Symptom Medication Research Articles

Sex differences in deep brain shape and asymmetry persist across schizophrenia and healthy individuals: A meta-analysis from the ENIGMA-Schizophrenia Working Group.

Schizophrenia (SCZ) is characterized by a disconnect from reality that manifests as various clinical and cognitive symptoms, and persistent neurobiological abnormalities. Sex-related differences in clinical presentation imply separate brain substrates. The present study characterized deep brain morphology using shape features to understand the independent effects of diagnosis and sex on the brain, and to determine whether the neurobiology of schizophrenia varies as a function of sex. This study analyzed multi-site archival data from 1,871 male (M) and 955 female (F) participants with SCZ, and 2,158 male and 1,877 female healthy controls (CON) from twenty-three cross-sectional samples from the ENIGMA Schizophrenia Workgroup. Harmonized shape analysis protocols were applied to each site's data for seven deep brain regions obtained from T1-weighted structural MRI scans. Effect sizes were calculated for the following main contrasts: 1) Sex effects;2) Diagnosis-by-Sex interaction; 3) within sex tests of diagnosis; 4) within diagnosis tests of sex differences. Meta-regression models between brain structure and clinical variables were also computed separately in men and women with schizophrenia. Mass univariate meta-analyses revealed more concave-than-convex shape differences in all regions for women relative to men, across diagnostic groups ( d = -0.35 to 0.20, SE = 0.02 to 0.07); there were no significant diagnosis-by-sex interaction effects. Within men and women separately, we identified more-concave-than-convex shape differences for the hippocampus, amygdala, accumbens, and thalamus, with more-convex-than-concave differences in the putamen and pallidum in SCZ ( d = -0.30 to 0.30, SE = 0.03 to 0.10). Within CON and SZ separately, we found more-concave-than-convex shape differences in the thalamus, pallidum, putamen, and amygdala among females compared to males, with mixed findings in the hippocampus and caudate ( d = -0.30 to 0.20, SE = 0.03 to 0.09). Meta-regression models revealed similarly small, but significant relationships, with medication and positive symptoms in both SCZ-M and SCZ-F. Sex-specific variation is an overriding feature of deep brain shape regardless of disease status, underscoring persistent patterns of sex differences observed both within and across diagnostic categories, and highlighting the importance of including it as a critical variable in studies of neurobiology. Future work should continue to explore these dimensions independently to determine whether these patterns of brain morphology extend to other aspects of neurobiology in schizophrenia, potentially uncovering broader implications for diagnosis and treatment. Statistical analyses revealed significant main effects for diagnosis and sex in deep brain shape morphology. Among patients with schizophrenia, there was a pattern of thinning and surface contraction in the bilateral hippocampus, amygdala, accumbens, and thalamus, and a pattern of significant thickening and surface expansion in the bilateral putamen and pallidum compared to healthy control participants. Between males and females, there was a pattern of significant thinning and surface contraction in the bilateral thalamus, pallidum, putamen, and amygdala in females compared to males.There was no significant interaction between diagnosis and biological sex, suggesting that sex differences in deep brain shape and asymmetry among patients with schizophrenia reflect those observed in healthy individuals.Small but statistically significant relationships exist between brain structure and clinical correlates of schizophrenia were similar for both men and women with the disease, such that higher CPZ was associated with shape-derived thinning and surface contraction in the caudate, accumbens, hippocampus, amygdala, and thalamus, and elevated positive symptoms were associated with shape-derived thinning and surface contraction in the bilateral caudate, right hippocampus, and right amygdala.

Exploring Health Care Professionals' Perspectives on the Use of a Medication and Care Support System and Recommendations for Designing a Similar Tool for Family Caregivers: Interview Study Among Health Care Professionals.

