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Clinical Reviews in Allergy & Immunology Aug 2023Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by... (Review)
Review
Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by itching, photophobia, white mucous discharge, lacrimation, foreign body sensation, and pain due to corneal involvement of shield ulcers. Vernal keratoconjunctivitis is categorized within ocular diseases. The diagnosis is clinical, as no sure biomarkers pathognomonic of the disease have yet been identified. The VKC therapy relies on different types of drugs, from antihistamines and topical steroids to cyclosporine or tacrolimus eye drops. In extremely rare cases, there is also the need for surgical treatment for the debridement of ulcers, as well as for advanced glaucoma and cataracts, caused by excessive prolonged use of steroid eye drops. We performed a systematic review of the literature, according to PRISMA guideline recommendations. We searched the PubMed database from January 2016 to June 2023. Search terms were Vernal, Vernal keratoconjunctivitis, and VKC. We initially identified 211 articles. After the screening process, 168 studies were eligible according to our criteria and were included in the review. In this study, we performed a systematic literature review to provide a comprehensive overview of currently available diagnostic methods, management of VKC, and its treatments.
Topics: Humans; Conjunctivitis, Allergic; Ulcer; Cyclosporine; Tacrolimus; Ophthalmic Solutions
PubMed: 37658939
DOI: 10.1007/s12016-023-08970-4 -
Clinical Journal of the American... Aug 2023Sodium-glucose cotransporter 2 (SGLT2) inhibitors attenuate incident cardiovascular outcomes, irrespective of baseline GFR, in conservatively managed CKD. As this...
BACKGROUND
Sodium-glucose cotransporter 2 (SGLT2) inhibitors attenuate incident cardiovascular outcomes, irrespective of baseline GFR, in conservatively managed CKD. As this condition inexorably progresses to demanding KRT, drug withdrawal is supported by the current lack of evidence of safety of SGLT2 inhibitors in dialysis.
METHODS
This study was a prospective, single-center, open-label trial ( ClinicalTrials.gov identifier: NCT05343078 ) aimed at assessing the pharmacokinetic properties and safety of dapagliflozin in patients with kidney failure on regular dialysis regimens compared with those with type 2 diabetes and age- and sex-matched controls with normal kidney function. Peripheral blood samples were collected from both groups every 30 minutes for 4 hours and again after 48 hours after ingestion of dapagliflozin 10 mg, which occurred immediately before dialysis session initiation in the kidney failure group. This protocol occurred in drug-naïve patients and again after six daily doses of dapagliflozin to assess whether the drug had accumulated. The plasma and dialysate levels of dapagliflozin at each time point were determined by liquid chromatography and used to calculate pharmacokinetics parameters (peak concentration [C max ] and area under the plasma concentration-versus-time curve) for each participant.
RESULTS
Dapagliflozin C max was 117 and 97.6 ng/ml in the kidney failure and control groups, respectively, whereas the corresponding accumulation ratios were 26.7% and 9.5%. No serious adverse events were reported for either group. Dapagliflozin recovered from dialysate corresponded to 0.10% of the administered dose.
CONCLUSIONS
In patients with kidney failure on dialysis, dapagliflozin was well tolerated, was slightly dialyzable, and had nonaccumulating pharmacokinetic properties.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients (DARE-ESKD 1), NCT05343078.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Prospective Studies; Peritoneal Dialysis; Renal Dialysis; Renal Insufficiency; Dialysis Solutions
PubMed: 37227937
DOI: 10.2215/CJN.0000000000000196 -
Nature Reviews. Nephrology Aug 2023Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon... (Review)
Review
Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon footprint. Innovative dialysis technologies such as portable, wearable and implantable artificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An important challenge for these technologies is the need for continuous regeneration of a small volume of dialysate. Dialysate recycling systems based on sorbents have great potential for such regeneration. Novel dialysis membranes composed of polymeric or inorganic materials are being developed to improve the removal of a broad range of uraemic toxins, with low levels of membrane fouling compared with currently available synthetic membranes. To achieve more complete therapy and provide important biological functions, these novel membranes could be combined with bioartificial kidneys, which consist of artificial membranes combined with kidney cells. Implementation of these systems will require robust cell sourcing; cell culture facilities annexed to dialysis centres; large-scale, low-cost production; and quality control measures. These challenges are not trivial, and global initiatives involving all relevant stakeholders, including academics, industrialists, medical professionals and patients with kidney disease, are required to achieve important technological breakthroughs.
