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The application of a tube combustion system (pyrolyzer) for the batch combustion of low carbon content environmental matrices, such as soil and sediment, for determining 14C specific activity is examined. The samples were combusted at 600°C, and the CO2 species produced were trapped in 3N NaOH, precipitated as BaCO3 by adding BaCl2, and subjected to acid-hydrolysis to transfer the CO2 species to the absorber-scintillator mixture for liquid scintillation counting (LSC). The method was validated by analyzing the samples by accelerator mass spectrometry (AMS) method. The minimum detectable activity (MDA) for the method, at 2σ confidence level, was 10 Bq kg–1C (4 pMC) for a counting time of 500 min and 7 Bq kg–1C (3 pMC) for 1000 min. The capability of the method to quantify a small excess of 14C specific activity (a few Bq kg–1C or pMC) in the environment of a nuclear facility, when compared to the ambient natural background level, was demonstrated by analyzing a total of 23 soil and 7 sediment samples from the vicinity of a pressurized heavy water reactor (PHWR) nuclear power plant (NPP) at Kaiga, India. The maximum excess 14C specific activity values recorded for soil and sediment matrices were 37 ± 7 Bq kg–1C and 11 ± 7 Bq kg–1C, respectively, confirming minimal radioecological impact of the operation of the NPP on the environment. The 14C specific activity ratio for the recently fallen leaf litter and the soil underneath at most of the sampling points in the vicinity of the NPP had a mean value of 1.03 with an associated standard deviation of 0.07. Statistical tests confirm that the mean values of the data set of 14C specific activity of leaf litter and underlying soil are not significantly different.
Polar ring galaxies (PRGs) are a unique class of galaxies characterised by a ring of gas and stars orbiting nearly orthogonal to the main body. This study delves into the evolutionary trajectory of PRGs using the exemplary trio of NGC 3718, NGC 2685, and NGC 4262. We investigate the distinct features of PRGs by analysing their ring and host components to reveal their unique characteristics through spectral energy distribution (SED) fitting. Using CIGALE, we performed SED fitting to independently analyse the ring and host spatially resolved regions, marking the first decomposed SED analysis for PRGs, which examines stellar populations using high-resolution observations from AstroSat UVIT at a resolved scale. The UV-optical surface profiles provide an initial idea that distinct patterns in the galaxies, with differences in FUV and NUV, suggest three distinct stages of ring evolution in the selected galaxies. The study of resolved-scale stellar regions reveals that the ring regions are generally younger than their host galaxies, with the age disparity progressively decreasing along the evolutionary sequence from NGC 3718 to NGC 4262. Star formation rates (SFR) also exhibit a consistent pattern, with higher SFR in the ring of NGC 3718 compared to the others, and a progressive decrease through NGC 2685 and NGC 4262. Finally, the representation of the galaxies in the HI gas fraction versus the NUV–$\text r$ plane supports the idea that they are in three different evolutionary stages of PRG evolution, with NGC 3718 in the initial stage, NGC 2685 in the intermediate stage, and NGC 4262 representing the final stage. This study concludes that PRGs undergo various evolutionary stages, as evidenced by the observed features in the ring and host components. NGC 3718, NGC 2685, and NGC 4262 represent different stages of this evolution, highlighting the dynamic nature of PRGs and emphasising the importance of studying their evolutionary processes to gain insights into galactic formation and evolution.
The brachyuran crab fauna (Crustacea: Decapoda: Brachyura) collections in the extensive exploratory fishery survey cruises from the northeast coast of India was studied from June 2018 to March 2020. During the study period, 81 species of brachyuran crabs belonging to 19 families and 46 genera were recorded. Among these, 21 species were newly recorded from the northeast coast of India, and 1 species, Naxioides taurus (Pocock, 1890) represents a new record for the mainland coasts of India. This study serves as a baseline for understanding the diversity and distribution of brachyuran crabs in the region. It provides valuable insights for future research and conservation efforts.
Medical students have been under immense pressure throughout their studies, impacting their mental health and academic performance. Stress reduction is a fundamental skill that all students require to manage their studies and lives efficiently. Biofeedback devices providing information about physiological states have been shown to aid stress reduction. Methods to reduce stress should be taught to medical students to help them tackle the challenges of medical school.
Objectives
Our goal was to teach stress reduction methods such as extracurricular activities and paced breathing aided by biofeedback training and its application in simulated healthcare situations to medical students.
Methods
15 medical students who completed medical physiology were recruited for an elective course of 7 sessions on practical techniques in stress management. One credit was offered to those who completed the course requirements consisting of participation in sessions and individual biofeedback training.
