather than relying solely on self-report.Even though pharmaceutical treatment was supposed to remain stable during the treatment period, some participants reduced or stopped medication, and others started medication, which could have affected the results. This finding underscores the need to monitor medication use during an RCT. | PMC10266649 |
Conclusions | IUT, depression, psychiatric | We found that primary health care patients were willing to participate in a pilot study that compared two protocols for treating GAD. Therapists working in regular primary health care could provide protocol-based psychological treatment with some competence and adherence after brief training and regular supervision. We therefore conclude that it is feasible to carry out a full-scale RCT that compares the effectiveness of IUT and MCT for primary health care patients with GAD.The preliminary evaluation of treatment effects suggests that both IUT and MCT effectively reduce worry, depression, and functional impairment, and increase quality of life for at least six months after treatment. However, MCT had superior effects on all outcomes, including recovery. MCT also achieved these outcomes in fewer sessions, which is relevant in primary health care setting. As these findings are similar to those of previous studies that compared MCT to IUT or other CBT in psychiatric outpatient clinics, we conclude that further studies of CBT, and specifically MCT, for primary health care patients with GAD are crucial to establish more knowledge and increase the availability of such treatments in primary health care. | PMC10266649 |
|
Supporting information | PMC10266649 |
|||
Consort checklist. | (DOC)Click here for additional data file. | PMC10266649 |
||
Original study protocol translated. | (DOCX)Click here for additional data file. | PMC10266649 |
||
Original study protocol Swedish. | (DOCX)Click here for additional data file. | PMC10266649 |
||
Translated ethical application. | (DOCX)Click here for additional data file.We thank our research nurse, Christina Stalby, and the participating patients and therapists at Liljeholmen Primary Health Care Center. We also thank scientific editor Kimberly Kane for useful comments on the text. | PMC10266649 |
||
Objective | CUTANEOUS LEISHMANIASIS, EPITHELIALIZATION | Autologous platelet gel (APG) is used in most surgeries to treat a variety of tissue defects because of its healing factors composition. This randomized parallel clinical trial was conducted to investigate the healing effects of APG on cutaneous leishmaniasis (CL) wounds. Eighteen male patients with CL wounds were recruited and followed for two months. The patients had more than one cutaneous wound, one of which was examined as the control and the other one as the intervention wound. APG was applied to the intervention wounds once a week, up to eight times. The primary endpoint was wound healing which defined as complete epithelialization and tissue granulation. Other clinical evaluation criteria were assessment of the wound size, and histopathology analyses. | PMC10493010 |
|
Results | Of 18 patients, 15 patients completed the trial (83.3%, mean age 28 years). The use of APG on the wounds was associated with complete and faster healing in 66% of the wounds and partial healing in 34% of the wounds. During the study, none of the control wounds were completely healed. The wound area in the intervention cases showed a statistically significant decrease throughout the study (P < 0.01) compared with controls. Following treatment of CL lesions with APG, the inflammatory process in the epidermis and dermis were decreased significantly (P < 0.01) compared with controls. | PMC10493010 |
||
Keywords | PMC10493010 |
|||
Introduction | Leishmaniasis | LEISHMANIASIS, SCARRING, DISEASE | Leishmaniasis is a protozoan disease transmitted through the bites of female sandflies [At present, there are physical methods (cryotherapy, laser therapy, thermotherapy), topical drugs (injection of Glucantime, Emetine hydrochloride, and application of Paromomycin ointment), and systemic drugs (Pentavalent antimony (SbV) compounds of Meglumine antimoniate and Sodium stibogluconate), which are either used alone or in combination with each other for the treatment of CL. In addition to the side effects of the mentioned drugs and their invasive injection, scarring is one of the problems that affect the patients’ physical appearance after CL [Platelet gel, a blood product used for wound healing, was first developed as a byproduct of platelet rich plasma (PRP) [ | PMC10493010 |
Materials and methods | PMC10493010 |
|||
Ethical standards | The protocol was approved by the | PMC10493010 |
||
