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Abstract Background The optimal retreatment strategy with rituximab for rheumatoid arthritis (RA) remains a point of discussion. Depending on local guidelines, rituximab can either be administered at fixed intervals or when losing disease control, balancing therapeutic effectiveness with drug overexposure. However, treatment based on loss of disease control may significantly affect patients’ lives, provoking uncertainty and potentially leading to progressive joint damage. Moreover, as low-dose rituximab proved to be effective in treating RA while decreasing toxicity, drug exposure may be limited by tapering down rituximab doses guided by disease activity. Methods RITUXERA is a 104-week open-label multicentre randomised controlled superiority trial. In total, 134 patients with RA treated with rituximab will be 1:1 randomised when in need of retreatment (DAS28-CRP ≥ 3.2 with previous rituximab administration at least 24 weeks earlier) to either a treat-to-target-driven fixed dose retreatment strategy (usual care group) or fixed interval disease-activity guided dose optimisation strategy (experimental group). The usual care group will be retreated with fixed rituximab doses (1 × 1000 mg IV) in case of loss of disease control (DAS28-CRP ≥ 3.2). The experimental group will receive a 24-weekly rituximab treatment while tapering down the dose in a decreasing sequence if DAS28-CRP ≤ 3.2: 1 × 1000 mg IV (maximal dose), 1 × 500 mg IV, and 1 × 200 mg IV (minimal dose). If DAS28-CRP exceeds 3.2 at the six-monthly retreatment, patients will receive and remain on the previous effective dose. Study visits are planned every 12 weeks. Primary outcome is the comparison of longitudinal patient-reported disease impact over 104 weeks, measured with the Rheumatoid Arthritis Impact of Disease (RAID) instrument, analysed using a linear mixed model. Main secondary outcome is the comparison of longitudinal disease activity (DAS28-CRP) over 104 weeks. Discussion The RITUXERA trial aims to explore the optimal retreatment strategy with rituximab for RA in terms of long-term patient-reported disease impact, by proposing a fixed interval disease activity-guided dose optimisation strategy as compared to a treat-to-target fixed dose strategy. Trial registration CTIS 2023–506638-59–01 (registration date: 07 September 2023), ClinicalTrials.gov NCT06003283 (registration date: 17 August 2023).

Current recommendations for RA treatment determine the need to reduce the dose and duration of glucocorticoid(GC) use. This is due to the wide spectrum and high frequency (up to 100%) of serious adverse events (AE) during GC treatment. However, in real practice GCs in RA are used very often (in Russia, Western Europe and the USA they are used in about 50% of patients), and often in long-term courses. This is explained by the fact that the combination of disease-modifying antirheumatic drugs (DMARDs), including biologics (bDMARDs) and Janus kinase inhibitors (JAK), with GCs allows to achieve faster improvement of patients’ condition and therefore is very “convenient” for many patients and physicians.However, it is very difficult to ensure dose reduction and (especially!) complete discontinuation of GC administration afterwards. Clinical and observational studies show that 30–40% of patients manage to discontinue the use of GCs during treatment with bDMARDs and JAK. In addition, discontinuation of GCs may significantly increase the risk of RA flare, even with complex pathogenetic therapy.Nevertheless, prolonged use of GCs, including low doses (less than 7.5 mg/day of prednisolone) should be considered as an indicator of the severity of the disease course and inadequacy of the current therapy. Therefore, we should strive for personalization of RA therapy, selection of DMARDs based on the assessment of the disease phenotype and predictors of response to treatment with different drugs, achieving the main goal of therapy – remission/low disease activity and achievement of acceptable quality of life, without the use of GCs.

Abstract Background 80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient’s feeling of autonomy and psychiatric rehabilitation. Case presentation We present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders– 10th Edition codes F20.0–5, F20.7–9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down. Conclusions Reducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse. Impact and implications Some patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery.

ObjectivesTapering biologic agents can be considered for patients with stable disease activity in rheumatoid arthritis (RA). However, the specific strategy for abatacept is uncertain. This study aimed to examine the impact of tapering abatacept on disease activity in RA patients and assess the potential influence of concomitant methotrexate (MTX) treatment.MethodsUsing data from the KOBIO registry, we included 505 1 year intervals from 176 patients with RA that initiated abatacept with concomitant MTX at baseline. The intervals were divided into two groups based on the dose quotient (DQ) of abatacept during each period (i.e., the tapering group (DQ

Introduction We report our initial experience with a novel ureteroplasty technique that combines the advantages of excisional tapering and folding. Methods and cases Following dissection of the megaureter, the distal ureteral end was transected at a point with an appropriate caliber to create a neo‐orifice, which was left intact. Only the proximally redundant part of the ureter was excised and closed over a 10F catheter, following which the ureter was anastomosed to the bladder with an indwelling ureteral stent. This procedure was performed in four pediatric patients. Case 1 involved a 6‐year‐old girl with continuous urinary incontinence due to ureteral ectopia in a duplex system. Cases 2 and 3 involved infants with refluxing megaureter. Case 4 involved a 9‐year‐old boy with a ureteral stone impacted in a megaureter. All four patients achieved successful outcomes without ureteral obstruction. Conclusion This ureteroplasty technique is a promising alternative in specific patients.

Abstract Background Many people experience withdrawal symptoms when they attempt to stop antidepressants. Withdrawal symptoms are readily misconstrued for relapse or ongoing need for medication, contributing to long-term use (> 12 months). Long-term antidepressant use is increasing internationally yet is not recommended for most people. Long-term use is associated with adverse effects including weight gain, sexual dysfunction, lethargy, emotional numbing and increased risk of falls and fractures. This study aims to determine the effectiveness of two multi-strategy interventions (RELEASE and RELEASE+) in supporting the safe cessation of long-term antidepressants, estimate cost-effectiveness, and evaluate implementation strategies. Methods Design 3-arm pragmatic cluster randomised controlled trial effectiveness-implementation hybrid type-1. Setting: primary care general practices in southeast Queensland, Australia. Population: adults 18 years or older taking antidepressants for longer than 1 year. Practices will be randomised on a 1.5:1:1 ratio of Usual care:RELEASE:RELEASE+. Intervention: RELEASE for patients includes evidence-based information and resources and an invitation to medication review; RELEASE for GPs includes education, training and printable resources via practice management software. RELEASE+ includes additional internet support for patients and prescribing support including audit and feedback for GPs. Outcome measures: the primary outcome is antidepressant use at 12 months self-reported by patients. Cessation is defined as 0 mg antidepressant maintained for at least 2 weeks. Secondary outcomes: at 6 and 12 months are health-related quality of life, antidepressant side effects, well-being, withdrawal symptoms, emotional numbing, beliefs about antidepressants, depressive symptoms, and anxiety symptoms; and at 12 months 75% reduction in antidepressant dose; aggregated practice level antidepressant prescribing, and health service utilisation for costs. Sample size: 653 patients from 28 practices. A concurrent evaluation of implementation will be through mixed methods including interviews with up to 40 patients and primary care general practitioners, brief e-surveys, and study administrative data to assess implementation outcomes (adoption and fidelity). Discussion The RELEASE study will develop new knowledge applicable internationally on the effectiveness, cost-effectiveness, and implementation of two multi-strategy interventions in supporting the safe cessation of long-term antidepressants to improve primary health care and outcomes for patients. Trial registration ANZCTR, ACTRN12622001379707p. Registered on 27 October 2022.

