Perspectives and experiences of health care professionals and patients regarding treatments for type 2 diabetes.

BACKGROUND: Several treatment options exist for type 2 diabetes, but little is known about the factors considered by health care providers (HCPs) and patients in Canada in making therapeutic decisions. This study explores perceptions and practices of HCPs and patients related to add-on (i.e., second-line) therapy for type 2 diabetes when initial therapy no longer provides adequate glycemic control. METHODS: HCPs (pharmacists, family physicians, diabetes educators, endocrinologists and nurse practitioners) and patients with type 2 diabetes in Ottawa and Halifax were randomly selected to participate in the study. Phone interviews were conducted with endocrinologists and nurse practitioners and focus groups with the other HCPs and patients. RESULTS AND INTERPRETATION: Sixty HCPs and 14 patients participated in the study. Metformin was consistently reported by prescribers (physicians and nurse practitioners) as the preferred initial therapy. Important factors in choosing second-line therapy (once glycemic control was inadequate with metformin) were antihyperglycemic efficacy, risk of hypoglycemia and weight gain, and long-term safety. Other considerations were cost, insurance coverage and patient preference. There were differences within and between HCP groups in how these other factors were considered and in the perceived advantages and disadvantages of each drug class. Some patients expressed anxiety when second-line agents were prescribed, and others felt poorly informed about treatment options. CONCLUSION: In choosing a second-line therapy for type 2 diabetes, most HCPs placed a high priority on antihyperglycemic efficacy, although there was considerable variability in the relative weight placed on other factors. These findings point to an opportunity for pharmacists to collaborate more actively with other HCPs to ensure that treatment decisions are based on the best available evidence and to educate and involve patients in these decisions.

Bypassing health providers: the quest for better price and quality of health care in Chad.

This paper investigates individuals' bypassing behavior in the health sector in Chad and the determinants of individuals' facility choice. We introduce a new way for measuring bypassing which uses the patients' own knowledge of alternative health providers available to them, instead of assuming perfect information as previously done. We analyze how objective and perceived health care quality and prices impact patients' bypassing decisions. The analysis uses data from a health sector survey carried out in 2004 covering 281 primary health care centers and 1801 patients. We observe that income inequalities translate into health service inequalities. We find evidence of two distinct types of bypassing activities in Chad: (1) patients from low-income households bypass high quality facilities they cannot afford and go to low-quality facilities, and (2) rich individuals bypass low-quality facilities and aim for more expensive facilities which also offer a higher quality of care. These significant differences in patients' facility choices are observed across income groups as well as between rural and urban areas.

Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome. METHODS: A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988-2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFRe), histopathology, type and duration of treatment, and clinical status at final evaluation. RESULTS: 13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 +/- 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 +/- 2.5 and all patients had a normal GFRe. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications - prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 +/- 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 +/- 3.1. The mean GFRe was 127 +/- 57 mL/min/m2. Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive. CONCLUSION: IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.

Clinical spectrum of gross hematuria in pediatric patients.

Although isolated gross hematuria is a disturbing symptom, there have been few studies of this finding in pediatric patients. Therefore, this study was performed to examine the associated symptoms and causes of gross hematuria in children and adolescents who presented with this problem as their major clinical manifestation. It also determined the long-term outcome of patients in whom no etiology was found. A retrospective review was performed on the medical records of 100 consecutive patients referred for evaluation of gross hematuria between 1992 and 1999. The etiology was determined based on standard urinalysis methods, clinical laboratory tests, and imaging studies. Patients with gross hematuria in whom an etiology was not found were followed up through 2001. Of the 100 patient records reviewed, 18 were excluded because the clinical evaluation was incomplete. The remaining 82 patients (59 M: 23 F) had a mean age of 9.2 +/- 5.0 years. Glomerular gross hematuria was found in 24 patients. A cause was found in all of these patients, most commonly immunoglobulin A (IgA) nephropathy (n=13) and Alport syndrome (n=6). Nonglomerular gross hematuria was found in 56 patients, and the most common etiologies were hypercalciuria (n=9), urethrorrhagia (n=8), and hemorrhagic cystitis (n=7). No etiology was found in 26 patients with nonglomerular gross hematuria. No diagnosis was made in the case of 2 patients whose hematuria could not be defined as glomerular or nonglomerular. Telephone follow-up was performed in 18 of these children 4.0 +/- 3.2 years (range: 1-9 years) after the initial evaluation and showed that only 3 of these patients had had recurrences of gross hematuria. They and all of the other patients remained otherwise well. The urinalysis, including microscopic examination, was the most important diagnostic test in a patient with isolated gross hematuria. Nonglomerular problems were more than twice as common as glomerular diseases as a cause of isolated gross hematuria in pediatric patients The distribution of the etiologies of gross hematuria was consistent with previous studies. Although nearly half of the patients with nonglomerular gross hematuria could not be given a diagnosis, their long-term prognosis appeared to be good.