Study design and participants | sepsis, hypovolemic, diabetes | PLATELET DISORDERS, SEPSIS, RECRUITMENT, DIABETES | This randomized, single-center, controlled, parallel clinical trial was carried out from February 2019 to January 2020. There were no important changes to methods after trial commencement.Eighteen eligible patients with confirmed CL were enrolled in this study, out of which 15 completed the trial. The study population consisted of adult male patients with CL referred to Ghafouri Specialized Laboratory in Jahrom, Iran.In the present study, all enrolled patients had more than one skin wound that involved the upper and lower limbs. Going for wounds of the same size and on the same limb, one of the wounds was randomly selected as the control and the other as the intervention wound.Age older than 15 years, and the presence of at least 2 wounds with the same dimensions on the hands and feet of the patients were considered as inclusion criteria. Also, hemoglobin < 10 mg/dl, qualitative and quantitative platelet disorders, abnormal screening tests, positive history of diabetes, positive history of severe hypovolemic conditions, sepsis, and anti-inflammation medications consumption during the past 2 weeks were defined as the exclusion criteria.After obtaining written consent and confirming that the prothrombin time (PT) and partial thromboplastin time (PTT) coagulation screening tests were within the normal range, 15 ml of citrated blood samples (once per week, up to 8 weeks) were taken from the patients. The recruitment and follow up flow of the participants is shown in a Consolidated Standards of Reporting Trials (CONSORT) diagram in Fig. CONSORT diagram showing flow of participants throughout the study | PMC10493010 |
Randomization and allocation | Randomization was done by one of the academic expert staff (not involved in this research) using randomly permuted blocks method (block size was two). Enrollment and assignment of participants to interventions was performed by the principal researcher (A.H.T) at | PMC10493010 |
||
Parasitological studies | Skin lesions | SKIN LESIONS, STERILE, LYSIS | In this study, the smears were taken for diagnosis of CL. Skin lesions were cleaned with antiseptic agent (70% alcohol), and then using a sterile lancet, 2–3 mm superficial incisions were made on the edges of the lesions. Two smears of dermal tissue scrapings were prepared from each patient, then air-dried, fixed in methanol, and giemsa-stained. Each smear was completely scanned for Leishman body. Samples were then screened via nested PCR. Using a sterile surgical blade, the dry smear was scraped from slide, and inserted into micro tube containing 200 μl of lysis buffer (50 mg ethylene diamine tetra-acetic acid (EDTA) pH 7.4, 50 mM NaCl, 200 μg proteinase K/ml, and 1% Triton X-100). The mixture was incubated at 56 °C for 3 h. The lysate was extracted with phenol–chloroform, and finally re-suspended in 50 µl double-distilled water and kept at − 20 °C until used. Characterization of the CL isolates was done using nested PCR by specific primers of CSB1XR, and CSB2XF as external primers, and also LiR, and 13Z as internal primers, which can specifically differentiate CL species [ | PMC10493010 |
Leishmaniasis wound management | STERILE | The control wound received routine treatment, including systemic injection of glucantime in a dose of 20 mg/kg/body weight, intramuscularly, daily for 14 days, and the intervention wound received APG-GF product in addition to the routine treatment. APG-GFs was prepared freshly, and applied to the wound site once per week, up to eight weeks. Before applying the gel, the supernatant containing GFs was injected into the inflamed and active area of the wound site using an insulin syringe. In addition, the wound site received approximately 3 ml of APG and was then covered and fixed with sterile gauze dressing (Fig. | PMC10493010 |
|
Follow-up and evaluation of the outcome | infection, erythema, swelling | DELAYED WOUND HEALING, ERYTHEMA, EPITHELIALIZATION, INDURATION, INFECTION, SECONDARY, HEAT, SECONDARY INFECTION, COMPLICATIONS | In this study, patients with CL wounds were evaluated every week for two months at the outpatient clinic by the principal investigator. The investigator was blinded to the type of treatment given to each group. Clinical evaluation of the wounds included assessment of the wound size, wound tissue granulation, epithelialization, and wound healing. The primary endpoint was complete wound healing characterized by 100% epithelialization. Reduction in wound size, and wound complications were considered as the secondary endpoints. In both groups, images were taken of the wound site before and after healing, and the dimensions of the wounds were measured using a Vernier caliper. The patients’ wounds were also examined clinically for secondary infections. Clinical criteria that were considered for local infection include erythema, heat, pus, induration, swelling, colour change, smell of exudate, and delayed wound healing. | PMC10493010 |
Biopsy collection and histopathological analysis | cutaneous lesions, ulcer, acanthosis, spongiosis | DYSKERATOSIS, ULCER, HYPERKERATOSIS, SPONGIOSIS | Biopsy samples from CL lesions were evaluated by expert pathologist before (day 0) and 8 weeks after intervention. The skin biopsy specimens were taken from the edge of cutaneous lesions with a 4 mm in thickness Harris punch, preceded by the application of local anesthesia and anti-septic agent. All specimens were fixed in 10% buffered formalin, and processed within a period of not more than 48 h to dispose of the paraffin tissue block. All specimens were dehydrated, cleared, embedded in paraffin, cut into 4 μm thick sections and stained with Hematoxylin–Eosin (HE). The histopathological changes in the epidermis (acanthosis, dyskeratosis, spongiosis, exocytosis, hyperkeratosis, and ulcer) before and after the last intervention was characterized using an optical microscope at 400 × magnification. At the same time, the intensity and distribution of inflammatory reactions in the dermis were evaluated. | PMC10493010 |
