Worsening Of Symptoms Research Articles

Worsening of myasthenic symptoms associated with statins

Introduction/AimsThe common presentations of statin intolerance are muscle-specific symptoms. Although statins are one type of drug reported to cause myasthenic worsening, myasthenic worsening has not been recognized as statin intolerance. The purpose of the present study is to investigate in a large cohort the safety profiles of statins in patients with myasthenia gravis (MG). MethodsA total of 1710 consecutive patients with MG who visited sites associated with the Japan MG registry 2021 group between April and October 2021 were reviewed. Statin-associated myasthenic worsening was defined as worsening of any myasthenic symptoms on statin use and improvement of the symptom by stopping the statin or by undertaking additional treatment with patient and doctor confirmation. ResultsAmong the 400 patients who used statins, 8 (2%) patients experienced statin intolerance and 6 (1.5%) patients experienced myasthenic worsening. No patients developed MG on the statin. Ptosis was a main symptom of myasthenic worsening in 4 (67%) patients. Atorvastatin was used in all patients with statin-associated myasthenic worsening. The symptoms of statin intolerance and statin-associated myasthenic worsening were improved within 2 months and 3 months, respectively, in all patients by cessation of statin use. DiscussionRegarding statin-associated myasthenic worsening, prevalence was low, and severity was mild; with cessation of statin use, symptoms improved within a few months, and outcomes were generally good. Although statins can be used in MG patients with little concern, statin-associated myasthenic worsening should be noted in addition to the classical statin intolerance associated with statin use.

Neuroimaging and clinical features of bilateral Wallerian degeneration of middle cerebellar peduncles subsequent to pontine infarction.

Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its infrequency, there is limited research on its characteristics. This study aims to present three cases of WD of MCPs following pontine infarction and to analyze the prognosis, clinical manifestations, and neuroimaging features by amalgamating our cases with previously reported ones. The cohort consisted of 25 cases, comprising 18 men and 7 women aged 29 to 77 years (mean age: 66.2 years). The majority of patients (94%) exhibit risk factors for cerebrovascular disease, with hypertension being the primary risk factor. Magnetic resonance imaging (MRI) can detect WD of MCPs within a range of 21 days to 12 months following pontine infarction. This degeneration is characterized by bilateral symmetric hyperintensities on T2/FLAIR-weighted images (WI) lesions in the MCPs. Moreover, restricted diffusion, with hyperintensity on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) signal intensity may be observed as early as 21 days after the infarction. Upon detection of WD, it was observed that 20 patients (80%) remained asymptomatic during subsequent clinic visits, while four (16%) experienced a worsening of pre-existing symptoms. These findings underscore the importance of neurologists enhancing their understanding of this condition by gaining fresh insights into the neuroimaging characteristics, clinical manifestations, and prognosis of individuals with WD of bilateral MCPs.

A Study on Symptoms of Pelvic Floor Dysfunction in Assigned Female at Birth Patients Diagnosed with Gender Dysphoria Undergoing Vaginectomy.

A person diagnosed with gender dysphoria who was assigned female at birth (AFAB) may request a vaginectomy as part of gender-affirming treatment. The aim of this study was to investigate the impact of vaginectomy on symptoms of pelvic floor dysfunction (PFD). This is a cohort study on patient-reported symptoms of PFD in patients who were AFAB, diagnosed with gender dysphoria, and undergoing vaginectomy in a single surgical center. Patients responded to a questionnaire preoperatively and 1 year postoperatively. The questionnaire consisted of 33 questions, including a modified short-form version of the Pelvic Floor Distress Inventory (PFDI-20). Twenty-three consecutive patients were included in the study and 20 patients (87%) completed the 1-year follow-up. The preoperative median PFDI-20 score was 24 (0-114) compared with 32 (0-168) at the 1-year follow-up (P = 0.07). Patients who had previously undergone neophallus construction with a metoidioplasty (n = 15) had no significant change between the preoperative and the 1-year postoperative PFDI-20 score [median 17.5 (0-114) and 27.5 (0-145) (P = 0.65), respectively]; whereas those with a groin flap phalloplasty (n = 5) had a significant increase in reported symptoms [median 37 (10-95) and 124 (45-168), respectively (P = 0.04)]. Overall, vaginectomy could be performed without any major impact on symptoms of PFD. However, this seemed to be true mainly for patients with previous metoidioplasty, whereas patients with previous groin flap phalloplasty reported worsening of symptoms.

