Improvement In Individual Symptoms Research Articles

E.3 fMRI correlates of symptom-specific improvement in STN deep brain stimulation

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal symptoms of Parkinson’s disease (PD). However, the therapeutic mechanisms are incompletely understood. By leveraging patient-specific brain responses to DBS using functional magnetic resonance imaging (fMRI) acquired during stimulation, we identify and validate symptom-specific networks associated with clinical improvement. Methods: Forty PD patients with STN-DBS were enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. The four cardinal motor outcomes of PD were chosen a priori and measured using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, part III (MDS-UPDRSIII): axial instability, tremor, rigidity, bradykinesia. Stimulation-dependent changes in blood oxygen level-dependent (BOLD) signal were correlated with each symptom. Results: The relationship between BOLD response and outcomes revealed significant networks of clinical response (p<0.001). Using BOLD responses from the network hubs, each symptom-specific model was significantly predictive of actual improvement: axial instability (R2=0.38, p=0.000026), bradykinesia (R2=0.29, p=0.00033), rigidity (R2=0.40, p=0.000013), tremor (R2=0.26, p=0.00073). Conclusions: Using patient-specific imaging, we provide evidence of an association between DBS-evoked fMRI response and individual symptom improvement. Brain networks associated with clinical improvement were different depending on the PD symptom examined, suggesting the presence of symptom-specific networks of efficacy which may allow personalization of DBS therapy.

Effectiveness and Tolerability of Ectoin® Mouth and Throat Spray Althaea Honey (ERS09) for Sore Throat due to Acute Pharyngitis and Dry Cough: A Multicentre, Actively Controlled, Open Label Study in Germany.

Acute pharyngitis can cause sore throat. This multicentre, active-controlled, randomised, open-label, and parallel-group study, conducted according to the German Medical Devices Act, compared the effectiveness and tolerability of ERS09 mouth and throat spray with a well-established device for the treatment of sore throat caused by acute pharyngitis and dry cough. Patients were randomised 1:1 into ERS09/comparator groups (EMSER® Sore Throat Spray) for 7 ± 2 days. Patients and investigators reported effectiveness (change in total symptom score [TSS]) and safety endpoints (incidence of adverse events [AEs]; adverse device effects [ADEs]). A total of 186 patients were included (ERS09: n = 92; comparator: n = 94). The baseline-adjusted mean TSS over 7 days was -90.14 and -74.91 in the ERS09 and comparator groups, respectively (p < 0.05). The majority of patients reached a 50% reduction in symptoms by day 6 (ERS09 = 78.85; comparator = 75.8%). Most patients reported a soothing effect within five minutes (ERS09 = 82%; comparator = 71%). Improvements in individual symptoms were similar with no significant differences between groups; more patients in the ERS09 group reported an improvement in pharyngeal redness/swelling. Three AEs unrelated to medication, one ADE following ERS09, and no serious AE/ADE were reported. ERS09 was as well tolerated and effective as the established device, showing greater improvement in the management of some symptoms and greater patient preference.

Clinical-functional brain connectivity signature predicts longitudinal symptom improvement after acupuncture treatment in patients with functional dyspepsia.

Whilst acupuncture has been shown to be an effective treatment for functional dyspepsia (FD), its efficacy varies significantly among patients. Knowing beforehand how each patient responds to acupuncture treatment will facilitate the ability to produce personalized prescriptions, therefore, improving acupuncture efficacy. The objective of this study was to construct the prediction model, based on the clinical-neuroimaging signature, to forecast the individual symptom improvement of FD patients following a 4-week acupuncture treatment and to identify the critical predictive features that could potentially serve as biomarkers for predicting the efficacy of acupuncture for FD. Clinical-functional brain connectivity signatures were extracted from samples in the training-test set (100 FD patients) and independent validation set (60 FD patients). Based on these signatures and support vector machine algorithms, prediction models were developed in the training test set, followed by model performance evaluation and predictive features extraction. Subsequently, the external robustness of the extracted predictive features in predicting acupuncture efficacy was evaluated by the independent validation set. The developed prediction models possessed an accuracy of 88% in predicting acupuncture responders, as well as an R2 of 0.453 in forecasting symptom relief. Factors that contributed significantly to stronger responsiveness of patients to acupuncture therapy included higher resting-state functional connectivity associated with the orbitofrontal gyrus, caudate, hippocampus, and anterior insula, as well as higher baseline scores of the Symptom Index of Dyspepsia and shorter durations of the condition. Furthermore, the robustness of these features in predicting the efficacy of acupuncture for FD was verified through various machine learning algorithms and independent samples and remained stable in univariate and multivariate analyses. These findings suggest that it is both feasible and reliable to predict the efficacy of acupuncture for FD based on the pre-treatment clinical-neuroimaging signature. The established prediction framework will promote the identification of suitable candidates for acupuncture treatment, thereby improving the efficacy and reducing the cost of acupuncture for FD.

