Entire 24-hour Period Research Articles

Twenty-Four-Hour Ambulatory Blood Pressure Monitoring Parameters During Pregnancy: A Pilot Study.

Introduction: Maternal blood pressure (BP) is a critical cardiovascular marker with profound implications for maternal and fetal well-being, particularly in the detection of hypertensive disorders during pregnancy. Although conventional clinic-based BP (CBP) measurements have traditionvally been used, monitoring 24-hour ambulatory BP (ABP) has emerged as a more reliable method for assessing BP levels and diagnosing conditions such as gestational hypertension and preeclampsia/eclampsia. This study aimed to assess the feasibility and acceptability of 24-hour ABP monitoring in pregnant women and report on various ABP parameters, including ambulatory blood pressure variability (ABPV). Method: A prospective cross-sectional study design was employed, involving 55 multipara pregnant women with and without prior adverse pregnancy outcomes (APOs). The participants underwent baseline assessments, including anthropometrics, resting CBP measurements, and the placement of ABP and actigraphy devices. Following a 24-hour period with these devices, participants shared their experiences to gauge device acceptability. Pregnancy outcomes were collected postpartum. Results: Twenty-four-hour ABP monitoring before 20 weeks of gestation is feasible for women with and without prior APOs. Although some inconvenience was noted, the majority of participants wore the ABP monitoring device for the entire 24-hour period. Pregnant women who later experienced APOs exhibited higher 24-hour ABP and ABPV values in the early stages of pregnancy. Conclusion: The study highlights the potential benefits of 24-hour ABP monitoring as a valuable tool in prenatal care, emphasizing the need for further research in this area.

Power Bill Optimization for Grid-tie Solar PV-Battery House

This study focuses on the optimization of power bills for a house equipped with a grid-tie solar PV-battery system. Rather than adhering to conventional load scheduling practices or minimizing grid power usage at each time interval, a novel approach is adopted wherein the optimization is performed for the entire 24-hour period simultaneously. By directly incorporating time-of-use rates into the cost function, an absolute optimal solution is attained. The findings indicate that compared to single time step optimization, the proposed method results in a reduction of the power bill ranging from 6% to 10%, depending on load-generation variations. Furthermore, if the utility or government enforces the summer tariff consistently throughout the year, the savings escalate to a range of 15% to 22%. Introducing a more intelligent tariff structure can thus serve as an effective means to expedite the transition towards renewable energy by incentivizing individual investments in solar PV, battery systems, and smart home energy management.

Effect of initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy on ambulatory blood pressure indices

Abstract Background The QUARTET trial showed that a combination of four ultra-low-dose blood pressure (BP) medications lowered mean unattended office BP more effectively than initial monotherapy. Purpose To investigate the effects of a combination of four ultra-low-dose blood pressure (BP) medications on ambulatory BP changes. Methods Australian adults (≥18 years) with hypertension who were untreated or on monotherapy were eligible for participation in the QUARTET study. Overall, 591 participants were randomly assigned to receive either the quadpill (containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or an indistinguishable monotherapy control (irbesartan 150 mg). The difference in 24-hour, daytime and night-time systolic and diastolic ambulatory BP at 12 and 52 weeks were pre-defined secondary outcomes. Reported parameters for this analysis were derived from ambulatory BP recordings of 576 participants that fulfilled pre-defined validation criteria. Results Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At baseline, 24-h systolic/diastolic BP was 139.2/81.0 mmHg in the monotherapy vs. 139.8/81.3 in the quadpill group, daytime BP was 142.5/83.5 vs 143.4/84.0 mmHg, and night-time BP was 125.1/70.7 vs. 125.4/70.7 mmHg. At 12 weeks, mean 24-h ambulatory systolic and diastolic BP were 7.7 (95%CI: 9.6, 5.8) and 5.3 (95%CI: 6.5, 4.1) mmHg lower in the quadpill versus monotherapy group (p<0.001 for both). Similar reductions were observed for daytime (8.1/5.7 mmHg lower in quadpill compared to montherapy group) and night-time (6.3/4.0 mmHg lower in quadpill compared to monotherapy group) BP (all p<0.001) at 12 weeks. The reduction in systolic and diastolic ambulatory BP variability were more pronounced in the quadpill group at 12 weeks, the 24-h standard deviation was reduced by -1.2 (-1.8, -0.5) mmHg for systolic and -0.9 (-1.5, -0.4) mmHg diastolic BP. The rate of BP control (24 hours BP ≥130 and/or ≥80 mmHg) at 12 weeks was higher in the quadpill group (77% vs 50%; p<0.001). These effects were maintained at 52 weeks. Conclusion A quadruple quarter-dose combination compared to monotherapy resulted in greater ambulatory BP lowering across the entire 24-hour period with higher ambulatory BP control rates at both 12 and 52 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy – which has been previously shown not to increase the rate of side effects - and extends it to ambulatory BP measurements.