Successful Recanalization by Mechanical Thrombectomy in a Child with Arterial Thrombotic Stroke Involving Posterior Circulation: A Case Report with Review of the Literature

Background: Mechanical thrombectomy (MT) for arterial ischemic stroke, although established in adults, is not endorsed routinely for children. The procedure is even rare in children with stroke involving posterior circulation. Here we describe, a child with ischemic stroke due to thrombotic occlusion in the posterior circulation, which was successfully treated with MT. Clinical Description: A 12-year-old boy presented with sudden-onset vertigo, imbalance, slurring of speech, inability to stand, associated with headache and vomiting for 8 hours, without any associated fever, trauma, or seizures. On initial examination, his National Institute of Health Stroke Scale (NIHSS) score was 8. Other systems were within normal limits and there was no cutaneous rash. Management and Outcome: Investigations revealed a normal complete hemogram, lipid profile, serum homocysteine, fibrinogen, and D-dimer levels along with a normal hemoglobin electrophoresis profile. The electrocardiography, two-dimensional echocardiography were normal and even antinuclear antibodies, antiphospholipid antibodies were negative. Magnetic resonance imaging (MRI) of the brain demonstrated multiple acute infarcts in bilateral cerebellar hemispheres, pons, and right anterior thalamus. Noncontrast MR angiography (MRA) of the head and digital subtraction angiography showed distal basilar artery cutoff and right vertebral artery dominance. As the NIHSS score worsened to 10, a MT with solitaire was done (after 12 hours of onset of symptoms), and reperfusion was achieved in two passes. The child showed remarkable improvement in NIHSS score to 2 by 5 days. At discharge, the child had residual mild ataxia. Despite investigations, the cause of thrombosis remained unknown. Conclusion: Our case highlights that in case of significant large arterial occlusion with rapid worsening of symptoms, MT may be considered, even if it involves posterior circulation, and the child presents beyond the usual window of 4–6 hours.

Progressive worsening of posttraumatic stress symptoms in Syrian and Iraqi refugees associated with cumulative and victimization trauma: A longitudinal study.

War and forced migration expose refugees to trauma and ongoing stress, often contributing to long-term psychological consequences. Typically, trauma exposure is assessed cumulatively; yet, trauma type may better predict psychological outcomes. This study examined the differential impact of cumulative trauma and trauma subtypes (victimization, death threat, accidental/injury) on postmigration trajectories of posttraumatic stress and anxiety in refugees. Seventy-seven Syrian (88.3%) and Iraqi (9.1%) adult refugees self-reported prior trauma exposure and psychological symptoms at time of arrival in the United States and 2 years post. Linear mixed-effects modeling was performed to assess for associations between trauma variables and symptom trajectories. Models using cumulative trauma as a predictor were compared to models including the three trauma subtype variables as predictors, using pseudo-R² values to compare variance explained between the two methods of trauma measurement. Linear mixed-effects modeling indicated that prior exposure to victimization predicted progressively worsening posttraumatic stress disorder (PTSD) symptoms over time postmigration (b = .97, SE = .45, t = 2.14, p = .036). Cumulative trauma also predicted increasing PTSD symptoms (b = .124, SE = .06, t = 2.09, p = .041), but explained less variance than victimization (9% vs. 18.1%). Direct effects of cumulative trauma (p = .009) and victimization (p = .002) on anxiety severity emerged; however, anxiety symptoms did not change over time depending on prior trauma exposure. Accidents/injuries and death threats did not predict PTSD or anxiety. These findings can be leveraged toward focused identification of those at highest risk for progressive illness postmigration, thus providing empirical guidance for allocation of interventions and resources for refugees. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Trajectories of improvement with repetitive transcranial magnetic stimulation for treatment-resistant major depression in the BRIGhTMIND trial

Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive brain stimulation treatment for major depressive disorder, but there is marked inter-individual variability in response. Using latent class growth analysis with session-by-session patient global impression ratings from the recently completed BRIGhTMIND trial, we identified five distinct classes of improvement trajectory during a 20-session treatment course. This included a substantial class of patients noticing delayed onset of improvement. Contrary to prior expectations, members of a class characterised by early and continued improvement showed greatest inter-session variability in stimulated location. By relating target locations and inter-session variability to a well-studied atlas, we estimated an average of 3.0 brain networks were stimulated across the treatment course in this group, compared to 1.1 in a group that reported symptom worsening (p < 0.001, d = 0.893). If confirmed, this would suggest that deliberate targeting of multiple brain networks could be beneficial to rTMS outcomes.

A novel controlled metabolic accelerator for the treatment of obesity-related heart failure with preserved ejection fraction: Rationale and design of the Phase 2a HuMAIN trial.

Compared with those without obesity, patients with obesity-related heart failure with preserved ejection fraction (HFpEF) have worse symptoms, haemodynamics, and outcomes. Current weight loss strategies (diet, drug, and surgical) work through decreased energy intake rather than increased expenditure and cause significant loss of skeletal muscle mass in addition to adipose tissue. This may have adverse implications for patients with HFpEF, who already have reduced skeletal muscle mass and function and high rates of physical frailty. Mitochondrial uncoupling agents may have unique beneficial effects by producing weight loss via increased catabolism rather than reduced caloric intake, thereby causing loss of adipose tissue while sparing skeletal muscle. HU6 is a controlled metabolic accelerator that is metabolized to the mitochondrial uncoupling agent 2,4-dinotrophenol. HU6 selectively increases carbon oxidation from fat and glucose while also decreasing toxic reactive oxygen species (ROS) production. In addition to sparing skeletal muscle loss, HU6 may have other benefits relevant to obesity-related HFpEF, including reduced specific tissue depots contributing to HFpEF; improved glucose utilization; and reduction in systemic inflammation via both decreased ROS production from mitochondria and decreased cytokine elaboration from excess, dysfunctional adipose. We describe the rationale and design of HuMAIN-HFpEF, a Phase 2a randomized, double-blind, placebo-controlled, dose-titration, parallel-group trial in patients with obesity-related HFpEF to evaluate the effects of HU6 on weight loss, body composition, exercise capacity, cardiac structure and function, metabolism, and inflammation, and identify optimal dosage for future Phase 3 trials. HuMAIN will test a promising novel agent for obesity-related HFpEF.

COVID-19 clinical rebound after treatment with nirmatrelvir/ritonavir.

Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical rebound syndrome whereby individuals experience a relapse of symptoms shortly after completing successful treatment. There is a lack of information on frequency of COVID-19 rebound after NM/r in routine clinical care, contributing factors, and clinical outcomes. We reviewed electronic medical records to verify COVID-19 diagnosis, symptoms, and treatment with NM/r from January-June 2022. We defined COVID-19 clinical rebound as clear improvement in symptoms followed by recurrence or worsening of symptoms within 30 days of a five-day course of NM/r. We studied 268 adults with median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, 80% vaccinated and boosted against SARS-CoV-2, and 68% with any co-morbidity. Sixteen (6.0%) of studied patients were determined to have COVID-19 clinical rebound. The median time from starting NM/r to rebound was 11 days (IQR 9, 13). Notable demographic and clinical factors with higher proportion (not statistically significant) among COVID-19 rebound patients were female sex (75% rebound vs 54.5% no rebound), Black race (12.5% rebound vs 4.9% no rebound), presence of at least one co-morbidity (81.3% rebound vs 67.5% no rebound), and lack of prior SARS-CoV-2 infection (100% rebound vs 92.9% no rebound). Only one patient (6.25%) was hospitalized after COVID-19 rebound. COVID-19 clinical rebound after treatment with NM/r is mild with favorable outcomes and more common than previously reported from real-world clinical care studies.