With the aging population on the rise, the demand for effective health care solutions to address adverse drug events is becoming increasingly urgent. Telemedicine has emerged as a promising solution for strengthening health care delivery in home care settings and mitigating drug errors. Due to the indispensable role of family caregivers in daily patient care, integrating digital health tools has the potential to streamline medication management processes and enhance the overall quality of patient care. This study aims to explore health care professionals' perspectives on the use of a medication and care support system (MCSS) and collect recommendations for designing a similar tool for family caregivers. Fifteen interviews with health care professionals in a home care center were conducted. Thematic analysis was used, and 5 key themes highlighting the importance of using the MCSS tool to improve medication management in home care were identified. All participants emphasized the necessity of direct communication between health care professionals and family caregivers and stated that family caregivers need comprehensive information about medication administration, patient conditions, and symptoms. Furthermore, the health care professionals recommended features and functions customized for family caregivers. This study underscored the importance of clear communication between health care professionals and family caregivers and the provision of comprehensive instructions to promote safe medication practices. By equipping family caregivers with essential information via a tool similar to the MCSS, a proactive approach to preventing errors and improving outcomes is advocated.

Pharmacological Correction of Gastrointestinal Motility in Patients with Functional Gastrointestinal Disorders

Actuality. Functional gastrointestinal disorders (FGID) represent a significant public public health issue. The foundation of effective therapy for FGID with overlap syndrome - functional dyspepsia (FD, epigastric pain syndrome) with gastric hypersecretion and irritable bowel syndrome (IBS)-is considered to be pathogenetic therapy or the combined use of symptomatic medications. Aim. Assessment of the impact of pathophysiological therapy with the drug Kolofort and symptomatic treatments, including proton pump inhibitors (PPIs) and the myotropic antispasmodic mebeverine hydrochloride in prolonged-release capsules, on the clinical manifestations of FGIDs with overlap syndrome - FD (pain syndrome in the epigastric region) with gastric hypersecretion and IBS - includes evaluating effects on myoelectric activity of the gastrointestinal tract. Design. (conception) An open cohort-controlled comparative study on the effects of Kolofort, omeprazole, rabeprazole, and mebeverine hydrochloride in prolonged-release capsules on intestinal motility in patients with FGID and overlap syndrome - functional dyspepsia (FD, epigastric pain syndrome) with gastric hypersecretion and IBS. Materials and Methods. A total of 107 patients suffering from FGID with overlap syndrome - functional dyspepsia (FD, epigastric pain syndrome) with gastric hypersecretion and IBS - were examined. Results. A one-month course of Kolofort significantly improved the psychological status of IBS patients and enhanced intestinal myoelectric activity. Since there is no available literature on Kolofort’s effect on gastric secretion levels, PPIs and mebeverine hydrochloride were used in the treatment of patients with FGID - FD (epigastric pain syndrome) with gastric hypersecretion and IBS overlap syndrome. The use of PPIs, such as omeprazole and rabeprazole, in these patients eliminated gastric hypersecretion and abdominal pain. Rabeprazole demonstrated faster effects than omeprazole and also normalized gastrointestinal motility more efficiently. For patients with FGIDs - FD with gastric hypersecretion and overlap syndrome with IBS, a combined therapy of omeprazole and the myotropic antispasmodic mebeverine hydrochloride in prolonged-release capsules is recommended. This combination, within two weeks, resolved clinical symptoms in 97% of cases, improved the quality of life, and normalized intestinal motility and gastrointestinal myoelectric activity. However, monotherapy with rabeprazole at a daily dose of 20 mg more rapidly addressed symptoms of gastric hypersecretion and and normalized gastrointestinal motility.

Can Digital Health Improve Therapeutic Compliance in Oncology?

Therapeutic compliance, or adherence, is critical in oncology because of the complexity and duration of cancer treatment regimens. Nonadherence can lead to suboptimal therapeutic outcomes, increased disease progression, higher mortality rates, and elevated health care costs. Traditional methods to enhance compliance, such as patient education and regular follow-ups, have shown limited success. This review examines the potential of digital health technologies to improve adherence in oncology. Various studies and trials are analyzed to assess the effectiveness of these technologies in supporting patients with cancer. mHealth applications have been shown to improve medication adherence through features like medication reminders and symptom tracking. Telemedicine facilitates continuous care and reduces the need for travel, significantly improving adherence and patient satisfaction. Patient-reported outcome measures enhance clinical decision making and personalized treatment plans by incorporating patient feedback. Electronic medical records and patient portals improve compliance by providing easy access to medical information and fostering better patient-provider communication. Connected pillboxes aid in consistent medication intake and reduce dispensing errors. Digital health technologies offer significant benefits in oncology by enhancing patient engagement, improving adherence to treatment protocols, and enabling comprehensive cancer care management. However, challenges such as the digital divide, data privacy concerns, and the need for tailored interventions must be addressed. Future research should focus on evaluating the effectiveness of digital interventions and developing personalized digital health tools to maximize therapeutic compliance.

Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials

IntroductionTracking of emergent symptoms (ES) in de novo Parkinson Disease (PD) patients using Parts Ib and II of the MDS-UPDRS rating scale has been proposed as an outcome measure for PD clinical trials, based on observations in the Safety, Tolerability and Efficacy Assessment of Isradipine for PD (STEADY-PD3) clinical trial. MethodsIndividual item-level data was extracted from the SURE-PD3 study (coded as “PD-1018” in the C-path pooled dataset). We sought to confirm the observations made in the STEADY-PD3 dataset by analyzing data from a different Phase 3 clinical trial, the Phase 3 Study of Urate Elevation in Parkinson Disease (SURE-PD3), in which MDS-UPDRS was assessed more frequently than the 12-month intervals in STEADY-PD3, using similar methodology. ResultsWe were able to broadly validate results that demonstrated the frequency of ES, lack of impact of the introduction of symptomatic medications, and in the reduction in sample size required to demonstrate slowing of disease progression at a group level compared with the traditional total MDS-UPDRS summed score scoring methods. Counts of ES generally correlated modestly with summed MDS-UPRDS scores, both for the various sub-parts and for the overall scale as well. However, instability of individual item responses, especially during the first 6 months of observation complicated the assessment of the temporal evolution and stability of ES over time in the course of the SURE-PD3 study. ConclusionFurther validation using data sets with frequent administration of MDS-UPDRS is necessary to assess value of this approach as an outcome measure in PD clinical trials.

Aberrant salience in acute versus chronic schizophrenia: Do medication and positive symptoms make a difference?

The nature of aberrant salience in schizophrenia, whether it is a state or a trait phenomenon, remains unclear. To assess and compare aberrant salience in patients with schizophrenia at different stages of the illness and to explore its association with symptom severity and medication use. A total of 113 subjects were included, comprising 83 patients with schizophrenia divided into three groups: group A (acute drug-free symptomatic stage, n = 23), group B (chronic-medicated symptomatic stage, n = 30), and group C (chronic-medicated asymptomatic stage, n = 30). These were compared with a healthy control group (group D, n = 30). Participants were assessed using the Aberrant Salience Inventory (ASI) and clinical rating scales, including Psychotic Symptom Rating Scales, Scale for Assessment of Positive Symptoms, and Scale for Assessment of Negative Symptoms (SANS). Significant differences were observed across almost all domains of aberrant salience. The most notable differences were between the symptomatic groups (A, B) and the healthy controls (D). Subgroup analysis showed no significant differences between the acute (A) and chronic groups (B, C), but significant differences were found between the symptomatic (A, B) and asymptomatic (C) groups in several domains and in the total ASI score. A highly significant positive correlation was noted between the total ASI score and the symptom rating scales, except for SANS. Aberrant salience is significantly elevated in patients with prominent positive symptoms, particularly delusions and hallucinations. It appears comparable to the general population in chronic remitted patients, suggesting that aberrant salience is state-dependent. Medication did not significantly influence aberrant salience as both medicated and nonmedicated symptomatic patients continued to exhibit it. However, medication may contribute to reducing aberrant salience by alleviating positive psychotic symptoms.

