Subjective Improvement Research Articles

Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector.

To report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector. Single-center, retrospective chart review. In this case series, four patients between the ages of six and 11years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated. Three out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector. We observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes. Caution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.

MDB-30. ZOLPIDEM, A PROMISING DRUG TO IMPROVE POSTOPERATIVE CEREBELLAR MUTISM SYNDROME (CMS): RETROSPECTIVE STUDY OF 19 PEDIATRIC PATIENTS WITH POSTERIOR FOSSA TUMORS

Abstract INTRODUCTION Postoperative Cerebellar Mutism Syndrome (CMS) affects up to 25% of patients undergoing surgeries for posterior fossa (PF) tumors. There is no established treatment for CMS, although zolpidem has become widespread after reporting remarkable responses in some cases. However, there is very limited scientific evidence, prompting us to document our experience with zolpidem. OBJECTIVES To evaluate the efficacy and safety of zolpidem in patients with postoperative CMS in PF tumors. METHODS Observational, descriptive, retrospective study conducted at our institution. Patients <21 years diagnosed with CMS following PF tumor surgery between 2011-2023 and treated with zolpidem were included. Demographic and clinical data, therapies, CMS scales, and outcomes were collected. RESULTS Nineteen patients met the criteria, 84% males, median age 8 years (range, 9 months-19 years), and median follow-up time 30 months (range, 2-126). Diagnoses included 58% medulloblastoma, 21% pilocytic astrocytoma, 10.5% ependymoma, 10.5% others. CMS mutism scale was rated mild, moderate and severe in 5%, 21% and 74%, respectively. Median zolpidem administration was 31 days (range, 2-241) and median maximum dose was 0.25 mg/kg/day (range, 0.10-0.90). Mutism scores improved in 37% (7/19), 53% (8/15) and 64% (9/14) of patients that received zolpidem for at least 48h, 7 and 14 days, respectively. Subjective improvement in communication and interaction was observed in 74% (14/19). Only three patients with mild somnolence and one with initial irritability and insomnia were reported. CONCLUSIONS To our knowledge, this is the largest study of patients treated with zolpidem for CMS. A considerable proportion of children improved their language abilities within the first 24-48h, but some patients may even benefit from more prolonged treatment. Most children showed an adequate tolerance with very few side effects. Further studies are urgently needed, preferably within a randomized clinical trial, to find the real efficacy, appropriate dosage, and duration of zolpidem.

(124) GENITOURINARY SYNDROME OF LACTATION (GSL): A NEW PERSPECTIVE ON POSTPARTUM AND LACTATION-RELATED GENITOURINARY SYMPTOMS

Abstract Introduction Genitourinary syndrome of menopause (GSM) is a well-documented and researched condition characterized by a range of genitourinary symptoms in peri- and postmenopausal women. Similar to GSM, postpartum and lactating women experience significantly reduced estrogen and androgen levels. However, there is limited research on the occurrence and impact of similar symptoms during the postpartum and breastfeeding period, as well as possible treatment options. Objective The aim of this project was to review the available literature for genitourinary health in the postpartum breastfeeding population and summarize the key findings and potential treatment options. Methods We performed a comprehensive literature review utilizing several databases and the following keywords individually or in combination “physiology of postpartum” or “physiology of lactogenesis” or “vulvovaginal health” or “vaginal atrophy” or “vaginal dryness” or “dyspareunia” or “urinary incontinence” or “lactation” or “breastfeeding” or “vaginal estrogen.” Full text review of 75 articles was performed, and ultimately 50 articles were included in this review. Results During lactation, high levels of prolactin inhibit estrogen and androgen secretion via negative feedback mechanisms (1). These hormonal changes lead to an increased prevalence (of up to 50% higher) of vulvovaginal atrophy in lactating and breastfeeding women compared to non-breastfeeding women (2,3). The shift in hormones also contributes to increased rates (~30% higher) of dyspareunia (4–7), likely due to a lack of vaginal lubrication (up to 46%) among breastfeeding women (8). Decreased sexual desire is also common and reported to be experienced by up to 46% of postpartum women (8). Despite these highly prevalent and potentially devastating symptoms, there is a lack of consistent screening at postpartum visits and no treatment guidelines available to healthcare providers. Similar to GSM, vaginal lubricants can be used by breastfeeding women with vaginal dryness. However, for lactating women with refractory vaginal dryness or significant vulvovaginal changes, vaginal estrogen or DHEA therapy may be considered. Studies have shown minimal or no transfer of estrogen to breast milk even at high concentrations, and no reduction in breast milk supply (9–11), likely because vaginal estrogen is not a systemic dose. Studies on vaginal estrogen therapy in postpartum women are limited, but one randomized placebo-controlled trial showed excellent compliance and a subjective improvement in women utilizing vaginal estrogen (12). Conclusions Postpartum breastfeeding women experience similar physiology and symptoms to the postmenopausal phase, as seen in GSM. We propose the introduction of a novel term to describe the genitourinary changes seen in breastfeeding individuals: Genitourinary Syndrome of Lactation (GSL). The creation and diagnostic use of a syndrome, such as GSL, will equip healthcare providers with an all-encompassing term to bring awareness to the symptoms experienced by postpartum breastfeeding individuals. This awareness can lead to improved screening and treatment guidelines for the high numbers of breastfeeding individuals suffering from these genitourinary changes. Disclosure No.

