Greater Symptom Improvement Research Articles

P0666 Early symptom improvements predict later clinical response and remission at week 12 for patients with ulcerative colitis treated with mirikizumab in the LUCENT-1 study

Abstract Background Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is effective in inducing clinical remission at Week(W) 12 and maintaining clinical remission through 3 years in patients with moderately-to-severely active ulcerative colitis (UC) (LUCENT-1, NCT03518086; LUCENT-2, NCT03524092; LUCENT-3, NCT03519945).1, 2 Here we determine whether early symptom response predicts clinical response and clinical remission at the end of induction. Methods Receiver operating characteristic (ROC) curves were used to assess if LUCENT-1 patients’ symptomatic improvement (≥ 30% symptom response of stool frequency and rectal bleeding) at W2, W4, W6, and W8, in response to mirikizimab therapy predicts W12, clinical remission and clinical response. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to assess predictive value while the area under the ROC curve (AUC) provided the overall predictability. PPV was defined as the percentage of patients with clinical response and remission at W12 after achieving symptomatic score improvement from baseline. NPV was defined as the percentage of patients without clinical response (or clinical remission) at W12 when achieving symptom improvement from baseline. Youden’s Index, defined as sensitivity + specificity - 1, was used to identify the optimum prediction threshold. Results A significantly greater proportion of patients treated with mirikizumab achieved symptom improvements compared to placebo as early as W2 and through W12 (Figure 1). ROC curve analysis of symptomatic improvement over time versus W12 clinical remission, showed increasing predictability from W2 (66%), and W4 (76%), to W6 (79%), and W8 (78%). Similar predictabilities of symptomatic improvement from W2 (69%), W4 (78%), W6 (82%), to W8 (83%) versus W12 clinical response were observed (Figure 2). As early as W2, patients with symptomatic improvement of ≥30% from baseline, had 83% NPV and the NPV reached 90%, 97%, and 96%, respectively at W4, W6, W8 for achieving clinical remission at W12. Conclusion Patients treated with mirikizumab for induction achieved significantly greater symptom response or greater symptom improvements (≥30%) versus placebo as early as W2. A minimum of 30% improvement in symptomatic scores at W4 and W6 could provide an optimum prediction for both clinical response and clinical remission at W12. Additional studies need to be done to assess the value of these thresholds.

The Combined Effect of Multisensory Stimulation and Therapist Support on Physical and Mental Health of Older Adults Living in Nursing Homes: Pilot Randomized Controlled Trial.

Increasing life expectancy has led to a rise in nursing home admissions, a context in which older adults often experience chronic physical and mental health conditions, chronic pain, and reduced well-being. Nonpharmacological approaches are especially important for managing older adults' chronic pain, mental health conditions (such as anxiety and depression), and overall well-being, including sensory stimulation (SS) and therapist support (TS). However, the combined effects of SS and TS have not been investigated. This randomized controlled trial examines the specific and combined effects of brief SS and TS interventions on older adults' physical and mental health and pain intensity levels, among individuals living in nursing homes. A total of 96 patients aged 65-99 years from a nursing home were randomly assigned to 3 groups: SS, TS, and combined SS+TS interventions, each delivered as four 20-minute sessions. SS was implemented using a multisensory Snoezelen room. Pain intensity levels (per a Visual Analog Scale), blood pressure, heart rate, blood oxygen saturation, and hand grip strength (using a Jamar hand dynamometer) were measured before and after each of the 4 weekly therapeutic sessions. In addition, life satisfaction (per the Satisfaction with Life Scale) and anxiety (per the 7-item General Anxiety Disorder Scale) were evaluated before and after the whole intervention. Mixed model analyses tested the relative efficacy of the 3 interventions, applying simple slope analysis with Tukey correction. Study rationale and analytical plans were preregistered. The combined intervention of SS and TS (SS+TS) resulted in reduced pain levels compared with SS (B=0.209, P=.006) and TS alone (B=0.23, P=.002) over 4 sessions (F6,266=2.62; P=.017; R2=0.23). Further, the combined SS+TS intervention resulted in reduced systolic blood pressure versus SS (B=0.09, P=.01) and TS alone (B=0.016, P<.001) groups (F6,272=5.42; P<.001; R2=0.29). In addition, the combined SS+TS intervention resulted in an increased grip strength versus SS (B=-0.35, P=.003) and TS alone (B=-0.032, P=.008) groups (F6,273=2.25; P=.04; R2=0.19). Moreover, combined SS+TS resulted in an improvement in life satisfaction (B=-4.29, P<.0001) compared with SS (B=-2.38, P=.0042) and TS alone (B=-1.20, P=.13) groups (F2,39=3.47; P=.04). Finally, SS+TS demonstrated greater improvement in symptoms of general anxiety disorder (B=10.64, P<.0001) compared with SS (B=3.30 P=.01) and TS alone (B=1.13, P=.37) (F2,38=13.5; P<.001) groups. No differences between the interventions were shown for blood oxygen saturation (F6,273=2.06; P=.06), diastolic blood pressure (F6,272=1.12; P=.35), and heart rate (F6,273=1.33; P=.23). The combined intervention of SS and TS showed therapeutic benefits for pain management and physical and mental health of older adults living in nursing homes, relative to each therapeutic component in isolation. This brief intervention can be readily implemented to improve well-being and optimize therapeutic resources in nursing home settings. ClinicalTrials.gov NCT05394389; https://clinicaltrials.gov/ct2/show/NCT05394389.

