Steven Daniel Crowley, MD

• Associate Professor of Medicine
• Member of the Duke Cancer Institute

https://medicine.duke.edu/faculty/steven-daniel-crowley-md

Successful use of Tesio catheters in pediatric patients receiving chronic hemodialysis impotence from priapism surgery generic 20mg forzest with visa. Arteriovenous fistula for chronic hemodialysis in pediatric candidates for renal transplantation: technical details and refinements impotence after 40 purchase forzest discount. For infants who require long-term renal replacement therapy as a bridge to renal recovery or transplant erectile dysfunction medicine for heart patients generic forzest 20mg otc, peritoneal dialysis is the preferred modality because of decreased morbidity and mortality erectile dysfunction pills wiki forzest 20mg. Furthermore erectile dysfunction caused by obesity order forzest toronto, provision of hemodialysis for infants requires additional staff with specialized training impotence natural remedies forzest 20mg cheap. Recurrent peritonitis may limit the utility of peritoneal dialysis if adequate clearance and ultrafiltration cannot be achieved. The goal of dialysis is to achieve enough clearance and ultrafiltration to allow for ongoing support of the infant as well as to allow for provision of nutrition. Vascular Access Hemodialysis requires a central venous catheter, and in infants this poses technical challenges because of their smaller vessel size and the likelihood that they may require vascular access throughout their lifetime if end-stage renal disease is present. Thus, use of central lines other than those designed for dialysis is not recommended. Historically, umbilical lines were sometimes used for infant hemodialysis access but this has fallen out of favor with the availability of small diameter hemodialysis lines. In this case, the tip of the umbilical vein catheter should be above the diaphragm, and the tip of the umbilical artery catheter should be below the renal arteries. If umbilical catheters are used for dialysis, the arterial and venous lines cannot be reversed. The choice of a temporary (uncuffed, nontunneled) versus semipermanent (cuffed, tunneled) hemodialysis catheter depends on whether the infant is expected to require therapy short- or long-term. Placement of a hemodialysis catheter should be performed with fluoroscopy to confirm placement. The line with the largest possible gauge should be placed in order to allow for optimum blood flows. However, placement of a line that is too broad can result in occlusion of the vessel. Catheter insertion site should be determined individually as each infant requiring hemodialysis may have specific circumstances precluding one site or another. Femoral catheters are associated with an increased risk of infection, and thus should not be used long term. With noncentral placement of catheters, there is an increased risk of recirculation as well as blood flow limitations. Complications of hemodialysis access include infection, clotting, venous outflow obstruction, and failure of the access, which may be related to placement, kinking, or breaking of the line. Because these complications result in an inability to provide dialysis urgently and may require surgical replacement of the line, dialysis lines should be used only by trained dialysis staff. To maintain patency of the lines, anticoagulation is used during dialysis, and the details of this are reviewed in Chapter 77. Equipment/Preparation Equipment for hemodialysis includes the dialysis machines, blood lines, and dialyzer. Each must be carefully considered to provide the safest and most efficient treatment for the infant. Many dialysis machines will now allow low blood flows, although none provides specific indications for infant dialysis, and thus provision of infant dialysis is an off-label use of the machine. Of critical importance in selecting a dialysis machine to use for the infant is the availability of accurate control of ultrafiltration. In the infant, even small volumes of ultrafiltration may result in hemodynamic changes. One must have information regarding the priming volume of the blood lines and the dialyzer. For small patients, use of blood to prime the circuit is required to avoid hemodynamic compromise and hemodilution. Consideration when using blood primes includes the potential for sensitization when exposing an infant to multiple blood donors, which may complicate future transplantation. Donated blood is anticoagulated with citrate, which can lead to hypocalcemia in the infant, and thus serum calcium should be assessed and supplemental calcium provided if indicated. Blood primes also contain a significant amount of potassium and, if possible, one should provide fresh blood or washed red cells to avoid hyperkalemia. At the end of a treatment initiated with a blood prime, blood in the lines is not returned to the patient because this would represent a large-volume transfusion and can lead to hypervolemia, hypertension, and/or pulmonary edema. Lines may need to be warmed to prevent hypothermia in the infant undergoing hemodialysis. Infant Hemodialysis 879 For infants undergoing hemodialysis, typically the smallest dialysis filter available is appropriate, as smaller filters will still allow for adequate clearance given the low total blood volume. There are currently a wide variety of filters with various blood volumes available, and each institution may have its own preferable filters based on local experience. Given the low number of small children receiving hemodialysis each year, there are no formal studies comparing the safety and efficacy of different dialysis machines and filters in infants. Dialysis Prescription for the Infant: Special Considerations Infants undergoing hemodialysis require special considerations when generating the dialysis prescription, with regard to the clearance, blood flow, and other parameters (Table 73. Thus, a stepwise approach should be used in those with marked uremia or hypernatremia by providing increasing clearance each day to allow for gradual equilibrium. Initial clearance for an infant with significant uremia should be limited to provide 30% urea reduction rate on the first day, followed by sequential increases in urea reduction (30%, 50%, 70%) to avoid disequilibrium. If the desired ultrafiltration cannot be achieved in the same time frame, one can continue with ultrafiltration only to achieve the desired effect. Dialysis initiated for removal of other substances without significant uremia should focus on removal of that particular substance. In this case, maximal clearance should be attempted with each therapy including the initial treatment. However, in the smallest infants, this may still be insufficient to maintain blood flow through the circuit. Lower blood flows will increase the risk of clotting, and thus if the infant can tolerate blood flows of 50 mL/min this is preferred. At low blood flow rates, the dialyzer clearance of the solute for the blood flow Table 73. After each treatment, using the urea reduction rate achieved, one can back-calculate the actual clearance of urea and use this for calculating the next prescription. In