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Background: Relapsing seizures following discontinuation of antiseizure drugs (ASDs) has been the focus of several researches in recent years. This research aimed to identify the predictive factors of seizure recurrence after anti-seizure drugs withdrawal among epileptic patients who had achieved two years seizures remission. Methods: A total of 60 epileptic patients who had achieved two years seizures remission and began ASDs withdrawal were followed prospectively for one year. The patients were divided into two groups; patients with and without relapsed seizures. Clinical and demographic details were recorded. National Hospital Seizure Severity Scale (NHS3) was used to assess theseverity of epilepsy. Regular Electroencephalogram (EEG) monitoring was done. Anxiety and depressive symptoms were assessed by using generalized anxiety disorder 7 (GAD7) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) scales respectively. Results: Risk of post-withdrawal relapsed seizures increased with; history of status epilepticus (p=0.002), focal seizures (p=0.005), late remission of initial epileptic seizures (p=0.002), delay of ASD therapy (p<0.001), Poly-therapy (p<0.001), post-withdrawal epileptiform EEG (p<0.001), high NHS3, GAD7, NDDI-E scores (p<0.001) Conclusions: Risk of relapsing seizures after ASDs withdrawal during the first year was 60%. The decision to withdraw ASDs necessitates individual evaluation of each case with accurate assessment of risk factors associating with relapsed seizures. [ABSTRACT FROM AUTHOR]

Purpose: Removing medicines from market may benefit public health by preventing adverse drug reactions (ADRs), which should be quantified. This study's aim was to identify a model to quantify the impact of medicines' marketing authorisation (MA) withdrawal and revocation in terms of preventing morbidity and mortality. Methods: MA withdrawals and revocations for safety reasons in France, Germany and/or the United Kingdom between July 2012 and December 2016 were identified for prescription medicines. Annual exposure was estimated for each medicine, using IQVIA Medical Research Data (IMRD)‐France, IMRD‐Germany and IMRD‐UK primary care electronic health record databases. European Medicines Agency records provided reasons for regulatory action for each medicine. Absolute risks of ADRs which led to MA withdrawal were estimated for patients exposed to each medicine by systematic review of quantitative research. Public health impact, expressed as annual number of ADRs avoided, was estimated by modelling exposure and ADR risk. Results: Four MA withdrawals and two revocations met study inclusion criteria. Each product's usage decreased following MA withdrawal or revocation. Absolute risk for ADRs was 0.1%–41.25%. To estimate impact of each withdrawal or revocation, its average annual exposure within each IMRD population was multiplied by the absolute risk to give the crude number of ADRs prevented annually due to regulatory action. Conclusions: This model quantifies the public health impact of MA withdrawal and revocation in terms of serious morbidity, resulting from eliminated or reduced usage of medicines. This method can be applied to products in other settings to quantify the impact of other pharmacovigilance actions. [ABSTRACT FROM AUTHOR]

This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic outcomes, barriers and facilitators, and tools for deprescribing are presented. The Medline database was used. The search was limited to systematic reviews and meta-analyses published in English up to April 2022. Reviews reporting deprescribing were included, while those where depre-scribing was not planned and supervised by a healthcare professional were excluded. A total of 94 systematic reviews (23 meta--analyses) were included. Most explored clinical or humanistic outcomes (70/94, 74 %); less explored attitudes, facilitators, or barriers to deprescribing (17/94, 18 %); few focused on tools (8/94, 8.5 %). Reviews assessing clinical or humanistic outcomes were divided into two groups: reviews with deprescribing intervention trials (39/70, 56 %; 16 reviewing specific deprescribing interventions and 23 broad medication optimisation interventions), and reviews with medication cessation trials (31/70, 44 %). Deprescribing was feasible and resulted in a reduction of inappropriate medications in reviews with deprescribing intervention trials. Complex broad medication optimisation interventions were shown to reduce hospitalisation, falls, and mortality rates. In reviews of medication cessation trials, a higher frequency of adverse drug withdrawal events underscores the importance of prioritizing patient safety and exercising caution when stopping medicines, particularly in patients with clear and appropriate indications.

