Seth L. Schulman

BIOFEEDBACK METHODOLOGY: DOES IT MATTER HOW WE TEACH CHILDREN HOW TO RELAX THE PELVIC FLOOR DURING VOIDING?

PURPOSEnBiofeedback is a noninvasive treatment that has been documented to be helpful for children with daytime wetting and/or urinary tract infection secondary to voiding dysfunction. We wish to determine the effectiveness of biofeedback in a large population of children presenting with voiding dysfunction, and evaluate differences between 2 different methods with regard to resolution of symptoms, improvement of objective measurements and patient satisfaction.nnnMATERIALS AND METHODSnThe charts of 102 consecutive patients treated with biofeedback were reviewed. Of the patients 21 were asked to void 4 to 8 times in 6 hours seated in front of a uroflow device while receiving coaching by a staff member (method 1), 56 were taught pelvic floor relaxation techniques in front of a computer monitor that displayed electromyogram readings for 45 to 90 minutes (method 2), and both methods were used in 25. Outcome variables were obtained through chart review and telephone contact, and included resolution of symptoms, elimination of urinary tract infection, character of voiding curve, post-void residual, decrease in relaxation score and parental satisfaction.nnnRESULTSnFemales comprised 79% of the population and median age at first treatment was 7.7 years (range 4.3 to 15.4 y). Daytime wetting was seen in 84% and recurrent urinary tract infection in 66% of patients. Among children with daytime wetting there was 100% success or improvement with method 1, 91% with method 2 and 80% with both methods (p not significant). Among those with urinary tract infection, 25% had subsequent infection with method 1, 25% with method 2 and 31% with both methods (p not significant). Normalization of the flow curve was seen in 94% with method 1, 67% with method 2 and 30% with both methods. Patients using both methods had a significantly greater post-void residual compared to patients using method 1 (0 versus 33%, p = 0.003). Relaxation scores decreased a median of 6.5% in with method 2 and 20% with both methods. After a median followup of 1.8 years 98% of parents expressed satisfaction with biofeedback with more than 80% indicating a high degree of satisfaction.nnnCONCLUSIONSnReduction of daytime wetting and urinary tract infection can be achieved regardless of the type of biofeedback used. Although symptoms improved, patients using a shorter but more intensive approach aimed at teaching control of the pelvic floor musculature were more likely to demonstrate persistent post-void residuals and abnormal flow curves. A considerable degree of enthusiasm was reported using both of these non-invasive forms of treatment.

THE EFFICACY AND SAFETY OF ORAL DESMOPRESSIN IN CHILDREN WITH PRIMARY NOCTURNAL ENURESIS

PURPOSEnWe confirmed findings that oral desmopressin safely decreases the number of wet nights in children with enuresis and identified doses at which acceptable responses can be obtained.nnnMATERIALS AND METHODSnWe evaluated the safety and efficacy of oral desmopressin in a double-blind, placebo controlled, parallel group, randomized, multicenter trial of 193 children 6 to 16 years old with documented primary nocturnal enuresis. The study was conducted in 2 phases: 1) a 2-week dose ranging phase in which children received desmopressin (0.2, 0.4 or 0.6 mg.) or placebo at bedtime and 2) an 8-week dose titration phase that followed a 2-week placebo washout. Patients received 0.2 mg. desmopressin or placebo for the first 2 weeks and then the dose was increased in 0.2 mg. increments at 2-week intervals until the patient was completely dry or was receiving 0.6 mg. Patients were instructed to limit fluid intake. Mean decrease from baseline in the number of wet nights, percentage of responding patients and safety were assessed at 2-week intervals.nnnRESULTSnThere was a statistically significant linear response to oral desmopressin at doses from 0.2 to 0.6 mg. during the dose ranging phase (p < or =0.05). The decrease in wet nights after 2 weeks of treatment with desmopressin was 27%, 30% and 40% at 0.2, 0.4 and 0.6 mg. doses, respectively, compared to 10% with placebo. All doses were statistically significantly different from placebo (p < or =0.05). During the dose titration phase all placebo treated and 87% of desmopressin treated patients were receiving the maximum dose of 3 tablets nightly because they had not been completely dry in the previous 2 weeks. Nevertheless, 44% of desmopressin treated patients had achieved at least a 50% reduction from baseline in the number of wet nights per 2 weeks at the lower doses of 0.2 and 0.4 mg. Most adverse events (rhinitis, pharyngitis, headache and increased cough) were mild to moderate in severity, unrelated to treatment and resolved before the study was completed.nnnCONCLUSIONSnOral desmopressin administered at bedtime to children with primary nocturnal enuresis was significantly better than placebo for decreasing episodes of bed-wetting (p <0.05). A linear dose-response relationship was observed (p <0.05). An acceptable response to treatment (50% or greater reduction from baseline in wet nights per 2 weeks) was seen at all doses of desmopressin. Oral desmopressin, up to 0.6 mg. for 8 weeks, was well tolerated.

