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BMJ Open Jun 2024Colposcopy is the most important diagnostic tool to detect cervical precancerous lesions and thereby prevention of cervical cancer. Due to age-dependent changes of the...
Improving diagnostic of cervical dysplasia among postmenopausal women aged ≥50 years using local vaginal oestrogen treatment prior to colposcopy: study protocol for a multicentre randomised controlled trial (the IDEAL study).
INTRODUCTION
Colposcopy is the most important diagnostic tool to detect cervical precancerous lesions and thereby prevention of cervical cancer. Due to age-dependent changes of the cervix, colposcopy is challenging in postmenopausal women, as the majority will have a non-visible transformation zone, resulting in increased risk of missing disease, a diagnostic cone biopsy and prolonged follow-up with repeated colposcopies. This study will be among the first to investigate, if treatment with vaginal oestrogen prior to colposcopy will improve the colposcopy performance, to ensure accurate and timely diagnosis of precancerous cervical lesions among postmenopausal women.
METHODS AND ANALYSIS
A randomised blinded controlled multicentre study. Enrolment will be performed at gynaecology departments in Central Denmark Region and Region of Southern Denmark. A total of 150 postmenopausal women aged ≥50 years referred for colposcopy due to abnormal cervical screening results will be randomised 1:1 to either pretreatment with vaginal application of Vagifem 30 µg or placebo once a day for 14 days prior to colposcopy. The primary outcome will be to compare the percentage of women in the two groups with a visible transformation zone at colposcopy, and biopsies representative of the transformation zone. Secondary outcomes will be the proportion of detected cervical intraepithelial neoplasia grade 2 or higher in the cervical biopsies; the proportion of diagnostics cone biopsies; the patients' report on possible side effects and compliance to the pretreatment.
ETHICS AND DISSEMINATION
The study has been approved by the Central Denmark Region Committee on Biomedical Research Ethics (1-10-72-34-22), the Central Denmark Regions' Research Unit (1-16-02-72-22) and The Danish Health Authority (Danish Medicine Agency; 2022015030). The study's EudraCT number is (1-23-456; 2022-000269-42) and it is registered on www.
CLINICALTRIALS
gov. The local Good Clinical Practice (GCP) unit will supervise and monitor the study closely before, during and after the study period. Findings will be disseminated in peer-reviewed scientific journals and presented in relevant conferences.
TRIAL REGISTRATION NUMBER
NCT05283421.
Topics: Humans; Female; Colposcopy; Uterine Cervical Dysplasia; Postmenopause; Middle Aged; Administration, Intravaginal; Uterine Cervical Neoplasms; Estrogens; Denmark; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Early Detection of Cancer
PubMed: 38910002
DOI: 10.1136/bmjopen-2023-082833 -
BMC Oral Health Jun 2024One of the main goals for pediatric dentists is to offer a painless anesthesia experience. Laser photobiomodulation is among the suggested strategies to decrease... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
One of the main goals for pediatric dentists is to offer a painless anesthesia experience. Laser photobiomodulation is among the suggested strategies to decrease injection pain. So, this study aimed to assess the impact of laser photobiomodulation on local anesthesia (LA) injection pain in children and its effect on the efficacy of LA during pulpotomy and SSC procedures.
METHODS
The research was carried out as a randomized controlled clinical trial with two parallel group design. It involved 64 cooperative healthy children, age range from 5 to 7 years, each having at least one maxillary molar indicated for pulpotomy. Children were randomly allocated to one of the two groups based on the pre-anesthetic tissue management technique used: test group received laser photobiomodulation, while control group received topical anesthetic gel. Pain during injection, pulpotomy, and SSC procedures was assessed using physiological measures (Heart Rate (HR)), subjective evaluation (modified Face-Pain-Scale (FPS), and objective analysis (Sound-Eye-Motor scale (SEM)).
RESULTS
A total of 64 children with mean age 6.23 ± 0.78 participated in this research. The mean HR scores were significantly lower in the laser PBM group during buccal and palatal infiltration injections. The SEM mean scores were significantly lower in the laser PBM group during both injections. For the FPS scale, the number of children who recorded satisfaction during injection was significantly higher in laser PBM group. There was no statistically significant difference in mean HR as well as in SEM and FPS scores between the two groups during pulpotomy and SSC procedures. Comparisons between the two study groups were performed using independent samples t- and Mann-Whitney U tests. Significance was set at p value < 0.05.
CONCLUSION
Laser photobiomodulation is a promising non-pharmacological pre-anesthetic tissue management technique in children that offered less painful injection compared to topical anesthetic gel without compromising the effectiveness of LA.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05861154. Registered on 16/5/2023.
