Search

Objective: To characterize the prevalence, onset, and burden of urinary and bowel dysfunction in adult patients with adrenoleukodystrophy (ALD) and to evaluate any sex differences in symptom presentation.Methods: In this retrospective and prospective study, we performed medical record review (n = 103), analyzed the results of clinically indicated urodynamic testing (n = 11), and developed and distributed a symptom and quality of life (QOL) survey (n = 59).Results: Urinary and bowel symptoms are highly prevalent in both males (75.0%) and females (78.8%) in this population, most commonly urinary urgency, often leading to incontinence. Time to onset of first urinary or bowel symptom occurs approximately a decade earlier in males. Seventy-two percent of symptomatic patients report a limitation to QOL. Urodynamic evaluation provides evidence of three distinct mechanisms underlying lower urinary tract dysfunction: involuntary detrusor contractions (indicating uncontrolled neuronal stimulation with or without leakage), motor underactivity of the bladder, and asynergy between detrusor contraction and sphincter relaxation.Conclusions: Beyond gait and balance difficulties, urinary and bowel symptoms are common in adults with ALD and impair QOL. Males are affected at a younger age but both sexes experience a higher symptom burden with age. As this population also experiences gait and balance impairment, patients with ALD are more vulnerable to urinary urgency leading to incontinence. Urodynamic evaluation may help better elucidate the pathophysiologic mechanisms underlying neurogenic lower urinary tract dysfunction, which can allow more targeted treatment. [ABSTRACT FROM AUTHOR]

Background: Postoperative inflammation is a common consequence of surgery and the ensuing stress response. Local anesthetics have anti-inflammatory properties. The primary aim of this study was to evaluate if LA administrated intraperitoneally perioperatively might inhibit expression of inflammatory cytokines.Methods: This was a, randomized, double blind, placebo-controlled study (ClinicalTrial.gov reg no: NCT02256228) in patients undergoing surgery for ovarian cancer. Patients were randomized to receive: intraperitoneal ropivacaine (Group IPLA) or saline (Group P) perioperatively. Except for study drug, patients were treated similarly. At the end of surgery, a multi-port catheter was inserted intraperitoneally, and ropivacaine 2 mg/mL or 0.9% saline, 10 mL was injected intermittently every other hour during 72 hours postoperatively. Systemic expression of cytokines and plasma ropivacaine were determined before and 6, 24, and 48 hours after surgery. Stress response was measured by serum glucose, cortisol, and insulin.Results: Forty patients were recruited, 20 in each group. There was no statistical significant difference in systemic cytokine between the groups at any time point. Serum cortisol was significantly lower in the IPLA group at 6 hours, median 103 nmol/L (IQR 53-250) compared to placebo, median 440 nmol/L (IQR 115-885), P = 0.023. Serum glucose and insulin were similar between the groups. Total and free serum concentrations of ropivacaine were well below toxic concentrations.Conclusion: In this small study, perioperative intraperitoneal ropivacaine did not reduce the systemic inflammatory response associated with major abdominal surgery. Total and free ropivacaine concentrations were below known toxic concentrations in humans. [ABSTRACT FROM AUTHOR]

