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Non-motor symptoms and healthcare utilization before diagnosis of myasthenia gravis: a nationwide cohort study.

BACKGROUND: Non-motor symptoms have been reported prior to myasthenia gravis (MG) diagnosis. However, the temporal patterns of non-motor symptoms and healthcare utilization before MG diagnosis remain unclear. METHODS: We conducted a retrospective, population-based cohort study using the Korean National Health Insurance Service (KNHIS) database from 2011 to 2021. Incident MG cases were identified using the International Classification of Diseases, Tenth and Rare Intractable Disease codes. Individuals younger than 20  years or with missing health screening data were excluded. Each MG case was matched 1:10 by age, sex, and index date to controls. Non-motor symptoms and healthcare utilization were defined using operational criteria derived from KNHIS claims data. Rate ratios (RRs) and 95 % confidence intervals (CIs) were estimated across four prespecified intervals (0-1, 1-2, 2-5, and 5-10  years) before MG diagnosis. RESULTS: We included 8,355 MG patients and 83,550 controls (mean age, 53.7  years; male, 44 %). MG patients had higher rates of any non-motor symptoms over 10  years(RR 1.34; 95 % CI 1.30-1.39), with the sharpest increase in the year before diagnosis. Depression, anxiety, migraine, constipation, and insomnia consistently showed higher RRs across all intervals. Hospitalizations (RR 1.66; 95 % CI 1.61-1.71) and outpatient clinic visits (RR 1.10; 95 % CI 1.04-1.17) were consistently higher across 10  years, peaking during the 0-1 year before MG diagnosis. CONCLUSION: Non-motor symptoms and healthcare utilization increased years before MG diagnosis. Earlier recognition of these symptom patterns may facilitate timelier evaluation for MG and improve diagnostic pathways.

Humans

Feasibility and effectiveness of the Bergen 4-Day Treatment for obsessive-compulsive disorder in Australia: A pilot comparison with 3-week inpatient obsessive-compulsive disorder treatment.

OBJECTIVES: Obsessive-compulsive disorder is a debilitating and chronic condition that, when untreated or unresponsive to treatment, imposes a significant health and economic burden on individuals and families. This prospective non-randomised inpatient study compared the acceptability and clinical outcomes of the Bergen 4-Day Treatment programme with those of a standard 3-week specialised treatment programme for obsessive-compulsive disorder in Australia. METHOD: Twenty-five participants diagnosed with obsessive-compulsive disorder were non-randomly assigned to Bergen 4-Day Treatment (n = 12) or a 3-week standard (n = 13) inpatient programme. Independent assessments were completed at pre-treatment, 10 days post treatment and at 3-month follow-up. The Yale-Brown Obsessive-Compulsive Scale was rated to assess obsessive-compulsive disorder severity, while secondary measures of depression, anxiety, obsessive beliefs and wellbeing were self-rated by participants. RESULTS: Baseline characteristics of both groups were comparable, with obsessive-compulsive disorder symptom severity within the moderate to severe range. After treatment, obsessive-compulsive disorder symptoms as well as secondary depression and anxiety symptoms were reduced in both treatment groups. Participants receiving Bergen 4-Day Treatment had significantly lower Yale-Brown Obsessive-Compulsive Scale scores at 10 days (M = 13.46) and 3 months (M = 11.84), compared to standard treatment (M = 19.04 and M = 19.15, respectively). Response (91.9%) and remission (45.8%) rates for the Bergen 4-Day Treatment group were significantly higher at both post-treatment timepoints, compared to the standard treatment group. No dropouts occurred in the Bergen 4-Day Treatment group, and participant satisfaction was high. CONCLUSION: The findings of this pilot open-label study suggest that Bergen 4-Day Treatment shows promise as an acceptable, efficient and effective treatment for obsessive-compulsive disorder, warranting further investigation as a scalable alternative for improving access to specialised obsessive-compulsive disorder treatment in Australia.

Humans

Bacterial Lysates Add-On Therapy to Reduce Postoperative Recurrence in Nasal Polyps.