Affect integration, metacognitions, and early maladaptive schemas as predictors of outcome in cognitive and metacognitive therapies for social anxiety disorder

Objective Few reliable patient characteristics have emerged as significant predictors of outcomes for Social Anxiety Disorder (SAD). This study aimed to explore whether affect integration, metacognitions, and maladaptive schemas could serve as predictors of therapeutic outcomes for patients with SAD. Relationships between these psychological constructs and baseline SAD symptomatology were also examined. Methods Eighty-eight patients across three sites participated in Cognitive Behavioral Therapy (CBT) or Metacognitive Therapy (MCT) for SAD in inpatient or outpatient clinics. Measures of predictors and SAD symptomatology were repeatedly assessed. Statistical analyses included longitudinal, multilevel modeling. Results Difficulties with affect integration, metacognitions and early maladaptive schemas clearly related to higher levels of SAD symptoms at baseline but were not generally predictive of changes in SAD symptoms during therapy. However, examining sub-domains revealed that difficulties with the integration of jealousy and tenderness, and the maladaptive schema of defectiveness/shame, predicted poorer outcomes. In contrast, initial difficulties with the integration of sadness, a greater lack of cognitive confidence, and the maladaptive schema of dependence/incompetence were associated with greater symptom improvement. Conclusion Identifying issues of affect integration and core self-other beliefs prior to therapy may enhance patient selection and allow for a more individualized treatment.

The benefits and harms of inpatient involuntary psychiatric treatment: a scoping review

This scoping review examined quantitative research comparing involuntary inpatient groups with voluntary inpatients or other comparator group. Ten themes were identified: patient knowledge of legal status, experienced or perceived coercion, effects on medication use, clinical effects measured on outcome scales, effects on psychiatric readmission, use of restraints and seclusion, effects on suicide and deaths, patient satisfaction, length of stay and carer experiences. The review found that involuntary inpatient admission was associated with harms including increased subjective and objective coercion, increased cost and decreased patient satisfaction. In addition, it found that there may be significant confusion among both voluntary and involuntary patients regarding their legal rights. However, patients admitted on an involuntary basis experienced greater improvements in symptoms and function, possibly due to greater symptom burden prior to admission. Involuntary treatment carries the potential for both benefit and harms that should be acknowledged and mitigated by service providers.

Examining the impact of weight loss and exercise on pelvic organ prolapse (POP) management