Patient perspectives on their outcomes from strabismus surgery undertaken for psychosocial reasons

BackgroundStrabismus surgery undertaken for psychosocial reasons aims to align the eyes in a straighter position, reduce the psychosocial symptoms experienced and improve health related quality of life (HRQoL). Greater evidence of the postoperative outcomes in adults undergoing strabismus surgery for psychosocial reasons is required to inform funding and commissioning decisions about strabismus surgery.MethodsSemi-structured interviews were conducted with adults who had previously undergone strabismus surgery for psychosocial reasons to explore their perceptions of their postoperative outcomes. Maximum variation sampling was used to recruit males and females, younger and older participants. Interviews were transcribed and analysed using thematic analysis following the principles of grounded theory.ResultsThirteen adults were recruited and interviewed, mean 12.2 months postoperatively (range 4.5–20 months). Participants reported a range of improvements in vision, task performance, physical symptoms and confidence and emotions. Some worsening of physical symptoms was reported.ConclusionDespite undergoing strabismus surgery for psychosocial reasons, a range of improvements in vision, task performance and physical symptoms were reported by adult patients postoperatively, in addition to the expected improvements in confidence and emotions.

Progression patterns, resistant mechanisms and subsequent therapy for ALK-positive NSCLC in the era of second-generation ALK-TKIs

BackgroundIn the era of second-generation ALK tyrosine kinase inhibitors (ALK-TKIs), there was a paucity of data regarding the progression patterns, resistant mechanisms, and subsequent therapeutic approaches for ALK-positive (ALK+) non-small cell lung cancer (NSCLC).MethodsPatients with advanced ALK+ NSCLC were retrospectively selected from our center. Cohort 1 consisted of patients who experienced disease progression after receiving first-line alectinib treatment (n = 20), while Cohort 2 included patients who progressed following sequential treatment with crizotinib and second-generation ALK-TKIs (n = 53). Oligo-progression was defined as the occurrence of disease progression in no more than three lesions. Symptomatic progression was determined when patients developed new symptoms or experienced worsening of pre-existing symptoms during radiological progression.ResultsThe incidence of central nervous system (CNS) progression and symptomatic CNS progression was significantly lower in Cohort 1 compared to patients treated with crizotinib, with rates of 15.0% vs. 56.6% (p = 0.002) and 5.0% vs. 32.1% (p = 0.016), respectively. A total of 60.3% (44/73) patients underwent repeated biopsy and next-generation sequencing subsequent to the second-generation ALK-TKI resistance, with secondary mutation in ALK kinase domain emerging as the predominant mechanism of resistance (56.8%). Local therapy was applied to 50% of oligo-progression cases. Subsequent ALK-TKIs demonstrated significantly prolonged progression-free survival (PFS) (8.6 m vs. 2.7 m, p = 0.021, HR = 0.43, 95%CI: 0.15–0.85) and long-term overall survival (OS) (NA vs. 11.9 m, p = 0.132, HR = 0.50, 95%CI: 0.18–1.25) in patients harboring ALK resistance mutations, compared to those without such mutations. For patients without ALK-resistant mutations following progression on second-generation ALK-TKIs, there was no statistically significant difference in survival outcomes between subsequent chemotherapy or alternative ALK-TKI treatments.ConclusionsFirst-line alectinib demonstrated superior efficacy in protecting the CNS compared to crizotinib. For patients with ALK-resistant mutations following the resistance to second-generation ALK-TKIs, appropriate sensitive ALK-TKI should be administered; for those without such mutations, the selection of chemotherapy or third-generation ALK-TKI should be based on the patient’s overall physical health and personal preferences.

A Study of Phenomenology and Treatment Adherence in Patients with Obsessive-compulsive Disorder during COVID-19 Pandemic

Background and Objective: The WHO declared COVID-19 to be a public health emergency which has affected every sphere of life including mental health and is expected to affect the patients of obsessive-compulsive disorder (OCD) adversely. This study aimed to study phenomenology and treatment adherence in patients with the OCD during COVID-19 pandemic. Materials and Methods: The sample consisted of 96 old and new patients of OCD between the age of 18 and 60 years, with the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) ≥16 and onset of illness prior to COVID-19 (March 2020). Diagnosis was made as per ICD-10-DCR, the likelihood of treatment adherence was assessed using the Medication Adherence Rating Scale, and the severity of OCD was assessed on Y-BOCS. The current and past phenomenologies as per D-YBOCS were compared. Among the patients adherent to treatment, subjective response on the current severity of symptoms as compared to before the onset of COVID-19 was recorded. Results: The likelihood of treatment adherence was high (according to the Medication Adherence Scale) in 59.2% of cases. Pandemic reasons were reported by 69% of patients with low likelihood of treatment adherence. Few patients developed new symptoms, but no statistically significant change was found when compared to the pre-COVID-19 phenomenology. Conclusions: Majority of the treatment adherent patients experienced a decrease or no change in their symptom severity as compared to the before COVID-19 severity, suggesting that no worsening of OCD symptoms during the pandemic was observed if the patients were adherent to medications. However, there is a need for long-term considerations and plan interventions accordingly to minimize this deleterious effect.

