Discontinuous Strategy Research Articles

Effect of antipsychotic dose reduction on cognitive function in schizophrenia

Cognitive deficits are predictors of social functioning but remain an unmet therapeutic challenge. While lowering the antipsychotics carries a risk of relapse, it possibly has a beneficial effect on cognitive function. However, this has not been examined in a real-world setting. A prospective naturalistic 6-month follow-up study (n = 71) was conducted with patients between 18 and 45 years in their first five years of illness and the maintenance phase of the treatment. Brief Assessment of Cognition in Schizophrenia (BACS) was administered to assess cognitive functions. Patients were divided into three groups based on the change in dose of antipsychotics. The data were analyzed using linear mixed-effects modeling (LMEM) to examine the group differences. At the end of six months, those with decreased antipsychotic dose had significant improvement in BACS total score, token test, and symbol coding compared to those with no change in the dose of antipsychotic. Reducing the dose of antipsychotics during the maintenance phase was associated with improved cognitive functions without an increased risk of relapse. Antipsychotic dose reduction may be better than discontinuation as the relapse risk is higher with the discontinuation strategy. Clinicians must balance the improvements in cognitive functions and relapse risk.

Evaluation and comparison of sideband harmonics and acoustic responses with continuous and discontinuous PWM strategies in permanent magnet synchronous motor for electric vehicles

Evaluation and comparison of sideband harmonics and acoustic responses with continuous and discontinuous PWM strategies in permanent magnet synchronous motor for electric vehicles

Evaluation and comparison of sideband harmonics and acoustic responses with continuous and discontinuous PWM strategies in permanent magnet synchronous motor for electric vehicles

High-frequency vibro-acoustics, introduced by voltage source inverter (VSI) and control strategies, are the critical features affecting the noise, vibration and harshness (NVH) performances of electric vehicles (EVs). In this paper, a comprehensive evaluation and comparison into sideband current harmonics and high-frequency vibro-acoustic responses has been studied with different control strategies in the study case of permanent magnet synchronous motor (PMSM). At first, the principles and implementation of continuous and discontinuous pulse-width modulations (PWM) techniques are explored. Then, the features of the sideband current harmonic and radial electromagnetic forces are deduced with analytical derivations, in which the frequency characteristics are also presented. Furthermore, all PWM schemes have been improved by a standard periodic dithering modulation with square signal-based to reduce the sideband harmonics. The experimental results show that the sideband current harmonics and vibro-acoustics are generally clustered around the carrier frequency and have a particular orders and spectral distributions. The overall level of the obtained DPWM schemes present a slight deterioration compared to the SVPWM ones. With the periodisation of the carrier frequency, the sideband components show a significant suppression, which is above 15 dBA reduced in the acoustic noise responses.

Predictors of successful discontinuation of antipsychotics and antidepressants.

To offer support for patients who decide to discontinue antipsychotic and antidepressant medication, identifying which potentially modifiable factors correlate with discontinuation success is crucial. Here, we analyzed the predictive value of the professional support received, circumstances prior to discontinuation, a strategy of discontinuation, and use of functional and non-functional coping strategies during discontinuation on self-reported discontinuation success and on objective discontinuation. Patients who had attempted discontinuing antipsychotics (AP) and/or antidepressants (AD) during the past 5 years (n = 316) completed an online survey including questions on subjective and objective discontinuation success, sociodemographic, clinical and medication-related factors, and scales to assess the putative predictors. A regression model with all significant predictors explained 20-30% of the variance in discontinuation success for AD and 30-40% for AP. After controlling for baseline sociodemographic, clinical and medication-related factors, the most consistent predictor of subjective discontinuation success was self-care behavior, in particular mindfulness, relaxation and making use of supportive relationships. Other predictors depended on the type of medication: For AD, good alliance with the prescribing physician predicted higher subjective success whereas gradual tapering per se was associated with lower subjective success and a lower chance of full discontinuation. In those tapering off AP, leaving time to adjust between dose reductions was associated with higher subjective success and fewer negative effects. The findings can inform evidence-based clinical guidelines and interventions aiming to support patients during discontinuation. Further studies powered to take interactions between variables into account are needed to improve the prediction of successful discontinuation.