BRACHY: A Randomized Trial to Evaluate Symptom Improvement in Advanced Non-Small Cell Lung Cancer Treated With External Beam Radiation With or Without High-Dose-Rate Intraluminal Brachytherapy

Uncontrolled studies suggest that the addition of high-dose-rate intraluminal brachytherapy (HDRIB) to external beam radiation therapy (EBRT) may improve palliation for patients with advanced non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the potential clinical benefit of adding HDRIB to EBRT in a multicenter randomized trial. Patients with symptomatic stage III or IV NSCLC with endobronchial disease were randomized to EBRT (20 Gy in 5 daily fractions over 1 week or 30 Gy in 10 daily fractions over 2 weeks) or the same EBRT plus HDRIB (14 Gy in 2 fractions separated by 1 week). The primary outcome was the proportion of patients who achieved symptomatic improvement in patient-reported overall lung cancer symptoms on the Lung Cancer Symptom Scale (LCSS) at 6 weeks after randomization. Secondary outcomes included improvement in individual symptoms, symptom-progression-free survival, overall survival, and toxicity. The planned sample size was 250 patients based on detection of symptomatic improvement from 40% to 60% with a 2-sided α of .05 and 80% power. A total of 134 patients were randomized over 4.5 years: 67 to each arm. The study closed early owing to slow accrual. The mean age was 69.8 years, and 67% of patients had metastatic disease. At 6 weeks, 19 patients (28.4%) in the EBRT arm and 20 patients (29.9%) in the EBRT plus HDRIB arm experienced an improvement in lung cancer symptoms (P=.84). When limited to patients who completed the LCSS, percentages were 40.4% versus 47.6%, respectively (P=.49). Between group differences in mean change scores (0.3-0.5 standard deviations) in favor of EBRT plus HDRIB were observed for overall symptoms, but only hemoptysis was significantly improved (P=.03). No significant differences were observed in progression-free or overall survival. Grade 3/4 toxicities were similar between groups. Small to moderate improvements were seen in symptom relief with the combined therapy, but they did not reach statistical significance. Further research is necessary before recommending HDRIB in addition to EBRT for palliation of lung cancer symptoms.

Improvement in Individual Symptoms and Total Symptom Score (TSS) and Matching-Adjusted Indirect Comparison (MAIC) Analysis to Compare TSS As a Continuous Endpoint in Patients with Myelofibrosis Treated with Pelabresib in Combination with Ruxolitinib Versus Janus Kinase Inhibitor Monotherapy