Introduction: Pelvic organ prolapse is a descent of pelvic organs such as the bladder, cervix, apex of the vagina, and rectum which create herniation and slide into the direction of the vagina entrance. Pelvic prolapse is caused by ligament and muscle weakness, and its risk increases with age, parity, and obesity. Proper exercise and weight loss can be a key component of pelvic prolapse management, especially in the I-III stages. Those interventions may decrease the need for pelvic surgery and the risk of complications that can arise from it. Purpose of the study: This study aimed to explore the effectiveness of weight loss and exercise on pelvic organ prolapse (POP) symptoms and staging. Materials and methods: A comprehensive analysis of research papers available on PubMed, and Google Scholar was undertaken using the keywords: ‘weight loss pelvic prolapse’, ‘exercise in pelvic prolapse’, ‘pelvic floor dysfunction’, ‘pelvic floor muscle training’, ‘hypopressive exercises’, ‘biofeedback prolapse’ Results: Conventional weight loss does not reduce the intensity of the pelvic prolapse symptoms. However, weight loss that is achieved via bariatric surgery is effective in reducing symptoms arising from pelvic organ prolapse. Furthermore, the bigger the amount of weight loss the greater improvement in symptoms. Pelvic floor muscle training showed improvement in symptoms and in the staging of pelvic organ prolapse. Hypopressive exercises are not as effective as pelvic floor muscle training. Biofeedback and supervised exercises are helpful in proper exercise execution, and thus may improve the strength of the pelvic floor muscles.

Meibography signal intensity as a novel image biomarker for meibomian gland function: evidence from cross-sectional and longitudinal analyses.

Meibomian gland dysfunction (MGD), one of the most common ocular surface diseases, can induce dry eye and reduce patients' quality of life. Methodological limitations have resulted in contradictory interpretations of gland function. This study sought to investigate the correlation between meibography signal intensity (SI) and meibomian gland (MG) function and to validate an MGD classification strategy based on different levels of SI. A multicenter, cross-sectional analysis was conducted on 817 eyes from 361 patients with MGD and 52 healthy controls. Additionally, 78 eyes from 39 patients with MGD who had undergone LipiFlow treatment were recruited for longitudinal analyses. The SI value was obtained via meibography using an automated analyzer, and all participants underwent ocular surface examinations. A cross-sectional analysis was performed to determine SI distribution and its relationship to clinical characteristics via a generalized estimating equation model. Longitudinal analyses were conducted on the treatment cohort using a mixed-effects model to explore the outcome in different SI levels. Regression analysis revealed significant correlations between SI and lipid layer thickness (β=0.016), meibum expressibility (β=-0.676), meibum quality (β=-0.251), and fluorescein-stained tear-film break-up time (FBUT) (β=0.064) (all P values <0.001 for the above associations). Low-level SI MGD cases exhibited the most severe clinical signs, including the worst meibum expressibility (16% for level 3) and quality scores (19% for level 3), the shortest FBUT (3.82±0.13 s), and the thinnest lipid layer (65.68±2.58 nm), (all P values <0.05, respectively). Patients with medium SI showed the lowest ocular surface disease index (OSDI) value (26.64±1.06), the longest FBUT (4.56±0.08 s), and the thickest lipid layer (80.20±2.90 nm). After treatment, the high SI values reduced significantly at each follow-up point compared to baseline (all P values <0.05). The medium SI group demonstrated the greatest improvement in symptoms and signs, followed by the high SI group, and the low SI group. Automated measurements of SI can effectively reflect MG secretory activity. The proposed low, medium, and high SI classifications represent different functional subtypes of MGD.

Transcranial Magnetic Stimulation–Induced Plasticity Improving Cognitive Control in Obsessive-Compulsive Disorder, Part I: Clinical and Neuroimaging Outcomes From a Randomized Trial

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for obsessive-compulsive disorder (OCD). The neurobiological mechanisms of rTMS in OCD have been incompletely characterized. We compared clinical outcomes and changes in task-based brain activation following 3 different rTMS protocols, all combined with exposure and response prevention. MethodsIn this 3-arm proof-of-concept randomized trial, 61 treatment-refractory adult patients with OCD received 16 sessions of rTMS immediately before exposure and response prevention over 8 weeks, with task-based functional magnetic resonance imaging scans and clinical assessments before and after treatment. Patients received high-frequency rTMS to the left dorsolateral prefrontal cortex (n = 19 [13 women/6 men]), high-frequency rTMS to the left pre-supplementary motor area (preSMA) (n = 23 [13 women/10 men]), or control rTMS to the vertex (n = 19 [13 women/6 men]). Changes in task-based functional magnetic resonance imaging activation before/after treatment were compared using both a Bayesian region of interest and a general linear model whole-brain approach. ResultsMean OCD symptom severity decreased significantly in all treatment groups (Δ = −10.836, p < .001, 95% CI −12.504 to −9.168), with no differences between groups. Response rate in the entire sample was 57.4%. The dorsolateral prefrontal cortex rTMS group showed decreased planning-related activation after treatment that was associated with greater symptom improvement. No group-level activation changes were observed for the preSMA and vertex rTMS groups. Participants in the preSMA group with greater symptom improvement showed decreased error-related activation, and symptom improvement in the vertex group was associated with increased inhibition-related activation. ConclusionsrTMS to preSMA and dorsolateral prefrontal cortex combined with exposure and response prevention led to activation decreases in targeted task networks in individuals showing greater symptom improvement, although we observed no differences in symptom reduction between groups.