many institutions, the dialysate flow is set at a minimum of 300 or 500 mL/min. Conversely, in cases of malignant hyperthermia, room temperature or cooled blood lines can be used to lower core temperature. However, there are specific considerations for the infant undergoing hemodialysis, which will be discussed here. Use of heparin poses risks in the neonate, including intracranial hemorrhage and bleeding from surgical sites. Infants with preexisting conditions such as bleeding or recent surgery may require hemodialysis sessions without heparin. In this case, frequent flushes of saline can be provided prefilter to prevent clotting, and the volume of the flushes can be removed by ultrafiltration. Use of citrate for anticoagulation poses the potential risk of hypocalcemia and requires close monitoring. Although patients receiving chronic hemodialysis typically undergo three sessions each week, the infant undergoing hemodialysis will require more frequent treatments. Infants in the intensive care unit should undergo daily dialysis to allow for more stable metabolic balance and provide ultrafiltration to allow them to receive adequate nutrition without worsening fluid overload. If ultrafiltration is required despite the need to avoid excessive clearance, such as in the case of significant uremia, dialysate can be stopped once the desired clearance is achieved, and one can continue ultrafiltration alone as noted above. In this case, there will be a small amount of clearance due to solvent drag/convective clearance. When dialyzing infants, the rate of ultrafiltration volume must be considered relative to the size of the infant and effective circulating volume. Thus, treatment time may be extended beyond that required for clearance, to allow for adequate ultrafiltration. Furthermore, current dialysis machines may not report precise ultrafiltration volumes, and small margins of error could be significant to the infant undergoing hemodialysis. High rates of clearance can lead to hypokalemia, hypophosphatemia, and other electrolyte derangements. Close monitoring of electrolytes and repletion as needed, as well as adjustment of dialysate to avoid life-threatening electrolyte abnormalities, is paramount to the care of the infant receiving hemodialysis. Thus, the primary team should be Infant Hemodialysis 881 prepared to increase the doses of these medications while the infant is receiving hemodialysis. Antibiotics and other medications may need to be dose-adjusted when the infant is receiving hemodialysis. Otherwise, drug-dosing resources can be used to determine whether dosing adjustments are required. Blood products and medications often result in large volumes being administered to the infant. Thus, provision of blood products to the infant with renal failure should be done while on dialysis when possible. If other medications require a large volume but are not dialyzed, they can be provided during dialysis and the volume removed by ultrafiltration to result in no net fluid administration to the patient. When considering dialysis for a toxin ingestion or overdose, it is critical to review the toxin and its metabolites to determine what will be cleared. Substances that are dialyzed most easily are those that are water soluble, low-molecular-weight, and not protein bound. However, some toxins that are protein-bound may have metabolites that are present in a free state, and thus assessment of the utility of dialysis should be undertaken on a case-by-case basis depending on the compound in question. Dialysis performed for indications other than renal failure, such as hyperammonemia, often requires a different approach and may require maximizing clearance beyond that which is recommended for infants with renal failure. In this case, one does not need to consider disequilibrium as the patient is not usually uremic, and removal of the solute or toxin may dictate changes to the dialysis prescription. Patients who require hemodialysis in the acute setting may be transitioned to peritoneal dialysis if they will be dependent on renal replacement therapy long term. Chronic Hemodialysis the infant requiring chronic hemodialysis is at increased risk of mortality. In this case, meticulous attention to growth and nutrition is required and is best accomplished with the use of a multidisciplinary team to assess all needs of the infant. This team should include a pediatric nephrologist, experienced pediatric dialysis nurses, renal dietitian, social worker, and pharmacist if possible. Infants undergoing hemodialysis who are otherwise not critically ill will still typically require at least four to five sessions per week to allow for adequate nutrition and growth. Urea kinetic modeling is used to determine dialysis adequacy and is described in detail in Chapter 74. Outcomes of dialysis initiated during the neonatal pediod for treatment of end-stage renal disease: a north american pediatric renal trials and collaborative studies special analysis. Hemodialysis vascular access options in pediatrics: considerations for patients and practitioners. This review outlines the various vascular access options, describes complications associated with each, and caveats regarding placement of access. Guidelines published by the European Pediatric Dialysis Working Group outlining resources required for dialysis as well as variables in the prescription. This review addresses the requirements specific to children and infants requiring renal replacement therapy. In this review, a detailed discussion of vascular access and technical aspects of peritoneal and hemodialysis in children is provided. Narrative review encompassing all aspects of care for the child with end-stage renal disease. This includes recommendations regarding vascular access and treatment of infections, as well as evidence that children who undergo more frequent dialysis than thrice weekly demonstrate improved control of anemia, mineral and bone disorders, hypertension, and fluid status as well as improved growth and nutrition. Despite this increased focus on dialysis adequacy in children, limited data on long-term outcomes of dialyzed children continue to exist, especially analyzed in the context of certain standards of adequacy. They specify that because of limited specific pediatric data, many recommendations are based on extrapolation from the much broader experience in adults. Unfortunately, many outcome measures looking at dialysis adequacy in adults are focused on narrowly assessing mortality rates or specific organ system morbidity over time and do not consider clinical variables of special import to assessing the adequacy and effectiveness of renal replacement therapy in children. Moreover, as the child grows, the prescription must be reformulated cognizant of ongoing changes in total body water and evolving nutritional requirements.

Syndromes

• Have noticed any change in urine color?
• Using light waves to view the retina (optical coherence tomography)
• Cap the container. Keep it in the refrigerator or a cool place during the collection period. Label the container with your name, the date, the time of completion, and return it as instructed.
