-
Revista Da Associacao Medica Brasileira... Jan 2020Peritoneal dialysis (PD) is a renal replacement therapy based on infusing a sterile solution into the peritoneal cavity through a catheter and provides for the removal... (Review)
Review
Peritoneal dialysis (PD) is a renal replacement therapy based on infusing a sterile solution into the peritoneal cavity through a catheter and provides for the removal of solutes and water using the peritoneal membrane as the exchange surface. This solution, which is in close contact with the capillaries in the peritoneum, allows diffusion solute transport and osmotic ultrafiltration water loss since it is hyperosmolar to plasma due to the addition of osmotic agents (most commonly glucose). Infusion and drainage of the solution into the peritoneal cavity can be performed in two ways: manually (continuous ambulatory PD), in which the patient usually goes through four solution changes throughout the day, or machine-assisted PD (automated PD), in which dialysis is performed with the aid of a cycling machine that allows changes to be made overnight while the patient is sleeping. Prescription and follow-up of PD involve characterizing the type of peritoneal transport and assessing the offered dialysis dose (solute clearance) as well as diagnosing and treating possible method-related complications (infectious and non-infectious).
Topics: Anti-Bacterial Agents; Dialysis Solutions; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory
PubMed: 31939534
DOI: 10.1590/1806-9282.66.S1.37 -
Clinical Journal of the American... Feb 2023AKI is a common complication of critical illness and is associated with substantial morbidity and risk of death. Continuous KRT comprises a spectrum of dialysis... (Review)
Review
AKI is a common complication of critical illness and is associated with substantial morbidity and risk of death. Continuous KRT comprises a spectrum of dialysis modalities preferably used to provide kidney support to patients with AKI who are hemodynamically unstable and critically ill. The various continuous KRT modalities are distinguished by different mechanisms of solute transport and use of dialysate and/or replacement solutions. Considerable variation exists in the application of continuous KRT due to a lack of standardization in how the treatments are prescribed, delivered, and optimized to improve patient outcomes. In this manuscript, we present an overview of the therapy, recent clinical trials, and outcome studies. We review the indications for continuous KRT and the technical aspects of the treatment, including continuous KRT modality, vascular access, dosing of continuous KRT, anticoagulation, volume management, nutrition, and continuous KRT complications. Finally, we highlight the need for close collaboration of a multidisciplinary team and development of quality assurance programs for the provision of high-quality and effective continuous KRT.
Topics: Humans; Renal Replacement Therapy; Renal Dialysis; Dialysis Solutions; Acute Kidney Injury; Critical Illness
PubMed: 35981873
DOI: 10.2215/CJN.04350422 -
Eye (London, England) Feb 2022Preservatives in multidose formulations of topical ophthalmic medications are crucial for maintaining sterility but can be toxic to the ocular surface. Benzalkonium... (Review)
Review
Preservatives in multidose formulations of topical ophthalmic medications are crucial for maintaining sterility but can be toxic to the ocular surface. Benzalkonium chloride (BAK)-used in approximately 70% of ophthalmic formulations-is well known to cause cytotoxic damage to conjunctival and corneal epithelial cells, resulting in signs and symptoms of ocular surface disease (OSD) including ocular surface staining, increased tear break-up time, and higher OSD symptom scores. These adverse effects are more problematic with chronic exposure, as in lifetime therapy for glaucoma, but can also manifest after exposure as brief as seven days. Multiple strategies are available to minimize or eliminate BAK exposure, among them alternative preservatives, preservative-free formulations including sustained release drug delivery platforms, and non-pharmacological therapies for common eye diseases and conditions. In this paper, we review the cytotoxic and clinical effects of BAK on the ocular surface and discuss existing and emerging options for ocular disease management that can minimize or eliminate BAK exposure.
Topics: Antihypertensive Agents; Benzalkonium Compounds; Glaucoma; Humans; Ophthalmic Solutions; Preservatives, Pharmaceutical
PubMed: 34262161
DOI: 10.1038/s41433-021-01668-x -
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 -
International Journal of Molecular... Feb 2022Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are... (Review)
Review
Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are usually the first line of treatment for patients with DED. Despite the large variety of tear substitutes available on the market, few studies have been performed to compare their performance. There is a need to better understand the specific mechanical and pharmacological roles of each ingredient composing the different formulations. In this review, we describe the main categories of ingredients composing tear substitutes (e.g., viscosity-enhancing agents, electrolytes, osmo-protectants, antioxidants, lipids, surfactants and preservatives) as well as their effects on the ocular surface, and we provide insight into how certain components of tear substitutes may promote corneal wound healing, and/or counteract inflammation. Based on these considerations, we propose an approach to select the most appropriate tear substitute formulations according to the predominant etiological causes of DED.