Longitudinal association of exclusive and dual use of cigarettes and cigars with asthma exacerbation among US adults: a cohort study

BackgroundCigar use among adults in the United States has remained relatively stable in the past decade and occupies a growing part of the tobacco marketplace as cigarette use has declined. While studies have established the detrimental respiratory health effects of cigarette use, the effects of cigar use need further characterization. In this study, we evaluate the prospective association between cigar use, with or without cigarettes, and asthma exacerbation.MethodsWe used data from Waves 1–5 (2013–2019) of the Population Assessment of Tobacco and Health Study to run generalized estimating equation models examining the association between time-varying, one-wave-lagged cigarette and cigar use and self-reported asthma exacerbation among US adults (18+). We defined our exposure as non-established (reference), former, exclusive cigarette, exclusive cigar, and dual use. We defined an asthma exacerbation event as a reported asthma attack in the past 12 months necessitating oral or injected steroid medication or asthma symptoms disrupting sleep at least once a week in the past 30 days. We adjusted for age, sex, race and ethnicity, household income, health insurance, established electronic nicotine delivery systems use, cigarette pack-years, secondhand smoke exposure, obesity, and baseline asthma exacerbation.ResultsExclusive cigarette use (incidence rate ratio (IRR): 1.26, 95% confidence interval (CI): 1.03–1.54) and dual use (IRR: 1.41, 95% CI: 1.08–1.85) were associated with a higher rate of asthma exacerbation compared to non-established use, while former use (IRR: 1.01, 95% CI: 0.80–1.28) and exclusive cigar use (IRR: 0.70, 95% CI: 0.42–1.17) were not.ConclusionWe found no association between exclusive cigar use and self-reported asthma exacerbation. However, exclusive cigarette use and dual cigarette and cigar use were associated with higher incidence rates of self-reported asthma exacerbation compared to non-established use. Studies should evaluate strategies to improve cigarette and cigar smoking cessation among adults with asthma who continue to smoke.

Sex Differences in the Expression of Central Sensitization Symptoms in Migraine: An Observational Study.

Background: Migraine is the fourth most common cause of disability in women and the eighth most common cause in men. Central sensitization phenomena predispose to chronic migraine and are generally more pronounced in women. Objective: The aim of this retrospective observational study was to look for sex differences in a population of migraine subjects attending a tertiary headache center, focusing on symptoms of central sensitization such as allodynia and pericranial tenderness. Methods: This study is based on data collected at a tertiary headache center between January 1, 2018, and December 31, 2022. The clinical interview included the main features of migraine, allodynia, a disability questionnaire, the pericranial tenderness score, and anxiety and depression scales. Results: We selected a total of 1,087 migraine subjects (233 men). Osmophobia predominated in women, as did nausea. Disability scores, headache intensity, allodynia, anxiety, and depression predominated in women, without menopausal age playing a role. The frequency of symptomatic medication use was similar in both sexes. Allodynia score was the largest discriminating factor between women and men. Conclusions: Women with migraine are more likely than men to report acute allodynia, nausea, and osmophobia and are also more likely to be anxious, depressed, and disabled. These features appear to be independent of fertile age and are probably related to sex-specific genetic characteristics. These symptoms represent a tendency toward sensory hypersensitivity and central sensitization that should be carefully assessed in both women and men with migraine with a view to possibly predicting chronic development.

Three-month treatment outcome of medication-overuse headache according to classes of overused medications, use of acute medications, and preventive treatments

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications.

Narcolepsy and rapid eye movement sleep.

Since the first description of narcolepsy at the end of the 19th Century, great progress has been made. The disease is nowadays distinguished as narcolepsy type 1 and type 2. In the 1960s, the discovery of rapid eye movement sleep at sleep onset led to improved understanding of core sleep-related disease symptoms of the disease (excessive daytime sleepiness with early occurrence of rapid eye movement sleep, sleep-related hallucinations, sleep paralysis, rapid eye movement parasomnia), as possible dysregulation of rapid eye movement sleep, and cataplexy resembling an intrusion of rapid eye movement atonia during wake. The relevance of non-sleep-related symptoms, such as obesity, precocious puberty, psychiatric and cardiovascular morbidities, has subsequently been recognized. The diagnostic tools have been improved, but sleep-onset rapid eye movement periods on polysomnography and Multiple Sleep Latency Test remain key criteria. The pathogenic mechanisms of narcolepsy type 1 have been partly elucidated after the discovery of strong HLA class II association and orexin/hypocretin deficiency, a neurotransmitter that is involved in altered rapid eye movement sleep regulation. Conversely, the causes of narcolepsy type 2, where cataplexy and orexin deficiency are absent, remain unknown. Symptomatic medications to treat patients with narcolepsy have been developed, and management has been codified with guidelines, until the recent promising orexin-receptor agonists. The present review retraces the steps of the research on narcolepsy that linked the features of the disease with rapid eye movement sleep abnormality, and those that do not appear associated with rapid eye movement sleep.