• Blood pressure
• Widened (dilated) vessels in the clear tissue covering the white of the eye
• Muscle cramps
• Making sure the person gets enough calories, to prevent low blood sugar and promote growth
• Pregnancy

K/V is the fractional clearance erectile dysfunction drugs patents generic forzest 20mg on line, which can be easily calculated from the exponential fall in concentration during dialysis erectile dysfunction generics cheap forzest 20 mg with amex. The reason for targeting urea clearance erectile dysfunction caused by obesity purchase generic forzest line, as explained in Chapter 19 erectile dysfunction pills for sale best order forzest, is the success of dialysis itself erectile dysfunction age young order forzest 20mg online, which removes small erectile dysfunction causes high blood pressure generic forzest 20mg with amex, easily dialyzed solutes like urea almost exclusively. A perhaps disappointing conclusion from the above logic is that we can accurately measure the life-saving effect of dialysis but we have poor measurements of the uremic state itself, the target of dialysis. Current and future efforts to identify the causes of each aspect of uremia can extend knowledge about the syndrome with the promise to develop additional specific treatments. Classification of Uremic Toxins Several excellent reviews of suspected and confirmed uremic toxins have appeared in the literature and are periodically updated. The reader is referred to these comprehensive reviews listed at the end of this chapter for further information. Today, well over 200 retained compounds have been identified; most but not all are easily removed by therapeutic dialysis. Solutes in both categories are tagged as "uremic" when measured serum concentrations are significantly higher than concentrations found in people without kidney disease. Classification as a toxin, however, requires both a higher concentration than normal and a demonstration of toxicity using a variety of in vivo and in vitro methods. For solutes that accumulate but are poorly dialyzable, demonstration of toxicity is especially critical since failure of removal by dialysis despite recovery from uremia implies a lack of toxicity. Some of these solutes may contribute, however, to the subacute residual syndrome discussed above. The latter diffuse easily across dialyzer membranes in free form, but overall removal is impeded by substantial binding to serum macromolecules, principally albumin. Small Water-Soluble (Dialyzable) Solutes Except for urea, the guanidino compounds shown in Table 18. All are derived from the metabolism of the amino acid arginine, and all are found in the serum, cerebrospinal fluid, and brain, where they may have significant neurologic toxicity, contributing to encephalopathy and polyneuropathy by a variety of suspected mechanisms, including interference with amino acid receptors and neurotransmitters, demyelination, and oxidative injury. Symmetric and asymmetric dimethylarginine have also been shown to cause vasoconstriction by inhibiting nitric oxide. In vitro and in vivo animal studies have focused on the neuroexcitatory properties of the guanidine compounds, alluding to seizures that are occasionally seen in patients suffering from advanced uremia. But as a whole and perhaps in concert, the guanidine compounds may be the most important contributors to the severe life-threatening aspects of uremia that are reversed by dialysis and appears to be without permanent sequelae in most patients. Of course many drugs and vital cofactors as well as hormones exert their effects at very low concentrations, so toxicity is not ruled out simply because the substance is present in tiny amounts. Larger Solutes (Molecular Weight > 500 Da) Larger less-well-dialyzed solutes likely contribute to the residual syndrome, but the magnitude of their contribution is debated. However, rigorous controlled clinical trials designed to show a benefit of these methods, using B2M (molecular weight 11,800 Da) as a surrogate, have been disappointing at best. The observation that older cellulosic membranes that had an absolute molecular weight cutoff of ~10,000 Da did not remove larger molecules including B2M but successfully reversed advanced life-threatening uremia demonstrates the greater importance of small solutes as perpetrators of the uremic syndrome. Accumulation and polymerization of B2M causes dialysis-related amyloidosis, a complication of both hemodialysis 2. Data were adjusted for demographic factors and multiple other potential confounders at baseline. In several studies of high- versus low-flux membranes, secondary analyses of patient subgroups (diabetic kidney disease, low serum albumin concentrations, longer dialysis vintage) suggest a benefit, but overall mortality rates have not been improved by either high-flux dialysis or hemofiltration. Perhaps future more sophisticated separation techniques will be able to identify a toxic fraction in the larger-molecular-weight spectrum that will justify removal efforts. Protein-Bound Solutes Binding to macromolecules lowers the concentration of the free, presumably toxic fraction, which is also the driving force for diffusion across dialysis membranes. Several are indoles derived from gut-derived bacterial action on tryptophan, and 0. In contrast to urea levels, which average about 4 times the concentration in normal compared to patient serum, the concentration of some protein-bound solutes can reach as high as 100 times the concentration found in people without kidney disease. Nearly all of the binding occurs relatively loosely to albumin, the most abundant and widely studied circulating protein. Serum albumin has several nonspecific binding sites to accommodate a variety of ligands, most notably fatty acids and bilirubin, but also the amino acid tryptophan, and a variety of drugs including salicylate and phenytoin. Accumulation in patients with kidney failure shows that native kidneys eliminate them, but since binding limits filtration, elimination is primarily by tubular secretion, which also favors solutes with nonpolar moieties. Passage through the renal peritubular capillaries releases the ligands most likely by pure diffusion across the huge capillary surface area followed by active transport across the tubular basement membrane. The robust anionic and cationic transporters positioned in the basolateral membranes of the proximal tubule puzzled investigators in the past who postulated a need to eliminate very toxic substances. More likely they serve to maintain a low but continuous concentration gradient across the capillary membranes. The rate of dissociation from albumin far exceeds the transport rate, so the removal rate can be substantial. All are >90% bound to serum albumin and have demonstrated toxicity in vivo and in vitro. These include indoles that derive mostly from degradation of tryptophan but also from degradation of phenylalanine and tyrosine by intestinal bacteria, particularly colonic Escherichia coli. Hemodialysis patients with a previous colectomy have much lower serum concentrations of indoles as well as hippurate, methylamine, and dimethylamine. As noted above, dialysis caregivers today encourage protein-energy intake to maintain nutrition, assuming that the toxic byproducts of protein intake are removed by dialysis, which also improves appetite. Outcome studies also show lower survival Uremic Toxicity 257 rates in patients with low protein intakes. However, in more recent times, restricting protein intake as well as use of prebiotics and probiotics has re-emerged as a method to reduce the availability of substrate for production of potential uremic toxins by intestinal microflora. By quantitatively reducing the generation of the most abundant bound solutes, the binding of other ligands, some of which may be very toxic, is shifted to the left, reducing their toxicity indirectly by enhancing their binding. Sequestered Solutes Sequestered solutes are usually small and easily dialyzed but their removal by dialysis is impeded by delayed diffusion within body compartments. All solutes exhibit this property, including urea, which has the least sequestration. During dialysis, concentrations of solutes other than urea fall more rapidly because the solute is extracted from a relatively small dialyzed compartment that equilibrates slowly with remote compartments. The dialyzed compartment in most cases is the