Topics: Humans; Child; Low-Level Light Therapy; Female; Child, Preschool; Male; Pain Measurement; Pulpotomy; Anesthetics, Local; Injections; Anesthesia, Dental; Anesthesia, Local; Pain Management; Heart Rate
PubMed: 38909229
DOI: 10.1186/s12903-024-04430-3 -
BMJ Open Jun 2024Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently marketed for type 2 diabetes and obesity, may offer novel mechanisms to delay or prevent neurotoxicity... (Randomized Controlled Trial)
Randomized Controlled Trial
Protocol for a double-blind placebo-controlled randomised controlled trial assessing the impact of oral semaglutide in amyloid positivity (ISAP) in community dwelling UK adults.
INTRODUCTION
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently marketed for type 2 diabetes and obesity, may offer novel mechanisms to delay or prevent neurotoxicity associated with Alzheimer's disease (AD). The impact of semaglutide in amyloid positivity (ISAP) trial is investigating whether the GLP-1 RA semaglutide reduces accumulation in the brain of cortical tau protein and neuroinflammation in individuals with preclinical/prodromal AD.
METHODS AND ANALYSIS
ISAP is an investigator-led, randomised, double-blind, superiority trial of oral semaglutide compared with placebo. Up to 88 individuals aged ≥55 years with brain amyloid positivity as assessed by positron emission tomography (PET) or cerebrospinal fluid, and no or mild cognitive impairment, will be randomised. People with the low-affinity binding variant of the rs6971 allele of the Translocator Protein 18 kDa (TSPO) gene, which can interfere with interpreting TSPO PET scans (a measure of neuroinflammation), will be excluded.At baseline, participants undergo tau, TSPO PET and MRI scanning, and provide data on physical activity and cognition. Eligible individuals are randomised in a 1:1 ratio to once-daily oral semaglutide or placebo, starting at 3 mg and up-titrating to 14 mg over 8 weeks. They will attend safety visits and provide blood samples to measure AD biomarkers at weeks 4, 8, 26 and 39. All cognitive assessments are repeated at week 26. The last study visit will be at week 52, when all baseline measurements will be repeated. The primary end point is the 1-year change in tau PET signal.
ETHICS AND DISSEMINATION
The study was approved by the West Midlands-Edgbaston Research Ethics Committee (22/WM/0013). The results of the study will be disseminated through scientific presentations and peer-reviewed publications.
TRIAL REGISTRATION NUMBER
ISRCTN71283871.
Topics: Humans; Glucagon-Like Peptides; Double-Blind Method; Alzheimer Disease; Positron-Emission Tomography; United Kingdom; Administration, Oral; Male; Middle Aged; Female; tau Proteins; Aged; Brain; Randomized Controlled Trials as Topic
PubMed: 38908839
DOI: 10.1136/bmjopen-2023-081401 -
Microbiome Jun 2024Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a...
BACKGROUND
Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a live biotherapeutic containing the Lactobacillus crispatus strain CTV-05, reduced BV recurrence and vaginal inflammation; however, 3 months after product cessation, CTV-05 colonization was only sustained in 48% of participants.
RESULTS
This nested sub-study in 32 participants receiving LACTIN-V finds that 72% (23/32) demonstrate clinically relevant colonization (CTV-05 absolute abundance > 10 CFU/mL) during at least one visit while 28% (9/32) of women demonstrate colonization resistance, even during product administration. Immediately prior to LACTIN-V administration, the colonization-resistant group exhibited elevated vaginal microbiota diversity. During LACTIN-V administration, colonization resistance was associated with elevated vaginal markers of epithelial disruption and reduced chemokines, possibly due to elevated absolute abundance of BV-associated species and reduced L. crispatus. Colonization permissive women were stratified into sustained and transient colonization groups (31% and 41% of participants, respectively) based on CTV-05 colonization after cessation of product administration. These groups also exhibited distinct genital immune profiles during LACTIN-V administration.
CONCLUSIONS
The genital immune impact of LACTIN-V may be contingent on the CTV-05 colonization phenotype, which is in turn partially dependent on the success of BV clearance prior to LACTIN-V administration.
Topics: Humans; Female; Vaginosis, Bacterial; Vagina; Lactobacillus crispatus; Adult; Probiotics; Administration, Intravaginal; Microbiota; Young Adult; Phenotype
PubMed: 38907268
DOI: 10.1186/s40168-024-01828-7 -
BMC Ophthalmology Jun 2024Retinopathy of prematurity (ROP) is a proliferative disorder of the developing retina. Intravitreal bevacizumab injection (IVB) is an emerging treatment for severe forms...
BACKGROUND
Retinopathy of prematurity (ROP) is a proliferative disorder of the developing retina. Intravitreal bevacizumab injection (IVB) is an emerging treatment for severe forms of ROP, which does not restrict the visual field in comparison to laser therapy. The present study aimed to determine and evaluate the risk factors for ROP recurrence following IVB injection.