As loud as a construction site: Noise levels in the emergency department

BackgroundThe Emergency Department (ED), while being an integral part of healthcare systems, frequently experiences noise levels surpassing the World Health Organization's recommended thresholds. These excessive noise levels could considerably compromise the safety and wellbeing of both patients and staff. MethodsTo evaluate noise levels throughout the ED environment, this study utilized dosimeters to measure noise levels over a 24-hour period in six distinct locations, including the ED Waiting Room and Treatment areas. ResultsThe study found that noise exceeded the WHO recommendations in all six areas of the ED for the entire 24-hour period. Peak noise levels were recorded up to 102.8 dB, which is as loud as noise levels at a construction site. The ED Waiting Room exhibited high peak and average noise levels, indicating the urgent need for quality improvement efforts. These findings align with the results of previous research, thereby suggesting that noise levels in the ED have remained problematic for more than a decade. ConclusionThe findings of this study underscore the importance of addressing excessive noise levels in the ED to create a safe and therapeutic hospital environment for both patients and staff. Healthcare organizations must implement proactive measures to address excessive noise levels in the ED.

DIFFERENCES IN AMBULATORY BP LEVELS AND INTENSITY OF ANTIHYPERTENSIVE TREATMENT BETWEEN MEN AND WOMEN UNDERGOING PERITONEAL DIALYSIS

Objective: The aim of the present study was to compare the ambulatory blood pressure (BP) levels and intensity of antihypertensive treatment between men and women with end-stage kidney disease receiving long-term peritoneal dialysis (PD). Design and method: Following a case-control design, 48 male PD patients from Northern Greece were matched for age and history of heart failure with 48 female patients in a 1:1 ratio. All patients underwent 24-hour ambulatory BP monitoring with the oscillometric device Mobil-O-Graph (IEM, Stolberg, Germany). The BP-lowering medications actually taken by the patients were prospectively recorded. Results: Age, dialysis vintage and the burden of cardiovascular comorbidities did not differ between men and women. There were no significant sex differences in ambulatory systolic BP (24-hour period: 129.0±17.8 vs. 128.5±17.5 mmHg, P = 0.138; daytime: 129.6±17.5 vs. 129.7±17.4 mmHg, P = 0.991; nighttime: 127.0±19.8 vs. 125.9±18.8 mmHg, P = 0.776). However, the levels of ambulatory diastolic BP were consistently higher in men than in women over the entire 24-hour period (81.5±12.1 vs. 76.8±10.3 mmHg, P<0.05) as well as during daytime (82.5±11.8 vs. 78.1±10.4 mmHg, P<0.05) and during nighttime (78.8±13.9 vs. 73.8±11.1 mmHg, P<0.05). The proportion of patients with 24-hour ambulatory BP <130/80 mmHg was numerically lower in men than in women (35.4% vs. 43.8%), despite the greater intensity of antihypertensive treatment in men. As compared with women, men were receiving a higher average number of BP-lowering medications daily (2.4±1.1 vs. 1.8±1.1, P<0.05) and were being treated more commonly with beta-blockers (85.1% vs. 66.7%, P<0.05) and dihydropyridine calcium-channel-blockers (70.2% vs. 43.8%, P = 0.01). Conclusions: The present study shows that among patients undergoing PD, the ambulatory BP levels and intensity of antihypertensive treatment are higher in men than in women. Prospective observational studies are needed to explore whether these sex differences in the severity of hypertension contribute to a higher risk for adverse health outcomes in men receiving long-term PD.

