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Patients treated with maintenance dialysis are at high risk of polypharmacy given their many comorbidities as well as complications from their disease state and treatment. The prescribing patterns and burden of polypharmacy in patients treated with maintenance dialysis, and specifically the difference between hemodialysis (HD) and peritoneal dialysis (PD) prescribing, are not well characterized.The objectives of this study were to review the prescribing patterns for patients treated with maintenance dialysis, to compare prescribing pattern between HD and PD, and to identify opportunities for deprescription.This is a retrospective cohort study.This study was conducted in all dialysis centers in British Columbia, Canada.Patients who were receiving chronic dialysis (120 days on the same dialysis modality) between June 3 and October 1, 2015, and registered in the British Columbia (BC) Renal Patient Records and Outcomes Management Information System.Patient demographics as well as both prescription and non-prescription medications were collected. Comparison of discrete and continuous variables was made by chi-square analysis and independentMedications were classified by indication: (1) management of renal complications, (2) cardiovascular (CV) medications, (3) diabetes medications, or (4) management of symptoms, and then classified as to whether they were a "potentially inappropriate medication" (PIM) or not. Ethics approval was granted from the University of British Columbia Research and Ethics Board.In total, 3017 patients met inclusion criteria (2243 HD, 774 PD). The mean age was 66.2 ± 14.8 years. The HD group had more patients over 80 years old (22.1% vs 12.5%) and more patients with diabetes and CV disease. The mean number (standard deviation [SD]) of discrete prescribed medications was 17.71 (5.72) overall with more medications in the HD group versus the PD group. The mean number of medications increased with dialysis vintage in both groups. HD patients were on more medications for renal complications and management of symptoms than PD patients. Of the total number of medications prescribed, 5.02 (2.78) were classified as a PIM, with the number of PIMs higher in HD vs PD patients: 5.37 (2.83) versus 4.02 (2.37).In BC, some of the medications are prescribed through standardized protocols and may not be comparable with other Canadian provinces. We report here prescribing patterns, not utilization patterns, as we are not able to ascertain actual consumption of prescribed medication.This study reviews and characterizes both the prescription and non-prescription medication prescribed to HD patients and PD patients in BC. Pill burden in both groups is high, as is the prescription of PIMs. Patients receiving maintenance HD receive more overall medications and more PIMs. These results highlight areas of opportunities for future systematic and patient-informed deprescription initiatives in both patient groups.Les patients sous dialyse à long terme, en raison de leurs nombreuses comorbidités et des complications inhérentes à leur état de santé et à leur traitement, s’exposent à un plus grand risque de polypharmacie. On en sait toutefois peu sur le fardeau qu’elle représente pour ces patients et sur leurs profils de prescription, particulièrement sur les possibles différences entre les patients traités par hémodialyse ou par dialyse péritonéale.Comparer les profils de prescription des patients traités par hémodialyse (HD) et par dialyse péritonéale (DP), et cerner les possibilités de déprescription.Étude de cohorte rétrospective.Tous les centres de dialyse de la Colombie-Britannique (Canada).Les patients sous dialyse chronique (plus de 120 jours avec la même modalité) entre le 3 juin et le 1Les caractéristiques démographiques des patients et la liste des médicaments, prescrits ou non. Une analyse du chi-carré (variables discontinues) et un test t indépendant (variables continues) ont été employés pour comparer les différentes variables. Tous les tests statistiques étaient bilatéraux. Une valeur de P inférieure à 0,05 a été jugée significative.Les médicaments ont été classés par indication : (1) traitement des complications rénales, (2) contre les maladies cardiovasculaires (3) contre le diabète et (4) traitement des symptômes. Ils ont ensuite été classés comme étant ou non un « médicament potentiellement inapproprié » (MPI). L’approbation déontologique a été octroyée par le comité d’éthique de la recherche de l’Université de la Colombie-Britannique.Un total de 3 017 patients, dont l’âge moyen était de 66,2 ± 14,8 ans, satisfaisaient les critères d’inclusion (2243 HD, 774 DP). Le groupe HD comportait davantage de patients âgés de plus de 80 ans (22,1 % contre 12,5 %) et de patients souffrant de diabète et de maladies cardiovasculaires. Le nombre moyen de prescriptions (écart-type) s’élevait à 17,71 (5,72) avec des nombres globaux plus élevés dans le groupe HD. Le nombre moyen de médicaments augmentait avec le temps passé en dialyse dans les deux groupes. Les patients HD prenaient davantage de médicaments pour traiter les symptômes et les complications rénales que les patients DP. Dans l’ensemble, une moyenne de 5,02 (2,78) médicaments ont été classés MPI, et leur nombre était plus élevé dans le groupe HD que dans le groupe DP (5,37 [2,83] contre 4,02 [2,37]).En C.-B., certains médicaments sont prescrits selon des protocoles standardisés, et ceci pourrait ne pas être comparable aux autres provinces canadiennes. L’article présente des profils de prescription et non des schémas de prise de médicaments, car nous ne pouvions vérifier la consommation réelle des médicaments prescrits.Cette étude examine et caractérise les médicaments sous ordonnance et en vente libre qui sont prescrits aux patients britanno-colombiens traités par HD et DP. La charge médicamenteuse est élevée dans les deux groupes, de même que le nombre d’ordonnances de MPI. Les patients traités par HD se voient prescrire davantage de médicaments et de MPI. Ces résultats montrent que des initiatives de déprescription systématiques et informées sont possibles pour ces deux groupes de patients.

Objective To develop a list of renal Quality Indicator Drug therapy problems (QI-DTPs) that serve to advance renal pharmacy practice to improve patient care. Methods Eighteen (18) renal, clinical pharmacists participated in an internet-based three-round modified Delphi survey. Each of the three rounds took approximately 2 weeks to complete. Panellists rated 30-candidate renal QI-DTPs using seven selection criteria and one overall consensus criterion on a nine-point Likert scale. Consensus was reached if 75% or more of panellists assigned a score of 7–9 on the consensus criterion during the third Delphi round. Key findings All panellists completed three rounds of Delphi survey. Seventeen-candidate renal QI-DTPs met the consensus definition. Conclusions A Delphi panel of renal clinical pharmacists successfully identified 17 consensus renal QI-DTPs. Assessment and implementation of these QI-DTPs will serve to advance renal pharmacy practice and improve patient care.