Summary of seven Swedish case reports on the microwave syndrome associated with 5G radiofrequency radiation.

The fifth generation, 5G, for wireless communication is currently deployed in Sweden since 2019/2020, as well as in many other countries. We have previously published seven case reports that include a total of 16 persons aged between 4 and 83 years that developed the microwave syndrome within short time after being exposed to 5G base stations close to their dwellings. In all cases high radiofrequency (RF) radiation from 4G/5G was measured with a broadband meter. RF radiation reached >2,500,000 to >3,180,000 μW/m2 in peak maximum value in three of the studies. In total 41 different health issues were assessed for each person graded 0 (no complaint) to 10 (worst symptoms). Most prevalent and severe were sleeping difficultly (insomnia, waking night time, early wake-up), headache, fatique, irritability, concentration problems, loss of immediate memory, emotional distress, depression tendency, anxiety/panic, dysesthesia (unusual touched based sensations), burning and lancinating skin, cardiovascular symptoms (transitory high or irregular pulse), dyspnea, and pain in muscles and joints. Balance disorder and tinnitus were less prevalent. All these symptoms are included in the microwave syndrome. In most cases the symptoms declined and disappeared within a short time period after the studied persons had moved to a place with no 5G. These case histories are classical examples of provocation studies. They reinforce the urgency to inhibit the deployment of 5G until more safety studies have been performed.

Role of exosomes in exacerbations of asthma and COPD: a systematic review.

Asthma and chronic obstructive pulmonary disease are chronic respiratory disorders characterized by airways obstruction and chronic inflammation. Exacerbations lead to worsening of symptoms and increased airflow obstruction in both airways diseases, and they are associated with increase in local and systemic inflammation. Exosomes are cell-derived membrane vesicles containing proteins, lipids, and nucleic acids that reflect their cellular origin. Through the transfer of these molecules, exosomes act as mediators of intercellular communication. Via selective delivery of their contents to target cells, exosomes have been proved to be involved in regulation of immunity and inflammation. Although, exosomes have been extensively investigated in different diseases, little is currently known about their role in asthma and COPD pathogenesis, and particularly in exacerbations. This review aims to systemically assess the potential role of exosomes in asthma and COPD exacerbations.

(133) SELF-REPORTED EFFICACY OF PELVIC FLOOR PHYSICAL THERAPY AS A TREATMENT FOR PUDENDAL NEURALGIA: A CROSS-SECTIONAL STUDY

Abstract Introduction Pudendal neuralgia (PN) is a devastating sexual pain disorder characterized as pain of the genital and/or perineal regions and is often due to injury, irritation, or entrapment of the pudendal nerve. Pelvic floor physical therapy (PFPT) is a recommended treatment for PN despite the lack of clinical evidence supporting its use. Objective We aimed to understand the efficacy of PFPT for treating PN by evaluating self-reported efficacy from PN patients. Methods An online survey was conducted on PN patients who had participated in PFPT as a treatment for PN. Participants were asked to evaluate the efficacy of PFPT specifically regarding its effects on PN symptoms using a seven-point Patient Global Impression of Change (PGIC) scale: 1=very much worse, 2=much worse, 3=minimally worse, 4=no change, 5=minimally improved, 6=much improved, 7=very much improved. If lasting symptom improvement was achieved, participants were asked how many sessions before they first noticed an improvement in symptoms. Results The average PGIC score among participants was 4.6 ± 1.3 (n=144), indicating no to minimal improvement in symptoms. Twelve percent of participants scored 3 or lower, indicating worsening of symptoms, and only 22% scored 6 or 7, indicating much or very much improvement of symptoms. For those who had symptom improvement, 14.6% of participants reported improvement after only one PFPT session, and five was the median number of sessions before first noticing improvement. Conclusions PFPT is a minimally effective, and sometimes harmful, treatment for pudendal neuralgia. Better transparency should be provided to patients regarding PFPT’s lack of efficacy and potential harm for treating PN symptoms. Disclosure No.

