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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 -
Blood Transfusion = Trasfusione Del... Jan 2019Red blood cells (RBCs) are a specialised organ that enabled the evolution of multicellular organisms by supplying a sufficient quantity of oxygen to cells that cannot... (Review)
Review
Red blood cells (RBCs) are a specialised organ that enabled the evolution of multicellular organisms by supplying a sufficient quantity of oxygen to cells that cannot obtain oxygen directly from ambient air via diffusion, thereby fueling oxidative phosphorylation for highly efficient energy production. RBCs have evolved to optimally serve this purpose by packing high concentrations of haemoglobin in their cytosol and shedding nuclei and other organelles. During their circulatory lifetimes in humans of approximately 120 days, RBCs are poised to transport oxygen by metabolic/redox enzymes until they accumulate damage and are promptly removed by the reticuloendothelial system. These elaborate evolutionary adaptions, however, are no longer effective when RBCs are removed from the circulation and stored hypothermically in blood banks, where they develop storage-induced damages ("storage lesions") that accumulate over the shelf life of stored RBCs. This review attempts to provide a comprehensive view of the literature on the subject of RBC storage lesions and their purported clinical consequences by incorporating the recent exponential growth in available data obtained from "omics" technologies in addition to that published in more traditional literature. To summarise this vast amount of information, the subject is organised in figures with four panels: i) root causes; ii) RBC storage lesions; iii) physiological effects; and iv) reported outcomes. The driving forces for the development of the storage lesions can be roughly classified into two root causes: i) metabolite accumulation/depletion, the target of various interventions (additive solutions) developed since the inception of blood banking; and ii) oxidative damages, which have been reported for decades but not addressed systemically until recently. Downstream physiological consequences of these storage lesions, derived mainly by in vitro studies, are described, and further potential links to clinical consequences are discussed. Interventions to postpone the onset and mitigate the extent of the storage lesion development are briefly reviewed. In addition, we briefly discuss the results from recent randomised controlled trials on the age of stored blood and clinical outcomes of transfusion.
Topics: Blood Preservation; Erythrocyte Transfusion; Erythrocytes; Humans; Oxygen; Pharmaceutical Solutions; Time Factors
PubMed: 30653459
DOI: 10.2450/2019.0217-18 -
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 -
The Cochrane Database of Systematic... Oct 2018Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to favourably influence some patient-level outcomes, albeit based on generally sub-optimal quality studies. Several additional randomised controlled trials (RCT) evaluating biocompatible solutions in PD patients have been published recently. This is an update of a review first published in 2014.
OBJECTIVES
This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD.
SEARCH METHODS
The Cochrane Kidney and Transplant Specialised Register was searched up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All RCTs and quasi-RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate-buffered, low GDP; neutral pH, bicarbonate(± lactate)-buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid-based solutions were excluded.
DATA COLLECTION AND ANALYSIS
Two authors extracted data on study quality and outcomes. Summary effect estimates were obtained using a random-effects model, and results were expressed as risk ratios and 95% confidence intervals (CI) for categorical variables, and mean differences (MD) or standardised mean differences (SMD) and 95% CI for continuous variables.
MAIN RESULTS
This review update included 42 eligible studies (3262 participants), including six new studies (543 participants). Overall, 29 studies (1971 participants) compared neutral pH, low GDP PD solution with conventional PD solution, and 13 studies (1291 participants) compared icodextrin with conventional PD solution. Risk of bias was assessed as high for sequence generation in three studies, allocation concealment in three studies, attrition bias in 21 studies, and selective outcome reporting bias in 16 studies.Neutral pH, low GDP versus conventional glucose PD solutionUse of neutral pH, low GDP PD solutions improved residual renal function (RRF) preservation (15 studies, 835 participants: SMD 0.19, 95% CI 0.05 to 0.33; high certainty evidence). This approximated to a mean difference in glomerular filtration rate of 0.54 mL/min/1.73 m (95% CI 0.14 to 0.93). Better preservation of RRF was evident at all follow-up durations with progressively greater preservation observed with increasing follow up duration. Neutral pH, low GDP PD solution use also improved residual urine volume preservation (11 studies, 791 participants: MD 114.37 mL/day, 95% CI 47.09 to 181.65; high certainty evidence). In low certainty evidence, neutral pH, low GDP solutions may make little or no difference to 4-hour peritoneal ultrafiltration (9 studies, 414 participants: SMD -0.42, 95% CI -0.74 to -0.10) which approximated to a mean difference in peritoneal ultrafiltration of 69.72 mL (16.60 to 122.00 mL) lower, and may increase dialysate:plasma creatinine ratio (10 studies, 746 participants: MD 0.01, 95% CI 0.00 to 0.03), technique failure or death compared with conventional PD solutions. It is uncertain whether neutral pH, low GDP PD solution use led to any differences in peritonitis occurrence, hospitalisation, adverse events (6 studies, 519 participants) or inflow pain (1 study, 58 participants: RR 0.51, 95% CI 0.24 to 1.08).Glucose polymer (icodextrin) versus conventional glucose PD solutionIn moderate certainty evidence, icodextrin probably reduced episodes of uncontrolled fluid overload (2 studies, 100 participants: RR 0.30, 95% CI 0.15 to 0.59) and augmented peritoneal ultrafiltration (4 studies, 102 participants: MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising RRF (4 studies, 114 participants: SMD 0.12, 95% CI -0.26 to 0.49; low certainty evidence) which approximated to a mean creatinine clearance of 0.30 mL/min/1.73m higher (0.65 lower to 1.23 higher) or urine output (3 studies, 69 participants: MD -88.88 mL/d, 95% CI -356.88 to 179.12; low certainty evidence). It is uncertain whether icodextrin use led to any differences in adverse events (5 studies, 816 participants) technique failure or death.