Treatment of oral graft-versus-host disease with intraoral nbUVB phototherapy.

There are limited treatment options available for hematopoietic stem-cell transplant patients (HSCT) with oral graft-versus-host disease (GVHD). Intraoral phototherapy is a novel, yet promising therapeutic regimen. To assess the safety and effectiveness of intraoral narrowband UVB (nbUVB) phototherapy in the treatment of oral GVHD. This case series evaluated 10 patients with refractory oral GVHD, who were treated at Northwestern Memorial Hospital with nbUVB between July 2019 and October 2023. Primary outcomes were to evaluate the safety and efficacy of phototherapy. Efficacy was measured by objective improvement in symptom scores and subjective improvement in patient reported symptoms. Safety was determined by the withdrawal due to adverse events. Total nbUVB exposure, number of treatments, and change in systemic immunosuppressive medications were also examined. The study cohort comprised 10 patients who developed oral GVHD at a median of 9.5months after HSCT. The total median dose of nbUVB was 36J/cm2, and the median number of sessions was 55. All 10 patients demonstrated some degree of improvement in symptoms. Notably, there was a reduction in the number of patients who reported symptoms of oral pain (83%), bleeding (67%), xerostomia (50%), and oral sensitivity (78%) after initiating phototherapy. There was also a statistically significant decrease in the levels of pain, erythema, and edema (p ≤ 0.001, < 0.001, 0.01, respectively). Most patients tolerated phototherapy well, but 1 patient withdrew from treatment due to adverse effects. Seventy-five percent of patients who were on immunosuppressive medications were able to decrease or stop these medications. This case series suggests that nbUVB phototherapy is well tolerated and efficacious in patients with oral GVHD.

Bloom's taxonomy-Can evidence-based teaching improve junior medical officers' knowledge of the mental health and guardianship acts?

To determine whether a brief educational intervention for Junior Medical Officers (JMOs), using teaching methods aimed at achieving higher outcomes on Bloom's Taxonomy, significantly improved participant confidence and knowledge in decision making about restrictive care. JMOs received a teaching session on restrictive medical and mental health care. Groups were randomly assigned to either sessions including a component of modern pedagogical interventions (Think-Pair-Share and SNAPPS), or sessions including a control period focusing on reviewing a condensed summary of relevant information. Pre- and post-intervention measures were recorded for subjective self-ratings of confidence and scores on standardized clinically relevant extended matching questions (EMQs). There was no difference in subjective confidence improvement between groups; however, the group receiving the modern pedagogical intervention demonstrated significantly greater objective performance on knowledge-based EMQs. A brief modern pedagogical intervention using interactive teaching methods shows promise for improving knowledge of restrictive care and the Mental Health and Guardianship Acts. In the control group, similarly increased confidence in knowledge did not equate to increased competence on a knowledge assessment. Refurbishing educational interventions presents opportunities for improving clinical outcomes and engaging junior doctors in psychiatry.

Randomized double-blind placebo-controlled trial evaluating pregabalin for chronic cough in patients with lung cancer.