Background: Pelabresib (CPI-0610; PELA) is a bromodomain and extraterminal domain (BET) inhibitor in development for the treatment of myelofibrosis (MF). PELA combined with ruxolitinib (RUX) has shown a 56% response rate for ≥50% reduction in total symptom score (TSS) at Wk 24 from baseline (BL; TSS50) in Janus kinase inhibitor (JAKi) treatment-naïve patients (pts) with intermediate or high-risk MF in Arm 3 of the open-label Phase 2 MANIFEST study (NCT02158858). TSS50 is a standard measure of symptom improvement; however, the 50% response threshold does not capture clinical benefit in pts with TSS reduction <50% or pts who achieve TSS50 but could benefit from further symptom improvement (Dueck A, et al. European Hematology Association 2017. Poster E1331). Here, we present percentage change in TSS and subdomains as a continuous endpoint from Arm 3 of MANIFEST and indirect comparisons with historical double-blind JAKi trials in MF. Aims: To assess clinically meaningful changes in TSS with PELA in combination with RUX. TSS subdomains were analyzed to assess the underlying impact of PELA + RUX on symptom scores. In the absence of head-to-head studies of PELA + RUX vs JAKi monotherapy, naïve and matching-adjusted indirect comparison (MAIC) analysis (correcting for potential imbalances in baseline characteristics) were used to investigate improvement in TSS as a continuous endpoint in pts treated with PELA + RUX in Arm 3 of the MANIFEST study with historical double-blind Phase 3 JAKi trials: COMFORT-I (RUX), SIMPLIFY-1 (RUX, momelotinib [MOM]) and JAKARTA (fedratinib [FED]). Methods: In MANIFEST, percentage change in TSS and subdomains (fatigue, night sweats, itching, abdominal discomfort, pain under ribs, feeling of fullness and bone pain) from BL at Week (Wk) 12, 24, 36 and 48 were calculated. Pts with BL score = 0 were excluded. For the MAIC analysis, individual pt level data were available for MANIFEST Arm 3, and study-level data were extracted from published waterfall plots using WebPlotDigitizer (Rohatgia A. https://automeris.io/) for COMFORT-I, SIMPLIFY-1 and JAKARTA (FED 400 mg arm). Unanchored MAIC was conducted, whereby pts were reweighted to adjust for imbalances in key prognostic BL characteristics: gender, MF subtype, International Prognostic Scoring System risk status (IPSS), previous hydroxyurea use, platelet count, hemoglobin levels, spleen volume and JAK2V617F status; as a result, bias due to potential unmeasured differences is unlikely. The weights were used to calculate the effective sample size. Pts with IPSS intermediate-1 were excluded from the analysis. Weighted and unweighted treatment effects in terms of difference in least square (LS) means with their 95% confidence intervals using robust sandwich estimators for variance are presented. Studies used different TSS questionnaire versions; however, variations are subtle, and so comparisons across versions are valid (Dueck A, et al.Blood 2017;130:2168). Results: Comparable mean BL TSS scores were observed: 16.1 in MANIFEST Arm 3 and 17.5-19.4 across comparator Phase 3 studies. In MANIFEST Arm 3, a median reduction from BL of >50% was observed for TSS and all subdomains, and this reduction remained consistent across Wk 12 to Wk 48. TSS distribution in MANIFEST at Wk 24 showed greater median and mean reductions from BL vs JAKi monotherapy studies (Figure 1 shows comparison with RUX in SIMPLIFY-1). Complete summary level balance was achieved in the weighted distributions of the prognostic factors in MANIFEST Arm 3 versus comparators. After adjusting for imbalances, >20% greater reduction in LS mean percentage change in TSS from BL at Wk 24 was observed for all comparisons of MANIFEST Arm 3 vs historical studies, as shown in Figure 2. P values for all MAIC analyses were statistically significant. Conclusions: Analyzing TSS as a continuous endpoint in addition to responder analysis overcomes limitations of using TSS50 alone. TSS50 rates in MANIFEST Arm 3 were higher than all comparator MF studies, and clinically relevant improvements in TSS and its subdomains were observed as early as Wk 12 and were durable over time. When indirectly comparing Arm 3 of the Phase 2 MANIFEST study with historical Phase 3 MF studies using MAIC analysis, improved estimates of changes in TSS with PELA + RUX vs RUX, MOM or FED monotherapy were observed. A randomized Phase 3 MANIFEST-2 study of PELA + RUX vs RUX monotherapy in JAKi-naïve pts is ongoing (NCT04603495). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Treatment with Imetelstat Improves Myelofibrosis-Related Symptoms and Other Patient-Reported Outcomes in Patients with Relapsed or Refractory Higher-Risk Myelofibrosis

Treatment with Imetelstat Improves Myelofibrosis-Related Symptoms and Other Patient-Reported Outcomes in Patients with Relapsed or Refractory Higher-Risk Myelofibrosis

Self-Reported Improvement for Chronic Rhinosinusitis Major Symptoms in Patients Treated with Omalizumab

Objective: To evaluate the clinical effect of omalizumab therapy on the symptoms of patients with chronic rhinosinusitis (CRS). Methods: This cross-sectional study evaluated CRS major symptom improvement in patients with CRS on omalizumab therapy and patients who met omalizumab therapy indications, but could not access coverage for omalizumab. Changes in overall chronic rhinosinusitis symptom burden and each of the major symptoms of CRS were rated on a 10 cm visual analogue scale (VAS). The Mann–Whitney test was used to compare the symptom improvement between groups. Results: Omalizumab therapy provided a mean overall symptom improvement of 69.5% (individual symptom improvement: facial pain 78.5%, nasal obstruction 69.8%, rhinorrhea 56.2%, and olfaction 55.8%). For the control group, mean overall symptom improvement since omalizumab screening was 16.8% (individual symptom improvement: rhinorrhea 16.4%, nasal obstruction 15.3%, no improvement in facial pain or olfaction). Overall, and for each major symptom, improvement was significantly greater for omalizumab treated patients (p &lt; 0.05). Conclusion: Omalizumab treatment provided significant improvement in every major clinical symptom of CRS in the treated cohort of patients with recalcitrant CRS, in comparison to the control cohort. A well-designed randomized clinical trial is needed to further assess the efficacy and safety of omalizumab treatment for CRS.