An important aspect of malnutrition is deficiency of different micronutrients during pregnancy or early childhood. We systematically reviewed the role of nutrition in child growth (weight or height gain) and development.A comprehensive literature search was done on PubMed/Cochrane Library browsing through 38,795 abstracts until December 31, 2016 to select systematic reviews/meta-analyses and individual randomized controlled trials (RCTs) of micronutrient supplementation.Micronutrients studied included iron, iodine, folate, zinc, calcium, magnesium, selenium, vitamin D, vitamin A, vitamin B complex, and multiple micronutrients. We summarize evidence with details and results of RCTs, highlight strengths/weaknesses, and critically interpret findings. Effects of breastfeeding-promotion, food-supplementation (complementary and school feeding), conditional-cash-transfers, and integrated nutrition/psychosocial interventions are discussed.Based on this evidence we make policy and programmatic recommendations for supplementation to mothers and children at high-risk of deficiency.

Background Immunosuppression (IS) is the main treatment for most types of glomerulonephritis (GN). Quantifying the cost of IS is necessary to ensure equitable access to therapies and optimal health outcomes, but the real-world cost of IS treatment for GN is largely unknown. We examined temporal changes in the population-level IS medication costs for GN over a 14-year period in a large Canadian province. Methods We linked a provincial pathology database (containing all GN cases from 2000 to 2012) with renal and medication administrative databases to capture clinical characteristics and IS medications, with follow-up until 2013. The primary outcome (mean IS medication cost per treated patient each year) was evaluated for trends over time. Results The cohort included 2983 GN patients followed for a mean of 5.7 years. The yearly per-patient medication cost increased 6.8-fold from $205 to $1394 (P

Physical and psychological symptom burden in patients with advanced chronic kidney disease (CKD) is significantly debilitating; yet, it is often inadequately treated. Legalization of cannabis in Canada may attract increasing interest from patients for its medical use in refractory symptom management, but its indications and long-term adverse health impacts are poorly established, creating a challenge for clinicians to support its use. In this review, we summarize key clinical studies and the level of evidence for nonsynthetic cannabinoids in the treatment of common symptoms encountered in advanced stages of CKD, including chronic pain, nausea and vomiting, anorexia, pruritus, and insomnia.Medline and Embase.A search was conducted in MEDLINE and EMBASE (inception to March 1, 2018) on cannabis and CKD symptoms of interest, complemented with a manual review of bibliographies. Studies that examined synthetic cannabinoids that are manufactured to mimic the effects of ∆9-tetrahydrocannabinol such as dronabinol, levonantradol, nabilone, and ajulemic acid were excluded. We focused on studies with higher level of evidence where available, and quality of studies was graded based on the Oxford Centre for Evidence-based Medicine Levels of Evidence (1a to 5).Based on studies conducted in patients without renal impairment, those treated with nonsynthetic cannabinoids were 43% to 300% more likely to report a ≥30% reduction in chronic neuropathic pain compared with placebo. However, there is currently insufficient evidence to recommend nonsynthetic cannabinoids for other medical indications, although preliminary investigation into topical endocannabinoids for uremia-induced pruritus in end-stage renal disease is promising. Finally, any benefits of cannabis may be offset by potential harms in the form of cognitive impairment, increased risk of mortality post-myocardial infarction, orthostatic hypotension, respiratory irritation, and malignancies (with smoked cannabis).Nonsynthetic cannabinoid preparations were highly variable between studies, sample sizes were small, and study durations were short. Due to an absence of studies conducted in CKD, recommendations were primarily extrapolated from the general population.Until further studies are conducted, the role of nonsynthetic cannabinoids for symptom management in patients with CKD should be limited to the treatment of chronic neuropathic pain. Clinicians need to be cognizant that nonsynthetic cannabinoid preparations, particularly smoked cannabis, can pose significant health risks and these must be cautiously weighed against the limited substantiated therapeutic benefits of cannabis in patients with CKD.Les symptômes physiques et psychologiques ressentis par les patients souffrant d’insuffisance rénale chronique (IRC) sont particulièrement débilitants, et souvent traités inadéquatement. La légalisation du cannabis au Canada pourrait susciter un intérêt croissant chez ces patients avec l’emploi médical de cette substance pour le traitement de ces symptômes. Cependant, les indications thérapeutiques du cannabis et ses effets nocifs sur la santé à long terme sont mal connus, rendant difficile son soutien par les cliniciens. L’article présente l’état des preuves et une synthèse des principales études cliniques portant sur l’usage des cannabinoïdes non synthétiques dans le traitement des symptômes fréquemment observés aux stades avancés de l’IRC, soit la douleur chronique, les nausées, les vomissements, l’anorexie, le prurit et l’insomnie.Medline et Embase.On a procédé à une recherche dans MEDLINE et EMBASE (de leur création jusqu’au 1Des études menées chez des patients non atteints d’insuffisance rénale montraient que les sujets recevant des cannabinoïdes non synthétiques étaient 43 à 300 % plus susceptibles de rapporter une réduction d’au moins 30 % de la douleur neuropathique chronique comparativement aux sujets recevant un placebo. Mais pour l’heure, les preuves permettant de recommander les cannabinoïdes non synthétiques à d’autres fins médicales sont insuffisantes; quoique des résultats préliminaires soient prometteurs avec les endocannabinoïdes topiques dans le traitement du prurit provoqué par l’urémie en contexte d’IRC. Cependant, tout bienfait du cannabis pourrait se voir neutralisé par de potentiels effets nocifs tels que troubles cognitifs, risque accru de mortalité après un infarctus du myocarde, hypotension orthostatique, irritation des voies respiratoires ou tumeurs malignes (dues à l’inhalation).Les préparations de cannabinoïdes non synthétiques employées dans les études retenues étaient très variables, les échantillons étaient faibles et les études de courte durée. En absence d’études menées en contexte d’IRC, les résultats présentés sont principalement extrapolés d’une population générale.Jusqu’à ce que d’autres études soient menées, l’utilisation des cannabinoïdes non synthétiques chez les patients atteints d’IRC devrait se limiter au soulagement des douleurs neuropathiques chroniques. Les cliniciens doivent comprendre que les cannabinoïdes non synthétiques, particulièrement lorsqu’ils sont inhalés, comportent des risques significatifs pour la santé et que ceux-ci doivent être examinés avec prudence en regard des bienfaits thérapeutiques limités du cannabis chez les patients atteints d’IRC.

