Remote image based retinopathy of prematurity diagnosis: a receiver operating characteristic analysis of accuracy.

BACKGROUND/AIMS: Telemedicine offers potential to improve the accessibility and quality of diagnosis of retinopathy of prematurity (ROP). The aim of this study was to measure accuracy of remote image based ROP diagnosis by three readers using receiver operating characteristic (ROC) analysis. METHODS: 64 hospitalised infants who met ROP examination criteria underwent two consecutive bedside procedures: dilated examination by an experienced paediatric ophthalmologist and digital retinal imaging with a commercially available wide angle camera. 410 images from 163 eyes were reviewed independently by three trained ophthalmologist readers, who classified each eye into one of four categories: no ROP, mild ROP, type 2 prethreshold ROP, or ROP requiring treatment. Sensitivity and specificity for detection of mild or worse ROP, type 2 prethreshold or worse ROP, and ROP requiring treatment were determined, compared to a reference standard of dilated ophthalmoscopy. ROC curves were generated by calculating values for each reader at three diagnostic cut-off levels: mild or worse ROP (that is, reader was asked whether image sets represented mild or worse ROP), type 2 prethreshold or worse ROP (that is, reader was asked whether image sets represented type 2 prethreshold or worse ROP), and ROP requiring treatment. RESULTS: Areas under ROC curves ranged from 0.747-0.896 for detection of mild or worse ROP, 0.905-0.946 for detection of type 2 prethreshold or worse ROP, and 0.941-0.968 for detection of ROP requiring treatment. CONCLUSIONS: Remote interpretation is highly accurate among multiple readers for the detection of ROP requiring treatment, but less so for detection of mild or worse ROP.

Iron supplementation in adolescent hemodialysis patients.

AIMS: Iron supplementation is necessary in children on hemodialysis, but the optimal protocol remains unknown. We studied the effects of changing our unit's protocol from oral iron with periodic doses of parenteral iron dextran to routine administration of parenteral sodium ferric gluconate on anemia and iron parameters. METHODS: We followed seven hemodialysis patients aged 15 20 years (mean 17 years). Hemoglobin, hematocrit, serum iron, transferrin saturation, ferritin, erythropoietin dose, total elemental iron dose and total iron cost for the six months prior to the protocol change were compared to the same variables during the six months following the change. RESULTS: There was no statistically significant difference between the doses of parenteral iron between the two protocols; however, the total dose of elemental iron administered in the oral iron plus iron dextran protocol was greater than in the sodium ferric gluconate protocol (19.6+/-13.1 (mean+/-SD) mg/kg/week versus 1.1+/-0.3 mg/kg/week; p = 0.03). Both protocols had equivalent efficacy with respect to hemoglobin, ferritin and other measures of iron stores. On the other hand, the costs of sodium ferric gluconate were significantly higher than those of oral iron plus intermittent iron dextran (157.75+/-45.94 $/patient/month versus 52.08+/-49.88 $/patient/month; p = 0.01). CONCLUSIONS: Routine administration of sodium ferric gluconate is equivalent if not superior to use of oral iron plus iron dextran for maintenance of iron stores in adolescents on hemodialysis, but more expensive.

Episodic gross hematuria in association with allergy symptoms in a child.

BACKGROUND: A relationship between allergy and the development of various renal diseases has been postulated, but never proven. MATERIALS AND METHODS: We present the case of a child with idiopathic episodic gross hematuria. The child also has significant environmental allergies, and his episodes of hematuria coincide with flares of his allergic symptoms. The available literature on hematuria and allergy was reviewed in order to further explore the potential role that allergy may play in the pathogenesis of genitourinary tract disease. CONCLUSIONS: This case, as well as others reported in the literature, suggest that allergy should be considered as a possible diagnosis in children with otherwise unexplained hematuria.

Choice of dialysis modality for management of pediatric acute renal failure.

Acute renal failure in children requiring dialysis can be managed with a variety of modalities, including peritoneal dialysis, intermittent hemodialysis, and continuous hemofiltration or hemodiafiltration. The choice of dialysis modality to be used in managing a specific patient is influenced by several factors, including the goals of dialysis, the unique advantages and disadvantages of each modality, and institutional resources. This review will examine these aspects of acute renal failure management, with the goal of providing practical guidance regarding modality selection to the physician involved in the management of pediatric acute renal failure.

What's new in pediatric hypertension?

