Meaningful Improvements In Symptoms Research Articles

Rehabilitation of Persistent Symptoms and Neurocognitive Deficits Following Sports-Related Concussion in a Professional Hockey Player: Case Study

To demonstrate decreased post-concussive symptomatology and neurocognitive improvements in a professional hockey player following a multimodal, functional neurology approach to neurorehabilitation. Hockey is one of the top 3 sports in which concussions occur and has one of the top 10 highest participation numbers of sports in the northern hemisphere. The investigation of treatment modalities is warranted given the prevalence of hockey throughout society. This case study presents a 31-year-old male professional hockey athlete who had sustained 5 diagnosed concussions with additional suspected concussions throughout his career. His symptoms remained after independently receiving physical therapy and vestibular rehabilitation, causing an inability to continue playing hockey at a professional level. The patient was prescribed 10 treatment sessions over 5 contiguous days at an outpatient neurorehabilitation center specializing in functional neurology. The C3Logix neurocognitive assessment and graded symptom checklist were utilized at intake and discharge. Multimodal treatment interventions included transcranial photobiomodulation, non-invasive neuromodulation of the lingual branch of the trigeminal nerve, hand-eye coordination training, vestibular rehabilitation utilizing a three-axis whole-body off-axis rotational device, and cognitive training. On intake, their composite symptom score was reported as 16/162, Trail Making Test Part B was 24.1 seconds, Simple Reaction Time was 274 milliseconds, and Choice Reaction Time was 496 milliseconds. On discharge, the patient experienced an 81% in self-reported symptoms, Trail Making Test Part B improved to 17 seconds (+29.46%), Simple Reaction Time was 252 milliseconds (8% faster), and Choice Reaction Time was 465 milliseconds (24% faster). The present case study results demonstrated meaningful improvements in both self-rated concussion symptoms and neurocognitive performance for this patient. The Press suggest further investigation into functional neurology-based, multimodal, intensive approaches to decrease chronic post-concussion symptoms and improve neurocognitive performance in athletes that engage in hockey.

Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study

Idiopathic hypersomnia is a central hypersomnolence disorder mainly characterised by excessive daytime sleepiness, with prolonged night-time sleep and pronounced sleep inertia. Until August, 2021, no medication had regulatory approval for the treatment of idiopathic hypersomnia. This study aimed to evaluate the safety and efficacy of lower-sodium oxybate in idiopathic hypersomnia. This was a phase 3, multicentre (50 specialist sleep centres; six EU countries and the USA), placebo-controlled, double-blind, randomised withdrawal study. Participants (aged 18-75 years) with idiopathic hypersomnia (meeting criteria from the International Classification of Sleep Disorders, 2nd or 3rd editions) began lower-sodium oxybate treatment (oral solution once or twice nightly) in an open-label titration and optimisation period (10-14 weeks), followed by a 2-week, open-label, stable-dose period. After these open-label periods, participants were randomised (1:1) by means of an interactive web recognition system, stratified by participants' baseline medication use, to either placebo or lower-sodium oxybate (individually optimised dose; range 2·5-9·0 g/night) during a 2-week, double-blind, randomised withdrawal period. To maintain masking of treatment assignment, placebo and lower-sodium oxybate oral solutions were matched in volume, appearance, and taste. During the double-blind, randomised withdrawal period, participants and investigators were unaware of treatment assignments. The primary efficacy endpoint was change in Epworth Sleepiness Scale (ESS) score from the end of the stable-dose period to the end of the double-blind, randomised withdrawal period, which was assessed in the modified intention-to-treat population (defined as all participants who were randomly assigned, took at least one dose of study medication during the double blind, randomised withdrawal period, and had at least one set of post-randomisation assessments for the primary or key secondary endpoints). Adverse events were assessed in the safety population (defined as all participants who took at least one dose of study medication). This study is registered at ClinicalTrials.gov, NCT03533114, and at EU Clinical Trials, 2018-001311-79, and is complete. Between Nov 27, 2018, and March 6, 2020, 154 participants were enrolled and comprised the safety population. ESS scores decreased from a mean of 15·7 (SD 3·8) at baseline to 6·1 (4·0) by the end of the stable-dose period. After the open-label periods, 115 participants were randomly assigned either placebo (n=59) or lower-sodium oxybate (n=56) and comprised the modified intention-to-treat population. During the double-blind, randomised withdrawal period, ESS scores increased (worsened) in participants randomly assigned to placebo but remained stable in those assigned to lower-sodium oxybate (least squares mean difference -6·5; 95% CI -8·0 to -5·0; p<0·0001). Treatment-emergent adverse events included nausea (34 [22%] of 154), headache (27 [18%] of 154), dizziness (19 [12%] of 154), anxiety (17 [11%] 154), and vomiting (17 [11%] 154). No deaths were reported during the study. Lower-sodium oxybate treatment resulted in a clinically meaningful improvement in idiopathic hypersomnia symptoms, with an overall safety profile consistent with that reported for narcolepsy. Lower-sodium oxybate was approved in August, 2021, by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. Jazz Pharmaceuticals.

