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The performance of hypersonic vehicles in the take-off stage considerably influences their capability of accomplishing the flight tasks. This study is aimed at enhancing the take-off performance of a cruise aircraft using the improved chimp optimisation algorithm. The proposed algorithm, which uses the Sobol sequence for initial population generation and a function of the weight factors, can effectively overcome the problems of premature convergence and low accuracy of the original algorithm. In particular, the Sobol sequence aims to obtain a better fitness value in the first iteration, and the weight factor aims to accelerate the convergence speed and avoid the local optimal solution. The take-off mass model of the hypersonic vehicle is constructed considering the flight data obtained using the pseudo-spectral method in the climb phase. Simulations are performed to evaluate the algorithm performance, and the results show that the algorithm can rapidly and stably optimise the benchmark function. Compared to the original algorithm, the proposed algorithm requires 28.89% less optimisation time and yields an optimised take-off mass that is 1.72kg smaller.
In this study, an active defence cooperative guidance (ADCG) law that enables cheap and low-speed airborne defence missiles with low manoeuverability to accurately intercept fast and expensive attack missiles with high manoeuverability was designed to enhance the capability of aircraft for active defence. This guidance law relies on the line-of-sight (LOS) guidance method, and it realises active defence by adjusting the geometric LOS relationship involving an attack missile, a defence missile and an aircraft. We use a nonlinear integral sliding surface and an improved second-order sliding mode reaching law to design the guidance law. This can not only reduce the chattering phenomenon in the guidance command, but it can also ensure that the system can reach the sliding surface from any initial position in a finite time. Simulations were carried out to verify the proposed law using four cases: different manoeuvering modes of the aircraft, different speed ratios of the attack and defence missiles, different reaching laws applied to the ADCG law and a robustness analysis. The results show that the proposed guidance law can enable a defence missile to intercept an attack missile by simultaneously using information about the relative motions of the attack missile and the aircraft. It is also highly robust in the presence of errors and noise.
Weapon target allocation (WTA) is an effective method to solve the battlefield fire optimisation problem, which plays an important role in intelligent automated decision-making. We researched the multitarget allocation problem to maximise the attack effectiveness when multiple interceptors cooperatively attack multiple ground targets. Firstly, an effective and reasonable fitness function is established, based on the situation between the interceptors and targets, by comprehensively considering the relative range, relative angle, speed, capture probability and radiation source matching performance and thoroughly evaluating them based on the advantage of the attack effectiveness. Secondly, the optimisation performance of the particle swarm optimisation (PSO) algorithm is adaptively improved. We propose an adaptive simulated annealing-particle swarm optimisation (SA-PSO) algorithm by introducing the simulated annealing algorithm into the adaptive PSO algorithm. The proposed algorithm can enhance the convergence speed and overcome the disadvantage of the PSO algorithm easily falling into a local extreme point. Finally, a simulation example is performed in a scenario where ten interceptors cooperate to attack eight ground targets; comparative experiments are conducted between the adaptive SA-PSO algorithm and PSO algorithm. The simulation results indicate that the proposed adaptive SA-PSO algorithm demonstrates great performance in convergence speed and global optimisation capabilities, and a maximised attack effectiveness can be guaranteed.
The cooperative guidance problem of multiple inferior missiles intercepting a hypersonic target with the specific impact angle constraint in the two-dimensional plane is addressed in this paper, taking into consideration variations in a missile’s speed. The guidance law is designed with two subsystems: the direction of line-of-sight (LOS) and the direction of normal to LOS. In the direction of LOS, by applying the algebraic graph theory and the consensus theory, the guidance command is designed to make the system convergent in a finite time to satisfy the goal of cooperative interception. In the direction of normal to LOS, the impact angle is constrained to transform into the LOS angle at the time of interception. In view of the difficulty of measuring unknown target acceleration information in real scenarios, the guidance command is designed by utilising a super-twisting algorithm based on a nonsingular fast-terminal sliding mode (NFTSM) surface. Numerical simulation results manifest that the proposed guidance law performs efficiently and the guidance commands are free of chattering. In addition, the overall performance of this guidance law is assessed with Monte Carlo runs in the presence of measurement errors. The simulation results demonstrate that the robustness can be guaranteed, and that overall efficiency and accuracy in intercepting the hypersonic target are achieved.