Sessions (classes) consisted of presentations on good sleeping and eating patterns, group simulations of stressful hospital environments, visiting a science centre with interactive displays, an orchestra performance, and nature walks. Before biofeedback training, heart and respiration rates were taken individually by a biofeedback device during the first week of the course. Data was processed using a code created in statistical software. Heartbeats per minute and heart rate variability (HRV) for every 10 seconds were calculated and plotted on a graph. Two measurements were taken with each student: a baseline measurement for 10 minutes and another measurement during controlled breathing paced at 6 breaths per minute for 15 minutes, of which the first 10 minutes were used for calculation and plotting. Students provided narrative feedback in an essay submitted after the course was completed.
Results
5 males and 10 females from years 2-5 registered for the elective, and 12 participated in individually scheduled sessions. Heart beats per minute decreased, whereas HRV increased during paced breathing sessions in 83% of them. Most students reported feeling calm and drowsy during the sessions, and 2 students fell asleep by the end.
Feedback from 11 students showed that the music session and the science centre visit were the highlights throughout the elective. Improvements recommended were to have a consistent time slot for all sessions and fewer simulations.
Conclusions
In concert with the literature, biofeedback training seems to be a feasible and effective method for relaxation in medical students. This method could be offered as part of mental health services for students. Data could be used to follow students’ progress and identify those requiring extra support. Providing them with avenues to de-stress while emphasizing activities outside medicine could boost their confidence and improve their coping skills.
Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring.
Aims
To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK.
Method
We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment.
Results
We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally.
Conclusions
Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.
We compared the number of blood-culture events before and after the introduction of a blood-culture algorithm and provider feedback. Secondary objectives were the comparison of blood-culture positivity and negative safety signals before and after the intervention.
Design:
Prospective cohort design.
Setting:
Two surgical intensive care units (ICUs): general and trauma surgery and cardiothoracic surgery
Patients:
Patients aged ≥18 years and admitted to the ICU at the time of the blood-culture event.
Methods:
We used an interrupted time series to compare rates of blood-culture events (ie, blood-culture events per 1,000 patient days) before and after the algorithm implementation with weekly provider feedback.
Results:
The blood-culture event rate decreased from 100 to 55 blood-culture events per 1,000 patient days in the general surgery and trauma ICU (72% reduction; incidence rate ratio [IRR], 0.38; 95% confidence interval [CI], 0.32–0.46; P < .01) and from 102 to 77 blood-culture events per 1,000 patient days in the cardiothoracic surgery ICU (55% reduction; IRR, 0.45; 95% CI, 0.39–0.52; P < .01). We did not observe any differences in average monthly antibiotic days of therapy, mortality, or readmissions between the pre- and postintervention periods.
Conclusions:
We implemented a blood-culture algorithm with data feedback in 2 surgical ICUs, and we observed significant decreases in the rates of blood-culture events without an increase in negative safety signals, including ICU length of stay, mortality, antibiotic use, or readmissions.
Carrot is an important vegetable crop worldwide valued for its fleshy edible roots of varied colours. Owing to its highly cross-pollinated nature and small flower size, cytoplasmic male sterility (CMS) is being utilized for hybrid development. Among different types of male sterility, petaloid CMS is widely used for hybrid carrot breeding globally. This study aimed to develop selection criteria for parents in developing heterotic F1 hybrids using CMS lines. A large number of agro-morphological traits and Simple Sequence Repeats (genomic-SSRs) were used to assess the diversity among parental lines. We developed 60 F1 hybrids by crossing four petaloid CMS lines and 15 testers in line × tester mating design and evaluated them in replicated randomized block design trial for four vegetative and 11 economic traits. The mean squares of all the traits in line × tester interactions were significant. The estimates of genetic components of variance indicated predominance of non-additive gene action except for root maturity, root length and core diameter. The hybrids with highest per se performance also had significant positive specific combining ability effects. The root yield and root weight showed highest heterosis percentage (33%). The best performing heterotic hybrids were DCatH-5392, DCatH-700 and DCatH-9892. Correlation between genetic distance and relative heterosis of economic traits indicated no significant association and thus genetic distance could not be used to predict heterosis. As most of the yield-related traits were controlled by non-additive gene action, heterosis breeding could be potentially used along with combining ability analysis to reduce time in selection of best parents and crosses in tropical carrot.
Leadership in healthcare organisations is crucial to continually improve and provide high quality compassionate care. Leadership development and training enables the psychiatrists in developing these essential skills. Focusing on how to enhance leadership development through leadership skills training and experiential learning should be a priority. However, little is known about the extent to which this leadership skills training is available across Europe in the early stage of the career of psychiatrists.