Behavioral characteristics of children with daytime wetting.

PURPOSEnWe hypothesized in this descriptive investigation that children with daytime wetting demonstrate unique emotional/behavioral patterns, independent of gender and age, compared to children with nocturnal wetting.nnnMATERIALS AND METHODSnTwo groups of children 5 to 17 years old with day wetting and urinary tract infections in the absence of organic etiology were recruited for study. There were 488 children in group 1 and 418 in group 2. Group 1 was given a short set of behavioral questions and group 2 was evaluated for behavioral characteristics with a revised and longer set of questions. Also in group 2 children with nocturnal wetting only were recruited as a comparison group. A subgroup of 58 children was randomly selected from group 2 and administered 2 standardized questionnaires.nnnRESULTSnChildren with day wetting and urinary tract infection had a significantly higher rate of constipation (35%) than those with day wetting and no infection (25%, p <0.02). Parents of group 1 children reported the level of frustration and anger to be similar whether the children had urinary tract infection or not. Parents also reported that only 3.8% of children had significant learning or school problems. Parents of group 2 did not report any differences between nighttime and daytime wetting with respect to positive outlook, organizational skills or willingness to talk. Differences were noted, with daytime wetters perceived as more stubborn (p <0.0001), secretive (p <0.0001), refusing to follow parental requests (p <0.002) and constipation (p <0.0003). Of the subsample group the incidence of verified attention deficit/hyperactivity disorder was highest in children with daytime wetting and no infection (21%), and nighttime wetting (22%) compared to 0% in daytime wetting and infection. The Child Behavioral Checklist results on this sample suggested that 35% of the children with daytime wetting and no infection earned significant T scores of mixed or externalizing symptoms, while the nocturnal enuresis group demonstrated 16% significant T scores, primarily externalizing. All females with the daytime wetting and infection showed significant T scores within the internalizing domain. The Child Behavioral Checklist defines externalizing behaviors as aggressive and acting out behaviors, while internalizing behaviors include withdrawn and anxious/depressed behaviors. Mixed behaviors on this questionnaire include social, attention and thought problems.nnnCONCLUSIONSnThese data suggest that a minority of children with daytime wetting and infection tend to show an internalizing style of problems (11%) and constipation, while those with daytime wetting and no infection show a more mixed style of psychological problem (35%). In contrast, the nighttime wetting group tends to show externalizing problems (16%). Based on a subsample of the data children with daytime wetting and no infection, and nighttime wetting showed a significantly incidence of verified attention deficit/hyperactivity disorder compared to the general population. According to parent perceptions, stubbornness and secretiveness seem to describe a style that the children with daytime wetting exhibit that is not present in those with nighttime wetting. There is a possible role of uncontrol and over control psychological styles to the development and treatment of daytime wetting as well as the relationship of these styles to treatment outcome. Further research is needed to clarify the psychological style of children with daytime wetting to customized treatment protocols.