LBA12082 Background: Chronic cough is a distressing symptom that detracts from the quality of life (QoL) of patients with cancer. Developing effective therapies for cough is an unmet need, with no approved medicines available. Neuromodulators like pregabalin may act centrally as cough suppressants. Methods: Randomized double-blind placebo-controlled study in the Department of Medical Oncology at Tata Memorial Hospital (Mumbai, India) in patients with locally advanced/metastatic non-small-cell lung cancer (NSCLC) with at least 2 weeks history of moderate or severe cough. Patients had ECOG PS 0-2, and creatinine clearance &gt; 60 mL/min. Randomization was 1:1 to pregabalin 300 mg orally daily or matching placebo, both administered for 9 weeks. Primary endpoint was the difference in cough severity as measured by Visual Analog Scale (VAS) after 9 weeks treatment with pregabalin versus placebo. Secondary endpoints included cough severity on day 7 and week 9 measured by VAS, and Manchester Cough in Lung Cancer Scale (MCLCS); side-effects, and QoL assessed by EORTC QLQ C30 and LC13. Means of the change from baseline scores were calculated for patients in each arm, and compared between two arms by independent samples Mann Whitney U test. P &lt; 0.05 was considered significant. Results: Between Jul 2022 and Dec 2023, we enrolled 166 patients: 83 to each arm. Median age was 56 years (IQR, 47-62.5); 112 (67.5%) were male, and 149 (89.8%) had metastatic NSCLC. Baseline cough severity was grade 2 in 127 (76.5%) and grade 3 in 37 (22.6%); median cough duration was 163 days. The therapy (pregabalin/placebo) was well tolerated in both arms, with no difference in grade &gt; 3 toxicities between the two arms; P=0.908. Systemic cancer-directed therapy was started in 95.2% and 91.4% of patients in the pregabalin and placebo arms, respectively; P=0.328. By week 9, subjective improvement in cough was reported by 45 (57%) patients in pregabalin arm, and 40 (52.6%) patients in placebo arm; P=0.846. The mean VAS score (in mm) decreased from 71.58 at baseline, to 45.32 at day 7, and 19.73 by week 9 in the pregabalin arm; corresponding values in the placebo arm were 71.74, 46.23, and 21.18, respectively; P=0.530. Cough assessment by mean MCLCS scores showed a similar decrease throughout the course of the study, with no statistically significant differences between the two arms (Pregabalin-Baseline: 27.63, Day 7: 23.49, Week 9: 17.39; Placebo-Baseline: 27.28, Day 7: 23, Week 9: 17.34); P=0.455. There was no significant difference in QoL between the two arms. Mean LCCO (cough symptom question on QLQ LC13) score decreased from 75.9 (baseline) to 54.2 (day 7) to 36.4 (week 9) in pregabalin arm, vs 66.3, 54, and 31.4, respectively, in placebo arm; P=0.150. Conclusions: Pregabalin does not lead to a significant decrease in cough in patients with lung cancer. Systemic cancer-directed therapy is the most effective antitussive therapy for cancer-induced cough. Clinical trial information: CTRI/2020/11/029275 .

BERTIVITS: The Posterior Encoder Fusion of Pre-Trained Models and Residual Skip Connections for End-to-End Speech Synthesis

Enhancing the naturalness and rhythmicity of generated audio in end-to-end speech synthesis is crucial. The current state-of-the-art (SOTA) model, VITS, utilizes a conditional variational autoencoder architecture. However, it faces challenges, such as limited robustness, due to training solely on text and spectrum data from the training set. Particularly, the posterior encoder struggles with mid- and high-frequency feature extraction, impacting waveform reconstruction. Existing efforts mainly focus on prior encoder enhancements or alignment algorithms, neglecting improvements to spectrum feature extraction. In response, we propose BERTIVITS, a novel model integrating BERT into VITS. Our model features a redesigned posterior encoder with residual connections and utilizes pre-trained models to enhance spectrum feature extraction. Compared to VITS, BERTIVITS shows significant subjective MOS score improvements (0.16 in English, 0.36 in Chinese) and objective Mel-Cepstral coefficient reductions (0.52 in English, 0.49 in Chinese). BERTIVITS is tailored for single-speaker scenarios, improving speech synthesis technology for applications like post-class tutoring or telephone customer service.

Functional Level and Dynamic Posturography Results Two Years after Vestibular Neurectomy in Patients with Severe Meniere's Disease.

Objectives: The aim of this study was to evaluate the functional outcomes and balance compensation in patients with severe Meniere's disease after vestibular neurectomy. Methods: Pre- and postoperative results were analyzed in twenty patients with unilateral Meniere's disease before and two years after vestibular neurectomy. Clinical evaluation was performed using a subjective grading scale proposed by the American Academy of Otolaryngology-Head and Neck Surgery and the Dizziness Handicap Inventory. Sensory organization test results were analyzed to assess the balance system before and after the surgery. Results: All patients reported a complete resolution of vertigo attacks after the vestibular neurectomy; 95% of patients reported functional level improvement according to a scale proposed by the American Academy of Otolaryngology-Head and Neck Surgery, and the average score decreased from 4.5 to 1.6. Clinical improvement, evaluated with the Dizziness Handicap Inventory, was present in all patients, with the average result decreasing from 81.7 to 16.4. Analyzing both grading systems, differences between pre- and postoperative results were statistically significant. No statistically significant differences were found between the sensory organization test results before and after vestibular neurectomy. Significant correlations were found between a patient's age and postoperative results of the Dizziness Handicap Inventory and posturography. Conclusions: Vestibular neurectomy is an effective vertigo treatment in patients with severe Meniere's disease with no clinical improvement despite conservative treatment. It results in subjective physical, functional, and emotional improvement, enabling patients to return to daily activities and work. An appropriate qualification of patients and comprehensive preoperative evaluation are essential to obtaining satisfactory clinical outcomes.