Baseline monocyte count predicts symptom improvement during intravenous ketamine therapy in treatment-resistant depression: a single-arm open-label observational study.

Neuroinflammatory processes in depression are associated with treatment resistance to conventional antidepressants. Ketamine is an effective new therapeutic option for treatment-resistant depression (TRD). Its well-established immunomodulatory properties are hypothesized to mediate its antidepressant effect. In this context, higher levels of inflammation may predict a better treatment response. However, conclusive evidence for this hypothesis is lacking. We thus investigated whether standard peripheral inflammatory cell markers and C-reactive protein (CRP) levels could predict symptom improvement during intravenous ketamine therapy in TRD patients. 27 participants with TRD were treated with six weight-adjusted intravenous ketamine infusions (0.5 mg/kg bodyweight) over three weeks. Baseline assessments included CRP, absolute monocyte count (AMC), and absolute neutrophil count (ANC). Depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline (D1), after the first (D3) and before the last ketamine infusion (D18). Raters were blinded for the baseline laboratory assessments. 13 participants responded to ketamine treatment, and 8 participants partially responded. Baseline AMC showed a strong negative correlation with MADRS change at D3 (r=-0.57, p=0.002) and at D18 (r =-0.48, p=0.010), indicating that a high baseline AMC was associated with greater symptom improvement. A generalized linear model confirmed the association of baseline AMC with symptom improvement during ketamine treatment when additionally accounting for age, sex, and body mass index. Specifically, baseline AMC demonstrated predictive value to discriminate responders and partial responders from non-responders, but lacked discriminative ability between partial responders and responders. Baseline ANC correlated with the MADRS changes at D3 (r=-0.39, p=0.046), while CRP values did not correlate at all. Our prospective single-arm open-label observational study demonstrated that baseline AMC reliably predicted symptom improvement during intravenous ketamine treatment in TRD patients. AMC could therefore serve as a simple and easily accessible marker for symptom improvement during ketamine therapy in daily clinical practice. Future studies with larger sample sizes and a more detailed longitudinal assessment of AMC subtypes are needed to better understand the specific relationship between monocytes and the neuromodulatory effects of ketamine.

MANAGEMENT OF SIDHMA KUSTA: A CASE STUDY.

Psoriasis is an immune mediated disease with an unclear cause that is characterised by inflammation caused by Dysfunction of the immune system. Psoriatic plaque shows epidermic hyperplasia. Erythrodermic psoriasis is an acute condition in which almost all body surface is inflamed. This study is to show better management through ayurvedic treatment. In this case, a 35-year-old male patient diagnosed with erythrodermic psoriasis all over body predominantly on hands which is accompanied by erythema, dry, thin scaly lesions and itching. The condi-tion managed by Snehana(oleation), Pitta rechana(purgation), internal medicines, external application with Taila which is given according to avasthanusara(stage wise). Observation and results: The outcome is positive, significant in terms of reduction of erythema, itching, scales, dryness and healing of lesions produced noticeable improvement. Ayurvedic principles provide great im-provement in signs and symptoms and increase the quality of life in the treatment of psoriasis.