Beryl from Xuebaoding, Sichuan Province, western China is known for its unusual tabular habit and W–Sn–Be paragenesis in a greisen-type deposit. The crystals are typically colourless transparent to pale blue, often with screw dislocations of hexagonal symmetry on the (0001) crystal faces. Combining electron microprobe analyses and laser ablation inductively coupled plasma mass spectrometry with single-crystal X-ray diffraction (XRD), correlated with Raman and micro-infrared (IR) spectroscopy and imaging, the crystal chemical characteristics are determined. The contents of Na+ (0.24–0.38 atoms per formula unit (apfu)) and Li+ up to 0.38 apfu are at the high end compared to beryl from other localities worldwide. Li+ substitution for Be2+ on the tetrahedral (T2) site is predominantly charge balanced by Na+ on the smaller channel (C2) site, with Na+ ranging from 91.5% to 99.7% (apfu) of the sum of all other alkali elements. Cs+ and minor Rb+ and K+ primarily charge balance the minor M2+ substitution for Al3+ at the A site; all iron at the A site is suggested to be trivalent. The a axis ranges from 9.2161(2) to 9.2171(4) Å, with unit-cell volume from 678.03(3) to 678.48(7) Å3. The c/a ratio of 1.0002–1.0005 is characteristic for T2-type beryl with unit-cell parameters controlled primarily by Be2+ substitution. Transmission micro-IR vibrational spectroscopy and imaging identifies coordination of one or two water molecules to Na+ (type IIs and type IId, respectively) as well as alkali free water (type I). Based on IR absorption cross section and XRD a C1 site water content of 0.4–0.5 apfu is derived, i.e. close to 50% site occupancy. Secondary crystal phases with a decrease in Fe and Mg, yet increase in Na, suggest early crystallisation of aquamarine, with goshenite being late. With similar crystal chemistry to beryl of columnar habit from other localities worldwide, the tabular habit of Xuebaoding beryl seems to be unrelated to chemical composition and alkali content.
Previous studies have revealed associations of meteorological factors with tuberculosis (TB) cases. However, few studies have examined their lag effects on TB cases. This study was aimed to analyse nonlinear lag effects of meteorological factors on the number of TB notifications in Hong Kong. Using a 22-year consecutive surveillance data in Hong Kong, we examined the association of monthly average temperature and relative humidity with temporal dynamics of the monthly number of TB notifications using a distributed lag nonlinear models combined with a Poisson regression. The relative risks (RRs) of TB notifications were >1.15 as monthly average temperatures were between 16.3 and 17.3 °C at lagged 13–15 months, reaching the peak risk of 1.18 (95% confidence interval (CI) 1.02–1.35) when it was 16.8 °C at lagged 14 months. The RRs of TB notifications were >1.05 as relative humidities of 60.0–63.6% at lagged 9–11 months expanded to 68.0–71.0% at lagged 12–17 months, reaching the highest risk of 1.06 (95% CI 1.01–1.11) when it was 69.0% at lagged 13 months. The nonlinear and delayed effects of average temperature and relative humidity on TB epidemic were identified, which may provide a practical reference for improving the TB warning system.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
Radiocarbon (14C) dating of anthropogenic carbonates (CaCO3) such as ash, lime plaster and lime mortar, has proven a difficult task due to the occurrence of a number of contaminants embedded within the CaCO3 pyrogenic binder. These include 14C-free geologic components and/or secondary phases bearing an unknown amount of 14C, and thus the alteration of the original pyrogenic isotopic signature of the material results in major age offsets when carbon recovery is performed through acid hydrolysis. Here we present a characterization/quantification approach to anthropogenic carbonates that includes Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, thin section petrography, thermogravimetric analysis and scanning electron microscopy coupled with high-resolution cathodoluminescence, with which we identified the pyrogenic CaCO3 fraction in an aerial lime plaster and two hydraulic mortars. The preserved pyrogenic component was then isolated by density separation and its purity checked again using FTIR. Carbon was recovered through thermal decomposition in vacuum. The resulting 14C age matches the expected age of the lime plaster, whereas hydraulic mortars are slightly offset due to the carbonation of calcium hydroxide lumps. This approach highlights the importance of a dedicated characterization strategy prior to dating and may be applied to aerial lime plasters to obtain accurate ages.