Effects of undergraduate ultrasound education on cross-sectional image understanding and visual-spatial ability - a prospective study

Introduction/aimRadiological imaging is crucial in modern clinical practice and requires thorough and early training. An understanding of cross-sectional imaging is essential for effective interpretation of such imaging. This study examines the extent to which completing an undergraduate ultrasound course has positive effects on the development of visual-spatial ability, knowledge of anatomical spatial relationships, understanding of radiological cross-sectional images, and theoretical ultrasound competencies.Material and methodsThis prospective observational study was conducted at a medical school with 3rd year medical students as part of a voluntary extracurricular ultrasound course. The participants completed evaluations (7-level Likert response formats and dichotomous questions “yes/no”) and theoretical tests at two time points (T1 = pre course; T2 = post course) to measure their subjective and objective cross-sectional imaging skills competencies. A questionnaire on baseline values and previous experience identified potential influencing factors.ResultsA total of 141 participants were included in the study. Most participants had no previous general knowledge of ultrasound diagnostics (83%), had not yet performed a practical ultrasound examination (87%), and had not attended any courses on sonography (95%). Significant subjective and objective improvements in competencies were observed after the course, particularly in the subjective sub-area of “knowledge of anatomical spatial relationships” (p = 0.009). Similarly, participants showed improvements in the objective sub-areas of “theoretical ultrasound competencies” (p < 0.001), “radiological cross-section understanding and knowledge of anatomical spatial relationships in the abdomen” (p < 0.001), “visual-spatial ability in radiological cross-section images” (p < 0.001), and “visual-spatial ability” (p = 0.020).ConclusionUltrasound training courses can enhance the development of visual-spatial ability, knowledge of anatomical spatial relationships, radiological cross-sectional image understanding, and theoretical ultrasound competencies. Due to the reciprocal positive effects of the training, students should receive radiology training at an early stage of their studies to benefit as early as possible from the improved skills, particularly in the disciplines of anatomy and radiology.

Effectiveness of Abdominal Massage Versus Kinesio Taping in Women With Chronic Constipation: A Randomized Controlled Trial.

Chronic constipation is an important public health problem and significantly affects women's lives. It is important to investigate nonpharmacological applications that can be used in the treatment of chronic constipation. The aim is to assess how abdominal massage and Kinesio taping impact constipation severity, quality of life (QOL), and perception of subjective improvement in women with chronic constipation. Following the Rome IV diagnostic criteria, women with constipation were randomly sorted into 3 distinct groups for study: massage group (lifestyle recommendations + abdominal massage, n = 22), taping group (lifestyle recommendations + Kinesio taping, n = 22), and control group (lifestyle recommendations, n = 22). Constipation Severity Instrument (CSI) (for constipation severity), 7 days bowel diary (for bowel function), Patient Assessment of Constipation QOL (PAC-QOL) questionnaire (for QOL), 4-item Likert-type scale (for perception of subjective improvement) was used. The group x time interaction effect was significant in all CSI, bowel diary and PAC-QQL parameters, except for incomplete evacuation and PAC-QOL-worries/concerns, and a large effect size was found (Partial η2 > 0.14). Improvement scores of all parameters (except CSI-obstructive defecation, incomplete evacuation, PAC-QOL-worries/concerns) were similar in the massage and taping groups and were better than the control group. Noteworthy perceptions of subjective improvement and normalization of stool type predominantly manifested in the massage group (P < 0.05). Abdominal massage and Kinesio taping are recommended as initial conservative interventions for managing chronic constipation within the therapeutic spectrum.