OBJECTIVE: This study aimed to investigate the potential role of OM-85 in reducing polyp recurrence (PR). METHODS: A single-center randomized, prospective study was performed to compare the inter-group PR rate, patient-reported outcome measures (PROMs), CT and endoscopic scores. Hundred patients were randomized to receive either add-on OM-85 (34/50) or control group (43/50); 77 participants completed the 12-month follow-up. The OM-85 group received oral treatment for 10&#x2009;days, followed by a 20-day washout (Months 1-3 and 7-9). Primary outcome was the PR rate. Secondary outcomes included PROMs, Lund-Kennedy (L-K) scores, Lund-Mackay (L-M) scores, and complete blood count (CBC) parameters. RESULTS: The PR rate was significantly lower in the OM-85 group (8.82%) than in the control group (27.91%, &#x3c7; 2&#x2009;=&#x2009;4.408, p&#x2009;=&#x2009;0.036). Univariable analysis identified pre-operative Lund-Mackay (L-M) score (p&#x2009;=&#x2009;0.008) and hyposmia VAS score (p&#x2009;=&#x2009;0.031) as significant predictors of PR. In multivariable analysis, the L-M score remained an independent predictor (OR&#x2009;=&#x2009;1.15, p&#x2009;=&#x2009;0.012), with an optimal cutoff of 10. The OM-85 group showed significant improvements in nasal obstruction, olfactory dysfunction, and mucopurulent discharge at 6 and 12&#x2009;months (p&#x2009;<&#x2009;0.05). Lund-Kennedy (L-K) score and 22-item Sinonasal Outcome Test (SNOT-22) score were also significantly improved (p&#x2009;<&#x2009;0.05). Furthermore, the OM-85 group exhibited elevated white blood cell counts and lymphocyte percentages from 6&#x2009;months onward (p&#x2009;<&#x2009;0.05). CONCLUSION: Adjuvant OM-85 may reduce postoperative PR, with improved endoscopic and symptom scores, potentially mediated by enhanced systemic immune function.

Humans

Long-term outcomes of surgical correction of ventral penile curvature in children: Patient-reported measures, surgical results, and decisional regret.

INTRODUCTION: There is a dearth of data on long-term outcomes, including patient-reported outcomes (PROMs), decisional regret, and complication rates for surgical correction of isolated ventral penile curvature in childhood. PATIENTS AND METHODS: Twenty-six children treated for ventral curvature between 1993 and 2008 were identified; 24 met inclusion criteria (isolated ventral curvature without hypospadias or need for urethral reconstruction). Surgical correction consisted of degloving alone or degloving with Nesbit-like dorsal plication when residual curvature >20&#xb0; persisted after degloving. PROMs were collected via pre-mailed validated questionnaires after puberty: Danish Prostatic Symptom Score (DAN-PSS) for LUTS, Erection Hardness Score (EHS) for erectile function, Penile Perception Score (PPS) for cosmetic perception, and items assessing decisional regret and perceived appropriateness of surgical timing. RESULTS: Curvature was corrected intraoperatively in all 24 patients. Twelve underwent degloving alone and 12 required additional dorsal plication. During long-term follow-up (median 14.2 years), one patient (4%) underwent re-operation for residual curvature, and three (13%) underwent cosmetic revisions; two (8%) underwent cystoscopy for flow concerns. 71% returned PROMs at a median age of 16.2 years. LUTS were uncommon, with low bother scores. Erectile function was favorable: 87% (13/15) reported EHS 4 and 93% (14/15) reported ejaculation. Cosmetic outcomes were favorable, with PPS dissatisfaction rates comparable to controls. Two patients reported dissatisfaction with overall appearance, and one with residual subjective curvature. No patient expressed decisional regret, and 88% felt timing of surgery was appropriate. CONCLUSION: Early surgical correction of isolated ventral penile curvature using degloving with or without dorsal plication provided durable anatomical correction and favorable long-term functional and cosmetic outcomes. These findings support early intervention as an effective approach with sustained patient-perceived benefits.

Humans

Early and late CTCAE and patient-reported outcomes following lung cancer radiotherapy: A sex-stratified descriptive analysis from the REQUITE cohort.