Sample size estimation | The study was designed to recruit 18 patients per treatment group. Based on previous studies and considering the following formula as the sample size equation, effect size = 0.8, α = 5%, β = 20%, the sample size was estimated at 15 patients. The sample size was increased from 15 to 18 patients to accommodate drop-outs. | PMC10493010 |
||
Statistical analysis | Data analysis was conducted using SPSS software (version 22.0 SPSS, Inc., Chicago, IL, USA). Control and intervention cases were matched based on the confounding variables (e.g. wound size). Data were described as mean ± standard deviation (SD). Welch test was used for comparing between groups. The Kaplan–Meier method was used for the analysis of time to healing. To compare the two survival curves, the log-rank test was used. Graphs were depicted by GraphPad Prism (version 8.3). | PMC10493010 |
||
Results | PMC10493010 |
|||
Histopathological finding | spongiosis, dyskeratosis, hyperkeratosis, acanthosis, TablesAnalysis, ulcer | SPONGIOSIS, INFILTRATE, DYSKERATOSIS, HYPERKERATOSIS, EVENTS, ULCER | The histopathological analysis of the 15 skin biopsies of patients with CL showed morphological alterations in both epidermis and dermis before treatment. In treated wounds with APG and glucantime, alterations of the epidermis were observed in 80% (11/15) of skin biopsies; and were mainly characterized by acanthosis in 86.7% (13/15), spongiosis in 33.3% (5/15), hyperkeratosis in 73.3% (11/15), dyskeratosis in 40.0 (6/15), exocytosis in 26.7% (4/15), and ulcer in 46.6% (7/15) of skin biopsies. The histopathological alterations in the dermis were determined mainly by a lymphohistocytic pattern of variable intensity, with diffuse or focal distribution. The inflammatory pattern was intense in 40% (6/15), moderate in 53.3% (8/15) and light in 6.7% (1/15) of cases with diffuse distribution in 40% (6/15), and focal in 60% (9/15). The inflammatory infiltrate was characterized by predominance of lymphocytes (61%), followed by inflammatory cells. After 8 weeks of treatment with APG and glucantime, the inflammatory cells infiltrate patterns in the epidermis and dermis were decreased significantly. In treated wounds with glucantime only, a decrease in the histopathological features of the epidermis and dermis were also observed. The pattern of decrease was less significant, and some events continued in patients after the therapies (TablesAnalysis of histopathological changes in epidermis before and after treatmentDermal histopathological characteristics before and after treatmentHistopathological findings observed in the CL lesions in control and intervention groups. | PMC10493010 |
Discussion | ulcer, diabetic foot ulcer, diabetic wounds | DIABETIC FOOT ULCER, EPITHELIALIZATION, INFILTRATES, ULCER, INFLAMMATORY RESPONSE | Partial or poor response of CL to standard pentavalent antimony (SbV) treatment caused by host, parasite factors [We have therefore looked for additional healing effects of a topical treatment of CL wounds in addition to systemic SbV treatment with APG and its plasma secreted growth factors (APG-GF) which has become increasingly popular to improve healing of chronic non-leishmania wounds during the last decade. This study is the first report on the use of APG-GF for CL wound healing. We evaluated the pre- and post-treatment pathohistology of the CL lesions to find hints on a shorter and hence more cosmetic healing.Our preliminary findings suggest that in patients with 2 CL lesions treated with 20 mg /kg body weight, SbV daily for 14 days, additionally receiving topical APG-GF for one lesion once weekly for 8 weeks improves clinical healing of this lesion in comparison to the lesion left without topical treatment.10 (66%) of the APG-GF treated wounds healed completely till day 56, and 5 (34%) lesions showed partial healing. The Kaplan–Meier wound of both lesion groups confirm faster healing of the APG-GF treated CL lesions. Meanwhile, no statistically significant change was observed in the wound healing, as well as wound area over time in the control group.Martins et al. study showed that the use of platelet gel can be highly effective in the treatment of various types of chronic wounds [Researches on wound healing have shown that platelet gels accelerate wound healing, epithelialization, and angiogenesis. Platelets induce an intense inflammatory response in the used site and play a key role in the healing of the injured tissue [Gupta et al., reported that the inflammatory response and tissue repair of burn lesions treated with autologous platelet concentrate were significantly different compared to the control group. In