Evaluation of a Machine Learning Model Based on Pretreatment Symptoms and Electroencephalographic Features to Predict Outcomes of Antidepressant Treatment in Adults With Depression

Despite the high prevalence and potential outcomes of major depressive disorder, whether and how patients will respond to antidepressant medications is not easily predicted. To identify the extent to which a machine learning approach, using gradient-boosted decision trees, can predict acute improvement for individual depressive symptoms with antidepressants based on pretreatment symptom scores and electroencephalographic (EEG) measures. This prognostic study analyzed data collected as part of the International Study to Predict Optimized Treatment in Depression, a randomized, prospective open-label trial to identify clinically useful predictors and moderators of response to commonly used first-line antidepressant medications. Data collection was conducted at 20 sites spanning 5 countries and including 518 adult outpatients (18-65 years of age) from primary care or specialty care practices who received a diagnosis of current major depressive disorder between December 1, 2008, and September 30, 2013. Patients were antidepressant medication naive or willing to undergo a 1-week washout period of any nonprotocol antidepressant medication. Statistical analysis was conducted from January 5 to June 30, 2019. Participants with major depressive disorder were randomized in a 1:1:1 ratio to undergo 8 weeks of treatment with escitalopram oxalate (n = 162), sertraline hydrochloride (n = 176), or extended-release venlafaxine hydrochloride (n = 180). The primary objective was to predict improvement in individual symptoms, defined as the difference in score for each of the symptoms on the 21-item Hamilton Rating Scale for Depression from baseline to week 8, evaluated using the C index. The resulting data set contained 518 patients (274 women; mean [SD] age, 39.0 [12.6] years; mean [SD] 21-item Hamilton Rating Scale for Depression score improvement, 13.0 [7.0]). With the use of 5-fold cross-validation for evaluation, the machine learning model achieved C index scores of 0.8 or higher on 12 of 21 clinician-rated symptoms, with the highest C index score of 0.963 (95% CI, 0.939-1.000) for loss of insight. The importance of any single EEG feature was higher than 5% for prediction of 7 symptoms, with the most important EEG features being the absolute delta band power at the occipital electrode sites (O1, 18.8%; Oz, 6.7%) for loss of insight. Over and above the use of baseline symptom scores alone, the use of both EEG and baseline symptom features was associated with a significant increase in the C index for improvement in 4 symptoms: loss of insight (C index increase, 0.012 [95% CI, 0.001-0.020]), energy loss (C index increase, 0.035 [95% CI, 0.011-0.059]), appetite changes (C index increase, 0.017 [95% CI, 0.003-0.030]), and psychomotor retardation (C index increase, 0.020 [95% CI, 0.008-0.032]). This study suggests that machine learning may be used to identify independent associations of symptoms and EEG features to predict antidepressant-associated improvements in specific symptoms of depression. The approach should next be prospectively validated in clinical trials and settings. ClinicalTrials.gov Identifier: NCT00693849.

Acetic acid disinfection as a potential adjunctive therapy for non-severe COVID-19.

PurposeSARS-CoV-2 is a new pandemic influenza caused by a coronavirus which main route of transmission is through exhaled droplets that primarily infect the nose and the nasopharynx. The aim of this paper is to evaluate the effect of acetic acid, the active component of vinegar, as a potential disinfectant agent for upper airways.MethodsTwenty-nine patients were enrolled and divided into two groups: group 1 (14 patients) was composed of patients treated with off-label hydroxychloroquine and lopinavir/ritonavir, whereas group 2 (15 patients) was composed of patients treated with hydroxychloroquine only, combined with the inhalation of acetic acid disinfectant at a 0.34% concentration. A questionnaire-based evaluation of symptoms was performed after 15 days in both groups.ResultsIt appears that the number of patients treated with acetic acid (group 2) that experienced improvement in individual symptoms was double that of the other group of patients (group 1), although numbers are too small for robust statistical analysis.ConclusionsConsidering its potential benefits and high availability, acetic acid disinfection appears to be a promising adjunctive therapy in cases of non-severe COVID-19 and deserves further investigation.

