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BMJ Open Jul 2024Amblyopia is a neurodevelopmental vision disorder typically affecting one eye, resulting in compromised binocular function. While evidence-based treatments exist for...
SPEctacle Correction for the TReatment of Amblyopia (SPECTRA): study protocol for a prospective non-randomised interventional trial in adults with anisometropic/mixed mechanism amblyopia.
INTRODUCTION
Amblyopia is a neurodevelopmental vision disorder typically affecting one eye, resulting in compromised binocular function. While evidence-based treatments exist for children, there are no widely accepted treatments for adults. This trial aims to assess the efficacy of appropriate optical treatment in improving vision and visual functions in adults with amblyopia. This is hypothesised to significantly improve visual acuity of the amblyopic eye and other visual functions.
METHODS AND ANALYSIS
SPEctacle Correction for the TReatment of Amblyopia is a prospective non-randomised interventional trial. The following criteria for amblyopia will be used: best corrected visual acuity (BCVA) in the amblyopic eye of 0.3 to 1.0 (inclusive) logMAR VA and in the fellow eye, 0.1 logMAR or better, with an interocular VA difference of ≥2 logMAR lines. Eligible participants aged 18-39 will receive full/near-full optical treatment requiring wear for at least half their waking hours for the trial duration. A difference of ≥1.00D spherical equivalent between a participant's current refractive correction and the study prescription is required for eligibility. Primary outcome is the change in amblyopic eye BCVA from baseline to 24-week postenrolment. Secondary outcomes include distance and near VA of both eyes, stereoacuity, contrast sensitivity, interocular suppression, angle of strabismus and fixation stability measured at monthly intervals. Visual evoked potentials will also be measured at baseline, week 12 and week 24. Treatment compliance and quality of life for all participants will be monitored.Analyses comparing baseline and week 24 will utilise pairwise comparisons. Linear mixed models will be fitted to the data for measures taken monthly. This allows estimates and inferences to be drawn from the coefficients of the model, while handling missing data.
ETHICS AND DISSEMINATION
Human ethics approval was obtained from the respective ethics board of the Hong Kong Polytechnic University (HSEARS20210915002) and the University of Waterloo (#44235). The study protocol will conform to the principles of the Declaration of Helsinki. Results will be disseminated through peer-reviewed journals and conferences.
TRIAL REGISTRATION NUMBER
NCT05394987; clinicaltrials.org.
Topics: Humans; Amblyopia; Eyeglasses; Visual Acuity; Prospective Studies; Adult; Young Adult; Adolescent; Male; Female; Treatment Outcome; Non-Randomized Controlled Trials as Topic; Vision, Binocular
PubMed: 38950991
DOI: 10.1136/bmjopen-2023-080151 -
BMJ Open Jul 2024Orthodontic treatment using face mask protraction combined with an alternate rapid maxillary expansion and constriction/protraction face mask (Alt-RAMEC/PFM) protocol is...
Impact of tonsillectomy on the efficacy of Alt-RAMEC/PFM treatment protocols in children with class III malocclusion and tonsillar hypertrophy: protocol for a cluster randomised controlled trial.
INTRODUCTION
Orthodontic treatment using face mask protraction combined with an alternate rapid maxillary expansion and constriction/protraction face mask (Alt-RAMEC/PFM) protocol is effective in the early treatment of patients with class III malocclusion, but the stability of treatment outcomes represents a major concern. Previous studies have suggested that tonsillar hypertrophy can be a risk factor for class III malocclusion and tonsillectomy may prompt the normalisation of dentofacial growth. However, these studies had a low-to-moderate level of evidence. This study was designed to identify the impact of tonsillectomy before orthodontic treatment on the efficacy and stability of Alt-RAMEC/PFM protocols and the sleep quality and oral health in children with anterior crossbite and tonsillar hypertrophy.