Fresh frozen plasma (FFP) for hypogammaglobulinemia (HypoG) in patients (Pts) with recurrent infections (Infxs) after B-cell directed treatment: A single institution experience with economic impact analysis.

e13519 Background: The incidence of hypoG with recurrent infxs has rapidly increased in pts undergoing B-cell targeted therapies, including monoclonal and bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies, for benign and malignant diseases. These novel therapies produce life-threatening hypoG due to persistently severe depletion of B cells. The standard of care (SoC) for hypoG is intravenous immunoglobulin (IVIG) infusion, which is costly with limited efficacy. FFP is known to have B cell-related immunologic elements (IgM, A, &amp; D) and complement that are essential for fighting infx. Methods: We retrospectively identified pts between January 2020 and 2024 diagnosed with hypoG who received FFP or IVIG for recurrent infx from B-cell targeted therapies (67% received anti-CD20 agents). Data was collected 12 months (mos) before and after FFP or IVIG infusion. HypoG-related recurrent infx are usually chronic with no documented positive cultures. Therefore, we reviewed each pt’s subjective reports of infectious improvement. Our primary endpoint was the annualized infx rate before and after FFP or IVIG, with a secondary outcome comparing hospitalization rates. Infxs were measured by courses of antimicrobial therapy. A Kaplan-Meier analysis was performed with accompanying log-rank testing for the primary outcome. Results: 21 pts met inclusion criteria, 5 received FFP and 16 received IVIG. Median (mdn) age was 72 years (range, 46 - 87) and 57.1% were female. 66.6% received FFP/IVIG after therapy for hematologic cancers (62% B cell lymphoma), 28.6% for solid tumors, and 4.8% for autoimmune disorders. The mdn number of infxs in the 12 mos preceding FFP and IVIG were 3 (2 - 5) and 3 (0 - 13), respectively, while the mdn number of infx-related hospitalizations prior to intervention was 2 (1 - 3) and 0 (0 - 6). The mdn number of infxs in the 12-mo period following FFP initiation was 1 (0 - 2) versus 0 (0 - 3) after IVIG initiation, and mdn number of infx-related hospitalizations post-intervention was 0 (0 - 1) and 2 (0 - 7). The mdn time to first infx on FFP and IVIG were 5 mos (2 - 12) and 4 mos (1 - 12), respectively, with one pt in each cohort not having an outcome. All 5 pts in the FFP cohort had documented subjective improvement of infectious symptoms after first infusion, as opposed to none in the IVIG cohort (p = 0.000). There was no significant difference in mdn time to first infx (p = 0.591). Conclusions: IVIG costs about 10,000 USD per infusion compared to 120 USD for FFP, excluding labor, distribution and facility charges. The estimated total IVIG market share in the US is about 5 billion in 2024. Replacement of IVIG with FFP will alleviate supply constraints and save US healthcare at least 4.95 billion USD yearly. Comparable rates of infx with FFP versus IVIG suggest that FFP is non inferior to the SoC for treating hypoG.

How Does Individual Psychotherapy Promote Recovery for Persons with Psychosis? A Systematic Review of Qualitative Studies to Understand the Patient's Experience.

Psychotherapy for individuals with psychosis is an effective treatment that promotes recovery in various ways. While there is strong quantitative evidence across modalities, less is known from the patient's perspective. There are many varied forms of psychotherapy, and gaining the patient's perspective can improve understanding of salient elements of psychotherapy and increase engagement, ultimately improving recovery rates. The purpose of this review is to identify and integrate data from published studies of patient perspectives of psychotherapy for psychosis to understand essential elements across approaches, differences between approaches, and how psychotherapy impacts recovery. We aimed to understand further: what are the perceptions about individual psychotherapy from the perspective of individuals with psychosis? The current study was a systematic review using PRISMA guidelines of studies that included qualitative interviews with persons with experiences of psychosis who participated in psychotherapy. All three authors participated in the literature search using Pubmed, APA PsycInfo, and Psychiatry Online. We identified N = 33 studies. Studies included cognitive therapies, acceptance and mindfulness approaches, trauma therapies, metacognitive therapy, and music therapy. All studies reported participants' perceived benefit with the therapeutic relationship as especially salient. Participants described diverse aspects of objective (e.g., symptoms, functioning) and subjective (e.g., self-experience or quality of life) recovery improvements, with perceived mechanisms of change, and with music therapy having some unique benefits. Participants also reported challenges and suggestions for improvement. Study findings highlight the salient aspects of psychotherapy identified by patients that may help therapists to individualize and improve approaches to psychotherapy when working with individuals experiencing psychosis. Overall, findings support the potential for integrative psychotherapy approaches for maximal treatment personalization.

Assessment of Outer and Middle Ear Pathologies in Lilongwe, Malawi.