Topics: Humans; Kidneys, Artificial; Quality of Life; Renal Dialysis; Dialysis Solutions; Wearable Electronic Devices
PubMed: 37277461
DOI: 10.1038/s41581-023-00726-9 -
JAMA Network Open Nov 2023Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown...
IMPORTANCE
Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown and has not been compared.
OBJECTIVE
To determine cost-effective options for controlling myopia progression in children.
DESIGN, SETTING, AND PARTICIPANTS
In this cost-effectiveness analysis, a Markov model was designed to compare the cost-effectiveness of interventions for controlling myopia progression over 5 years from a societal perspective in a simulated hypothetical cohort of patients aged 10 years with myopia. Myopia interventions considered included atropine eye drops, 0.05% and 0.01%, defocus incorporated multiple segment spectacles, outdoor activity, soft contact lenses (daily disposable and multifocal), rigid gas-permeable contact lenses, progressive addition lenses, bifocal spectacle lenses, orthokeratology, highly aspherical lenslets (HALs), and red light therapy; all interventions were compared with single-vision lenses. Deterministic and probabilistic sensitivity analysis determined the association of model uncertainties with the cost-effectiveness. Costs were obtained from the charges of the Hospital Authority of Hong Kong and The Chinese University of Hong Kong Eye Center.
MAIN OUTCOME AND MEASURES
The mean costs (in US dollars) per child included the cost of hospital visits, medications, and optical lenses. The outcomes of effectiveness were the annual spherical equivalent refraction (SER) and axial length (AL) reductions. Incremental cost-effectiveness ratios (ICERs) were calculated for each strategy relative to single-vision lenses over a time horizon of 5 years.
RESULTS
Outdoor activity, atropine (0.05%), red light therapy, HALs, and orthokeratology were cost-effective. The ICER of atropine, 0.05%, was US $220/SER reduction; red light therapy, US $846/SER reduction; and HALs, US $448/SER reduction. Outdoor activity yielded a savings of US $5/SER reduction and US $8/AL reduction. Orthokeratology resulted in an ICER of US $2376/AL reduction.
CONCLUSIONS AND RELEVANCE
These findings suggest that atropine eye drops, 0.05%, and outdoor activity are cost-effective for controlling myopia progression in children. Though more expensive, red light therapy, HALs, and orthokeratology may also be cost-effective. The use of these interventions may help to control myopia in a cost-effective way.
Topics: Humans; Child; Cost-Effectiveness Analysis; Myopia; Refraction, Ocular; Atropine; Ophthalmic Solutions
PubMed: 37917061
DOI: 10.1001/jamanetworkopen.2023.40986 -
Ophthalmology Oct 2023To evaluate the safety and efficacy of lotilaner ophthalmic solution 0.25% compared with vehicle for the treatment of Demodex blepharitis. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the safety and efficacy of lotilaner ophthalmic solution 0.25% compared with vehicle for the treatment of Demodex blepharitis.
DESIGN
Prospective, randomized, double-masked, vehicle-controlled, multicenter, phase 3 clinical trial.
PARTICIPANTS
Four hundred twelve patients with Demodex blepharitis were assigned randomly in a 1:1 ratio to receive either lotilaner ophthalmic solution 0.25% (study group) or vehicle without lotilaner (control group).