(1) Background: Intraperitoneal injections of the endogenous N-acyl amino acid N-Oleoyl alanine (OlAla) effectively reduces both the affective and somatic responses produced by opioid withdrawal in preclinical models. To increase the translational appeal of OlAla in clinical drug applications, the current experiments tested whether oral OlAla pretreatment also attenuates opioid withdrawal in rats. (2) Methods: In Experiment 1, to assess its impact on affective withdrawal behavior, OlAla (0, 5, 20 mg/kg) was orally administered during the conditioning phase of an acute naloxone-precipitated morphine withdrawal conditioned place avoidance task. In Experiment 2, to assess its impact on somatic withdrawal behavior, OlAla (5–80 mg/kg) was orally administered prior to naloxone-precipitated withdrawal from chronic heroin exposure. (3) Results: Pretreatment with oral OlAla at the higher (20 mg/kg), but not lower (5 mg/kg) dose, reduced the establishment of an acute morphine withdrawal-induced conditioned place aversion. Instead, the lower dose of oral OlAla (5 mg/kg) reduced heroin withdrawal-induced abdominal contractions and diarrhea, whereas higher doses were without effect. (4) Conclusions: The results suggest a dose-dependent reduction of opioid withdrawal responses by orally administered OlAla, and further highlight the potential utility of this compound for opioid withdrawal in clinical populations. [ABSTRACT FROM AUTHOR]

Rationale: Withdrawal syndrome (WDS) has been described after discontinuation of antipsychotics. WDS could be the consequence of an over-activation of the dopaminergic pathway. Antipsychotics with a higher affinity for dopamine D2 receptors could be associated with a higher risk of WDS. This study aims to address this statement and evaluate the risk difference for withdrawal syndrome between antipsychotics based on pharmacovigilance data. Methods: We collected individual reports registered in Vigibase® between 01/01/2000 and 31/12/2022 of patients treated with antipsychotics and who had presented WDS. A disproportionality analysis was performed to evaluate the risk of reporting WDS with each antipsychotic compared to all other antipsychotics. We performed a correlation analysis to assess the correlation between the risk of reporting WDS for each antipsychotic in relation with their pKi for D2 and 5HT2A receptors. Results: The most frequent psychiatric withdrawal symptoms after antipsychotic discontinuation were insomnia, anxiety and depression. Tremor, headache and dizziness were among the most frequently reported neurologic withdrawal symptoms. Tiotixene had the highest risk of reporting WDS (ROR 7.08; 95%CI 3.49 – 14.35) followed by pimozide (ROR 4.35; 95%CI 1.93 – 9.77), quetiapine (ROR 4.24; 95%CI 3.87 – 4.64), thioridazine (ROR 4.17; 95%CI 2.50—6.98) and ziprasidone (ROR 2.98; 95%CI 2.41—3.67). We found a poor correlation between D2/5HT2A binding affinity and the risk of reporting withdrawal syndrome (R2 = 0,094). Conclusion: Our results suggest that there might be a risk difference for WDS between antipsychotics. Tiotixene, pimozide and quetiapine were associated with a higher risk of reporting a WDS whereas this risk was lower with chlorpromazine, clozapine and fluphenazine. We could not address the issue of withdrawal psychosis, withdrawal dyskinesia, rebound psychosis or supersensitivity psychosis due to the lack of specific WHO medDRA coded terms to identify potential cases. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a serious global health problem, and chronic HBV infection significantly increases the risk of liver fibrosis, cirrhosis, and even hepatocellular carcinoma in patients. Current first-line therapeutics such as nucleos(t)ide analogues and interferons are unable to completely clear cccDNA, so the vast majority of patients need to take long-term or even lifelong medication. However, long-term virological and biochemical responses can be achieved in some patients after drug withdrawal. Successfully screening these patients with drug withdrawal advantages is difficult. Hepatitis-B-core-related antigen (HBcrAg) is a new HBV serological marker that which can reflect the level and transcription activity of cccDNA in hepatocytes. Therefore, HBcrAg has potential value in guiding patients in drug withdrawal. This review summarizes previous reports on HBcrAg and evaluates the application value of HBcrAg in safe drug discontinuation. [ABSTRACT FROM AUTHOR]

