Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p

The Clinical Pattern of Primary Hyperoxaluria in Pediatric at Queen Rania Abdulla Children Hospital

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Diagnosis Of Sebaceous Lymphadenoma By Fine Needle Aspiration In A Patient With Cowden Syndrome: Case Report And Review Of The Literature

Sebaceous lymphadenoma (SLA) is a rare benign tumor of the salivary gland that commonly arises in the parotid gland in adults. It is rarely diagnosed correctly preoperatively. In addition, to the best of our knowledge, SLA has not been described yet in the literature in association with Cowden′s syndrome (CS). We present an extremely rare case of parotid SLA that was diagnosed preoperatively by fine needle aspiration in a patient with CS

A multiple methods approach to determine adherence with prescribed mycophenolate in children with kidney transplant

AIMS: The aim of the present study was, to use a multiple methods approach, including, for the first time, dried blood spot (DBS) sampling with PopPK interpretation, to assess adherence to mycophenolate in children with kidney transplant. A second aim was to identify patient/parental factors that influenced adherence and to link adherence behaviour to clinical outcomes. METHODS: A convenience sample of 33 children with kidney transplant (≤18 years old) who had been prescribed mycophenolate for at least 3 months were recruited from participating outpatient clinics in the UK and Jordan. Medication adherence was determined via self-report questionnaires, medication refill data from dispensing records, and via mycophenolic acid concentrations in plasma and DBS samples obtained from children during a clinic visit. RESULTS: Through triangulation of results from the different methodological approaches a total of 12 children (36.4%) were deemed to be non-adherent with their prescribed mycophenolate treatment. Logistic regression analysis indicated that non-adherence was significantly associated with the presence of mycophenolate side effects. Poor adherence was positively linked to measures of poor clinical outcomes (hospitalisation and the need for kidney biopsy). CONCLUSIONS: Despite the imperative regarding medication adherence to help prevent organ rejection, a significant proportion of children are not fully adherent with their therapy. Side-effects appear to be an important factor leading to non-adherence. Measurement of mycophenolate in DBS, coupled with the use of PopPK modelling, was a convenient direct approach to assessing adherence in children with kidney transplant and has the potential to be introduced into routine practice

Hypercalcemia, hypercalciuria and nephrocalcinosis in a breast-fed term newborn: A rare presentation

Although hypercalcemia and hypercalciuria are known to occur in breast-fed pre-term infants, to the best of our knowledge, it has never been reported in a term baby previously. We report a term male baby who was followed-up during pregnancy for having bright kidneys, but a follow-up renal ultrasound (US) after birth had revealed normal scan. Laboratory inves-tigations revealed normal serum calcium (Ca), phosphorous (PO 4 ) and alkaline phosphatase (ALP). The baby was being fed by breast milk. Follow-up US two months later showed early nephrocalcinosis along with hypercalcemia and hypercalciuria; by the age of three months, nephrocalcinosis was more extensive and the serum Ca level was more than 12 mg/L with hypercalciuria. Parathyroid hormone (PTH), phosphorous (PO 4 ), ALP and thyroid function tests were all normal. Antenatal history revealed a hypothyroid mother who was maintained on L-thyroxin, calcium and vitamin D supplement during pregnancy. Her blood tests showed normal serum Ca, low PO 4 and elevated PTH. The baby was diagnosed to have hypercalciuria and hypercalcemia secondary to maternal hypophosphatemia (maternal vitamin D deficiency). Breast feeding was stopped and the baby was started on formula, whereby he showed remarkable improvement both for his blood chemistry as well as his hypercalciuria

Pediatric focal segmental glomerulosclerosis in Jordan: A tertiary hospital experience

Our objective is to study the demographical data, clinical course and outcome of children with primary focal segmental glomerulosclerosis (FSGS) in Jordan. A retrospective chart review of patients with a diagnosis of FSGS at a tertiary care hospital from the period July 2010 to July 2016 was conducted. A total of 99 patients were analyzed. The mean age of presentation was 3.71 ± 2.59 years, 66% were male. At presentation, 66.6% of patients were steroid-resistant, 10% had a steroid dependant course and 20.2% had familial FSGS. Cyclosporine was used in 66.6% of children with a response rate of 46.9%. Long-term follow-up showed complete remission in 29.3%, partial remission in 31.3%, end-stage renal disease in 22.2%, and death in 11.1%. There is a high prevalence of familial FSGS in our Jordanian cohort with a high rate of progression to end-stage kidney disease

Asthma Inhalers Sale without Medical Prescription in Riyadh, Saudi Arabia: A Cross Sectional Study

This study aims to quantify the sale of inhalers without a prescription, describe the degree of difficulty for obtaining these inhalers without a prescription and assess if pharmacists educate patients about the correct use of the inhaler. A cross-sectional study of a quasi-random sample of 252 pharmacies stratified by the five regions of Riyadh. Each pharmacy was visited once by two investigators who used simulated patient methodology with governance of good research principles who simulated having a relative with difficulty of breathing due to airborne dust. Asthma inhalers were dispensed without prescription from 181 pharmacies (72%). Of these, 12 % prescribed the inhaler after trying thelevel 1 of demand and 68 % after the third level. Only 31 pharmacists(17%) explained how to use the inhalers. Asthma inhaler could be obtained in Riyadh without a medical prescription or an evidence-based indication with disobedience of pharmacists to educate on the appropriate use of inhalers

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. Diagnosis of PH is often delayed or missed owing to its rarity, variable clinical expression and other diagnostic challenges. Management of patients with PH and kidney failure is also extremely challenging. However, in the past few years, several new developments, including new outcome data from patients with infantile oxalosis, from transplanted patients with type 1 PH (PH1) and from patients with the rarer PH types 2 and 3, have emerged. In addition, two promising therapies based on RNA interference have been introduced. These developments warrant an update of existing guidelines on PH, based on new evidence and on a broad consensus. In response to this need, a consensus development core group, comprising (paediatric) nephrologists, (paediatric) urologists, biochemists and geneticists from OxalEurope and the European Rare Kidney Disease Reference Network (ERKNet), formulated and graded statements relating to the management of PH on the basis of existing evidence. Consensus was reached following review of the recommendations by representatives of OxalEurope, ESPN, ERKNet and ERA, resulting in 48 practical statements relating to the diagnosis and management of PH, including consideration of conventional therapy (conservative therapy, dialysis and transplantation), new therapies and recommendations for patient follow-up