Predicting antidepressant response through early improvement of individual symptoms of depression incorporating baseline characteristics of patients: An individual patient data meta-analysis

Overall early improvement in depression after commencement of antidepressant treatment could be associated with subsequent response or remission, but its predictive ability is not adequate. We aimed to investigate whether early improvement of individual depressive symptoms and important baseline characteristics of patients including the number of previous depressive episodes and the duration of index episode, better predicts response or remission. We requested pharmaceutical companies in Japan for individual patient data from randomized placebo-controlled trials focusing on the efficacy of second-generation antidepressants. Primary and secondary outcomes were response and remission at week 6, respectively. We compared models that only included improvement in the overall depression severity at week 2 with models that also included improvement in individual symptoms and baseline characteristics, by conducting an individual patient data meta-analysis. We obtained data from three trials comprising 997 participants. For the response outcome, the model incorporating individual symptoms and baseline characteristics demonstrated better predictive values than those in the model including early improvement in overall depression only. However, the area under the receiver operating characteristic curve, and positive and negative predictive values were 0.65, 0.70, and 0.64, respectively, suggesting that 30% and 36% of the participants still had false-negative and false-positive predictions, respectively. For the remission outcome, the corresponding values in the latter model were 0.72, 0.62, and 0.68, respectively. We suggest that clinical judgement on early discontinuation of antidepressant from non-early improvement at week 2 should be carefully made.

LONG-TERM SAFETY AND EFFICACY OF OLOPATADINE/MOMETASONE COMBINATION NASAL SPRAY IN PATIENTS WITH PERENNIAL ALLERGIC RHINITIS

Introduction The efficacy and safety of GSP301 nasal spray, a newly developed investigational fixed-dose combination of olopatadine hydrochloride/mometasone furoate, was demonstrated in large 2-week seasonal allergic rhinitis studies. This study compared the 52-week safety (primary endpoint) and efficacy (secondary endpoint) of GSP301 in patients with perennial allergic rhinitis (PAR). Methods In this randomized, double-blind, parallel-group study (NCT02709538), 601 patients with PAR (≥12 years) were randomized 4:1:1 to twice-daily GSP301 (olopatadine 665μg/mometasone 25μg) and two GSP301 vehicle formulations (placebo pH 3.7 or 7.0). Treatment-emergent adverse events (TEAEs) were analyzed using descriptive statistics. Mean change from baseline in average 24-hour AM reflective and instantaneous Total Nasal Symptom Scores (rTNSS, iTNSS) for GSP301 vs placebo pH 3.7 were analyzed using mixed-effect model repeated measures (P Results At week 52, TEAEs occurred in 51.7%, 41.4%, and 53.5% of patients in the GSP301, placebo pH 3.7 and 7.0 groups. The most frequently reported TEAEs included upper respiratory tract infection, epistaxis, and headache. No clinically meaningful differences were observed in TEAE incidences or other safety assessments across treatments. At weeks 6 and 30, GSP301 significantly improved rTNSS and iTNSS vs placebo pH 3.7 (PPP=0.001) vs placebo pH 3.7, with significant improvements in individual symptoms (P Conclusions In this long-term study, GSP301 was well tolerated and provided significant and clinically meaningful improvements in PAR symptoms vs placebo.

Comparing Longitudinal Overall and Individual Symptom Outcomes on Neuromodulator versus Prokinetic Drugs in Patients With Symptoms Suspicious for Gastroparesis but With Non—Delayed Gastric Emptying