Safety and Efficacy of Antibiotic De-escalation and Discontinuation in High-Risk Hematological Patients With Febrile Neutropenia: A Single-Center Experience.

BackgroundThere is currently no consensus on optimal duration of antibiotic treatment in febrile neutropenia. We report on the clinical impact of implementation of antibiotic de-escalation and discontinuation strategies based on the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations in high-risk hematological patients.MethodsWe studied 446 admissions after introduction of an ECIL-4–based protocol (hereafter “ECIL-4 group”) in comparison to a historic cohort of 512 admissions. Primary clinical endpoints were the incidence of infectious complications including septic shock, infection-related intensive care unit (ICU) admission, and overall mortality. Secondary endpoints included the incidence of recurrent fever, bacteremia, and antibiotic consumption.ResultsBacteremia occurred more frequently in the ECIL-4 group (46.9% [209/446] vs 30.5% [156/512]; P < .001), without an associated increase in septic shock (4.7% [21/446] vs 4.5% [23/512]; P = .878) or infection-related ICU admission (4.9% [22/446] vs 4.1% [21/512]; P = .424). Overall mortality was significantly lower in the ECIL-4 group (0.7% [3/446] vs 2.7% [14/512]; P = .016), resulting mainly from a decrease in infection-related mortality (0.4% [2/446] vs 1.8% [9/512]; P = .058). Antibiotic consumption was significantly reduced by a median of 2 days on antibiotic therapy (12 vs 14; P = .001) and 7 daily antibiotic doses (17 vs 24; P < .001) per admission period.ConclusionsOur results support implementation of ECIL-4 recommendations to be both safe and effective based on real-world data in a large high-risk patient population. We found no increase in infectious complications and total antibiotic exposure was significantly reduced.

A Carrier-Based Discontinuous PWM Strategy of NPC Three-Level Inverter for Common-Mode Voltage and Switching Loss Reduction

For the conventional carrier-based pulse width modulation (CBPWM) strategies of neutral point clamped (NPC) three-level inverters, the higher common-mode voltage (CMV) is a major drawback. However, with CMV suppression strategies, the switching loss is relatively high. In order to solve the above issue, a carrier-based discontinuous PWM (DPWM) strategy for NPC three-level inverter is proposed in this paper. Firstly, the reference voltage is modified by the twice injection of zero-sequence voltage. Switching states of the three-phase are clamped alternatively to reduce both the CMV and the switching loss. Secondly, the carriers are also modified by the phase opposite disposition of the upper and lower carriers. The extra switching at the border of two adjacent regions in the space vector diagram is reduced. Meanwhile, a neutral-point voltage (NPV) control method is also presented. The duty cycle of the switching state that affects the NPV is adjusted to obtain the balance control of the NPV. Still, the switching sequence in each carrier period remains the same. Finally, the feasibility and effectiveness of the proposed DPWM strategy are tested on a rapid control prototype platform based on RT-Lab.

A041702: A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients (≥ 70 Years of Age) with Chronic Lymphocytic Leukemia (CLL)

A041702: A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients (≥ 70 Years of Age) with Chronic Lymphocytic Leukemia (CLL)

Radical Target Setting and China’s Great Famine

AbstractThis article empirically examines the role of radical targets for grain yields in triggering China’s Great Famine (1959–61), one of the largest man-made catastrophes in human history. Beginning in 1958, the Chinese central government assigned different targets for grain yields in most counties, based on their geographic location. All targets seemed unrealistically high. Using novel county-level data, combined with a spatial regression discontinuity strategy, we find evidence that these radical grain targets prompted excessive procurement and subsequent famine. Our estimates show that a one-standard deviation increase in grain yield targets led to an 18‰ higher death rate in 1960. This article sheds new light on the consequences of target-setting in an authoritarian regime without considering local contexts. (JEL O21, N45, P26).