Idiopathic hypersomnia: does first to approval mean first-line treatment?

Idiopathic hypersomnia is a chronic sleep–wake disorder that causes excessive daytime sleepiness, despite normal or long nocturnal sleep durations, often accompanied by pronounced sleep inertia when awakening from overnight sleep or naps. Several drugs are prescribed off-label for patients with idiopathic hypersomnia, including modafinil, sodium oxybate, and psychostimulants. 1 Maski K Trotti LM Kotagal S et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021; 17: 1881-1893 Crossref PubMed Scopus (6) Google Scholar Oxybate medications are prescribed and dispensed in the USA under a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy programme and carry several so-called black box warnings for serious side-effects. In August, 2021, the FDA approved calcium, magnesium, potassium, and sodium oxybate (known as lower-sodium oxybate) for the treatment of adults with idiopathic hypersomnia. 2 US Food and Drug AdministrationFDA grants first of its kind indication for chronic sleep disorder treatment. https://www.fda.gov/news-events/press-announcements/fda-grants-first-its-kind-indication-chronic-sleep-disorder-treatmentDate: 2021 Date accessed: November 3, 2021 Google Scholar This approval is an important milestone for people living with idiopathic hypersomnia, making lower-sodium oxybate the first and only FDA-approved medication for the treatment of this disorder. Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal studyLower-sodium oxybate treatment resulted in a clinically meaningful improvement in idiopathic hypersomnia symptoms, with an overall safety profile consistent with that reported for narcolepsy. Lower-sodium oxybate was approved in August, 2021, by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. Full-Text PDF

Lumbar Discectomy With Barricaid Device Implantation in Patients at High Risk of Reherniation: Initial Results From a Postmarket Study.

BackgroundPatients with large defects in the annulus fibrosus following lumbar discectomy have high rates of symptomatic reherniation and reoperation. An FDA randomized controlled trial (RCT) with a bone-anchored device (Barricaid, Intrinsic Therapeutics, Woburn, MA) that occludes the annular defect reported significantly lower risk of symptomatic reherniation and reoperation compared to patients receiving discectomy only. However, results of the Barricaid device in real-world use remain limited. MethodsThis was a post-market study to determine the real-world outcomes of the Barricaid device when used in addition to primary lumbar discectomy in patients with large annular defects. Main outcomes included leg pain severity, Oswestry Disability Index (ODI), adverse events, symptomatic reherniation, and reoperation. Imaging studies were read by an independent imaging core laboratory. This paper reports the initial three-month primary endpoint results from the trial; one-year patient follow-up is ongoing.ResultsAmong 55 patients (mean age 41±13 years, 60% male), the mean percent reduction in leg pain severity was 92%, and the mean percent reduction in ODI score was 79%. The three-month rate of symptomatic reherniation was 3.6% and the rate of reoperation was 1.8%. The serious adverse event rate was 5.5%; no device migrations or fractures were observed. ConclusionAmong patients with large annular defects following lumbar discectomy treated with the Barricaid device in real-world conditions, early results demonstrated clinically meaningful improvements in patient symptoms and low rates of symptomatic reherniation, reoperation, and complications, which were comparable to those observed with the device in an FDA-regulated trial.