Peripheral Nerve Blockade for Medial Patellofemoral Ligament Reconstruction in Pediatric Patients: The Addition of a Proximal Single-Injection Sciatic Nerve Block Provides Improved Analgesia.

PurposeWe tested the hypothesis that the addition of a single-injection proximal sciatic nerve block to an adductor canal block would significantly reduce pain scores and opioid requirements compared to a group of patients that received only an adductor canal or femoral nerve block for medial patellofemoral ligament reconstruction in pediatric patients. The primary end-point is the number of patients achieving a Patient Acceptable Symptom State (PASS) (pain score less than four) for the entire 24-hour postoperative period in patients with and without a proximal sciatic block.Patients and MethodsThis is a retrospective cohort study of 144 consecutive pediatric patients, ages 10 to 18 years, undergoing medial patellofemoral ligament reconstruction with peripheral nerve blockade for postoperative analgesia from 2016–2020 at a pediatric orthopedics children’s hospital. Patients were divided into 2 cohorts with and without a proximal sciatic nerve block: group A/F: adductor canal or femoral CPNB and group AS: adductor canal CPNB and a proximal single-injection sciatic nerve block.ResultsThere was strong evidence for an increase in the number of patients who reported a pain score less than four for the entire 24-hour postoperative period in the group that received the additional proximal sciatic block. (PASS: A/F 13/62 (21%) vs AS 43/82 (52%), p<0.001) There was strong evidence for a reduction in mean and maximum pain scores and opioid requirements in the first 24-hours after surgery in the proximal sciatic group.ConclusionThe addition of a proximal sciatic nerve block was associated with significantly reduced mean and maximum pain scores and opioid requirements after medial patellofemoral ligament reconstruction in pediatric patients and supports a randomized clinical trial to confirm these findings. Based on the results of this study we recommend the addition of a proximal sciatic nerve block, anterior or posterior, to an adductor canal block to provide improved analgesia and reduced opioid requirements in the 24-hours after MPFLR in pediatric patients.

Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma.

The application of large-scale metabolomic profiling provides new opportunities for realizing the potential of omics-based precision medicine for asthma. By leveraging data from over 14,000 individuals in four distinct cohorts, this study identifies and independently replicates 17 steroid metabolites whose levels were significantly reduced in individuals with prevalent asthma. Although steroid levels were reduced among all asthma cases regardless of medication use, the largest reductions were associated with inhaled corticosteroid (ICS) treatment, as confirmed in a 4-year low-dose ICS clinical trial. Effects of ICS treatment on steroid levels were dose dependent; however, significant reductions also occurred with low-dose ICS treatment. Using information from electronic medical records, we found that cortisol levels were substantially reduced throughout the entire 24-hour daily period in patients with asthma who were treated with ICS compared to those who were untreated and to patients without asthma. Moreover, patients with asthma who were treated with ICS showed significant increases in fatigue and anemia as compared to those without ICS treatment. Adrenal suppression in patients with asthma treated with ICS might, therefore, represent a larger public health problem than previously recognized. Regular cortisol monitoring of patients with asthma treated with ICS is needed to provide the optimal balance between minimizing adverse effects of adrenal suppression while capitalizing on the established benefits of ICS treatment.

Impact of shift working on the potential for self-powering via kinetic energy harvesting in wearable devices.

Wearable devices are having a transformative impact on personalised monitoring and care. However, they frequently have limited battery life, requiring charging every few days; a major source of user frustration. Kinetic energy harvesting may help overcome this, collecting energy from the user's motion to allow the device to self-charge. While there are many works which have investigated wearable energy harvesting potential, none have incorporated socio-economic factors which affect activity, such as occupation type, on energy harvesting potential. We use the UK Biobank free-living accelerometer dataset to investigate the impact of occupational patterns on energy harvesting potential for the first time. We identify that those following shift patterns have a different distribution of when power is available, with those who work shifts having the most power intense period spread over a longer period of the day compared to controls. When stratifying into day or night shift work, we identify that those who work night shifts have a large variation between participants, as their most energy dense period is spread over the entire 24-hour period. This is compared to day shift workers who have the most power concentrated within a substantially smaller window, typically in the morning. Considering these socio-economic factors may affect system design of wearable energy harvesters.

