Opioids and pediatric urology: A prospective study evaluating prescribing habits and patient postoperative pain and narcotic utilization.

INTRODUCTION: Few pediatric urologists believe patients require a majority of the doses of opioids prescribed to them postoperatively. Seeking a better understanding of postoperative pain and analgesia in pediatric urology patients may help reduce opioid over prescription while still adequately managing postoperative pain. OBJECTIVE: We sought to better understand: 1) the postoperative pain levels experienced by pediatric urology patients, 2) the factors that correlate with postoperative pain and number of opioids consumed following pediatric urologic procedures, and 3) the patients who do not require opioids after surgery. STUDY DESIGN: Pediatric patients undergoing circumcision, inguinal hernia repair, orchidopexy, or hypospadias repair were eligible to participate. Patients were enrolled in the prospective cohort on the day of the procedure. For each of the first 7 postoperative days, patients' parents completed a text message-based questionnaire, quantifying their child's pain level and the doses of pain medication the child consumed. RESULTS: 165 participants were enrolled. 57 patients underwent circumcision, 54 underwent orchiopexy, 32 underwent hypospadias repair, and 22 underwent inguinal hernia repair. For all procedure types, pain scores (p < 0.01) and doses of oxycodone consumed were highest on postoperative day one and steadily declined thereafter. Overall, average 7-day pain score (2.02; 0.86-5.14) and doses of narcotics consumed (3.50; 0-5) were low. Patients in each surgical subgroup were prescribed narcotics in excess of what was consumed. There was an average excess of 10.9 doses (0-39.0) for hypospadias repair, 8.6 (1.0-30.0) for circumcision, 9.0 (3.0-21.0) for inguinal hernia repair, and 6.1 (0-22.0) for orchiopexy. DISCUSSION: Overall, reported pain scores and number of narcotics consumed were low regardless of surgery type. Opioids were overprescribed regardless of surgery type. CONCLUSIONS: Our findings indicate that level of pain and opioid use varies by procedure type, but that number of narcotics prescribed greatly exceeds number needed.

The utility of renal medullary pyramidal thickness measurements on the first and second postnatal ultrasound in infants with congenital hydronephrosis.

INTRODUCTION: Prior studies with postnatal ultrasound measurements of the medullary pyramid thickness (PT) demonstrate a PT < 3 mm as a significant risk factor for the diagnosis of UPJ obstruction and pyeloplasty. These studies used the postnatal ultrasound demonstrating the largest degree of hydronephrosis. Since early identification of children at increased risk of obstruction and pyeloplasty would be clinically useful, we reviewed the PT on the first and second postnatal ultrasound in infants with congenital hydronephrosis. OBJECTIVE: The aims of the study were to determine the prognostic value of: 1) PT on the first and second postnatal ultrasound, 2) a change in PT between first and second ultrasounds, and 3) ratio of PT in the hydronephrotic kidney to the contralateral PT in the normal kidney in those with unilateral hydronephrosis. We hypothesized that a smaller PT on either the first or second ultrasound, as well as a decreasing PT between the first and second ultrasound, and a decreased ratio of hydronephrotic PT to the contralateral normal kidney, would each be early predictors of subsequent pyeloplasty. STUDY DESIGN: A retrospective chart and ultrasound review of children with a diagnosis of isolated high grade (SFU grade 3 or 4) hydronephrosis was performed. This study also analyzed the impact on predictive ability of the PT obtained on an ultrasound obtained before 3 days of life compared to those in which the first ultrasound was obtained after 3 days of life. 91 infants (77 boys and 14 girls) met eligibility criteria (105 kidneys). The median age (IQR) at first ultrasound was 1.5 (1.0-15.0) days and 54.0 (27.5-123.0) days at the second ultrasound. DISCUSSION AND CONCLUSION: For the group overall, a smaller PT on both the first and second ultrasound was associated with increased risk of pyeloplasty, however, a PT obtained on an ultrasound prior to 3 days of life was not demonstrated to be predictive. Of note, PT was predictive in this same group of patients on their second ultrasound. A PT of <3 mm on an ultrasound obtained beyond 3 days of life was associated with higher risk of pyeloplasty. The PT ratio of hydronephrotic to normal contralateral kidney of the children who had their first ultrasound after 3 days of life was also significant in predicting the odds of having surgery. In addition, a decreasing PT between the first and second ultrasound was also identified as a risk factor for pyeloplasty.

Phase-adaptive brain stimulation of striatal D1 medium spiny neurons in dopamine-depleted mice.