AUTHORS' CONCLUSIONS
This updated review strengthens evidence that neutral pH, low GDP PD solution improves RRF and urine volume preservation with high certainty. These effects may be related to increased peritoneal solute transport and reduced peritoneal ultrafiltration, although the evidence for these outcomes is of low certainty due to significant heterogeneity and suboptimal methodological quality. Icodextrin prescription increased peritoneal ultrafiltration and mitigated uncontrolled fluid overload with moderate certainty. The effects of either neutral pH, low GDP solution or icodextrin on peritonitis, technique survival and patient survival remain uncertain and require further high quality, adequately powered RCTs.
Topics: Adult; Bicarbonates; Child; Dialysis Solutions; Glucose; Humans; Hydrogen-Ion Concentration; Icodextrin; Kidney; Peritoneal Dialysis; Peritoneum; Pharmaceutical Solutions; Randomized Controlled Trials as Topic; Urine
PubMed: 30362116
DOI: 10.1002/14651858.CD007554.pub3 -
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 :... 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 -
The British Journal of Ophthalmology Nov 2018Preservatives continue to be in widespread use in ophthalmic medications due to the convenience they provide, regulatory requirements and the higher cost of... (Review)
Review
Preservatives continue to be in widespread use in ophthalmic medications due to the convenience they provide, regulatory requirements and the higher cost of alternatives. Benzalkonium chloride (BAK) remains the most commonly used preservative but there is a trend towards the use of preservative-free (PF) drops for glaucoma, although at a higher price. An extensive body of literature explores BAK toxicity on ocular structures in animal and laboratory studies (in vitro and in vivo). Non-randomised controlled studies have provided some supporting evidence of its toxicity in patients, especially in those with pre-existing ocular surface disease (OSD) or on multiple medications. However, there have been very few randomised controlled trials that compare the same medication with and without BAK preservative. Several of these trials have never been published in any peer reviewed journals. Notwithstanding, those that have been published, have not demonstrated any clear benefits of the BAK-free formulations. Short duration and exclusion of those with OSD are limitations of these studies. There is a lack of evidence of clinically significant harm from a small number of BAK preserved drops in patients without OSD. This means that generally more expensive PF glaucoma medications should only be recommended for those on poly pharmacy or those with OSD but are not necessarily required for all patients.
Topics: Anterior Eye Segment; Antihypertensive Agents; Glaucoma; Humans; Ophthalmic Solutions; Preservatives, Pharmaceutical
PubMed: 29973365
DOI: 10.1136/bjophthalmol-2017-311544 -
Nefrologia : Publicacion Oficial de La... 2017The measure of intraperitoneal pressure in peritoneal dialysis is easy and provides clear therapeutic benefits. However it is measured only rarely in adult peritoneal... (Review)
Review
The measure of intraperitoneal pressure in peritoneal dialysis is easy and provides clear therapeutic benefits. However it is measured only rarely in adult peritoneal dialysis units. This review aims to disseminate the usefulness of measuring intraperitoneal pressure. This measurement is performed in supine before initiating the drain of a manual exchange with "Y" system, by raising the drain bag and measuring from the mid-axillary line the height of the liquid column that rises from the patient. With typical values of 10-16 cmHO, intraperitoneal pressure should never exceed 18 cmHO. With basal values that depend on body mass index, it increases 1-3 cmHO/L of intraperitoneal volume, and varies with posture and physical activity. Its increase causes discomfort, sleep and breathing disturbances, and has been linked to the occurrence of leaks, hernias, hydrothorax, gastro-esophageal reflux and enteric peritonitis. Less known and valued is its ability to decrease the effectiveness of dialysis significantly counteracting ultrafiltration and decreasing solute clearance to a smaller degree. Because of its easy measurement and potential utility, should be monitored in case of ultrafiltration failure to rule out its eventual contribution in some patients. Although not yet mentioned in the clinical practice guidelines for PD, its clear benefits justify its inclusion among the periodic measurements to consider for prescribing and monitoring peritoneal dialysis.
Topics: Adult; Ascitic Fluid; Body Mass Index; Dialysis Solutions; Humans; Hydrostatic Pressure; Kidney Failure, Chronic; Manometry; Peritoneal Dialysis; Pressure; Reference Values; Supine Position; Ultrafiltration
PubMed: 28739249
DOI: 10.1016/j.nefro.2017.05.014