Abstract Background Chronic use of hypnotic agents is prevalent in older adults, who as a result are at increased risk for certain adverse events, such as day-time drowsiness and falls. Multiple strategies to discontinue hypnotics have been tested in geriatric patients, but evidence remains scarce. Hence, we aimed to investigate a multicomponent intervention to reduce hypnotic drug use in geriatric inpatients. Methods A before-after study was performed on the acute geriatric wards of a teaching hospital. The before group (= control group) received usual care, while intervention patients (= intervention group) were exposed to a pharmacist-led deprescribing intervention, comprising education of health care personnel, access to standardized discontinuation regimens, patient education and support of transitional care. The primary outcome was hypnotic drug discontinuation at one month after discharge. Secondary outcomes among others were sleep quality and hypnotic use at one and two weeks after enrolment and at discharge. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) upon inclusion, two weeks after enrolment and one month after discharge. Determinants for the primary outcome were identified using regression analysis. Results A total of 173 patients were enrolled, with 70.5% of patients taking benzodiazepines. Average age was 85 years (interquartile range 81–88.5) and 28.3% were male. A higher discontinuation rate at one month after discharge was observed in favour of the intervention (37.7% vs. 21.9%, p = 0.02281). No difference in sleep quality was found between both groups (p = 0.719). The average sleep quality was 8.74 (95% confidence interval (CI): 7.98–9.49) and 8.57 (95% CI: 7.75–9.39) in the control and intervention groups respectively. Determinants for discontinuation at one month were: the intervention (odds ratio (OR) 2.36, 95% CI: 1.14–4.99), fall on admission (OR 2.05; 95% CI: 0.95–4.43), use of a z-drug (OR 0.54, 95% CI: 0.23–1.22), PSQI score on admission (OR 1.08, 95% CI: 0.97–1.19) and discontinuation prior to discharge (OR 4.71, 95% CI: 2.26–10.17). Conclusions A pharmacist-led intervention in geriatric inpatients was associated with a reduction of hypnotic drug use one month after discharge, without any loss in sleep quality. Trial registration ClinicalTrials.gov Identifier: NCT05521971 (retrospectively registered on 29th of August 2022).

Eosinophil-related diseases represent a group of pathologic conditions with highly heterogeneous clinical presentation and symptoms ranging from mild to critical. Both systemic and localized forms of disease are typically treated with glucocorticoids. The approval of novel biologic therapies targeting the interleukin-5 pathway can help reduce the use of systemic glucocorticoids (SGC) in eosinophilic diseases and reduce the risk of SGC-related adverse effects (AEs). In this article, a panel of experts from different medical specialties reviewed current evidence on the use of SGC in two systemic eosinophilic diseases: Eosinophilic Granulomatosis with PolyAngiitis (EGPA) and HyperEosinophilic Syndrome (HES); and in two single-organ (respiratory) eosinophilic diseases: Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) and Severe Asthma with Eosinophil Phenotype (SA-EP), and contrasted it with their experience in clinical practice. Using nominal group technique, they reached consensus on key aspects related to the dose and tapering of SGC as well as on the initiation of biologics as SGC-sparing agents. Early treatment with biologics could help prevent AEs associated with medium and long-term use of SGC.

AbstractObjective To evaluate the long-term effects of a multilevel community intervention to improve the quality of prescription practice of potentially addictive medications (PAMs).Design We conducted a retrospective study, using anonymized data from the Norwegian prescription registry.Setting Based on an initiative from the GPs in Molde Municipality in Norway, a multilevel community intervention was initiated by the municipal chief physician in 2018. The intervention targeted GPs, patients, and the public.Subjects We retrieved prescription data from 26 of 36 GPs.Main outcome measures By using the standardized defined daily dose (DDD), we compared prescription of three groups of PAMs from before the intervention (2017) throughout the intervention in 2018, and through 2020 to determine long-term effects.Results Three years after the intervention, the GPs in our study sample prescribed 26% less opioids, 38% less benzodiazepines, and 16% less z-hypnotics. Overall prescription of PAMs decreased by 27%. The number of individuals receiving at least 90 DDD of benzodiazepines and z-hypnotics were reduced from 9 to 7 and 34 to 24 per 1000, respectively. Also, the number of individuals receiving two and three PAMs concomitantly were reduced.Conclusion Addressing prescription practice among GPs in a community as a joint intervention, combined with addressing patients and the public may be a feasible method to obtain long-term reduction of PAM prescriptions.Key pointsNon-therapeutic prescriptions of potentially addictive medications (PAMs) are both a public health concern and a frequent challenge in general practice.A multilevel community intervention, targeting general practitioners, patients, and the public, led to 27% reduction in prescription of PAMs.Both the number of daily users and concomitant use of several PAMs were reduced.The reduction in prescription persisted for three years.

Abstract Background Biologic disease-modifying antirheumatic drugs (bDMARDs) have changed the treatment of juvenile idiopathic arthritis (JIA) patients notably, as bDMARDs enable substantially more patients to achieve remission. When sustained remission is achieved, tapering or even discontinuation of the bDMARD is advocated, to reduce side effects and costs. However, when and how to discontinue bDMARD therapy and what happens afterwards, is less known. Objectives With this scoping review we aim to collect available data in current literature on relapse rate, time to relapse (TTR) and possible flare associated variables (such as time spent in remission and method of discontinuation) after discontinuing bDMARDs in non-systemic JIA patients. Methods We performed a literature search until July 2022 using the Pubmed database. All original studies reporting on bDMARD discontinuation in non-systemic JIA patients were eligible. Data on patient- and study characteristics, the applied discontinuation strategy, relapse rates and time to relapse were extracted in a standardized template. Results Of the 680 records screened, 28 articles were included in this review with 456 non-systemic JIA patients who tapered and/or stopped bDMARD therapy. Relapse rate after discontinuation of bDMARDs, either abruptly or following tapering, were 40–48%, 36.8–45.0% and 60–78% at 6, 8 and 12 months respectively. Total relapse rate ranged from 26.3% to 100%, with mean time to relapse (TTR) of 2 to 8.4 months, median TTR 3 to 10 months. All studies stated a good response after restart of therapy after flare. JIA subtype, type of bDMARD, concomitant methotrexate use, treatment duration, tapering method, age, sex, and time in remission could not conclusively be related to relapse rate or TTR. However, some studies reported a positive correlation between flare and antinuclear antibodies positivity, younger age at disease onset, male sex, disease duration and delayed remission, which were not confirmed in other studies. Conclusion Flares seem to be common after bDMARD discontinuation, but little is known about which factors influence these flares in JIA patients. Follow up after discontinuation with careful registration of patient variables, information about tapering methods and flare rates are required to better guide tapering and/or stopping of bDMARDs in JIA patients in the future.

BackgroundPersistent opioid use frequently leads to substantial negative impacts on quality of life, and as the outlook for numerous cancer types continues to improve, these complications become increasingly crucial. It is essential to acknowledge that extended or excessive opioid use may result in adverse effects in patients who completed radiation therapy (RT).MethodsIn this time-series analysis, we compared the outcomes of patients who participated in the pharmacist-led opioid de-escalation (PLODE) program after completing concurrent radiotherapy (CRT) between June 2018 and February 2019 against patients who completed CRT between June 2017 and March 2018 and did not participate in the program.ResultsAmong 61 patients, 16 (26%) used opioids after completing CRT and participated in the PLODE program. Before starting the program, 93 patients completed CRT between June 2017 and March 2018 and 32 (34%) used opioids at CRT completion. These patients were deemed the control group. In the PLODE group, outpatient pharmacist intervention was performed, with 29 total interventions related to opioid use, of which 16 (55%) recommended tapering or discontinuing opioids according to the definition of this program. Patients who participated in the PLODE program discontinued opioids significantly earlier than those in the control group (median time to opioid discontinuation 11 days vs. 24.5 days, p < 0.001). None of the patients in the PLODE group resumed opioid use following discontinuation or escalated opioid dosing due to worsening pain.ConclusionThis study showed the utility of pharmacist-initiated interventions for opioid use in patients with head and neck cancer who had completed CRT.

Introduction: Some patients presenting with dilated short bowel suffer from dysmotility, leading to stasis and consequent bacterial overgrowth. These patients are candidates for intestinal reconfiguration surgery. We suggest a technique of lengthening and tapering of the dilated short bowel segment named segmental intestinal reconfiguration (SIR) based on the modified Yang-Monti principle and submit the first clinical experience. Case presentation: The SIR technique was applied in a 10 years old patient with segmental bowel dilation of ultra-short bowel due to intestinal atresia and resection, who received parenteral nutrition 50% of the daily requirements. He was diagnosed with liver disease associated with intestinal failure, metabolic bone disorder, and polyarthritis. The dilated bowel loop was transected in three places to produce two segments 6 cm long. Antimesenteric borders of the segments were incised along, resulting in 2 rectangular flaps 12x6 cm. The flaps were closed into a tube diagonally to form two neosegments, sutured together and with the open intestinal ends. The length of the reconfigured bowel loop after SIR increased from 12 to 26 cm. The signs of dysmotility disappeared 3 weeks after the operation. In 18 months, the mid-term outcome was evaluated. There were no bacterial overgrowth or dysmotility episodes during this period. The child has become active, gaining weight and height. Parenteral nutrition was reduced in half. Conclusion: First clinical application of the SIR technique showed its simplicity, feasibility and positive effect on the motility.