BACKGROUND: Long-term prospective data on lung cancer patients treated with radiotherapy are limited, restricting understanding of outcomes and sex-specific characteristics. The multicentre REQUITE study provides standardized follow-up data from an international cohort. METHODS: We analysed longitudinal data from 530 lung cancer patients treated with radical radiotherapy (sequential or concurrent chemoradiotherapy, or stereotactic body radiation therapy [SBRT]) between 2014 and 2017 at 16 centres in Europe and the USA. Healthcare professionals prospectively recorded 21 pulmonary, oesophageal, neurological, cardiac, and skin adverse events using CTCAE v4.0. Patient-reported outcomes assessed symptoms, quality-of-life, fatigue, and physical activity. Adverse event incidence was stratified by sex, radiotherapy technique, chemotherapy administration, smoking status, and other clinical factors. RESULTS: At 12&#xa0;months, 309 patients were evaluable, with 151 having follow-up beyond one year. Pulmonary adverse events were most frequent (40% grade&#xa0;&#x2265;&#xa0;2), mainly dyspnoea and cough. Women had higher rates of oesophagitis, and more frequently reported dysphagia, and chest wall pain, while men experienced a higher frequency of cardiac adverse events. Exploratory subgroup analyses identified significant sex-related differences in grade&#xa0;&#x2265;&#xa0;3 pulmonary adverse events following SBRT and in overall grade&#xa0;&#x2265;&#xa0;2 oesophageal adverse events among patients with clinical stage I-II and those aged >70&#xa0;years. Patient-reported outcomes showed persistent fatigue and reduced physical activity, particularly in females. Symptom prevalence and severity varied by sex, age, treatment modality, smoking status, and clinical stage. CONCLUSION: The REQUITE-Lung cohort provides prospectively collected real-world data on radiotherapy-related adverse events in lung cancer patients. This study describes patterns of adverse events and patient-reported outcomes according to sex, age, and treatment characteristics. These findings are hypothesis-generating and may support future validation in independent and pooled datasets.

Patient-reported outcomes

Effects of aromatherapy on menopausal symptoms: a systematic review and meta-analysis.

BACKGROUND: The postmenopausal period presents a significant challenge to women's health, characterised by vasomotor, psychological, and sleep disturbances. This systematic review and meta-analysis synthesised evidence on aromatherapy for menopausal symptoms. METHODS: We searched Cochrane Library, Web of Science, ScienceDirect, PubMed, Scopus, SID, and Google Scholar until January 2, 2026. The protocol was registered (PROSPERO: CRD420261303084). Randomised controlled trials and quasi-experimental studies were included. The Cochrane Risk of Bias tool and GRADE approach were used for quality assessment and certainty of evidence. Meta-analyses were performed using RevMan 5.3. RESULTS: Of 4435 records, 21 articles from 17 studies (n&#x2009;=&#x2009;1347) were included. Aromatherapy significantly improved sexual function (MD: 7.05, 95% CI: 3.64-10.45), sleep quality (MD: -3.95, 95% CI: -5.94 to -1.97), overall menopausal symptoms (SMD: -1.00, 95% CI: -1.43 to -0.58), vasomotor symptoms (SMD: -0.79, 95% CI: -1.11 to -0.47), physical symptoms (SMD: -0.78, 95% CI: -1.10 to -0.46), somatic symptoms (MD: -1.34, 95% CI: -2.46 to -0.23), psychological symptoms (SMD: -0.59, 95% CI: -0.96 to -0.23), anxiety (SMD: -0.63, 95% CI: -1.10 to -0.16), and depression (SMD: -0.57, 95% CI: -0.85 to -0.28). No significant effect was found for urogenital symptoms. GRADE certainty was 'Very Low' for sexual function and sleep quality, and 'Low' for other outcomes. CONCLUSIONS: Preliminary evidence suggests that aromatherapy may be a beneficial complementary therapy for alleviating some menopausal symptoms. However, given the substantial heterogeneity, methodological limitations, and limited number of studies for subgroup analyses, firm clinical recommendations cannot be made at this time. More rigorous, large-scale, multi-centre randomised controlled trials with standardised interventions and consistent adverse event reporting are required before definitive clinical recommendations can be made.

Humans

A randomized study of antibiotic prophylaxis after hypospadias repair in children.