British Columbia has a unique funding model for renal care in Canada. Patient care is delivered through six health authorities, while funding is administered by the Provincial Renal Agency using an activity-based funding model. The model allocates funding based on a schedule of costs for every element of renal care, excluding physician fees. Accountability, transparency of allocation and tracking of outcomes are key features that ensure successful implementation. The model supports province-wide best practices and equitable care and fosters innovation. Since its introduction, the outpatient renal services budget has grown less than the population, while maintaining or improving clinical outcomes.

BACKGROUND AND OBJECTIVES Patients with intestinal failure (IF) require parenteral nutrition (PN) support to obtain enough nutrients to sustain growth; long-term PN use is associated with significant liver damage. The aim of this study was to analyze the use of a noninvasive test, the aspartate aminotransferase to platelet ratio index (APRI), in the diagnosis of liver disease in pediatric patients with IF. METHODS Medical records of all Boston Children's Hospital patients who received PN and underwent a liver biopsy from January 2006 until November 2010 were reviewed. Patients with IF with a clinical diagnosis were selected. APRI was calculated as (aspartate aminotransferase [U/L]/upper normal limit) × 100/platelets (10(9) cells/L). Presence of fibrosis and cirrhosis was estimated using the METAVIR score in liver biopsies. RESULTS Sixty-two liver biopsies from 48 patients (22 girls) were studied. Mean APRI values in the different METAVIR categories (0-1, 2-3, 4) were 1.80, 1.17, and 4.24, respectively (analysis of variance P = 0.053; Bonferroni test for cirrhosis vs fibrosis P = 0.048). APRI could significantly predict cirrhosis (odds ratio 1.2; 95% confidence interval [CI] 1.001-1.43) but not fibrosis (METAVIR 2-3, odds ratio 1.00; 95% CI 0.86-1.18). Area under the receiver operating characteristic curve for cirrhosis was 0.67 (95% CI 0.45-0.89; P = 0.13). CONCLUSIONS APRI, a noninvasive, easy-to-obtain bedside test, significantly predicts cirrhosis but not fibrosis in pediatric patients with IFALD. Because the clinicians need a noninvasive test to differentiate among different stages of liver fibrosis rather than differentiating cirrhosis from normal, we cannot recommend the use of this test in pediatric patients with IFALD for this purpose.

Serum citrulline concentration is used as a biomarker of enterocyte mass and enteral tolerance, and low serum concentrations are correlated with bacteremia in immunosuppressed adults undergoing hematopoietic stem cell transplant. The authors sought to determine if citrulline was associated with the development of catheter-related bloodstream infections (CRBSIs) in children with intestinal failure.Data were reviewed from 66 children treated in a multidisciplinary intestinal rehabilitation program, who had serum concentration citrulline measured between January 2007 and August 2009. All patients had a diagnosis of intestinal failure requiring parenteral nutrition (PN) support. Exclusion criteria included central venous catheter in situ30 days, creatinine clearance20 mL/minute, or a history of organ transplant/immunosuppression.A total of 15 patients were excluded because of the above criteria. In this cohort of 51 patients, 26 (51%) developed CRBSIs. Both groups were similar in terms of gestational age, diagnosis, nutrition status, and biochemical liver function tests. The mean (± standard deviation [SD]) minimum serum citrulline concentration was significantly lower in patients who developed CRBSIs (6.7 ± 4.6 µmol/L) than in those who did not (11.3 ± 6.4 µmol/L, P = .004). Multivariate logistic regression analysis identified lower minimum serum citrulline concentration and longer central venous catheter duration as independently associated with CRBSI (P = .003 and P = .038, respectively).Low serum citrulline concentration and longer central venous catheter time are independently associated with CRBSI in children with intestinal failure. Serum citrulline concentration may be a useful biomarker to identify patients with intestinal failure who are at high risk of developing a CRBSI.

Background Parenteral nutrition-associated liver disease (PNALD) is a serious condition affecting many children with short bowel syndrome. The aim of this study was to longitudinally assess serum alanine aminotransferase (ALT), a marker for hepatocyte injury, in enterally fed children with PNALD. Methods Retrospective chart review of 31 patients treated from 1999 to 2006 by the Center for Advanced Intestinal Rehabilitation at Children's Hospital Boston (Mass). Inclusion criteria included PN duration of greater than 3 months with subsequent tolerance of full enteral nutrition and evidence of PN-associated liver injury. Time to normalize ALT and direct bilirubin were estimated using Kaplan-Meier and Cox proportional hazards methods. Results Mean age PN cessation was 6 months (range, 2-14 months). Median PN duration was 18 weeks (interquartile range [IQR], 13-33 weeks), and median follow-up was 24 weeks (IQR, 14-48 weeks). After transition to full enteral nutrition, 74% of children normalized direct bilirubin, whereas only 50% normalized ALT. Kaplan-Meier median time to direct bilirubin and ALT normalization were 13 weeks and 35 weeks, respectively (P = .001). Conclusion Children with PNALD who have achieved PN independence have persistent ALT elevation despite normal direct bilirubin levels. This implies that hepatic injury may be ongoing beyond the time of bilirubin normalization in this cohort of patients.