extracellular or intravascular compartment, and the remote compartment is often the intracellular space. The behavior of sequestered solutes during hemodialysis has been used to explain the inefficiency of intermittent dialysis. Solute profiles coincide with those predicted by the peak concentration hypothesis (see Chapter 19, Urea Kinetic Modeling for Guiding Hemodialysis Therapy in Adults), which adds support for the concept of standard Kt/V, a measure of dialysis that attempts to express the dose as a continuous equivalent measurement. A familiar example of solute sequestration is seen in the kinetics of serum phosphorus during hemodialysis. Other solutes show a similar larger rebound than urea but not as large as phosphorus. If the critical uremic toxins behaved like phosphorus, dialysis would not be successful, because adequate removal of phosphorus requires supplemental treatment with oral phosphate binders. Sequestration of otherwise easily dialyzed drugs like digoxin explains the inability of dialysis to reverse the toxicity of digoxin and similar sequestered compounds. Markers of Uremic Toxicity: Role of Urea Identifying a marker toxin has been the holy grail of investigators for more than a century. The required properties of a marker solute that can reliably denote the severity of uremic toxicity are listed in Table 18. To qualify, its accumulation must depend on native kidney function for elimination, and levels must correlate with other toxins and their toxicity. Because of the latter requirement, it is unlikely that concentrations of a single compound would apply at all times to all individuals. Because the concentration of retained solutes depends on both their generation and elimination, it would be necessary to monitor the levels of each toxin on a frequent basis to tailor the dialysis for control of each. The required frequency of measurement would depend on the toxin generation rate, which could vary from time to time and from patient to patient. Focus on just one toxin might leave some of the others at toxic levels if the generation rates differ. Today, lacking such a compound, clinicians rely on measurements of solute clearance. The horizontal lines represent the upper and lower boundaries for serum phosphate concentrations in normal people. Because of the last requirement, probably no one single substance would qualify as ideal. Urea is a poor candidate for a marker of uremic toxicity, as it fails to meet all of the requirements listed in Table 18. In past experiments, when urea was added to the hemodialysate to prevent its removal, recovery from uremia still occurred. Normal kidneys apparently do not consider urea very toxic either, because they reclaim most of it by reabsorption along the tubule and use it as a medullary osmotic Uremic Toxicity 259 agent to assist with water conservation. Elasmobranchs, such as sharks, have also employed urea as an osmotic agent to combat the rising salinity of the oceans, often achieving concentrations in their blood over 1000 mg/dL, without apparently suffering any harmful toxicity. Other easily dialyzed solutes such as creatinine or cystatin-c could be used to measure dialyzer clearance, but urea happens to be available in high concentrations and is easily measured by all clinical laboratories. Role of Salt and Water Accumulation Fluid accumulation is not an essential feature of the uremic syndrome but frequently accompanies it. If urine output matches input, patients may progress to an advanced stage of uremia or even succumb to it without accumulating fluid. Conversely, restoration and maintenance of fluid balance are not enough to reverse uremia, so it must be considered as adjunctive therapy, albeit a vital one in most patients. Accumulation of fluid is increasingly recognized as a major component of the residual uremic syndrome, contributing to hypertension, peripheral and pulmonary edema, ventricular hypertrophy, and congestive heart failure. Adverse Effects of Dialysis It is important to distinguish the residual syndrome from the potential adverse effects of dialysis listed in Table 18. For example, nephrologists have become increasingly aware of myocardial and cerebral ischemia caused by excessively rapid ultrafiltration during hemodialysis. The resulting myocardial and cerebral stunning can be exacerbated by warm dialysate and hemoconcentration because of overzealous treatment with erythropoiesis-stimulating agents. Medication side effects are especially important to anticipate and detect because, in the absence of native kidney function, higher levels are achieved that persist longer in the blood and tissues. In theory, uremia-induced renal toxicity would generate a vicious cycle of renal damage leading to more renal damage. Although initial efforts met with success, a recent controlled clinical trial designed to prevent this damage in humans with oral charcoal sorbents to reduce the absorption of gut-derived toxins has failed to show a benefit. The native kidney eliminates filtered foreign substances by simply ignoring them as they flow through the renal tubules and are washed into the urine. The vital constituents of the plasma filtrate such as glucose and amino acids are recovered by active reabsorption during transit through the renal tubule. Therapeutic dialysis attempts to accomplish this feat by nonselective diffusion against a dialysate that contains the vital blood components, a much less efficient but effective method that involves a theoretical risk of depleting unidentified vital solutes. Amino acid losses are substantial but fortunately represent a small fraction of the usual daily intake generated from dietary protein. However, when kidney function is restored by transplantation, even welldialyzed patients report significant improvements in well-being, despite the need for immunosuppression. Release from the burden of dialysis, the euphoric effect of glucocorticoids, and the restoration of a normal or near normal hemoglobin level may be more important to the sense of well-being than solute removal, especially in the past when higher doses of steroids were given and pretransplant anemia was more severe. Other possible benefits provided by the transplanted organ include endocrine and paracrine secretions and continuous volume control, which avoids the dialysis-induced abrupt shifts in blood pressure and tissue perfusion noted above. Restoration of tubular secretion may also assist with removal of protein-bound toxins as discussed above. Other effects of dialysis such as fluid removal, endotoxin adsorption, and large molecule clearance cannot be given credit for this life-sustaining effect of dialysis, although they may add measurably to the long-term benefit. They can be removed effectively by prolonging the treatment or by increasing its frequency to allow for the slow transport into the blood compartment from remote locations in the body. Short infrequent treatments require supplemental methods, usually by intestinal adsorption, to remove phosphate and prevent long-term accumulation that may eventually be life threatening. The removal of protein-bound solutes can be augmented by increasing the dialyzer membrane surface area, analogous to the first (diffusional) step in their removal by native kidneys across the huge peritubular capillary surface. Other methods with demonstrated efficacy for removing protein-bound solutes include increasing the dialysate flow relative to blood flow Table 18. Experimental methods include separation and extraction of or discarding plasma proteins as well as addition to the blood of nontoxic competitive inhibitors of binding. Removal of protein-bound solutes by dialysis is not affected by membrane pore size and is minimally affected by convective filtration. Effect of Residual Kidney Function the remnant kidney contributes measurably to removal of uremic toxins, perhaps more so than is apparent to the patient and clinician. Even very low clearances, in the range of 0 to 3 mL/min appear to afford much longer survival, an observation that has prompted efforts to preserve renal function after initiating dialysis. For protein-bound toxins, the effect is magnified by the contribution of renal tubular secretion, a supplemental purging mechanism that could account for the survival advantage. Data adjusted for age, primary kidney disease, comorbidity, subjective assessment of quality of life, and body mass index.