BACKGROUND AND OBJECTIVE: Antibiotic resistance is a challenge in contemporary world. Urethroplasty for hypospadias is one of the most common urological surgeries performed around the world, yet, there is still no consensus on the use of antibiotics pre- and post-operatively. Our objective was to analyze the effectiveness of antibiotic prophylaxis and therapy before, during, and after hypospadias repair in children. METHODS: A prospective randomized trial was carried out including patients with coronal hypospadias who underwent urethroplasty performed by one surgeon. Urethral catheters were used in all cases for 10 days. Study participants were randomly assigned in a 1:1:1 ratio to receive a single intraoperative administration of antibiotics (Group I); an intraoperative antibiotic prophylaxis and antibiotic therapy for 10 days until the removal of urethral catheter (Group II); no antibiotic administration (Group III). Randomization was performed using computer-generated permuted blocks with randomly varying block sizes, prepared by an independent statistician. The results were analyzed using the analysis of variance (ANOVA). The following criteria were compared: postoperative functional complications, such as: urethral fistula, stenosis, diverticulum; wound infection symptoms: hyperemia of surgical site, pain during palpation, and symptomatic urinary tract infection. RESULTS: A total of 300 patients were included in the study. Two patients (2%) in Group I, two patients (2%) in Group II, and four patients (4%) in Group III had urethral fistulas, requiring surgery 6 months after primary repair, yet without statistical difference between groups. We found no significant difference in frequency of symptomatic UTIs between three groups (p = 0.182). CONCLUSION: There is no effect of antibiotic prophylaxis and therapy on the frequency of postoperative surgical and infectious complications after urethroplasty for coronal hypospadias repair in children.

Humans

Care Experience Disparities in Individuals With Lower Urinary Tract Symptoms: Systematic Review and Content Analysis.

OBJECTIVES: In this study, we aimed to characterize the landscape of the literature and describe lower urinary tract symptom (LUTS) care experiences using the Agency for Healthcare Research and Quality's (AHRQ's) patient experience framework, describe the characteristics of the studies, and identify critical knowledge gaps. METHODS: We performed a systematic search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus of peer-reviewed publications from 1995 to 2024. The search terms were related to LUTSs, drivers of healthcare inequities, and the domains of the AHRQ. We then performed a content analysis of the included studies. RESULTS: Of the 4597 articles reviewed, we included 11 studies in the analysis. The most studied LUTS was urinary incontinence (10/11, 91%). Of the included studies, six were comparative, and most (4/6, 66.7%) found worse care experience in patients with limited English proficiency and low socioeconomic status. When examining the studies using the care experience framework of the AHRQ, the most frequently evaluated domains of care experience were communication with clinicians (8/11, 73%) and access to care (8/11, 73%). For communication with clinicians, language barriers (3/11, 27%) and symptom minimization by clinicians (3/11, 27%) were common, especially among patients with limited English proficiency and of older age, respectively. In regard to access to care, concerns about healthcare costs (5/11, 45%) and patients' fear or embarrassment about accessing LUTS care (4/11, 36%) were commonly occurring themes, especially among racially minoritized groups. CONCLUSIONS: The findings of this systematic review demonstrated that patients with limited English proficiency, older age, low socioeconomic status, and racially minoritized backgrounds have poor LUTS care experiences.

Humans

The role of psychological resilience in the relationship between complex post-traumatic stress disorder symptom severity and functioning impairment in mental health support-seeking Australian defence force veterans: A cross-sectional study.

OBJECTIVE: Military veterans have high rates of mental health conditions; complex post-traumatic stress disorder may be the most functionally impaired trauma diagnosis in this patient group. Psychological resilience acts as a protective factor for mental health. Still, it is unclear how this may influence relationships between the two main symptom clusters of complex post-traumatic stress disorder and functioning impairment in veterans. Therefore, we investigated the relationships between psychological resilience, trauma symptom severity, trauma exposure and work/social functional impairment among Australian Defence Force veterans. METHODS: Cross-sectional survey including 148 mental health support-seeking former-serving Australian Defence Force veterans in primary care. Relationships between variables were explored using correlations, mean difference tests and mediation analysis to examine the role of resilience in the relationship between complex post-traumatic stress disorder symptoms and functional impairment. RESULTS: Resilience showed significant negative correlations with functioning impairment. The number of traumas showed weak positive correlations with disturbances in self-organisation symptoms, post-traumatic stress disorder symptoms and functional impairment. The complex post-traumatic stress disorder group had significantly lower resilience and functioning than those with no diagnosis. After controlling for the number of trauma exposures, resilience partially mediated the association between post-traumatic stress disorder symptoms and functioning (indirect effect&#x2009;=&#x2009;0.141, p&#x2009;<&#x2009;0.05), and partially mediated the association between disturbances in self-organisation symptoms and functioning (indirect effect&#x2009;=&#x2009;0.157, p&#x2009;<&#x2009;0.05). CONCLUSIONS: Psychological resilience was associated with better functioning in veterans regardless of trauma diagnosis. Resilience also partially mediates the relationship between disturbances in self-organisation/post-traumatic stress disorder symptoms and functioning in those with International Classification of Diseases, 11th Revision, complex post-traumatic stress disorder, indicating it is an important intervention target in Australian Defence Force veterans with polytrauma.