The advent of novel nonlinear materials has stirred unprecedented interest in exploring the use of temporal inhomogeneities to achieve novel forms of wave control, amidst the greater vision of engineering metamaterials across both space and time. When the properties of an unbounded medium are abruptly switched in time, propagating waves are efficiently converted to different frequencies, and partially coupled to their back-propagating phase-conjugate partners, through a process called time-reversal. However, in realistic materials the switching time is necessarily finite, playing a central role in the resulting temporal scattering features. By identifying and leveraging the crucial role of electromagnetic momentum conservation in time-reversal processes, here we develop a general analytical formalism to quantify time-reversal due to temporal inhomogeneities of arbitrary profile. We deploy our theory to develop a formalism, dual to spatial tapering, that enables the tailoring of a desired time-reversal spectral response, demonstrating its use for the realization of broadband frequency converters and filters.

Abstract Background Biological disease-modifying anti-rheumatic drugs (bDMARDs) are effective in the treatment of rheumatoid arthritis (RA) but are expensive and increase the risk of infection. Therefore, in patients with a stable low level of disease activity or remission, tapering bDMARDs should be considered. Although tapering does not seem to affect long-term disease control, (short-lived) flares are frequent during the tapering process. We have previously developed and externally validated a dynamic flare prediction model for use as a decision aid during stepwise tapering of bDMARDs to reduce the risk of a flare during this process. Methods In this investigator-initiated, multicenter, open-label, randomized (1:1) controlled trial, we will assess the effect of incorporating flare risk predictions into a bDMARD tapering strategy. One hundred sixty RA patients treated with a bDMARD with stable low disease activity will be recruited. In the control group, the bDMARD will be tapered according to “disease activity guided dose optimization” (DGDO). In the intervention group, the bDMARD will be tapered according to a strategy that combines DGDO with the dynamic flare prediction model, where the next bDMARD tapering step is not taken in case of a high risk of flare. Patients will be randomized 1:1 to the control or intervention group. The primary outcome is the number of flares per patient (DAS28-CRP increase > 1.2, or DAS28-CRP increase > 0.6 with a current DAS28-CRP ≥ 2.9) during the 18-month follow-up period. Secondary outcomes include the number of patients with a major flare (flare duration ≥ 12 weeks), bDMARD dose reduction, adverse events, disease activity (DAS28-CRP) and patient-reported outcomes such as quality of life and functional disability. Health Care Utilization and Work Productivity will also be assessed. Discussion This will be the first clinical trial to evaluate the benefit of applying a dynamic flare prediction model as a decision aid during bDMARD tapering. Reducing the risk of flaring during tapering may enhance the safety and (cost)effectiveness of bDMARD treatment. Furthermore, this study pioneers the field of implementing predictive algorithms in clinical practice. Trial registration Dutch Trial Register number NL9798, registered 18 October 2021, https://www.trialregister.nl/trial/9798 . The study has received ethical review board approval (number NL74537.041.20).

Although different strategies have been implemented to manage recovery-fatigue status in athletes, there is still a lack of consensus on which recovery protocols have the greatest impact and effectiveness when implemented with basketball players, including both physiological and psychological recovery methods. Thus, the purpose of this systematic review is to: (a) determine which recovery methods attain the greatest benefit in restoring the process of attenuating fatigue and (b) provide sports practitioners with guidelines on how some of the most effective recovery strategies can be used to optimize athletes’ recovery and ultimately enhance their performance. Using the PRISMA guidelines, a total of 3931 research reports were obtained through four database searches (i.e., PubMed, Scopus, Cochrane, and Web of Science), from which only 25 met the inclusion and exclusion criteria. The recovery protocols analyzed in this systematic review were: sleep, nutrition, hydration, ergogenic aids, cold-water immersion, compression garments, massage, acupuncture, tapering, mindfulness, and red-light irradiation. The results revealed that all recovery strategies are capable of attenuating fatigue and enhancing recovery in basketball players to a certain degree. However, an individualized approach should be promoted, where a combination of proactive recovery modalities appears to result in the most rapid rates of recovery and athletes’ ability to maintain high-level performance. Recovery should be programmed as an integral component of training regimens. Also, cooperation and communication between coaches, players, and the rest of the team staff members are essential in minimizing the risk of non-functional overreaching or injury and optimizing basketball players’ on-court performance.

Abstract Background Patients with remitted psychosis wish to reduce antipsychotic doses yet facing increased risks of relapse. Examining dose-tapering processes may provide insights to re-evaluate the risk-to-benefit balance. We aimed to depict and subgroup tapering trajectories, and explore factors associated with different dose-reduction patterns. Methods A 2-year open-label randomized prospective comparative trial from August 2017 to September 2022 in Taiwan. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomizing a proportion to conduct guided dose reduction. We depicted the trajectories of individual patients and named subgroups based on dose-tapering patterns. Predictors of baseline characteristics for designated subgroups were examined by logistic regression analysis; changes in outcomes were compared by paired t-test. Results Fifty-one patients undergoing guided dose reduction, 18 (35.3%) reduced 4 steps consecutively (sequential reducers, SR), 14 (27.5%) reduced 1 to 3 steps (modest reducers, MR), 3 (5.9%) re-escalated to previous level (alert reducers, AR), 7 (13.7%) returned to baseline level (baseline returners, BR), 6 (11.7%) relapsed (failed reducers, FR) and 3 (5.9%) withdrew without relapse (early exits, EE). Patients with a history of relapse assumed a conservative dose-tapering pace; only the SR subgroup exhibited significant improvements in functioning and quality of life while failing to identify variables for predicting who would become SR or FR. Conclusions Guided dose reduction comprises dynamic processes with differences between individual trajectories. The proposed naming of dose-tapering patterns/subgroups provides a framework depicting patients undergoing dose-tapering. Longer-term observation and more flexible tapering approaches are anticipated to reveal favorable outcomes.

The article presents a numerical study of self-design taper algorithms for free-electron lasers (FELs) with planar and helical undulators. Tapering is a technique that changes the undulator parameters in order to increase the efficiency and the radiation power in FELs. Undulator tapering is one of the methods for designing multi-terawatt X-ray FELs (XFELs), which are necessary for research in the field of non-linear optics and 3D bioimaging. In this article, we study methods to optimize the taper profile K(z) that can enhance the efficiency of extracting energy from the electron beam in FELs with planar and helical undulators. Using the numerical code we apply the Kroll–Morton–Rosenbluth (KMR) model and its modification to a case of the FEL at the MAX IV Laboratory, as well as a case of the European XFEL, compare our results with previous ones and discuss the new results. The program was validated on the PAL-XFEL experiment. The application of the modified KMR method for FELs with helical undulators is also studied.

Deloading refers to a purposeful reduction in training demand with the intention of enhancing preparedness for successive training cycles. Whilst deloading is a common training practice in strength and physique sports, little is known about how the necessary reduction in training demand should be accomplished. Therefore, the purpose of this research was to determine current deloading practices in competitive strength and physique sports. Eighteen strength and physique coaches from a range of sports (weightlifting, powerlifting, and bodybuilding) participated in semi-structured interviews to discuss their experiences of deloading. The mean duration of coaching experience at ≥ national standard was 10.9 (SD = 3.9) years. Qualitative content analysis identified Three categories: definitions, rationale, and application. Participants conceptualised deloading as a periodic, intentional cycle of reduced training demand designed to facilitate fatigue management, improve recovery, and assist in overall training progression and readiness. There was no single method of deloading; instead, a reduction in training volume (achieved through a reduction in repetitions per set and number of sets per training session) and intensity of effort (increased proximity to failure and/or reduction in relative load) were the most adapted training variables, along with alterations in exercise selection and configuration. Deloading was typically prescribed for a duration of 5 to 7 days and programmed every 4 to 6 weeks, although periodicity was highly variable. Additional findings highlight the underrepresentation of deloading in the published literature, including a lack of a clear operational definition.