MATERIALS AND METHODS
In this retrospective study, 98 eyes of 49 infants with ROP who had received IVB injections as the primary treatment for type 1 ROP are included.
RESULTS
Fifty-four eyes (55.1%) had aggressive retinopathy of prematurity (A-ROP), and forty-four (44.9%) had Stage III Plus ROP in Zone II. ROP recurred in 13 eyes (13.26%) of 8 infants. The mean period between IVB and the ROP recurrence was 8.08 (95% CI:5.32-10.83) weeks. The infants who had ROP recurrence had lower birth weight (P value = 0.002), lower postmenstrual age at IVB injection (P value = 0.001), lower IVB injection gap period from birth (P value = 0.044), higher oxygen therapy requirement rate after IVB injection (P value < 0.001, OR:19.0) and higher oxygen therapy duration (P value = 0.006). The ROP severity, gestational age at birth, and diet were not statistically different between the recurrence and complete regression groups. Out of 13 eyes treated with laser photocoagulation because of ROP relapse, macula dragging occurred in one eye, and all the cases met the complete regression.
CONCLUSION
Low birth weight and oxygen therapy are the most important risk factors for ROP relapse, which requires meticulous oxygen treatment guidelines for premature infants.
Topics: Humans; Retinopathy of Prematurity; Bevacizumab; Intravitreal Injections; Retrospective Studies; Angiogenesis Inhibitors; Female; Male; Recurrence; Infant, Newborn; Gestational Age; Vascular Endothelial Growth Factor A; Risk Factors; Infant; Follow-Up Studies; Infant, Premature
PubMed: 38907228
DOI: 10.1186/s12886-024-03528-0 -
Scientific Reports Jun 2024Diabetic retinopathy (DR) is a multifactorial disease displaying vascular-associated pathologies, including vascular leakage and neovascularization, ultimately leading...
Diabetic retinopathy (DR) is a multifactorial disease displaying vascular-associated pathologies, including vascular leakage and neovascularization, ultimately leading to visual impairment. However, animal models accurately reflecting these pathologies are lacking. Vascular endothelial growth factor A (VEGF-A) is an important factor in the development of micro- and macro-vascular pathology in DR. In this study, we evaluated the feasibility of using a cumate-inducible lentivirus (LV) mediated expression of vegf-a to understand DR pathology in vitro and in vivo. Retinal pigment epithelial cells (ARPE-19) were transduced with cumate-inducible LV expressing vegf-a, with subsequent analysis of vegf-a expression and its impact on cell proliferation, viability, motility, and permeability. Cumate tolerability in adult Wistar rat eyes was assessed as an initial step towards a potential DR animal model development, by administering cumate via intravitreal injections (IVT) and evaluating consequent effects by spectral domain optical coherence tomography (SD-OCT), flash electroretinography (fERG), ophthalmic examination (OE), and immunohistochemistry. Transduction of ARPE-19 cells with cumate-inducible LV resulted in ~ 2.5-fold increase in vegf-a mRNA and ~ threefold increase in VEGF-A protein secretion. Transduced cells displayed enhanced cell proliferation, viability, permeability, and migration in tube-like structures. However, IVT cumate injections led to apparent retinal toxicity, manifesting as retinal layer abnormalities, haemorrhage, vitreous opacities, and significant reductions in a- and b-wave amplitudes, along with increased microglial activation and reactive gliosis. In summary, while cumate-inducible LV-mediated vegf-a expression is valuable for in vitro mechanistic studies in cellular drug discovery, its use is not a feasible approach to model DR in in vivo studies due to cumate-induced retinal toxicity.
Topics: Animals; Vascular Endothelial Growth Factor A; Diabetic Retinopathy; Lentivirus; Rats; Retinal Pigment Epithelium; Humans; Rats, Wistar; Cell Proliferation; Disease Models, Animal; Cell Line; Intravitreal Injections; Male; Cell Movement; Cell Survival; Tomography, Optical Coherence; Genetic Vectors
PubMed: 38906906
DOI: 10.1038/s41598-024-63590-y -
Indian Journal of Ophthalmology Jul 2024
Comparative Study
Topics: Humans; Intravitreal Injections; Administration, Oral; Rifampin; Central Serous Chorioretinopathy; Vascular Endothelial Growth Factor A; Propranolol; Angiogenesis Inhibitors; Adrenergic beta-Antagonists
PubMed: 38905466
DOI: 10.4103/IJO.IJO_2774_23 -
Indian Journal of Ophthalmology Jul 2024To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS). (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS).
DESIGN
Prospective, placebo-controlled, double-blind, cross-over study.
METHODS
Setting- A tertiary eye care center. Patients- Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention- Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure- Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position.