Topics: Drug Compounding; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Viscosity
PubMed: 35269576
DOI: 10.3390/ijms23052434 -
Peritoneal Dialysis International :... Mar 20211.1 Peritoneal dialysis is a suitable renal replacement therapy modality for treatment of acute kidney injury in children. ()2. Access and fluid delivery for acute PD...
1.1 Peritoneal dialysis is a suitable renal replacement therapy modality for treatment of acute kidney injury in children. ()2. Access and fluid delivery for acute PD in children.2.1 We recommend a Tenckhoff catheter inserted by a surgeon in the operating theatre as the optimal choice for PD access. () ()2.2 Insertion of a PD catheter with an insertion kit and using Seldinger technique is an acceptable alternative. () ()2.3 Interventional radiological placement of PD catheters combining ultrasound and fluoroscopy is an acceptable alternative. () ()2.4 Rigid catheters placed using a stylet should only be used when soft Seldinger catheters are not available, with the duration of use limited to <3 days to minimize the risk of complications. () ()2.5 Improvised PD catheters should only be used when no standard PD access is available. () ()2.6 We recommend the use of prophylactic antibiotics prior to PD catheter insertion. () ()2.7 A closed delivery system with a Y connection should be used. () () A system utilizing buretrols to measure fill and drainage volumes should be used when performing manual PD in small children. () ()2.8 In resource limited settings, an open system with spiking of bags may be used; however, this should be designed to limit the number of potential sites for contamination and ensure precise measurement of fill and drainage volumes. () ()2.9 Automated peritoneal dialysis is suitable for the management of paediatric AKI, except in neonates for whom fill volumes are too small for currently available machines. (1D)3. Peritoneal dialysis solutions for acute PD in children3.1 The composition of the acute peritoneal dialysis solution should include dextrose in a concentration designed to achieve the target ultrafiltration. ()3.2 Once potassium levels in the serum fall below 4 mmol/l, potassium should be added to dialysate using sterile technique. () () If no facilities exist to measure the serum potassium, consideration should be given for the empiric addition of potassium to the dialysis solution after 12 h of continuous PD to achieve a dialysate concentration of 3-4 mmol/l. () ()3.3 Serum concentrations of electrolytes should be measured 12 hourly for the first 24 h and daily once stable. () () In resource poor settings, sodium and potassium should be measured daily, if practical. () ()3.4 In the setting of hepatic dysfunction, hemodynamic instability and persistent/worsening metabolic acidosis, it is preferable to use bicarbonate containing solutions. () () Where these solutions are not available, the use of lactate containing solutions is an alternative. () ()3.5 Commercially prepared dialysis solutions should be used. () () However, where resources do not permit this, locally prepared fluids may be used with careful observation of sterile preparation procedures and patient outcomes (e.g. rate of peritonitis). () ()4. Prescription of acute PD in paediatric patients4.1 The initial fill volume should be limited to 10-20 ml/kg to minimize the risk of dialysate leakage; a gradual increase in the volume to approximately 30-40 ml/kg (800-1100 ml/m) may occur as tolerated by the patient. ()4.2 The initial exchange duration, including inflow, dwell and drain times, should generally be every 60-90 min; gradual prolongation of the dwell time can occur as fluid and solute removal targets are achieved. In neonates and small infants, the cycle duration may need to be reduced to achieve adequate ultrafiltration. ()4.3 Close monitoring of total fluid intake and output is mandatory with a goal to achieve and maintain normotension and euvolemia. ()4.4 Acute PD should be continuous throughout the full 24-h period for the initial 1-3 days of therapy. ()4.5 Close monitoring of drug dosages and levels, where available, should be conducted when providing acute PD. ()5. Continuous flow peritoneal dialysis (CFPD)5.1 Continuous flow peritoneal dialysis can be considered as a PD treatment option when an increase in solute clearance and ultrafiltration is desired but cannot be achieved with standard acute PD. Therapy with this technique should be considered experimental since experience with the therapy is limited. ( 5.2 Continuous flow peritoneal dialysis can be considered for dialysis therapy in children with AKI when the use of only very small fill volumes is preferred (e.g. children with high ventilator pressures). (.