Qualitative study of facilitators and barriers for continued follow-up care as perceived and experienced by young people with congenital heart disease in Sweden

In-depth understanding of factors perceived by young people with congenital heart disease (CHD) to affect continued follow-up care is needed to tailor preventive strategies for discontinuation of follow-up care. To...

Finite-time bipartite synchronization of coupled neural networks with uncertain parameters

This paper investigates the finite-time bipartite synchronization (FTBS) of coupled neural networks (CNNs) with uncertain parameters. Under signed graphs, two control strategies are designed to guarantee FTBS of CNNs with or without external disturbances, respectively. For the disturbed CNNs, a discontinuous adaptive control strategy is proposed to overcome the impacts caused by uncertain parameters and disturbances with the help of non-smooth analysis and Lyapunov stability theory. For the undisturbed CNNs, a periodically intermittent adaptive control strategy is developed to achieve FTBS. Finally, two numerical examples are provided to demonstrate the effectiveness of theoretical results.

Association of External Ventricular Drain Wean Strategy with Shunt Placement and Length of Stay in Subarachnoid Hemorrhage: A Prospective Multicenter Study.

Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparingrapid vs. gradual EVDweaning protocols is justified.

Antidepressant Discontinuation: In Need of Scientific Evidence.

The topic of patients' discontinuing use of antidepressants has received increasing attention. Patients and physicians can encounter challenges regarding the three major questions in the field of antidepressant discontinuation: who can discontinue, what is the best time to discontinue; and what is the best method to discontinue. This commentary summarizes the current state of the evidence related to antidepressant discontinuation. There is limited evidence underlying the extremely relevant clinical topic of antidepressant discontinuation. It is poorly understood which patients, after response to antidepressants, benefit (most) from discontinuation. Moreover, established and validated markers of an individual's risk of relapse after antidepressant cessation are lacking, and non-sponsored discontinuation studies are rare. Many discontinuation studies do not distinguish between relapse and antidepressant discontinuation symptoms, and very few studies compared different discontinuation strategies, with none of the compared strategies exceeding 2 weeks of tapering. Finally, blinding of discontinuation strategies is often insufficient to properly address placebo and nocebo aspects, whereas the pharmacological characteristics of different antidepressants in relation to discontinuation have hardly been studied. Antidepressant discontinuation is a clinically relevant topic. There is a strong need for more robust evidence to indicate who can discontinue antidepressants, when and in which manner (how). Blinded randomized controlled trials are pivotal to optimally advise physicians, patients and policy-makers. This scientific knowledge can guide evidence-based decision making in clinical practice.

Can Testing Predict SARS-CoV-2 Infectivity? The Potential for Certain Methods To Be Surrogates for Replication-Competent Virus.

ABSTRACTSince the beginning of the COVID-19 pandemic, molecular methods (e.g., real-time PCR) have been the primary means of diagnosing the disease. It is now well established that molecular tests can continue to detect SARS-CoV-2 genomic RNA for weeks or months following the resolution of clinical illness. This has prompted public health agencies to recommend a symptom- and/or time-based strategy for discontinuation of isolation precautions, which, for hospitalized patients, results in significant use of personal protective equipment. Due to the inability of current molecular diagnostic assays to differentiate between the presence of remnant viral RNA (i.e., noninfectious) and replication-competent (i.e., infectious) virus, there has been interest in determining whether laboratory tests can be used to predict an individual’s likelihood of transmitting the virus to others. This review will highlight what is currently known about the potential for existing assays, such as real-time PCR and antigen tests, to predict active viral infection. In addition, data on the performance of new methods, such as molecular tests targeting viral RNA intermediates (e.g., subgenomic RNA), will be discussed.