their study, all patients who received the intervention demonstrated significantly better graft uptake rate when compared to patients in the control group [In another study, Elsaid et al. showed that platelet gel dressing is clinically effective in healing diabetic wounds and use of platelet gel dressing for diabetic foot ulcer resulted in a more significant reduction in the size of the ulcer when compared to routine dressing.Also, the time to reach the point of maximal healing with the least wound dimensions was significantly shorter when using platelet gel [APG is rich in growth factors and its application on the injury site summons the inflammatory cells and causes the onset of cell differentiation, which in turn accelerates the wound healing process and can be used as an auxiliary treatment in wound healing [The results of the present study showed that the use of APG accelerates the formation of granulation tissue. An increase in granulation tissue and accelerated wound healing was observed in the patients who used APG, which is consistent with the results of similar studies on this subject [In the present study, histopathological findings of CL lesions were also represented.Botelho et al. found that evaluation of histopathological samples is important for analyzing and understanding of the tissue healing process [Although, in some cases even after complete treatment of patients, when the CL lesions were considered clinically healed, an inflammatory pattern still persisted in lesions. Similar histopathological features have been described in Viana, et al. reports [Generally, the results of present study showed that wounds caused by CL may heal faster and more effectively with the additional use of APG than the standard anti-protozoal chemotherapy with SbV alone. The presence of moderate to intense infiltrates of inflammatory cells noticed before APG-GF treatment start was not absent after the end of APG-GF treatment, even with a complete clinical cure, the subjects still showed a mild inflammatory process. | PMC10493010 |
Limitations | One of the limitations of this study was that we could not use APG continuously due to the short life span of platelets at room temperature, and for optimal healing effect, it should be prepared fresh. In addition, further trials are needed to confirm our preliminary findings by increasing the patient number and the duration of treatment and by eventually adding a second clinical design by comparing three lesions in one patient, one treated with topical SbV first and with APG-GF thereafter and the second lesion with APG-GF first, and with topical SbV only, if there is insufficient healing after 8 weeks. | PMC10493010 |
||
Acknowledgements | This study has been supported by the Jahrom University of Medical Sciences. We would particularly like to thank all patients who participated in this study. | PMC10493010 |
||
Author contributions | AHT | All authors contributed to study design. ES and AHT contributed to all parts of the study. KS and FS contributed to study implementation. AHT, AM, and ES collaborated in the analysis and interpretation of data. AT and AHT collaborated in the manuscript writing and revision. All the authors commented on the drafts of the manuscript and approved the final version of the article. | PMC10493010 |
|
Funding | The research was funded by Jahrom University of Medical Sciences. | PMC10493010 |
||
Availability of data and materials | The datasets that analyzed during the current study is available through corresponding author on reasonable request. | PMC10493010 |
||
Declarations | PMC10493010 |
|||
Ethics approval and consent to participate | The study complied with the guidelines for human studies. The procedures of study were approved by Ethical Committee of Jahrom University of Medical Sciences (IR.JUMS.REC.1397.033), and registered with Iran Randomized Clinical Trial Center under the registration number IRCT20190212042694N1. Written informed consent was obtained from patients (or their parent or legal guardian in the case of children under 17) prior to participation in this study. | PMC10493010 |
||
Consent for publication | Not applicable. | PMC10493010 |
||
Competing interests | The authors have no relevant financial or non-financial interests to disclose. | PMC10493010 |
||
References | PMC10493010 |
|||
Background | This study investigated the effects of intraoperative goal-directed hemodynamic therapy (GDHT) on postoperative outcomes in patients undergoing open radical cystectomy. | PMC10561433 |
||
Methods | stroke | STROKE, POSTOPERATIVE COMPLICATIONS | This prospective, single-center, randomized controlled trial included 82 patients scheduled for open radical cystectomy between September 2018 and November 2021. The GDHT group (n = 39) received the stroke volume index- and cardiac index-based hemodynamic management using advanced hemodynamic monitoring, while the control group (n = 36) received the standard care under the discretion of attending anesthesiologists during surgery. The primary outcome was the incidence of a composite of in-hospital postoperative complications during hospital stays. | PMC10561433 |