Randomized controlled trial of ragweed sublingual immunotherapy tablet in the subpopulation of Canadian children and adolescents with allergic rhinoconjunctivitis

BackgroundPost hoc analyses of randomized placebo-controlled trials have demonstrated efficacy and tolerability of the ragweed sublingual immunotherapy (SLIT)-tablet in Canadian adults with ragweed pollen-induced allergic rhinitis/conjunctivitis (AR/C). This post hoc analysis evaluated the efficacy and tolerability of the ragweed SLIT-tablet in the subpopulation of Canadian children and adolescents with AR/C in a previously described randomized, double-blind, placebo-controlled trial.MethodsThe trial (NCT02478398) was conducted in North American and European children/adolescents ages 5–17 years with ragweed pollen-induced AR/C with or without asthma (FEV1 ≥ 80% predicted). Participants were randomized to daily ragweed SLIT-tablet (12 Amb a 1-U) or placebo for up to 28 weeks. The primary endpoint was the average total combined score (TCS; sum of rhinoconjunctivitis daily symptom score [DSS] and daily medication score [DMS]) during peak ragweed pollen season (RPS). Key secondary endpoints were TCS during the entire RPS, and DSS and DMS during peak RPS. Post hoc analyses of the primary and key secondary endpoints were conducted in the subpopulation of Canadian participants.ResultsOf the 1025 randomized participants, 246 (SLIT-tablet, n = 116; placebo, n = 130) were in the Canadian subpopulation. In the total study population, relative TCS (95% CI) improvement with ragweed SLIT-tablet versus placebo was − 38.3% (− 46.0%, − 29.7%; least square [LS] mean difference, − 2.73; P < 0.001) during peak RPS. In the Canadian subpopulation, relative TCS improvements with ragweed SLIT-tablet versus placebo were − 40.8% (− 54.5%, − 20.2%; LS mean difference, − 1.59; P = 0.001) during peak RPS and − 36.6% (− 50.2%, − 16.5%; LS mean difference, − 1.36; P = 0.002) during the entire RPS. DSS and DMS during peak RPS in the Canadian subpopulation improved with SLIT-tablet versus placebo by − 30.6% (− 45.2%, − 7.7%; LS mean difference, − 0.94; P = 0.010) and − 77.2% (− 97.5%, − 44.2%; LS mean difference, − 0.66; P = 0.003), respectively. No events of anaphylaxis, airway compromise, intramuscular epinephrine administration, eosinophilic esophagitis, or severe treatment-related systemic allergic reactions were reported in the overall population or Canadian subpopulation.ConclusionEfficacy and safety of the ragweed SLIT-tablet in Canadian children/adolescents with ragweed pollen-induced AR/C was consistent with the total study population. The ragweed SLIT-tablet resulted in clinically meaningful improvement in symptoms, decreased symptom-relieving medication use, and was well tolerated in Canadian children/adolescents.Trial registration: clinicaltrials.gov, NCT02478398. Registered June 23, 2015, https://clinicaltrials.gov/ct2/show/NCT02478398?term=NCT02478398&draw=2&rank=1

Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: Effect of Demographics and Baseline Disease Characteristics on Efficacy.