Outer and middle ear pathologies are known to disproportionately affect low-income countries but data is limited. We aim to quantify the prevalence rate of patients presenting with middle/outer ear pathologies at ABC Hearing Clinic and Training Centre in Lilongwe, Malawi. Audiological consultations (adult and paediatric) from 2018-2020 were reviewed for outer and middle ear pathologies. Secondary outcomes included patient type (private vs. community) compared to otoscopy findings, tympanometry findings, need for follow up, and follow up compliance. Out of 1576 patients reviewed, the proportion of abnormal cases' was 98.2%, with 41.4% being unilateral and 57.4% bilateral. Eighty-three percent presented with outer/middle ear pathologies. 68% of those presented with a pathology often associated with some degree of conductive hearing loss (occluding wax, perforation, discharge, Type B/Type C tympanogram). Average age was 29 + 0.527 years; 41.6% private and 58.2% community patients. Cerumen impaction was most common finding (51%). Higher rates of otoscopic abnormalities and type B tympanograms were noted in community vs. private patient (~40% vs. ~30%; ~70% vs. ~30%). Adherence to follow up was higher for community vs. private patients (29% vs. 17%); ~70% reported subjective improvement upon follow up. The majority required multiple interventions on follow up. Secondary follow up was recommended in 64.8%. A significant disease burden of outer and middle ear pathologies was identified. Further research is required to understand the disease burden and promote health policy.

#1636 Treatment of Tolvaptan related polyuria with bendroflumethiazide for ADPKD: Does it really work?

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease worldwide and accounts for 10% of patients on renal replacement therapy. Currently, the arginine vasopressin (AVP) V2 receptor antagonist Tolvaptan is the only available treatment for ADPKD which slows cyst formation and thus the progression of kidney disease by inducing AVP resistance. However, its aquaretic side effects can be debilitating and is the most common reason for medication discontinuation. Thiazides such as bendroflumethiazide are natriuresis-promoting diuretics through their action on the sodium-chloride channel in the distal convoluted tubule that are widely used to treat polyuria in inherited AVP deficiency or resistance. However, there is limited information about their effect in patients treated with Tolvaptan. The aim of this observational study is to review the impact on patients’ quality of life by using a low dose bendroflumethiazide with Tolvaptan in patients with ADPKD who are suffering from Tolvaptan induced aquaretic side effects. Method Details of all patients with ADPKD who are on Tolvaptan with or without bendroflumethiazide who are currently attending the polycystic kidney disease (PKD) clinic at Royal Free London NHS Foundation Trust were obtained, and their medications reviewed. Patients who have previously been or were currently on bendroflumethiazide to enable them to continue Tolvaptan therapy were identified. Information about the impact of bendroflumethiazide on their quality of life and their aquaretic side effects were obtained via phone call. If they discontinued bendroflumethiazide, the reason for this was explored. In addition, eGFR, sodium, potassium, and calcium at the time of bendroflumethiazide initiation as well as at three, six, nine and twelve months post bendroflumethiazide initiation were obtained. Results Out of 136 patients receiving Tolvaptan for treatment of ADPKD at our centre, eight (5.8%) were prescribed bendroflumethiazide for treatment of their aquaretic side effects from Tolvaptan. Two of these eight patients (25%) stopped bendroflumethiazide due to adverse reactions. The remaining six patients (75%) remained on the medication, and all reported significant subjective improvement in their symptoms of polyuria, nocturia and in their overall quality of life. Two of the six patients (33.3%) that remained on bendroflumethiazide had also subsequently increased their Tolvaptan dose. No electrolyte disturbances were noted after initiation of bendroflumethiazide. Conclusion Using bendroflumethiazide appears to improve the quality of life through reduction of polyuria and nocturia in patients suffering from Tolvaptan-induced aquaretic side effects with some patients subsequently able to increase their Tolvaptan dose by taking bendroflumethiazide which might result in augmented therapeutic benefit of Tolvaptan. Further placebo-controlled randomised studies with longitudinal will be needed to determine the true benefit-disbenefit balance of thiazide therapy in patients taking tolvaptan, especially to determine whether there is a negative effect on efficacy of tolvaptan on the underlying ADPKD. However, based on our small observational study, the number of patients needed to determine whether bendroflumethiazide improves the tolerability and medication adherence in patients who are debilitated by the aquaretic side effects of Tolvaptan would be small.