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.
Introduction: Acute heart failure (AHF) is a common emergency department (ED) presentation and may be associated with poor outcomes. Conversely, many patients rapidly improve with ED treatment and may not need hospital admission. Because there is little evidence to guide disposition decisions by ED and admitting physicians, we sought to create a risk score for predicting short-term serious outcomes (SSO) in patients with AHF. Methods: We conducted prospective cohort studies at 9 tertiary care hospital EDs from 2007 to 2019, and enrolled adult patients who required treatment for AHF. Each patient was assessed for standardized real-time clinical and laboratory variables, as well as for SSO (defined as death within 30 days or intubation, non-invasive ventilation (NIV), myocardial infarction, coronary bypass surgery, or new hemodialysis after admission). The fully pre-specified, logistic regression model with 13 predictors (age, pCO2, and SaO2 were modeled using spline functions with 3 knots and heart rate and creatinine with 5 knots) was fitted to the 10 multiple imputation datasets. Harrell's fast stepdown procedure reduced the number of variables. We calculated the potential impact on sensitivity (95% CI) for SSO and hospital admissions and estimated a sample size of 170 SSOs. Results: The 2,246 patients had mean age 77.4 years, male sex 54.5%, EMS arrival 41.1%, IV NTG 3.1%, ED NIV 5.2%, admission on initial visit 48.6%. Overall there were 174 (7.8%) SSOs including 70 deaths (3.1%). The final risk scale is comprised of five variables (points) and had c-statistic of 0.76 (95% CI: 0.73-0.80): 1.Valvular heart disease (1) 2.ED non-invasive ventilation (2) 3.Creatinine 150-300 (1) ≥300 (2) 4.Troponin 2x-4x URL (1) ≥5x URL (2) 5.Walk test failed (2) The probability of SSO ranged from 2.0% for a total score of 0 to 90.2% for a score of 10, showing good calibration. The model was stable over 1,000 bootstrap samples. Choosing a risk model total point admission threshold of >2 would yield a sensitivity of 80.5% (95% CI 73.9-86.1) for SSO with no change in admissions from current practice (48.6% vs 48.7%). Conclusion: Using a large prospectively collected dataset, we created a concise and sensitive risk scale to assist with admission decisions for patients with AHF in the ED. Implementation of this risk scoring scale should lead to safer and more efficient disposition decisions, with more high-risk patients being admitted and more low-risk patients being discharged.