IntroductionWe present certolizumab pegol (CZP) efficacy data across patient demographic and baseline disease characteristic subgroups from a phase 2/3 trial investigating CZP treatment in Japanese patients with moderate to severe plaque psoriasis (PSO; ClinicalTrials.gov identifier: NCT03051217).MethodsPatients were randomised 1:2:2 to placebo once every 2 weeks (Q2W), CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0, 2 and 4) for 16 weeks. Patients who achieved ≥ 50% reduction in their baseline Psoriasis Area and Severity Index (PASI 50) score at week 16 continued therapy to week 52. PASI 75/90 (75% and 90% reduction, respectively) and Physician’s Global Assessment (PGA) 0/1 responder rates at weeks 16 and 52 were reported for patient demographic and baseline disease characteristic subgroups, including body mass index (BMI), PASI, disease duration and prior biologic use. Non-responder imputation was used.ResultsOf the randomised patients, 2/26 patients in the placebo group, 47/53 patients in the CZP 400 mg Q2W group and and 39/48 patients in the CZP 200 mg Q2W group completed week 52. In the subgroups evaluated, week 16 efficacy was generally maintained through week 52. At week 52, PASI 75 was achieved by 84.2, 85.7 and 80.0% of patients receiving CZP 400 mg Q2W in the low (15.0–23.7 kg/m2)/intermediate (> 23.7–27.4 kg/m2)/high (> 27.4–47.0 kg/m2) BMI subgroups, respectively, and by 77.8, 70.6 and 69.2%, respectively of patients treated with CZP 200 mg Q2W. PASI 75 at week 52 was achieved by 92.9, 75.0 and 84.2% of patients receiving CZP 400 mg Q2W in the low (12.0–18.0)/intermediate (> 18.0–27.0)/high (> 27.0–67.2) baseline PASI subgroups, respectively, and by 85.0, 58.3 and 68.8% of patients receiving CZP 200 mg Q2W, respectively. Similar responses were observed across other subgroups evaluated for both CZP doses in PASI 75/90 and PGA 0/1.ConclusionClinically meaningful improvements in signs and symptoms of PSO were maintained through week 52 for CZP dosed at 400 mg Q2W or 200 mg Q2W, across patient subgroups. In general, a numerically greater response was observed for patients receiving CZP 400 mg Q2W versus those receiving CZP 200 mg Q2W across patient subgroups.Trial RegistrationClinicalTrials.gov identifier, NCT03051217.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00645-2.

Effect of a Novel Omega-3 and Omega-6 Fatty Acid Supplement on Dry Eye Disease: A 3-month Randomized Controlled Trial.

Supplementing diet with a novel combination of omega-3 and omega-6 fatty acids significantly improved symptoms in extremely symptomatic participants with dry eye disease (DED). This study aimed to determine the effect of daily intake of a novel combination of essential fatty acids on signs and symptoms of DED. Participants with moderate to severe DED were enrolled in a prospective, randomized, double-masked parallel group study. Participants ingested either the treatment supplement containing omega-3 and omega-6 fatty acids (1200 mg eicosapentaenoic acid, 300 mg docosahexaenoic acid, 150 mg γ-linoleic acid) or the placebo (coconut and olive oil) daily for 3 months. To determine compliance, Omega-3 Index blood tests were conducted. At baseline and at 1 and 3 months, the following assessments were conducted: Ocular Surface Disease Index (OSDI) questionnaire and Symptom Assessment Questionnaire in Dry Eye, noninvasive tear breakup time, tear meniscus height, tear osmolarity, ocular redness, surface staining, Schirmer test, and meibography. Fifty participants (mean ± standard deviation baseline OSDI score, 52.2 ± 16.5) completed the study: 24 randomized to treatment and 26 randomized to placebo. Although there was an improvement in OSDI score at 3 months for both groups (treatment: -13.4 points, P = .003; placebo: -7.8 points, P = .02), participants with baseline OSDI scores >52 demonstrated an even larger significant improvement in symptoms with the treatment at 3 months compared with baseline (n = 13, -20.8 points, P = .002). There were no significant changes in any of the ocular assessments at 1 or 3 months (all P > .05). After 3 months, Omega-3 Index increased by 34% in the treatment group (baseline, 5.3 ± 0.8; 3 months, 8.0 ± 2.1; P < .001) and did not change in the placebo group (baseline, 4.8 ± 0.8; 3 months, 4.8 ± 0.6; P = .95). Supplementation with eicosapentaenoic acid, docosahexaenoic acid, and γ-linoleic acid resulted in a significant and clinically meaningful improvement of dry eye symptoms in extremely symptomatic participants with DED (OSDI ≥52).