Objectives
To investigate the access to leadership development opportunities among European psychiatric trainees and early career psychiatrists (ECPs) and their perceptions related to leadership skills training.
Methods
Cross-sectional study, using an online survey consisting of multiple-choice questions and free text responses.
Results
Participants from 33 European countries took part in this survey, where the majority were female. More than half were general adult psychiatric trainees and more than a quarter ECPs. About half indicated having no access to leadership skills training within their training program, with only about 10% being satisfied with the training received. About half sought additional training outside their program. A vast majority requested training in leadership skills to be included in a psychiatric training program.
Conclusions
Our study provides an overview of important gaps in availability and access to leadership skills training amongst psychiatric trainees and ECPs across Europe. We hope that this study will help inform future actions pertaining to development and improvement of leadership skills training for trainees and ECPs across Europe.
MeerTime is a five-year Large Survey Project to time pulsars with MeerKAT, the 64-dish South African precursor to the Square Kilometre Array. The science goals for the programme include timing millisecond pulsar (MSPs) to high precision (${<} 1 \unicode{x03BC} \mathrm{s}$) to study the Galactic MSP population and to contribute to global efforts to detect nanohertz gravitational waves with the International Pulsar Timing Array (IPTA). In order to plan for the remainder of the programme and to use the allocated time most efficiently, we have conducted an initial census with the MeerKAT ‘L-band’ receiver of 189 MSPs visible to MeerKAT and here present their dispersion measures, polarisation profiles, polarisation fractions, rotation measures, flux density measurements, spectral indices, and timing potential. As all of these observations are taken with the same instrument (which uses coherent dedispersion, interferometric polarisation calibration techniques, and a uniform flux scale), they present an excellent resource for population studies. We used wideband pulse portraits as timing standards for each MSP and demonstrated that the MeerTime Pulsar Timing Array (MPTA) can already contribute significantly to the IPTA as it currently achieves better than $1\,\unicode{x03BC}\mathrm{s}$ timing accuracy on 89 MSPs (observed with fortnightly cadence). By the conclusion of the initial five-year MeerTime programme in 2024 July, the MPTA will be extremely significant in global efforts to detect the gravitational wave background with a contribution to the detection statistic comparable to other long-standing timing programmes.
Background: Neonatal cerebral sinovenous thrombosis (CSVT) can lead to severe brain injury and long-term neurodevelopmental impairments. Previous studies of neonatal CSVT have mainly included term infants. In this study, we examined the clinical and radiological features, treatment and outcome of CSVT in preterm infants. Methods: This was a retrospective cohort study of preterm infants born <37 weeks with radiologically confirmed CSVT. All MRI/MRV and CT/CTV scans were re-reviewed. Clinical and radiological data were analysed using descriptive statistics, ANOVA and chi-square tests. Results: A total of 26 preterm infants with CSVT were included. Of these, 65% were late preterm, 27% very preterm and 8% extreme preterm. Most were symptomatic (seizures 50%, abnormal exam 50%). Radiological features included transverse sinus (85%) and sagittal sinus thrombosis (42%), intraventricular hemorrhage (42%) and venous infarction (19%). Most preterm infants with CSVT (69%) were treated with anticoagulation. Anticoagulation was not associated with new or worsening intracranial hemorrhage. Outcome at follow-up ranged from no impairment (39%), mild impairment (19%), severe impairment (19%) and death (23%). Conclusions: Preterm infants with CSVT are often symptomatic and present with a distinct pattern of brain injury. Anticoagulation treatment of preterm CSVT appeared to be safe. Further studies and treatment guidelines for preterm CSVT are needed.
Background: Neonatal Arterial Ischemic Stroke (NAIS) is a common form of paediatric stroke often affecting classical language areas. The post-stroke reorganization of functional language networks may provide insight into later-emerging language deficits and may help to identify at-risk children with NAIS. Methods: A cross-sectional study of fourteen children with left (n=8; 2M; 11.1±2.2 years) or right (n=6; 3M; 12.4±4 years) middle cerebral artery (MCA) NAIS, as well as seven neurotypical children (5M; 13.4±2.7 years), was conducted. Children listened to correct/incorrect syntactic sentences while MEG was recorded, and task-related functional connectivity in the time window and frequency band of interest was determined. Language outcomes were assessed using a battery of neuropsychological tests. Results: A network-based analysis of syntactic language processing (4-7 Hz, 1.2-1.4s) revealed a dysfunctional bilateral frontal-temporal network involving language areas in patients (p=0.01). Patients with right-MCA stroke exhibited a positive correlation between left hemispheric connectivity and measures of language skill (p<0.01), resembling the neurotypical children. In left-MCA stroke patients, greater bilateral connectivity or right laterality in the language network is correlated with good outcome (p<0.05). Conclusions: Depending on the hemispheric location of stroke, certain patterns of language network reorganization may account for impairments in a bilateral frontal-temporal language subnetwork and support language outcome.