RESULTS
A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture).
UNLABELLED
A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy.
CONCLUSIONS
While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence.
Topics: Humans; Carbonic Anhydrase Inhibitors; Double-Blind Method; Male; Female; Visual Acuity; Prospective Studies; Cross-Over Studies; Thiazines; Sulfonamides; Administration, Topical; Child; Adult; Ophthalmic Solutions; Adolescent; Nystagmus, Congenital; Treatment Outcome; Young Adult; Follow-Up Studies; Middle Aged; Eye Movements; Vision, Binocular
PubMed: 38905461
DOI: 10.4103/IJO.IJO_1010_23 -
Medicine Jun 2024Accurate detection of the levator scapulae muscle is critical for effective diagnostic and therapeutic interventions. The commonly used surface anatomy approach has not...
Accurate detection of the levator scapulae muscle is critical for effective diagnostic and therapeutic interventions. The commonly used surface anatomy approach has not been validated and is less accurate than ultrasound-guided techniques. Therefore, we determined the needle insertion point for the levator scapulae using a new technique based on the anatomy of the scapula. This investigation used 15 fresh-frozen cadavers to explore the relationship between the acromial angle and medial tip of the scapular spine (O) of the scapular spine. Based on the x-axis (the distance [L] from Point O to point acromial angle) and the y-axis perpendicular to the x-axis passing through Point O, the barycentric coordinates were determined through the intersections of each axis and the superior angle of the scapula with the levator scapulae. Various ratios involving the established distance L) were ascertained, we compared the measurements and ratios between the male and female groups, and the accuracy of the new technique was compared with the conventional technique. The optimal site of the new technique was within 6 to 7% of distance L on the x-axis and 42 to 44% of distance L on the y-axis. This technique was significantly more accurate than the conventional technique (P = .006). Although ultrasound allows for accurate injections via real-time visualization, its unavailability in some cases highlights the importance of understanding surface anatomy landmarks. Our new technique, based on the anatomy of the scapula and relative measurements, is more accurate than the conventional technique. This should enable more precise detection of the levator scapulae for accurate and efficient diagnostic and therapeutic procedures.
Topics: Humans; Cadaver; Male; Female; Scapula; Injections, Intramuscular; Aged; Aged, 80 and over; Muscle, Skeletal; Middle Aged
PubMed: 38905373
DOI: 10.1097/MD.0000000000038598 -
Frontiers in Pharmacology 2024The available evidences suggest the inherent instability and interconvertibility of [6]-gingerol and [6]-shogaol. However, limited data on their interconversion hinder...
Unraveling the interconversion pharmacokinetics and oral bioavailability of the major ginger constituents: [6]-gingerol, [6]-shogaol, and zingerone after single-dose administration in rats.
BACKGROUND
The available evidences suggest the inherent instability and interconvertibility of [6]-gingerol and [6]-shogaol. However, limited data on their interconversion hinder understanding of their influence on the pharmacokinetic profiles.
PURPOSE
This study presents the first comprehensive investigation aiming to determine the interconversion pharmacokinetics in rats, and elucidate the oral bioavailability, target distribution, biotransformation, and excretion profiles of the key ginger constituents, [6]-gingerol, [6]-shogaol, and zingerone.
METHODS
The pharmacokinetics was investigated through single intravenous (3 mg/kg) or oral (30 mg/kg) administration of [6]-gingerol, [6]-shogaol, or zingerone, followed by the determination of their tissue distribution after oral dosing (30 mg/kg). Intravenous pharmacokinetics was leveraged to evaluate the interconversion, circumventing potential confounders associated with the oral route.
RESULTS
All rats tolerated these compounds throughout the pharmacokinetic study. The parent compounds exhibited rapid but partial absorption, and extensive organ distribution with substantial biotransformation, thereby limiting the oral bioavailability of each compound to below 2% when administered as pure compounds. Conversion of [6]-gingerol to [6]-shogaol after intravenous administration, demonstrated a significantly larger clearance compared to the reverse conversion ([6]-shogaol to [6]-gingerol). The irreversible metabolic clearance for both compounds was significantly greater than their reversible bioconversions. Furthermore, [6]-gingerol underwent biotransformation to zingerone. Conjugated glucuronides were eliminated partly through renal excretion, with minimal fecal excretion.
CONCLUSION
This investigation demonstrates the influence of interconversion on the disposition kinetics of [6]-gingerol, [6]-shogaol, and zingerone, as evidenced by the findings in the systemic circulation. The study further highlights the importance of considering this interconversion and tissue distribution when determining the administration dosage of ginger constituent combinations for therapeutic benefits and clinical applications.
PubMed: 38904001
DOI: 10.3389/fphar.2024.1391019