Natural history of voiding dysfunction

Voiding dysfunction leads to daytime wetting, night-time wetting, and recurrent urinary tract infection (UTI). Our interdisciplinary center has been committed to treating children with dysfunctional voiding since 1992. We describe the long-term follow-up of a large cohort of children using our approach to treatment. We reviewed the records of 199 children with symptoms of voiding dysfunction seen between March 1992 and December 1993. We contacted 98 parents and 51 patients by phone at least 6.5xa0years after initial presentation and asked about current symptoms, effective strategies, and satisfaction of care. Of the initial group of contacted parents, 81 (83%) were female with a median age of 7.8xa0years. Patients were followed in the clinic for a mean time of 1.6xa0years and a median of three visits. Of the 90 patients with daytime wetting, 82 (91%) reported complete resolution with a median time of resolution of 2.9xa0years. Parents felt that maturation was the most important factor leading to improvement. Of the patients that were directly contacted (41 females, 10 males, median age 15.2xa0years), all were dry and 86% denied any sense of urgency; 86% of parents and 87% of patients were highly satisfied with their care. Almost every child improved within 5xa0years of the initial evaluation. Only small fractions are still wet, are infected, or have urgency. Maturation seems to be the most important factor leading to improvement. Most parents and patients are satisfied with this form of treatment.

Increased urinary transforming growth factor- beta1 excretion in children with posterior urethral valves

OBJECTIVESnPatients with posterior urethral valves (PUV) are at significant risk for progression to end-stage renal disease, despite early correction of the obstruction. Experimental models of urinary obstruction demonstrate increased renal expression of the profibrotic inflammatory mediator, transforming growth factor-beta(1) (TGF-beta(1)). Urinary TGF-beta(1) excretion is elevated in certain glomerular diseases, but has not been well studied in patients with obstructive lesions. The objective of this study was to examine urinary TGF-beta(1) excretion in children with PUV.nnnMETHODSnFourteen patients with PUV, aged 3.2 to 14.5 years, with estimated glomerular filtration rates (GFRs) of 12.8 to 139 mL/min/1.73 m(2) were enrolled. Sixteen normal subjects (9 male, 7 female), aged 4.3 to 20.5 years, served as controls. Total urinary TGF-beta(1) concentration was assayed by enzyme-linked immunoabsorbent assay, and expressed as a ratio to urinary creatinine concentration.nnnRESULTSnUrinary TGF-beta(1) excretion was significantly greater in patients with PUV (range 0 to 0.063, median 0.019 ng/mg urine creatinine) compared with that of healthy controls (range 0 to 0.022, median 0.005 ng/mg urine creatinine) (P <0.01). There was no correlation between urinary TGF-beta(1) excretion and estimated GFR, past urinary diversion surgery, or bladder wall thickening. Among healthy controls, urinary TGF-beta(1) was not correlated with age or gender.nnnCONCLUSIONSnResults from this study suggest that TGF-beta(1) may contribute to progressive renal insufficiency in patients with PUV. Further studies are indicated to determine if agents that affect TGF-beta(1) expression, such as angiotensin-converting enzyme inhibitors, can slow the progression of renal disease in PUV.

Interaction between tacrolimus and chloramphenicol in a renal transplant recipient.

BACKGROUNDnThe metabolism of tacrolimus is influenced by several medications when they are given concurrently. We report the interaction between tacrolimus and chloramphenicol in a renal transplant recipient.nnnMETHODSnAn adolescent with vancomycin-resistant Enterococcus was given standard doses of chloramphenicol. Tacrolimus trough levels increased, and the dose was adjusted to maintain the target trough level. Pharmacokinetic studies were obtained during chloramphenicol administration and 14 days after its discontinuation.nnnRESULTSnToxic levels of tacrolimus were seen on the second day of chloramphenicol administration, requiring an 83% reduction in the tacrolimus dose. The dose-adjusted area under the curve value for tacrolimus was 7.5-fold greater while the patient was on chloramphenicol. These data are consistent with inhibition of tacrolimus clearance by chloramphenicolnnnCONCLUSIONSnChloramphenicol interferes with tacrolimus metabolism. Careful monitoring of tacrolimus trough levels during concomitant chloramphenicol therapy is recommended to avoid toxicity.