METHODS AND ANALYSIS
This is a two-arm, parallel-group, superiority cluster randomised controlled trial, with four clinics randomly assigned to the surgery-first arm and the orthodontic-first arm in a 1:1 ratio. The Alt-RAMEC protocol involves alternate activation and deactivation of the expander's jet screw over 6 weeks to stimulate maxillary suture distraction. Patients will be instructed to wear the PFM for a minimum of 14 hours per day. The primary outcomes are changes in Wits appraisal and the degree of maxillary advancement from baseline to the end of orthodontic treatment. Lateral cephalometric radiographs, polysomnography, Obstructive Sleep Apnoea-18 questionnaire and Oral Health Impact Profile-14 questionnaire will be traced, collected and measured. We will recruit 96 patients intofor the study. To assess differences, repeated multilevel linear mixed modelling analyses will be used.
ETHICS AND DISSEMINATION
This study has been granted ethical approval by the Ethics Committee of the School & Hospital of Stomatology, Wuhan University (approval No. 2023-D10). Written informed consent will be obtained from the participants and their guardians. The results of the trial will be disseminated through academic conferences and journal publications.
TRIAL REGISTRATION NUMBER
ChiCTR2300078833.
Topics: Humans; Tonsillectomy; Child; Malocclusion, Angle Class III; Palatine Tonsil; Palatal Expansion Technique; Hypertrophy; Female; Extraoral Traction Appliances; Randomized Controlled Trials as Topic; Male; Treatment Outcome; Sleep Quality; Adolescent
PubMed: 38950988
DOI: 10.1136/bmjopen-2024-084703 -
BMJ Open Jul 2024Spirometry is a point-of-care lung function test that helps support the diagnosis and monitoring of chronic lung disease. The quality and interpretation accuracy of... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparing performance of primary care clinicians in the interpretation of SPIROmetry with or without Artificial Intelligence Decision support software (SPIRO-AID): a protocol for a randomised controlled trial.
INTRODUCTION
Spirometry is a point-of-care lung function test that helps support the diagnosis and monitoring of chronic lung disease. The quality and interpretation accuracy of spirometry is variable in primary care. This study aims to evaluate whether artificial intelligence (AI) decision support software improves the performance of primary care clinicians in the interpretation of spirometry, against reference standard (expert interpretation).
METHODS AND ANALYSIS
A parallel, two-group, statistician-blinded, randomised controlled trial of primary care clinicians in the UK, who refer for, or interpret, spirometry. People with specialist training in respiratory medicine to consultant level were excluded. A minimum target of 228 primary care clinician participants will be randomised with a 1:1 allocation to assess fifty de-identified, real-world patient spirometry sessions through an online platform either with (intervention group) or without (control group) AI decision support software report. Outcomes will cover primary care clinicians' spirometry interpretation performance including measures of technical quality assessment, spirometry pattern recognition and diagnostic prediction, compared with reference standard. Clinicians' self-rated confidence in spirometry interpretation will also be evaluated. The primary outcome is the proportion of the 50 spirometry sessions where the participant's preferred diagnosis matches the reference diagnosis. Unpaired t-tests and analysis of covariance will be used to estimate the difference in primary outcome between intervention and control groups.
ETHICS AND DISSEMINATION
This study has been reviewed and given favourable opinion by Health Research Authority Wales (reference: 22/HRA/5023). Results will be submitted for publication in peer-reviewed journals, presented at relevant national and international conferences, disseminated through social media, patient and public routes and directly shared with stakeholders.
TRIAL REGISTRATION NUMBER
NCT05933694.
Topics: Humans; Spirometry; Artificial Intelligence; Primary Health Care; Randomized Controlled Trials as Topic; Software; United Kingdom; Decision Support Systems, Clinical
PubMed: 38950987
DOI: 10.1136/bmjopen-2024-086736 -
The Journal of Rheumatology Jul 2024Rheumatoid arthritis (RA) has been associated with an elevated dementia risk. The study aimed to examine how different diagnostic dementia definitions perform in those...
