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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 -
Clinical Journal of the American... Feb 2019Approximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and... (Review)
Review
Approximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.
Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Body Water; Dialysis Solutions; Diet, Sodium-Restricted; Diuretics; Humans; Hypertension; Icodextrin; Kidney Failure, Chronic; Mortality; Peritoneal Dialysis, Continuous Ambulatory; Prevalence; Renal Dialysis
PubMed: 30341090
DOI: 10.2215/CJN.07480618 -
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 -
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 -
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 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 -
The Cochrane Database of Systematic... Dec 2011Sclerotherapy has been used in clinical practice for centuries, but there is still no consensus about which, if any, sclerosing agent provides the best results. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sclerotherapy has been used in clinical practice for centuries, but there is still no consensus about which, if any, sclerosing agent provides the best results.
OBJECTIVES
To assess the effectiveness and safety of sclerosing agents in the treatment of telangiectasias of the lower limbs.
SEARCH METHODS
The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialised Register (last searched 26 May 2011) and CENTRAL (2011, Issue 2). We searched references within identified studies and from the Cited References in the Web of Science. We contacted study authors and pharmaceutical companies. There were no language restrictions.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials on the treatment of telangiectasias comparing sclerotherapy with a normal saline placebo, no treatment or an alternative sclerotherapy regimen.
DATA COLLECTION AND ANALYSIS
Both authors determined which studies to include, extracted the data and rated risk of bias. One author (LS) contacted study authors and pharmaceutical companies and analysed the results.
MAIN RESULTS
Ten studies involving 484 patients were included. There was no evidence suggesting superior efficacy of any one sclerosant over another, but there was evidence of superiority of sclerotherapy to placebo.The evidence did not suggest an increase in patient satisfaction with any one agent versus another, but there was evidence that patients were less satisfied with placebo.There was some evidence suggesting that polidocanol (POL) was more likely to cause adverse reactions at a concentration of 1% compared with lower concentrations or hypertonic saline, and that sodium tetradecyl sulfate (STS) was more likely to cause adverse reactions at a concentration of 1% compared with POL at 0.5%.There was some evidence suggesting that STS was more painful than POL, heparsal (20% saline mixed with heparin 100 units/mL) or placebo, and that POL was no more painful than placebo. Evidence from one study suggested that hypertonic saline (HS) was more painful than POL.The data were not suitable for meta-analysis.
AUTHORS' CONCLUSIONS
The evidence did not suggest superior efficacy or patient satisfaction for any one sclerosing agent used in the treatment of telangiectasias of the lower limbs, but the agents studied showed superiority to a normal saline placebo. However, the amount of available evidence in this field is small and the overall methodological quality of the research was poor, as was the quality of reporting. More research is needed to determine the optimal agent(s) and the ideal dosing to achieve the best results and maximize patient satisfaction. Future research efforts should incorporate more demographic data and symptom measures to allow for comparison with findings from observational studies, thereby aiding assessment of how various risk groups respond to treatment.
Topics: Heparin; Humans; Leg; Patient Satisfaction; Polidocanol; Polyethylene Glycols; Randomized Controlled Trials as Topic; Sclerosing Solutions; Sclerotherapy; Sodium Chloride; Sodium Tetradecyl Sulfate; Telangiectasis
PubMed: 22161437
DOI: 10.1002/14651858.CD008826.pub2 -
Nutrients Mar 2013Parenteral nutrition (PN) has become an integral part of clinical management of very low birth weight premature neonates. Traditionally different components of PN are... (Review)
Review
Parenteral nutrition (PN) has become an integral part of clinical management of very low birth weight premature neonates. Traditionally different components of PN are prescribed individually considering requirements of an individual neonate (IPN). More recently, standardised PN formulations (SPN) for preterm neonates have been assessed and may have advantages including better provision of nutrients, less prescription and administration errors, decreased risk of infection, and cost savings. The recent introduction of triple-chamber bag that provides total nutrient admixture for neonates may have additional advantage of decreased risk of contamination and ease of administration.
Topics: Chemistry, Pharmaceutical; Cost-Benefit Analysis; Drug Contamination; Drug Costs; Equipment Contamination; Equipment Design; Gestational Age; Humans; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Parenteral Nutrition; Parenteral Nutrition Solutions; Practice Guidelines as Topic; Treatment Outcome
PubMed: 23538938
DOI: 10.3390/nu5041058 -
Clinical & Experimental Optometry Sep 2017Contact lenses as a means to deliver pharmaceuticals to the eye have seen a significant increase in research interest in the past few years. This review will detail the... (Review)
Review
Contact lenses as a means to deliver pharmaceuticals to the eye have seen a significant increase in research interest in the past few years. This review will detail the in vitro experiments which have investigated use of these contact lenses in the context of the desired pharmacological treatment goals in the management of infectious, inflammatory, allergic and glaucomatous diseases of the eye. The techniques researchers have employed to modify and tailor drug release rates from these materials, including the use of vitamin E diffusion barriers, modified ionicity, molecular imprinting and incorporation of drug reservoirs, will be discussed, as well as their impact on drug release kinetics. Finally, the demonstration of the feasibility of these materials when applied in vivo in animal models as well as in humans with and without disease will be presented and their results discussed relating to their implications for the future of the field.
Topics: Contact Lenses, Hydrophilic; Drug Delivery Systems; Humans; Ophthalmic Solutions; Pharmaceutical Preparations
PubMed: 28940532
DOI: 10.1111/cxo.12592