A patient with Wilms' tumor and severe failure to thrive required total parenteral nutrition (TPN) for "catch-up" growth. This case underscores how TPN might be useful in the management of a child with cancer. Cancer cachexia, chemotherapy, radiation, and infections caused by immune suppression can lead to potentially serious macro- and micronutrient deficiencies.

Pediatric short bowel syndrome (SBS) remains a management challenge with significant mortality. In 1999, we initiated a multidisciplinary pediatric intestinal rehabilitation program. The purpose of this study was to determine if the multidisciplinary approach was associated with improved survival in this patient population.The Center for Advanced Intestinal Rehabilitation includes dedicated staff in surgery, gastroenterology, nutrition, pharmacy, nursing, and social work. We reviewed the medical records of all inpatients and outpatients with severe SBS treated from 1999 to 2006. These patients were compared to a historical control group of 30 consecutive patients with severe SBS who were treated between 1986 and 1998.Fifty-four patients with severe SBS managed by the multidisciplinary program were identified. Median follow-up was 403 days. The mean residual small intestinal length was 70 +/- 36 vs 83 +/- 67 cm in the historical controls (P = NS). Mean peak direct bilirubin was 8.1 +/- 7.9 vs 9.0 +/- 7.4 mg/dL in controls (P = NS). Full enteral nutrition was achieved in 36 (67%) of 54 patients with severe SBS vs 20 (67%) of 30 patients in the control group (P = NS). The overall survival rate, however, was 89% (48/54), which is significantly higher than in the historical controls (70%, 21/30; P.05).A multidisciplinary approach to intestinal rehabilitation allows for fully integrated care of inpatients and outpatients with SBS by fostering coordination of surgical, medical, and nutritional management. Our experience with 2 comparable cohorts demonstrates that this multidisciplinary approach is associated with improved survival.

Objective We discuss 26 y of home parenteral nutrition (HPN) in an otherwise healthy patient with severe short bowel syndrome demonstrating a decrease in life-threatening complications after various management changes. Methods The patient is a 41-y-old male with a midgut volvulus from malrotation who developed short bowel syndrome and has been HPN dependent since the age of 15 y. His surgical and nutritional data were collected retrospectively and prospectively and included nutritional history, anthropometric parameters, laboratory results, activity levels and types, and treatments for complications. His entire HPN course has been prospectively followed. Results Since becoming HPN dependent, the patient’s energy intake range has been 20–45 kcal · kg −1 · d −1 , with 0.8–1.6 g of protein · kg −1 · d −1 . He receives HPN with electrolytes, multivitamins, and trace elements nightly and his intravenous fat emulsion ranges from one to seven times per week. Adjustments to magnesium, iron, zinc, selenium, vitamin E, and carnitine are often required. During his first years of HPN, he had six episodes of catheter-related sepsis and two central venous catheter occlusions. The current central venous catheter has been in place for >13 y without infection or replacement. He developed mild osteopenia but has maintained an active lifestyle without fractures. In the second and third decades of HPN, episodes of hepatic dysfunction occurred, with improvement or resolution using various interventions including oral fish oil. Conclusion This case illustrates the successful management of a life-long HPN-dependent patient in whom PN complications have been minimized, including a very recent occurrence of parenteral nutrition–associated cholestasis.

Glomerulonephritis (GN) is a common cause of end-stage renal disease in Canada and worldwide, and results in significant health care resource utilization and patient morbidity. However, GN has not been a traditional priority of provincial renal health care organizations, despite the known benefits to health services delivery and patient outcomes from integrated provincial care in other types of chronic kidney disease. To address this deficiency, the British Columbia (BC) Provincial Renal Agency created the BC GN Network in 2013 to coordinate provincial GN health services delivery informed by robust population-level data capture on all GN patients in the province via the BC GN Registry. This report describes the use of the BC GN Network infrastructure to systematically develop and evaluate a provincial GN drug formulary to improve patient and physician access to evidence-based immunosuppressive treatments for GN in a cost-efficient manner that successfully halted historical trends of increasing medication costs. An example is provided of using the provincial infrastructure to implement and subsequently evaluate an evidence-informed health policy of converting brand to generic tacrolimus for the treatment of GN. The BC GN Network, including the provincial drug formulary and data infrastructure, is an example of the benefits of expanding the mandate of provincial renal health administrative organizations to include the care of patients with GN, and constitutes a viable health delivery model that can be implemented in other Canadian provinces to achieve similar goals.La glomérulonéphrite (GN) est une cause courante de néphropathie terminale à l’échelle canadienne et mondiale. Elle est liée à une forte exploitation de ressources en santé et à un taux de morbidité élevé. La GN demeure toutefois négligée par les organismes provinciaux en santé rénale, bien que les effets bénéfiques d’un système de soins provincial intégré sur la prestation des services et l’état de santé des patients soient démontrés dans le cas d’autres types de néphropathie chronique. Pour combler cette lacune, la

Parenteral nutrition has been used with success for the past two decades. In pediatrics, parenteral nutrition has been shown to improve nitrogen balance and growth. However, controversies exist including indications, requirements, duration, outcomes, and costs of parenteral nutrition in the pediatric population. This review provides a brief summary of current indications for pediatric parenteral nutrition and requirements for intravenous nutrients. Guidelines outlined by the American Society for Parenteral and Enteral Nutrition for the pediatric patient are also presented.