Research activities in the field of pediatric hypertension have been increasing in recent years, leading to important new findings in the epidemiology, diagnosis, and treatment of hypertension in children. This review summarizes recent work in these areas, focusing on the epidemic of obesity-related hypertension in children, advances in the drug therapy of childhood hypertension, and the increasing use of ambulatory blood pressure monitoring in evaluation of hypertensive children. Each of these three areas will no doubt develop further over the years ahead, resulting in further advances in the field of childhood hypertension.

Indications, results, and complications of tacrolimus conversion in pediatric renal transplantation.

It is the practice of many pediatric renal transplant programs to 'convert' children taking cyclosporin A (CsA) to tacrolimus, although the indications for, outcome, and complications of this practice remain obscure. To better understand these aspects of tacrolimus 'conversion', a fax survey was sent to 119 North American pediatric renal transplant centers. Analyzable responses were received from 52 centers (44%), and included data from approximately 1,815 pediatric renal transplants performed between 1991 and 98. Strong indications for tacrolimus conversion were: antibody-resistant rejection, CsA-resistant rejection, and CsA intolerance (strong indication in 72%, 65%, and 52% of centers, respectively). Steroid-resistant rejection and cosmetic side-effects were considered strong indications less often. Initial anti-rejection therapy was usually increased corticosteroid dose (47/52 centers). Antibody therapy was most commonly used for steroid-resistant rejection (44 centers). For steroid- and antibody-resistant rejection, tacrolimus conversion was most common (33 centers). Tacrolimus conversion for antibody-resistant rejection led to improvement of serum creatinine (SCr) in 27% of patients, stabilization of SCr in 46%, worsening of SCr in 11%, and graft loss in 16%. Reported complications after tacrolimus conversion included hyperglycemia, hyperkalemia, lymphoproliferative disorder, infection, and neurologic problems. We conclude that the major indication for tacrolimus conversion in pediatric transplant programs appears to be rejection. Outcome after tacrolimus conversion appears good, with the majority of patients experiencing stable or improved allograft function. These data provide direction for further study, including timing of tacrolimus conversion and interaction with other therapies.

Peritoneal dialysis for management of pediatric acute renal failure.

BACKGROUND: While the use of continuous renal replacement therapies in the management of children with acute renal failure (ARF) has increased, the role of peritoneal dialysis (PD) in the treatment of pediatric ARF has received less attention. DESIGN: Retrospective database review of children requiring PD for ARF over a 10-year period. SETTING: Pediatric intensive care unit at a tertiary-care referral center. PATIENTS: Sixty-three children without previously known underlying renal disease who required PD for treatment of ARF. RESULTS: Causes of ARF were congestive heart failure (27), hemolytic-uremic syndrome (13), sepsis (10), nonrenal organ transplant (7), malignancy (3), and other (3). Mean duration of PD was 11 +/- 13 days. Children with ARF were younger (30 +/- 48 months vs 88 +/- 68 months old, p < 0.0001) and smaller (11.9 +/- 15.9 kg vs 28 +/- 22 kg, p < 0.0001) than children with known underlying renal disease who began PD during the same time period. Percutaneously placed PD catheters were used in 62% of children with ARF, compared to 4% of children with known renal disease (p < 0.0001). Hypotension was common in patients with ARF (46%), which correlated with a high frequency of vasopressor use (78%) at the time of initiation of PD. Complications of PD occurred in 25% of patients, the most common being catheter malfunction. Recovery of renal function occurred in 38% of patients; patient survival was 51%. CONCLUSIONS: Peritoneal dialysis remains an appropriate therapy for pediatric ARF from many causes, even in severely ill children requiring vasopressor support. Such children can be cared for without the use of more expensive and technology-dependent forms of renal replacement therapies.

Delayed compared with immediate use of peritoneal catheter in pediatric peritoneal dialysis.

Delayed use of the peritoneal catheter may be one method of reducing catheter-related complications in chronic peritoneal dialysis (PD); however, the risks and benefits of immediate as compared with delayed use have not been examined in children. We retrospectively analyzed 33 peritoneal catheter placements in 27 children between 1997 and 2000. Eleven catheters were used for PD immediately following insertion (group I); 22 catheters were used only after a delay averaging 20 days (group D). Characteristics of the children in the two groups were similar. Catheter-related complications within the first 3 months after placement--including dialysate leak, fibrin plug, outflow obstruction, cuff extrusion, herniation, exit-site and tunnel infection, peritonitis, and catheter revision and replacement--were evaluated. Rates of individual complications in the two groups were similar, but several trends were noted. Dialysate leaks were more common in group I (rate of 0.36 in group I vs 0.09 in group D), and infectious complications were more common in group D (rate of exit-site or tunnel infection of 0.14 in group D vs 0.09 in group I; rate of peritonitis of 0.36 in group D vs 0.18 in group I). We conclude from this small study that delayed use of the peritoneal catheter does not appear to convey significant advantages over immediate use; however, immediate use may be associated with more frequent dialysate leaks. On the other hand, delayed use may be associated with a greater risk of infection. Further studies involving larger numbers of children will be necessary to confirm these findings.