Introduction: Wide variability exists in emergency department (ED) syncope management. The Canadian Syncope Risk Score (CSRS) was derived and validated to predict the probability of 30-day serious outcomes after ED disposition. The objective was to identify barriers and facilitators among physicians for CSRS use to stratify risk and guide disposition decisions Methods: We conducted semi-structured interviews with physicians involved in ED syncope care at 8 Canadian sites. We used purposive sampling, contacting ED physicians, cardiologists, internists, and hospitalists until theme saturation was reached. Interview questions were designed to understand whether the CSRS recommendations are consistent with current practice, barriers and facilitators for application into practice, and intention for future CSRS use. Interviews were conducted via telephone or videoconference. Two independent raters coded interviews using an inductive approach to identify themes, with discrepancies resolved through consensus. Our methods were consistent with the Knowledge to Action Framework, which highlights the need to assess barriers and facilitators for knowledge use and for adapting new interventions into local contexts. Results: We interviewed 14 ED physicians, 7 cardiologists, and 10 hospitalists/internists across 8 sites. All physicians reported the use of electrocardiograms for patients with syncope, a key component in the CSRS criteria. Almost all physicians reported that the low risk recommendation (discharge without specific follow-up) was consistent with current practice, while less consistency was seen for moderate (15 days outpatient monitoring) and high risk recommendations (outpatient monitoring and/or admission). Key barriers to following the CSRS included a lack of access to outpatient monitoring and uncertainty over timely follow-up care. Other barriers included patient/family concerns, social factors, and necessary bloodwork. Facilitators included assisting with patient education, reassurance of their clinical gestalt, and optimal patient factors (e.g. reliability to return, support at home, few comorbidities). Conclusion: Physicians are receptive to using the CSRS tool for risk stratification and decision support. Implementation should address identified barriers, and adaptation to local settings may involve modifying the recommended clinical actions based on local resources and feasibility.
Introduction: Emergency department (ED) syncope management is extremely variable. We developed practice recommendations based on the validated Canadian Syncope Risk Score (CSRS) and outpatient cardiac monitoring strategy with physician input. Methods: We used a 2-step approach. Step-1: We pooled data from the derivation and validation prospective cohort studies (with adequate sample size) conducted at 11 Canadian sites (Sep 2010 to Apr 2018). Adults with syncope were enrolled excluding those with serious outcome identified during index ED evaluation. 30-day adjudicated serious outcomes were arrhythmic (arrhythmias, unknown cause of death) and non-arrhythmic (MI, structural heart disease, pulmonary embolism, hemorrhage)]. We compared the serious outcome proportion among risk categories using Cochran-Armitage test. Step-2: We conducted semi-structured interviews using observed risk to develop and refine the recommendations. We used purposive sampling of physicians involved in syncope care at 8 sites from Jun-Dec 2019 until theme saturation was reached. Two independent raters coded interviews using an inductive approach to identify themes; discrepancies were resolved by consensus. Results: Of the 8176 patients (mean age 54, 55% female), 293 (3.6%; 95%CI 3.2-4.0%) experienced 30-day serious outcomes; 0.4% deaths, 2.5% arrhythmic, 1.1% non-arrhythmic outcomes. The serious outcome proportion significantly increased from low to high-risk categories (p < 0.001; overall 0.6% to 27.7%; arrhythmic 0.2% to 17.3%; non-arrhythmic 0.4% to 5.9% respectively). C-statistic was 0.88 (95%CI0.86–0.90). Non-arrhythmia risk per day for the first 2 days was 0.5% for medium-risk, 2% for high-risk and very low thereafter. We recruited 31 physicians (14 ED, 7 cardiologists, 10 hospitalists/internists). 80% of physicians agreed that low risk patients can be discharged without specific follow-up with inconsistencies around length of ED observation. For cardiac monitoring of medium and high-risk, 64% indicated that they don't have access; 56% currently admit high-risk patients and an additional 20% agreed to this recommendation. A deeper exploration led to following refinement: discharge without specific follow-up for low-risk, a shared decision approach for medium-risk and short course of hospitalization for high-risk patients. Conclusion: The recommendations were developed (with online calculator) based on in-depth feedback from key stakeholders to improve uptake during implementation.
We report the results from the first 12 months of a 2-year maintenance phase of a study evaluating long-term efficacy and safety of venlafaxine extended-release (XR) in preventing recurrence of depression.