Peripheral intravenous cannula (PIVC) insertion is one of the most common invasive procedures performed in neonates and is frequently associated with adverse events. There are no studies in the neonatal population looking at the possibility of reducing the risk of PIVC-related complications by elective replacement of PIVC. A randomised, non-blinded, control trial was conducted in a tertiary level neonatal unit in Melbourne, Australia, to examine rates of extravasation in neonates with elective replacement of PIVC as compared to standard practice. Neonates born at 32 weeks of gestation or more were randomly assigned to have their PIVC replaced electively (every 72-96 h) or when clinically indicated in a 1:1 allocation ratio after parental consent. Primary outcome studied was rate of extravasation. Secondary outcomes included rates of phlebitis, leakage or spontaneous dislodgement of PIVC. One hundred thirteen infants were enrolled. Extravasation was noted in 33 (60%) of standard practice group vs. 28 (48.3%) of elective replacement (RR 0.80, CI 0.57-1.13, p = 0.21) infants. Time to first extravasation was similar between the groups (hazard ratio 0.69, CI 0.42-1.15). Extravasation events per 1000 IV hours were also similar between groups. Similar results were seen by both intention to treat and per protocol analyses. There was an increase in leaking rates (HR1.98, CI 1.03-3.81, p = 0.04) in the elective group, while phlebitis and spontaneous dislodgement rates were similar to standard group.Conclusion: Elective replacement of PIVC in neonates is not associated with reduction in extravasation rates.Trial registration: This trial has been registered with the Australian and New Zealand Clinical Trials Register. Identifier: ACTRN12615000827538. What is Known: • The reported incidence of extravasation injury is as high as 70% in the neonatal and paediatric population and has an association with cannula dwell time. • Adult studies have done to look at the possibility of reducing intravenous cannula-related complications with routine replacement of the cannulas but no similar studies have been done in the neonatal population. What is New: • Routine replacement of intravenous cannula in neonates between 72 and 96 h of use does not reduce the rate of extravasation injuries. • There might be some added complications associated with such a practice. [ABSTRACT FROM AUTHOR]

Study Design: This study investigated whether access to genitourinary medicine (GUM) clinics meets UK-recommended standards.Methods: In January 2014 and 2015, postal questionnaires about appointment and service characteristics were sent to lead clinicians of UK GUM clinics. In February 2014 and 2015, researchers posing as symptomatic and asymptomatic 'patients' contacted clinics by telephone, requesting to be seen. Clinic and patient characteristics associated with the offer of an appointment within 48 hours were examined using unadjusted and UK country and patient gender adjusted multivariable logistic regression analyses. In March 2015, a convenience sample (one in four) of clinics was visited by researchers with the same clinical symptoms. Ability to achieve a same-day consultation and waiting time were assessed.Results: In 2015, 90.8% of clinics offered symptomatic 'patients' an appointment within 48 hours when contacted by telephone, compared with 95.5% in 2014 (aOR=0.46 (0.26 to 0.83); p<0.01). The decline was greatest in women (96.0% to 90.1%; p<0.05), and clinics in England (96.2% to 90.7%; p<0.01). For asymptomatic patients, the proportion offered an appointment within 48 hours increased from 50.7% in 2014 to 74.5% in 2015 (aOR=3.06 (2.23 to 4.22); p<0.001), and in both men (58.2% to 90.8%; p<0.001) and women (49.0% to 59.6%; p<0.01). In adjusted analysis, asymptomatic women were significantly less likely to be offered an appointment than asymptomatic men (aOR=0.33 (0.23 to 0.45); p value<0.001). 95% of clinics were able to see symptomatic patients attending in person.Conclusions: Access to GUM services has worsened for those with symptoms suggestive of an acute STI and is significantly poorer for asymptomatic women. This evidence may support the reintroduction of process targets. [ABSTRACT FROM AUTHOR]

Background: Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age.Methods: Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos.Results: Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p < .05. These decrements were relatively stable over time. Findings did not vary depending on the hormone therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase.Conclusions: CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years. [ABSTRACT FROM AUTHOR]

