Tricyclic and related drugs for nocturnal enuresis in children.

BACKGROUND: Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs can be great. Tricyclics have been used to treat enuresis since the 1960s. OBJECTIVES: To assess the effects of tricyclic and related drugs compared with other interventions for treating children with enuresis. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (containing trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings), on 30 November 2015, and reference lists of relevant articles. SELECTION CRITERIA: We included all randomised and quasi-randomised trials comparing a tricyclic or related drug with another intervention for treating enuresis. We also included combination therapies that included tricyclics. We excluded trials for treating daytime wetting. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the quality of the eligible trials, and extracted data. We settled differences by discussion with a third review author. MAIN RESULTS: Sixty-four trials met the inclusion criteria, involving 4071 children. The quality of many trials was poor, with comparisons addressed by single studies. Minor adverse effects were common, and reported in 30 trials. These included dizziness, headache, mood changes, gastrointestinal discomforts and neutropenia. More serious side-effects can occur but were not reported. Seven trials reported no adverse effects.Tricyclics are more effective than placebo, particularly for short-term outcomes. Compared to placebo, imipramine resulted in one fewer wet nights per week (mean difference (MD) -0.95, 95% confidence interval (CI) -1.40 to -0.50; 4 trials, 347 children), with fewer failing to achieve 14 consecutive dry nights (78% versus 95% for placebo, RR 0.74, 95% CI 0.61 to 0.90; 12 trials, 831 children). Amitriptyline and desipramine were more effective than placebo, but nortriptyline and mianserin showed no difference. Most tricyclics did not have a sustained effect after ceasing treatment, with 96% wetting at follow-up for imipramine versus 97% for placebo.Imipramine combined with oxybutynin is also more effective than placebo, with 33% failing to achieve 14 consecutive dry nights at the end of treatment versus 78% for placebo (RR 0.43, 95% CI 0.23 to 0.78; 1 trial, 47 children) and 45% wetting at follow-up versus 79% for placebo (RR 0.58, 95% CI 0.34 to 0.99; 1 trial, 36 children).There was insufficient evidence to judge the effect between different doses of tricyclics, and between different tricyclics. Treatment outcomes between tricyclic and desmopressin were similar, but were mixed when tricyclic was compared with an anticholinergic. However, when imipramine was compared with desmopressin plus oxybutynin (1 trial, 45 children), the combination therapy was more effective, with one fewer wet nights per week (MD 1.07, 95% CI 0.06 to 2.08) and 36% failing to achieve 14 consecutive dry nights versus 87% for imipramine (RR 2.39, 95% CI 1.35 to 4.25). Tricyclics were also more effective or showed no difference in response when compared to other drugs which are no longer used for enuresis.Tricyclics were less effective than alarms. Although there was no difference in the number of wet nights, 67% failed to achieve 14 consecutive dry nights for imipramine versus only 17% for alarms (RR 4.00, 95% CI 1.06 to 15.08; 1 trial, 24 children). Alarm therapy also had a more sustained effect after ceasing treatment with 100% on imipramine versus 58% on alarms wetting at follow-up (RR 1.67, 95% CI 1.03 to 2.69; 1 trial, 24 children).Imipramine was more effective than simple behavioural therapies during treatment, with one fewer wet nights per week compared with star chart plus placebo (MD -0.80, 95% CI -1.33 to -0.27; 1 trial, 250 children). At follow-up 40% were wet with imipramine versus 80% with fluids and avoiding punishment (RR 0.50, 95% CI 0.28 to 0.89; 1 trial, 40 children). However, imipramine was less effective than complex behavioural therapies, with 61% failing to achieve 14 consecutive dry nights for imipramine versus 33% for the three-step programme (RR 1.83, 95% CI 1.08 to 3.12; 1 trial, 72 children) and 16% for the three-step programme combined with motivational therapy and computer-led education (RR 3.91, 95% CI 2.30 to 6.66; 1 trial, 132 children) at the end of treatment, with similar results at follow-up.Tricyclics were more effective than restricted diet, with 99% failing to achieve 14 consecutive dry nights versus 84% for imipramine (RR 0.84, 95% CI 0.75 to 0.93; 1 trial, 147 children).There was insufficient evidence to judge the effect of tricyclics compared to the other miscellaneous interventions studied.At the end of treatment there were about two fewer wet nights for imipramine plus oxybutynin compared with imipramine monotherapy (MD -2.10, 95% CI -2.99 to -1.21; 1 trial, 63 children) and 48% on imipramine plus oxybutynin failed to achieve 14 consecutive dry nights compared with 74% on imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.92; 2 trials, 101 children). At follow-up, 45% on imipramine plus oxybutynin were wetting versus 83% on imipramine monotherapy (RR 0.55, 95% CI 0.32 to 0.92; 1 trial, 36 children).When imipramine combined with desmopressin was compared with imipramine monotherapy, there was no difference in outcomes. However, when imipramine plus desmopressin was compared with desmopressin monotherapy, the combination was more effective, with 15% not achieving 14 consecutive dry nights at the end of treatment for imipramine plus desmopressin versus 40% for desmopressin monotherapy (RR 0.38, 95% CI 0.17 to 0.83; 1 trial, 86 children). Tricyclics combined with alarm therapy were not more effective than alarm monotherapy, alarm combined with desmopressin or alarm combined with nortriptyline. The addition of a tricyclic to other behavioural therapies did not alter treatment response. AUTHORS' CONCLUSIONS: There was evidence that tricyclics are effective at reducing the number of wet nights during treatment, but do not have a sustained effect after treatment stops, with most children relapsing. In contrast, there was evidence that alarm therapy has better short- and long-term outcomes. There was some evidence that tricyclics combined with anticholinergics may be more effective that tricyclic monotherapy.

