Changes In Symptom Severity Research Articles

A51 ROLE OF GUT MICROBIOTA IN THE EPISODIC NATURE OF SYMPTOMS IN IRRITABLE BOWEL SYNDROME

BackgroundIrritable bowel syndrome (IBS) is a complex functional gastrointestinal disorder with likely heterogenous pathophysiology, multiple symptoms, and comorbidities. Growing evidence shows that the gut microbiota composition and function are altered in IBS patients. However, identifying the critical drivers of clinical expression remains challenging due to the episodic occurrence of IBS symptoms, the inherent variability in composition of gut microbiota across individuals, and high sensitivity of gut microbiota to dietary and environmental cues.AimsTo identify whether changes in gut microbiota composition accompany or, predict the occurrence of symptoms.Methods28 IBS patients (IBS-D n=20, IBS-C n=8) and 10 healthy controls (HC) were followed longitudinally for 25 weeks, collecting stool samples, and recording their symptoms weekly. Stool microbiota profiles were assessed by 16S rRNA gene sequencing using Illumina platform. The sequences were preprocessed, filtered, and annotated using DADA2 and phyloseq pipelines; statistical analyses were performed using FactomineR and microbiomeanalyst packages in R. Statistical significance was set at p<0.05.ResultsMultifactorial analysis of clinical data classified 950 samples in 6 clusters. Distribution of samples among the clusters was based on Bristol stool scale defining symptomatic periods (scores <3 and >4 indicating abnormal stool) and asymptomatic periods (scores 3 or 4), with several gut and mood symptoms varying significantly between the two categories. IBS-D patients, but not IBS-C patients presented with changes in symptoms severity, such as pain, diarrhea, constipation, and anxiety during the symptomatic periods. Depression scores were, however, higher in IBS-C compared to IBS-D patients. In contrast, immune makers such as fecal b-defensin-2 and calprotectin were higher during asymptomatic periods in IBS-D, but not in IBS-C patients. Bacterial diversity profiles differed among IBS patients (IBS-D and IBS-C) and HC, namely Shannon index and Bray-Curtis distance, but they did not change significantly between the symptomatic and asymptomatic periods within each subtype. Despite this, several bacterial taxa unique to each cluster were identified using linear mixed models.ConclusionsOur results demonstrate the need to study patterns of co-occurrence of IBS symptoms and their severity during symptomatic and asymptomatic periods to better understand the role of identified bacterial taxa in the symptom generation. Identifying their temporal changes and cross-feeding patterns in individual patients will shed light on the underlying mechanistic role of gut microbiota in IBS, which might be otherwise obscured by group generalizations.Funding AgenciesCIHR

Impact of Treatment Setting and Format on Symptom Severity Following Cognitive Processing Therapy for Posttraumatic Stress Disorder

Preliminary data suggest cognitive processing therapy (CPT) significantly reduces posttraumatic stress disorder (PTSD) symptom severity among military personnel and veterans when delivered over 12 days and combined with daily recreational activities (Bryan et al., 2018). The present study aimed to examine how therapy pace (i.e., daily vs. weekly sessions) and setting (i.e., clinic vs. recreational) impacts change in PTSD symptom severity. Forty-five military personnel and veterans diagnosed with PTSD chose to receive CPT (a) daily at a recreational facility with recreational programming, (b) daily on a university campus without recreational programming, and (c) weekly on a university campus without recreational programming. PTSD symptom severity was assessed with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5). Reductions in CAPS-5 and PCL-5 scores were large and statistically significant across all three settings (Cohen’s ds > 2.1). As compared to reductions in CAPS-5 and PCL-5 scores in daily therapy at a recreational facility (CAPS-5: d = 1.63–2.40; PCL-5: d = 1.99–2.17), reductions in CAPS-5 and PCL-5 scores were significantly larger in daily therapy on campus, CAPS-5: t(80) = –2.9, p = .005, d = 2.23–2.69; PCL-5: t(78) = 2.6, p = .010, d = 2.54–4.43, but not weekly therapy on campus, CAPS-5: t(80) = 0.2, p = .883, d = 1.04–2.47; PCL-5: t(78) = 1.0, p = .310, d = 1.77–3.44. Participants receiving daily therapy on campus and weekly therapy on campus also had higher rates of clinically significant improvement and good end-state functioning. Results support the effectiveness of CPT across multiple treatment settings and formats and suggest that daily CPT may be less effective when delivered in combination with recreational activities.