Understanding Circadian Mechanisms of Sudden Cardiac Death: A Report From the National Heart, Lung, and Blood Institute Workshop, Part 1: Basic and Translational Aspects.

Sudden cardiac death (SCD), the unexpected death due to acquired or genetic cardiovascular disease, follows distinct 24-hour patterns in occurrence. These 24-hour patterns likely reflect daily changes in arrhythmogenic triggers and the myocardial substrate caused by day/night rhythms in behavior, the environment, and endogenous circadian mechanisms. To better address fundamental questions regarding the circadian mechanisms, the National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death. We present a 2-part report of findings from this workshop. Part 1 summarizes the workshop and serves to identify research gaps and opportunities in the areas of basic and translational research. Among the gaps was the lack of standardization in animal studies for reporting environmental conditions (eg, timing of experiments relative to the light dark cycle or animal housing temperatures) that can impair rigor and reproducibility. Workshop participants also pointed to uncertainty regarding the importance of maintaining normal circadian rhythmic synchrony and the potential pathological impact of desynchrony on SCD risk. One related question raised was whether circadian mechanisms can be targeted to reduce SCD risk. Finally, the experts underscored the need for studies aimed at determining the physiological importance of circadian clocks in the many different cell types important to normal heart function and SCD. Addressing these gaps could lead to new therapeutic approaches/molecular targets that can mitigate the risk of SCD not only at certain times but over the entire 24-hour period.

Heart Rate Variability as an Indicator of Autonomic Nervous System Disturbance in Behcet's Disease.

BackgroundBehçet’s disease (BD) is a multisystemic vasculiti where cardiac involvement is not common. Previous studies have shown that the incidence of ventricular arrhythmia and sudden cardiac death (SCD) is higher in patients with BD than in the healthy population. Among various possible explanations, autonomic nervous system (ANS) dysfunction has been suggested. Few studies have evaluated ANS function in patients with BD, and the results obtained are controversial.ObjectiveWe aimed to assess cardiac autonomic function by heart rate variability (HRV) in patients with BD; to evaluate circadian changes in HRV; and to study the relationship between HRV parameters and disease parameters.MethodsThirty-six patients with Behçet’s disease (median age 42 years, 28 men) and 36 age- and sex-matched healthy volunteers were included. HRV analyses were performed in the time and frequency domains for the entire 24-hour period and for the daytime and nighttime periods. BD activity was studied with Behcet’s disease current activity form (BDCAF).ResultsPatients with BD had significantly lower values of SDNN compared to controls. PNN50, RMSSD, and HF components mean values were significantly reduced in patients than in controls implying parasympathetic impairment. LF was comparable between the two groups, whereas LF/HF ratio was significantly higher in BD group. The circadian rhythm of HRV was preserved in patient group. There was no significant correlation of CRP or disease duration with HRV indices in Behçet’s subjects. BDCAF score was found to be negatively correlated with LF/HF.ConclusionPatients with BD, despite no cardiovascular involvement, have reduced parasympathetic activity compared with controls. However, circadian rhythms of autonomic function were preserved. As known, there is strong evidence for the role of the ANS in the pathogenesis of ventricular arrhythmias. Thus, being a practical tool, HRV can be an interesting approach for the rhythmic follow-up of BD patients.