Topics: Acute Kidney Injury; Child; Dialysis Solutions; Glucose; Humans; Infant; Infant, Newborn; Pediatrics; Peritoneal Dialysis
PubMed: 33523772
DOI: 10.1177/0896860820982120 -
European Review For Medical and... Sep 2020The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear... (Review)
Review
OBJECTIVE
The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear substitutes in the treatment of DED. The meeting focused especially on the main characteristics of lacrimal substitutes, the development of in vitro models to investigate DED pathophysiology and treatment, the importance of conducting rigorous clinical trials, the requirements of the upcoming European Legislation on medical devices, the advances in the formulation of safer preservatives, the peculiarities of treatment in younger subjects, and the importance of an updated terminology for lacrimal substitutes.
MATERIALS AND METHODS
A literature search was conducted using MEDLINE, with different combinations of pertinent keywords, depending on the subject under discussion, such as "dry eye disease"; "tear substitutes"; "in vitro models"; "ocular surface"; "clinical trials"; "European Regulation"; "preservatives" "younger patients". Also, each author included in the discussion selected articles from their personal library. Using a consensus-based method called nominal group technique to reach a conclusion and proposal for a new classification of eye drops used to improve the tear film and ocular surface epithelia, the experts also conducted a round table meeting.
RESULTS
The new terms proposed by the authors are "wetting agents", "multiple-action tear substitutes" or "ocular surface modulators". The new classification is needed to distinguish eye drops used to improve the tear film and ocular surface epithelia, in line with the new definition of DED, which recognizes the loss of ocular homeostasis, and the creation of a vicious circle of chronic inflammation and ocular damage as fundamental aspects of DED pathophysiology.
CONCLUSIONS
Although tear substitutes have been historically used to provide eye lubrication to the ocular surface, recent advances in the pathophysiology of dry eye disease (DED) clarified that treatment should not just focus on tear film quality or quantity, but address the loss of homeostasis of the ocular surface, blocking the vicious circle of chronic inflammation and ocular damage. Given the scant comparative evidence on tear substitutes currently on the market, further studies should focus on developing new agents, considering the advantages provided by in vitro models, importance of conducting rigorous clinical trials, availability of less harmful preservatives and obligations related to the new European legislation on medical devices. Based on the discussion of these topics, a group of experts held a consensus meeting to identify new and more appropriate terms for different tear substitutes. The proposed terms are wetting agents, multiple-action tear substitutes and ocular surface modulators. Regardless of the agent used, it is important to note that tear substitutes represent one of many options for DED treatment, which should not overlook the psychological aspects of the disease and the peculiarities of younger subjects, who seem to have a higher risk for DED, possibly related to digital devices excessive use.
Topics: Animals; Dry Eye Syndromes; European Union; Humans; Lubricant Eye Drops; Medical Device Legislation
PubMed: 32964952
DOI: 10.26355/eurrev_202009_22801 -
JAMA Ophthalmology May 2023Dry eye disease (DED) is a common public health problem with significant impact on vision-related quality of life and well-being of patients. Medications with rapid...
IMPORTANCE
Dry eye disease (DED) is a common public health problem with significant impact on vision-related quality of life and well-being of patients. Medications with rapid onset of action and a good tolerability profile remain an unmet need.
OBJECTIVE
To assess efficacy, safety, and tolerability of a water-free cyclosporine ophthalmic solution, 0.1% (CyclASol [Novaliq GmbH]), applied twice daily in DED compared with vehicle.
DESIGN, SETTING, AND PARTICIPANTS
CyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (ESSENCE-2) was a phase 3, multicenter, randomized, double-masked, vehicle-controlled clinical study conducted from December 5, 2020, to October 8, 2021. Following a 14-day run-in period with an artificial tear administered 2 times per day, eligible participants were randomly assigned 1:1 to the treatment groups. Patients with moderate to severe DED were included in the study.
INTERVENTIONS
Cyclosporine solution vs vehicle administered 2 times per day for 29 days.
MAIN OUTCOMES AND MEASURES
The primary end points were changes from baseline in total corneal fluorescein staining (tCFS; 0-15 National Eye Institute scale) and in dryness score (0-100 visual analog scale) at day 29. Conjunctival staining, central corneal fluorescein staining, and tCFS responders were also assessed.