Examining attendance patterns across integrated therapies for posttraumatic stress disorder and alcohol use disorder

A substantial body of evidence supports the use of integrated treatments for posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). Integrated trauma-focused exposure therapies reduce PTSD symptoms more than comparison treatments, including integrated coping skills therapies, but demonstrate lower attendance, raising questions regarding the relationships between attendance, outcomes, and treatment type. We aimed to examine these relationships in a RCT comparing integrated prolonged exposure (Concurrent Treatment for PTSD and Substance Use Disorders Using Prolonged Exposure, COPE; n = 58), to integrated coping skills therapy (Seeking Safety, SS; n = 52) offered in 12 sessions, with an option to extend up to four additional sessions. Participants were categorized based on number of sessions attended (0–4; 5–8; 9–12; 13–16). Multilevel modeling revealed that only when examining therapy attendance segments individually, clinical outcomes were comparable across treatments except in the 9–12 group, with COPE resulting in greater reductions in PTSD symptoms (p < 0.001), but not in alcohol use. Extending past 12 sessions was not associated with additional clinically meaningful symptom improvement for either treatment. These results suggest that attending a complete or near complete course of exposure therapy may enhance PTSD outcomes relative to non-trauma-focused therapies.

Dupilumab Provides Rapid and Sustained Clinically Meaningful Responses in Adults with Moderate-to-severe Atopic Dermatitis.

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a realworld setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo-controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis.

Updated Health-Related Quality of Life Results from the KarMMa Clinical Study in Patients with Relapsed and Refractory Multiple Myeloma Treated with the B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy Idecabtagene Vicleucel (ide-cel, bb2121)

Updated Health-Related Quality of Life Results from the KarMMa Clinical Study in Patients with Relapsed and Refractory Multiple Myeloma Treated with the B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy Idecabtagene Vicleucel (ide-cel, bb2121)

Mining Clinical Data for Novel Posttraumatic Stress Disorder Medications

BackgroundDespite the prevalence and negative impact of posttraumatic stress disorder (PTSD), there are few medications approved by the U.S. Food and Drug Administration for treatment, and approved medications do not work well enough. We leveraged large-scale electronic health record data to identify existing medications that may be repurposed as PTSD treatments. MethodsWe constructed a mechanistic tree of all Food and Drug Administration–approved medications and used the tree-based scan statistic to identify medications associated with greater than expected levels of clinically meaningful improvement in PTSD symptoms using electronic health record data from the U.S. Department of Veterans Affairs. Our cohort included patients with a diagnosis of PTSD who had repeated symptom measurements using the PTSD Checklist over a 20-year period (N = 168,941). We calculated observed numbers based on patients taking each drug or mechanistically related class of drugs and the expected numbers based on the tree as a whole. ResultsMedications typically used to treat PTSD, such as the Food and Drug Administration–approved agent sertraline, were associated with improvement in PTSD symptoms, but the effects were small. Several, but not all, direct-acting antivirals used in the treatment of hepatitis C virus demonstrated a strong association with PTSD improvement. The finding was robust to a sensitivity analysis excluding patients who received established PTSD treatments, including trauma-focused psychotherapy, concurrent with hepatitis treatment. ConclusionsOur exploratory approach both demonstrated findings that are consistent with what is known about pharmacotherapy for PTSD and uncovered a novel class of medications that may improve PTSD symptoms.

Ketamine-assisted psychotherapy for trauma-exposed patients in an outpatient setting: A clinical chart review study

Abstract Trauma exposure across the lifespan produces risks for posttraumatic stress disorder (PTSD), depression, anxiety, as well as global disability in functioning. This retrospective clinical chart review is the first of its kind to assess the utility of sublingual ketamine-assisted body-centered psychotherapy in trauma-exposed patients in a real world clinic setting. De-identified clinical records data on self-reported symptom measures were retrospectively analyzed for patients (N = 18; M age = 45.22, SD = 12.90) entering ketamine-assisted psychotherapy treatment in an outpatient clinic between 2018 and 2020. Patients who completed six sessions of ketamine therapy reported meaningful (e.g., medium effect size) improvements in PTSD symptoms (P = 0.058; d = −0.48) and global disability in functioning (P = 0.050; d = −0.52) and statistically significant and meaningful improvements in depression (P = 0.019; d = −0.53). There were no improvements in anxiety symptoms. Sublingual ketamine-assisted psychotherapy was associated with heterogenous clinical utility among patients with trauma-exposure in an outpatient setting. This study was underpowered and unrepresentative of the population of ketamine patients in the United States. Replication of these findings is needed with larger and more diverse patient samples.