Improvement in the emergency splinting of fractures after a simple educational exercise.

BACKGROUND: Splinting long bone fractures in the early stages of their management reduces pain, facilitates transport and helps prevent further soft tissue injury; but experience suggests that the rate of splinting is low. This study set out to quantify this rate and determine whether it could be improved with simple educational intervention. METHODS: Radiographs ordered in the emergency department over an 8-week control period were examined for fractures and presence of splints. The junior doctors responsible for these patients completed a questionnaire to assess how highly they rated early splinting. At the beginning of the next emergency term new junior doctors were given the same questionnaire followed by an information sheet relating to fracture management. The questionnaire was repeated after reading the information sheet to confirm comprehension. Radiographs performed over the following 8 weeks were examined. RESULTS: Ninety-six long bone fractures amenable to splinting were X-rayed in the control period, and of these 15 were splinted (16%). After the intervention this rose to 28 out of 98 fractures (29%, P < 0.05). The intervention group prior to reading the information sheet ranked splinting in a similar manner to the control group (P > 0.20) but significantly higher afterwards (P < 0.01). CONCLUSION: The rate of splinting of long bone fractures in the early stages of their management is low, and junior doctors do not regard this as a priority. We have shown that a simple teaching session significantly improves this rate and suggest that similar training should be provided to all emergency staff.

Use of a polymeric device to deliver growth factors to a healing fracture.

BACKGROUND: Fracture healing is a cascade of events regulated by systemic and local factors. Local growth factors are believed to play an integral role. The present study evaluates the effects of basic fibroblast growth factor (bFGF) and insulin-like growth factor-1 (IGF-1) using a controlled delivery system in a closed rodent femoral fracture model. METHODS: Female Wistar rats (n = 144) were used in the present study. Animals were randomly allocated to six groups, with each group divided into three time-points of 2, 4 and 8 weeks. Two groups had growth factor administered. The others had no operation or sham operations. Growth factors were delivered to the fracture site using a specialised delivery system. This consisted of a Kirschner-wire coated with ethylene vinyl acetate co-polymer embedded with growth factors, inserted as an intramedullary nail. Fractures were effected with a three-point bending device. Femurs were tested in four-point bending and structural properties of peak load and stiffness were obtained from the load-displacement graphs. Specimens were prepared for qualitative analysis under a light microscope and using immunohistochemistry, specimens were analysed for expression of bFGF, IGF-1 and transforming growth factor beta (TGF-beta). RESULTS: The growth factor-treated groups exhibited larger calluses at 2 and 4 weeks. Four-point bending showed weaker structural properties (stiffness and peak load) at 4 weeks in both growth factor-treated groups. Administration of bFGF or IGF-1 increased the ratio of cartilaginous to mesenchymal tissues in the fracture callus compared with non-treated animals at 2 and 4 weeks. Immunostaining intensity and distribution of both growth factors in the treated groups was greater than the non-treated groups. CONCLUSION: Exogenous delivery of bFGF or IGF-1 alters the course of fracture healing.