Aim: Chronic intestinal pseudo-obstruction has been associated with urinary disorders, myopathy, and ophthalmoplegia in adults and cholelithiasis in children. We observed a high percentage of total-parenteral-nutrition-dependent patients with pseudo-obstruction and recurrent infections requiring gammaglobulin infusions. Methods: All records for 23 children with chronic intestinal pseudo-obstruction (10 females and 13 males, mean age 9.8 y ± 4.9 y, range 4-24 y) referred for a nutritional evaluation from 1992 to 1995 were reviewed. Chronic intestinal pseudo-obstruction was diagnosed by clinical, radiographic findings and antroduodenal manometry. Intestinal full-thickness biopsies were performed in seven children. Results: Hypogammaglobulinemia was diagnosed in 18 patients (78%): 16 patients had various immunoglobulin deficiencies and 2 had selective antibody deficiency. Intravenous gammaglobulin was administered in 14 patients. Other medical conditions affecting the children are summarized as follows: autonomic dysfunction in 10 patients (43%), recurrent hypoglycemia in 9 (39%), asthma in 9 (39%), cholecystitis in 7 (30%), low serum carnitine level in 6 (26%), urinary dysfunction in 6 (26%), pancreatitis in 5 (22%), behavioral problems in 5 (22%), myopathy in 2 (9%), idiopathic thrombocytopenia in 2 (8%), velopharyngeal insufficiency in 1 (4%), oculocutaneous albinism in 1(4%), Pierre-Robin syndrome in 1 (4%), and protein C deficiency in 1 (4%). Munchausen syndrome was suspected in two patients. Conclusions: Chronic intestinal pseudo-obstruction appears to be associated with immune deficiencies. It is unclear if the immune deficiencies, intestinal pseudo-obstruction, and the other medical conditions have a common underlying etiology. Repeated infections may be due to impaired immune function in children with chronic intestinal pseudo-obstruction. We recommend screening for immune deficiencies in children with chronic intestinal pseudo-obstruction. Children, gut, immunity, motility disorders, parenteral nutrition.

Parenteral nutrition is an expensive therapy that is often necessary in certain situations, such as short-bowel syndrome. In many other conditions, its efficacy remains controversial. Providing optimal parenteral nutrition can be particularly challenging in premature infants while managing metabolic and catheter complications. Use of special nutrients, glutamine, and growth hormone may have benefits in the nutritional management of premature infants and trauma patients. Metabolic complications of parenteral nutrition such as cholestasis might be reduced by early enteral feedings, ursodeoxycholic acid, and cholecystokinin-octapeptide. Trace-element deficiencies may still occur, and thus patients must be monitored carefully. Methods that have been used to prevent or reduce catheter occlusion or infection include heparin, oral anticoagulants, antibiotics, and thrombolytic agents such as urokinase and tissue plasminogen activator.

Cholestasis often occurs in infants on total parenteral nutrition (TPN) for long periods. Amino acid formulations developed specifically for infants, namely Aminosyn PF and Trophamine, may protect against cholestasis associated with total parenteral nutrition (CATPN). The development of cholestasis may also be caused by other risk factors such as prematurity, surgery, sepsis, and extracorporeal membrane oxygenation (ECMO). To evaluate the relative effectiveness of the pediatric amino acid formulations in reducing CATPN, the courses of 70 infants or = 2 mg/dl subsequent to the initiation of TPN; CATPN was considered present when other factors related to cholestasis were ruled out. Liver function tests were recorded 24 h before starting TPN and at day 7, 15, and 21 during TPN infusion. Thirty infants (42.8%) developed cholestasis. CATPN was judged to have occurred in 15 (21.4%) of 70 infants, while 15 (21.4%) developed cholestasis secondary to other factors. Of the 15 CATPN patients, 7 had received Trophamine, 6 had received Aminosyn PF, and 2 had received both solutions. Aminosyn PF and Trophamine, along with other potential risk factors for CATPN such as antecedent surgery, sepsis, ECMO, prematurity, and nitrogen/calorie intake were analyzed by regression-analysis methods. None was statistically significant except the length of TPN (p = 0.0063). In conclusion, we cannot support the view that Trophamine is more effective than Aminosyn PF in the prevention of CATPN.

Inborn errors of metabolism are disorders caused by genetic defects that produce problems in normal metabolic processes. [1] Although each single gene disease is relatively rare, many more diseases have had their genetic basis elucidated because of recent research into the human genome. In a normal metabolic pathway, a substrate is converted into a product in a chemical reaction catalyzed by an enzyme, sometimes helped by a coenzyme. A genetic mutation producing a defective enzyme or cofactor is usually responsible for these diseases. Signs and symptoms of these disorders may appear due to the accumulation in blood or in other tissues of the substrate, to the production of toxic metabolites because of the use of alternative metabolic pathways, or to the lack of the final product. They result from variations in the structure and function of enzymes or other proteins. The aim of treatment is to correct the biochemical abnormality and may include the following

We sought to determine whether a regimen of 70% ethanol locks could reduce the rate of central venous catheter (CVC) infections in parenteral nutrition-dependent children with intestinal failure.We performed a retrospective review of 23 parenteral nutrition-dependent children in our multidisciplinary intestinal rehabilitation clinic who started ethanol lock therapy between September 2007 and June 2009. The treatment regimen consisted of a 70% ethanol lock instilled 3 times per week in each catheter lumen. The rate of CVC infections before and after initiation of ethanol lock therapy was compared using the Wilcoxon signed ranks test with significance set at P.05.The most common diagnoses leading to intestinal failure were necrotizing enterocolitis (26.1%), gastroschisis (21.7%), and intestinal atresia (14.3%). Ethanol locks were well tolerated with no reported adverse side effects. The infection rate decreased from 9.9 per 1000 catheter days prior to initiation of ethanol locks to 2.1 per 1000 catheter days during therapy (P = .03).A regimen of ethanol lock therapy administered three days per week appears to be a safe and effective means of reducing the rate of CVC infections in parenteral nutrition-dependent children with intestinal failure.