Efficacy of Lifitegrast Ophthalmic Solution, 5.0%, in Patients With Moderate to Severe Dry Eye Disease

An investigation of the treatment effect of lifitegrast ophthalmic solution, 5.0%, in different subgroups by severity of dry eye disease (DED) seems warranted. To explore the heterogeneity across different subgroups of DED and identify which participants were most likely to achieve clinically meaningful benefit with lifitegrast treatment. This post hoc responder analysis was performed using the data from the phase 3 OPUS-2 and OPUS-3 studies, which were 12-week, prospective, double-masked, multicenter, placebo-controlled, randomized, parallel-arm clinical trials that previously demonstrated the efficacy of lifitegrast in DED. Pooled data were stratified into 4 subgroups based on severity of inferior corneal staining score (ICSS; ≤1.5 vs >1.5) and eye dryness score (EDS; <60 or ≥60) at baseline. Data were collected from December 7, 2012, to October 5, 2015, and post hoc analysis was performed from April 14, 2020, to July 30, 2021. Lifitegrast or placebo twice daily for 84 days. Proportion of participants with (1) a clinically meaningful improvement in signs (ICSS or total corneal staining score [TCSS]) and symptoms (EDS or global visual analog scale [VAS]) and (2) a composite response for a given sign and symptom end point pair at day 84 were measured. Clinically meaningful improvement was defined as at least 30% improvement in symptoms (EDS or global VAS) and either at least a 1-point improvement in ICSS or at least a 3-point improvement in TCSS. For the composite responder analysis, the end point pairs were defined as at least a 30% reduction in EDS and at least a 1-point improvement in ICSS; at least a 30% reduction in EDS and at least a 3-point improvement in TCSS; at least a 30% improvement in global VAS and at least a 1-point improvement in ICSS; and at least a 30% improvement in global VAS and at least a 3-point improvement in TCSS. In total, 1429 participants (716 in the placebo group and 713 in the lifitegrast group) were analyzed (1087 women [76.1%]; mean [SD] age, 58.7 [14.3] years). For the overall pooled population, responder and composite responder rates favored lifitegrast vs placebo (odds ratio range, 1.29 [95% CI, 1.05-1.59] to 2.10 [95% CI, 1.68-2.61]; P ≤ .02). In the composite analysis, the subgroup with ICSS of greater than 1.5 and EDS of at least 60 at baseline (ie, moderate to severe DED) demonstrated a 1.70- to 2.11-fold higher odds of achieving clinically meaningful improvement with lifitegrast across all sign and symptom end point pairs (P ≤ .001). These post hoc findings suggest that lifitegrast ophthalmic solution, 5.0%, treatment may be associated with a response in participants with moderate to severe signs and symptoms of DED. ClinicalTrials.gov Identifier: NCT02284516.

Collaborative care for depression yields similar improvement among older and younger rural adults