Pralidoxime improves the hemodynamics and survival of rats with peritonitis-induced sepsis

Several studies have suggested that sympathetic overstimulation causes deleterious effects in septic shock. A previous study suggested that pralidoxime exerted a pressor effect through a mechanism unrelated to the sympathetic nervous system; this effect was buffered by the vasodepressor action of pralidoxime mediated through sympathoinhibition. In this study, we explored the effects of pralidoxime on hemodynamics and survival in rats with peritonitis-induced sepsis. This study consisted of two sub-studies: survival and hemodynamic studies. In the survival study, 66 rats, which survived for 10 hours after cecal ligation and puncture (CLP), randomly received saline placebo, pralidoxime, or norepinephrine treatment and were monitored for up to 24 hours. In the hemodynamic study, 44 rats were randomly assigned to sham, CLP-saline placebo, CLP-pralidoxime, or CLP-norepinephrine groups, and hemodynamic measurements were performed using a conductance catheter placed in the left ventricle. In the survival study, 6 (27.2%), 15 (68.1%), and 5 (22.7%) animals survived the entire 24-hour monitoring period in the saline, pralidoxime, and norepinephrine groups, respectively (log-rank test P = 0.006). In the hemodynamic study, pralidoxime but not norepinephrine increased end-diastolic volume (P <0.001), stroke volume (P = 0.002), cardiac output (P = 0.003), mean arterial pressure (P = 0.041), and stroke work (P <0.001). The pressor effect of norepinephrine was short-lived, such that by 60 minutes after the initiation of norepinephrine infusion, it no longer had any significant effect on mean arterial pressure. In addition, norepinephrine significantly increased heart rate (P <0.001) and the ratio of arterial elastance to ventricular end-systolic elastance (P = 0.010), but pralidoxime did not. In conclusion, pralidoxime improved the hemodynamics and 24-hour survival rate in rats with peritonitis-induced sepsis, but norepinephrine did not.

Temporal partitioning of diurnal bird and nocturnal small mammal visitors to a winter flowering endemic succulent

Floral nectar is an important attractant and reward for visitors, and is often produced in synchrony with peak activity of pollinators. Aloe peglerae flowers in winter, and previous studies have shown that it is pollinated primarily by diurnal generalist birds, with small mammals making additional contributions to pollination at night. Nectar produced during the day is the main attractant and reward for birds, but the nectar rewards available to small mammals are unknown. This paper investigates nectar availability in Aloe peglerae, because small mammals may be feeding on remaining, or freshly produced, nectar at night. Nectar availability over a 24-hour period was measured in screened and unscreened plants (n = ten plants per treatment), and the associated partitioning of visits by diurnal birds and nocturnal small mammals assessed. Nectar is constantly available over 24-hours, but in different quantities. Nectar volume of screened (nectar availability) and unscreened (standing crop) plants, is significantly higher early in the morning after sunrise, compared with all other sampling periods during the 24-hour period. Nectar concentration did not vary over 24-hours, averaging 11.5 ± 0.4% w/w (unscreened) across the entire 24-hour period. Peaks in visits by different guilds occurred at periods (i.e. diurnal birds and nocturnal small mammals) when nectar availability was high. Aloe peglerae has higher daytime nectar production, when its primary pollinators are most active, but the continual, albeit reduced, nectar availability at night attracts small mammals. Mobile diurnal birds, and less-mobile nocturnal small mammals, both rely on this nectar resource during dry and cold South African winters and, in turn, are important pollinators for this Critically Endangered Aloe species.

Interpreting blood GLUcose data with R package iglu.

Continuous Glucose Monitoring (CGM) data play an increasing role in clinical practice as they provide detailed quantification of blood glucose levels during the entire 24-hour period. The R package iglu implements a wide range of CGM-derived metrics for measuring glucose control and glucose variability. The package also allows one to visualize CGM data using time-series and lasagna plots. A distinct advantage of iglu is that it comes with a point-and-click graphical user interface (GUI) which makes the package widely accessible to users regardless of their programming experience. Thus, the open-source and easy to use iglu package will help advance CGM research and CGM data analyses. R package iglu is publicly available on CRAN and at https://github.com/irinagain/iglu.