OBJECTIVE
Rheumatoid arthritis (RA) has been associated with an elevated dementia risk. The study aimed to examine how different diagnostic dementia definitions perform in those with RA compared to individuals without RA.
METHODS
This study population included 2050 individuals (1025 with RA) from a retrospective population-based cohort in southern Minnesota and compared the performance of three code-based dementia diagnostic algorithms with medical record review diagnosis of dementia. For the overall comparison, no time frames were used, and each patient's complete medical history was used. Sensitivity analyses were performed using 1, 2, and 5-year windows around the date that dementia was identified in the medical record (reference standard).
RESULTS
Algorithms performed very similarly in persons with and without RA. The algorithms generally had high specificity, negative predictive values, and accuracy, regardless of the time window studied (>88%). Sensitivity and positive predictive values varied depending on the algorithm and the time window studied. Sensitivity values ranged from 56.5% to 95.9%, and positive predictive values ranged from 55.2% to 83.1%. Performance measures declined with more restrictive time windows.
CONCLUSION
Routinely collected electronic health record (EHR) data was used to define code-based dementia diagnosis algorithms with good performance (vs. diagnosis by medical record review). These results can inform future studies that use retrospective databases (especially in the same or similar EHR infrastructure) to identify dementia in individuals with RA.
PubMed: 38950951
DOI: 10.3899/jrheum.2024-0299 -
The British Journal of General Practice... Jul 2024Despite the considerable morbidity caused by recurrent UTIs (rUTIs), and the wider personal and public health implications from frequent antibiotic use, few studies...
BACKGROUND
Despite the considerable morbidity caused by recurrent UTIs (rUTIs), and the wider personal and public health implications from frequent antibiotic use, few studies adequately describe the prevalence and characteristics of women with rUTIs or those who use prophylactic antibiotics.
AIM
To describe the prevalence, characteristics, and urine profiles of women with rUTIs with and without prophylactic antibiotic use in Welsh primary care.
DESIGN AND SETTING
Retrospective cross-sectional study in Welsh General Practice using the SAIL Databank.
METHOD
We describe the characteristics of women aged ≥18 years with rUTIs or using prophylactic antibiotics from 2010-2020, and associated urine culture results from 2015 - 2020.
RESULTS
6.0% of women (n=92,213) had rUTIs, and 1.7% (n=26,862) were prescribed prophylactic antibiotics. Only 49% of prophylactic antibiotic users met the definition of rUTIs before initiation. 81% of women with rUTIs had a urine culture result in the preceding 12 months with high rates of resistance to trimethoprim and amoxicillin. 64% of women taking prophylactic antibiotics had a urine culture result before initiation, and 18% (n=320) of women prescribed trimethoprim had resistance to it on the antecedent sample.
CONCLUSION
A substantial proportion of women had rUTIs or incident prophylactic antibiotic use. However, 64% of women had urine cultured before starting prophylaxis. There was a high proportion of cultured bacteria resistant to two antibiotics used for rUTI prevention and evidence of resistance to the prescribed antibiotic. More frequent urine cultures for rUTI diagnosis and before prophylactic antibiotic initiation could better inform antibiotic choices.
PubMed: 38950943
DOI: 10.3399/BJGP.2024.0015 -
International Journal of Gynecological... Jul 2024To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line maintenance therapy in the phase III PRIMA/ENGOT-OV26/GOG-3012 study.
METHODS
In this post hoc analysis of PRIMA, patients randomized to niraparib were grouped based on investigator-assessed progression-free survival (progressive disease/censoring <2 years or ≥2 years after randomization). Variables assessed for predictive value were Eastern Cooperative Oncology Group performance status, International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis, clinical response to platinum-based chemotherapy, number of prior chemotherapy cycles, primary tumor location, body mass index, categorical age, debulking surgery type, number of baseline target lesions, number of baseline non-target lesions, /homologous recombination-deficiency status, residual disease status, and duration from end of chemotherapy to randomization. Logistic regression modeling using backward elimination (significance level=0.15) identified covariates associated with long-term progression-free survival (clinical cut-off date November 17, 2021).