Patients with recurrent unipolar depression (N=1096) were randomly assigned in a 3:1 ratio to 10-week treatment with venlafaxine XR (75 mg/d to 300 mg/d) or fluoxetine (20 mg/d to 60 mg/d). Responders (HAM-D17 total score ≤12 and ≥50% decrease from baseline) entered a 6-month, double-blind, continuation phase on the same medication. Continuation phase responders enrolled into the maintenance treatment period consisting of 2 consecutive 12-month phases. At the start of each maintenance phase, venlafaxine XR responders were randomly assigned to double-blind treatment with venlafaxine XR or placebo; fluoxetine responders continued for each period. Time to recurrence (HAM-D17 total score >12 and <50% reduction from acute phase baseline at 2 consecutive visits or the last visit prior to discontinuation) was evaluated using Kaplan-Meier methods and compared between groups using log-rank tests.
At the end of the continuation phase, venlafaxine XR responders were randomly assigned to venlafaxine XR (n=164) or placebo (n=172); 129 patients in each group were evaluated for efficacy. The cumulative probability of recurrence through 12 months was 23.1% (95% CI: 15.3, 30.9) for venlafaxine XR and 42.0% (95% CI: 31.8, 52.2) for placebo (P=0.005).
Twelve months of venlafaxine XR maintenance treatment was effective in preventing recurrence in depressed patients who had been successfully treated with venlafaxine XR during acute and continuation therapy.
This study evaluated the efficacy and safety of venlafaxine extended-release (XR) in preventing recurrence of depression.
Outpatients with recurrent unipolar depression (N=1096) were randomly assigned in a 3:1 ratio to 10-week treatment with venlafaxine XR (75 mg/d to 300 mg/d) or fluoxetine (20 mg/d to 60 mg/d). Responders (HAM-D17 ≤12 and ≥50% decrease from baseline) entered a 6-month, double-blind, continuation phase on the same medication. Continuation phase responders enrolled into maintenance treatment consisting of 2 consecutive 12-month phases. At the start of each maintenance phase, venlafaxine XR responders were randomized to double-blind treatment with venlafaxine XR or placebo; fluoxetine responders continued on fluoxetine. Time to recurrence (HAM-D17 >12 and <50% reduction from acute phase baseline at 2 consecutive visits or the last valid visit prior to discontinuation) was evaluated using Kaplan-Meier methods and compared between groups using log-rank tests.
In the second maintenance phase, the cumulative probabilities of recurrence through 12 months in the venlafaxine XR (n=43) and placebo (n=40) groups were 8.0% (95% CI: 0.0, 16.8) and 44.8% (95% CI: 27.6, 62.0), respectively (P<0.001). The probabilities of recurrence over 24 months for patients assigned to venlafaxine XR (n=129) or placebo (n=129) for the first maintenance phase were 28.5% (95% CI 18.3, 37.8) and 47.3% (95% CI 36.4, 58.2), respectively (P=0.005).
An additional 12 months of venlafaxine XR maintenance therapy was effective in preventing recurrence in depressed patients who had responded to venlafaxine XR after acute, continuation, and 12 months' initial maintenance therapy.
The efficacy of venlafaxine extended-release (XR) at doses between 75 mg/d and 300 mg/d has been demonstrated in patients with recurrent major depressive disorder (MDD) over 2.5 years. This analysis evaluated the long-term efficacy of venlafaxine XR ≤225 mg/d, the approved dosage in many countries.
In the primary multicenter, double-blind trial, outpatients with recurrent MDD (N=1096) were randomized to receive 10-week acute-phase treatment with venlafaxine XR (75 mg/d to 300 mg/d) or fluoxetine (20 mg/d to 60 mg/d), followed by a 6-month continuation phase. Subsequently, at the start of 2 consecutive, double-blind, 12-month maintenance phases, venlafaxine XR responders were randomized to receive venlafaxine XR or placebo. Data from the 24 months of maintenance treatment were analyzed for the combined end point of maintenance of response (ie, no recurrence of depression and no dose increase above 225 mg/d), and each component individually. Time to each outcome was evaluated with Kaplan-Meier methods using log-rank tests for venlafaxine XR-placebo comparisons.