Depressive disorders are among the most prevalent mental health conditions; however, significant barriers to treatment access persist. This study examined differences in depression outcomes between younger and older adults in a large-scale implementation demonstration of the collaborative care model (CoCM). Secondary data analysis of a longitudinal, observational implementation demonstration at eight primary care clinics across low-resourced rural or frontier areas of the Western United States. Seven of these clinics were federally qualified health centers. The sample consisted of 3722 younger (18-64 years) and older (65+ years) adult primary care patients diagnosed with unipolar depression. All participants received depression treatment via CoCM, which enhances usual primary care and makes efficient use of specialists by using a behavioral healthcare manager and a psychiatric consultant to support primary care providers. Clinics were followed for up to 27 months. Patients were followed until they completed treatment or dropped out. The Patient Health Questionnaire (PHQ-9) assessed depressive symptoms at baseline (enrollment) and at most follow-up contacts. The primary treatment outcome was a change between a patient's first and last recorded PHQ-9 scores. Across both age groups, there was an average overall reduction of 6.9 points on the PHQ-9. Older adults demonstrated a greater decrease in depression scores of 2.06 points (95% CI -2.98 to -1.14, p < 0.001) on the PHQ-9 compared with younger adults. Estimates were robust when adjusting for gender, race, and clinic. CoCM resulted in meaningful improvement in depressive symptoms across age groups.

Changes in Carcinoid Syndrome Symptoms Among Patients Receiving Telotristat Ethyl in US Clinical Practice: Findings from the TELEPRO-II Real-World Study.

BackgroundInadequately controlled symptoms incur a substantial burden on patients with neuroendocrine tumors and carcinoid syndrome (CS). The effectiveness of telotristat ethyl (TE) with a somatostatin analog for uncontrolled CS diarrhea has been demonstrated in clinical trials and observational studies. TELEPRO-II was a prospective observational study evaluating TE’s effectiveness in clinical practice over the first 3 months of treatment.MethodsPatients initiating TE in 2018 participated in an optional nurse support program reporting CS symptoms during interviews at baseline and 1, 2, and 3 months after TE initiation. Eligible patients received TE for ≥3 months and reported symptom burden at baseline and ≥1 follow-up visit within the first 3 months. Daily bowel movement (BM) frequency and flushing episodes were reported as events/episodes per day. Stool consistency, nausea severity, urgency severity, and abdominal pain were reported on a severity scale (1–10). Symptom changes were evaluated using paired-sample t-tests and Wilcoxon signed-rank tests. Analysis of symptoms based on achievement of <30% or ≥30% reduction in daily BM frequency was conducted using a cumulative distribution function.ResultsA total of 684/1603 (43%) patients were eligible for analysis. At baseline, patients reported a mean of 6.3 BM/day, nausea severity of 8.4/10 and stool urgency of 8.2/10. Significant improvements in all CS symptoms were observed after 3 months of TE. Mean daily BMs were reduced 64% after 3 months of TE (mean reduction [SD], –3.99 [3.8]; P<0.0001). Most patients (74%, n=503) reported ≥30% reduction in daily BM frequency; these patients also reported improvements in other symptoms (76–87%). Patients with <30% reduction in daily BMs also reported improvements in nausea severity (62%, n=24), daily flushing episodes (66%, n=98), abdominal pain (50%, n=60), urgency severity (38%, n=64), and stool consistency (24%, n=44).ConclusionPatients treated with TE in a real-world setting experienced significant, clinically meaningful improvements in CS symptoms.

FMRI Neurofeedback-Enhanced Cognitive Reappraisal Training in Depression: A Double-Blind Comparison of Left and Right vlPFC Regulation.

Affective disorders are associated with maladaptive emotion regulation strategies. In particular, the left more than the right ventrolateral prefrontal cortex (vlPFC) may insufficiently regulate emotion processing, e.g., in the amygdala. A double-blind cross-over study investigated NF-supported cognitive reappraisal training in major depression (n = 42) and age- and gender-matched controls (n = 39). In a randomized order, participants trained to upregulate either the left or the right vlPFC during cognitive reappraisal of negative images on two separate days. We wanted to confirm regional specific NF effects with improved learning for left compared to right vlPFC (ClinicalTrials.gov NCT03183947). Brain responses and connectivity were studied with respect to training progress, gender, and clinical outcomes in a 4-week follow-up. Increase of vlPFC activity was stronger after NF training from the left- than the right-hemispheric ROI. This regional-specific NF effect during cognitive reappraisal was present across patients with depression and controls and supports a central role of the left vlPFC for cognitive reappraisal. Further, the activity in the left target region was associated with increased use of cognitive reappraisal strategies (r = 0.48). In the 4-week follow-up, 75% of patients with depression reported a successful application of learned strategies in everyday life and 55% a clinically meaningful symptom improvement suggesting clinical usability.