RESULTS
Of 487 patients randomized to niraparib, 152 (31%) had progressive disease/censoring ≥2 years after randomization. Multivariable logistic regression modeling using backward elimination identified mutation/homologous recombination deficiency status (p<0.0001), FIGO stage (p=0.041), primary tumor location (p=0.095), and number of baseline non-target lesions (p=0.0001) to be associated with long-term progression-free survival. Patients significantly more likely to achieve progression-free survival of ≥2 years in the final model were those with - and -mutated/homologous recombination-deficient tumors or wild-type/not determined/homologous recombination-deficient tumors (vs wild-type/homologous recombination-proficient/not determined tumors), FIGO stage III (vs IV), and 0 or 1 baseline non-target lesions (vs ≥2 baseline non-target lesions).
CONCLUSIONS
The hypothesis-generating results of this analysis suggest that mutation/homologous recombination-deficiency status, FIGO stage, and number of baseline non-target lesions may predict progression-free survival of ≥2 years in patients with advanced ovarian cancer receiving niraparib first-line maintenance therapy.
TRIAL REGISTRATION NUMBER
NCT02655016.
Topics: Humans; Female; Indazoles; Piperidines; Progression-Free Survival; Ovarian Neoplasms; Middle Aged; Poly(ADP-ribose) Polymerase Inhibitors; Adult; Aged
PubMed: 38950925
DOI: 10.1136/ijgc-2024-005356 -
International Journal of Gynecological... Jun 2024Low-grade serous ovarian cancer was previously thought to be a subtype of high-grade serous ovarian cancer, but it is now recognized as a distinct disease with unique... (Review)
Review
Low-grade serous ovarian cancer was previously thought to be a subtype of high-grade serous ovarian cancer, but it is now recognized as a distinct disease with unique clinical and molecular behaviors. The disease may arise de novo or develop from a serous borderline ovarian tumor. Although it is more indolent than high-grade serous ovarian cancer, most patients have advanced metastatic disease at diagnosis and recurrence is common. Recurrent low-grade serous ovarian cancer is often resistant to standard platinum-taxane chemotherapy, making it difficult to treat with the options currently available. New targeted therapies are needed, but their development is contingent on a deeper understanding of the specific biology of the disease. The known molecular drivers of low-grade tumors are strong hormone receptor expression, mutations in the mitogen-activated protein kinase (MAPK) pathway (, , and ), and in genes related to the MAPK pathway (, and ). However, MAPK inhibitors have shown only modest clinical responses. Based on the discovery of mutations in low-grade serous ovarian cancer, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are now being tested in clinical trials in combination with hormone therapy. Additional mutations seen in a smaller population of low-grade tumors include , and but no specific therapies targeting them have been tested clinically. This review summarizes the clinical, pathologic, and molecular features of low-grade serous ovarian cancer as they are now understood and introduces potential therapeutic targets and new avenues for research.
PubMed: 38950921
DOI: 10.1136/ijgc-2024-005305 -
International Journal of Cardiology Jun 2024
PubMed: 38950787
DOI: 10.1016/j.ijcard.2024.132310 -
American Heart Journal Jun 2024Symptomatic severe aortic stenosis causes substantial morbidity and mortality when left untreated, yet recent data suggest its undertreatment.
Trial Designs A44002PZS Electronic Physician Notification to Facilitate the Recognition and Management of Severe Aortic Stenosis: Rationale, design, and methods of the randomized controlled DETECT AS Trial.
BACKGROUND
Symptomatic severe aortic stenosis causes substantial morbidity and mortality when left untreated, yet recent data suggest its undertreatment.