A Mediterranean-style eating pattern (MED-EP) may include moderate red meat intake. However, it is unknown if the pro-atherogenic metabolite trimethylamine N-oxide (TMAO) is affected by the amount of red meat consumed with a MED-EP. The results presented are from a secondary, retrospective objective of an investigator-blinded, randomised, crossover, controlled feeding trial (two 5-week interventions separated by a 4-week washout) to determine if a MED-EP with 200 g unprocessed lean red meat/week (MED-CONTROL) reduces circulating TMAO concentrations compared to a MED-EP with 500 g unprocessed lean red meat/week (MED-RED). Participants were seventy-seven women and twelve men (n 39 total) who were either overweight or obese (BMI: mean (30·5) (sem 0·3) kg/m2). Serum samples were obtained following an overnight fast both before (pre) and after (post) each intervention. Fasting serum TMAO, choline, carnitine and betaine concentrations were measured using a targeted liquid chromatography-MS. Data were analysed to assess if (a) TMAO and related metabolites differed by intervention and (b) if changes in TMAO were associated with changes in Framingham 10-year risk score. Serum TMAO was lower post-intervention following MED-CONTROL compared with MED-RED intervention (post-MED-CONTROL 3·1 (sem 0·2) µmv. post-MED-RED 5·0 (sem 0·5) µm, P < 0·001), and decreased following MED-CONTROL (pre- v. post-MED-CONTROL, P = 0·025). Exploratory analysis using mixed model ANCOVA identified a positive association between changes in TMAO and changes in homoeostatic model assessment of insulin resistance (P = 0·036). These results suggest that lower amounts of red meat intake lead to lower TMAO concentrations in the context of a MED-EP.
A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.
Objectives:
To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.
Methods:
Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.
Results:
Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).
Conclusion:
Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.
Coronavirus disease 2019 (COVID-19) has caused mild illness in children, until the emergence of the novel hyperinflammatory condition paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS). PIMS-TS is thought to be a post-SARS-CoV-2 immune dysregulation with excessive inflammatory cytokine release. We studied 25 hydroxyvitamin D (25OHD) concentrations in children with PIMS-TS, admitted to a tertiary paediatric hospital in the UK, due to its postulated role in cytokine regulation and immune response. Eighteen children (median (range) age 8·9 (0·3-14·6) years, male = 10) met the case definition. The majority were of Black, Asian and Minority Ethnic (BAME) origin (89 %, 16/18). Positive SARS-CoV-2 IgG antibodies were present in 94 % (17/18) and RNA by PCR in 6 % (1/18). Seventy-eight percentage of the cohort were vitamin D deficient (< 30 nmol/l). The mean 25OHD concentration was significantly lower when compared with the population mean from the 2015/16 National Diet and Nutrition Survey (children aged 4–10 years) (24 v. 54 nmol/l (95 % CI −38·6, −19·7); P < 0·001). The paediatric intensive care unit (PICU) group had lower mean 25OHD concentrations compared with the non-PICU group, but this was not statistically significant (19·5 v. 31·9 nmol/l; P = 0·11). The higher susceptibility of BAME children to PIMS-TS and also vitamin D deficiency merits contemplation. Whilst any link between vitamin D deficiency and the severity of COVID-19 and related conditions including PIMS-TS requires further evidence, public health measures to improve vitamin D status of the UK BAME population have been long overdue.
We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain (${\sim}2.8\,\mbox{K Jy}^{-1}$) low-system temperature (${\sim}18\,\mbox{K at }20\,\mbox{cm}$) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar $\mbox{J}0737{-}3039\mbox{A}$, pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR $\mbox{J}0540{-}6919$, and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR $\mbox{J}2241{-}5236$ exhibits a jitter limit of $<4\,\mbox{ns h}^{-1}$ whilst timing of PSR $\mbox{J}1909{-}3744$ over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities.
Approximately, 1.7 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). This has disproportionately impacted adults, but many children have been infected and hospitalised as well. To date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here, we share the approach to the cardiac workup and monitoring utilised at a large congenital heart centre in New York City, the epicentre of the COVID-19 pandemic in the United States.
