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Cornea Apr 2023The purpose of this study was to 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
Lotilaner Ophthalmic Solution, 0.25%, for the Treatment of Demodex Blepharitis: Results of a Prospective, Randomized, Vehicle-Controlled, Double-Masked, Pivotal Trial (Saturn-1).
PURPOSE
The purpose of this study was to evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25%, compared with vehicle for the treatment of Demodex blepharitis.
METHODS
In this prospective, randomized, controlled, double-masked, phase 2b/3 clinical trial, 421 patients with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution, 0.25% (study group), or vehicle without lotilaner (control group) bilaterally, twice daily for 43 days. Patients were evaluated at days 8, 15, 22, and 43. Outcome measures were complete collarette cure (collarette grade 0), clinically meaningful collarette cure (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes/erythema), and drop comfort. Adverse events were also evaluated.
RESULTS
At day 43, the study group achieved a statistically significantly higher proportion of patients with clinically meaningful collarette cure (81.3% vs. 23.0%; P < 0.0001), complete collarette cure (44.0% vs. 7.4%; P < 0.0001), mite eradication (67.9% vs. 17.6%; P < 0.0001), erythema cure (19.1% vs. 6.9%; P = 0.0001), and composite cure (13.9% vs. 1.0%; P < 0.0001) than the control group. Nearly 92.0% of patients rated the study drop as neutral to very comfortable. All ocular adverse events in the study group were mild, with the most common being instillation site pain.
CONCLUSIONS
Twice-daily treatment with a novel lotilaner ophthalmic solution, 0.25% for 43 days, is safe and effective for the treatment of Demodex blepharitis compared with the vehicle control.
Topics: Humans; Ophthalmic Solutions; Prospective Studies; Double-Blind Method; Blepharitis
PubMed: 35965392
DOI: 10.1097/ICO.0000000000003097 -
Peritoneal Dialysis International :... Jul 2021A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing...
GUIDELINE 1
A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. ().
GUIDELINE 2A
It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. () This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) () and subsequently when clinically indicated. ().
GUIDELINE 2B
A faster PSTR is associated with lower survival on PD. () This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. () Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. () Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. ().
GUIDELINE 3
UF This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is <400 ml (3.86% glucose/4.25% dextrose) or <100 ml (2.27% glucose /2.5% dextrose), () and/or (b) the daily UF is insufficient to maintain adequate fluid status. () Besides membrane dysfunction, low UF capacity can also result from mechanical problems, leaks or increased fluid absorption across the peritoneal membrane not explained by fast PSTR.
GUIDELINE 4A
Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. ().
GUIDELINE 4B
in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. ().
GUIDELINE 5
measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and 'lymphatic' reabsorption are not recommended for routine clinical practice but remain valuable research methods. ().
GUIDELINE 6
When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. ().
Topics: Adult; Dialysis Solutions; Glucans; Glucose; Humans; Icodextrin; Peritoneal Dialysis; Peritoneum; Sodium; Ultrafiltration
PubMed: 33563110
DOI: 10.1177/0896860820982218 -
Expert Opinion on Pharmacotherapy Jul 2020Fixed-combination glaucoma medications have altered the paradigm of ocular hypertension and glaucoma treatment and are in widespread use today. A comprehensive review of... (Review)
Review
INTRODUCTION
Fixed-combination glaucoma medications have altered the paradigm of ocular hypertension and glaucoma treatment and are in widespread use today. A comprehensive review of fixed-combination medications will help educate and inform providers for optimal patient care.
AREAS COVERED
In this review, the authors describe the composition, mechanism of action, efficacy, side effects, and safety profile of fixed-combination agents for the treatment of ocular hypertension and glaucoma as well as comparisons between the most frequently prescribed medications.
EXPERT OPINION
Fixed-combination therapeutics provide an effective and efficient means of lowering intraocular pressure with comparable side effects and outcomes to constituent parts with lower patient exposure to preservatives and improvement in compliance.
Topics: Antihypertensive Agents; Humans; Ocular Hypertension; Ophthalmic Solutions
PubMed: 32228188
DOI: 10.1080/14656566.2020.1743264 -
Seminars in Dialysis Sep 2022Standard high-flux hemodialysis (HD) clears urea very efficiently but is less efficient at clearing uremic toxins with larger molecule size, which diffuse more slowly.... (Review)
Review
Standard high-flux hemodialysis (HD) clears urea very efficiently but is less efficient at clearing uremic toxins with larger molecule size, which diffuse more slowly. Hemodiafiltration (HDF) provides much higher convection rates, thereby reliably increasing the clearance of these larger toxins. However, the high ultrafiltration volumes employed by HDF significantly increase the concentration of proteins and lipids in the dialyzer blood compartment. This has the effect of increasing plasma viscosity, which opposes solute diffusion, and increasing plasma oncotic pressure, which opposes convection. The negatively charged plasma proteins also influence the equilibration of ions between dialysate and blood compartments. These effects result in varying conditions for solute transport along the length of the dialyzer and along the radial distance from the membrane within the dialyzer fibers. High-flux dialyzers can be designed to augment solute diffusion and internal filtration, so that their performance approaches that of HDF. This avoids some of the mechanical complexity of HDF, but such enhanced dialyzers may be more difficult to manufacture, control and monitor. Here, we present and discuss the most important physical phenomena associated with HDF therapy, providing an overview of its main concepts and principles. In particular, we discuss the physics of solute diffusion and convection and the factors affecting them, and we compare predilution or postdilution HDF with enhanced HD.