Brain rhythms are strongly linked with behavior, and abnormal rhythms can signify pathophysiology. For instance, the basal ganglia exhibit a wide range of low-frequency oscillations during movement, but pathological "beta" rhythms at ~ 20 Hz have been observed in Parkinson's disease (PD) and in PD animal models. All brain rhythms have a frequency, which describes how often they oscillate, and a phase, which describes the precise time that peaks and troughs of brain rhythms occur. Although frequency has been extensively studied, the relevance of phase is unknown, in part because it is difficult to causally manipulate the instantaneous phase of ongoing brain rhythms. Here, we developed a phase-adaptive, real-time, closed-loop algorithm to deliver optogenetic stimulation at a specific phase with millisecond latency. We combined this Phase-Adaptive Brain STimulation (PABST) approach with cell-type-specific optogenetic methods to stimulate basal ganglia networks in dopamine-depleted mice that model motor aspects of human PD. We focused on striatal medium spiny neurons expressing D1-type dopamine receptors because these neurons can facilitate movement. We report three main results. First, we found that our approach delivered PABST within system latencies of 13 ms. Second, we report that closed-loop stimulation powerfully influenced the spike-field coherence of local brain rhythms within the dorsal striatum. Finally, we found that both 4 Hz PABST and 20 Hz PABST improved movement speed, but we found differences between phase only with 4 Hz PABST. These data provide causal evidence that phase is relevant for brain stimulation, which will allow for more precise, targeted, and individualized brain stimulation. Our findings are applicable to a broad range of preclinical brain stimulation approaches and could also inform circuit-specific neuromodulation treatments for human brain disease.

The utility of renal sonographic measurements in differentiating children with high grade congenital hydronephrosis.

INTRODUCTION: Current grading systems for hydronephrosis include a subjective determination of parenchymal 'thickness' and suffer from poor reliability. Use of more objective ultrasonographic measurements including medullary pyramidal thickness (PT) may be useful in augmenting current grading systems by decreasing subjectivity and enhancing prognostic ability. OBJECTIVE: To evaluate the utility of PT measurements in patients with SFU grades 3 and 4 hydronephrosis, we assessed the: 1) the inter-rater reliability of PT measurements, 2) the correlation between relative renal function on nuclear renal scan and PT, and 3) the pyeloplasty predictive ability of PT alone and in combination with SFU grade and/or other sonographic measurements in multivariate statistical models. STUDY DESIGN: We retrospectively reviewed 110 children with SFU grade III and IV hydronephrosis. Most patients presented with a history of prenatally detected hydronephrosis at a median age (IQR) of 1.7 months (0.6-5.2). Sixty-two kidneys were followed without operative intervention while 63 underwent pyeloplasty. Indications for surgery included an obstructive drainage pattern with a T1/2 > 20 min on diuretic renal scan in addition to decreased relative renal function less than 40%, increasing hydronephrosis on serial ultrasounds, and/or a decline in relative renal function >10% on serial renal scans. The median age at the time of pyeloplasty was 5.7 months (2.8-13.7). The median time from initial presentation to final follow-up for all patients was 28 months (18.3-44.6). The PT, APD, and renal length were measured on sonographic images. The inter-rater reliability for SFU grading was only fair whereas it was excellent for PT measurements. Receiver operating characteristic (ROC) curves were generated for inclusive multivariate models for prediction of pyeloplasty with and without SFU grade. DISCUSSION AND CONCLUSIONS: PT is a reliable and useful measurement to characterize the hydronephrotic kidney parenchyma and a PT > 3 mm occurs significantly more frequently in patients with a DRF ≥ 45% (p = 0.0056). PT alone was predictive of subsequent pyeloplasty (AUC = 0.781). A novel pyeloplasty predictive score (PPS) using only objective measurements including PT, APD, and renal length was more accurate than a PPS that incorporated SFU grade (AUC of 0.885 and 0.866, respectively). Utilization of PT ≤ 3 mm as a criterion for 'thinned parenchyma' in the SFU, UTD, and other hydronephrosis grading systems should be considered if confirmed by additional studies.

Axial levodopa-induced dyskinesias and neuronal activity in the dorsal striatum.

Levodopa-induced dyskinesias are abnormal involuntary movements that limit the effectiveness of treatments for Parkinson's disease. Although dyskinesias involve the striatum, it is unclear how striatal neurons are involved in dyskinetic movements. Here we record from striatal neurons in mice during levodopa-induced axial dyskinesias. We developed an automated 3-dimensional motion tracking system to capture the development of axial dyskinesias at ∼10ms resolution, and correlated these movements with neuronal activity of striatal medium spiny neurons and fast-spiking interneurons. The average firing rate of medium spiny neurons increased as axial dyskinesias developed, and both medium spiny neurons and fast-spiking interneurons were modulated around axial dyskinesias. We also found that delta field potential power increased in the striatum with dyskinesia, and that this increased delta power coupled with striatal neurons. Our findings provide insight into how striatal networks change as levodopa-induced dyskinesias develop, and suggest that increased medium spiny neuron firing, increased delta field potential power, and abnormal delta-coupling may be neurophysiological signatures of dyskinesias. These data could be helpful in understanding the role of the striatum in the pathogenesis of dyskinesias in Parkinson's disease.