Efficacy of mycophenolate mofetil in pediatric patients with steroid-dependent nephrotic syndrome.

Most patients with minimal change nephrotic syndrome are steroid responsive and tolerate this medication. However, a substantial number of patients relapse frequently and become steroid dependent. These patients often require treatment with alternative immunosuppressive drugs to maintain remission and minimize steroid toxicity. Previous studies have suggested that mycophenolate mofetil is effective in treating these patients. However, there are limited data on the effectiveness of this agent in pediatric patients, specifically those with steroid-dependent nephrotic syndrome. The purpose of this study was to assess the efficacy and safety of mycophenolate mofetil therapy in children and adolescents with steroid-dependent nephrotic syndrome who failed other treatments. A retrospective chart review was performed on all patients with steroid-dependent nephrotic syndrome. Clinical characteristics, laboratory data and the relapse rate were assessed prior to and during mycophenolate mofetil treatment. Twenty-one patients, ages 2-17 years, with steroid-dependent nephrotic syndrome who were treated with mycophenolate mofetil between 2001-2005 were included in this review. The indication for mycophenolate mofetil use was steroid dependence in 17 and steroid toxicity in 4 patients. The mean duration of treatment was 1.0+/-0.5 years (range: 0.2-2.0 years). Patients treated with mycophenolate mofetil had a reduction in relapse rate from 0.80+/-0.41 to 0.47+/-0.43 relapses per month ( P <0.02). Side effects were mild and mostly gastrointestinal in nature. In 1 child, mycophenolate mofetil was discontinued due to varicella infection and not restarted. The findings indicate that mycophenolate mofetil is a useful adjunctive therapy in the treatment of patients with steroid-dependent nephrotic syndrome. It lowers the relapse rate by 40% and is well tolerated by patients with steroid-dependent nephrotic syndrome.

Diagnostic yield of parathyroid hormone testing in children evaluated for hypercalciuria.

Hypercalciuria is a frequent cause of non-glomerular hematuria in pediatric patients. Because hypercalciuria can be secondary to primary hyperparathyroidism, measurement of serum parathyroid hormone (PTH) levels is often performed in children with this urinary abnormality. A retrospective chart review was performed to determine the diagnostic yield of PTH measurements when performed under these clinical circumstances. Over a 30-month period (January 1, 2001 to September 30, 2003), among 31 children who had a PTH determination, the level was elevated in 1 (3%) patient. Based on these findings and the serious nature of untreated primary hyperparathyroidism, serum PTH level should be measured in pediatric patients with newly diagnosed hypercalciuria.

Glomerular permeability activity: prevalence and prognostic value in pediatric patients with idiopathic nephrotic syndrome.