The extent to which secondary hyperparathyroidism may involute remains poorly defined. Renal transplantation offers a clinical situation in which metabolic stimuli for hyperparathyroidism are removed. To examine whether hyperparathyroidism resolves after transplantation, we evaluated 11 renal transplant recipients who had been normocalcemic 6 or more months after transplantation using a sensitive 2-site immunoradiometric assay for intact serum PTH. Nine of the 11 had PTH concentrations within the normal range. Of these 9, 6 were found to have abnormal parathyroid function when challenged with an iv calcium infusion. The other 2 patients demonstrated significantly elevated basal PTH concentrations and elevated ionized calcium despite normal total serum calcium and albumin concentrations. In both, the PTH response to infused calcium was markedly abnormal, confirming hyperparathyroidism. The estimated renal threshold phosphate concentration was low in 4 of 9 patients with normal basal PTH concentrations and in both with elevated basal PTH. Bone mineral density, measured at the radius by single photon absorptiometry and at the spine by dual energy x-ray absorptiometry, was normal in 8 of the 9 transplant recipients who had normal basal PTH concentrations.

A 74-year-old woman with end-stage renal disease presented with clinical symptoms of encapsulating peritoneal sclerosis 2 years after switching from peritoneal dialysis to haemodialysis. Imaging revealed a large cystic structure in her abdomen and her final diagnosis was made by exploratory laparotomy. A 10 cm×15 cm fibrous rind was excised from the peritoneum and the patient was subsequently started on tamoxifen 20 mg daily and prednisone 20 mg daily. Given her reduction in clinical symptoms and concerns about the long-term effects of corticosteroids, prednisone was tapered and she remained on tamoxifen monotherapy. 1 year postsurgery, she presented with symptoms of nausea, vomiting and anorexia. A repeat CT of the abdomen confirmed a recurrence of encapsulating peritoneal sclerosis. Prednisone and tamoxifen were restarted at increased dosages of 25 and 40 mg daily, respectively. The patient's symptoms were ameliorated within 2 weeks of drug therapy modification.

Liver dysfunction in children dependent on parenteral nutrition (PN) is well established, and the extent of hyperbilirubinemia has been shown to correlate with morbidity and mortality. The aim of this study was to assess whether increasing provisions of enteral nutrition can improve PN-associated hyperbilirubinemia over time.A retrospective review was conducted on infants in our institution's Short Bowel Syndrome Clinic from 1999 to 2004. Inclusion criteria included PN duration more than 1 month, serum direct bilirubin more than 3 mg/dL while on PN, and tolerance of full enteral nutrition with eventual discontinuation of PN. Paired t tests were used for statistical analyses.Twelve infants were identified with a PN duration of 5 +/- 1 months. Five patients underwent liver biopsy while on PN, and histological evidence of cholestasis was found on all specimens. Peak total and direct bilirubin levels were 10.5 +/- 1.9 and 7.0 +/- 1.6 mg/dL, respectively, and occurred at time of PN discontinuation. Only 2 patients had improvement in serum bilirubin levels before initiation of full enteral nutrition. After initiation of full enteral nutrition and discontinuation of PN, all patients achieved permanent normalization of bilirubin levels by 4 months (P.05) after a 1-month plateau phase. Alkaline phosphatase levels approached reference range within this time but were not significant.These data demonstrate for the first time that although PN-dependent infants can achieve normalization of marked hyperbilirubinemia with enteral nutrition, the improvement in liver function usually begins only after full enteral nutrition is tolerated and PN is withdrawn. These findings support the aggressive weaning of PN to enteral nutrition in infants with short bowel syndrome.

To determine the effectiveness of a clinical practice guideline (CPG) on the use of parenteral nutrition (PN) at a tertiary care pediatric hospital.Review of prospectively collected data on hospital-wide PN use 2 years before and 5 years after the establishment of the CPG. Effectiveness of the CPG was measured as the percentage of PN courses lasting fewer than 5 days and the number of PN starts per 1000 patient days.During the study period, 5745 PN courses were administered. The mean (SD) number of PN starts per 1000 inpatient days was 8.86 (0.78) before the CPG and 9.54 (2.49) afterwards (p = .28). The percentage courses of PN lasting for fewer than 5 days declined from 26.3% before the CPG to 18.4% afterwards (p.0001). A multivariate model confirmed that the rate of short-term PN starts declined after the CPG was issued. The mean (SD) number of PN courses shorter than 5 days in the 2 years before the CPG was 2.33 (0.42) per 1000 patient days versus 1.75 (0.45) in the 5 years after the CPG was instituted (p = .005), which is a 25% decline. The services with the highest volume of PN use showed the most significant decreases in short-term PN use. A cost savings to the hospital of more than $50,000 may have been realized.In a large pediatric tertiary care hospital, a CPG was successfully deployed. CPGs can favorably affect the use rates and costs of parenteral nutrition.

Objective: To determine correlates of clinical outcomes in patients with short bowel syndrome (SBS). Methods: Retrospective medical record review of neonates treated between 1986 and 1998 who met our criteria for SBS: dependence on parenteral nutrition (PN) for at least 90 days after surgical therapy for congenital or acquired intestinal diseases. Results: Thirty subjects with complete data were identified; 13 (43%) had necrotizing enterocolitis, and 17 (57%) had intestinal malformations. Mean (SD) residual small bowel length was 83 (67) cm. Enteral feeding with breast milk ( r = –0.821) or an amino acid–based formula ( r = –0.793) was associated with a shorter duration of PN, as were longer residual small bowel length ( r = –0.475) and percentage of calories received enterally at 6 weeks after surgery ( r = –0.527). Shorter time without diverting ileostomy or colostomy ( r = 0.400), enteral feeding with a protein hydrolysate formula ( r = –0.476), and percentage of calories received enterally at 6 weeks after surgery ( r = –0.504) were associated with a lower peak direct bilirubin concentration. Presence of an intact ileocecal valve and frequency of catheter-related infections were not significantly correlated with duration of PN. In multivariate analysis, only residual small bowel length was a significant independent predictor of duration of PN, and only less time with a diverting ostomy was an independent predictor of peak direct bilirubin concentration. Conclusions: Although residual small bowel length remains an important predictor of duration of PN use in infants with SBS, other factors, such as use of breast milk or amino acid–based formula, may also play a role in intestinal adaptation. In addition, prompt restoration of intestinal continuity is associated with lowered risk of cholestatic liver disease. Early enteral feeding after surgery is associated both with reduced duration of PN and less cholestasis. (J Pediatr 2001;139:27-33)