Humans

The feasibility and efficacy of weighted blankets as a sleep intervention for people with behavioural and psychological symptoms of dementia: a pilot randomised crossover trial.

Sleep disturbances contribute to disease progression in dementia and result in reduced quality of life. Non-pharmacological interventions are recommended for the management of sleep and other behavioural and psychological symptoms of dementia (BPSD), although these interventions can be challenging to implement. This pilot study assessed the feasibility and efficacy of weighted blankets as a sleep intervention for people with BPSD in a neurobehavioural unit. Fourteen residents, serving as their own control, slept two weeks with a weighted blanket and two weeks with usual bedding in a crossover trial. The primary outcomes were sleep duration and efficiency, measured via a Withing's sleep analyser and sleep disordered behaviours, measured by the sleep disorder inventory (SDI). Secondary outcomes included responsive behaviours, measured by the Neuropsychiatric index (NPI), falls incidents, restrictive practice incidents and use of pro re nata psychotropic medications. Generalised Estimation Equation (GEE) method was used for analysis. There was no statistical evidence that weighted blankets improved sleep or behavioural outcomes for people with BPSD, however fewer fall incidents, wakings and restrictive practices were reported during weighted blanket use. Weighted blankets were considered feasible and acceptable with high recruitment rates, nil participant withdrawals and no adverse outcomes, however there was variable compliance to the intervention protocol and the Withings did not adequately measure sleep. Whilst there is insufficient effectiveness evidence for further trials, weighted blankets can be offered to people living with dementia as a low risk sleep intervention option, with the caveat that there is currently no effectiveness evidence.

Behavioural Symptoms

Age at menopause and subjective cognitive symptoms predict digital cognitive outcomes at the gynecological Well-Woman visit.

INTRODUCTION: Women are at increased risk for Alzheimer's Disease (AD). Growing evidence suggests that the menopausal transition may represent a vulnerable window for development of AD-related pathology. Yet, women are diagnosed with AD later than men. Conducting routine cognitive screenings and integrating information about both cognitive symptoms and age at menopause may help address sex-based disparities in detection and prevention. This study investigated whether subjective cognitive symptoms, in combination with age at menopause, were associated with performance on a digital cognitive task in postmenopausal women. METHODS: 183 postmenopausal women (mean age&#x2009;=&#x2009;63.8, range&#x2009;=&#x2009;45-85) were recruited after their Well-Woman visit. Participants completed the Screener for Cognitive Problems in Everyday Life (SCoPE) to assess subjective cognitive symptoms, followed by a sensitive measure of objective cognition: the Linus Health Digital Clock and Recall (DCR&#x2122;). Information was also collected on age at menopause. We examined associations of subjective cognitive symptoms and age at menopause with digital cognitive performance, adjusting for age, education and depression. Model fit was evaluated using adjusted R2, AIC, and BIC. RESULTS: 48.1% of women reported one or more cognitive symptoms on the SCoPE. On objective testing, 73.2% scored in the normal range, 20.8% in the borderline range, and 6.0% in the impaired range. SCoPE total score was negatively associated with objective cognitive performance in adjusted models (B&#x2009;=&#x2009;-.12, p&#x2009;=&#x2009;.03). Age at menopause showed a significant quadratic association with cognitive performance (B&#x2009;=&#x2009;-0.006, p<.001). SCoPE total was not associated with DCR subtests, while age at menopause predicted both Delayed Recall and Clock Drawing. CONCLUSION: Subjective cognitive symptoms and age at menopause were associated with lower performance on a sensitive, objective cognitive test. Findings support routine cognitive screening and suggest that subjective cognitive symptoms as well as age at menopause are associated with cognitive function.