Examining initial post-concussion dizziness and postural stability as predictors of time to symptom resolution

ObjectivesTo examine the utility of a multimodal assessment battery of self-reported dizziness, clinician obtained postural stability, and symptom severity ratings within 14 days of concussion to predict symptom resolution time among children and adolescents. DesignProspective cohort. MethodsPatients ages 6–18 years completed evaluation ≤14 days post-concussion, including self-reported symptom severity using the Post-Concussion Symptom Inventory (PCSI) and postural stability assessments. We grouped patients as dizzy or not dizzy based on the difference in current and pre-injury PSCI dizziness ratings: difference between current and pre-injury dizziness ≥3 = dizzy; difference <3 = not dizzy. We evaluated postural stability using modified Balance Error Scoring System (mBESS) and tandem gait (TG). Our primary outcome was time from concussion to symptom resolution. Using a univariable Cox proportional hazard model, we examined the association between dizziness and symptom resolution time. We then used a multivariable Cox proportional hazard model to adjust for potential confounding variables. ResultsWe examined 89 patients and grouped each as dizzy (n = 34; age = 14.7 ± 2.7 years; 7.1 ± 3.4 days post-injury; symptom resolution time = 40.8 ± 5.7 days) or not dizzy (n = 55; age = 14.4 ± 2.3 years; 7.2 ± 3.1 days post-injury; symptom resolution time = 23.3 ± 3.2 days). Upon univariable examination, dizziness was independently associated with increased symptom resolution time (Hazard Ratio [HR] = 0.49; 95%CI: 0.28, 0.83; p = 0.009). After adjusting for potential confounders (total symptom severity, mBESS tandem stance errors, TG time, loss of consciousness), only symptom severity change was associated with symptom resolution time (HR = 0.98; 95%CI: 0.96, 0.997; p = 0.025). ConclusionsTotal symptom severity assessed within 14 days of concussion, but not dizziness or postural stability, was significantly associated with symptom resolution time among children and adolescents following concussion.

Identifying autism symptom severity trajectories across childhood

AbstractAn individual's autism symptom severity level can change across childhood. The prevalence and direction of change, however, are still not well understood. Nor are the characteristics of children that experience change. Symptom severity trajectories were evaluated from early to middle childhood (approximately ages 3–11) for 182 autistic children. Symptom severity change was evaluated using individual change scores and the Reliable Change Index. Fifty‐one percent of participants experienced symptom severity change: 27% of children decreased in severity, 24% increased and 49% were stable. Symptom severity decreases were more common during early childhood. Severity increases occurred at both early and middle childhood but increase in social affect severity was especially prominent during middle childhood. Most children experienced significant change during only one period and remained stable during the other. Girls decreased more and increased less in symptom severity than boys. Children that increased in severity decreased in adaptive functioning across childhood. Exploratory analyses indicated that a decrease in severity was associated with higher parental education level and older parental age at the time of the child's birth. Conversely, increase in autism severity was associated with lower parental education level and younger parental age at the child's birth. These findings extend recent observations that symptom severity change is more likely than previously appreciated. An understanding of the role of both biological and sociodemographic factors in determining a child's symptom trajectory may factor into future decisions on allocation and type of interventions distributed to young autistic children.Lay SummaryWe studied whether a child's autism severity changed from initial diagnosis until middle childhood (ages 3–11). We found that 27% of the children decreased in severity, 24% increased and the rest stayed the same. Symptom severity decreases were more common during early childhood while severity increases were more prominent during middle childhood. We also found that girls were more likely to decrease than boys. Whether a child decreased or increased is related, in part, to parental characteristics.

Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among US Veterans

IMPORTANCEPosttraumatic stress disorder (PTSD) is a prevalent and serious mental health problem. Although there are effective psychotherapies for PTSD, there is little information about their comparative effectiveness.OBJECTIVETo compare the effectiveness of prolonged exposure (PE) vs cognitive processing therapy (CPT) for treating PTSD in veterans.DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical trial assessed the comparative effectiveness of PE vs CPT among veterans with military-related PTSD recruited from outpatient mental health clinics at 17 Department of Veterans Affairs medical centers across the US from October 31, 2014, to February 1, 2018, with follow-up through February 1, 2019. The primary outcome was assessed using centralized masking. Tested hypotheses were prespecified before trial initiation. Data were analyzed from October 5, 2020, to May 5, 2021.INTERVENTIONSParticipants were randomized to 1 of 2 individual cognitive-behavioral therapies, PE or CPT, delivered according to a flexible protocol of 10 to 14 sessions.MAIN OUTCOMES AND MEASURESThe primary outcome was change in PTSD symptom severity on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from before treatment to the mean after treatment across posttreatment and 3- and 6-month follow-ups. Secondary outcomes included other symptoms, functioning, and quality of life.RESULTSAnalyses were based on all 916 randomized participants (730 [79.7%] men and 186 [20.3%] women; mean [range] age 45.2 [21–80] years), with 455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95% CI, 39.1–40.7] points) and 461 participants randomized to CPT (mean CAPS-5 score at baseline, 40.3 [95% CI, 39.5–41.1] points). PTSD severity on the CAPS-5 improved substantially in both PE (standardized mean difference [SMD], 0.99 [95% CI, 0.89–1.08]) and CPT (SMD, 0.71 [95% CI, 0.61–0.80]) groups from before to after treatment. Mean improvement was greater in PE than CPT (least square mean, 2.42 [95% CI, 0.53–4.31]; P = .01), but the difference was not clinically significant (SMD, 0.17). Results for self-reported PTSD symptoms were comparable with CAPS-5 findings. The PE group had higher odds of response (odds ratio [OR], 1.32 [95% CI, 1.00–1.65]; P < .001), loss of diagnosis (OR, 1.43 [95% CI, 1.12–1.74]; P < .001), and remission (OR, 1.62 [95% CI, 1.24–2.00]; P < .001) compared with the CPT group. Groups did not differ on other outcomes. Treatment dropout was higher in PE (254 participants [55.8%]) than in CPT (215 participants [46.6%]; P < .01). Three participants in the PE group and 1 participant in the CPT group were withdrawn from treatment, and 3 participants in each treatment dropped out owing to serious adverse events.CONCLUSIONS AND RELEVANCEThis randomized clinical trial found that although PE was statistically more effective than CPT, the difference was not clinically significant, and improvements in PTSD were meaningful in both treatment groups. These findings highlight the importance of shared decision-making to help patients understand the evidence and select their preferred treatment.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT01928732

Supervised machine learning to predict reduced depression severity in people with epilepsy through epilepsy self-management intervention

ObjectiveTo develop a classifier that predicts reductions in depression severity in people with epilepsy after participation in an epilepsy self-management intervention. MethodsNinety-three people with epilepsy from three epilepsy self-management randomized controlled trials from the Managing Epilepsy Well (MWE) Network integrated research database met the inclusion criteria. Supervised machine learning algorithms were utilized to develop prediction models for changes in self-reported depression symptom severity. Features considered by the machine learning classifiers include age, gender, race, ethnicity, education, study type, baseline quality of life, and baseline depression symptom severity. The models were trained and evaluated on their ability to predict clinically meaningful improvement (i.e., a reduction of greater than three points on the nine-item Patient Health Questionnaire (PHQ-9)) between baseline and follow-up (<=12 weeks) depression scores. Models tested were a Multilayer Perceptron (ML), Random Forest (RF), Support Vector Machine (SVM), Logistic Regression with Stochastic Gradient Descent (SGD), K-nearest Neighbors (KNN), and Gradient Boosting (GB). A separate, outside dataset of 41 people with epilepsy was used in a validation exercise to examine the top-performing model’s generalizability and performance with external data. ResultsAll six classifiers performed better than our baseline mode classifier. Support Vector Machine had the best overall performance (average area under the curve [AUC] = 0.754, highest subpopulation AUC = 0.963). Our analysis of the SVM features revealed that higher baseline depression symptom severity, study type (i.e., intervention program goals), higher baseline quality of life, and race had the strongest influence on increasing the likelihood that a subject would experience a clinically meaningful improvement in depression scores. From the validation exercise, our top-performing SVM model performed similarly or better than the average SVM model with the outside dataset (average AUC = 0.887). SignificanceWe trained an SVM classifier that offers novel insight into subject-specific features that are important for predicting a clinically meaningful improvement in subjective depression scores after enrollment in a self-management program. We provide evidence for machine learning to select subjects that may benefit most from a self-management program and indicate important factors that self-management programs should collect to develop improved digital tools.