(131) EFFECTIVENESS OF AN INTERACTIVE PATIENT LEARNING MODULE: INTIMACY IN PREGNANCY

Abstract Introduction Two-thirds of women experience negative sexual symptoms during their pregnancy. Women suffer with dyspareunia, arousal issues, decreased libido, and anorgasmia frequently throughout pregnancy, with a significant worsening of symptoms during the third trimester. Also, many women restrict their sexual activity due to fear and misconceptions of inducing preterm labor or harming the fetus and social parameters of sexual conduct during pregnancy. Due to the lack of readily available medical education regarding sexual function in pregnancy, many women of various religious backgrounds may feel lack of trusting asking family members or medical professionals regarding sexual wellness. Objective Patient education given during pregnancy will increase patient knowledge of intimacy during pregnancy as well as improve sexual satisfaction and relationship quality and mental health in pregnancy. Moreover, this module will address gaps in common misconceptions by introducing supportive literature findings regarding benefits of intercourse during pregnancy dispensing the social stigma. Methods This prospective study is a single group before and after pilot study. This study recruited 25 patients beyond 12 weeks’ gestation. We approached 34 of patients and 25 agreed to participate in review an educational module titled “Sexual Intimacy and Pregnancy” build from ACOG guidelines. This module was created at an 8th grade reading level. Patients completed a presurvey, used the module on an electronic device and then completed a post-module assessment. Results 68% of women currently experience sexual dysfunction as either one of more of the following: pain with sex, decreased libido, anorgasmia, or vaginal dryness. Compared to their pre-module response, more women correctly answered the items “What percentage of pregnant women experience sexual dysfunction?” (28.0% versus 76.0%; p = .001) and “Having sex will cause labor” (28.0% versus 4.0%; p = .03). Additionally, women were more comfortable asking their doctor about sex while pregnant following the module (OR = 2.26, 95% CI: 1.06 – 4.83; p = .04). Through the recruitment process, we noticed that patients more likely to participate based on age, level of education received and most significant gravidity. The key for this recruitment was to create an environment in the exam room where both parents were able to see and engage with the module. During the module, partners spoke about current sexual dysfunction initially followed by confirmation by the pregnant patient. Prior to viewing this module, most participants predicted a much smaller percentage of women would be afflicted by sexual dysfunction in pregnancy which illustrating the broad deficits in sexual health education. Conclusions All participants would recommend this educational module to fellow pregnant women and all participants rated the completion and content of this module at easy or very easy to follow. This education module demonstrates baseline improvement in knowledge of sexual function in pregnancy and increases comfort level of discussing sexual function during prenatal care. Future direction of this study aims to target education in various socioeconomic cultures where intimacy education is not discussed in the clinical setting. Disclosure No.

Reduction of long COVID symptoms after stellate ganglion block: A retrospective chart review study

The SARS-CoV-2 pandemic has left millions of individuals with a host of post-viral symptoms that can be debilitating and persist indefinitely. To date there are no definitive tests or treatments for the collection of symptoms known as “Long COVID” or Post-acute sequelae of COVID-19 (PASC). Following our initial case report detailing improvement of Long COVID symptoms after sequential bilateral stellate ganglion blockade (SGB), we performed a retrospective chart analysis study on individuals treated with the same protocol over the course of six months (2021−2022) in our clinic. Patients self-reported symptoms on a 10-point scale as part of optional patient follow-up using an online survey. After one month or more following treatment, patients reported striking reductions in Fatigue, Worsening of Symptoms following Mental and Physical Activity, Memory Problems, Problems Concentrating, Sleep Problems, Anxiety, and Depression. Loss of Taste and Loss of Smell in some individuals did not respond to treatment, likely indicating structural damage following infection. This study suggests that neuromodulation may provide relief of Long COVID symptoms for at least a subset of individuals, and provides support for prospective studies of this potential treatment.