Reversion of chronic to episodic migraine in working age and botulinum toxin-resistant patients treated with fremanezumab: A real-life study.

The objectives of this real-life study were to analyze the reversion of chronic migraine (CM) to episodic migraine (EM) with fremanezumab, evaluate its benefit on the symptomatology, and determine the influence of possible clinical features on the reversion. The clinical manifestations of CM have a high impact on the quality of life of patients, and monoclonal antibodies such as fremanezumab are used as prophylactic treatment. Diagnosed CM patients treated for at least 3 months with monthly fremanezumab were interviewed. The data to assess efficacy were before treatment and at the time of the interview: monthly headache days (MHDs), daily headache hours (DHHs), monthly symptomatic medication days (MSMDs), percentage of patients with symptomatic medication overuse (SMO), and pain intensity with the numerical rating scale (NRS) score. Possible predictors of reversion were analyzed: percentage of patients treated for at least 12 months, hypertension, diabetes mellitus, depression, anxiety, symptomatic control with non-steroidal anti-inflammatory drugs (NSAIDs), triptans or both, and amitriptyline prophylaxis. A total of 54 patients were included, of whom 40 (74.1%) were converters to EM. There were significant improvements in converters compared to pre-treatment in MHDs (28.0vs. 5.0 days), as well as on the variables DHHs, MSMDs, and SMO. The percentage of erenumab failures was significantly higher in non-converters than in converters, as was the percentage of patients with anxiety. High reversion from CM to EM was achieved with fremanezumab and notable symptomatological improvement, establishing previous failure to erenumab and anxiety as possible detrimental factors for reversion.

House dust mite immunotherapy: A real-world, prescription data-based analysis.

House dust mite (HDM) sensitisation can contribute to the development of allergic rhinoconjunctivitis (AR) or allergic asthma (AA). As treatment, allergen immunotherapy (AIT) is a promising approach, since it aims building immunotolerance against allergens, therewith establishing long-term efficacy. The evaluation of AIT has been investigated in many randomised controlled trials, whereas few real-world evidence studies are available. We used data from the longitudinal prescription data base IQVIA™ LRx. Data on initial AIT prescriptions against HDM from January 2009 to December 2013 was analysed regarding treatment (subcutaneous AIT with either depigmented polymerised allergen extract [dSCIT] or other allergens [oSCIT], or sublingual immunotherapy [SLIT]) and treatment duration. Treatment groups were compared with a control group of AR patients not receiving AIT. Data on symptomatic medication was collected until February 2017 and progression of AR and AA was compared. Data of 7260 patients with AIT prescriptions and of 21,780 control patients was analysed. AIT was associated with a significant decrease of AR medication intake compared with control (dSCIT: -34.0%, p<0.0001; oSCIT: -25.7%, p<0.0001; SLIT: -37.7%, p=0.0026). In asthmatics, SCIT was associated with a significant decrease of asthma medication compared with control (dSCIT: -45.2%, p<0.0001; oSCIT: -32.9%, p<0.0001). Further, a significantly reduced likelihood for onset of asthma medication was demonstrated in patients treated with SCIT compared with controls (dSCIT OR: 0.759, p=0.0476; oSCIT OR: 0.815, p=0.0339). Real-world data analyses indicate that AIT, particularly given via a subcutaneous route, reduces the need of medication against AR and AA and might delay the onset of asthma medication in patients with AR.

Treatment with the SQ tree sublingual immunotherapy tablet is safe and well tolerated in real-life.