Introduction: Most patients with suspected gastroparesis do not have delayed gastric emptying. These patients are often treated with prokinetic agents but neuromodulator drugs are also given to reduce symptoms. Relative benefits of each drug class are unknown. In a multicenter study, we hypothesized that patients with suspected gastroparesis with non—delayed gastric emptying on scintigraphy (GES) or wireless motility capsules (WMC) show differential symptom benefits after prescribing neuromodulator vs. prokinetic medications. Methods: Management plans were devised for 150 patients with suspected gastroparesis. Investigators reviewed concurrent GES and WMC results and recommended therapy changes for those patients with non—delayed gastric emptying by GES (<10% 4 hr retention) or WMC (emptying <5 hr). Symptom (GCSI/PAGI—SYM) scores at baseline and 6 months were related to neuromodulator and prokinetic recommendations.1201_A Figure 1. Overall GCSI Reductions on Neuromodulators and Prokinetics in Patients with Non—Delayed Gastric Emptying1201_B Figure 2. Improvements in Individual Symptoms on Neuromodulators and Prokinetics in Patients with Non—Delayed Gastric EmptyingResults: 76% and 65% of patients had non—delayed gastric emptying by GES and WMC. 64 were prescribed neuromodulators including antidepressants—42 (mirtazapine/tricyclics—35), gabapentin—10, buspirone—9, and other—5. 49 received prokinetics including dopamine receptor antagonists (DRAs) (metoclopramide/domperidone—34) and pure prokinetics (macrolides, pyridostigmine, botulinum toxin—22). At 6 months, neuromodulators and prokinetics reduced overall GCSI scores similarly (Table). DRAs but not pure prokinetics reduced overall scores. Of neuromodulators, antidepressants and buspirone but not gabapentin reduced overall GCSIs. Individual symptoms improved with both drug classes; N/V improved less than other symptoms on neuromodulators but not prokinetics (Figure). DRAs but not pure prokinetics reduced all individual symptoms (P<0.05). Antidepressants but not gabapentin reduced all individual symptoms with GES vs. fullness and pain with WMC (P<0.05). Buspirone lowered fullness and bloating (P<0.05). Conclusion: Neuromodulator and prokinetic drugs are associated with differential benefits in patients with suspected gastroparesis with non—delayed gastric emptying on GES and WMC testing. Both drug classes are associated with improved symptoms, but lower N/V responses on neuromodulators suggest they are less effective antiemetics than prokinetics. Dopamine antagonists are associated with better responses than pure prokinetics. Antidepressants and buspirone relate to better responses than gabapentin. Our results offer unique insight into treating this large, distinct patient group.

Predicting antidepressant response by monitoring early improvement of individual symptoms of depression: individual patient data meta-analysis

Improvement in depression within the first 2 weeks of antidepressant treatment predicts good outcomes, but non-improvers can still respond or remit, whereas improvers often do not.AimsWe aimed to investigate whether early improvement of individual depressive symptoms better predicts response or remission. We obtained individual patient data of 30 trials comprising 2184 placebo-treated and 6058 antidepressant-treated participants. Primary outcome was week 6 response; secondary outcomes were week 6 remission and week 12 response and remission. We compared models that only included improvement in total score by week 2 (total improvement model) with models that also included improvement in individual symptoms. For week 6 response, the area under the receiver operating characteristic curve and negative and positive predictive values of the total improvement model were 0.73, 0.67 and 0.74 compared with 0.77, 0.70 and 0.71 for the item improvement model. Model performance decreased for week 12 outcomes. Of predicted non-responders, 29% actually did respond by week 6 and 43% by week 12, which was decreased from the baseline (overall) probabilities of 51% by week 6 and 69% by week 12. In post hoc analyses with continuous rather than dichotomous early improvement, including individual items did not enhance model performance. Examining individual symptoms adds little to the predictive ability of early improvement. Additionally, early non-improvement does not rule out response or remission, particularly after 12 rather than 6 weeks. Therefore, our findings suggest that routinely adapting pharmacological treatment because of limited early improvement would often be premature.Declaration of interestNone.

In adults with irritable bowel syndrome (IBS), do probiotics improve gastrointestinal symptoms?

EVIDENCE-BASED ANSWER Yes, but the results do not appear to be dramatic. Probiotics lead to improvement in some global IBS symptom and quality-of-life scores, but inconsistent improvements in individual symptoms of pain and distension and no improvement in other individual symptoms. The most effective dose and probiotic strain/species is unknown (SOR: A, meta-analysis of RCTs and individual RCTs).

Effects of electroconvulsive therapy on amygdala function in major depression - a longitudinal functional magnetic resonance imaging study.

Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects. In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained. Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (r spearman = -0.48, p = 0.044), and by tendency also for the MED sample (r spearman = -0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample. In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.

Comparative study of intranasal hypertonic seawater saline versus intranasal normal saline in allergic rhinitis