Background: There is a growing number of service users looking to discontinue use of psychiatric medicines. Tapering is the recommended approach for reducing and/or discontinuing the use of psychiatric medicines. This involves gradually reducing the dose over time to minimise the potential for withdrawal symptoms. However, many uncertainties exist regarding the process of reducing and stopping psychiatric medicines. This study will use a James Lind Alliance Priority Setting Partnership to determine the Top 10 unanswered questions and uncertainties about reducing and stopping psychiatric medicines. Methods: The Priority Setting Partnership will be conducted using the James Lind Alliance methodology. It will involve seven stages: (i) creating an international Steering Group of representatives from key stakeholder groups that will include people with lived experience of taking and/or stopping psychiatric medicines, family members, carers/supporters and healthcare professionals, and identifying potential partners to support key activities (e.g. dissemination); (ii) gathering uncertainties about reducing and stopping psychiatric medicines from key stakeholders using an online survey; (iii) data processing and summarising the survey responses; (iv) checking the summary questions against existing evidence and verifying uncertainties; (v) shortlisting the questions using a second online survey; (vi) determining the Top 10 research questions through an online prioritisation workshop; (vii) disseminating results. Conclusions: This study will use a Priority Setting Partnership to generate a Top 10 list of research questions and uncertainties about reducing and stopping psychiatric medicines. This list will help to guide future research and deliver responsive and strategic allocation of research resources, with a view to ultimately improving the future health and well-being of individuals who are taking psychiatric medicines.

This paper proposes a design method to reduce cogging torque and torque ripple in the concentrated winding of IPMSMs (Interior Permanent Magnet Synchronous Motors) used in motors for the semiconductor ETCH process. IPMSMs can utilize reluctance torque through the difference in inductance between the d axis and q axis, but they are at a disadvantage in terms of reducing cogging torque while tapering the rotor and stator to reduce torque ripple. In addition, the existing single tapering can push the permanent magnets into the rotor. If the rotor’s permanent magnets are embedded, the magnetic reluctance will increase, and the overall performance of the motor will decrease. However, an optimum design method was derived in which the magnets do not move during rotor tapering. This geometric design is an optimum design method that reduces cogging torque and torque ripple. This paper compares and analyzes four models, the concentrated winding model, distributed winding model, conventional tapering model, and separated tapering model, using 2D and 3D finite element analysis (FEA).

Background: In the context of a recovery-oriented approach to mental healthcare, the role of psychotropic medication over extended or indefinite periods is increasingly being called into question. To minimise the risks of withdrawal symptoms and relapse, it is crucial that service users who want to discontinue psychotropic medication are supported throughout the tapering process. However, in the absence of effective interventions and supports, service users are increasingly relying on online resources for guidance and support. To date, the evidence base for mobile phone applications (‘apps’) and app-based interventions supporting discontinuation of psychotropic use has not been examined. This scoping review aims to examine the content, underpinning evidence base and impact of available mobile phone apps and app-based interventions to support psychotropic tapering. Methods: A scoping review will be conducted using the Joanna Briggs Institute guidance and results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA-ScR) guideline. Several electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, ACM and IEEE Xplore) will be searched from 2008 onwards. Searches of the major app stores will also be conducted, specifically Apple's App Store (iOS) and Google Play Store (Android). Following screening, key information will be extracted from the included studies and apps. Identified apps will be coded using the Behaviour Change Technique (BCT) Taxonomy. The findings will be described using narrative synthesis. Conclusions: This scoping review will provide a broad overview of available apps to support psychotropic tapering, including a summary of their content using the BCT Taxonomy. The review findings will guide future research relating to the development, implementation and evaluation of app-based interventions to support the tapering of psychotropic medication.

Abstract Background Opioids are still widely prescribed to long-term pain patients although they are no longer recommended for long-term treatments due to poor evidence for long-term efficacy, risks of serious side effects, and the possibility of inducing opioid hyperalgesia. In a Cochrane study from 2017, the authors identified an urgent need for more randomized controlled trials investigating the efficiency and effects of opioid tapering. The study aimed to assess (1) the efficiency of a structured intervention in causing stable reductions of opioid consumption in a population with long-term non-malignant pain and (2) effects on pain, pain cognitions, physical and mental health, quality of life, and functioning in response to opioid tapering. Methods The study is a randomized controlled trial. The sample size was set to a total of 140 individuals after estimation of power and dropout. Participants will be recruited from a population with long-term non-malignant pain who will be randomly allocated to (1) the start of tapering immediately or (2) the control group who return to usual care and will commence tapering of opioids 4 months later. A 12-month follow-up is included. When all follow-ups are closed, data from the Swedish drug register of the National Board of Health and Welfare will be collected and individual mean daily opioid dose in morphine equivalents will be calculated at three time points: baseline, 4 months, and 12 months after the start of the intervention. At the same time points, participants fill out the following questionnaires: Numeric Pain Rating Scale (NPRS), Tampa Scale of Kinesiophobia (TSK), Pain Catastrophizing Scale (PCS), Chronic Pain Acceptance Questionnaire (CPAQ-8), Hospital Anxiety and Depression Scale (HADS), and RAND-36. At baseline and follow-up, a clinical assessment of opioid use disorder is performed. Discussion A better understanding of the efficiency and effects of opioid tapering could possibly facilitate attempts to taper opioid treatments, which might prove beneficial for both the individual and society. Trial registration ClinicalTrials.gov NCT03485430 . Retrospectively registered on 26 March 2018, first release date. “Tapering of Long-term Opioid Therapy in Chronic Pain Population. RCT with 12 Months Follow up (TOPIO).” First patient in trial 22 March 2018.

Abstract Background Narrative communication is often more persuasive for promoting health behaviour change than communication using facts and figures; the extent to which narrative persuasiveness is due to patients’ identification with the storyteller vs engagement with the story is unclear. Objective To examine the relative impacts of patient engagement, age concordance and gender concordance on perceived persuasiveness of video‐recorded narrative clips about opioid tapering. Methods Patient raters watched and rated 48 brief video‐recorded clips featuring 1 of 7 different storytellers describing their experiences with opioid tapering. The dependent variable was clips’ perceived persuasiveness for encouraging patients to consider opioid tapering. Independent variables were rater engagement with the clip, rater‐storyteller gender concordance and rater‐storyteller age concordance (

Demand for high-speed motors is increasing. Surface-mounted permanent magnet synchronous motors (SPMSM) used in high-speed applications have magnets attached to the rotor, so there is a risk of damage and scattering due to centrifugal force as the speed increases. For this reason, applying the retaining sleeve to the rotor is essential. However, when using sleeves, there is a problem of reducing efficiency due to eddy current loss. In this paper, a study was conducted on a motor for a 100 kW building air conditioning system operating at a speed of 20,000 rpm. The purpose of the study is to reduce eddy current loss by optimizing the sleeve geometry. To this end, 3D finite element analysis (FEA) using JMAG 22.1 was conducted to analyze eddy current loss, the minimum safety factor was analyzed through mechanical stiffness analysis using ANSYS Workbench, and the validity of sleeve shape was proved through cause analysis. Through the research results, it is expected that the shape change of the sleeve will have the effect of reducing eddy current loss.

AimEvidence is insufficient regarding the consequences of discontinuing vs. maintaining antipsychotic medication in patients with first-episode schizophrenia. Our aim was to examine tapered discontinuation vs. maintenance treatment regarding remission of psychotic symptoms and impact on other areas.MethodsPatients included had a diagnosis of schizophrenia, were treated with antipsychotic medication, and were in remission of psychotic symptoms. Participants were randomized to tapered discontinuation or maintenance treatment with antipsychotic medication. Assessments were undertaken at baseline and after 1-year. The primary outcome was remission of psychotic symptoms without antipsychotic medication.ResultsThe trial was terminated due to insufficient recruitment. In total, 29 participants were included: 14 in the tapering/discontinuation group and 15 in the maintenance group. Adherence to maintenance treatment was poor. At 1-year follow-up, remission of psychotic symptoms without antipsychotic medication for 3 months was observed in five participants in the tapering/discontinuation group and two in the maintenance group.ConclusionDue to insufficient recruitment this study does not provide a conclusion on whether unfavorable outcomes or advantages follow tapering of antipsychotic medication. Recruitment and adherence to maintenance treatment encountered obstacles. Based on experiences from this trial, we discussed alternative study designs as consistent evidence is still needed on whether to continue or discontinue antipsychotic medication in remitted patients with first-episode schizophrenia.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000565-23/DK, EU Clinical Trials Register—EudraCT no. 2016–000565–23.