Systematic review and meta-analysis: proton pump inhibitors slightly decrease the severity of chronic cough

The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. We performed a meta-analysis to assess the effects of acid-suppressive medications in adults with non-specific chronic cough. The protocol was registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials evaluating the impact of acid-suppressive medications on persistent cough were included. The systematic search was performed on the 1st of November 2022 in three databases. A random-effects model was used for the calculations. The effect size was the standardized mean difference (SMD) with 95% confidence interval (CI). A total number of 11 double-blinded placebo-controlled randomized trials were included in the meta-analysis. Data showed that compared to placebo, PPIs decreased the severity of cough (SMD 0.33; CI 0.05; 0.61). Therapeutic response was not different in patients with non-specific chronic cough only, compared to those with laryngopharyngeal reflux. Prolonged treatment durations did not result in greater symptomatic improvement, with SMD 0.33 (CI − 0.22; 0.88), 0.31 (CI − 1.74; 2.35), 0.32 (CI − 0.29; 0.93) and 0.34 (CI − 0.16; 0.85), following 4, 6, 8 and 12 weeks of treatment, respectively. The pooled analysis of the improvement in quality of life with PPIs found an SMD of 0.39 (CI − 0.51; 1.29). PPIs mildly decrease the severity of non-specific chronic cough, irrespective of treatment duration.

Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis

ObjectiveTo determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.DesignSystematic review and meta-analysis.Data sourcesFive electronic databases of published literature (Cochrane Central Register of Controlled Trials,...

Serotonin Transporter (SLC6A4) and FK506-Binding Protein 5 (FKBP5) Genotype and Methylation Relationships with Response to Meditation in Veterans with PTSD.

Meditation-based interventions are novel and effective non-pharmacologic treatments for veterans with PTSD. We examined relationships between treatment response, early life trauma exposure, DNA polymorphisms, and methylation in the serotonin transporter (SLC6A4) and FK506-binding protein 5 (FKBP5) genes. DNA samples and clinical outcomes were examined in 72 veterans with PTSD who received meditation-based therapy in two separate studies of mindfulness-based stress reduction (MBSR) and Transcendental Meditation (TM). The PTSD Checklist was administered to assess symptoms at baseline and after 9weeks of meditation intervention. We examined the SLC6A4 promoter (5HTTLPR_L/S insertion/deletion + rs25531_A/G) polymorphisms according to previously defined gene expression groups, and the FKBP5 variant rs1360780 previously associated with PTSD disease risk. Methylation for CpG sites of SLC6A4 (28 sites) and FKBP5 (45 sites) genes was quantified in DNA samples collected before and after treatment. The 5HTTLPR LALA high expression genotype was associated with greater symptom improvement in participants exposed to early life trauma (p = 0.015). Separately, pre to post-treatment change of DNA methylation in a group of nine FKBP5 CpG sites was associated with greater symptom improvement (OR = 2.8, 95% CI 1.1-7.1, p = 0.027). These findings build on a wealth of existing knowledge regarding epigenetic and genetic relationships with PTSD disease risk to highlight the potential importance of SLC6A4 and FKBP5 for treatment mechanisms and as biomarkers of symptom improvement.

Client predictors of dropouts and outcomes in psychotherapy for generalized anxiety disorder: an exploratory study

ABSTRACT This study is a secondary analysis exploring client predictors of dropouts and outcomes in the treatment of generalized anxiety disorder (GAD). Data was taken from a feasibility randomized control trial (RCT) exploring the relative efficacy of emotion-focused therapy (EFT) compared with cognitive-behavioral therapy (CBT). Relationships between client characteristics and dropouts were explored using logistic regression analysis. Relationships between client characteristics and psychotherapy outcomes were explored using hierarchical linear regression analyses. For the full dataset (n = 58), a comorbid personality disorder predicted a higher number of dropouts. Eleven participants dropped out of therapy. Having a disability predicted less improvement in symptoms of depression and general distress. Being male-identified predicted a greater reduction in symptoms of anxiety and general distress, and comorbid agoraphobia predicted a greater reduction in symptoms of depression for the CBT condition (n = 21 completers). For the EFT condition (n = 26 completers), being older predicted greater improvements in symptoms of anxiety and comorbid panic disorder predicted a lower reduction in symptoms of depression. Caution should be taken in interpreting these findings given the small number of participants. However, they provide useful insights for the generation of hypotheses in relation to predictors of dropouts and outcomes for future studies.

Enhanced response and safety of combining dunhuang 'moxibustion classic' acupuncture with carbamazepine in treating neuropathic tinnitus and identifying risk factors affecting sleep quality.