Cognitive flexibility improves in cognitive behavioral therapy for irritable bowel syndrome but not nonspecific education/support

This study tested the novel hypothesis that CBT-treated IBS patients who learn to self-manage painful GI symptoms by targeting rigid cognitive style show improvement in cognitive flexibility, GI symptoms (e.g., abdominal pain), and quality of life. Participants included 130 Rome-III diagnosed IBS patients (M age = 40.3, F = 83%) with moderate-to-severe symptoms randomly assigned to either cognitive behavioral therapy (CBT; N = 86) or a nonspecific education/support (EDU) comparator (N = 44). Participants completed an assessment battery at baseline and post-treatment 2 weeks after 10-week acute treatment phase. Measures included cognitive flexibility, psychological flexibility, emotion regulation strategies, IBS symptom severity, quality of life (QOL), and distress. CBT but not EDU patients showed significant GI sympton improvement from baseline to post-treatment in cognitive flexibility. For CBT patients, changes in cognitive flexibility were significantly associated with changes in IBS symptom severity, abdominal pain, and IBS QOL. Neither condition showed significant changes in psychological flexibility (Acceptance and Action Questionnaire-II) or use of emotion regulation strategies (Emotion Regulation Questionnaire). The ability to self-manage painful IBS symptoms refractory to conventional medical and dietary treatments is related to the ability to respond flexibly across shifting contexts using cognitive change procedures featured in CBT for IBS.

Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

BackgroundVariation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 – 34 years), and using the more physiologically informative fixel-based analysis (FBA). MethodsData were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. ResultsClinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax = 1.092, standardized effect[SE] = 0.044, pFWE = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax = 3.775, SE = 0.051, pFWE = 0.019). ConclusionsAberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.

First Acute-Course Electroconvulsive Therapy for Moderate-to-Severe Depression Benefits Patients With or Without Accompanying Baseline Cognitive Impairment.

Researchers are increasingly investigating therapeutic response associated with new patient subgroups as a way to improve electroconvulsive therapy (ECT) treatment outcomes and reduce adverse events. This study is the first to examine baseline cognitive impairment status as a predictor of clinical outcome in first acute-course ECT patients. Baseline cognitive function at various thresholds and serial depressive symptom severity data from first-time ECT patients were examined using generalized linear mixed-effects models. Of 1345 patients who met the inclusion criteria, 617 had available data at their third assessment visit (~15th treatment visit). There was a robust improvement in depression symptoms over time (P < 0.0001), and cognitive function was not associated with baseline levels of depressive symptoms or serially measured change in self-reported symptom severity during acute-phase ECT. These results indicate that an acute course of ECT for the treatment of moderate-to-severe depression benefits patients with or without accompanying baseline cognitive impairment. These findings may be useful in informing shared decision-making discussions about ECT risks and expected benefits.

Examining depression symptoms within OCD: the role of experiential avoidance

Obsessive compulsive disorder (OCD) and depression commonly co-occur. Past research has evaluated underlying mechanisms of depression in the context of other diagnoses, but few to no studies have done this within OCD. This study examines the relationships between distress tolerance (DT), experiential avoidance (EA), depression, and OCD symptom severity across intensive/residential treatment (IRT) for OCD. It was hypothesized that all variables would be significantly moderately related and EA would emerge as a potential contributing factor to change in depression and OCD symptoms across IRT for OCD. The sample included 311 participants with a primary diagnosis of OCD seeking IRT. Correlations were performed between all variables at both admission and discharge. A two-step hierarchical regression with change in OCD symptoms and change in DT in the first block and change in EA in the second block examined if change in EA explained change in depression above and beyond change in OCD and DT ability. At both admission and discharge, higher EA, lower DT, and higher OCD symptom severity were significantly associated with more depressive symptoms. Change in EA explained a significant amount of variance in change in depression above and beyond change in OCD symptom severity and change in DT. This study expands past results within an OCD sample, emphasizing EA as an important treatment target in OCD. Future studies could utilize samples from other treatment contexts, use a measure of EA specific to OCD, and utilize a longitudinal model that takes temporal precedence into account.