Establishment of a human nasal epithelium model of histamine-induced inflammation to assess the activity of fexofenadine as an inverse agonist and its link to clinical benefit.

Fexofenadine (FEX) is an antihistamine that acts as an inverse agonist against histamine (HIS) receptor 1 (H1R), which mediates the allergic reaction. Inverse agonists may be more potent than neutral antagonists, as they bind the same receptor as the agonist (HIS) but stabilize the inactive form and induce an opposite pharmacological response, suppressing the basal activity of H1R and preventing HIS from binding. This study aims to establish and validate a model of HIS-induced inflammation based on fully reconstituted human nasal epithelial tissue to assess the activity of FEX as an inverse agonist in this model and explore its link to clinical benefit. The model was developed using nasal MucilAir™ (Epithelix) in vitro epithelium challenged by HIS. Two conditions were assessed in a side-by-side comparison: tissue was exposed to HIS + FEX with or without FEX pre-treatment (one-hour prior to HIS challenge). Tissue functionality, cytotoxicity, H1R gene expression, and inflammatory cytokines were assessed. HIS at 100µM induced significant 3.1-fold and 2.2-fold increases for inflammatory biomarkers interleukin (IL)-8 and IL-6, respectively (p < 0.0001), as well as rapid upregulation of H1R mRNA. Inflammatory biomarkers were inhibited by FEX and H1R expression was significantly reduced (p < 0.0001). FEX alone decreased H1R expression at all doses tested. With one-hour FEX pre-treatment, there was significantly higher downregulation of IL-8 (p < 0.05) and further downregulation of H1R expression and IL-6 versus without FEX pre-treatment; the effects of FEX were improved from 22% to 40%. A model of HIS-induced airway inflammation was established based on IL-8, IL-6 and H1R gene expression and was validated with FEX. FEX works as an inverse agonist, with a higher effect when used before+during versus only during the HIS challenge. Taking FEX before+during allergen exposure, or when symptoms first occur, may reduce basal activity and H1R gene expression, providing stronger protection against the worsening of symptoms upon allergen exposure.

Primary outcomes of the enhanced, EHR-facilitated cancer symptom control (E2C2) cluster-randomized, stepped wedge, pragmatic trial.

LBA12006 Background: Symptom burden and functional decline are prevalent, inconsistently treated, and associated with adverse health outcomes in patients with cancer. Symptom monitoring with electronic patient-reported outcome measures (ePROMs) has yielded mixed results due, in part, to care teams’ variable bandwidth and resourcing for symptom management. The collaborative care model (CCM) offers a validated means to address these issues and potentially improve clinical and health services outcomes. Capturing ePROMS through the electronic health record (EHR) for use in CCM delivery provides a potentially scalable approach to manage symptoms at the population level. Methods: E2C2 is a cluster-randomized, population-level, stepped wedge pragmatic trial that compares a bundled, EHR-facilitated, CCM-based intervention to improve control of SPPADE symptoms (Sleep interference, Pain, impaired Physical function, Anxiety, Depression, and Energy deficit/fatigue) with usual care. All patients, regardless of cancer type or stage, treated in the medical oncology clinics of a multi-state health system, were assigned to one of fifteen clusters. Control and intervention conditions monitored SPPADE symptoms with Epic EHR administered 11-point numerical rating scales (NRSs). Moderate and severe symptoms were defined as 4-6/10 and &gt;7/10, respectively. The intervention added EHR clinician decision support; automated delivery of symptom self-management information; and options to address severe symptoms with a dedicated symptom care manager. The primary outcome was post-baseline SPPADE scores assessed using multivariate regression of six cluster-period mean SPPADE symptom scores against E2C2 exposure, fixed cluster and secular time effects. Results: From March 2019 to January 2023, 50,559 patients were assigned to E2C2 clusters and 40,295 completed at least one ePROM. At first assessment, participants’ mean age was 63.3 years; 58% were female; 26% were rural, and the prevalences of moderate or worse symptoms were fatigue 42%, impaired function 34%, sleep disturbance 34%, anxiety 27%, pain 26%, and depression 23%. The intervention significantly reduced mean composite SPPADE symptom scores, p &lt;0.001, among all patients, as well as those with &gt;1 moderate or worse symptom. All mean symptom scores were lower in the intervention group, with the largest effects detected among patients with fatigue -0.2 (-0.4, -0.07), anxiety -0.14 (-0.2, -0.03), and depression -0.1 (-0.2, -0.002). Conclusions: In this large cluster-randomized trial, an EHR-facilitated, bundled intervention that scaled CCM-based surveillance and management of SPPADE symptoms significantly reduced population-level symptom burden, particularly for fatigue, anxiety, and depression. This study provides real world evidence and the foundation for future national efforts aimed at controlling symptoms in patients with cancer. Clinical trial information: NCT03892967 .