Abstract Background Strategic drug therapy for rheumatoid arthritis (RA) patients with prolonged remission is not well defined. According to recent guidelines, tapering biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) may be considered. We aimed to evaluate the effectiveness of long-term maintenance of tocilizumab (TCZ) treatment after the progressive tapering of infusions. Methods We conducted an exploratory, prospective, single-center, open-label study, on RA patients with sustained remission of at least 3 months and treated with TCZ infusions every 4 weeks. The initial re-treatment interval was extended to 6 weeks for the first 3 months. Thereafter, the spacing between infusions was determined by the clinician. Successful long-term maintenance following the tapering of TCZ infusions was defined by patients still treated after two years by TCZ with a minimum dosing interval of 5 weeks. Results Thirteen patients were enrolled in the study. Eight out of thirteen were still treated by TCZ after two years. Successful long-term maintenance was possible in six patients, with four patients maintaining a re-treatment interval of 8-weeks or more. We observed 5 patients with TCZ withdrawal: one showing adverse drug reaction (neutropenia) and four with secondary failure. Patients achieving successful long-term maintenance with TCZ were significantly younger than those with secondary failure (p

Background and Objectives: TPO-RAs (romiplostim/eltrombopag/avatrombopag) have broadly demonstrated high efficacy rates (59–88%), durable responses (up to three years) and a satisfactory safety profile in clinical trials. The effect of TPO-RAs is classically considered to be transient because platelet numbers usually dropped rapidly to baseline unless therapy was maintained. However, several groups have reported the possibility of successfully discontinuing TPO-RAs in some patients without further need for concomitant treatments. This concept is usually referred as sustained remission off-treatment (SROT). Materials and Methods: Unfortunately, we still lack predictors of the response to discontinuation even after the numerous biological, clinical and in vitro studies performed to study this phenomenon. The frequency of successful discontinuation is matter of controversy, although a percentage in the range of 25–40% may probably be considered a consensus. Here, we describe all major routine clinical practice studies and reviews that report the current position on this topic and compare them with our own results in Burgos. Results: We report our Burgos ten-step eltrombopag tapering scheme with which we have achieved an elevated percentage rate of success (70.3%) in discontinuing treatment. Conclusions: We hope this protocol may help successfully taper and discontinue TPO-RAs in daily clinical practice.

Objective: In the clinic, some patients with axial spondyloarthritis (axSpA) have to reduce tumor necrosis factor inhibitor (TNFi) for various reasons. However, there are few studies about how to balance the relapse and TNFi reduction. Here we retrospectively analyzed the structural progression of the sacroiliac joint (SIJ) and clinical features in axSpA during TNFi reduction.Methods: A total of 108 patients with axSpA who followed up for 2 years and completed at least baseline, 12-month, and 24-month MRI scans of SIJ were divided into the tapering group (n = 63) and withdrawal group (n = 45) according to whether TNFi was stopped. We divided 2 years into five intervals, calculating the average dose quotient (DQ) for each of 540 intervals from 108 patients. By using generalized estimation equations with inverse probability of treatment weighting, we investigated the unbiased effects of average DQ on structural progression and treatment response.Results: The disease activity (such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, and ASDAS-ESR) and relapse rate were lower in the tapering group at 12 and 24 months (p < 0.05). Δerosion (β = −0.0100, p = 0.00026) and Δthe Spondyloarthritis Research Consortium of Canada (SPARCC; β = −0.0959, p < 0.0001) were negatively correlated with average DQ. The average DQ 30 (74.8%, 80.0%) or 41.6 (76.5%, 83%) was best to discriminate the status of treatment response or the status of bone marrow edema, but considering operability, the average DQ 25 (78.0%, 63.3%) was also acceptable especially for patients with HLA-B27 negative and non-severe fat metaplasia.Conclusion: Complete TNFi withdrawal was not recommended. Our study provided a referable strategy (tapering then maintained the average DQ over 30 or even 25) for patients who need TNFi reduction. Higher dose usage of TNFi was associated with a slower erosion progression of SIJ.

Abstract Background Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. Methods We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. Discussion More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. Trial registration Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018).

Abstract Treat-to-target (T2T) and dose tapering after obtaining the therapeutic objective (called “treat-to-budget”-T2B-in this Commentary) are the two most commonly used therapeutic strategies in rheumatoid arthritis. In theory, both strategies could add value to the healthcare system, although they are focused on different objectives: T2T strategy improves outcomes but increases short-term costs, while the cost savings obtained through T2B are associated with higher relapse rates. The systematic implementation of both strategies must be founded on solid evidence of their effectiveness and efficiency. However, the level of evidence between guidelines and individual studies is inconsistent for both strategies and the number and the quality of cost-effectiveness analyses is scarce. Raising the level of evidence requires a move from generalization to individualization by conducting randomized clinical trials that assess each of the many strategies that fall under the umbrella of the overall T2T and T2B concepts. In addition, such studies should consider the therapeutic goals and impact of the disease from the perspective of individual patients, which is only possible by promoting shared decision-making. Funding Lilly Spain.

Abstract This study examines the spillover effects of U.S. monetary policy normalization on Nigeria 10-Year Treasury bond yield between 2011 and 2017, using the vector error correction model approach. Our results reveal that domestic factors, such as exchange rate and inflation, rather than the U.S. 10-Year sovereign bond yield, are the key drivers of Nigeria 10-Year bond yield. Additionally, the spillover effect from the U.S. monetary policy was amplified by oil price shocks and changes in Nigeria’s monetary policy rates. Our counterfactual analysis confirms the findings.

Abstract Background Antidepressant use continues to rise, mainly explained by an increase in the proportion of patients receiving long term treatment. Although treatment guidelines recommend discontinuation after sustained remission, discontinuing antidepressants appears to be challenging for both patients and general practitioners (GPs). Mindfulness-Based Cognitive Therapy (MBCT) is an effective intervention that reduces the risk of relapse in recurrent depression and might facilitate discontinuation by teaching patients to cope with withdrawal symptoms and fear of relapse. The current study aims to investigate the effectiveness of the combination of Supported Protocolized Discontinuation (SPD) and MBCT in comparison with SPD alone in successful discontinuation of long-term use of antidepressants in primary care. Methods This study involves a cluster-randomized controlled trial conducted in primary care patients with long-term use antidepressants with baseline and 6, 9 and 12 months follow-up assessments. Patients choosing to discontinue their medication will be offered a combination of SPD and MBCT or SPD alone. Our primary outcome will be full discontinuation of antidepressant medication (= 0 mg) within 6 months after baseline assessment. Secondary outcome measures will be the severity of withdrawal symptoms, symptoms of depression and anxiety, psychological well-being, quality of life and medical and societal costs. Discussion In theory, stopping antidepressant medication seems straightforward. In practice however, patients and their GPs appear reluctant to initiate and accomplish this process. Both patients and professionals are in need of appropriate tools and information to better support the process of discontinuing antidepressant medication. Trial registration ClinicalTrials.gov PRS ID: NCT03361514 retrospectively registered October 2017.

Th e purpose of the present study was to investigate the eff ects of exponential and linear tapering protocols on the distance covered according to playing positions among junior elite soccer players. One-hundred and fi ft y-eight junior elite soccer players (mean age: 17.07±0.79 years; mean height: 177.85±6.64 cm; mean weight: 71.27±7.96 kg; mean body-mass index: 22.50±1.66 kg/m²) were randomly selected into two groups: (1) exponential and (2) linear tapering group. Training sessions were conducted three times a week for eight weeks. Aft er four and eight weeks of the tapering period, participants were measured in the distance covered according to four basic playing positions on the fi eld: (1) goalkeepers, (2) defenders, (3) midfi elders, and (4) forwards. Th e results showed that the largest eff ects between the pre- and post-measurement had defenders in the exponential and goalkeepers in the linear group, goalkeepers in the distance covered by slow and medium running in both groups, forwards in fast running and sprinting in the exponential group, and midfi elders in the linear group. In conclusion, our results suggest that the exponential tapering protocol brought somewhat larger eff ects, especially in fast running and sprinting in forwards and slow and medium running in goalkeepers. Future studies need to implement both the exponential and the linear tapering protocols in order to enhance performance but favouring the exponential to produce larger eff ects.