The SQ tree sublingual immunotherapy (SLIT)-tablet is authorised for treatment of allergic rhinoconjunctivitis with or without asthma in trees of the birch homologous group in 21 European countries. The primary objective of this study was to explore the safety in real-life. In a prospective, non-interventional post-authorisation safety study (EUPAS31470), adverse events (AEs) and adverse drug reactions (ADRs) at first administration and follow-up visits, symptoms, medication use, and pollen food syndrome were recorded by physicians in 6 European countries during the first 4-6months of treatment. ADRs with the SQ tree SLIT-tablet were reported in 57.7% of 1069 total patients (median age 36.0years, 53.7% female) during the entire observation period (severity, mild-to-moderate: 70.1%, severe: 4.7%, serious: 0.7%) and in 45.9% after first administration. ADRs were not increased with pollen exposure at first administration. With coadministration of the SQ tree and grass SLIT-tablet AEs were reported in 73.8% of patients and in 52.8% with the SQ tree SLIT-tabletalone. Nasal and eye symptoms improved in 86.9% and 80.9% of patients and use of symptomatic medication in 76.0%. PFS with symptoms was reported in 43.0% of patients at baseline and in 4.3% at the individual last visit. The results of this non-interventional safety study with the SQ tree SLIT-tablet confirm the safety profile from placebo-controlled clinical trials and support effectiveness in real-life according to the published efficacy data. Safety was not impaired by pollen exposure at first administration or co-administration with other SLIT-tablets.

Conservative Management of Chronic Subdural Haematomas

Between Jan./2016 and Dec./2023(=8 years) chronic subdural haematoma cases were diagnosed in 82 patients at the Department of Neurosurgery. In this report we evaluate the therapeutic results retrospectively. The treatment was surgical in 44 patients, while 38 patients were treated medically, i.e., with corticosteroids, symptomatic medication and physiotherapy. Four surgical patients developed a recurrence which was then also treated medically. Of the 38 patients in the medically treated group, 3 had to undergo surgery later. Operose patients with distinct focal symptoms and comatose patients with incipient herniation received immediate surgical treatment. Of the 38 medically treated patients, (31 =81% were symptoms-free and 7= 19% showed residual symptoms).

A Simulation Study of the Effect of Clinical Characteristics and Treatment Choice on Reliever Medication Use, Symptom Control and Exacerbation Risk in Moderate-Severe Asthma.

The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). Reduction in reliever medication use (puffs/24h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phaseIII/IV clinical studies. Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01). We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.

Comprehensive Approach of the Diagnosis, Treatment, and Medical Rehabilitation of Patients with Spondylolisthesis

: Spondylolisthesis represents the slippage of one vertebra over another, and is widely diagnosed among patients accusing low back pain. Despite most patients being asymptomatic, spondylolisthesis can be the cause of extremely severe, irreversible, and invalidating symptoms. The most frequent types of spondylolisthesis are isthmic, degenerative, dysplastic, traumatic, pathologic, and iatrogenic. While numerous classification systems have been used to describe spondylolisthesis, the descriptive Wiltse classification and the Meyerding classification based on the severity of slippage are the most commonly used in current practice. The clinical evaluation is focused on the degree of pain, the presence of radiculopathy, and other neurological deficits, and is followed by diagnostic imaging, including standing anteroposterior and lateral spine radiographs, computed tomography, and magnetic resonance imaging. Therapeutic options include conserva-tive methods comprising symptomatic medication and physical therapy for lowgrade spondy-lolisthesis with good to excellent results in the long term, as well as surgical treatment with a variety of possible techniques that allow for the reduction of the grade of slippage and obtaining the fusion of the affected level, followed by a well-tailored physical therapy program. The most important role for a patient’s long-term satisfactory result is adequate medical rehabilitation, with consequent and properly designed regimens that the patients will adhere to for the rest of their lives. Keywords: spondylolisthesis; diagnosis; treatment; orthopedics; medical rehabilitation; radiology; magnetic resonance imaging

Clinical efficacy and safety of mTOR inhibitor in patients with advanced unresectable epithelioid hemangioendothelioma (EHE).