To evaluate the response and safety of combining acupuncture based on the Dunhuang "Moxibustion Classic" with carbamazepine in the treatment of neuropathic tinnitus. A retrospective analysis was conducted on 105 patients with neuropathic tinnitus treated at The First People's Hospital of Lanzhou City from January 2019 to February 2023. Of these, 49 patients received acupuncture based on the Dunhuang "Moxibustion Classic" (research group), while 56 patients received conventional acupuncture (control group). Both groups were treated with carbamazepine in combination. The Tinnitus Handicap Inventory (THI), Tinnitus Evaluation Questionnaire (TEQ), Visual Analogue Scale for Aural Fullness (VAS), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD) scores were compared between the two groups. Treatment response and Pittsburgh Sleep Quality Index (PSQI) scores were also analyzed. Logistic regression analysis was performed to identify risk factors affecting patients' sleep quality. The overall response rate in the control group was significantly lower than that in the research group (P = 0.037). After treatment, THI, PSQI, TEQ, VAS, HAMA, and HAMD scores were higher in the control group than in the research group (P<0.05). The incidence of adverse reactions was significantly higher in the control group than in the research group (P = 0.025). Multivariate logistic regression analysis identified treatment options (P = 0.002, OR = 8.612, 95% CI = 2.466-39.565), disease duration (P = 0.687, OR = 0.779, 95% CI = 0.219-2.544), pre-treatment THI (P = 0.002, OR = 7.061, 95% CI = 2.17-26.368), pre-treatment TEQ (P<0.001, OR = 14.654, 95% CI = 4.196-65.376), and pre-treatment HAMA (P = 0.019, OR = 3.805, 95% CI = 1.271-12.209) as independent risk factors for impaired sleep quality. The combination of Dunhuang "Moxibustion Classic" acupuncture with carbamazepine is an effective and safe treatment for neuropathic tinnitus, leading to greater improvements in symptoms, sleep quality, anxiety, and depression compared to conventional acupuncture.

Predictors of response after single session interventions for emotional distress: using enhanced psychoeducation in crisis situations.

Single-session interventions are an effective strategy for reducing emotional distress. Enhanced psychoeducation, which includes empathic listening, risk stratification, symptom monitoring, and habit modification is particularly suitable for single-session interventions. We investigated predictors of response to an online enhanced psychoeducation intervention among essential service professionals during the COVID-19 pandemic in Brazil. The TelePSI Project, financed by the Brazilian Ministry of Health, was a nationwide initiative that served more than 3,300 individuals in various psychotherapeutic modalities. Data were collected from April 2020 to December 2021. We included all participants with high levels of emotional distress who received single-session interventions. The final sample included 460 individuals (89.1% women, 81.1% health professionals). After 1 month, 300 participants were reassessed. Overuse of social media, use of social networks to contact family and friends, playing video games, smoking, drinking alcohol, and spending time with pets were associated with less improvement in symptoms, whereas playing an instrument and previous psychological treatment were associated with greater symptom improvement. This highlights the impact of lifestyle factors on the efficacy of single-session interventions. These results underscore the importance of considering individual lifestyle factors when implementing single-session interventions and contribute to a growing body of evidence that supports tailored application of psychoeducational strategies in mental health interventions, particularly in high-stress environments.

Abstract 15569: The Effect of Cardiac Pulmonary Nerve Stimulation on Cardiac Inotropy and Quality of Life in Patients With Acute Decompensated Heart Failure

Background: Acute decompensated heart failure (ADHF) results in over 1 million hospitalizations annually and involves neurohormonal disruption as well as autonomic dysfunction. Neuromodulation of the cardiac plexus using cardiopulmonary nerve stimulation (CPNS), currently being evaluated in clinical trials, is a novel strategy to treat ADHF. Methods: An interim analysis of 12 patients from ongoing trials was conducted. Patients were admitted with a principal diagnosis of ADHF (elevated NT-proBNP and LVEF≤50%) and underwent implant of a 16-electrode catheter (Figure 1A) in the right pulmonary artery, allowing cardiac plexus stimulation for 48 hrs. Stimulation was performed at 20 Hz frequency, 2.0 ms pulse width, and stimulation amplitude/vector (2.5-10 mA) to optimize cardiac function. LV pressure, arterial pressure, and ECG were concurrently recorded. An additional 12 patients not implanted were followed as a parallel standard of care (SOC) cohort. Results: There were no device-related serious adverse events (SAEs) during the index hospitalization or at 30 days post-discharge. Two SAEs unrelated to device occurred in 2 patients (clonic seizure and post-discharge pneumonia resulting in death). In response to stimulation, there was a statistical increase in maximum LV dP/dt (from 799 to 824 mmHg/sec, p&lt;0.01) and a statistical decrease in pressure time index (from 27.9 to 27.5 mmHg*sec, p&lt;0.05). Patients that received CPNS reported a significantly greater improvement in symptoms, function, and quality of life at 30 days (KCCQ-12; from 14.1 to 74.7, p&lt;0.0001) compared to patients in the SOC cohort (Figure 1B; 60.6 vs. 8.4, p&lt;0.05). Conclusion: In-hospital CPNS therapy is feasible and well-tolerated in ADHF patients. Stimulation increased cardiac inotropy, decreased energy consumption, and improved symptoms, function, and quality of life. Further investigation is required to determine if CPNS therapy leads to sustained improvement in clinical outcomes.