Intravenous nicardipine for treatment of severe hypertension in children.

OBJECTIVE: To examine the effect of intravenous nicardipine in the treatment of children with severe hypertension. METHODS: The medical records of 29 children (mean age 94 months) treated with intravenous nicardipine were retrospectively reviewed. The mean duration of severe hypertension before nicardipine use was 12.5 hours. Most (74%) patients were receiving other antihypertensive agents before nicardipine. RESULTS: The initial nicardipine dose was 0.8 +/- 0.3 microg/kg/min (mean +/- SD). The mean effective dose was 1.8 +/- 1.0 microg/kg/min (range, 0.3 to 4.0). Blood pressure control was achieved within 2.7 +/- 2.1 hours after nicardipine was started. Nicardipine treatment produced a 16% reduction in systolic blood pressure, a 23% reduction in diastolic blood pressure, and a 7% increase in heart rate. Nicardipine was effective as a single agent on 26 (84%) of 31 occasions. Adverse effects included tachycardia, flushing, palpitations, and hypotension. CONCLUSIONS: When administered in the intensive care unit setting with close patient monitoring, intravenous nicardipine effectively lowered blood pressure in children with severe hypertension. Larger prospective studies should be conducted to confirm these findings.

Treatment of Henoch-Schönlein Purpura glomerulonephritis in children with high-dose corticosteroids plus oral cyclophosphamide.

BACKGROUND: Henoch-Schönlein Purpura (HSP) is a common childhood vasculitis with manifestations in numerous organ systems, including glomerulonephritis. Patients with more severe HSP-associated glomerulonephritis may develop chronic renal failure. Currently, no widely accepted treatment protocols exist for patients with significant renal involvement. METHODS: We retrospectively reviewed the clinical courses of 12 children (mean age 9 years) with HSP glomerulonephritis treated with high-dose corticosteroids plus oral cyclophosphamide. All patients had nephrotic-range proteinuria, and all had significant histopathologic changes on biopsy, including crescentic nephritis in 10 patients. Treatment consisted of either intravenous pulse methylprednisolone or oral prednisone followed by oral cyclophosphamide (2 mg/kg/day) for 12 weeks, along with either daily or alternate-day oral prednisone. Prednisone was tapered following completion of cyclophsophamide. RESULTS: Serum albumin rose significantly after treatment from 2.8 +/- (SD) 0.5 to 3.7 +/- 0.4 g/dl (p < 0.001), and there was a concurrent reduction in proteinuria, as reflected by decreasing serial protein-to-creatinine ratios: from 6.3 +/- 4.4 to 0.8 +/- 0.8 (p = 0.002). Renal function remained normal in all patients. Hypertension developed during treatment in 10 patients, all but 1 of whom were normotensive at last follow-up, 35 +/- 17 months following biopsy. CONCLUSIONS: We conclude that treatment of children with HSP nephritis with high-dose corticosteroids plus oral cyclophosphamide is safe and, as in nephrotic syndrome, appears to significantly reduce proteinuria which is a known risk factor for the development of renal insufficiency in HSP. Further studies with larger numbers of patients should be conducted to confirm this finding.

Hemodialysis followed by continuous hemofiltration for treatment of lithium intoxication in children.

Hemodialysis is the usual recommended treatment for severe lithium intoxication; however, rebound of lithium levels may require repeated hemodialysis treatments. We proposed that the addition of continuous hemofiltration after hemodialysis would prevent rebound by providing ongoing clearance of lithium. We report two pediatric patients with lithium intoxication treated by hemodialysis followed by continuous venovenous hemofiltration with dialysis (CVVHD). Both patients were symptomatic at presentation and had initial lithium levels more than three times the usual therapeutic range. Hemodialysis followed by CVVHD resulted in rapid resolution of symptoms, followed by continuous clearance of lithium without requiring repeated hemodialysis sessions. Both patients had return of normal mental status during CVVHD treatment, and neither patient experienced complications of hemodialysis or CVVHD. Total duration of treatment with hemodialysis followed by CVVHD was 34.5 hours for the first patient and 26 hours for the second patient. We conclude that hemodialysis followed by CVVHD is a safe and effective approach to the management of lithium intoxication in children.