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Allergic rhinitis (AR) is a chronic disease with variable response to therapy.&lt;strong&gt; &lt;/strong&gt;Nasal irrigation with saline, including hypertonic saline, has been recommended for sinonasal conditions&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; All consecutive patients reporting with AR symptoms established by ARIA at a zonal and tertiary care referral hospital from July 1 to September 30, 2015 were enrolled in the study. Patients were randomly divided into two groups. Patients in Group A were treated with hypertonic seawater saline (HSS) 2.2% Group B with normal saline (NS) 0.9% respectively. Symptoms were assessed at the start of the treatment and after 2 months using 4 point scale.&lt;strong&gt;&lt;/strong&gt;60 patients were included in final analysis&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The mean total nasal symptoms post treatment when compared to pre-treatment were low in both the groups [2.19 (pre- treatment) vs. 1.03 (post treatment) in Group A and 2.18 (pre-treatment) vs. 1.46 (post treatment) in Group B] and the difference was statistically significant for both groups (P =0.0001). On comparing post-treatment symptom scores between both groups, Group a benefitted more than Group B and it was statistically significant (P =0.002). The difference in individual symptom improvement (except sneezing) post treatment exhibited a statistical significance in Group A.No side-effects were seen with either of the sprays&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; In our study, both treatments provided clinically meaningful responses, but the overall result favored HSS. Hence, HSS can be an effective and safe therapy for AR&lt;span lang="EN-IN"&gt;.&lt;/span&gt;&lt;/p&gt;

Retrospective Chart Review Study of Patients Receiving Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI) for Nutritional Management of Irritable Bowel Syndrome with Diarrhea (IBS-D)

Introduction: IBS-D is a common condition with few effective treatment options. The prescription medical food, SBI, has been shown to manage chronic loose and frequent stools in IBS-D patients. The safety and effectiveness of SBI as a therapy for IBS-D was further examined in this multi-center, IRB-reviewed study for overall and individual symptom response. Methods: Symptom data including stool frequency and consistency (Bristol Stool Scale 1-7), abdominal pain intensity (0 = no pain to 10 = worst pain) and adverse events (AEs) were collected from medical charts on 116 patients. Criteria for inclusion in primary analysis were patients having baseline recorded scores for stool consistency and abdominal pain, failure of standard-of-care (SOC) treatment, and not having received confounding IBS-D medications while on SBI. Results: The majority of patients who met criteria for analysis (n = 34) were white (94%), female (71%) with a median age of 53 (28, 85) and received SBI therapy for a mean duration of 23.2±24.1 wks [median 15.5 wks (0.4, 97.9)]. Mean baseline symptom scores were: stool frequency 5.24 (range 2 to 20); stool consistency 6.00 (range 4 to 7) and abdominal pain 4.56 (range 2 to 10). Twenty-five of the 34 patients had baseline abdominal pain scores >2 and stool consistency scores ≥ 5 to assess overall response; nine patients were excluded based on absence of pain (recorded score = 0) and normal stool score (Bristol Stool Scale = 4) at baseline. Of the 25 patients, 16 (64%) were responders with stool consistency < 5 and a 30% reduction in abdominal pain scores following SBI therapy. Using a generalized linear regression model for individual symptoms, the number of stools per day decreased by 3.24 (95% Confidence Interval (CI) 0.50, 5.98; P = 0.022), stool consistency improved by 1.86 (95% CI, 1.39, 2.33; P < 0.0001) and abdominal pain/discomfort intensity decreased by 3.03 (95% CI 1.668, 4.39; P < 0.0001). Thirteen of the 116 patients experienced one or more AEs while on SBI therapy. The main AEs were nausea (n = 5 patients) and an increase abdominal discomfort (n = 2 patients). No serious AEs were reported. Conclusion: Though retrospective, the inclusion criteria of SOC failure prior to SBI administration with demonstrated high combined abdominal pain and stool consistency response, as well as statistically significant individual symptom improvement, demonstrate SBI's clinical utility in IBS-D management. Additional chart reviews continue.

Patient Satisfaction With IBS Symptom Relief Using a Novel Peppermint Oil Delivery System in a Randomized Clinical Trial and by the General Patient Population

Introduction: A recent 4-week, placebo controlled, randomized clinical trial (RCT) with a novel peppermint oil (PO) targeted delivery system demonstrated significant relief of IBS symptoms compared to placebo1. In addition to individual symptom improvement, patient satisfaction is an important clinical trial endpoint, Post-marketing patient satisfaction and dosing frequency is also important to assess. 1IBSREST Trial Outcome Presented at DDW 2015, May 16-19 in Washington, DC. Methods: The IBSREST RCT included an end-of-study questionnaire to evaluate the overall satisfaction with the relief of IBS symptoms for subjects in the active arm. A separate survey study (IBSACT) was conducted with patients who were using the same active PO preparation in the general patient population to assess satisfaction and dosing frequency. The frequency of dosing in the clinical trial was fixed at 2 capsules TID, while the general patient population was allowed flexible dosing. Results: 35 subjects randomized to PO in the RCT and 285 patients in the general population completed the surveys. The questions and responses for the questionnaire in the RCT and IBSACT are shown in Table 1. Dosage frequency in the general population was much lower (60.8% used only 1 to 2 capsules per day) compared to 6 capsules per day in the RCT. There was a very high satisfaction rate (>80%) with the novel PO delivery system in both surveys. The response for all questions from patients in each trial was remarkably similar despite the lower capsule intake by patients in the general population.Table 1Conclusion: The novel PO delivery system showed a high rate of patient satisfaction in an RCT and the general patient population. Patients recruited for IBSREST had moderate to severe IBS symptoms. Their overall satisfaction rate of greater than 80% for all questions is encouraging since patients with severe IBS are historically not satisfied even with improvement of individual IBS symptoms2. In the general IBS patient population the overall satisfaction was also high (85%), even with much lower usage of capsules. 2Whitehead, WE et al. Reports of “Satisfactory Relief” by IBS Patients Receiving Usual Medical Care Are Confounded by Baseline Symptom Severity and Do Not Accurately Reflect Symptom Improvement. Am J Gastroenterol 2006; 101:1057-1065.

Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: a subgroup analysis and Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study.

Results from this randomized, placebo-controlled study of aripiprazole augmentation to antidepressant therapy (ADT) in Japanese patients with major depressive disorder (MDD) (the Aripiprazole Depression Multicenter Efficacy [ADMIRE] study) revealed that aripiprazole augmentation was superior to ADT alone and was well tolerated. In subgroup analyses, we investigated the influence of demographic- and disease-related factors on the observed responses. We also examined how individual symptom improvement was related to overall improvement in MDD. Data from the ADMIRE study were analyzed. Subgroup analyses were performed on the primary outcome measures: the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI) treatment to the end of the randomized treatment. Changes in the MADRS total scores were consistently greater with aripiprazole than placebo in each of the subgroups. Efficacy was not related to sex, age, number of adequate ADT trials in the current episode, MDD diagnosis, number of depressive episodes, duration of the current episode, age at first depressive episode, time since the first depressive episode, type of SSRI/SNRI, or severity at the end of SSRI/SNRI treatment phase. Compared to placebo, aripiprazole resulted in significant and rapid improvement on seven of the 10 MADRS items, including sadness. These post-hoc analyses indicated that aripiprazole was effective for a variety of Japanese patients with MDD who had exhibited inadequate responses to ADT. Additionally, we suggest that aripiprazole significantly and rapidly improved the core depressive symptoms.

Evaluation of the Effect of Lactobacillus paracasei (HF.A00232) in Children (6–13 years old) with Perennial Allergic Rhinitis: A 12-week, Double-blind, Randomized, Placebo-controlled Study

Dietary supplementation with probiotics alters intestinal microflora of children and may have immunomodulatory effects in prevention of allergic diseases. The aim of this study was to evaluate the effects of Lactobacillus paracasei (LP), strain HF.A00232, as a supplementary agent to levocetirizine in treating children with perennial allergic rhinitis (AR). This study was a 12-week, double-blind, randomized, placebo-controlled trial. Sixty children with AR aged 6-13 years with nasal total symptoms score (NTSS) ≥5 who fulfilled the inclusion criteria were enrolled. Patients were randomized into two groups with 28 participants receiving levocetirizine plus placebo and 32 participants receiving regular levocetirizine plus LP (HF.A00232) for the first 8 weeks, with a shift to levocetirizine as rescue treatment during the following 4 weeks. Parameters evaluated, including nasal, throat, and eye TSS (NTSS, TTSS, and ETSS, respectively), TSS and levocetirizine use, were recorded daily. Physical examinations and Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQs) were administered at each visit. In addition, blood samples were obtained for evaluation of cytokines including interleukin-4, interferon-γ, interleukin-10, and transforming growth factor-β at baseline, Week 8, and Week 12. The LP (HF.A00232) group had significantly lower PRQLQ scores even after discontinuing regular levocetirizine from Week 9 to Week 12 (p<0.01). There was more improvement in individual parameters in the PRQLQ, including sneezing (p=0.005), itchy nose (p=0.040), and swollen puffy eyes (p=0.038), in the LP (HF.A00232) group. No significant differences in TSS, NTSS, TTSS, ETSS, or cytokine levels were found between the two groups. Dietary supplementation with LP (HF.A00232) provided no additional benefit when used with regular levocetirizine in treating AR in the initial 8 weeks of our study, but there was a continuing decrease in PRQLQ scores, as well as a significant improvement in individual symptoms of sneezing, itchy nose, and swollen eyes, after discontinuing regular levocetirizine treatment.