Dual-rotator mueller matrix polarimeter for high-accuracy and high-precision measurements of glucose concentration

A Mueller matrix polarimeter incorporating two rotating retarders is proposed for determining the glucose concentration in aqueous solutions. In the proposed system, the accuracy and precision of the Mueller matrix measurements are enhanced through an effective compensation of both the systematic errors in the polarimeter and the environmental errors. Moreover, the synchronization of the two retarders is effectively controlled through the use of a simple discontinuous rotation strategy. The validity of the proposed compensation method is demonstrated numerically and experimentally using an air sample for illustration purposes. It is shown that the maximum error and maximum standard deviation of the measured Mueller matrix elements are ±0.0102 and ±0.0008, respectively. In addition, the response time is just 1 min. In experimental trials performed in the transmission mode using aqueous glucose samples, the maximum standard deviation of the optical rotation angle is found to be just 0.0388 degrees with a path length of 40 mm. Moreover, the extracted rotation angle varies linearly (R2 = 0.9176) with the glucose concentration over the concentration range of 100–500 mg/dL. Hence, the feasibility of the calibrated Mueller matrix polarimeter for glucose determination applications is confirmed.

Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial

Semaglutide is an effective treatment for type 2 diabetes; however, 20-30% of patients given semaglutide 1·0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea. We did a 40-week, randomised, active-controlled, parallel-group, double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics in ten countries. Participants (≥18 years) with inadequately controlled type 2 diabetes (HbA1c 8·0-10·0%) with metformin and with or without sulfonylurea were randomly assigned (1:1) by an interactive web-response system to 2·0 mg or 1·0 mg once-weekly semaglutide. Participants, site personnel, the clinical study group, and investigators were masked to the randomised treatment. Outcomes included change from baseline at week 40 in HbA1c (primary outcome) and bodyweight (secondary confirmatory outcome), evaluated through trial product estimand (no treatment discontinuation or without rescue medication) and treatment policy estimand (regardless of treatment discontinuation or rescue medication) strategies. This study is registered with ClinicalTrials.gov, NCT03989232; EudraCT, 2018-004529-96; and WHO, U1111-1224-5162. Between June 19 and Nov 28, 2019, of 1515 adults assessed for eligibility, 961 participants (mean age 58·0 years [SD 10·0]; 398 [41%] women) were included. Participants were randomly assigned to once-weekly semaglutide 2·0 mg (n=480 [50%]) or 1·0 mg (n=481 [50%]); 462 (96%) patients in the semaglutide 2·0 mg group and 471 (98%) in the semaglutide 1·0 mg group completed the trial. Mean baseline HbA1c was 8·9% (SD 0·6; 73·3 mmol/mol [SD 6·9]) and BMI was 34·6 kg/m2 (SD 7·0). Mean change in HbA1c from baseline at week 40 was -2·2 percentage points with semaglutide 2·0 mg and -1·9 percentage points with semaglutide 1·0 mg (estimated treatment difference [ETD] -0·23 percentage points [95% CI -0·36 to -0·11]; p=0·0003; trial product estimand) and -2·1 percentage points with semaglutide 2·0 mg and -1·9 percentage points with semaglutide 1·0 mg (ETD -0·18 percentage points [-0·31 to -0·04]; p=0·0098; treatment policy estimand). Mean change in bodyweight from baseline at week 40 was -6·9 kg with semaglutide 2·0 mg and -6·0 kg with semaglutide 1·0 mg (ETD -0·93 kg [95% CI -1·68 to -0·18]; p=0·015; trial product estimand) and -6·4 kg with semaglutide 2·0 mg and -5·6 kg with semaglutide 1·0 mg (ETD -0·77 kg [-1·55 to 0·01]; p=0·054; treatment policy estimand). Gastrointestinal disorders were the most commonly reported adverse events (163 [34%] in the 2·0 mg group and 148 [31%] in the 1·0 mg group). Serious adverse events were similar between treatment groups, reported for 21 (4%) participants given semaglutide 2·0 mg and 25 (5%) participants given semaglutide 1·0 mg. Three deaths were reported during the trial (one in the semaglutide 1·0 mg group and two in the semaglutide 2·0 mg group). Semaglutide 2·0 mg was superior to 1·0 mg in reducing HbA1c, with additional bodyweight loss and a similar safety profile. This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control. Novo Nordisk.