Although this may be as simple as an Internet-enabled camera erectile dysfunction meds list generic forzest 20 mg, this communication may be as complex as to involve a remote robot erectile dysfunction melanoma forzest 20 mg otc, with the ability to "see" the patient and gather some vital information impotence in young males buy forzest us, through the use of a remote microphone erectile dysfunction exercises purchase 20 mg forzest otc, stethoscope impotence with condoms buy forzest 20 mg on line, and so on chlamydia causes erectile dysfunction proven 20mg forzest. The central nephrologist reviews streaming data or real-time data at the central site. Because these patients have much less frequent direct contact with their caregivers today, there is a significant opportunity for remote monitoring to identify instances when interventions from caregivers may improve the overall health of patients and ultimately prevent hospitalization episodes or other adverse events. As capabilities are developed to leverage these existing connectivity points, this has the potential to significantly reduce the cost of delivering telemedicine to these patients, which strengthens the business case for broader adoption. Other Miscellaneous Use Cases Other use cases for teledialysis include building trust with high-risk patients, follow-up on missed rounding because of schedule or timing conflicts, discussion of and review of medications (including viewing medication and bottles), updated history and physical examinations, and reviewing future appointments. Because of legal and compliance restrictions, video interactions may be limited to credentialed caregivers. Integrated Kidney Care (Global Capitation) Use Case the goal of integrated care is to improve the quality of patient care at lower cost. Telemedicine can be a helpful tool in this model to improve the efficiency of care delivery while retaining or improving outcomes through increased and immediate access. Typically, dialysis centers are not credentialed to provide additional services; however, centers in the future may provide patients with multiple rounding consultations while receiving their dialysis 1124 Application of Telemedicine to Patients With End-Stage Renal Disease treatment. Given the significant comorbidities that exist with dialysis patients and the transportation challenges for many patients, the dialysis center of the future could be a one-stop shop for comprehensive patient care. Teledialysis Technology Requirements Technology changes so quickly that best practice recommendations quickly go out of date. That said, constant change and increased investment in telemedicine technology is much more of an opportunity for teledialysis than a concern, including improved bandwidths and connections, new technologies, and increased access to smartphones. There are foundational elements that will likely be a necessary part of teledialysis in the coming years. For example, tablets cost significantly less, take up less space, and may be easier to manage in more confined treatment areas at many inpatient centers. Rounding "robots" may be useful in hospital settings because of their mobility, but they require significant upfront costs and may be cumbersome to store, maintain, and upgrade. Video A video link is preferred and can be integrated or delivered by split monitor. Installation should preferably be one camera per dialysis station with the ability for the nephrologist or data access technician to focus in on a specific station on his or her screen. This may be facilitated by the use of in-ceiling or camera microphones to allow the originating site to communicate with the receiving central monitoring site to facilitate two-way communication. Other Digital hardware is advancing rapidly, which will give physicians more control rather than fully relying on clinic teammates. As an example, consider the use of digital stethoscopes that connect through the video conferencing software without additional software required. Dialysis Machine Data Teledialysis requires a clear understanding of how the needed data elements will flow from remote to originating site. Dialysis Machine Data At present, there is an absence of consistency in the data format that can be streamed from various dialysis machines. This results in the need for a custom interface for each type of dialysis machine. Solving this issue as a dialysis community is important for large-scale implementation and adoption of teledialysis. Dimensions of this data model include mandatory and optional date fields, unified field names with crosswalk to each machine type, and the frequency of data transmission. Although reacting to alarms is a local clinic responsibility, it may be beneficial to have the alarms centrally monitored in a remote monitoring application. A sample minimum data set for dialysis data streaming may include the following: 1. Lowest blood flow rate Nontechnology Teledialysis Requirements Policy and Procedures Given the complexity of the medical and regulatory parameters that govern the use of teledialysis, it is crucial to have a solid set of policies and procedures to ensure success. Essential policies and procedures include a scope of service template, a Application of Telemedicine to Patients With End-Stage Renal Disease 1127 quality review policy template, a physician credentialing policy template, a chairside physician communication policy template, and a complaint response policy. Given that regulations around scope of practice and telemedicine are country and even state specific, proper attention toward the appropriate regionalization of these policies and procedures is critical. Documentation is another regulatory aspect that requires formalized evaluation and description. The first is consultative only; it includes no documentation other than the originating site stating that it contacted the central nephrologist. Although either may be acceptable, the second is preferable to ensure continuity of care in a patient centric informatics environment. Program Management and Implementation A proper program management framework is critical to program success. This can be done by highlighting how teledialysis can improve the efficiency and effectiveness of their work, improve clinical outcomes, or save time. Having participating nurses comfortable with the technology and pilot testing is key to ensuring that nurses are motivated to keep patient adherence high, especially when it comes to patient compliance with remote monitoring data. This could include dedicated and detailed support to supervise nurses, ensure adherence, and answer challenges nurses face during rollout, which helps increase the viability and sustainability of the program. Engaged physicians who are excited about testing new technology for patient care, especially if there are reimbursement hurdles 4. This should include one dedicated staff member responsible for data collection and liaising with hospitals to ensure collection of admissions data. The project manager is ideally responsible for collecting and publishing monthly data on specific types of hospitalizations, readmissions, and patient churn. The project manager may need to be supplemented with a technical representative who makes sure remote monitoring patients are installing and using the devices properly. To ensure that any investment in telemedicine is worthwhile, it is important to measure success. At least one member of the remote dialysis unit should be trained in the facile operation of the equipment. Nurses need to be trained in the types of issues that may or may not be amenable to teledialysis. Nephrologist training includes training on the technology system as well as training on documentation. Examples of Teledialysis in Use Today the concept of teledialysis is not theoretical. For example, the DaVita Colombia dialysis clinics are testing a teledialysis system to allow