Humans

Peripheral immune markers and choroid plexus volumes as predictors of change in depressive symptoms: Insights from the EMBARC study.

Changes in choroid plexus (ChP) volume and peripheral inflammation have been associated with Major Depressive Disorder (MDD), yet their individual and combined impact on depressive symptoms is unclear. This study investigated whether baseline immune markers and ChP volumes predict changes in depressive symptoms during the 8-week treatment period among Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study participants who received either sertraline or placebo. Adults (n&#x202f;=&#x202f;222) with MDD with peripheral blood samples were included. Circulating chemokines and cytokines were examined using a 40-plex assay. Depressive symptoms were assessed over 8 weeks using the Hamilton Depression Rating Scale (HAMD-17). Principal component analysis (PCA) was used for dimension reduction. Mixed-effects models were used to examine whether immune profiles and ChP volumes, and their interaction predicted HAMD-17, adjusting for demographic/clinical covariates and baseline depression severity. PCA identified three immune profiles. One profile, characterized by higher levels of cytokines and chemokines including IL-6, TNF-&#x3b1;, and IL-1&#x3b2;, was associated with greater depression severity, higher BMI, age, and CRP at baseline. Higher levels of these immune markers were associated with less improvement in depressive symptoms at 8 weeks (estimate = 1.211, p&#x202f;=&#x202f;0.018) in models adjusting for right and left ChP volume (right ChP model: estimate = 1.034, p&#x202f;=&#x202f;0.005; left ChP model: estimate = 0.993, p&#x202f;=&#x202f;0.007). Interactions between immune markers and ChP volumes were not significant. Future investigations are warranted to examine the relationships between immune markers and ChP volume beyond structural changes in the context of depression symptoms.

Adult

Cannabis and cannabinoids for the treatment of mental and substance use disorders and symptoms: A systematic review and meta-analysis of experimental and observational studies.

BACKGROUND: Interest in cannabinoids for mental and substance use disorders is increasing. We examined experimental and observational evidence for treating these disorders and their symptoms. METHODS: Systematic review and meta-analysis (PROSPERO CRD42023467536). We searched CENTRAL, MEDLINE, Embase and PsycINFO to May 2025 for studies of cannabinoids in adults (&#x2265;18 years) with ADHD, anxiety, depression, PTSD, psychosis or Tourette syndrome, or alcohol, cannabis, opioid or tobacco use disorders. Two reviewers screened, extracted and assessed quality using a risk-of-bias tool and GRADE. RESULTS: We included 82 experimental and 118 observational studies. In RCTs, cannabinoids reduced anxiety symptoms (SMD=-0.40; 95% CI: -0.57, -0.23; I&#xb2;=90%) and, in one small trial, PTSD symptoms (SMD=-2.60; 95% CI: -4.58, -0.62; n=20), with trivial-to-no effect on depression (SMD=-0.20; 95% CI: -0.43, 0.04; I&#xb2;=91.6%), ADHD, psychosis and Tourette syndrome. Much anxiety and depression evidence came from symptoms measured as secondary outcomes in other primary conditions. Cannabinoids worsened cannabis use disorder severity in one RCT (SMD=2.35; 95% CI: 1.49, 3.21), with no effect on craving or withdrawal; evidence for alcohol, opioid and tobacco use disorders was very limited. Observational studies suggested improvements but had high risk of bias. The only significant safety finding was increased withdrawals due to adverse events with THC (OR=2.78; 95% CI: 1.66, 4.65). Certainty was predominantly very low. DISCUSSION: The evidence base shows very low certainty, high heterogeneity and methodological limitations, and is insufficient to support cannabinoids as first-line treatment. Signals for anxiety and PTSD are limited by indirectness and low certainty; no benefit was evident for depression; THC-related safety signals warrant careful consideration.

Humans

Isometric Exercises for Tendinopathies: A Systematic Literature Review.