More than one-third of adult Americans are obese. A major portion of the diseases that cause the highest morbidity and mortality, eg, heart disease, cancer, diabetes, stroke, and hypertension, can be attributed to diet. Yet, despite the demand for more nutrition education, few medical schools have an adequate nutrition curriculum. Many medical schools are reducing the number of lecture hours in favor of problem-based tutorial discussions, so an addition of another mandatory lecture course is not likely. The organization of nutrition as a theme throughout the 4-y medical school curriculum can pull together many hours of nutrition information taught during various courses, eg, biochemistry, physiology, pathophysiology, clinical clerkships, and electives. Emphasis should be placed on the identification of available resources (eg, faculty throughout the medical school and affiliated hospitals, textbooks, research, and clinical experiences) and applied to practical clinical situations so that students are able to identify, assess, and appropriately manage the frequent nutritional problems seen in outpatients and inpatients. Strategies and techniques such as curriculum analysis, computer-aided instruction modules, Internet Web sites, case-based tutorial discussions, use of physician nutrition specialists and dietitians, administratively separate nutrition units, observed structured clinical examinations, and faculty development are listed and discussed in this article.

Background: Central-venous-line infections can be successfully treated with appropriate antibiotics, thus avoiding the need for catheter removal. Based on our experience, vancomycin, gentamicin, piperacillin, ceftazidime, and amphotericin, alone or in combination, are usually administered, pending sensitivity results. This empirical list, however, has never been verified against actual sensitivity results nor has it been tested for cost or efficacy. Methods: Medical records of inpatients on hyperalimentation over 1 year were reviewed. Success rate, therapy duration, and drug acquisition cost and charge were assessed for central-venous-line infections. Antibiotics then were paired and evaluated in terms of charge and efficacy against all microorganisms as determined by sensitivity results. Results: In 500 inpatients receiving hyperalimentation for 9698 patient-days, 8.4 central-venous-line infections/1000 patient-days occurred. Staphylococcus non-aureus, Candida species, Enterococcus faecium, and Staphylococcus aureus predominantly were isolated. Of the infections, 51 (67%) were sensitive to one or more of the initial antibiotics. A 2-week course of antibiotics successfully treated 50 (66%) catheter infections without line removal. Appropriate initial therapy on average reduced treatment duration by 8 to 10 days and drug charges by $400 to $700. Conclusions: Amikacin-vancomycin appears to be the most cost-effective selection for presumed central-venous-line infections, pending sensitivity results, followed by valid alternatives. Lower failure rates are well worth the extra cost in pharmaceutical charges.

In Europe, epoetin subsequent entry biologics (SEBs) have been in use since 2007. Canadian patents of erythropoietin stimulating agents are expiring in 2014, therefore it is predicted that epoetin SEBs will penetrate the Canadian market in the near future.To estimate the economic impact and costs offsets associated with the uptake and use of one or more epoetin SEBs in Canada for the treatment of anemia in chronic kidney disease.A Canada-wide epidemiological-based budget impact analysis was conducted to estimate cost outcomes under two scenarios: with and without the availability of epoetin SEB.The analysis was conducted from the perspective of the Canadian healthcare payer, over a 5-year time horizon from 2015 to 2019.Patients included in the model were those with chronic kidney disease stages 3 to 5, who have renal anemia and require treatment with erythropoietin stimulating agents.Only direct medical costs pertaining to drug acquisition of currently available erythropoietin stimulating agents in Canada were incorporated in the model. Cost of epoetin SEBs, market shares, uptake rates, and other model inputs were estimated from published sources or databases. No discounting of future costs was applied.Based on our analysis, under market phenomena similar to those seen in the Europe and without considering potential switching from originator epoetin to epoetin SEB, we could expect that Canadian adoption of epoetin SEBs could result in $35 million (2013 CAD, year 1) to $50 million (year 5) cost savings annually, with cumulative savings of $221 million after 5 years. In one-way sensitivity analyses, model variables with substantial impact on cost savings were the prevalence of chronic kidney disease and epoetin SEB uptake rates.We did not take into account costs associated with overhead, administration, or adverse events.The advent of SEBs represents an opportunity to relieve financial pressure in our healthcare system. Under the assumption that the efficacy and safety of epoetin SEBs are non-inferior to originator products, we have shown that the adoption of epoetin SEBs can lead to cost savings for the Canadian payer.L’époétine biosimilaire est utilisée en sol européen depuis 2007. Puisque les brevets d’utilisation des agents stimulant l’érythropoïèse (ASE) viennent à échéance en 2014, il est à prévoir que l’époétine biosimilaire, qui est un produit biologique ultérieur, fera son entrée sur le marché canadien dans un avenir rapproché.Estimer l’impact économique et les coûts de compensation qui découlent de l’utilisation d’une ou de plusieurs formes d’époétines biosimilaires, dans le traitement de l’anémie associée à la maladie rénale chronique, au Canada.Une analyse d’impact budgétaire pancanadienne basée sur des données épidémiologiques a été réalisée afin d’estimer les coûts reliés à deux scénarios éventuels: le premier avec époétine biosimilaire sur le marché, et le deuxième sans cette disponibilité.L’analyse a été menée à partir de la perspective du contribuable au système de soins de santé canadien, sur un horizon de cinq ans, soit de 2015 à 2019.Le modèle ne tient compte que des patients atteints d’une maladie rénale chronique de stades 3 à 5, souffrant d’anémie reliée à la maladie rénale, et nécessitant un traitement avec des agents stimulant l’érythropoïèse.Les seuls coûts pris en compte par le modèle sont les coûts médicaux directs découlant de l’achat des agents stimulant l’érythropoïèse disponibles au Canada. Les coûts reliés à l’époétine biosimilaire, les parts de marché, les coûts de compensation, et les autres entrées du modèle ont été estimés à partir de sources publiées ou de bases de données. Aucune actualisation des coûts futurs n’a été estimée.Selon notre analyse, qui ne tient pas compte de la possibilité d’utiliser l’époétine biologique de référence avant de passer à l’époétine biosimilaire, et sous des conditions de marché similaires à celles observées en Europe, l’adoption à l’échelle canadienne de l’époétine biosimilaire pourrait résulter en une économie de 35 millions $ (2013 $ CAN, année 1) à 50 millions $ (année 5) par année, pour une économie cumulative potentielle de 221 millions $ après cinq ans. L’analyse de sensibilités unidirectionnelles montre que la prévalence de la maladie rénale chronique et les coûts de compensation reliés à l’époétine biosimilaire sont les variables du modèle ayant le plus d’impact économique.Nous n’avons pas tenu compte des frais généraux, d’administration, ou découlant d’imprévus.Les produits biologiques ultérieurs peuvent aider à alléger les difficultés financières de notre système de santé actuel. En supposant que l’époétine biosimilaire présente une efficacité et une innocuité qui ne sont pas inférieures à celles des époétines biologiques de référence, nous montrons que l’utilisation de l’époétine biosimilaire peut mener à des économies pour le contribuable canadien.