The Dietary Intake of Carrot-Derived Rhamnogalacturonan-I Accelerates and Augments the Innate Immune and Anti-Viral Interferon Response to Rhinovirus Infection and Reduces Duration and Severity of Symptoms in Humans in a Randomized Trial.

Acute respiratory infections are an important health concern. Traditionally, polysaccharide-enriched extracts from plants, containing immunomodulatory rhamnogalacturonan-I (RG-1), were used prophylactically. We established the effects of dietary supplementation with carrot-derived RG-I (cRG-I, 0–0.3–1.5 g/day) in 177 healthy individuals (18–65 years) on symptoms following infection with rhinovirus strain 16 (RV16). Primary outcomes were changes in severity and duration of symptoms, and viral load in nasal lavage. Secondary outcomes were changes in innate immune and anti-viral responses, reflected by CXCL10 and CXCL8 levels and cell differentials in nasal lavage. In a nested cohort, exploratory transcriptome analysis was conducted on nasal epithelium. Intake of cRG-I was safe, well-tolerated and accelerated local cellular and humoral innate immune responses induced by RV16 infection, with the strongest effects at 1.5 g/d. At 0.3 g/d, a faster interferon-induced response, induction of the key anti-viral gene EIF2AK2, faster viral clearance, and reduced symptom severity (−20%) and duration (−25%) were observed. Anti-viral responses, viral clearance and symptom scores at 1.5 g/d were in between those of 0 and 0.3 g/d, suggesting a negative feedback loop preventing excessive interferon responses. Dietary intake of cRG-I accelerated innate immune and antiviral responses, and reduced symptoms of an acute respiratory viral infection.

Examining the impact of the COVID-19 pandemic through the lens of the network approach to psychopathology: Analysis of the Brazilian Longitudinal Study of Health (ELSA-Brasil) cohort over a 12-year timespan

Cohort studies have displayed mixed findings on changes in mental symptoms severity in 2020, when the COVID-19 pandemic outbreak started. Network approaches can provide additional insights by analyzing the connectivity of such symptoms. We assessed the network structure of mental symptoms in the Brazilian Longitudinal Study of Health (ELSA-Brasil) in 3 waves: 2008–2010, 2017–2019, and 2020, and hypothesized that the 2020 network would present connectivity changes. We used the Clinical Interview Scheduled-Revised (CIS-R) questionnaire to evaluates the severity of 14 common mental symptoms. Networks were graphed using unregularized Gaussian models and compared using centrality and connectivity measures. The predictive power of centrality measures and individual symptoms were also estimated. Among 2011 participants (mean age: 62.1 years, 58% females), the pandemic symptom 2020 network displayed higher overall connectivity, especially among symptoms that were related to general worries, with increased local connectivity between general worries and worries about health, as well as between anxiety and phobia symptoms. There was no difference between 2008 and 2010 and 2017–2019 networks. According to the network theory of mental disorders, external factors could explain why the network structure became more densely connected in 2020 compared to previous observations. We speculate that the COVID-19 pandemic and its innumerous social, economical, and political consequences were prominent external factors driving such changes; although further assessments are warranted.