Objectives: We aim to evaluate the proportion and characteristics of enthesitis-related arthritis (ERA) patients in whom medications can be withdrawn in daily practice and to analyze the factors associated with flare-ups during medication tapering of these patients.Methods: We retrospectively reviewed records of patients under 16 years old diagnosed with ERA from April 2001 to March 2020 in one tertiary medical center in Taiwan. Patients were categorized by different medication uses: conventional disease modifying anti-rheumatic drugs (cDMARDs) only and cDMARDs plus biologics. Demographics, laboratory data, presence of uveitis, and medication withdrawal rate were analyzed. Subgroup analysis was performed in the patients with cDMARDs plus biologics to identify factors associated with flare-ups during medication tapering of these patients. Statistical analysis was performed using R (v3.6.0).Results: There were 75 juvenile ERA patients with a median onset age of 10.28 years old. Nineteen (25.3%) patients used cDMARDs for disease control; 56 (74.7%) patients depended on cDMARDs plus biologics. Poly-articular involvement was noted in 29 (38.7%) patients, and it occurred more frequently in the cDMARDs plus biologics subgroup (cDMARDs only, 5.3%; cDMARDs plus biologics, 53.6%; P = 0.0001). ANA positivity was observed in 18 (24.0%) patients, and it occurred more frequently in the cDMARDs plus biologics subgroup (cDMARDs, 0%; cDMARDs plus biologics, 32.1%; P = 0.0038). The overall medication withdrawal rate was 34.7%, and it occurred more frequently in patients with cDMARDs only (cDMARDs only, 84.2%; cDMARDs plus biologics, 17.9%; P < 0.001). In the subgroup analysis of patients with cDMARDs plus biologics, patients on biologics tapering with flare-up had a significantly longer time interval between disease onset and initiation of cDMARDs (biologics tapering without flare-up: 0.27 (0.11–0.73) years; biologics tapering with flare-up: 1.14 (0.39–2.02) years; ever withdrawing biologics: 0.26 (0.18–0.42) years, P = 0.0104).Conclusion: Juvenile ERA patients with polyarticular involvement had a higher risk of developing cDMARDs refractory and progressing to biologics use. Patients with a long time interval between disease onset and initiation of cDMARDs were prone to experience flare-up during tapering of biologics.

Research on the calculation of tapering from lung's images of patients with pleural effusion and normal lungs has been carrying out using the thresholding segmentation method. The tapering calculation was done using the Matlab programming language by applying the thresholding segmentation method's image processing theory. Images sharpness was obtaining from calculating the longest distance from all distances that were searching in the program. The steps taken in this research were image quality improvement, determination of the region of interest (ROI), thresholding segmentation, and calculating the tilt. Taper count was performing on eight lung images identified pleural effusion and eight lung images identified as normal. In 8 images of lungs pleural effusions, each taper was obtained 166; 159; 167; 167; 150; 157; 114; and 149. Whereas in 8 images of normal lungs, it was obtained that the respective curls were 187; 174; 181; 198; 199; 195; 179; and 195. The analysis showed that the lung's images of pleural effusion patients had a tapering of less than 171. In contrast, normal lung images had a tapering of more than 171, so that one characteristic was obtained that could distinguish between normal lungs and pleural effusions. It can facilitate medical personnel in the early detection of pleural effusion patients so that they can be handled quickly and accurately.

Withdrawal symptoms after discontinuation of antidepressants are common and have long been known. Typical symptoms after dose reduction or discontinuation of antidepressants are dizziness, drowsiness, headache, flu-like symptoms, hyperarousal, imbalance, insomnia, irritability, and nausea. Rebound, relapse, or recurrence associated with the underlying mental disorder may also occur. The occurrence of obsessive-compulsive symptoms (OCS) following abrupt discontinuation of antidepressants have not yet been reported. Here we report the development of OCS (obsessional suicidal thoughts) in a patient with major depressive disorder and absence of a previous obsessive-compulsive disorder following abrupt discontinuation of venlafaxine. Treatment with escitalopram facilitated remission of OCS. We discuss a possible causal link between abrupt discontinuation of venlafaxine and development of OCS under consideration of pathophysiologic aspects regarding obsessive compulsive disorders, the chronological sequence of symptoms in the present case, and pharmacodynamic and -kinetic aspects. Our case report suggests the possibility of the occurrence of obsessive-compulsive symptoms following abrupt discontinuation of venlafaxine.

Abstract An investigation of thixotropic parameter influence on blood flow in a stenosed tapered vessel has been carried out by means of analytical and numerical methods. We have studied how variation of a parameter in a range [0,1] $[0,1]$, chosen following the evolution of transient shear, flows with time in this particular range and impacts the dynamics of an unsteady, non-Newtonian fluid flow. An approximation of a simpler dynamical system was approached with the help of a particular set of non-dimensional variables. Unique representations of axial velocity, shear stress and flow rate have been made such that their dependence on pressure gradient can be further analysed. Some factors that either impede the flow or help to accelerate it in a narrow channel in addition to varying yield stress and thixotropic parameter have been numerically investigated. The purpose of the current investigation is also to decide whether the particular model parameter regulates the dynamics of flow in a vessel differently from other known non-Newtonian models and what specific range or values of this parameter bring this model’s results to coincide with other models’ results

Rationale. Clinicians need to have evidence-based information regarding the feasibility of tapering biologics in ankylosing spondylitis (AS). Objective. The study aims to identify significant predictors of tapering in clinical practice. Methods and results. AS patients on their first tumor necrosis factor alpha inhibitor (iTNFα) were enrolled between 2015-2017 and followed until the end of the observation or until tapering or switch of their iTNFα. Binary logistic regression was used to predict tapering (“0” for “non-tapering”, meaning switches and original posology; “1” for “tapering”), significant if p < 0.05. Of the 120 included patients, 50.8% had adalimumab, 21.7% etanercept, 4.2% golimumab and 23.3% infliximab. During follow-up, 40.8% tapered their initial iTNFα, 40.8% remained on its original posology, 16.7% switched it and 1.7% were lost. Judging by odds ratios (OR), inflammatory markers (e.g. odds ratio ORCRP = 0.936, p = 0.014) and activity scores (ORBASDAI = 0.565, p = 0.005) significantly reduced the chance for tapering. Compared to patients on the original posology, patients on tapering had a significantly lower prevalence of uveitis ever (6.8% compared to 11.0%, p = 0.008, post-hoc χ2 test). Discussion. In a real life setting, no more than half of AS patients treated with TNFα inhibitors can undergo tapering. High baseline inflammatory markers and disease activity indices significantly lower the chance of tapering. From a therapeutic point of view, a non-responsive disease phenotype of AS can be hypothesized and it includes extra-spinal manifestations such as uveitis.

Variation in the dynamics of a steady-state blood flow through a stenosed tapered artery has been investigated corresponding to changes in thixotropic parameter λ over the range [0,1]. To probe the role of parameter λ and differentiate the current model from other known non-Newtonian models, expressions of axial velocity, shear stress, wall shear stress and flow rate have been calculated depending upon this parameter and pressure gradient. Also, pressure gradient has been deduced uniquely with the help of the continuity equation. Our choice of calculating pressure gradient has led to obtaining shear stress such that its dependence on the structural parameter of our model, unlike most available results, motivates for further investigation. The simultaneous effects of varying yield stress and parameter λ on axial velocity, flow resistance and flow rate have been studied such that the differences between the Herschel–Bulkley fluid model and our current model can be pointed out. To validate the suitability of our model and some results in history, we have also obtained limiting results for particular values of λ.