BACKGROUND: A circulating factor that increases in vitro glomerular permeability to albumin (P alb ) has been isolated from patients with recurrence of focal segmental glomerulosclerosis in their renal allografts. The prevalence and prognostic significance of permeability activity has not been examined in children with idiopathic nephrotic syndrome (INS). METHODS: P alb activity level was determined in sera from 26 children with new-onset INS before the initiation of therapy by using an in vitro assay. Permeability factor was considered present if P alb was greater than 0.5. The following clinical and laboratory data for patients were tabulated: demographic information, serum albumin and cholesterol concentrations, calculated glomerular filtration rate, age at disease onset, response to corticosteroid treatment, and long-term outcome. RESULTS: Patients ranged in age from 2 to 18 years, and 19 patients (73%) were male. Mean P alb was 0.45 +/- 0.04 (SEM). P alb in patients with a steroid-responsive course (n = 17) did not differ from that of patients with steroid-resistant disease (n = 9). Percentages with P alb greater than 0.5 did not differ between patients with steroid-responsive and steroid-resistant disease (47% and 33%, respectively). P alb was determined after 41 +/- 5 months in 6 patients with steroid-responsive INS. These patients had normal serum creatinine concentrations, and 4 of 6 patients were in prolonged remission. P alb at the onset of INS before therapy was 0.51 +/- 0.09 (P alb > 0.5 in 2 patients) and was not changed at follow-up (P alb = 0.40 +/- 0.12; P alb > 0.5 in 2 patients). CONCLUSION: Permeability activity, defined as P alb greater than 0.5, is present in pretreatment serum samples from nearly half the children with INS. The presence of permeability activity does not predict clinical response to steroid treatment, renal histopathologic characteristics, or clinical outcome at up to 5 years of follow-up.

Cardiac disease in children with primary glomerular disorders-role of focal segmental glomerulosclerosis.

Anecdotal reports suggest a higher frequency of serious cardiac complications, particularly cardiomyopathy and congestive heart failure (CHF), in children with focal segmental glomerulosclerosis (FSGS). We report the occurrence of cardiac disease in children with FSGS compared with other glomerular causes of primary nephrotic syndrome (NS). A chart review was performed on all patients evaluated at the Schneider Children's Hospital between 1985 and 2003 with a diagnosis of membranoproliferative glomerulonephritis (MPGN), membranous nephropathy (MN), focal global glomerulosclerosis (FGGS), and FSGS. Clinical and demographic data were compiled, specifically whether or not the patient had clinically evident cardiac disease. The blood pressure (BP) and hematocrit in patients with FSGS and chronic renal failure (CRF) (glomerular filtration rate <30 ml/min per 1.73 m(2)) in the 3 months prior to the development of cardiac complications were compared with the values in FSGS patients with CRF but no cardiac complications, and in patients with the other causes of primary NS in whom CRF developed. There were 48 patients with FSGS, 22 with MPGN, 19 with MN, and 4 with FGGS. Cardiac disease occurred in 6 children (mean age 11 years), all with FSGS. Four of these patients were black and 5 were female. CHF occurred in all patients, cardiomyopathy in 4, and left ventricular hypertrophy in 5 patients. There was no significant difference in the BP and the hematocrit levels between the 6 patients with both FSGS and cardiac disease, 3 patients with FSGS and CRF but no cardiac disease, and the 5 patients with the other glomerulopathies in whom CRF occurred ( P>0.1). Our findings suggest that there is a clinical association between FSGS and cardiac disease in pediatric patients. We speculate that the immune mechanism responsible for the development of FSGS may also affect the heart.

Evaluation of failure to thrive: diagnostic yield of testing for renal tubular acidosis.