PURPOSE: Musculoskeletal disorders are among the most common reasons for medical consultation, with tendinopathies accounting for up to 30% of such presentations. Although exercise remains the cornerstone of management, the most effective modality continues to be debated. Eccentric exercise has long been the mainstay, but the role of isometric exercise in pain modulation and functional recovery remains unclear. This systematic review aims to evaluate the current evidence on the efficacy of isometric exercises in the management of tendinopathies across various anatomic sites. METHODS: A systematic search was conducted in PubMed, MEDLINE, Embase, and the Cochrane Library from inception to August 1, 2025. Eligible studies included randomized controlled trials and prospective or retrospective cohort studies assessing isometric exercise interventions for tendinopathy, with or without comparator groups. Case series and case reports were excluded. Data extracted included participant demographic characteristics, site of tendinopathy, symptom duration, treatment duration, adherence, and outcome measures such as Victorian Institute of Sports Assessment (A, P, or G), visual analog scale, Patient-Specific Functional Scale, 36 item short form health survey (SF-36), and EuroQol 5-Dimension questionnaires. Imaging outcomes (ultrasound or magnetic resonance imaging) were recorded where available. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias tool in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. FINDINGS: The search identified 304 articles, of which 13 randomized controlled trials met the inclusion criteria, encompassing 336 participants (40% female). Tendinopathy sites included the patellar (n = 4), Achilles (n = 3), lateral elbow (n = 2), rotator cuff (n = 2), wrist extensor (n = 1), and gluteal (n = 1) tendons. Median symptom duration was 23 months (interquartile range, 3-51 months). Intervention periods ranged from a single 45-minute session to 4-month exercise programs. Treatment adherence was high initially (nearly 100%) but declined over time, with 70% of participants in the isometric and 58% in the control (isotonic) groups completing &#x2265;80% of sessions. Pain reduction and functional improvement were statistically significant in only 3 studies. Imaging-based outcomes were inconsistently reported, and study heterogeneity precluded meta-analysis. Overall methodological quality was rated as good in 3 studies and poor in 10. IMPLICATIONS: Current evidence provides limited support for the superiority of isometric exercise in tendinopathy management. Although isometric regimens appear tolerable and may confer short-term analgesic benefits, their long-term efficacy relative to eccentric or isotonic protocols remains uncertain. Future research should prioritize standardized outcome measures, longer follow-up, and uniform diagnostic criteria to strengthen the evidence base for exercise prescription in tendinopathies.

Humans

Effectiveness of psychologically informed physical therapy, tendon-specific exercise program and routine physical therapy in prolonged unilateral shoulder pain and symptom correlations with imaging: a single-center, randomized, parallel-group, three-arm study (RESPECT).

BACKGROUND: Shoulder complaints are one of the most common musculoskeletal ailments. Patient-specific characteristics such as obesity, depression and physical labor are established risk factors, whereas imaging findings are common and associations between specific imaging findings and symptomatology is limited. General exercises are considered useful in treatment whereas evidence for specific tendon exercises is lacking. Biopsychosocial model is also recommended, but has not been extensively studied concerning shoulder symptoms. This article describes the study protocol designed to evaluate the effectiveness and the cost-effectiveness of routine and specific physical therapy (PT) interventions. Imaging is performed for descriptive, longitudinal and imaging-symptom correlation studies. METHODS: The Rehabilitation of Shoulder Pain: Evaluation and Clinical Trial (RESPECT) is a randomized three-arm parallel-group study involving 300 participants aged 20 to 60&#xa0;years with prolonged unilateral shoulder pain. Participants will receive either routine PT, physiotherapist-guided tendon-specific exercise program or psychologically informed PT. Bilateral shoulder radiographs, ultrasound and magnetic resonance imaging will be done at the baseline and at 12 and 36&#xa0;months. Electronic surveys will be completed at the baseline and at 3, 6, 12 and 36&#xa0;months. The primary outcome will be patient-specific functional scale (PSFS) at 12&#xa0;months, analyzed using analysis of covariance (ANCOVA), adjusted for baseline PSFS. DISCUSSION: RESPECT will provide systematic and controlled data regarding different PT interventions in prolonged shoulder symptoms, which is currently limited. Being one of the most common sources of musculoskeletal pain, improved management could reduce symptom-related burden and prolonged functional impairment at individual and population level. CLINICALTRIALS: gov; Registration number NCT07235969; Registered November 18th, 2025; Version: 1.0.