Infant formulas provide nutritional support to health infants that promotes growth and development equivalent to that in healthy infants fed human milk. Formula-fed infants are not as well protected against infections, and there remain infants whose health, growth, and development may not be supported optimally by either the formulas currently available or human milk. Some infants may be better supported by genetically engineered formulas that contain immunity-enhancing antibodies or antigens. Formulas that contain cytokines promoting epithelial cell growth and integrity may be protective against necrotizing enterocolitis. Formulas containing proteins with genetically excluded allergenic epitopes or formulas with tolerogenic peptides may be useful in treating allergic diseases of suppressing the development of autoimmune disorders later in life. Formulas with genetically engineered biologically active substances might increase the absorption of nutrients in infants with compromised absorption or digestion, enhance host immunity and mucosal integrity, and, potentially militate or protect against the risk of disease.

To document the current prevalence of protein-energy malnutrition compared with that reported from the same institution in 1976.All inpatients of this tertiary-care facility were assessed by anthropometric, laboratory, and clinical nutrition assessment methods in a 1-day cross-sectional survey. The comparison study from 1976 was also a 1-day cross-sectional survey.A tertiary-care facility in Boston, Mass.The entire inpatient population was assessed on a single weekday in September 1992.Prevalence of acute and chronic malnutrition as judged by anthropometric and laboratory data. Data on demographics, admission classification, underlying disease, route of nutrition, and global nutritional status were also assessed.The prevalence of acute protein-energy malnutrition (weight for height) based on the Waterlow criteria was as follows: severe, 1.3%; moderate, 5.8%; mild, 17.4%; and none, 75.5%. The prevalence of chronic protein-energy malnutrition (height for age) was as follows: severe, 5.1%; moderate, 7.7%; mild, 14.5%; and none, 72.8%. Although the prevalence of acute and chronic protein-energy malnutrition was significantly less in 1992 than in 1976 (P = .03 and P.001, respectively), the numbers are still alarmingly high. Children younger than 2 years and older than 18 years and those with chronic medical conditions had a higher prevalence of protein-energy malnutrition. Twenty-four percent of patients had a serum albumin level less than 30 g/L, 34.8% had a total lymphocyte count less than 1.5 x 10(9)/L, and 24.9% had a hemoglobin concentration less than 105 g/L. One fourth of all patients were obese (120% weight for height), with the greatest prevalence in children aged 2 to 18 years.Acute and chronic protein-energy malnutrition remains common in hospitalized pediatric patients in the United States. Important risk factors may be underlying chronic disease, periods of normally rapid growth, and recognized need for nutrition intervention.

Growth in children with congenital heart disease (CHD) is often compromised. For several decades, investigators have tried to identify the factors affecting growth in children with CHD. Cardiac malformations are undoubtedly responsible for malnutrition, which may range from mild undernutrition to severe failure to thrive (FTT). Malnutrition may then significantly undermine the outcome of corrective surgical operations and postoperative recovery. Mechanisms linking CHD to malnutrition may be related either to decreased energy intake and/or to increased energy requirements. Decreased energy intake can involve deficiencies of specific nutrients, or insufficient total caloric intake. Increased respiratory rate accompanying congestive heart failure may be responsible for increased energy requirements. Different types of cardiac malformations and consequent interventions may have different effects on growth and require diverse strategies. Most treatment strategies aim to facilitate “catch-up” growth, providing extra calories and protein that exceed the Recommended Dietary Allowance for age. However, there is no generally accepted set of guidelines that define appropriate caloric intake for catch-up growth. We attempt to identify the most important causes of malnutrition and highlight the most effective nutrition strategies for children with CHD.

Whole-body alanine kinetics were studied using continuous infusions of [15N]-, [3,3,3-2H3]-, [1-13C]-, and [3-13C]alanine tracers in healthy male subjects in the postabsorptive state. Alanine kinetics were highly dependent on the choice of isotopically labeled alanine. Highest rates of alanine flux (mean +/- SE) were obtained with the [3,3,3-2H3]alanine (474 +/- 41 mumol X kg-1 X h-1). [1-13C]- and [3-13C]alanine tracers gave intermediate values (297 +/- 12 and 317 +/- 22 mumol X kg-1 X h-1, respectively). The slowest rates of alanine turnover were measured with [15N]alanine (226 +/- 7 mumol X kg-1 X h-1). These results emphasize the heterogeneous metabolism of different portions of the alanine molecule and the importance of choosing an appropriate alanine tracer for studying different aspects of alanine metabolism.