METHODS
Patients with Demodex blepharitis treated at 21 United States clinical sites were assigned either to the study group (n = 203) to receive lotilaner ophthalmic solution 0.25% or to the control group (n = 209) to receive vehicle without lotilaner bilaterally twice daily for 6 weeks. Collarettes and erythema were graded for each eyelid at screening and at all visits after baseline. At screening and on days 15, 22, and 43, 4 or more eyelashes were epilated from each eye, and the number of Demodex mites present on the lashes was counted with a microscope. Mite density was calculated as the number of mites per lash.
MAIN OUTCOME MEASURES
Outcome measures included collarette cure (collarette grade 0), clinically meaningful collarette reduction to 10 collarettes or fewer (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes as well as erythema), compliance with the drop regimen, drop comfort, and adverse events.
RESULTS
At day 43, the study group achieved a statistically significant (P < 0.0001) higher proportion of patients with collarette cure (56.0% vs. 12.5%), clinically meaningful collarette reduction to 10 collarettes or fewer (89.1% vs. 33.0%), mite eradication (51.8% vs. 14.6%), erythema cure (31.1% vs. 9.0%), and composite cure (19.2% vs. 4.0%) than the control group. High compliance with the drop regimen (mean ± standard deviation, 98.7 ± 5.3%) in the study group was observed, and 90.7% of patients found the drops to be neutral to very comfortable.
CONCLUSIONS
Twice-daily treatment with lotilaner ophthalmic solution 0.25% for 6 weeks generally was safe and well tolerated and met the primary end point and all secondary end points for the treatment of Demodex blepharitis compared with vehicle control.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Animals; Humans; Mite Infestations; Prospective Studies; Ophthalmic Solutions; Blepharitis; Mites; Eyelashes; Erythema; Eye Infections, Parasitic
PubMed: 37285925
DOI: 10.1016/j.ophtha.2023.05.030 -
Phlebology May 2024
Topics: Humans; Varicose Veins; Sclerotherapy; Sclerosing Solutions; Treatment Outcome
PubMed: 38103047
DOI: 10.1177/02683555231222678 -
American Journal of Ophthalmology Aug 2023To evaluate the efficacy and safety of NOV03 (perfluorohexyloctane) ophthalmic drop for the treatment of signs and symptoms of dry eye disease (DED) associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the efficacy and safety of NOV03 (perfluorohexyloctane) ophthalmic drop for the treatment of signs and symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD).
DESIGN
Randomized, double-masked, controlled trial.
METHODS
Patients ≥18 years of age with a history of DED and signs of MGD were randomly assigned 1:1 to treatment with NOV03 or hypotonic saline (0.6%) 4 times daily for 8 weeks. The primary sign and symptom endpoints were change from baseline to week 8 in total corneal fluorescein staining (tCFS; National Eye Institute scale) and eye dryness score (0-100 visual analog scale), respectively.
RESULTS
A total of 620 patients (NOV03, n = 311; saline, n = 309) were randomized and treated. Least-squares (LS) mean change from baseline to week 8 was statistically significantly greater for NOV03 compared with saline for both tCFS (-2.3 vs -1.1; LS mean treatment difference, -1.2 [95% confidence interval -1.7 to -0.8]; P < .001) and visual analog scale dryness score (-29.4 vs -19.2; LS mean treatment difference, -10.2 [95% CI -14.4 to -6.1]; P < .001), with statistically significant between-group differences observed as early as week 2. The incidence of ocular adverse events was similar for NOV03 (12.9%) and saline (12.3%). There were no serious adverse events and no adverse events leading to treatment discontinuation.
CONCLUSIONS
In this randomized controlled trial of patients with DED associated with MGD, NOV03 significantly reduced both signs and symptoms of DED compared with hypotonic saline control. NOV03 was well tolerated, with an adverse event profile similar to that of saline.