PRN Medicines Management for Older People with Long-Term Mental Health Disorders in Home Care.

Older people with long-term mental health conditions who receive care in their own home are vulnerable to the inappropriate use of medications and polypharmacy given their underlying health conditions and comorbidities. Inappropriate use of pro re nata (PRN) medications in these older people can enhance their suffering and have negative consequences for their quality of life and well-being, leading to readmission to healthcare settings and the increased cost of health care. This narrative review on published international literature aims at improving our understanding of medicines management in home care and how to improve PRN medication use among older people with long-term health conditions in their own home. Accordingly, the improvement of PRN medicines management for these older people requires the development of an individualised care plan considering ‘reduction of older people’s dependence on PRN medications’, ‘empowerment of family caregivers’, and ‘support by healthcare professionals.’ PRN medication use should be reduced through deprescription and discontinuation strategies. Also, older people and their family caregivers should be encouraged to prioritize the use of non-pharmacologic methods to relieve physical and psychological problems. Besides the empowerment of family caregivers through role development, education and training about PRN medications, and involvement in decision-making, they need support by the multidisciplinary network in terms of supervision, monitoring, and home visits.

Oral Anticoagulation Discontinuation Following Catheter Ablation of Typical Atrial Flutter

Catheter ablation (CA) of typical atrial flutter (AFL) is the preferred treatment for typical AFL due to its excellent long-term success rate. However, current guidelines recommend pursuing oral anticoagulation (OAC) based on established indices of stroke regardless of the perceived success of ablation. We conducted a retrospective study of all patients who underwent typical AFL ablation at our institute from 2011 to 2017. All patients continued OAC for at least six weeks post-CA and underwent 24-hour Holter monitoring. OAC was discontinued if there was no evidence of recurrence at six weeks. In patients with low left ventricular ejection fraction or prior atrial fibrillation episodes, OAC was continued for six months with repeat Holter monitoring at six months. A total of 106 patients were included in our analysis, with a mean age of 64 ± 14 years and 78.3% of whom were male. The mean CHA2DS2-VASc score was 3 ± 1 points. OAC was discontinued by six weeks in 17% and at one year in 55.7% of patients, respectively, but was continued indefinitely in 44.3%. Over a mean follow-up period of 28.6 ± 27.3 months, there was one ischemic stroke in the OAC discontinuation group and no ischemic events in the continued OAC group. There were a total of three major bleeding events, all in the OAC group. In patients undergoing successful AFL ablation, a strategy of OAC discontinuation with close rhythm monitoring appears feasible. The benefit of continued OAC in this cohort may be outweighed by an adverse risk of bleeding. Further studies examining rhythm-guided OAC can minimize unnecessary exposure to long-term anticoagulation.

Antipsychotics and Attenuated Psychosis Syndrome: Transdiagnostic assessment and discontinuation strategies

Antipsychotics and Attenuated Psychosis Syndrome: Transdiagnostic assessment and discontinuation strategies

Immunoguided Discontinuation of Prophylaxis for Cytomegalovirus Disease in Kidney Transplant Recipients Treated With Antithymocyte Globulin: A Randomized Clinical Trial.

Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. NCT03123627.

Nonseparation Method-Based Finite/Fixed-Time Synchronization of Fully Complex-Valued Discontinuous Neural Networks.

This article mainly focuses on the problem of synchronization in finite and fixed time for fully complex-variable delayed neural networks involving discontinuous activations and time-varying delays without dividing the original complex-variable neural networks into two subsystems in the real domain. To avoid the separation method, a complex-valued sign function is proposed and its properties are established. By means of the introduced sign function, two discontinuous control strategies are developed under the quadratic norm and a new norm based on absolute values of real and imaginary parts. By applying nonsmooth analysis and some novel inequality techniques in the complex field, several synchronization criteria and the estimates of the settling time are derived. In particular, under the new norm framework, a unified control strategy is designed and it is revealed that a parameter value in the controller completely decides the networks are synchronized whether in finite time or in fixed time. Finally, some numerical results for an example are provided to support the established theoretical results.