PD04-06 SIGNIFICANT POST-PRANDIAL URINARY HYPEROXALURIA OBSERVED BY SPOT TESTING INDIVIDUAL URINARY VOIDS

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I (PD04)1 Apr 2020PD04-06 SIGNIFICANT POST-PRANDIAL URINARY HYPEROXALURIA OBSERVED BY SPOT TESTING INDIVIDUAL URINARY VOIDS William Donelan*, Pedro Espino-Grosso, Tina Esfandiary, Alexandria Voigt, Paul Dominguez-Gutierrez, Cuong Nguyen, and Benjamin Canales William Donelan*William Donelan* More articles by this author , Pedro Espino-GrossoPedro Espino-Grosso More articles by this author , Tina EsfandiaryTina Esfandiary More articles by this author , Alexandria VoigtAlexandria Voigt More articles by this author , Paul Dominguez-GutierrezPaul Dominguez-Gutierrez More articles by this author , Cuong NguyenCuong Nguyen More articles by this author , and Benjamin CanalesBenjamin Canales More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000824.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary oxalate is a vital component of supersaturation profiles and a major driving force for crystallization. Although routinely assessed by metabolic testing, the 24-hour urine collection lacks the ability to measure spikes in urine oxalate concentration, particularly those that follow the consumption of a high oxalate-containing meal. To determine whether oxalate spikes are important for predicting stone risk, we measured oxalate concentration in each void over a 24-hour period in individuals who ingested a high oxalate-containing meal. METHODS: After IRB approval, healthy non-stone formers (6 F, 5 M) were prospectively enrolled to collect consecutively voided urine specimens over a 24-hour period. Participants were given a dietary log and instructed to consume food low in oxalate throughout the entire collection period. At noon on their collection day, participants were asked to consume a high-oxalate load (HOL) in the form of 100g spinach. Participants collected urinary voids in separate containers approximately every 3 hours during the day. Oxalate levels were evaluated on each specimen as well as the final combined 24-hour collection using the Trinity Biotech Oxalate Assay. RESULTS: The 24-hour average urinary oxalate concentrations measured approximately 0.45mM, which is at the normal high end for healthy individuals. We found that within the time period 2-8 hours post-HOL, 43.7% of the daily oxalate excretion occurred, and participants had hyperoxaluric voids that were significantly higher compared to baseline levels or the mean of the entire 24-hour period. CONCLUSIONS: The study demonstrates that significant post-prandial urinary hyperoxaluric spikes occur that are missed using the classical 24-hour urine test. This, together with hyperoxaluria as a potential etiopathological entity in a variety of disease processes, underscores the need for regular temporal-based monitoring of urinary oxalate levels. Source of Funding: This work was supported in part by the Urology Care Foundation Research Scholar Award Program and The Endourological Society; and by The National Institutes of Health Grant 5T32DK094789-05. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e80-e80 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information William Donelan* More articles by this author Pedro Espino-Grosso More articles by this author Tina Esfandiary More articles by this author Alexandria Voigt More articles by this author Paul Dominguez-Gutierrez More articles by this author Cuong Nguyen More articles by this author Benjamin Canales More articles by this author Expand All Advertisement PDF downloadLoading ...

Circadian Misalignment of the 24-hour Profile of Endocannabinoid 2-Arachidonoylglycerol (2-AG) in Obese Adults.

The endocannabinoid (eCB) system partly controls hedonic eating, a major cause of obesity. While some studies suggested an overactivation of the eCB system in obesity, peripheral levels of eCBs across the 24-hour cycle have not been characterized in obese individuals despite the fact that in lean adults, levels of the eCB 2-arachidonoylglycerol (2-AG) vary across the day. We sought to examine 24-hour profiles of serum concentrations of 2-AG in healthy obese and nonobese adults, under well-controlled laboratory conditions. We also simultaneously assessed 24-hour profiles of 2-oleoylglycerol (2-OG), leptin, and cortisol in each participant. With fixed light-dark and sleep-wake cycles, blood sampling was performed over an entire 24-hour period, including identical meals at 0900, 1400, and 1900. Twelve obese (8 women, mean body mass index [BMI]: 39.1 kg/m2) and 15 nonobese (6 women; mean BMI: 23.6 kg/m2) healthy adults were studied. We observed a 24-hour variation of 2-AG levels in obese individuals but, relative to nonobese adults, the amplitude was dampened and the timings of the nadir and peak were delayed by 4 to 5 hours. The profile of 2-OG was similarly misaligned. In contrast, when expressed relative to the 24-hour mean level, the 24-hour rhythm of cortisol and leptin were similar in obese and nonobese participants. Obesity appears to be associated with a dampening and delay of the 24-hour variation of eCB activity relative to the central circadian signal as well as to the daily leptin rhythm. This misalignment may play a role in the pathophysiology of obesity.

Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Amisulpride as Treatment of Established Postoperative Nausea and Vomiting in Patients Who Have Had No Prior Prophylaxis.

Postoperative nausea and vomiting (PONV) occurs commonly in surgical patients despite widespread prophylactic antiemetic use. Rescue options are currently limited. 5HT3 antagonists are most frequently used for prophylaxis, but if they fail, additional doses are not effective as rescue medication. Intravenous (IV) amisulpride, a well-studied D2/D3 antagonist, has been shown in trials to prevent PONV. This study was designed to determine if amisulpride could be used to treat established PONV in patients at low-to-moderate risk of PONV who had not received any prior prophylaxis. Men and women aged over 18 years were permitted to enroll if they were to undergo general inhalational anesthesia, expected to last at least 1 hour, for an outpatient or inpatient surgical procedure. Patients who then suffered PONV were randomized equally to 1 of 3 single-dose IV regimens: placebo or 5 or 10 mg amisulpride. The primary end point was complete response, defined as no emesis in the period 30 minutes to 24 hours after study drug treatment and no use of rescue medication in the entire 24-hour period. One thousand nine hundred eighty-eight patients were enrolled preoperatively, of whom 560 were randomized to a treatment arm. Complete response occurred in 39 of 181 patients (21.5%) in the placebo group compared to 60 of 191 patients (31.4%; P = .016) and 59 of 188 patients (31.4%; P = .016) in the amisulpride 5 and 10 mg groups, respectively. The adverse event profile of amisulpride at either dose was similar to placebo. IV amisulpride at 5 and 10 mg was safe and efficacious in the treatment of established PONV in surgical patients undergoing general anesthesia with no prior PONV prophylaxis.

24-Hour Profile of Microvascular Liver Perfusion in Sickle Cell Disease Mice Following Hypoxia-Induced Vaso-Occlusion

Introduction: Sickle cell disease (SCD) is a debilitating genetic disorder of the red blood cells, leading to acute vaso-occlusive (VOC) events and chronic disease in multiple organs. In the liver, VOC events in the hepatic sinusoids can lead to fatal sickle cell intrahepatic cholestasis (SCIC), which is estimated to occur in approximately 10% of the SCD population. Using contrast enhanced ultrasound (CEUS), we have previously shown that microvascular liver perfusion (MVLP) at basal levels in SCD mice is significantly reduced compared with non-SCD control mice and that MVLP in SCD mice can be further reduced by hypoxia-induced VOC events. Additionally, treatment with the antisickling agent, 5-Hyroxymethylfurfural (5-HMF), can prevent hypoxia-induced VOC reduction in MVLP in SCD mice. A prior study investigated a single time point (1 hour) posthypoxia; the duration and effect beyond 1 hour posthypoxia remained unknown. This investigation was performed to address the duration of the reduction in MVLP and the preventative effect of 5-HMF over a 24-hour period.Methods: Townes sickle cell mice (SCD), homozygous for hα:βs-globulin, approximately 7−9 weeks of age (n=15) were utilized in these studies. CEUS perfusion imaging (Vevo® 2100) was performed on a central cross-section of the liver at the renal artery. Contrast agent was administered as an intravenous bolus via tail vein to anesthetized mice (isoflurane with ~21% O2) and peak perfusion intensity [PPI] measured in linear arbitrary units [l.a.u.]), and data were analyzed with VisualSonics software. Repeated CEUS measurements were obtained on SCD mice at baseline (prehypoxia), 1, 4, and 24 hours posthypoxic exposure (hypoxic exposure: 60 minutes with approximately 5.5.% O2). 5-HMF at 200 mg/kg PO or vehicle was administered following baseline PPI measurement and approximately 30 minutes before start of hypoxia.Results:Following hypoxia-induced VOC,MVLP in vehicle-treated SCD was significantly reduced by approximately 25% from baseline levels at 1 and 4 hours posthypoxia, before returning to baseline levels at 24 hours posthypoxia (Table 1). In contrast, SCD mice administered 5-HMF at 200 mg/kg PO showed no reduction in MVLP at 1, 4, and 24 hours posthypoxia. Sickle cell counts were obtained on surrogate animals and data are still pending.*Significant reduction from baseline, P<0.05, ANOVA with Tukey’s multiple comparison test.Summary: CEUS measured a reduction in MVLP in vehicle-treated SCD mice following hypoxia-induced VOC with a duration of at least 4 hours posthypoxia. By 24 hours posthypoxia, MVLP had returned to baseline (prehypoxia) levels. Prehypoxia treatment with the antisickling agent 5-HMF was able to prevent the hypoxia-induced VOC reduction in MVLP in SCD mice for the entire 24-hour period. These data suggest that prophylactic treatment with an antisickling agent prior to a VOC event may benefit SCD patients by maintaining organ perfusion. These results further validate CEUS as a noninvasive method to measure acute and chronic organ perfusion changes for evaluating new therapeutics for sickle cell-mediated VOC events and end-organ damage. [Display omitted] DisclosuresAbe:Bayer: Employment. Sim:Bayer: Employment. Alonso-Galicia:Bayer: Employment. Kauser:Bayer: Employment.

Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight

ObjectiveWe previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. MethodsAn adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. ResultsKO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR. Conclusions(P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

OHP-020 Preliminary study of the implementation of an integral electronic pharmacotherapy management system in a tertiary hospital

BackgroundDrugs continue to be prescribed manually for hospitalised patients, despite the existence of high medicines error rates and a subsequent transcription to pharmacists and nurses being required which is also...

Milnacipran effects on 24-hour ambulatory blood pressure and heart rate in fibromyalgia patients: a randomized, placebo-controlled, dose-escalation study

Objective:To characterize milnacipran effects on systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in fibromyalgia patients using 24-hour ambulatory blood pressure monitoring (ABPM).Methods:This dose-escalation study included a 7-week double-blind treatment period and 2-week single-blind discontinuation period. Patients were randomized 2:1 to milnacipran (n = 210) or placebo (n = 111), with 50% of patients classified as ‘hypertensive’ at baseline (SBP ≥130 mmHg, DBP ≥85 mmHg, or current antihypertensive medication). Analyses were conducted at Weeks 4 and 7, after milnacipran dosages were escalated to 100 and 200 mg/day, respectively. Outcome measures included changes from baseline in mean ambulatory SBP, DBP, and heart rate for the 12-hour periods following the morning dose (post-AM dose) or evening dose (post-PM dose), and the entire 24-hour monitoring period. Primary outcome parameter was change from baseline in mean SBP for the 12-hour period post-AM dose. Safety analyses included adverse events and sitting vital sign readings taken at study visits.Results:Milnacipran increased ABPM vital signs at Week 4 (100 mg/day) and Week 7 (200 mg/day). Increases in the 12-hour period post-AM dose were similar at Weeks 4 and 7 (both visits: SBP and DBP, 4 to 5 mmHg; HR, 13 to 14 bpm). Mean increases in ambulatory vital signs were generally comparable between hypertensive and normotensive patients over 24-hour periods. Normal patterns of diurnal variation in blood pressure and heart rate were maintained in patients receiving milnacipran. Sitting vital signs were consistent with ABPM findings. Nausea was the most common adverse event observed with milnacipran.Conclusions:Fibromyalgia patients receiving milnacipran in this ABPM study had mean increases in blood pressure and heart rate that were consistent with those observed in clinical efficacy trials. Diurnal variation was preserved and changes were not greater in hypertensive patients than in non-hypertensive patients. These findings cannot necessarily be generalized to other patient populations.Clinical trial registration:This study was registered on clinicaltrials.gov (ID: NCT00618956).