Mantra meditation as adjunctive therapy in major depression: A randomized controlled trial

• Mantra meditation is an effective add-on treatment in major depression. • Mantra meditation is superior to progressive muscle relaxation. • After 6 months, mantra meditation mainly improved mood rather than cognitive symptoms. • Untapped potentials of mantra meditation warrant further research. To investigate the efficacy of add-on mantra meditation compared to progressive muscle relaxation in major depression. This study was a two-arm, single-site, raterblinded, randomized controlled trial involving 123 inpatients at a psychiatric hospital diagnosed with major depression according to DSM-IV criteria (January 2017 to June 2020). The treatment group practiced mantra meditation (MAM, N = 60); the comparator group practiced progressive muscle relaxation (PMR, N = 63). Both treatments were delivered via an introductory lesson followed by 30-minute group sessions twice weekly, adjunctively to usual treatment for depressive inpatients (TAU). The primary outcome measure was change in clinician-rated depression symptom severity, measured by the MADRS interview. The secondary outcome measure was self-reported depression severity, measured by the BDI-II questionnaire. Intentionto-treat was analyzed using linear mixed models. The TAU + MAM group had significantly greater improvements in MADRS score than the TAU + PMR group, both at the 3- month follow-up (between-group difference = 4.78, 95% CI = -8.32 – -1.42; d = 0.62) and at the 6-month follow-up (between-group difference = -6.24, 95% CI = -9.80 – -2.69; d = 0.79). Posttreatment, self-reported depression symptom severity was not significantly lower in the TAU + MAM group than in the TAU + PMR group. Exploratory analysis of the differences between primary and secondary outcomes showed that mantra meditation mainly improved mood rather than cognitive symptoms. In inpatients with major depression, adjunctive mantra meditation led to clinically relevant reduction in depressive symptom severity. Further research would build evidence for the untapped potentials of mantra meditation. ClinicalTrials.gov Identifier : NCT03004430

Effect of PEP flute self-care versus usual care in early covid-19: non-drug, open label, randomised controlled trial in a Danish community setting

ObjectiveTo determine whether positive expiratory pressure (PEP) by PEP flute self-care is effective in reducing respiratory symptoms among community dwelling adults with SARS-CoV-2 infection and early stage covid-19.DesignNon-drug, open label,...

Clinical and MRI findings in lumbar spinal stenosis: baseline data from the NORDSTEN study

PurposeThe aim was to describe magnetic resonance imaging findings in patients planned for lumbar spinal stenosis surgery. Further, to describe possible associations between MRI findings and patient characteristics with patient reported disability or pain.MethodsThe NORDSTEN spinal stenosis trial included 437 patients planned for surgical decompression of LSS. The following MRI findings were evaluated before surgery: morphological (Schizas) and quantitative (cross-sectional area) grade of stenosis, disk degeneration (Pfirrmann), facet joint tropism and fatty infiltration of the multifidus muscle. Patients were dichotomized into a moderate or severe category for each radiological parameter classification. A multivariable linear regression analysis was performed to investigate the association between MRI findings and preoperative scores for Oswestry Disability Index, Zurich Claudication Questionnaire and Numeric rating scale for back and leg pain. The following patient characteristics were included in the analysis: gender, age, smoking and weight.ResultsThe percentage of patients with severe scores was as follows: Schizas (C + D) 71.3%, cross-sectional area (< 75 mm2) 86.8%, Pfirrmann (4 + 5) 58.1%, tropism (≥ 15°) 11.9%, degeneration of multifidus muscle (2–4) 83.7%. Regression coefficients indicated minimal changes in severity of symptoms when comparing the groups with moderate and severe MRI findings. Only gender had a significant and clinically relevant association with ODI score.ConclusionIn this cross-sectional study, the majority of the patients had MRI findings classified as severe LSS changes, but the findings had no clinically relevant association with patient reported disability and pain at baseline. Patient characteristics have a larger impact on disability and pain than radiological findings.Trial registrationwww.ClinicalTrials.gov identifier: NCT02007083, registered December 2013.