Sportowcy, trenerzy i uczeni zajmujący się sportem nieustannie pracują nad tym, aby maksymalizować tzw. formę sportową w terminie najważniejszych zawodów. Szczyt formy osiąga się zwykle wskutek obniżenia obciążenia treningowego we wcześniej zaplanowanym okresie przed zawodami. Taki okres „okrojonego” treningu określany jest jako tapering (taper). Tapering jest złożonym procesem, na który oddziałuje wiele czynników, między innymi objętość, intensywność oraz częstość treningu. Jeśli proces ten przebiega właściwie, to możliwe jest przygotowywanie formy szczytowej w terminie głównych zawodów. Tapering może się wiec stać jednym z najbardziej rozstrzygających czynników przygotowania sportowca do zawodów. Cel pracy i pytania badawczeBadania podjęto w ramach grantu nr RSA2 023 52, którego celem było wspomaganie sportu akademickiego. Celem pracy stało się zidentyfikowanie rodzaju i wielkości taperingu zastosowanego przez trenerów sekcji lekkoatletyki KS AZS AWF Wrocław w odniesieniu do zawodników elity, kandydujących do startów w Akademickich Mistrzostwach Świata, w Mistrzostwach Świata i Europy, a także w Igrzyskach Olimpijskich. Celem utylitarnym było opracowanie zaleceń, co do optymalnej strategii tapering.Metoda i materiał badawczyZastosowano metodę obserwacji i pomiaru. Rejestrowano obciążenia treningowe i reakcje na te obciążenia w mezocyklu bezpośredniego przygotowania startowego (BPS) w cyklu treningowym lekkoatletów w roku 2014. Badania dotyczyły dwóch grup treningowych prowadzonych przez trenerów TT i MR sekcji lekkoatletycznej AZS AWF we Wrocławiu.Materiał badawczy stanowiły zapiski trenerów, zapiski w dzienniczkach treningowych oraz notatki z pomiarów obciążeń dokonywanych bieżąco w czasie realizacji jednostek treningowych. Dane te weryfikowano poprzez dokonywanie pomiarów stężenia mleczanu i częstości tętna, co pozwoliło na kontrolę wybranych fizjologicznych efektów treningu.Najważniejsza informacja wynikająca z przeprowadzenia badań jest taka, że obaj trenerzy realizowali tapering wyłącznie w zakresie objętości treningu. W żadnym przypadku nie zmieniano częstotliwości treningów. Struktura 7-dniowego mikrocyklu została zachowana aż do dnia startu. Nie zrezygnowano z żadnej jednostki treningowej. Obaj trenerzy nigdy nie zmniejszali intensywności stosowanych środków, a nawet, poprzez pomiar czasu biegów i motywowanie zawodników, powodowali zwiększanie intensywności, czyli prędkości pokonywanych odcinków biegowych. Strategia taperingu przyjęta przez trenerów nie dotyczyła więc ani częstotliwości treningów, ani intensywności, a jedynie objętości stosowanych środków treningowych.Na podstawie uzyskanych wyników badań i ich analizy można sformułować następujące wnioski:1. Trenerzy realizują zindywidualizowane programy taperingu.2. W analizowanych przypadkach okres taperingu wynosił ok. 16 dni.3. Tapering polegał na zmniejszeniu objętości obciążenia do wartości 30-60% w zależności od rodzaju jednostki treningowej.4. Nie zmniejszano intensywności obciążenia oraz częstotliwości treningu.AbstractAthletes, coaches, and sports academics are constantly working to maximize the, so called, sports form during the most important competitions. The form peak is usually achieved by decreasing the training load in the pre-scheduled period before the competition. This period of "cut-down" training is referred to as the tapering (or the taper). Tapering is a complex process affected by the number of factors, including volume, intensity, and frequency of training. If this process is successful, it is possible to achieve the peak form at the time of the major competitions. Tapering can thus become one of the most decisive factors in preparing an athlete for a competition.Aim of the paper and research questions.The research was undertaken under the grant RSA2 023 52 aimed at supporting the academic sport. The aim of the study was to identify the type and size of tapering used by coaches from the athletic section of KS AZS AWF Wroclaw in relation to top ranked athletes competing for the Academic World Championships, World and European Championships, and the Olympic Games. The utilitarian purpose was to develop recommendations for optimal tapering strategies.Method and test materialThe method of observation and measurement was applied. The training loads and responses to these loads during the direct competing preparation mesocycle (BPS) were recorded during the athlete's training cycle in 2014. The study involved two training groups coached by the TT and MR coaches from the athletic section of AZS AWF in Wrocław.The research material consisted of coaches' recordings, training diary entries, and records of training loads measurements performed during training units. These data were verified by lactate level and pulse rate measurements, which allowed controlling the selected physiological effects of training.The most important information from the study is that both coaches performed tapering only in the volume of training. In no case did the training frequency change. The structure of the 7-day microcycle was kept until the start day. No training unit had been canceled. Both coaches had never decreased the intensity of the means used, and they even motivated the athletes by measurements of the running time to increase the intensity, i.e. the speed for the running sections. Therefore, the tapering strategy adopted by the coaches did not concern either the frequency or the intensity of trainings, but only the volume of training measures used.Based on the results of the research and their analysis, the following conclusions can be formulated:1. Trainers implement personal tapering programs.2. In the analyzed cases, the tapering period amounted to approximately 16 days.3. Tapering consisted in reducing the volume of workload to 30-60%, depending on the training unit type.4. No workload intensity and training frequency have been decreased.

Abstract Background The aim of the TAILOR trial is to investigate the effect of closely monitored tapering/discontinuation versus maintenance therapy with antipsychotic medication in patients with newly diagnosed schizophrenia or persistent delusional disorder and with minimum 3 months’ remission of psychotic symptoms. Methods and design Two hundred and fifty patients will be included from the psychiatric early intervention program, OPUS, in two regions in Denmark. Inclusion criteria are: ICD-10 diagnoses schizophrenia (F20, except F20.6) or persistent delusional disorder (F22), minimum 3 months’ remission of psychotic symptoms and in treatment with antipsychotic medication (except clozapine). The patients will be randomized to maintenance therapy or tapering/discontinuation with antipsychotic medication in a 1-year intervention. The tapering/discontinuation group will be using a smartphone application to monitor early warning signs of psychotic relapse. Patients will be assessed at baseline, 1-, 2- and 5-year follow-up regarding psychotic and negative symptoms, side-effects of antipsychotic medication, social functioning, cognitive functioning, perceived health status, patient satisfaction, substance and alcohol use, sexual functioning and quality of life. The primary outcome will be remission of psychotic symptoms and no antipsychotic medication after 1 year. Secondary outcome measures will include: co-occurrence of remission of psychotic symptoms and 0–1-mg haloperidol equivalents of antipsychotic medication after 1-year intervention; antipsychotic dose; antipsychotic side effects; negative symptoms; social functioning; cognitive functioning; and patient satisfaction. Exploratory outcomes will include remission, clinical recovery, substance and alcohol use, sexual functioning, quality of life, self-beliefs of coping and user experience of support from health workers. Safety measures will include death, admissions to psychiatric hospital, severe self-harm and psychotic relapses. Discussion The TAILOR trial will contribute knowledge about the effect of tapering/discontinuation of antipsychotic medication in the early phases of schizophrenia and related disorders and the results may guide future clinical treatment regimens of antipsychotic treatment. Trial registration EU Clinical Trials Register – EudraCT number: 2016-000565-23 . Registered on 5 February 2016.

This paper investigates the drivers of long term real interest rates in Brazil. It is shown that long term yield on inflation linked bonds are driven by yields on 10 year interest rates of United States (US) government bonds and 10 year risk premium, as measured by the Credit Default Swap (CDS). Long term interest rates in Brazil were on a downward trend, following US real rates and stable risk premium, until the taper tantrum in the first half of 2013. From then onwards, real interest rates rose due to the increase in US real rates in anticipation of the beginning of monetary policy normalization and, more recently, due to a sharp increase in Brazilian risk premium. Policy interest rates do not significantly affect long term real interest rates.