The treatment of early Parkinson's disease with dopaminergic agents remains the mainstay of symptomatic therapy for this incurable neurodegenerative disorder. However, clinical responses to dopaminergic drugs vary substantially from person to person due to individual-, drug- and disease-related factors that may in part be genetically determined. Using clinical data and DNA samples ascertained through the largest placebo-controlled clinical trial of the monoamine oxidase B inhibitor, rasagiline (ClinicalTrials.gov number, NCT00256204), we examined how polymorphisms in candidate genes associate with the clinical response to rasagiline in early Parkinson's disease. Variants in genes that express proteins involved in the pharmacokinetics and pharmacodynamics of rasagiline, and genes previously associated with the risk to develop Parkinson's disease were genotyped. The LifeTechnologies OpenArray NT genotyping platform and polymerase chain reaction-based methods were used to analyse 204 single nucleotide polymorphisms and five variable number tandem repeats from 30 candidate genes in 692 available DNA samples from this clinical trial. The peak symptomatic response to rasagiline, the rate of symptom progression, and their relation to genetic variation were examined controlling for placebo effects using general linear and mixed effects models, respectively. Single nucleotide polymorphisms, rs2283265 and rs1076560, in the dopamine D2 receptor gene (DRD2) were found to be significantly associated with a favourable peak response to rasagiline at 12 weeks in early Parkinson's disease after controlling for multiple testing. From a linear regression, the betas were 2.5 and 2.38, respectively, with false discovery rate-corrected P-values of 0.032. These polymorphisms were in high linkage disequilibrium with each other (r(2) = 0.96) meaning that the same clinical response signal was identified by each of them. No polymorphisms were associated with slowing the rate of worsening in Parkinson symptoms from Weeks 12 to 36 after correction for multiple testing. This is the largest and most comprehensive pharmacogenetics study to date examining clinical response to an anti-parkinsonian drug and the first to be conducted in patients with early stage Parkinson's disease receiving monotherapy. The results indicate a clinically meaningful benefit to rasagiline in terms of the magnitude of improvement in parkinsonian symptoms for those with the favourable response genotypes. Future work is needed to elucidate the specific mechanisms through which these DRD2 variants operate in modulating the function of the nigrostriatal dopaminergic system.media-1vid110.1093/brain/aww109_video_abstractaww109_video_abstract. [ABSTRACT FROM AUTHOR]

Telemedicine-based medication management improves hypertension control, but has been evaluated primarily in patients with low antihypertensive drug counts. Its impact on patients taking three or more antihypertensive agents is not well-established. To address this evidence gap, the authors conducted an exploratory analysis of an 18-month, 591-patient trial of telemedicine-based hypertension medication management. Using general linear models, the effect of medication management on blood pressure for patients taking two or fewer antihypertensive agents at study baseline vs those taking three or more was compared. While patients taking two or fewer antihypertensive agents had a significant reduction in systolic blood pressure with medication management, those taking three or more had no such response. The between-subgroup effect difference was statistically significant at 6 months (-6.4 mm Hg [95% confidence interval, -12.2 to -0.6]) and near significant at 18 months (-6.0 mm Hg [95% confidence interval, -12.2 to 0.2]). These findings suggest that baseline antihypertensive drug count may impact how patients respond to hypertension medication management and emphasize the need to study management strategies specifically in patients taking three or more antihypertensive medications. [ABSTRACT FROM AUTHOR]

Busulfan is an alkylating agent that is widely used in preparative regimens for bone marrow transplantation (BMT). We developed a high-performance liquid chromatographic (HPLC) assay for the determination of plasma busulfan concentrations in 30 patients who received oral doses of 1 mg/kg. Concentrations were fit by a one-compartment pharmacokinetic model with first-order absorption. The pattern of absorption and elimination varied widely between patients, with peak concentrations ranging from 1.2 to 10.4 mumol/l (mean, 4.25 +/- 2.49). The elimination half-life ranged from 58 to 433 min (harmonic mean, 140 min). The AUC contributed by a single oral dose ranged from 606 to 5,144 mumol-min/l (mean, 2,012 +/- 1,223). Patients were evaluated for the development of veno-occlusive disease (VOD), a treatment complication that occurs in 20% of patients undergoing BMT and causes 10% of transplantation-related deaths. All six patients who developed VOD had an AUC greater than the mean, and five of them had an AUC that was greater than 1 SD above the mean. The occurrence of VOD was highly correlated with an increased AUC (greater than 1 SD above the mean) (X2 = 18; P less than 0.0001). Using multivariate logistic regression, no other statistically significant pharmacokinetic predictor of VOD was found. The tenfold variability in the busulfan AUC and the statistical association of increased AUC with the development of VOD suggest a possible role for therapeutic monitoring in this setting. [ABSTRACT FROM AUTHOR]