Effect of a Mindfulness and Motivational Interviewing-Oriented Physical-Psychological Integrative Intervention for Community-Dwelling Spinal Cord Injury Survivors: A Mixed-Methods Randomized Controlled Trial

ObjectiveTo evaluate the feasibility, acceptability, and efficacy of a mindfulness and motivational interviewing-oriented physical-psychological integrated intervention in community-dwelling spinal cord injury (SCI) survivors. DesignA mixed-methods randomized controlled trial. SettingLocal organizations for handicapped in Hong Kong. ParticipantsCommunity-dwelling adults with SCI (N=72). InterventionsParticipants in the intervention group (n=36) received video-guided exercise for daily practice and online group psychological (mindfulness and motivational interviewing-oriented) weekly sessions for 8 weeks. Participants in the control group (n=36) received an 8-week online group didactic education on lifestyle discussions and general health suggestions. Main Outcomes MeasuresPrimary outcomes included quality of life, physical activity, depression, and chronic pain. Secondary outcomes included exercise self-efficacy and mindfulness. Outcomes were measured at baseline, postintervention, and 3-month follow-up. Focus-group interviews were conducted postintervention. ResultsThe recruitment, retention, and adherence rates were 84.7%, 100%, and 98.6%, respectively. The intervention showed significant positive effects on preventing declines in quality of life at 3-month follow-up (Cohen d=0.70, 95% CI=0.22-1.18). Positive trends manifested in physical activity, depression, chronic pain, and exercise self-efficacy. Three qualitative categories were identified: subjective improvements in exercise, physical, and social well-being; perceived changes in mindfulness and mental well-being; and intervention facilitators and barriers. ConclusionsThe mindfulness and motivational interviewing-oriented physical-psychological integrated intervention is feasible and acceptable. The significant prolonged effect in maintaining quality of life and positive effects on physical and psychosocial well-being indicate its value to address major health challenges of community-dwelling SCI survivors.

Effect of low dose honey on the apoptosis and inflammation gene expression in corneal limbal stem cells and keratocytes and its efficacy as an ophthalmic formulation in the treatment of dry eye: in-vitro and clinical study.

The use of honey as an eye treatment encounters challenges due to its high osmolarity, low pH, and difficulties in sterilization. This study addresses these issues by employing a low concentration of honey, focusing on both in-vitro experiments and clinical trials for treating dry eye disease in corneal cells. In the in-vitro experiment, we investigated the impact of a 1% honey-supplemented medium (HSM) on limbal stem cells (LSCs) and keratocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and real-time polymerase chain reaction (PCR) for BCL-2, BAX, and IL-1β gene expression. Simultaneously, in the clinical trial, 80 participants were divided into two groups, receiving either a 1% w/v honey ophthalmic formulation or a placebo for 3 months. Study outcomes included subjective improvement in dry eye symptoms, tear break-up time (TBUT), and Schirmer's test results. MTT results indicated that 1% HSM did not compromise the survival of corneal cells and significantly reduced the expression of the IL-1β gene. Additionally, participants in the honey group demonstrated a higher rate of improvement in dry eye symptoms and a significant enhancement in TBUT values at the three-month follow-up. However, there was no significant difference between the study groups in terms of Schirmer's test values. No adverse events were observed or reported. In conclusion, 1% honey exhibits anti-inflammatory and anti-infective properties, proving effective in ameliorating dry eye symptoms and enhancing tear film stability in patients with dry eye disease.Clinical Trial Registration: https://irct.behdasht.gov.ir/trial/63800.

Association of apnea-hypopnea index and lateral cephalometry pre- and post-surgery in obstructive sleep apnea patients

Background: Snoring and obstructive sleep apnea are new emerging medical entity and require early diagnosis and treatment because of their increasing implication on physical, mental, social and emotional health. Aim of this study is to assess severity of OSHAS and co-relate efficacy of various post-surgical parameter on objective and subjective improvement in patients. Methods: 43 patients having the symptoms were included in the study and followed over a period of three months and during their post operative visit their lateral cephalometric findings, ESS were recorded and compared to pre operative values to see if any association exists between them. Results: it was seen that various surgical interventions did bring about subjective and objective improvement in patients and these were statistically significant. Conclusions: OSHAS is a spectrum of disorders and has great impact on persons physical, mental and emotional well-being. Early diagnose and treatment eliminated the future risks. Surgical intervention helps improve symptoms of OSHAS and should be undertaken without delay wherever indicated.

Correlation of Orthognathic Surgical Movements to Perception of Facial Appearance in Patients With Cleft Lip and Palate.