RESULTS
A total of 834 study participants were randomly assigned to cyclosporine (423 [50.7%]) or vehicle (411 [49.3%]) groups at 27 sites. Participants had a mean (SD) age of 57.1 (15.8) years, and 609 (73.0%) were female individuals. The majority of participants self-identified in the following race categories: 79 Asian (9.5 %), 108 Black (12.9%), and 635 White (76.1%). Participants treated with cyclosporine solution had greater improvement in tCFS (-4.0 grades) than the vehicle group (-3.6 grades) at day 29 (change [∆] = -0.4; 95% CI, -0.8 to 0; P = .03). The dryness score showed treatment benefits from baseline in both groups: -12.2 points for cyclosporine and -13.6 points for vehicle (∆ = 1.4; 95% CI, -1.8 to 4.6; P = .38). In the cyclosporine group, 293 participants (71.6%) achieved clinically meaningful reductions of 3 grades or higher in tCFS vs 236 (59.7%) in the vehicle group (∆ = 12.6%; 95% CI, 6.0%-19.3%; P < .001). These responders showed greater improvement in symptoms at day 29 including dryness (∆ = -4.6; 95% CI, -8.0 to -1.2; P = .007) and blurred vision (Δ = -3.5; 95% CI, -6.6 to -4.0; P = .03) compared with nonresponders.
CONCLUSIONS AND RELEVANCE
The ESSENCE-2 trial confirmed that treatment with a water-free cyclosporine solution, 0.1%, results in early therapeutic effects on the ocular surface compared with vehicle. The responder analyses suggest that the effect is clinically meaningful in 71.6% of participants in the cyclosporine group.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04523129.
Topics: Humans; Female; Middle Aged; Male; Cyclosporine; Quality of Life; Treatment Outcome; Ophthalmic Solutions; Dry Eye Syndromes; Fluorescein; Lubricant Eye Drops; Double-Blind Method; Tears
PubMed: 37022717
DOI: 10.1001/jamaophthalmol.2023.0709 -
Ophthalmology Apr 2022To evaluate the efficacy and safety of OC-01 (varenicline solution) nasal spray for treatment of patients with dry eye disease. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the efficacy and safety of OC-01 (varenicline solution) nasal spray for treatment of patients with dry eye disease.
DESIGN
Randomized, multicenter, double-masked, vehicle-controlled, phase 3 study.
PARTICIPANTS
Adults 22 years of age or older with a diagnosis of dry eye disease, artificial tear use, Ocular Surface Disease Index score of 23 or more, and Schirmer test score (STS) of 10 mm or less. Eligibility was not restricted by eye dryness score (EDS).
METHODS
Patients (N = 758) were randomized in a 1:1:1 ratio to twice-daily treatment with 50-μl intranasal spray in each nostril of OC-01 0.03 mg (n = 260), OC-01 0.06 mg (n = 246), or vehicle (control; n = 252) for 4 weeks (ClinicalTrials.gov identifier, NCT04036292).
MAIN OUTCOME MEASURES
The primary efficacy end point was the percentage of patients achieving a 10-mm improvement or more in STS at week 4. Secondary end points included change from baseline to week 4 in STS and EDS in a controlled adverse environment (CAE) chamber and in the clinic. Treatment-emergent adverse events (TEAEs) were assessed.
RESULTS
A statistically significantly greater percentage of patients achieved the primary end point in both OC-01 treatment groups compared with the vehicle group (OC-01 0.03 mg, 47.3%; OC-01 0.06 mg, 49.2%; vehicle, 27.8%; P < 0.0001 for both doses). Change from baseline in STS at week 4 was statistically significantly greater for patients receiving OC-01 than vehicle (P < 0.0001 for both doses). Eye dryness score assessed at week 4 improved with OC-01 treatment compared with vehicle, although the difference was not significant for EDS measured in the CAE chamber and showed (nominal) significance in the clinic. Overall, 86.5% of patients (654/756) reported at least 1 TEAE during the treatment period; most were mild, nonocular (sneezing, cough, throat irritation, and instillation site irritation) and were reported by fewer patients in the vehicle group than in the OC-01 treatment groups (OC-01 0.03 mg, 97.3%; OC-01 0.06 mg, 99.2%; vehicle, 57%).
CONCLUSIONS
OC-01 nasal spray was well tolerated and showed a clinically meaningful effect on signs and symptoms of dry eye disease.
Topics: Adult; Double-Blind Method; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Nasal Sprays; Ophthalmic Solutions; Tears; Treatment Outcome; Varenicline
PubMed: 34767866
DOI: 10.1016/j.ophtha.2021.11.004 -
Peritoneal Dialysis International :... Jan 2021(1) Peritoneal dialysis (PD) should be considered a suitable modality for treatment of acute kidney injury (AKI) in all settings .
SUMMARY STATEMENTS
(1) Peritoneal dialysis (PD) should be considered a suitable modality for treatment of acute kidney injury (AKI) in all settings .