BACKGROUND: Failure to thrive (FTT) poses a diagnostic dilemma for pediatricians. The kidney disorder that is considered most often is renal tubular acidosis (RTA). However, the prevalence of RTA may be overestimated, leading to unnecessary referrals for subspecialty evaluation. Moreover, preliminary data suggest that venous blood gas (VBG) testing may provide a more accurate measurement of the serum bicarbonate concentration than routine biochemical testing. OBJECTIVE: 1) To compare the results of bicarbonate measurements by using VBG and routine clinical biochemistry methods under a variety of in vitro conditions; 2) to determine the frequency of RTA as a cause of FTT; and 3) to assess the utility of VBG measurement of serum bicarbonate in the clinical assessment of RTA. EXPERIMENTAL DESIGN AND METHODS: In blood samples collected from healthy volunteers, bicarbonate was measured by using a VBG apparatus and a clinical biochemistry analyzer under a variety of in vitro conditions including variation in time until sample processing (0-4 hours), variations in temperature (room temperature versus on ice), addition of sodium fluoride, or addition of heparin. A retrospective chart review was also performed of all children referred to the renal clinic for evaluation of FTT during the 5-year period of 1997 to 2002. The following data were collected for each case: demographic and clinical information and laboratory testing including serum bicarbonate determined by both routine biochemical testing and VBG analysis. Data are reported as mean +/- standard deviation. RESULTS: In the in vitro studies, VBG determination of bicarbonate concentration consistently yielded a value that was 3 to 6 mmol/L higher than routine biochemical analysis regardless of whether the sample was processed immediately or up to 4 hours later, maintained at room temperature or on ice until the measurement was performed, or the sample tube contained sodium fluoride or heparin. Thirty-six children were referred to exclude a renal etiology of FTT with a presumptive diagnosis of RTA in all cases. The patient group was comprised of 16 males and 20 females whose ages ranged from 4 to 156 months (mean: 27 +/- 33 months). The serum bicarbonate concentration determined by biochemical testing was 18 +/- 4 mmol/L, whereas the bicarbonate level by VBG was 24 +/- 3 mmol/L. The mean difference between the bicarbonate by VBG and bicarbonate by routine biochemistry measurements was 5.6 +/- 4.4. Only 1 child (2.8%) was confirmed to have RTA. CONCLUSIONS: RTA is a rare renal cause of FTT in children. VBG determination of serum bicarbonate yielded a significantly higher value than the result obtained by routine biochemical testing under both in vitro and in vivo conditions. These data suggest that reliance on routine biochemical testing results in an overestimation of the importance of RTA as a cause of FTT. We recommend the use of a VBG determination of serum bicarbonate concentration for the evaluation of a child with FTT who is thought to have a metabolic acidosis. Adoption of this practice will reduce the number of children suspected of having RTA and decrease the need for referral to a nephrologist for further evaluation.

Urinary tract infections, VUR, and autosomal dominant polycystic kidney disease.

This case series of 16 patients with autosomal dominant polycystic kidney disease (ADPKD) describes 4 girls who presented with a urinary tract infection (UTI). Radiological evaluation revealed that each of these patients had vesicoureteral reflux (VUR). The frequency of VUR was significantly higher in the patients with ADPKD compared with otherwise healthy age-matched children who underwent testing after a UTI (100% versus 15%, P<0.002). These findings suggest VUR is an associated somatic anomaly in children with ADPKD that may contribute to the occurrence of UTI in this patient population.

Long versus standard initial steroid therapy for children with the nephrotic syndromeA report from the Southwest Pediatric Nephrology Study Group.

A retrospective cohort study was conducted by the Southwest Pediatric Nephrology Study Group (SPNSG) to address whether a longer initial course of corticosteroids in patients with idiopathic nephrotic syndrome (INS) provides superior protection against relapse without increased adverse effects. In order to be included in the evaluation, patients with INS must have responded to an initial steroid course, either standard or long regimen as defined here, and completed at least 1 year of follow-up. The standard regimen consisted of prednisone 2.0+/-0.3 mg/kg per day or 60+/-10 mg/m(2) per day for 28+/-4 days, followed by alternate-day prednisone for 4-12 weeks. The long regimen consisted of daily prednisone 2.0+/-0.3 mg/kg per day or 60+/-10 mg/m(2) per day for 42+/-6 days, followed by alternate-day prednisone for 6-14 weeks. The primary outcome measure was relapse of NS within 12 months of discontinuing the initial course of prednisone. There were 151 children who met the criteria for the study; 82 received the standard regimen and 69 the long regimen. The two groups did not differ in age, race, blood pressure, serum albumin, or serum cholesterol prior to the initial steroid course. The cumulative prednisone dose was 49% higher in the long regimen group than in the standard regimen group. Relapse within 12 months was reported in 72.5% of patients who received the long regimen versus 84.1% of those who received the standard regimen. The odds ratio for relapse within 12 months was 0.496 (95% confidence interval 0.22, 1.088), long versus standard regimen. This did not reach statistical significance ( chi(2)=3.058, P=0.08). The odds ratio of experiencing at least one side effect was 3.76, long relative to standard regimen ( n=133, P<0.001). Our data suggest that prolongation of the steroid treatment for the initial episode of steroid-sensitive NS may have a beneficial effect, but at the cost of increased side effects. However, definitive conclusions are limited by the retrospective design of the study and the number of patients. This may have caused failure to achieve statistical significance on the basis of a type II error.