e23540 Background: Epithelioidhemangioendothelioma is a rare vascular soft tissue sarcoma, 90% of which contains WWTR1-CAMTA1 fusion gene. Studies have shown that mTOR inhibitors may have a certain effect on EHE patients. Methods: A retrospective analysis of the efficacy and safety of mTOR inhibitor everolimus in the treatment of advanced unresectable epithelioidhemangioendothelioma in our hospital in the past one year. Patients with advanced epithelioidhemangioendothelioma (EHE) confirmed by consultation in the pathological center received this regimen, everolimus 10mg, once a day orally for 28 days, every 4 weeks as a treatment cycle until the disease progressed or showed intolerable toxicity. Results: There were 3 females and 5 males, and their average age was 41.8 years old. All of them were unresectable with liver, lung, and shoulder primary lesions, and lungs, liver, pleura and bone metastasis. Ki67 is from 2% to 10%. 3 patients who received molecular pathological examination were all identified the WWTR1-CAMTA1 fusion gene, and one of them also had EWSR1 chromosome translocation. Previous antineoplastic treatments included gemcitabine, cisplatin, albumin paclitaxel, epirubicin, dacarbazine chemotherapy, anlotinib targeting, and toripalimab immune therapy. 5 patients were treated with first-line drugs, 2 cases with second-line and 1 case with third-line. In terms of overall efficacy, 1 case was not evaluated, 2 cases lost follow-up due to poor tolerance and economic factors, 2 cases were included in the clinical trails after reaching tumor control for 3 months, and the other 3 cases achieved tumor remission with a median PFS of 11.0 months, and the best curative effect was SDa. Severe oral mucositis can greatly affect the medication experience of patients, which can be relieved after symptomatic medication, or when interstitial pneumonia and hemogram decrease significantly, we can consider the oral administration of everolimus 5mg. Conclusions: At present, there is no standard treatment for EHE, we can roughly see the efficacy of mTOR inhibitor everolimus in some EHE patients, mainly disease stability. Emphasis on side effect management, improve tolerance, and systematic treatment of EHE needs to be further explored.

Efficacy of Shen Cao Gan Jiang Tang on Non-severe COVID-19 Patients: A Multicenter, Randomized, Open-Label Clinical Trial.

Background In the face of the escalating COVID-19 pandemic amid shortages of medications and vaccines, a Vietnamese herbal formula known as Shen Cao Gan Jiang Tang (SCGJT) has been put into use for non-severe COVID-19 patients. This study aims to assess its efficacy and safety. Methods A multicenter, open-label, randomized controlled trial was conducted on 300 patients with non-severe COVID-19, randomly assigned into two groups: 150 receiving standard care (control group) and 150 receiving additional SCGJT for 10 days (SCGJT group). Time to resolution of symptoms, symptom severity, disease progression, time to discharge, the National Early Warning Score 2 (NEWS2) score, usage of Western drugs, time to viral clearance, and safety outcomes were continuously monitored. Results The SCGJT group exhibited faster symptom resolution (median: 9 vs. 13 days) and improved symptom severity, including cough, fatigue, hypogeusia, muscle aches, nasal congestion, runny nose, and sore throat, compared to the control group. Although there was a lower rate of severe progression in the SCGJT group (0.7% vs. 4.7%), the difference was not statistically significant. The time to discharge was significantly shorter in the SCGJT group (median: 7 vs. 8 days). Changes in the NEWS2 score did not show significant differences between groups. SCGJT has been demonstrated to reduce the need for symptomatic relief medications and hasten SARS-CoV-2 viral clearance. No adverse events were reported, and routine tests showed no significant differences. Conclusions SCGJT is safe and has potential clinical efficacy in non-severe COVID-19 patients. However, data regarding preventing severe progression remains inconclusive. Further studies should be conducted in light of the current state of the COVID-19 pandemic.