Background: Obtaining accurate blood pressure (BP) readings is a challenge faced by health professionals. Clinical trials implement strict protocols, whereas clinical practices and studies that assess quality of care utilize a less rigorous protocol for BP measurement.Objective: To examine agreement between real-time clinic-based assessment of BP and the standard mercury assessment of BP.Design: Prospective reliability study.Patients: One hundred patients with an International Classification of Diseases-9th edition code for hypertension were enrolled.Measures: Two BP measurements were obtained with the Hawksley random-zero mercury sphygmomanometer and averaged. The clinic-based BP was extracted from the computerized medical records.Results: Agreement between the mercury and clinic-based systolic blood pressure (SBP) was good, intraclass correlation coefficient (ICC)=0.91 (95% confidence interval (CI): 0.83 to 0.94); the agreement for the mercury and clinic-based diastolic blood pressure (DBP) was satisfactory, ICC=0.77 (95% CI: 0.62 to 0.86). Overall, clinic-based readings overestimated the mercury readings, with a mean overestimation of 8.3 mmHg for SBP and 7.1 mmHg for DBP. Based on the clinic-based measure, 21% of patients were misdiagnosed with uncontrolled hypertension.Conclusions: Health professionals should be aware of this potential difference when utilizing clinic-based BP values for making treatment decisions and/or assessing quality of care. [ABSTRACT FROM AUTHOR]

Background Context: There has been renewed interest in the pelvic vertebrae by spinal surgeons recently. Those involved in working with patients with adult spinal deformity focus on the position of the fused spine as it relates to the pelvis, and determine success or failure by specific numbers for given pelvic parameters. The pelvic parameters that are commonly measured for these patients are pelvic tilt, sacral slope, and pelvic incidence (PI). Out of the three, PI has always been considered to be the fixed measurement, whereas pelvic tilt and sacral slope have the capacity to change in relation to external forces. The assumption that the PI does not change has not been proven in a healthy, asymptomatic population.Purpose: This study aimed to investigate the differences in PI between three pelvic positions used in common functional activities: resting baseline pelvic posture, maximal anterior pelvic rotation, and maximal posterior pelvic rotation.Study Design/setting: This was a randomized, prospective study of 50 healthy, asymptomatic, individuals who were recruited from the vicinity of our institution.Patient Sample: Fifty patients (16 men with a mean age of 26.5±12.1 years; 34 women with a mean age of 27.2±10.8 years) were recruited for this study. Initial screening occurred by telephone. The inclusion criteria consisted of participants being between 18 and 79 years of age, no previous history of spine, pelvic, or lower extremity pain which had lasted longer than 48 hours, or history of any disorder in the spine, pelvis, or lower extremity that had required medical care. Female patients could not be pregnant at the time of participation.Outcome Measures: Changes in PI were assessed by examining the differences between the values of the PI with each change in pelvic position: resting to maximal anterior pelvic rotation and resting to maximal posterior pelvic rotation. Inter-rater reliability was assessed using Cronbach's alpha.Methods: This study was funded by a Small Exploratory Grant from the Scoliosis Research Society. All subjects had an initial posterior-anterior and lateral radiograph taken in their resting pelvic position. If no spinal deformity was noted, each subject was instructed to maximally rotate their pelvis anteriorly and an immediate lateral radiograph was taken. The subject was then instructed to maximally rotate their pelvis posteriorly and an immediate lateral radiograph was again taken. Radiographic measurements of PI were independently measured by a board-certified, fellowship trained orthopedic spine surgeon and a board-certified musculoskeletal radiologist after defining and agreeing to the specific manner of measurement.Results: Pelvic incidence values changed in 44 of 50 subjects (88%) when they maximally anteriorly rotated their pelvis from the resting pelvic position. The mean change was 2.9°, with 23 of 50 subjects (46%) changing ≥3°. Pelvic incidence values changed in 40 of 50 subjects (80%) when they maximally posteriorly rotated their pelvis from the resting position. The mean change was 2.82° with 27 of 50 subjects (54%) changing by ≥3°.Conclusions: This study demonstrated that for a high percentage of the healthy subjects who participated, the PI changed when the subjects varied their pelvic position. This questions the assumption that PI is a fixed parameter and suggests a potential functional motion at the sacroiliac joint. It also supports the idea that intentionally changing one's posture could lead to a change in PI, an idea that could have ramifications in surgical cases. [ABSTRACT FROM AUTHOR]