Symptoms of Liver Disease During Tenofovir Therapy With or Without Peginterferon: Results from the Hepatitis B Research Network Immune Active Trial.

Evaluate patient-reported liver symptoms during treatment for chronic hepatitis B viral (HBV) infection and associations between changes in symptoms and levels of alanine aminotransferase (ALT) and viral markers. Data from 200 participants in the Hepatitis B Research Network Immune Active Trial who completed symptom assessments were analyzed. Patients were treated with tenofovir, with or without peginterferon (TDF + PegIFN vs. TDF alone) for 192weeks. Participants completed a Symptom Checklist at baseline and every 4-12weeks. A total symptom score was created, ranging from 0 (none) to 40 (severe). The SF-36 was completed every 48weeks. Associations of symptom scores with ALT and viral markers were evaluated at baseline and end of treatment. Participants were 65% male, 83% Asian, with a mean age of 42. Baseline symptoms were mild (median = 2, range 0-25) and associated with baseline ALT, HBV DNA levels and HBeAg + status. Patients on TDF alone experienced a more rapid and greater improvement in symptoms, but by week 192, symptom improvement was similar in both groups (54% vs 36%). Symptom improvements correlated with ALT and HBV DNA, most markedly among those with symptoms at baseline. Most patients (4 out of 6) who achieved HBsAg loss experienced symptom improvements. Overall, SF-36 scores did not change with treatment. Reduction in ALT and HBV DNA levels with therapy are associated with significant improvement in liver symptoms such as fatigue and pain over the liver, especially among those with higher ALT, HBV DNA, symptoms and HBeAg + status prior to treatment.

Response to Bronchodilators Administered via Different Nebulizers in Patients With COPD Exacerbation.

The recommended treatment of COPD exacerbations includes administration of short-acting bronchodilators that act to reverse bronchoconstriction, restore lung volumes, and relieve breathlessness. In vitro studies demonstrate vibrating mesh nebulizers (VMNs) provide greater drug delivery to the airway compared to standard small-volume nebulizers (SVNs). We examined whether the physiological and symptom response to nebulized bronchodilators during a COPD exacerbation differed between these 2 modes of bronchodilator delivery. Subjects hospitalized with a COPD exacerbation participated in a comparative clinical effectiveness study of 2 methods of nebulization. Using block randomization, 32 participants in this open-label trial were administered salbutamol 2.5 mg/ipratropium bromide 0.5 mg via vibrating mesh (VMN group, n = 16) or small-volume jet nebulizer (SVN group, n = 16) on one occasion. Spirometry, body plethysmography, and impulse oscillometry were performed and Borg breathlessness scores recorded pre bronchodilator and at 1 h post bronchodilator. Baseline demographics were comparable between groups. Mean FEV1 was 48% predicted. Significant changes in lung volumes and airway impedance were seen in both groups. Inspiratory capacity (IC) increased by 0.27 ± 0.20 L and 0.21 ± 0.20 L in the VMN and SVN group, respectively, between group difference P = .40. FVC increased in the VMN group by 0.41 ± 0.40 L compared to 0.19 ± 0.20 L with SVN, between group difference P = .053; and residual volume (RV) decreased by 0.36 ± 0.80 L and 0.16 ± 0.50 L in the VMN and SVN group, respectively, between group difference P = .41. The VMN group had a significant reduction in Borg breathlessness score, P = .034. Greater improvement in symptoms, and larger absolute change in FVC, was observed in response to equivalent doses of standard bronchodilators administered by VMN, compared to SVN, but no substantial difference in change in IC.