The burdens attributable to primary headache disorders in children and adolescents in Iran: estimates from a schools-based study

BackgroundWe recently found headache disorders to be highly prevalent among children (aged 6–11 years) and adolescents (aged 12–17) in Iran (gender- and age-adjusted 1-year prevalences: migraine 25.2%, tension-type headache 12.7%, undifferentiated headache [UdH] 22.1%, probable medication-overuse headache [pMOH] 1.1%, other headache on ≥ 15 days/month [H15+] 3.0%). Here we report on the headache-attributed burden, taking evidence from the same study.MethodsIn a cross-sectional survey, following the generic protocol for the global schools-based study led by the Global Campaign against Headache, we administered the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire in 121 schools, purposively selected to reflect the country’s diversities. Pupils self-completed these in class, under supervision. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of UdH (defined as mild headache with usual duration < 1 h). Burden enquiry was across multiple domains.ResultsThe analysed sample (N = 3,244) included 1,308 (40.3%) children and 1,936 (59.7%) adolescents (1,531 [47.2%] male, 1,713 [52.8%] female). The non-participating proportion was 3.4%. Mean headache frequency was 3.9 days/4 weeks, and mean duration 1.8 h. Estimated mean proportion of time in ictal state was 1.1% (1.4% for migraine, 16.5% for pMOH). Symptomatic medication was consumed on a mean of 1.6 days/4 weeks. Lost school time averaged 0.4 days/4 weeks overall (2%, assuming a 5-day week), but was eleven-fold higher (4.3 days; 22%) for pMOH. For most headache types, days of reported limited activity were several-fold more than days lost from school (45% for pMOH, 25% for other H15+). Almost one in 12 parents (7.9%) missed work at least once in 4 weeks because of their son’s or daughter’s headache. Emotional impact and quality-of-life scores reflected these measures of burden.ConclusionsHeadache, common in children and adolescents in Iran, is associated with symptom burdens that may be onerous for some but not for most. However, there are substantial consequential burdens, particularly for the 1.1% with pMOH and the 3.0% with other H15+, who suffer educational disturbances and potentially major life impairments. These findings are of importance to educational and health policies in Iran.

Exploring side effects of corticosteroids in myasthenia gravis: Unveiling alternatives for safer treatment

Myasthenia Gravis (MG) is a chronic organ-specific autoimmune disease that weakens voluntary muscles by affecting neuromuscular junctions. The formation of antibodies against acetylcholine receptors is the most prevalent cause. The incidence and prevalence rates of (MG) are increasing exponentially (1). In addition to symptomatic medication, corticosteroids continue to be the first-line treatment for MG due to their affordability, ease of access, and efficacy (2). Although corticosteroids are frequently prescribed, they are not without drawbacks. Long-term corticosteroid use can result in various side effects, including osteoporosis, weight gain, acne, elevated blood pressure, mood fluctuations, and a cushingoid appearance. It has also been linked to rare complications such as gastric and esophageal irritation, compressive fractures, and aseptic femoral head fracture (3). Given the hazards associated with long-term corticosteroid use in treating MG, researchers and healthcare professionals should investigate alternative MG treatments. By doing so, new and safer treatment options can be identified, which could contribute to improved treatment and substantially enhance the quality of life for MG-affected populations. Numerous nonsteroidal medications, including mycophenolate mofetil, methotrexate, and azathioprine, have demonstrated success in clinical trials for kidney transplantation, rheumatoid arthritis, and myasthenia gravis, respectively. To confirm the efficacy of these pharmaceuticals in the treatment of MG, urgent research and trials based on in vitro and animal models are required. Based on well-designed clinical trials, these also require human testing (4). The tapering of prednisone is an alternative option. Prednisone tapering is still a problem in the therapeutic management of patients with generalized MG because, although it is a useful treatment, it has a number of adverse effects that make it necessary to find the lowest possible effective dose as quickly as feasible. Rituximab and azathioprine enable quick tapering. It is necessary to evaluate and contrast the corticosteroid-sparing effect of novel treatments with that of azathioprine and rituximab. Given their impact on MG status, it's possible that these novel therapies will make it possible to drastically cut back on corticosteroids or possibly stop taking them entirely(5) The abnormal immune responses in MG can be managed and resolved with the new drugs that specifically target them. These agents include chimeric antigen receptor T [CART-T] cell therapy, autologous stem cell transplantation, B cell depleting agents (anti-CD 19 and 20, and B cell activating factor [BAFF] inhibitors), proteosome inhibitors, terminal complement C5 inhibitors, Fc receptor inhibitors, T cells, and cytokine-based therapies (subcutaneous immunoglobulin [SCIG]). ---Continue