Mechanisms of Change in Trauma-Focused Treatment for PTSD: The Role of Rumination

ObjectiveCognitive behavioral therapy (CBT) has been well established in the treatment of posttraumatic stress disorder (PTSD). In recent years, researchers have begun to investigate its underlying mechanisms of change. Dysfunctional cognitive content, i.e. excessively negative appraisals of the trauma or its consequences, has been shown to predict changes in PTSD symptoms over the course of treatment. However, the role of change in cognitive processes, such as trauma-related rumination, needs to be addressed. The present study investigates whether changes in rumination intensity precede and predict changes in symptom severity. We also explored the extent to which symptom severity predicts rumination. MethodAs part of a naturalistic effectiveness study evaluating CBT for PTSD in routine clinical care, eighty-eight patients with PTSD completed weekly measures of rumination and symptom severity. Lagged associations between rumination and symptoms in the following week were examined using linear mixed models. ResultsOver the course of therapy, both ruminative thinking and PTSD symptoms decreased. Rumination was a significant predictor of PTSD symptoms in the following week, although this effect was at least partly explained by the time factor (e.g., natural recovery or inseparable treatment effects). Symptom severity predicted ruminative thinking in the following week even with time as an additional predictor. ConclusionsThe present study provides preliminary evidence that rumination in PTSD is reduced by CBT for PTSD but does not give conclusive evidence that rumination is a mechanism of change in trauma-focused treatment for PTSD.

Feasibility of self-administered acupressure for allergic rhinitis: a pilot randomized controlled trial and lessons learnt for future studies.

Allergic rhinitis (AR) is an immunoglobulin (Ig)E-mediated inflammatory condition that is highly prevalent worldwide. The aim of this pilot trial was to evaluate the feasibility and safety of self-administered acupressure for AR. A randomized, single-blind, non-specific controlled clinical trial was conducted at Royal Melbourne Institute of Technology (RMIT) University, Melbourne, Australia. Fifteen AR patients were randomized into two groups: self-administered acupressure at five specific acupressure (SA) points or five non-specific acupressure (NSA) points (1 min/point, twice a day), and treated for 4 weeks with an 8-week follow-up period. The primary outcome was the change in 7-point scale symptom severity. Secondary outcomes included the rhinoconjunctivitis quality of life questionnaire and standardized activities (RQLQs), medication usage, adverse events and participants' opinions of the blinding method. The Statistical Package for the Social Science (SPSS) version 26 was used for data analyses. Fourteen participants completed the study and no major adverse events were reported. No statistically significant differences between SA and NSA groups were identified in 7-point scale symptom severity scores, RQLQs or medication usage. However, participants in the SA group believed that SA was useful for AR and recommended it for self-care. The credibility of the blinding method was successful. No adverse effects were considered to be related to the intervention. Acupressure is feasible and appears to be safe for self-administration by AR sufferers. Experience from this pilot study has guided minor amendments to the protocol. A large-scale randomized controlled trial is warranted to further investigate the efficacy and safety of self-administered acupressure for the management of AR.

Exploring the course of adolescent anxiety and depression: associations with white matter tract microstructure.

Cross-sectional Diffusion Tensor Imaging (DTI) studies have reported alterations in white matter (WM) microstructure in adolescents with internalizing psychopathology. Yet, longitudinal studies investigating the course of WM microstructure are lacking. This study explored WM alterations and its relation to clinical symptoms over time in adolescents with internalizing disorders. DTI scans were acquired at baseline and after three months in 22 adolescents with clinical depression and comorbid anxiety (INT), and 21 healthy peers (HC) (age: 12-18). Tract-based spatial statistics was used for three voxelwise analyses: i) changes in WM microstructure between and within the INT and HC group; ii) associations between changes in symptom severity and changes in WM microstructure within youths with INT; and iii) associations between baseline WM parameters with changes in symptom severity within youths with INT. Data did not reveal changes in WM microstructure between or within groups over three months' time nor associations between changes in WM microstructure and changes in self-reported symptoms (analyses corrected for age, gender and puberty stage). Lower baseline levels of fractional anisotropy (FA) in the right posterior corona radiata (PCR) and right cingulum were associated with a higher decrease of depressive symptoms within the INT group. Post hoc analysis of additional WM parameters in the significant FA clusters showed that higher levels of baseline mean diffusivity and radial diffusivity in the PCR were associated with a lower decrease in depressive symptoms. Baseline WM microstructure characteristics were associated with a higher decrease in depressive symptoms over time. These findings increase our understanding of neurobiological mechanisms underlying the course of internalizing disorders in adolescents.

