Exploratory pilot study of exogenous sustained-release melatonin on nocturia in Parkinson's disease.

INTRODUCTION: Nocturia is one of the commonest non-motor symptoms in Parkinson's disease (PD). Nocturia has evolved from being understood as a symptom of urological disorders or neurogenic bladder dysfunction to being considered as a form of circadian dysregulation. Exogenous melatonin is known to help circadian function and can be an effective strategy for nocturia in PD. METHODS: In this open-label, single-site, exploratory, phase 2 pilot study, adults with PD and nocturia underwent assessments using standardized questionnaires, urodynamics studies and a bladder scan. This was followed by completion of a frequency volume chart (FVC) and 2-week sleep diary. Sustained-release melatonin 2 mg was then administered once-nightly for 6 weeks. A repeat assessment using questionnaires, the FVC and sleep diary was performed whilst on treatment with melatonin. Companion or bed partners filled in sleep questionnaires to assess their sleep during the intervention. RESULTS: Twenty patients (12 males; mean age 68.2 [SD = 7.8] years; mean PD duration 8.0 [±5.5] years) with PD reporting nocturia were included. Administration of melatonin was associated with a significant reduction in the primary outcome bother related to nocturia measured using the International Consultation on Incontinence Questionnaire Nocturia (ICIQ-N) (p = 0.01), number of episodes of nocturia per night (p = 0.013) and average urine volume voided at night (p = 0.013). No serious adverse events were reported. No significant improvement was noted in bed partner sleep scores. CONCLUSIONS: In this preliminary open-label study, administration of sustained-release melatonin 2 mg was found to be safe for clinical use and was associated with significant improvements in night-time frequency and nocturnal voided volumes in PD patients.

Factors influencing return for maintenance treatment with percutaneous tibial nerve stimulation for the management of the overactive bladder.

OBJECTIVES: To identify factors influencing return for maintenance percutaneous tibial nerve stimulation (PTNS) treatment after successful completion of a 12-week course of treatment for overactive bladder (OAB). PATIENTS AND METHODS: Patients with OAB symptoms referred for PTNS treatment underwent 12 sessions of weekly PTNS treatment and were evaluated at baseline and week 12 using the International Consultation on Incontinence Questionnaire on OAB, the International Consultation on Incontinence Questionnaire on lower urinary tract symptom-related quality of life (ICIQ-LUTSqol) and a bladder diary (BD). Responders to treatment, evaluated using two patient-reported outcome measures, were invited to return for maintenance treatment when symptoms returned. A PTNS Service Evaluation Questionnaire was used to evaluate factors influencing return for maintenance treatment. RESULTS: Seventy-three patients were evaluated (mean age 58.9 [±14.7] years, 72.6% women) and clustered into three groups: group 1 (n = 25) did not respond to 12 weekly sessions of PTNS treatment; group 2 (n = 17) responded to treatment but did not return for maintenance treatment and group 3 (n = 31) responded to treatment and returned for maintenance treatment. There were no significant differences in demographic characteristics, diagnosis, baseline symptom scores and BD variables among the three groups. Patients belonging to groups 2 and 3 experienced a significant improvement from baseline to week 12 in total OAB scores (group 2: -1.54 ± 1.85; group 3: -1.85 ± 2.28; P < 0.05); however, patients returning for maintenance treatment reported significant improvements specifically in nocturia (BD difference = -0.4 ± 0.7 [P < 0.05] and ICIQ-LUTSqol difference -0.48 ± 0.94 [P < 0.05]), and perceived benefits of the treatment with regard to their OAB symptoms compared to those not returning for maintenance treatment (difference between the two groups 25.6%; P = 0.030). Improvements in nocturia and perceived benefits predicted return for maintenance treatment based on a logistic regression analysis. Factors related to the need for repeat clinic visits, such as transportation, distance and time commitment, were not found to differ between the two groups. CONCLUSIONS: Twelve-session weekly PTNS is a safe and effective treatment for OAB. Responders to treatment returning for maintenance PTNS more often reported significant improvements in nocturia and perceived benefits over time, compared to those not returning for maintenance treatment. The BD provides a more objective assessment of treatment outcome after PTNS treatment.

Hereditary evaluation of multiple developmental abnormalities in the Havanese dog breed.

The Havanese is a toy breed that presents with a wide range of developmental abnormalities. Skeletal defects, particularly osteochondrodysplasia (OCD), are the most frequently observed anomalies. Cataracts, liver shunts, heart murmurs, and missing incisors are also common in this breed. Estimates of heritability and complex segregation analyses were carried out to evaluate modes of transmission for these abnormalities. A moderate heritability was identified and evidence for a single major locus was found. Novel statistical analysis methods were used to identify four traits that co-segregate: cataracts, hepatic abnormalities, OCD, and cardiac abnormalities. A canine-specific microarray was used to identify changes in gene expression in the liver that accompany the aforementioned developmental problems. One hundred and thirteen genes were found to be differentially regulated in the Havanese.