The aim of the study presented in this paper is to analyze the correlation between the parameters of a spiral twist and the geometry of the tapered and double truncated cone solids on which it is applied, in order to design a helical trajectory with variable pitch, aesthetical harmonized with the shape and sizes of the furniture wood component. The property of the spiral twist with variable pitch (as helical trajectory on a double truncated surface) is that its axial pitch is proportional to the variable diameter of the wood part on which it is processed, so to create the maximum aesthetic effect of the proportion between the volumes and the dynamism required by the ornament function of the piece of furniture. The diameter size of a double truncated wooden part, which vary along its length, depends both on the position from the edge where the correlation is done and on the piece taper size. The proportion between the pitch measured on the part surface and the corresponding diameter has to comply with the proportion between the axial pitch and the corresponding diameter. The axial pitch cannot be measured, but it can be calculated depending on the pitch measured on the part’s surface. Correlation between the geometric parameters of the spiral twist with variable pitch and the geometry of the designed wooden part on which it is processed (Dmax, Dmin, ∝, ϴ) is very important for the aesthetic reason of the ornament and also for defining the kinematics during machining it.

The aim of the study presented in this paper is to analyze the correlation between the parameters of a spiral twist and the geometry of the tapered and double truncated cone solids on which it is applied, in order to design a helical trajectory with variable pitch, aesthetical harmonized with the shape and sizes of the furniture wood component. The property of the spiral twist with variable pitch (as helical trajectory on a double truncated surface) is that its axial pitch is proportional to the variable diameter of the wood part on which it is processed, so to create the maximum aesthetic effect of the proportion between the volumes and the dynamism required by the ornament function of the piece of furniture. The diameter size of a double truncated wooden part, which vary along its length, depends both on the position from the edge where the correlation is done and on the piece taper size. The proportion between the pitch measured on the part surface and the corresponding diameter has to comply with the proportion between the axial pitch and the corresponding diameter. The axial pitch cannot be measured, but it can be calculated depending on the pitch measured on the part’s surface. Correlation between the geometric parameters of the spiral twist with variable pitch and the geometry of the designed wooden part on which it is processed (Dmax, Dmin, ∝, ϴ) is very important for the aesthetic reason of the ornament and also for defining the kinematics during machining it.

En este artículo se comentan y revisan opiniones y conclusiones que se han llegado a determinar por los investigadores que trabajan en el FMI y que, como economistas, consideramos de vital importancia para su análisis y comprensión. En él, se establece que estamos asistiendo a un crecimiento e inflación mundial persistentemente débil e incierta, a pesar de haber tomado una serie de medidas correctivas después de la crisis del 2008; además, se aprecia un decaimiento del optimismo, marcando la pauta de una nueva normalidad, a la cual el FMI llama la “nueva mediocridad”. Todo esto está provocando un aumento de los riesgos macroeconómicos, por lo que el FMI recomienda que es imperativo que los hacedores de políticas públicas actúen hoy más que nunca de forma conjunta y cooperante, actuando más allá del actual escenario establecido, donde las políticas monetarias han sido las grandes protagonistas, de forma tal que facilite un ambiente de confianza que nos saque de esta normalidad ralentizada y promueva un sostenido crecimiento económico mundial evitando futuras crisis.

Athletes, coaches, and sports academics are constantly working to maximize the, so called, sports form during the most important competitions. The form peak is usually achieved by decreasing the training load in the pre-scheduled period before the competition. This period of "cut-down" training is referred to as the tapering (or the taper). Tapering is a complex process affected by the number of factors, including volume, intensity, and frequency of training. If this process is successful, it is possible to achieve the peak form at the time of the major competitions. Tapering can thus become one of the most decisive factors in preparing an athlete for a competition. Aim of the paper and research questions. The research was undertaken under the grant RSA2 023 52 aimed at supporting the academic sport. The aim of the study was to identify the type and size of tapering used by coaches from the athletic section of KS AZS AWF Wroclaw in relation to top ranked athletes competing for the Academic World Championships, World and European Championships, and the Olympic Games. The utilitarian purpose was to develop recommendations for optimal tapering strategies. Method and test material The method of observation and measurement was applied. The training loads and responses to these loads during the direct competing preparation mesocycle (BPS) were recorded during the athlete's training cycle in 2014. The study involved two training groups coached by the TT and MR coaches from the athletic section of AZS AWF in Wrocław. The research material consisted of coaches' recordings, training diary entries, and records of training loads measurements performed during training units. These data were verified by lactate level and pulse rate measurements, which allowed controlling the selected physiological effects of training. The most important information from the study is that both coaches performed tapering only in the volume of training. In no case did the training frequency change. The structure of the 7-day microcycle was kept until the start day. No training unit had been canceled. Both coaches had never decreased the intensity of the means used, and they even motivated the athletes by measurements of the running time to increase the intensity, i.e. the speed for the running sections. Therefore, the tapering strategy adopted by the coaches did not concern either the frequency or the intensity of trainings, but only the volume of training measures used. Based on the results of the research and their analysis, the following conclusions can be formulated: 1. Trainers implement personal tapering programs. 2. In the analyzed cases, the tapering period amounted to approximately 16 days. 3. Tapering consisted in reducing the volume of workload to 30-60%, depending on the training unit type. 4. No workload intensity and training frequency have been decreased

Los opioides usados durante más de cinco días, para sedación en paciente pediátrico, deben ser retirado de forma progresiva con el objetivo de prevenir abstinencia. Para este propósito las pautas de retirada con metadona enteral son frecuentemente utilizadas. Sin embargo, la dificultad en la apliación de protocolos y la diferencia entre pacientes, hacen que esta práctica no esté exenta de dificultad. En este artículo intentamos dar respuesta o al menos sugerir pautas, para realizar esta práctica. ABSTRACT Use of methadone for sedation weaning in critical ill patient Opioids used for more than five days in sedation, should be withdrawn progressively in order to prevent abstinence syndrome. Methadone are frequently used for this purpose. However, the difficulty in the application of protocols and the difference between patients, make this practice not free of difficulty. In this review we try to answer or at least suggest guidelines to carry out this practice.

Aim: This study was carried out to quantify risk of seizure recurrence after discontinuation of antiepileptic drugs (AEDs) after varying duration of seizure remission in children with epilepsy and to assess the variables modifying the risk of seizure recurrence. Materials and Methods: Randomized controlled trials that evaluate withdrawal of AEDs after varying periods of seizure remission in pediatric epilepsy patients, which could be unblinded, single-blind, or double-blind. The database searching included Cochrane Epilepsy Group Specialized Register, MEDLINE, EMBASE, CINAHL, WHO Clinical trial register, and the Cochrane Central Register of Controlled Trials. Two independent authors extracted the data and assessed trials for quality. Results: The pooled relative risk ratio (RR) for early AEDs withdrawal and late AEDs withdrawal was assessed as 1.22 (95% confidence intervals [CI]: 0.94-1.57), for type of epilepsy pooled relative risk was 1.52 (95% CI: 0.96-2.41), electroencephalogram (EEG) relative risk was assessed as 1.65 (95% CI: 1.08-2.51) and the underlying etiology relative RR was assessed as 1.65 (95% CI: 1.08-2.51). Conclusion: The high-grade evidence of this study supports that discontinuing AED medication prior to at least 2 seizure free years is associated with higher seizure recurrence risk than waiting for two or more seizure free years in children.

Prescribing guidelines do not recommend the long-term use of benzodiazepines since their effectiveness with chronic use is out-weighed by risks including dependence, memory and cognitive impairment, hip fractures and traffic accidents. Despite these guidelines, historical data points to an increasing proportion of inappropriate, repeat prescribing of benzodiazepines in Ireland and elsewhere, with up to 33% of patients who use these drugs doing so long-term. The typical long-term benzodiazepine user is an older, socio-economically disadvantaged patient who has been prescribed these medicines by their general practitioner (GP) and dispensed them by their community pharmacist. Misuse of benzodiazepines in nursing homes and psychiatric institutions is also of concern, with one Irish study indicating that almost half of all admissions to a psychiatric hospital were prescribed these drugs, usually despite a lack of clear clinical need. Discontinuation of benzodiazepines has proven to be of benefit, as it is followed by improvements in cognitive and psychomotor function, particularly in elderly patients. It is obvious that an inter-professional effort, focusing on the primary care setting, is required to address benzodiazepine misuse and to ensure appropriate pharmaceutical care. Pharmacists must be an integral part of this inter-professional effort, not least because they are uniquely positioned as the health professional with most frequent patient contact. There is already some supporting evidence that pharmacists’ involvement in interventions to reduce benzodiazepine use can have positive effects on patient outcomes. Here, this evidence is reviewed and the potential for pharmacists to play an expanded role in ensuring the appropriate use of benzodiazepines is discussed.