remote dialysis clinics to be connected and monitored by a centrally located nephrologist. As a result of this innovative new approach, patients can avoid having to travel great distances to receive dialysis. Another example is in Scotland, where a satellite dialysis unit is monitored from a central hospital. One of the oldest programs for teledialysis exists in the northern reaches of Finland, where remote rural units are monitored from a central university hospital using video and other communications media. Conclusions As the number of dialysis patients increases and the number of nephrologists continues to be rate limiting, teledialysis has the potential to allow nephrologists to continue to care for patients in multiple settings. In implementing a teledialysis program, it is fundamental to have a clear understanding of the local regulations and the technology and nontechnology requirements. The most common use cases for teledialysis can then be mapped against these requirements to ensure that the program is successful. Future efforts to standardize dialysis streaming and other data sets will continue to improve the efficiency and efficacy of teledialysis toward the goal of improving the lives of patients with renal disease. The empirical foundations of telemedicine interventions for chronic disease management. Impact of telemedicine on health care resource utilization (emergency department visits, hospital admissions and readmissions, length of stay, and mortality rates) for chronic conditions. Telestroke, tele-oncology and teledialysis: a systematic review to analyse the outcomes of active therapies delivered with telemedicine support. A systematic review of the literature for telemedicine for rural patients for stroke, medical oncology, and nephrology. Telerheumatology: diagnostic accuracy and acceptability to patient, specialist, and general practitioner. Acceptability and accuracy of telemedicine visits televisual to patients, general practitioners, and specialists. Telemedicine in haemodialysis: a university department and two remote satellites linked together as one common workplace. Description of teledialysis between the University Hospital of North Norway and two rural satellite dialysis units. Conceptual framework and overview of a study for the use of telemedicine for home dialysis. Effectiveness of school-based telehealth care in urban and rural elementary schools. Recent Developments in the Definition and Official Names of Virus Species 5 can do so. When the only necessary and sufficient property for belonging to any taxon is descent from a common ancestor, it has been suggested16 that descent may have become the new essence of the antiessentialists. Since a classification is only a conceptual construct, taxa will be considered to be real individuals only when concepts are conflated with their referents. The major shortcoming of bionominalism is that it fails to distinguish between species as concrete entities and species as abstract entities, that is, it does not distinguish a thing from its conceptual representation. It is also possible to conceive and establish classes of objects that exist on Earth for only limited amounts of time, and species are clearly such classes. The class of paintings belonging to the French impressionist school is an example of a class with a historical dimension. As argued by Mahner and Bunge,7 there is indeed good evidence that the mistaken ontology underlying bionominalism is responsible for its inability to provide an adequate philosophical framework for any biological classification. The Virus Species Problem the term species is used to denote the lowest category in a virus classification. Although viruses are not alive,17 they are considered to belong to biology, and as such they are classified using the categories species, genus, family, and order employed in biology. In the case of genera and families, virologists readily accept that these categories are conceptual constructions of the mind, which should not be confused with real objects, since a virus family, for instance, cannot be purified, centrifuged, sequenced, or visualized in an electron microscope. Concepts such as virus species, on the other hand, are often viewed as more "real" than genera and families because they tend to be perceived as individual kinds of viruses infecting particular hosts. Some philosophers claim that concepts and objects can both "exist" because of the ambiguity of the term "exist. Darwin regarded the species category to be no more real than the categories genus and family, and his unwillingness to argue over the definition of species has been called a modern solution to the species problem. A popular textbook of plant virology28 proposed that "virus species are strains whose properties are so similar that there seems little value in giving them separate names. Another definition proposed that "A virus species is a population of viruses sharing a pool of genes that is normally maintained distinct from gene pools of other viruses,"29 which was also deemed unsatisfactory because many viruses are replicated entirely by clonal means and do not possess gene pools. In 1989 the following definition was proposed: "A virus species is a polythetic class of viruses that constitute a replicating lineage and occupy a particular ecological niche. It also incorporated the notion of a shared ecological niche31 used by Mayr in his species definition, which is a relational, functional property of an organism or a virus rather than a vacant space waiting to be occupied. It should be stressed that the term polythetic only describes a particular distribution of properties present in a class and that the members of a class do not themselves possess polythetic or monothetic properties (see Section 7). Likewise, being a genetic parasite or having a vector is a property of viruses and not of classes. A concept such as a species class cannot have physical or material properties since only its members do. This means that species cannot be described but can only be defined by listing certain properties of their members. Individuals 1e4 constitute a polythetic class, each member possessing three of four properties with no common property being present in all the members. Individuals 5e6 and 7e8 form two monothetic classes with three properties present in all the members From Van Rijsbergen K. This misunderstanding led to a never ending debate about the presumed usefulness of a species definition for creating new species taxa and identifying their members (see Sections 5 and 7). It was also claimed that virus species could be defined monothetically by features of their gene sequences, and this led to the proposal that the term polythetic should be removed from the species definition. Properties Used for Defining Virus Species and Identifying Individual Viruses Properties are possessed by things and objects and cannot be detached from them. Intrinsic properties (or characters), such as chemical composition, are possessed regardless of other things whereas relational properties, such as being a genetic parasite or being vector-borne, are possessed by virtue of the relation of a virus to other things, such as a host or a vector. This distinction is important because not all predicates represent properties of real things. A thing either possesses property P or does not possess it, but it cannot possess the property "not P" since there are no negative properties. However, for every predicate, there is another predicate that is the negation of the first. Negation for instance may affect the proposition "tapeworms think" but not the property of thinking. Taxa are defined intensionally by sets of properties that provide the qualifications for membership in the class. The intension of a concept such as class is its meaning that, however, does not give it any reality outside the realm of intellectual constructions.