Results | POSTOPERATIVE COMPLICATIONS | A total of 75 patients were included in the final analysis. There was no significant difference in the incidence of in-hospital postoperative complications (28/39 [71.8%] vs. 30/36 [83.3%], risk difference [95% CI], -0.12 [-0.30 to 0.07], | PMC10561433 |
|
Conclusions | COMPLICATIONS | Intraoperative GDHT did not reduce the incidence of postoperative in-hospital complications during the hospital stay in patients who underwent open radical cystectomy. | PMC10561433 |
|
Trial registration | This study was registered at | PMC10561433 |
||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12871-023-02285-9. | PMC10561433 |
||
Keywords | PMC10561433 |
|||
Background | POSTOPERATIVE COMPLICATION, INVASIVE BLADDER CANCER, POSTOPERATIVE COMPLICATIONS | Radical cystectomy is the standard surgical treatment for invasive bladder cancer [Postoperative complications may be associated with an imbalance between oxygen demand and supply and impaired peripheral tissue perfusion [Thus, in the present study, we aimed to investigate the effects of intraoperative GDHT on the overall postoperative complications in patients who underwent open radical cystectomy. We hypothesized that GDHT during the surgery would have a better effect on clinical outcomes than standard care and compared the incidence of in-hospital postoperative complications, the severity of postoperative complications, the length of hospital stays, and the postoperative laboratory results among the patients. | PMC10561433 |
|
Methods | PMC10561433 |
|||
Ethics | This study was approved by the Institutional Review Board of Seoul National University Hospital (Seoul, Republic of Korea, Approval number: 1712-125-909) and was registered at ClinicalTrials.gov (registration number: NCT03505112, date of registration: 23/04/2018, principal investigator: Jin-Tae Kim). The study was conducted in accordance with the Declaration of Helsinki, and written informed consent was obtained from all the patients. All data were collected at the Seoul National University Hospital between April 2018 and October 2021. | PMC10561433 |
||
Participants | We evaluated patients (aged > 20 years) who were scheduled for open radical cystectomy and had American Society of Anesthesiologists (ASA) physical status I–III. We excluded patients who had compromised kidney function (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73m | PMC10561433 |
||
Sample size calculation | COMPLICATIONS, POSTOPERATIVE COMPLICATIONS | Our preliminary investigation of the incidence of in-hospital postoperative complications after open radical cystectomy at the Seoul National University Hospital showed that 40% of the patients had one or more complications after surgery during the hospital stay. Assuming that the incidence of postoperative complications can be reduced from 40 to 12% if patients were managed using GDHT, 37 patients were required, with an alpha of 0.05 and a power of 20% for each group. Considering a 10% drop-out rate, 82 patients were required. | PMC10561433 |
|
Randomization and blinding | On the day of surgery, patients were randomly assigned to either the group that received GDHT during the surgery (GDHT group) or the group that received standard care at the discretion of the attending anesthesiologists (control group), with 1:1 allocation based on a randomized computer-generated list, consisting of four and six block sizes. The group allocations were sealed in opaque envelopes by an investigator not involved in the study. Because the anesthesiologists in charge of the operating room managed the patients according to group allocation, blinding the attending anesthesiologists was impossible. However, the investigators who evaluated postoperative outcomes and surgeons were blinded to the group allocation. | PMC10561433 |
||
Anesthesia protocol | stroke | STROKE, EDWARDS | After the patients entered the operating room, standard monitoring was started, including pulse oximetry, noninvasive blood pressure, electrocardiogram, and bispectral index (BIS). Cerebral oxygenation was also monitored by cerebral oximetry (INVOS 5100 C; Somanetics Co., Troy, MI, USA). Anesthesia was induced with propofol (1.5–2 mg/kg) and remifentanil using a target-controlled infusion (3 ng/ml). After the loss of consciousness, rocuronium (0.6 mg/kg) was administered, and endotracheal intubation was performed. Mechanical ventilation was started using the mode of volume-controlled ventilation. Ventilation parameters were initially set to a tidal volume of 8 ml/kg ideal body weight, a fraction of inspired oxygen (FiOAfter anesthesia induction, a radial artery was catheterized and connected to the FloTrac/EV1000 system (Edwards Lifesciences, Irvine, CA, USA) for continuous monitoring of arterial blood pressure. Then, a central venous catheter was inserted into the right internal jugular vein, and central venous pressure (CVP) was monitored. Hemodynamic variables, including cardiac output (CO), cardiac index (CI), stroke volume index (SVI), and stroke volume variation (SVV), were measured every 20 s. | PMC10561433 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.