The analysis population included 114 patients who had received venlafaxine XR doses less than or equal to 225 mg/d prior to maintenance phase baseline (venlafaxine XR: n=55; placebo: n=59). Probability estimates for maintaining response were 70% for venlafaxine XR and 38% for placebo (P=0.007), for no dose increase were 76% and 58%, respectively (P=0.019), and for no recurrence were 87% vs 65%, respectively (P=.099).
These data confirm venlafaxine XR is effective maintaining response at doses ≤225 mg/d for up to 2.5 years in patients with MDD.
Recently, a triple-network model suggested the abnormal interactions between the executive-control network (ECN), default-mode network (DMN) and salience network (SN) are important characteristics of addiction, in which the SN plays a critical role in allocating attentional resources toward the ECN and DMN. Although increasing studies have reported dysfunctions in these brain networks in Internet gaming disorder (IGD), interactions between these networks, particularly in the context of the triple-network model, have not been investigated in IGD. Thus, we aimed to assess alterations in the inter-network interactions of these large-scale networks in IGD, and to associate the alterations with IGD-related behaviors.
DMN, ECN and SN were identified using group-level independent component analysis (gICA) in 39 individuals with IGD and 34 age and gender matched healthy controls (HCs). Then alterations in the SN-ECN and SN-DMN connectivity, as well as in the modulation of ECN versus DMN by SN, using a resource allocation index (RAI) developed and validated previously in nicotine addiction, were assessed. Further, associations between these altered network coupling and clinical assessments were also examined.
Compared with HCs, IGD had significantly increased SN-DMN connectivity and decreased RAI in right hemisphere (rRAI), and the rRAI in IGD was negatively associated with their scores of craving.
These findings suggest that the deficient modulation of ECN versus DMN by SN might provide a mechanistic framework to better understand the neural basis of IGD and might provide novel evidence for the triple-network model in IGD.
Individuals with attention-deficit/hyperactivity disorder (ADHD) may require long-term medication.
To measure growth and sexual maturation of children and adolescents with ADHD receiving lisdexamfetamine dimesylate (LDX) in a 2-year trial (SPD489-404).
To investigate the impact of long-term LDX treatment on growth and maturation.
Participants (6–17 years) received dose-optimized, open-label LDX (30–70 mg/day) for 104 weeks. Weight, height and BMI z-scores were derived using the Centers for Disease Control and Prevention norms . Sexual maturation was assessed using the Tanner scale (participant-rated as closest to their stage of development based on standardized drawings).
Of 314 enrolled participants, 191 (60.8%) completed the study. Mean z-scores at baseline and last on-treatment assessment (LOTA) were 0.53 (standard deviation, 0.963) and 0.02 (1.032) for weight, 0.61 (1.124) and 0.37 (1.131) for height, and 0.32 (0.935) and–0.27 (1.052) for BMI. In general, z-scores shifted lower over the first 36 weeks and then stabilized. At LOTA, most participants remained at their baseline Tanner stage or shifted higher, based on development of hair (males, 95.5%; females, 92.1%) or genitalia/breasts (males, 94.7%; females, 98.4%).
Consistent with previous studies of stimulants used to treat ADHD , z-scores for weight, height and BMI decreased, mostly in the first year, then stabilized. No clinically concerning trends of LDX treatment on sexual maturation or the onset of puberty were observed.
Disclosure of interest
Study funded by Shire Development LLC.
Dr Isabel Hernández Otero (Alicia Koplowitz Foundation, Eli Lilly, Forest, Janssen-Cilag, Junta de Andalucia, Roche, Shire, Shire Pharmaceuticals Iberica S.L., and Sunovion).
The long-term safety and efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention deficit/hyperactivity disorder (ADHD) was evaluated in a European 2-year, open-label study (SPD489-404).
To evaluate the time-course of treatment-emergent adverse events (TEAEs) in SPD489-404.