Coronavirus disease 2019 personal protective equipment has been reported to affect communication in healthcare settings. This study sought to identify those challenges experimentally.
Method
Bamford–Kowal–Bench speech discrimination in noise performance of healthcare workers was tested under simulated background noise conditions from a variety of hospital environments. Candidates were assessed for ability to interpret speech with and without personal protective equipment, with both normal speech and raised voice.
Results
There was a significant difference in speech discrimination scores between normal and personal protective equipment wearing subjects in operating theatre simulated background noise levels (70 dB).
Conclusion
Wearing personal protective equipment can impact communication in healthcare environments. Efforts should be made to remind staff about this burden and to seek alternative communication paradigms, particularly in operating theatre environments.
Introduction: Selecting appropriate patients for hospitalization following emergency department (ED) evaluation of syncope is critical for serious adverse event (SAE) identification. The primary objective of this study is to determine the association of hospitalization and SAE detection using propensity score (PS) matching. The secondary objective was to determine if SAE identification with hospitalization varied by the Canadian Syncope Risk Score (CSRS) risk-category. Methods: This was a secondary analysis of two large prospective cohort studies that enrolled adults (age ≥ 16 years) with syncope at 11 Canadian EDs. Patients with a serious condition identified during index ED evaluation were excluded. Outcome was a 30-day SAE identified either in-hospital for hospitalized patients or after ED disposition for discharged patients and included death, ventricular arrhythmia, non-lethal arrhythmia and non-arrhythmic SAE (myocardial infarction, structural heart disease, pulmonary embolism, hemorrhage). Patients were propensity matched using age, sex, blood pressure, prodrome, presumed ED diagnosis, ECG abnormalities, troponin, heart disease, hypertension, diabetes, arrival by ambulance and hospital site. Multivariable logistic regression assessed the interaction between CSRS and SAE detection and we report odds ratios (OR). Results: Of the 8183 patients enrolled, 743 (9.0%) patients were hospitalized and 658 (88.6%) were PS matched. The OR for SAE detection for hospitalized patients in comparison to those discharged from the ED was 5.0 (95%CI 3.3, 7.4), non-lethal arrhythmia 5.4 (95%CI 3.1, 9.6) and non-arrhythmic SAE 6.3 (95%CI 2.9, 13.5). Overall, the odds of any SAE identification, and specifically non-lethal arrhythmia and non-arrhythmia was significantly higher in-hospital among hospitalized patients than those discharged from the ED (p < 0.001). There were no significant differences in 30-day mortality (p = 1.00) or ventricular arrhythmia detection (p = 0.21). The interaction between ED disposition and CSRS was significant (p = 0.04) and the probability of 30-day SAEs while in-hospital was greater for medium and high risk CSRS patients. Conclusion: In this multicenter prospective cohort, 30-day SAE detection was greater for hospitalized compared with discharged patients. CSRS low-risk patients are least likely to have SAEs identified in-hospital; out-patient monitoring for moderate risk patients requires further study.
We evaluated the efficacy of eszopiclone (ESZ) and concurrent escitalopram oxalate (EO) in patients with insomnia and co-morbid GAD.
Methods:
Patients meeting DSM-IV-TR criteria for GAD and insomnia received 10 weeks of EO 10mg and co-therapy with ESZ 3mg or placebo (PBO) for 8 weeks. For the last 2 weeks, ESZ was replaced with single-blind PBO to evaluate discontinuation effects. Sleep, daytime functioning and anxiety measures were captured during the study.
Results:
ESZ+EO improved sleep and daytime functioning at each week and the double-blind period average (p<0.05). At Week 8, significantly more ESZ+EO patients had no clinically meaningful insomnia based on ISI</=7. Significant improvements with ESZ+EO (relative to PBO+EO) were observed in HAM-A total scores each week, and Weeks 4-10 excluding the insomnia item. ESZ+EO was significantly better at every timepoint on CGI-I (p<0.02); CGI-S was not different between treatments after Week 1. Median time to anxiolytic response was reduced with ESZ+EO based on HAM-A and CGI-I. HAM-A response and remission rates at Week 8 were higher with ESZ+EO, and HAM-D17 scores were improved at all timepoints (p<0.004). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and no treatment differences in sleep or daytime function. Significant treatment differences in anxiety and mood were maintained after discontinuation.
Conclusion:
In this study, ESZ+EO was well tolerated and associated with improved sleep and daytime function without evidence of tolerance. Improvements in anxiety and mood were observed with ESZ+EO.
Support for this study provided by Sepracor Inc., Marlborough, MA.