OBJECTIVE
To evaluate the efficacy of electronic physician notification to facilitate the guideline-directed management of patients with severe aortic stenosis.
HYPOTHESIS
We hypothesize that patients with severe aortic stenosis who are in the care of physicians who receive the notification are more likely to undergo aortic valve replacement within 1-year.
METHODS/DESIGN
The Electronic Physician Notification to Facilitate the Recognition and Management of Severe Aortic Stenosis (DETECT AS) trial is a randomized controlled trial and quality improvement initiative designed to evaluate the efficacy of electronic provider notification versus usual clinical care in the management of patients with severe aortic stenosis. Providers ordering an echocardiogram with findings potentially indicative of severe aortic stenosis, defined by an aortic valve area ≤1.0 cm2, are randomized in a 1:1 fashion to receive electronic notification (intervention) or usual care. Providers in the notification arm are sent a notification within the electronic health record inbox outlining customized guideline recommendations for the management of patients with severe aortic stenosis based on the 2020 ACC/AHA Clinical Practice Guidelines for Valvular Heart Diseases for the index and all subsequent echocardiograms. Providers in the control arm receive no notification. Randomization continues until 940 patients have been enrolled.
SETTING
Multi-centered, academic health system OUTCOMES: The primary endpoint is the proportion of patients with severe AS receiving an aortic valve replacement within 1-year of the index echocardiogram. Secondary endpoints include mortality, heart failure hospitalization, transthoracic echocardiogram utilization/surveillance, aortic stenosis billing code diagnosis, and cardiology/Heart Valve Team referral.
CONCLUSION
The DETECT AS trial will provide insight into whether electronic notification of providers on the presence of severe aortic stenosis and associated clinical guideline recommendations will facilitate recognition and guideline-directed management of severe aortic stenosis.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT05230225, https://clinicaltrials.gov/ct2/show/NCT05230225.
PubMed: 38950668
DOI: 10.1016/j.ahj.2024.06.009 -
Neurochemistry International Jun 2024Parkinson's disease (PD) is a devastating neurodegenerative disorder predominantly affecting the elderly, characterized by the loss of dopaminergic neurons in the...
Parkinson's disease (PD) is a devastating neurodegenerative disorder predominantly affecting the elderly, characterized by the loss of dopaminergic neurons in the substantia nigra. Reactive oxygen species (ROS) generation plays a central role in the pathogenesis of PD and other neurodegenerative diseases. An imbalance between cellular antioxidant activity and ROS production leads to oxidative stress, contributing to disease progression. Dopamine metabolism, mitochondrial dysfunction, and neuroinflammation in dopaminergic neurons have been implicated in the pathogenesis of Parkinson's disease. Consequently, there is a pressing need for therapeutic interventions capable of scavenging ROS. Current pharmacological approaches, such as L-dihydroxyphenylalanine (levodopa or L-DOPA) and other drugs, provide symptomatic relief but are limited by severe side effects. Researchers worldwide have been exploring alternative compounds with less toxicity to address the multifaceted challenges associated with Parkinson's disease. In recent years, plant-derived polyphenolic compounds have gained significant attention as potential therapeutic agents. These compounds exhibit neuroprotective effects by targeting pathophysiological responses, including oxidative stress and neuroinflammation, in Parkinson's disease. The objective of this review is to summarize the current understanding of the neuroprotective effects of various polyphenols in Parkinson's disease, focusing on their antioxidant and anti-inflammatory properties, and to discuss their potential as therapeutic candidates. This review highlights the progress made in elucidating the molecular mechanisms of action of these polyphenols, identifying potential therapeutic targets, and optimizing their delivery and bioavailability. Well-designed clinical trials are necessary to establish the efficacy and safety of polyphenol-based interventions in the management of Parkinson's disease.
PubMed: 38950626
DOI: 10.1016/j.neuint.2024.105798