Participants aged 6–17 years received open-label LDX (30, 50 or 70 mg/day) for 104 weeks (4 weeks dose-optimization; 100 weeks dose-maintenance).
All enrolled participants (n = 314) were included in the safety population and 191 (60.8%) completed the study. TEAEs occurred in 282 (89.8%) participants; most were mild or moderate. TEAEs considered by the investigators as related to LDX were reported by 232 (73.9%) participants with the following reported for ≥ 10% of participants: decreased appetite (49.4%), weight decreased (18.2%), insomnia (13.1%). TEAEs leading to discontinuation and serious TEAEs occurred in 39 (12.4%) and 28 (8.9%) participants, respectively. The median (range) time to first onset and duration, respectively, of TEAEs identified by the sponsor as being of special interest were: insomnia (insomnia, initial insomnia, middle insomnia, terminal insomnia), 17.0 (1–729) and 42.8 (1–739) days; weight decreased, 29.0 (1–677) and 225.0 (26–724) days; decreased appetite, 13.5 (1–653) and 169.0 (1–749) days; headache, 22.0 (1–718) and 2.0 (1–729) days. Reports of insomnia, weight decreased, decreased appetite and headache were highest in the first 4–12 weeks.
TEAEs associated with long-term LDX treatment were characteristic of stimulant medications, with the greatest incidence observed during the first 4–12 weeks.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
This study evaluated the quality of YouTube content focusing on common paediatric otolaryngology procedures, as this content can influence the opinions and medical decisions of patients.
A total of 120 YouTube videos were compiled to review using the terms ‘adenoid removal’, ‘adenoidectomy’, ‘ear tubes’, ‘tympanostomy’, ‘tonsil removal’ and ‘tonsillectomy’. The Discern criteria was used to rate the quality of health information presented in each video.
The mean bias Discern score was 3.18 and the mean overall Discern score was 2.39. Videos including US board certified physicians were rated significantly higher (p < 0.001) than videos without (bias Discern score = 3.00 vs 2.38; overall Discern score = 3.79 vs 1.55). The videos had been viewed a total of 176 769 549 times.
Unbiased, high quality videos on YouTube are lacking. As patients may rely on this information when making medical decisions, it is important that practitioners continually evaluate and improve this video content. Otolaryngologists should be prepared to discuss YouTube content with patients.
Patients with severe mental disorders in low-resource settings have limited access to services, resulting in overwhelming caregiving burden for families. In extreme cases, this has led to the long-term restraining of patients in their homes. China underwent a nationwide initiative to unlock patients and provide continued treatment. This study aims to quantify household economic burden in families after unlocking and treatment, and to identify factors associated with increased burden due to schizophrenia.
A total of 264 subjects were enrolled from three geographically diverse provinces in 2012. Subjects were patients with schizophrenia who were previously put under restraints and had participated in the ‘unlocking and treatment’ intervention. The primary outcome was the current household economic burden, obtained from past year financial information collected through on-site interview. Patient disease characteristics, treatment, outcomes and family caregiving burden were collected as well. Univariate and multivariate linear regression were used to construct risk factor models for indirect economic burden.
After participating in the intervention, 85% of patients continued to receive mental health services, 70% used medication as prescribed and 80% were never relocked. Family members reported significantly decreased caregiving burden after receiving the intervention. Mean direct and indirect household economic burdens were CNY963 (US$31.7) and CNY11 724 (US$1670) per year, respectively, while family total income was on average CNY12 108 (US$1913) per year. Greater disease severity and poorer patient psychosocial function at time of study were found to be independent factors related to increased indirect burden.
The ‘unlocking and treatment’ intervention has improved the lives of patients and families. Indirect burden due to disease is still a major economic issue that needs to be addressed, potentially through improving treatment and patient functioning. Our findings contribute to the unravelling and eventual elimination of chronic restraining of mentally ill patients in low-resource settings.