GUIDELINE 2: ACCESS AND FLUID DELIVERY FOR ACUTE PD IN ADULTS
(2.1) Flexible peritoneal catheters should be used where resources and expertise exist .(2.2) Rigid catheters and improvised catheters using nasogastric tubes and other cavity drainage catheters may be used in resource-poor environments where they may still be life-saving .(2.3) We recommend catheters should be tunnelled to reduce peritonitis and peri-catheter leak .(2.4) We recommend that the method of catheter implantation should be based on patient factors and locally available skills .(2.5) PD catheter implantation by appropriately trained nephrologists in patients without contraindications is safe and functional results equate to those inserted surgically .(2.6) Nephrologists should receive training and be permitted to insert PD catheters to ensure timely dialysis in the emergency setting (2.7) We recommend, when available, percutaneous catheter insertion by a nephrologist should include assessment with ultrasonography .(2.8) Insertion of PD catheter should take place under complete aseptic conditions using sterile technique .(2.9) We recommend the use of prophylactic antibiotics prior to PD catheter implantation .(2.10) A closed delivery system with a Y connection should be used . In resource poor areas, spiking of bags and makeshift connections may be necessary and can be considered .(2.11) The use of automated or manual PD exchanges are acceptable and this will be dependent on local availability and practices .
GUIDELINE 3: PERITONEAL DIALYSIS SOLUTIONS FOR ACUTE PD
(3.1) In patients who are critically ill, especially those with significant liver dysfunction and marked elevation of lactate levels, bicarbonate containing solutions should be used (. Where these solutions are not available, the use of lactate containing solutions is an alternative .(3.2) Commercially prepared solutions should be used . However, where resources do not permit this, then locally prepared fluids may be life-saving and with careful observation of sterile preparation procedure, peritonitis rates are not increased .(3.3) Once potassium levels in the serum fall below 4 mmol/L, potassium should be added to dialysate (using strict sterile technique to prevent infection) or alternatively oral or intravenous potassium should be given to maintain potassium levels at 4 mmol/L or above .(3.4) Potassium levels should be measured daily . Where these facilities do not exist, we recommend that after 24 h of successful dialysis, one consider adding potassium chloride to achieve a concentration of 4 mmol/L in the dialysate
GUIDELINE 4: PRESCRIBING AND ACHIEVING ADEQUATE CLEARANCE IN ACUTE PD
(4.1) Targeting a weekly / of 3.5 provides outcomes comparable to that of daily HD in critically ill patients; targeting higher doses does not improve outcomes . This dose may not be necessary for most patients with AKI and targeting a weekly / of 2.2 has been shown to be equivalent to higher doses . Tidal automated PD (APD) using 25 L with 70% tidal volume per 24 h shows equivalent survival to continuous venovenous haemodiafiltration with an effluent dose of 23 mL/kg/h .(4.2) Cycle times should be dictated by the clinical circumstances. Short cycle times (1-2 h) are likely to more rapidly correct uraemia, hyperkalaemia, fluid overload and/or metabolic acidosis; however, they may be increased to 4-6 hourly once the above are controlled to reduce costs and facilitate clearance of larger sized solutes .(4.3) The concentration of dextrose should be increased and cycle time reduced to 2 hourly when fluid overload is evident. Once the patient is euvolemic, the dextrose concentration and cycle time should be adjusted to ensure a neutral fluid balance .(4.4) Where resources permit, creatinine, urea, potassium and bicarbonate levels should be measured daily; 24 h / and creatinine clearance measurement is recommended to assess adequacy when clinically indicated .(4.5) Interruption of dialysis should be considered once the patient is passing >1 L of urine/24 h and there is a spontaneous reduction in creatinine .
UNLABELLED
The use of peritoneal dialysis (PD) to treat patients with acute kidney injury (AKI) has become more popular among clinicians following evidence of similar outcomes when compared with other extracorporeal therapies. Although it has been extensively used in low-resource environments for many years, there is now a renewed interest in the use of PD to manage patients with AKI (including patients in intensive care units) in higher income countries. Here we present the update of the International Society for Peritoneal Dialysis guidelines for PD in AKI. These guidelines extensively review the available literature and present updated recommendations regarding peritoneal access, dialysis solutions and prescription of dialysis with revised targets of solute clearance.
Topics: Acute Kidney Injury; Adult; Dialysis Solutions; Humans; Peritoneal Dialysis; Peritoneum; Peritonitis
PubMed: 33267747
DOI: 10.1177/0896860820970834