Parenteral supplementation with a fish-oil emulsion prolongs survival and improves rat lymphocyte function during sepsis.

Nutritional intervention with omega-3 fatty acids during trauma and infection has been shown to improve the clinical outcome of patients and the survival rate in laboratory animals. This study evaluated the effects of parenteral administration of lipid emulsions containing fish oil (FO) or soybean oil (SBO) on survival and T-lymphocyte response during sepsis. Male Sprague-Dawley rats (250-275 g) were prepared for parenteral feeding 4 d before inducing sepsis by cecal ligation and puncture (CLP). Standard resuscitation was provided with normal saline. Thirty minutes after completing CLP, sham control or CLP rats were infused continuously with saline or a parenteral diet containing SBO or a 1:1 FO:SBO emulsion. The survival rate was significantly improved in rats receiving the FO-supplemented diet, with 50% alive by 120 h in comparison with the saline-infused, chow-fed rats (0% alive by 120 h) or the SBO-fed rats (12% alive at 120 h). The T-lymphocyte response was evaluated at 24 h after CLP. Sepsis led to a decline in lymphocyte proliferation in rats infused with saline or the SBO emulsion, which was associated with a greater release of splenocyte interleukin-10, transforming growth factor-beta and prostaglandin E2. Administering the 1:1 FO:SBO parenteral diet during sepsis improved the survival rate and prevented the sepsis-induced suppression of lymphocyte proliferation and interleukin-2 release. The FO effect on lymphocyte function was associated with decreased splenocyte release of transforming growth factor-beta and prostaglandin E2.

Pretransplant varicella vaccination is cost-effective in pediatric renal transplantation.

Because of the severe complications that may result from varicella zoster virus (VZV) infection following renal transplantation (Tx), transplanted varicella-susceptible children exposed to varicella are typically given varicella zoster immunoglobulin (VZIG) as prophylaxis or are admitted and treated with parenteral acyclovir if VZIG prophylaxis fails. As both VZIG and hospitalization are costly, prevention of varicella infection by vaccination could potentially result in significant cost savings in addition to decreasing morbidity and mortality. To test this hypothesis, we developed a decision-analysis model to evaluate the cost-effectiveness of vaccinating patients with chronic renal failure (CRF) against varicella prior to renal transplant. Under baseline assumptions, vaccination for varicella pretransplant was a cost-effective strategy, with a cost of $211 per patient vaccinated compared with $1,828 per patient not vaccinated. The magnitude of cost savings from vaccination was sensitive to variations in the cost of varicella vaccine, the percentage of patients hospitalized for treatment with acyclovir, and the percentage of patients exposed to varicella infection. One- and two-way sensitivity analyses confirmed that vaccination was the dominant cost-effective strategy under all conditions examined. We conclude that vaccination for varicella pretransplant is cost-effective for patients with CRF, and that the magnitude of cost savings is sensitive to the cost of hospitalization, the percentage of patients exposed to varicella, and the cost of varicella vaccination. Pending results of ongoing studies of the safety and efficacy of VZV vaccine in children with CRF, we recommend that VZV vaccine be given to all children with CRF.

Renal transplantation after Streptococcus pneumoniae-associated hemolytic uremic syndrome.

Of the several causes of nondiarrheal hemolytic uremic syndrome (HUS), infection with Streptococcus pneumoniae is infrequent, but important, because of its unique pathogenesis. A comprehensive literature review found 37 well-documented cases of S pneumoniae-associated HUS (SP-HUS), only 2 of which progressed to end-stage renal disease (ESRD). We report the third such child, and the first to receive a renal transplant following SP-HUS. Her course illustrates several unique characteristics of SP-HUS common to previous patients reported in the literature, including a greater duration of oligoanuria compared with cases not progressing to ESRD, the significant adverse effect of unwashed blood products, and a possible influence of female gender on outcome. Clinicians caring for children with SP-HUS should be aware of these differences and modify therapy appropriately to avoid known risk factors for poor outcome, specifically the use of unwashed blood products.

Evaluation and management of hypertension in childhood.

Hypertension, a relatively uncommon problem in childhood except in certain groups of children, is an important cardiovascular risk factor that can have significant health implications, especially the tendency for an elevated blood pressure in childhood to predict the development of adult hypertension. Common causes of childhood hypertension include renal and cardiac disease, as well as essential hypertension in adolescents. Given these factors, it is usually possible to evaluate the hypertensive child in a focused manner that should reveal not only the underlying cause of hypertension, but also its severity. Treatment should incorporate non-pharmacologic approaches as well as antihypertensive medications, and should take into account other cardiovascular risk factors such as hyperlipidemia. This review highlights these and other important issues in the evaluation and management of hypertensive children, and provides practical guidance to the practitioner involved in caring for such patients.