Humans

BMT4me En Espa&#xf1;ol: Multisite Feasibility and Usability Testing of a Spanish-Language mHealth Adherence Support App for Spanish-Speaking Caregivers of Children After Hematopoietic Stem Cell Transplantation and Cancer Treatment.

BACKGROUND: Medication nonadherence during the first 100 days after pediatric hematopoietic stem cell transplantation (HSCT) and during oncology treatment increases risk for complications. BMT4me is a caregiver-facing mobile health (mHealth) application providing medication reminders, symptom tracking, and note-taking features to support medication management. Spanish-speaking caregivers are frequently excluded from digital adherence interventions due to the lack of language-accessible tools. PROCEDURE: We conducted a multisite, mixed-methods usability testing of a Spanish-language version of BMT4me ("BMT4me en Espa&#xf1;ol") with Spanish-speaking caregivers of children (ages 2-17 years) post-HSCT or with an oncology diagnosis on active treatment. Caregivers completed a facilitated, three-step usability session (unobtrusive observation, interactive observation, and debriefing), followed by a semi-structured interview, and then completed the system usability scale (SUS). Quantitative outcomes were summarized descriptively; qualitative data were analyzed using content analysis with constant comparison. RESULTS: Fifteen participants enrolled at each site for a total of 30 participants. Across both sites, the recruitment rate was 91%. All participants completed all parts of the study. The SUS score (M&#xa0;=&#xa0;80.09; SD&#xa0;=&#xa0;17.35) was above average (>68). Two key qualitative themes emerged: (1) the perceived positive impact of BMT4me on managing a serious illness and (2) the acceptance and sociocultural relevance of BMT4me for Spanish-speaking families. Caregivers also shared suggestions to add educational content and multiuser functionalities to BMT4me. CONCLUSIONS: The acceptance and perceived positive impact of the Spanish BMT4me app indicates that socioculturally relevant, Spanish mHealth interventions have strong potential to support Spanish-speaking caregivers in pediatric oncology and HSCT settings. CLINICAL TRIALS NCT: NCT06361173.

Adolescent

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4&#xa0;days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9&#xa0;&#xb1;&#xa0;12.7; active/sham 50/54). The model yielded a Time &#xd7; Novelty Seeking interaction (&#x3b2;&#xa0;=&#xa0;-1.70, p&#xa0;=&#xa0;0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p&#xa0;=&#xa0;0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

Humans

Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: results from the phase 3 DeLLphi-304 trial.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is associated with a high symptom burden and impaired health-related quality of life (HRQoL). This prespecified analysis from the phase 3 DeLLphi-304 trial evaluated patient-reported outcomes (PROs) for tarlatamab versus standard-of-care (SoC) chemotherapy following first-line platinum-based therapy. METHODS: DeLLphi-304 is a multicenter, open-label, randomized phase 3 study in adults with ES-SCLC. PROs were assessed using validated instruments, including the EORTC QLQ-C30, EORTC QLQ-LC13, FACT-G GP5, BPI-SF, and the EQ-5D-5L visual analogue scale. Change from baseline, response rates, and time to deterioration in these PROs were analyzed. RESULTS: PRO data from all 509 patients enrolled were evaluated. Compliance with QLQ-C30 and QLQ-LC13 assessments remained above 69% through 19&#xa0;weeks. A higher proportion of patients receiving tarlatamab achieved symptom or functional improvement at 19&#xa0;weeks compared with SoC in chest pain (19% vs 10%), cough (35% vs 26%), dyspnea (22% vs 7%), physical functioning (13% vs 8%), and global health status (23% vs 15%), respectively. Tarlatamab also delayed deterioration in symptoms, physical functioning, and pain at worst relative to SoC. FACT-G GP5 results indicated that patients receiving tarlatamab were less bothered by treatment side effects over time. CONCLUSIONS: In addition to its previously reported antitumor activity, tarlatamab demonstrated clinically meaningful improvements in symptoms and HRQoL compared with SoC. These findings support a favorable benefit-risk profile of tarlatamab in patients previously treated for ES-SCLC.

Humans