Adverse neurologic events associated with rebound hypertension after using short-acting nifedipine in childhood hypertension

Introduction Short-acting nifedipine (SA-NIF) is widely prescribed for acute hypertension (HTN) in children despite reports of ischemic complications in adults. We describe two children with neurologic events caused by rebound hypertension following SA-NIF use. Cases Patient 1 is a 7-year-old with acute nephritis and blood pressure (BP) of 185/130. She received SA-NIF which decreased BP to 114/79. When BP rebounded to 160/103, she developed severe cortical visual impairment. Head CT demonstrated edema and petechial hemorrhages in the watershed region. Patient 2 is a 10-year-old renal transplant recipient who received SA-NIF for a BP of 155/98, which resulted in a prompt decrease to 114/74. Two hours later he developed aphasia and right-sided neglect. His BP increased to 168/88 and he developed partial complex seizures. Brain MRI showed high signal intensity in the watershed areas with early gadolinium enhancement. Discussion The temporal association of the neurologic events with the rebound increase in BP suggests a possible role for the SA-NIF, consistent with its pharmacokinetic profile. Although the adult literature has focused on the unpredictable decline in BP after SA-NIF treatment, these cases suggest that rapid increases in BP following the maximal SA-NIF effect may be associated with impaired cerebral autoregulation and encephalopathy in children. These cases underscore the need for frequent blood pressure determinations and therapy to prevent rebound hypertension.

Effectiveness of Treatments for Nocturnal Enuresis in a Heterogeneous Population

The objective of this study was to determine the effectiveness of various treatments for nocturnal enuresis in a large, diverse population of children. A retrospective cohort review of patients with nocturnal enuresis was undertaken. All patients selected treatment after a single visit that included a history, examination, and demonstration of treatments. Families were contacted 1 year later to determine what treatment they chose and whether their child still wet. Families primarily chose an alarm (31%), followed by desmopressin acetate (22%) and oxybutynin (9%). Some preferred no treatment (23%). Fifty-six percent of patients using the alarm were completely dry compared to 18% using desmopressin acetate (p&lt0.0001), 16% using oxybutynin, and 28% receiving no treatment. In a heterogeneous population 1 year after a single visit, children whose parents chose the nocturnal enuresis alarm were most likely to be completely dry.

An Analysis of the Approach to Management of Childhood Nephrotic Syndrome by Pediatric Nephrologists

The value of a renal biopsy for a child with frequently relapsing corticosteroid-responsive or corticosteroid-dependent nephrotic syndrome is unresolved. This was the subject of two independent surveys done by North American pediatric nephrologists. In one study, 59% of the respondents indicated that they would nearly always perform a biopsy prior to starting cytotoxic therapy, while 23% would do so rarely. Less experienced pediatric nephrologists were more inclined to recommend a biopsy (P < 0.05). The indications for a renal biopsy were to provide prognostic information and to make decisions concerning further therapy. In the second survey, 33% of pediatric nephrologists said they would perform a renal biopsy in children with frequent relapses, while 91% would recommend a biopsy in children with corticosteroid resistance (P < 0.001). Once a biopsy was performed, therapy was based on the histopathologic findings regardless of the previous clinical response to corticosteroids. At this time, there is no standard approach to the evaluation and management of children with frequently relapsing, corticosteroid-dependent nephrotic syndrome. Some physicians rely on their clinical acumen, whereas others depend on the histopathologic findings.

Comparison of alarms, desmopressin, and combined therapy in Chinese children with nocturnal enuresis

Comparison of alarms, desmopressin, and combined therapy in Chinese children with nocturnal enuresis