Screening for retinopathy of prematurity employing the retcam 120: sensitivity and specificity.

OBJECTIVES: To compare the method of photographic screening using the RetCam 120 to the standard method of screening for retinopathy of prematurity (ROP) by ophthalmologic examination. METHODS: A total of 100 RetCam 120 photoscreening examinations of the retina were performed on 32 premature infants. These were stored in a separate file from which all identifying information was removed. At this same examination, a detailed ophthalmological evaluation, employing the indirect ophthalmoscope with scleral depression, was performed by an experienced examiner. Masked examiners performed an evaluation of the fundus photographs to identify presence or absence of ROP, the location and extent of the disease, and the presence or absence of plus disease. These data were then compared with the results of the ophthalmological examination to determine the specificity, sensitivity, and the positive and negative predictive value (PPV and NPV) of the method. RESULTS: Retinopathy of prematurity was detected in 68 of 100 subjects by ophthalmologic examinations and in 58 of 100 subjects' photoscreening examinations. No ROP was detected in 32 of 100 subjects. The sensitivity of the method was 56 (82.4%) of 68 and the specificity was 30 (93.8%) of 32. The PPV was 96.6%; NPV, 76.9%. CONCLUSIONS: The sensitivity of the method was low. The ROP that was missed was peripheral stage 1 or stage 2 disease in peripheral zone 2 or zone 3. This was largely due to the technical limitations of the speculum-camera interface preventing a better view of the periphery. The ROP cases that were missed by the photographic examination regressed spontaneously on follow-up. No disease more posterior to peripheral zone 2 was overlooked. These results detail the accuracy of the method employing the technique of photoscreening as a potential substitute for detailed ophthalmological examination. At present there are clear technical limitations to such a substitution. The study is part of an ongoing project to determine the feasibility of employing neonatal nurses trained to take digitized images of the premature infant's retina and telemeter the results to be read by an experienced ophthalmologist remote from the site.

The outcome of retinopathy of prematurity: screening for retinopathy of prematurity using an outcome predictive program.

PURPOSE: The purpose of this study was to compare the calculated risk of progression to threshold retinopathy of prematurity (ROP) and risk of an unfavorable structural outcome using the computer program, RM-ROP, with the observed incidence for infants born at Jackson Memorial Hospital (JMH) and to determine how many children would have been treated unnecessarily if the threshold criteria for treatment were lowered on the basis of the clinical findings and RM-ROP risk calculations. DESIGN: Noncomparative interventional case series. PARTICIPANTS: All 292 surviving premature infants weighing 1250 g or less at birth and born at JMH between January 1, 1997, and December 31, 1998, were included in the study. METHODS: Baseline demographic factors and data from sequential ophthalmic examinations were entered into the RM-ROP program for risk calculation. Infants reaching threshold disease received diode laser indirect photocoagulation of the avascular retina. Three-month follow-up was obtained for infants receiving laser treatment. MAIN OUTCOME MEASURES: The development of threshold ROP and an unfavorable structural outcome, defined as a posterior retinal fold or posterior retinal detachment occurring within 3 months of threshold disease. RESULTS: Thirty-eight eyes were diagnosed with threshold ROP, with 18 of 20 subjects having bilateral disease. Three-month posttreatment follow-up was obtained on all 20 children, with 19 having good structural outcomes. Thirty-two percent of eyes (12 of 38) reaching threshold never had a risk estimate greater than 0.10. However, only 6% of eyes (35 of 546) that did not reach threshold ever had a model predicted risk greater than 0.15. All right eyes with zone 1 prethreshold disease, 60% of those with zone 2 stage 2+ disease, and 23% with zone 2 stage 3 disease progressed to threshold ROP. CONCLUSIONS: The similarity between the risk distributions for the Miami and the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity study indicates the similarity in the populations with respect to risk factors identified as important by the model. The Miami data validated the model, with eyes reaching threshold having higher risks than eyes that did not. Actual risk estimates for eyes reaching threshold can be small. Changing the threshold criteria for treatment on the basis of various clinical and computer-generated prethreshold risk levels in our population would have resulted in the unnecessary treatment of many infants who never progressed to threshold disease. In the Miami population, if the model were used to manage an individual subject, close attention would have to be paid to small differences in risk. Although the RM-ROP software program may be a useful tool for following premature infants with ROP, the clinical examination remains the "gold standard."