Outcome after renal transplantation in children: results of follow-up by nephrologists in a primary referral center.

Pediatric patients who receive a kidney transplant require extended follow-up to monitor graft function and for management of complications. Because of convenience, most patients are sent back to the nephrologists who referred them for transplantation (the primary nephrologist) for long-term care. As a consequence, many pediatric nephrologists who provide this extended care are not associated with a transplant center. It is not known if this arrangement yields satisfactory outcomes for children and adolescents who receive a kidney transplant. The objective was to determine if clinical outcomes are satisfactory in pediatric renal transplant recipients who were followed up by their primary nephrologists after the procedure. A chart review was carried out on all renal transplant recipients seen in the renal clinic at Schneider Children's Hospital (SCH) from 1982 to 2001. Patients were eligible if they were followed up by the primary referring nephrologists at SCH for a minimum of 6 months after transplantation. Relevant demographic and clinical outcome data were compiled. Twenty-eight patients who received a total of 33 renal allografts [living related donors (LRD) 15 and cadaveric donors (CD) 18] were seen during the study period. The transplantations in 19 children (68%) were carried out at Montefiore Hospital (Bronx, NY, USA), while the rest were performed at other centers. There were three (11%) deaths, two LRD patients and one CD patient. The group of 25 surviving patients consisted of 17 males and eight females, age range 4-28 yr (mean 17.2 yr). The mean duration of renal allograft survival was 6.3 +/- 5.3 yr and the mean duration of follow-up was 6.1 +/- 5.3 yr. The most recent serum creatinine ranged from 0.5 to 3.8 mg/dL with a mean of 1.3 +/- 0.8 mg/dL. There were several complications including acute rejection, renal artery stenosis, and hydronephrosis in the allograft. The team of primary referring nephrologists successfully treated all of these except the child with hydronephrosis. The primary nephrologist who refers pediatric patients to a tertiary care transplant center can accomplish long-term follow-up of renal transplant recipients after discharge from the transplant center. The clinical outcomes are acceptable and compare favorably with the results described in the literature that have been achieved in patients followed up at transplant centers. Problems rarely developed that required referral back to the transplant center for management. This approach to care is recommended because it is more likely to foster compliance by both patients and parents.

Angiotensin converting enzyme inhibitor therapy in children with Alport syndrome: effect on urinary albumin, TGF-beta, and nitrite excretion.

BACKGROUND: Angiotensin converting enzyme inhibitors are routinely prescribed to patients with chronic kidney disease because of their known renoprotective effects. We evaluated the effect of short-term therapy with the angiotensin converting enzyme inhibitor, enalapril, in early Alport syndrome, defined as disease duration less than 10 years and a normal glomerular filtration rate. METHODS: 11 children with early Alport syndrome were investigated. Two consecutive early morning urine specimens were collected at the start of the study for measurement of urinary creatinine, total protein, albumin, TGF-beta, and nitrite excretion. Patients were treated with enalapril, congruent with 0.2 mg/kg/day, once a day for 14 days. Two early morning urine specimens were collected on days 13 and 14 of enalapril treatment and two weeks later for measurement of urinary creatinine, total protein, albumin, TGF-beta, and nitrite excretion. RESULTS: Prior to treatment, urinary excretion of transforming growth factor-beta and nitrite, the major metabolite of nitric oxide, was within normal limits in all patients. Administration of enalapril for 2 weeks did not alter urinary albumin, transforming growth factor-beta, or nitrite excretion. CONCLUSION: These findings suggest that early Alport syndrome represents a disease involving exclusively intrinsic glomerular barrier dysfunction. At this stage of the illness, there is no evidence of angiotensin II-mediated proteinuria or increased production of transforming growth factor-beta and, therefore, routine treatment with an angiotensin converting enzyme inhibitor may not be warranted.