Topics: Humans; Infant, Newborn; Meibomian Gland Dysfunction; Fluorescein; Ophthalmic Solutions; Dry Eye Syndromes; Administration, Ophthalmic; Meibomian Glands; Tears
PubMed: 36948372
DOI: 10.1016/j.ajo.2023.03.008 -
Drugs Nov 2023Lotilaner ophthalmic solution 0.25% (XDEMVY™), a gamma-aminobutyric acid-gated chloride channel (GABA-Cl) inhibitor selective for mites, is being developed by Tarsus... (Review)
Review
Lotilaner ophthalmic solution 0.25% (XDEMVY™), a gamma-aminobutyric acid-gated chloride channel (GABA-Cl) inhibitor selective for mites, is being developed by Tarsus Pharmaceuticals for the treatment of Demodex blepharitis and meibomian gland dysfunction in patients with Demodex lid infestation (Demodex-induced meibomianitis). On 24 July 2023, lotilaner ophthalmic solution 0.25% received its first approval in the USA for the treatment of Demodex blepharitis. The agent is also currently in phase 3 development for Demodex blepharitis in China and phase 2 development for Demodex-induced meibomianitis in the USA. This article summarizes the milestones in the development of lotilaner ophthalmic solution 0.25% leading to this first approval for the treatment of Demodex blepharitis in the USA.
Topics: Humans; Mite Infestations; Blepharitis; Ophthalmic Solutions; Eye Infections, Parasitic; Meibomitis
PubMed: 37843754
DOI: 10.1007/s40265-023-01947-9 -
Peritoneal Dialysis International :... Sep 2023The peritoneal equilibration test (PET), first described in 1987, is a semiquantitative assessment of peritoneal transfer characteristics in patients undergoing... (Review)
Review
The peritoneal equilibration test (PET), first described in 1987, is a semiquantitative assessment of peritoneal transfer characteristics in patients undergoing peritoneal dialysis. It is typically performed as a 4-h exchange using 2.27/2.5% dextrose dialysate with serial measurements of blood and dialysate creatinine, urea, and glucose concentrations. The percentage absorption of glucose and D/P creatinine ratio are used to determine peritoneal solute transfer rates. It is used to both help guide peritoneal dialysis prescriptions and to prognosticate. There are several derivative tests which have been described in the literature. In this review, we describe the original PET, the various iterations of the PET, the information gleaned, and the use in the setting of poor solute clearance and in the diagnosis of membrane dysfunction, and limitations of the PET.
Topics: Humans; Peritoneal Dialysis; Creatinine; Peritoneum; Dialysis Solutions; Glucose
PubMed: 36350033
DOI: 10.1177/08968608221133629 -
Seminars in Dialysis 2024There have been significant advances in the understanding of peritoneal dialysis (PD) in the last 40 years, and uptake of PD as a modality of kidney replacement therapy...
There have been significant advances in the understanding of peritoneal dialysis (PD) in the last 40 years, and uptake of PD as a modality of kidney replacement therapy is increasing worldwide. PD fluids, therefore, remains the lifeline for patients on this treatment. Developing these fluids to be efficacious in solute clearance and ultrafiltration, with minimal adverse consequences to peritoneal membrane health and systemic effects is a key requirement. Since the first PD fluid produced in 1959, modifications to PD fluids have been made. Nonetheless, the search for that ideal PD fluid remains elusive. Understanding the components of PD fluids is a key aspect of optimizing the successful delivery of PD, allowing for individualized PD prescription. Glucose remains an integral component of PD fluids; however, its deleterious effects continue to be the impetus for the search of an alternative osmotic agent, and icodextrin remains the main alternative. More biocompatible PD fluids have been developed and have shown benefits in preserving residual kidney function. However, high cost and reduced accessibility remain deterrents to its widespread clinical use in many countries. Large-scale clinical trials are necessary and very much awaited to improve the narrow spectrum of PD fluids available for clinical use.
Topics: Humans; Renal Dialysis; Peritoneal Dialysis; Dialysis Solutions; Peritoneum; Icodextrin; Glucose
PubMed: 35212029
DOI: 10.1111/sdi.13063