The typical Western diet has a high phosphate content impotence herbal remedies cheap 20 mg forzest fast delivery, which comes from dairy products and protein sources erectile dysfunction treatment south africa buy discount forzest 20mg online. Since protein energy malnutrition is highly prevalent in patients on chronic dialysis erectile dysfunction treatment toronto forzest 20mg without a prescription, we generally do not recommend dietary protein restriction erectile dysfunction female doctor purchase cheapest forzest. In general erectile dysfunction medications causing 20mg forzest with amex, animal protein has higher phosphorus bioavailability compared to plant protein erectile dysfunction medication online pharmacy purchase forzest 20 mg otc. Foods with a high phosphate load include nuts, hard cheeses, egg yolk, meat, poultry, and fish. Plant protein, especially grains, have a lower phosphate-toprotein ratio because most of the phosphate is in the form of phytate, which is not absorbed. Phosphorus in the form of phosphate salts (phosphoric acid, pyrophosphate, polyphosphate, and phosphate) is used in industrial food processing as food preservatives and as a color or flavor enhancer. Inorganic phosphate salts from the additives are almost completely absorbed in the gastrointestinal tract. Phosphorus additives are common and the amount of phosphorus load is considerable compared to the phosphorus content in natural food. Leon et al reviewed the food labels of ~2400 best-selling branded grocery products and found that 44% of these grocery items contained phosphorus additive-prepared frozen food (72%), dry food mixes (70%), packaged meat (65%), bread and baked goods (57%), and yogurt (51%). It can be challenging to limit dietary phosphate intake because many foods contain phosphorus. It is crucial to differentiate the source of phosphorus, choose plant protein over animal protein, and to avoid foods with phosphorus-containing additives. The degree of mineral loss (calcium, phosphorus, sodium, and potassium) is proportional to the cooking time, amount of boiling water, and the size of the pieces. Oral phosphate binders limit the absorption of dietary phosphate and include calcium-containing and non-calciumcontaining binders. Calcium-containing binders are less costly compared to noncalcium-containing binders, but they may result in a positive calcium balance and vascular calcification resulting in higher cardiovascular mortality. The impact of calcium load from calcium-containing binders on vascular calcification is greater in the presence of adynamic bone disease. Aluminum-containing binders are no longer used because of aluminum toxicity, which can manifest as dementia, osteomalacia, anemia, and arthritis. Ferric citrate appears comparable to sevelamer in terms of phosphorus control and supplies iron, which may help to maintain hemoglobin levels. Because of the hypocalcemic effect of calcimimetics and the risk of symptomatic hypocalcemia, calcimimetics should not be started if serum calcium is <8. In the unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events. Subsequent subgroup analysis showed that cinacalcet decreased the risk of death and major cardiovascular events in older, but not younger, patients on hemodialysis. Vitamin D therapy should not be started until serum phosphorus has been controlled (<5. There have been no prospective studies demonstrating that the use of vitamin D or its analogs has any effect on cardiovascular mortality. Optimal Dialysis Prescription Phosphate is distributed unevenly in various compartments of the body with only a small amount in the plasma compartment and the majority in muscles, cell walls, and bone. Although hemodialysis can effectively remove phosphate, transferring of phosphate from these spaces to the plasma is relatively slow. Standard hemodialysis (4 hours per treatment) removes approximately as much phosphorus as is absorbed in a single day. Phosphate clearance can be improved through increasing the frequency of the dialysis treatments. Several studies have shown that patients undergoing short daily or nocturnal dialysis had better phosphorus control and required lower dose of phosphate binders. Besides use of calcium-containing binders and vitamin D, a high dialysate calcium concentration also contributes to positive calcium balance in patients on hemodialysis. They found calcium balance was positive with all dialysate calcium concentrations and increased progressively with a higher dialysate calcium bath. Once the bone becomes fully mineralized, the additional calcium contributes to calcification in soft tissue such as arterial media. Management of this complex disorder includes lowering dietary phosphate intake, administration of phosphate binders, use of calcimimetics, vitamin D, and appropriate dialysis treatments. Using the data from the United States Renal Data System, this article describes the incidence and relative risk of hip fractures in patients on dialysis. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. The prevalence of phosphorus-containing food additives in top-selling foods in grocery stores. This study determines the prevalence of phosphorus-containing food additives in best-selling processed grocery products and compares the phosphorus content of a subset of top-selling foods with and without phosphorus additives. Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Relationship between moderate to severe kidney disease and hip fracture in the United States. Uncorrected and albumin-corrected calcium, phosphorus, and mortality in patients undergoing maintenance dialysis. Despite a global heightened awareness of the causes and consequences of elevated serum phosphate and in spite of advances in therapeutic interventions targeting this mineral disorder, only modest progress has been made toward routinely achieving the international recommendation of a "normal" P level of <4. Effective control requires thoughtful attention to all aspects of phosphate homeostasis including diet, dialysis prescription, control of secondary hyperparathyroidism, and individualized prescription of medication to reduce intestinal phosphate absorption. Phosphate Physiology Phosphorus is the second most abundant element in the human body after calcium. Approximately 85% of phosphorus is located in bones and teeth, 14% is intracellular, and only 1% is extracellular. This represents the net balance of daily dietary intake, intestinal absorption, skeletal influx/efflux, cellular redistribution, and urinary phosphate excretion. These estimates however are now suspected to substantially underestimate actual phosphorus intake because of the routine use of phosphate additives in food processing. Substantial quantities of phosphate in the form of additives have now been reported in commonly prescribed medications and common beverages as well. Foods high in phosphate are typically those also high in protein and include dairy products, meats, eggs, and cereal; however, the bioavailability of meat-based phosphate far exceeds that of plant-based phosphate because of the lack of naturally occurring phytase in the human gastrointestinal tract. Intestinal absorption of phosphate is greatest in the jejunum and ileum and occurs passively via a paracellular route and actively via a phosphate sodium-dependent cotransporter (NaPi-2b). Basal phosphate absorption is a linear, nonsaturable function of oral intake that is normally approximately 70% of ingested; however, this may go up or down with NaPi-2b regulation by diet or active vitamin D. Phosphate binder therapy affects only the passive, nonregulated component of P absorption, a finding likely underlying the similar clinical efficacy of all available treatments. These