Topics: Blood Proteins; Dialysis Solutions; Hemodiafiltration; Humans; Lipids; Physics; Renal Dialysis; Urea
PubMed: 35869627
DOI: 10.1111/sdi.13111 -
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 -
In Vivo (Athens, Greece) 2021Regenerative medicine is a branch of medicine that incorporates tissue-engineering, biomaterials, and cell therapy approaches to replace or repair damaged cells and... (Review)
Review
Regenerative medicine is a branch of medicine that incorporates tissue-engineering, biomaterials, and cell therapy approaches to replace or repair damaged cells and tissues. Umbilical cord serum (UCS) is an important liquid component of cord blood, which has a reliable source of innumerable growth factors and biologically active molecules. Usually, serum can be prepared from different sources of blood. In therapeutic application, cord serum can be prepared and used in the form of eye drops for the treatment of severe dry eye diseases, ocular burns, glaucoma, persistent corneal epithelial defects and neurotrophic keratitis. In addition, cord serum combined with synthetic bio scaffold materials is used to regenerate different types of tissues including tympanic membrane regeneration, bone regeneration and nerve regeneration. Absence of animal origin viruses and bacteria, lack of xenoproteins and cost-effective features make cord serum a feasible choice as replacement of fetal bovine serum in cell culture techniques. Thus, this review emphasizes the role of cord serum in regenerative therapy and clinical uses.
Topics: Animals; Fetal Blood; Ophthalmic Solutions; Regenerative Medicine; Serum; Umbilical Cord
PubMed: 33622862
DOI: 10.21873/invivo.12310 -
Eye & Contact Lens Jun 2023To describe the labeling, packaging practices, and characteristics of compounded 0.01% ophthalmic atropine. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To describe the labeling, packaging practices, and characteristics of compounded 0.01% ophthalmic atropine.
METHODS
A convenience sample of parents of children who had previously been prescribed low-concentration atropine for myopia management were randomized to obtain 0.01% atropine ophthalmic solution from one of nine compounding pharmacies. The products were analyzed for various important quality attributes. The main outcomes were labeling practices, concentration of atropine and degradant product tropic acid, pH, osmolarity, viscosity, and excipients in 0.01% atropine samples obtained from nine US compounding pharmacies.
RESULTS
Twenty-four samples from nine pharmacies were analyzed. The median bottle size was 10 mL (range 3.5-15 mL), and eight of nine pharmacies used clear plastic bottles. Storage recommendations varied and were evenly split between refrigeration (33%), room temperature (33%), and cool, dark, dry location (33%). Beyond use dates ranged from 7 to 175 days (median, 91 days). Median pH of samples was 7.1 (range, 5.5-7.8). Median measured concentration relative to the prescribed concentration was 93.3% (70.4%-104.1%). One quarter of samples were under the 90% minimum target concentration of 0.01%.
CONCLUSIONS
An inconsistent and wide variety of formulation and labeling practices exist for compounding 0.01% atropine prescribed to slow pediatric myopia progression.
Topics: Humans; Child; Atropine; Drug Compounding; Myopia; Ophthalmic Solutions
PubMed: 37022143
DOI: 10.1097/ICL.0000000000000990 -
Ophthalmology Jul 2020
Topics: Double-Blind Method; Dry Eye Syndromes; Humans; Ophthalmic Solutions
PubMed: 32564818
DOI: 10.1016/j.ophtha.2020.01.048 -
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 -
NeoReviews Feb 2020The clinical goals of intravenous lipid emulsions (ILEs) have changed since their initial development. In the past, 100% soybean oil was used to provide energy and... (Review)
Review
The clinical goals of intravenous lipid emulsions (ILEs) have changed since their initial development. In the past, 100% soybean oil was used to provide energy and prevent an essential fatty acid deficiency. Now, different oil sources are used with the goal of improving nutritional status and preventing common neonatal comorbidities. We now have a better understanding of specific ILE constituents, namely, fatty acids, vitamin E, and phytosterols, and how these components contribute to complications such as intestinal failure-associated liver disease. This review addresses the development and composition of different ILEs and summarizes how individual ILE ingredients affect infant metabolism and health.
Topics: Fat Emulsions, Intravenous; History, 20th Century; History, 21st Century; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Intensive Care, Neonatal
PubMed: 32005721
DOI: 10.1542/neo.21-2-e109