Intranasal Carbetocin Reduces Hyperphagia and Anxiety and Distress Behaviors in Prader-Willi Syndrome: Results From the CARE-PWS Randomized, Double-Blind, Placebo-Controlled Study

Prader-Willi syndrome (PWS) is a complex genetic disorder associated with multiple neuroendocrine abnormalities, including significantly decreased hypothalamic oxytocin levels, resulting in symptoms of severe hyperphagia (an unrelenting false sense of starvation) and multiple severe neuropsychiatric and behavioral issues. CARE-PWS, a multi-center, randomized, double-blind, placebo-controlled phase 3 study, has evaluated the efficacy, safety and tolerability of intranasal carbetocin, a selective oxytocin receptor agonist, in participants with PWS. Eligible participants aged 7 through 18 with genetically confirmed PWS were randomized in equal proportions to three treatment arms for the 8-week placebo-controlled period of the study: carbetocin 9.6 mg, carbetocin 3.2 mg, or a matching placebo, administered by nasal spray three times a day with meals. The primary endpoint assessed changes from baseline to week 8 in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) or Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores for the carbetocin 9.6 mg arm vs placebo, and the first secondary endpoint assessed changes from baseline to week 8 in HQ-CT or CY-BOCS scores for the carbetocin 3.2 mg arm vs placebo. Additional secondary endpoints included changes from baseline to week 8 in PWS Anxiety and Distress Questionnaire (PADQ) scores, and Clinical Global Impression of Change (CGI-C) scores evaluating the overall change in severity of PWS symptoms at week 8. Due to COVID-19, enrollment was closed early with 119 evaluable participants for the primary analysis. In the carbetocin 9.6 mg arm, trends toward numerically greater improvements in HQ-CT and CGI-C scores relative to placebo were observed but did not reach statistical significance; however, the carbetocin 3.2 mg arm demonstrated a significant improvement in HQ-CT scores (LS mean improvement vs placebo -3.14 points, p=0.016). In the 3.2 mg arm, additional consistent evidence of improvements versus placebo was seen in multiple secondary endpoints, including CGI-C (p=0.027) and PADQ (p=0.027). Numeric trends toward improvement in CY-BOCS scores were observed in each dose arm, but did not reach statistical significance versus placebo. During the subsequent long-term follow-up period of the study, both carbetocin arms have experienced continued numeric improvements from baseline across multiple endpoints. Intranasal carbetocin was generally well-tolerated; the most frequently reported adverse event was flushing, which was generally mild and transient. In conclusion, results of the CARE-PWS study support that intranasal carbetocin appears to be safe and well tolerated, and reduces hyperphagia and anxiety and distress behaviors in PWS.

Contextualizing the road to recovery: A novel method of assessing outcome trajectories in clinical trials.

In clinical trials, standardized assessment conducted by research staff facilitates identification of treatment benefit. Narrative notes completed by clinicians offer a novel source to characterize and contextualize outcomes. In this study, we examine qualitative analysis of clinical notes as a method to augment quantitative outcome measures and supply meaningful context in clinical trials. Two hundred eighty-four clinical progress notes from 19 participants with schizophrenia or schizoaffective disorder assigned to receive either auditory-targeted cognitive training or treatment as usual were included. Qualitative analysis of weekly progress notes written by clinicians involved in ongoing care of the participants was used to identify overall outcome trajectories and specific changes in program participation, social functioning, and symptom severity. Trajectories were compared with the parent study's 2 primary outcome measures. Qualitative analysis identified personalized and complex trajectories for individual participants. Approximately half the participants improved overall. Most participants displayed improved program participation and social functioning, whereas most participants experienced symptom deterioration. Engagement in targeted cognitive training did not impact change in trajectories. Qualitative trajectories were congruent (e.g., both indicated improvement) with the 2 primary outcome measures for 26-36% of the participants depending on the comparison. Including qualitative analysis of clinician progress notes provides useful context and identifies underlying processes not captured in quantitative data. However, they cannot replace quantitative outcome measurement. Better alignment with clinician- and patient-targeted outcomes may strengthen clinical trials. Qualitative analysis of routinely collected data can benefit research and programmatic decision making in usual care settings. (PsycInfo Database Record (c) 2021 APA, all rights reserved).