Clinical characteristics and the risk factors for the exacerbation of symptoms in patients with inflammatory bowel disease during the COVID-19 pandemic.

In 2023, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant caused a large-scale outbreak of coronavirus disease 2019 (COVID-19) in China. It is not clear the risk factors that lead to the exacerbation of symptoms in patients with inflammatory bowel disease (IBD) after COVID-19 infection. Our study aims to find out the risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection and to provide guidance for the clinical management of IBD. This is a retrospective, observational study. The online questionnaire was distributed to conduct a survey to collect demographic, clinical, and IBD related characteristics in IBD patients. Univariate and multivariate regression analyses were conducted to assess the independent effects. In total, 534 cases of IBD patients were analyzed in our study. Among them, 466 (87.3%) cases diagnosed with COVID-19, 160 (34.3%) cases experienced exacerbation of IBD symptoms, and 84 (18.0%) patients opted for medication discontinuation. Male sex (OR 2.04, 95% CI 1.34-3.49, p = 0.001), and the decrease in body mass index (BMI) (OR 0.93, 95% CI 0.87-1.00, p = 0.035) were positively correlated with the exacerbation of IBD symptoms. Furthermore, the medication discontinuation (OR 2.60, 95% CI 1.58-4.30, p < 0.001) was strongly positively correlated with the exacerbation of IBD symptoms. No significant association was seen between age, comorbidities, smoking, disease activity, vaccination, therapy for COVID-19 and the worsening of IBD symptoms. This study confirms that the infection rate of COVID-19 in China IBD patients was comparable to the general population. Male sex, the decrease in BMI and medication discontinuation are significant risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection.

Symptom phenotyping in people with cystic fibrosis during acute pulmonary exacerbations using machine-learning K-means clustering analysis

IntroductionPeople with cystic fibrosis (PwCF) experience frequent symptoms associated with chronic lung disease. A complication of CF is a pulmonary exacerbation (PEx), which is often preceded by an increase in symptoms and a decline in lung function. A symptom cluster is when two or more symptoms co-occur and are related; symptom clusters have contributed meaningful knowledge in other diseases. The purpose of this study is to discover symptom clustering patterns in PwCF during a PEx to illuminate symptom phenotypes and assess differences in recovery from PExs. MethodsThis study was a secondary, longitudinal analysis (N = 72). Participants at least 10 years of age and being treated with intravenous antibiotics for a CF PEx were enrolled in the United States. Symptoms were collected on treatment days 1–21 using the CF Respiratory Symptom Diary (CFRSD)-Chronic Respiratory Symptom Score (CRISS). K-means clustering was computed on day 1 symptom data to detect clustering patterns. Linear regression and multi-level growth models were performed. ResultsSymptoms significantly clustered based on severity: low symptom (LS)-phenotype (n = 42), high symptom (HS)-phenotype (n = 30). HS-phenotype had worse symptoms and CRISS scores (p< 0.01) than LS-phenotype. HS-phenotype was associated with spending 5 more nights in the hospital annually (p< 0.01) than LS-phenotype. HS-phenotype had worse symptoms over 21 days than LS-phenotype (p< 0.0001). ConclusionSymptoms significantly cluster on day 1 of a CF-PEx. PwCF with HS-phenotype spend more nights in the hospital and are less likely to experience the same resolution in symptoms by the end of PEx treatment than LS-phenotype.