adverse effects are complementary yet distinct from those seen with elevations in serum phosphate, which is universally recognized to accelerate the development of vascular calcification and subsequent arterial stiffening. Phosphate Binder Therapy Although elevated phosphate levels are consistently associated with adverse outcomes in multivariable adjusted analyses, there are no randomized controlled trials demonstrating clinical benefit with their use. It remains undetermined if the current practice pattern of prescribing phosphate binders is associated with net benefit or harm, particularly when one considers that mean achieved phosphate remains at or above 5. Several observational studies have reported survival benefits associated with phosphate binder use (independent of serum phosphate) although these are quite susceptible to bias inherent among dialysis patients who do not require phosphate binders. A variety of agents have been used to create poorly soluble phosphorus complexes in the intestinal lumen and in doing so limit passive phosphate absorption. These agents include aluminum salts, calcium salts, magnesium salts, nonabsorbed polymers, and most recently iron-containing compounds. As expected, gastrointestinal side effects are particularly common with intestinal phosphate binders. Heavy Metal Compounds Aluminum salts are highly effective phosphate binders, independent of pH. Unfortunately, despite limited total systemic absorption, clinical experience from the 1980s demonstrated that long-term use results in dementia, encephalopathy, microcytic anemia, and profound osteomalacia. Thus, in the United States, aluminum salts typically are used only as short-term therapy when other means of controlling phosphate have failed. Calcium-Based Compounds After the discovery of the detrimental effects of aluminum-based binders, calciumbased binders became the most commonly prescribed phosphate binders and, in many parts of the world, remain so today. Calcium carbonate and calcium acetate are widely available, relatively inexpensive, and effective at reducing serum phosphate. However, they have a lower affinity for phosphorus compared with aluminum compounds and hence require larger doses with increased number of pills in order to achieve a satisfactory control of phosphate. In addition, they may provide a large calcium load, particularly if coadministered with concomitant active vitamin D compounds. Although current recommendations suggest limiting total daily calcium intake to 1500 mg/day (estimating 500 mg/day from the diet), few data exist to support this target. It is well known that serum calcium levels are effectively maintained within the normal range despite wide variation in calcium intake (low or high) and calcium balance (positive or negative). Despite the low cost and widespread availability of calcium-containing binders, they have not significantly improved phosphorus control in patients receiving dialysis over the past two decades. Additionally, they increase the calcium burden, increase the risk of hypercalcemia, and are associated with the development of calcific uremic arteriopathy (formerly known as calciphylaxis). Although it is unclear whether the effect on mortality is mainly driven by one specific compound, calcium-free phosphate binders reduce the risk of all-cause mortality by 22% when compared to calcium-containing phosphate binders (risk ratio 0. It is for these reasons that it is our opinion that calcium-based phosphate binders should be considered third-line therapy for the control of serum phosphate. It is unclear based on available data if there is any "safe" dose of exogenous calcium. This synthetic ion-exchange polymer is as effective as calcium-containing binders and is generally well tolerated, with an adverse event profile similar to placebo. Its major drawbacks are the large pill burden, gastrointestinal side effects, and high cost. In a different study, sevelamer use significantly attenuated coronary artery calcification progression in patients new to hemodialysis when compared to calcium-based binders. It remains to be seen whether alternative, non-calcium-containing phosphate binders have similar aggregate benefits. Cost and pill burden remain significant obstacles from a global and individual patient perspective. Magnesium-Based Binders There is a resurgence of interest in using magnesium salts as potential alternatives to calcium given the inverse association between magnesium and cardiovascular events in the general population and data suggesting that magnesium may have a protective role with regard to vascular calcification. In general, magnesium-based phosphate binders are less potent than most calcium salts and can have significant systemic absorption resulting in increased serum magnesium levels, although a recent observational study has demonstrated that mortality in dialysis patients is highest among those with the lowest serum magnesium. Although the use of magnesium-free dialysate to help avoid hypermagnesemia in the setting of administration of magnesium salts is poorly tolerated, low magnesium dialysate concentrations of 0. Recently, combination magnesium carbonate (60 mg elemental magnesium)/calcium acetate (110 mg elemental calcium) has been approved for hyperphosphatemia management after it was demonstrated to have similar clinical efficacy to other phosphate binders with similar tolerability. Interestingly, this combination magnesium/calcium P binder has been shown to reduce (favorably) the serum propensity to calcify when measured ex vivo. Experimental and clinical data support the notion that magnesium carbonate/ calcium acetate effectively lowers serum phosphate and may attenuate vascular calcification progression as well as improve the bone and cardiovascular risk profile. Iron-Based Therapy Awareness of the risks associated with calcium-based phosphate binders has hastened the development of alternative treatment options. It has been recognized for many years that iron-based compounds could effectively bind phosphate, and two such compounds have recently been approved for the reduction of phosphate in patients on dialysis. Sucroferric oxyhydroxide was demonstrated to be as effective in reducing serum P as compared to active control (primarily sevelamer and calcium) but with a substantially reduced pill burden of <4 pills/day. Tolerability was comparable to active control, with the obvious exception of dark stools common to all iron preparations. Ferric citrate was also compared to active control over a 52-week trial period and demonstrated equivalent P control while simultaneously increasing iron saturation and ferritin. Tolerability was again comparable to active control although there were significantly fewer serious adverse events, including a reduced hospitalization for cardiovascular, infectious, and gastrointestinal reasons. Future Therapies Several new or repurposed compounds are being investigated as future phosphatereducing treatments. Nicotinamide is a nicotinic acid derivative (and component of niacin) that in a rat model has been found to inhibit sodium-dependent phosphorus cotransport via the NaPi-2b transporter located in the intestinal brush border membrane. Recently, it has been reported that a non-absorbed inhibitor of the sodium-hydrogen exchanger type 3 (tenapanor) was effective in reducing intestinal sodium and phosphate absorption in healthy volunteers whereas animal data supported a positive effect on attenuating the development of vascular calcification. Phase 1 clinical trials with tenapanor in dialysis patients confirmed the efficacy of this novel compound to reduce serum phosphate when given twice daily unrelated to meals.

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