27394 Dupilumab provides clinically meaningful improvement in atopic dermatitis (AD) signs, symptoms, and quality of life in children with severe AD: Results from the LIBERTY AD PEDS phase 3 clinical trial

Background: Patients with atopic dermatitis (AD) suffer from a multidimensional disease burden. We report clinically meaningful improvements in AD signs, symptoms, and quality of life in children treated with FDA-approved doses of dupilumab.

Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial.

Peppermint oil is often used to treat irritable bowel syndrome (IBS); however, the overall quality of previous studies is low, and findings have been heterogeneous. This study aimed to compare the effects of peppermint oil vs placebo in relieving IBS symptoms. In a 6-week, randomized, double-blind, placebo-controlled trial at a single academic center in the United States, individuals diagnosed with IBS (Rome IV criteria), with moderate to severe symptoms based on the IBS Severity Scoring System (IBS-SSS score ≥175), were randomized to enteric-coated peppermint oil 180 mg 3 times daily vs placebo in a 1:2 ratio. The primary outcome was mean change in IBS-SSS scores from baseline to 6-week endpoint. A modified intent-to-treat analysis revealed that there were substantial mean improvements from baseline to 6-week endpoint in the main outcome measure (IBS-SSS) for both peppermint oil (90.8, SD = 75.3) and placebo (100.3, SD = 99.6). Although the peppermint oil group reported numerically lower improvement than the placebo group, the effect size was small (d = -0.11), and the difference between the groups was not statistically significant (P = 0.97). Similarly, both groups reported substantial improvements on the secondary endpoints; but again, there were no statistically significant differences between the groups on any of the secondary measures. Sensitivity analyses using multiple imputation to replace missing data produced similar results and revealed no significant differences between peppermint oil and placebo on any outcome measure. Peppermint oil and placebo both showed clinically meaningful improvement in IBS symptoms. However, there were no significant differences between the groups. Further large, rigorous trials are needed to evaluate the role of peppermint oil for the treatment of IBS.

Internet-delivered cognitive-behaviour therapy (ICBT) for obsessive-compulsive disorder when delivered as routine clinical care: A phase IV clinical trial

Cognitive-behaviour therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), but many patients experience difficulty accessing this treatment. Internet-delivered CBT (ICBT) enhances access to CBT for individuals with OCD and has been shown to be efficacious in Phase I, II, and III clinical trials. However, there are fewer studies investigating ICBT for OCD in Phase IV clinical trials, which demonstrate the effectiveness of the intervention when provided as part of routine care. The aim of the present study was to report on the effectiveness of ICBT for OCD, using data from Australia’s MindSpot Clinic, a federally funded treatment service that provides free ICBT to Australian adults with anxiety, depression, and pain conditions. A total of 225 MindSpot users (68 % female; Mage = 34.82; SD = 11.02) were included in the study. Within-group effect sizes at post-treatment on the Yale-Brown Obsessive-Compulsive Scale, indicated medium effect sizes (g = 0.6; 95 % CI: 0.5−0.7), increasing to large effects at three-month follow up (g = 0.9; 95 % CI: 0.8–1.0). Effects on secondary outcome measures including measures of depression, generalized anxiety, and psychological distress ranged from (g = 0.5–0.6) at post-treatment and (g = 0.5–0.7) at three-month follow up. Results from benchmarking analyses indicated that the results from routine care were significantly smaller than those found in a recent clinical trial using the same treatment protocol. The results indicate that ICBT delivered in real world settings is associated with meaningful improvements in OCD symptoms, however future research may wish to examine which patients respond best to this treatment approach and how to enhance outcomes.

An Open-Label, Phase II Study Of The JAK1 Inhibitor INCB039110 In Patients With Myelofibrosis

An Open-Label, Phase II Study Of The JAK1 Inhibitor INCB039110 In Patients With Myelofibrosis