Change in Prostate Volume and Symptom Improvement in Men Treated With Rezūm Water Vapor Therapy

To evaluate the change in prostate volume (PV) and relationship to improvement in urinary symptom scores following Rezūm therapy. Quality of life outcomes and PV were assessed at baseline and 12months postprocedure. Percent change from baseline in outcomes and PV were calculated, as was the number of Rezum injection to baseline PV ratio. Association between total number of injections and changes in outcomes and PV were evaluated using linear regression models. A total of 49 men (mean age=67.8; standard deviation=9.4) underwent the procedure between April 2019 and September 2020, with a median baseline PV of 71.5 cc (range 24-150) and median number of vapor injections of 11.0 (range 4-21). At 12months, the median percent change in PV was -34.0% (interquartile range: -49.2%, -16.7%), with 45/49 (91.8%) patients having reduced volume. Among the 45 patients with reduced volume at 12months, every 10% increase in volume reduction was associated with a 7.5% (95% confidence interval, 1.4%-13.6%; P=.02) improvement in the International Prostate Symptom Score. There was no significant association between total number of injections or injection to baseline volume ratio and change in PV. In this cohort of men treated with Rezūm therapy for benign prostatic hyperplasia, it was demonstrated that there is a correlation between greater PV reduction and greater symptomatic improvement. This study showed no association between more injections or the ratio of injections to PV changes, refuting the claim that more injections are better.

Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease

Dry eye disease (DED) is a common public health problem with significant impact on vision-related quality of life and well-being of patients. Medications with rapid onset of action and a good tolerability profile remain an unmet need. To assess efficacy, safety, and tolerability of a water-free cyclosporine ophthalmic solution, 0.1% (CyclASol [Novaliq GmbH]), applied twice daily in DED compared with vehicle. CyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (ESSENCE-2) was a phase 3, multicenter, randomized, double-masked, vehicle-controlled clinical study conducted from December 5, 2020, to October 8, 2021. Following a 14-day run-in period with an artificial tear administered 2 times per day, eligible participants were randomly assigned 1:1 to the treatment groups. Patients with moderate to severe DED were included in the study. Cyclosporine solution vs vehicle administered 2 times per day for 29 days. The primary end points were changes from baseline in total corneal fluorescein staining (tCFS; 0-15 National Eye Institute scale) and in dryness score (0-100 visual analog scale) at day 29. Conjunctival staining, central corneal fluorescein staining, and tCFS responders were also assessed. A total of 834 study participants were randomly assigned to cyclosporine (423 [50.7%]) or vehicle (411 [49.3%]) groups at 27 sites. Participants had a mean (SD) age of 57.1 (15.8) years, and 609 (73.0%) were female individuals. The majority of participants self-identified in the following race categories: 79 Asian (9.5 %), 108 Black (12.9%), and 635 White (76.1%). Participants treated with cyclosporine solution had greater improvement in tCFS (-4.0 grades) than the vehicle group (-3.6 grades) at day 29 (change [∆] = -0.4; 95% CI, -0.8 to 0; P = .03). The dryness score showed treatment benefits from baseline in both groups: -12.2 points for cyclosporine and -13.6 points for vehicle (∆ = 1.4; 95% CI, -1.8 to 4.6; P = .38). In the cyclosporine group, 293 participants (71.6%) achieved clinically meaningful reductions of 3 grades or higher in tCFS vs 236 (59.7%) in the vehicle group (∆ = 12.6%; 95% CI, 6.0%-19.3%; P < .001). These responders showed greater improvement in symptoms at day 29 including dryness (∆ = -4.6; 95% CI, -8.0 to -1.2; P = .007) and blurred vision (Δ = -3.5; 95% CI, -6.6 to -4.0; P = .03) compared with nonresponders. The ESSENCE-2 trial confirmed that treatment with a water-free cyclosporine solution, 0.1%, results in early therapeutic effects on the ocular surface compared with vehicle. The responder analyses suggest that the effect is clinically meaningful in 71.6% of participants in the cyclosporine group. ClinicalTrials.gov Identifier: NCT04523129.