Cephalometric scans were compared before and after surgery to assess the degree of correction. Correlations between skeletal movements and survey outcomes were determined using multivariate regression analysis. This study aims to identify relationships between subjective observer-reported improvements in esthetics and emotional appearance with specific surgical movements. Ten patients at a single tertiary institution (average age: 18.1 ± 0.8), 9 males and 1 female, underwent orthognathic repair and had comprehensive cephalometric records. Standardized anterior posterior and lateral pre and postoperative photographs of patients were included in a survey to clinicians to assess noncognitive domains on a Likert Scale (1-10). CLEFT-Q was administered to gauge patient satisfaction in categories of appearance, speech, and quality of life. Per clinicians, multiple domains increased including facial attractiveness (4.1 ± 0.7 versus 7.3 ± 0.7, P < 0.001), friendliness (4.5 ± 0.4 versus 7.3 ± 0.5, P < 0.001), confidence (4.1 ± 0.4 versus 7.1 ± 0.4, P < 0.001), and recommendation for surgery decreased (8.9 ± 0.1 versus 3.6 ± 0.5, P < 0.001). Speech distress decreased with increased SNA and convexity, whereas Psychological and Social scores decreased with an increased ANB. Functional eating and drinking scores increased with maxillary depth. Orthognathic surgery improves many noncognitive domains in patients with cleft lip and palate as assessed by both patients and clinicians on all aspects of facial attractiveness and perception. These findings demonstrate objective bases of skeletal adjustments for perceived improvements in facial appearance and emotion.

Long-term use of interleukin-1 inhibitors reduce flare activity in patients with fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is one of the most catastrophic forms of genetic heterotopic ossification (HO). FOP is characterized by severe, progressive inflammatory flare-ups, that often lead to HO. The flare-ups are associated with increased inflammatory cytokine production, suggesting auto-inflammatory features driven by IL-1β. This study describes the short- and long-term responses of FOP patients to anti-IL-1 therapy. Previously, we reported that a patient with FOP treated with anti-IL-1 agents showed dramatically lower rates of flare-ups, improved flare-up symptoms, decreased use of glucocorticoids and apparently decreased size of residual lesions. Plasma analyses also showed marked elevation in IL-1β levels during a FOP flare, further supporting a role of IL-1β in the pathogenesis of FOP flares. Here, we report results from long-term therapy with IL-1 inhibitors in that patient and describe 3 additional patients, from two medical centres. All 4 patients showed persistent improvement in flare activity during treatment with IL-1 inhibitors, with minimal formation of new HO sites. Two patients who stopped therapy experienced a resurgence of flare activity that was re-suppressed upon re-initiation. These patients had IL-1β levels comparable to those in IL-1β-driven diseases. Child Health Assessment Questionnaires confirmed extensive subjective improvements in the pain and general health visual analogue scales. This case series demonstrates significant benefits from IL-1 inhibitors for reducing flare activity and improving the general health of patients with FOP. These data provide strong support for additional studies to better understand the function of IL-1 inhibition, primarily in reducing the formation of new HO. RH received support from the International FOP Association ACT grant; ECH received support from NIH/NIAMS R01AR073015 and the UCSF Robert Kroc Chair in Connective Tissue and Rheumatic Diseases III.

A COMPARATIVE STUDY ON NASAL BONE FRACTURE ASSOCIATED WITH SEPTAL DEVIATION CORRECTED WITH SEPTOPLASTY VERSUS CLOSED REDUCTION

Objective: The dorsum of the nose formed by nasal bones helps to maintain the airway and esthetic appearance of the nose. Faciomaxillary trauma is associated with a nasal bone fracture with or without nasal septal fractures. Nasal bone fractures can lead to deviation of the external nose and nasal obstruction. The management includes correction of nasal bone deformity with either septoplasty or reduction of nasal septal deviation by the non-surgical method. A study was conducted to compare the results of septal deviation corrected by septoplasty and non-surgical reduction of septal deviation combined with nasal bone fracture reduction.The aim of this study was to compare the results of septal deviation corrected by septoplasty and non-surgical reduction of septal deviation combined with nasal bone fracture reduction. Materials: Sixty-two patients with nasal bone fractures with varying degrees of external nose deformity and nasal septal deviation were divided into two groups. Group A consisted of patients treated with septoplasty and nasal bone fracture correction and Group B consisted of patients treated with non-surgical reduction of septal deviation and nasal bone fracture correction. Type I, II, and II nasal bone fractures were included with all types of septal deviations. The subjective improvement in nasal obstruction was assessed using the visual analog scale in both groups. Results: There were 26 males (81.25%) and 06 (18.75%) females in Group A and 25 (83.33%) males and 05 (16.67%) females in Group B. In Group A, 12 (37.5%) patients were aged between 18 and 27 years, 10 (31.25%) patients were aged between 28 and 27 years, 07 (21.87%) patients were aged between 38 and 47 years, and 03 (09.37%) patients were aged between 48 and 57 years. The mean age was 23.54±2.30 years. Conclusion: Nasal bone fractures cause not only esthetic facial deformity but also functional airway obstruction. A thorough clinical examination, computed tomography scan, and patient counseling are necessary. There is no statistically significant difference in the final outcome between the septoplasty and closed reduction of the septal deviation undertaken to relieve nasal obstruction in patients with associated nasal bone fractures.