• Microglia depletion prevented cocaine-induced increases in NAc dendritic spines and CP-AMPAR. • Microglia depletion prevented cocaine-induced conditioned hyperlocomotion. • Microglia displayed reduced arborization area and control domain at late withdrawal. • Microglia are necessary for the synaptic adaptations in NAc synapses during cocaine withdrawal. During withdrawal from cocaine, calcium permeable-AMPA receptors (CP-AMPAR) progressively accumulate in nucleus accumbens (NAc) synapses, a phenomenon linked to behavioral sensitization and drug-seeking. Recently, it has been suggested that neuroimmune alterations might promote aberrant changes in synaptic plasticity, thus contributing to substance abuse-related behaviors. Here, we investigated the role of microglia in NAc neuroadaptations after withdrawal from cocaine-induced conditioned place preference (CPP). We depleted microglia using PLX5622-supplemented diet during cocaine withdrawal, and after the place preference test, we measured dendritic spine density and the presence of CP-AMPAR in the NAc shell. Microglia depletion prevented cocaine-induced changes in dendritic spines and CP-AMPAR accumulation. Furthermore, microglia depletion prevented conditioned hyperlocomotion without affecting drug-context associative memory. Microglia displayed fewer number of branches, resulting in a reduced arborization area and microglia control domain at late withdrawal. Our results suggest that microglia are necessary for the synaptic adaptations in NAc synapses during cocaine withdrawal and therefore represent a promising therapeutic target for relapse prevention. [ABSTRACT FROM AUTHOR]

Purpose of Review: With the widespread implementation of contemporary disease-modifying heart failure therapy, the rates of normalization of ejection fraction are continuously increasing. The TRED-HF trial confirmed that heart failure remission rather than complete recovery is typical in patients with dilated cardiomyopathy who respond to therapy. The present review outlines key points related to the management and knowledge gaps of this growing patient group, focusing on patients with non-ischaemic dilated cardiomyopathy. Recent Findings: There is substantial heterogeneity among patients with normalized ejection fraction. The specific etiology is likely to affect the outcome, although a multiple-hit phenotype is frequent and may not be identified without comprehensive characterization. A monogenic or polygenic genetic susceptibility is common. Ongoing pathophysiological processes may be unraveled with advanced cardiac imaging, biomarkers, multi-omics, and machine learning technologies. There are limited studies that have investigated the withdrawal of specific heart failure therapies in these patients. Diuretics may be safely withdrawn if there is no evidence of congestion, while continued therapy with at least some disease-modifying therapy is likely to be required to reduce myocardial workload and sustain remission for the vast majority. Summary: Understanding the underlying disease mechanisms of patients with normalized ejection fraction is crucial in identifying markers of myocardial relapse and guiding individualized therapy in the future. Ongoing clinical trials should inform personalized approaches to therapy. [ABSTRACT FROM AUTHOR]

Abstract Objective Guidelines suggest considering antiseizure medication (ASM) discontinuation in patients with epilepsy who become seizure‐free. Little is known about how discontinuation decisions are being made in practice. We measured the frequency of, and factors associated with, discussions and decisions surrounding ASM discontinuation. Methods We performed a multicenter retrospective cohort study at the University of Michigan (UM) and two Dutch centers: Wilhelmina Children's Hospital (WCH) and Stichting Epilepsie Instellingen Nederland (SEIN). We screened all children and adults with outpatient epilepsy visits in January 2015 and included those with at least one visit during the subsequent 2 years where they were seizure‐free for at least one year. We recorded whether charts documented (1) a discussion with the patient about possible ASM discontinuation and (2) any planned attempt to discontinue at least one ASM. We conducted multilevel logistic regressions to determine factors associated with each outcome. Results We included 1058 visits from 463 patients. Of all patients who were seizure‐free at least one year, 248/463 (53%) had documentation of any discussion and 98/463 (21%) planned to discontinue at least one ASM. Corresponding frequencies for patients who were seizure‐free at least 2 years were 184/285 (65%) and 74/285 (26%). The probability of discussing or discontinuing increased with longer duration of seizure freedom. Still, even for patients who were 10 years seizure‐free, our models predicated that in only 49% of visits was a discontinuation discussion documented, and in only 16% of visits was it decided to discontinue all ASMs. Provider‐to‐provider variation explained 18% of variation in whether patients discontinued any ASM. Significance Only approximately half of patients with prolonged seizure freedom had a documented discussion about ASM discontinuation. Discontinuation was fairly rare even among low‐risk patients. Future work should further explore barriers to and facilitators of counseling and discontinuation attempts.

Xiaoli Zhang,1,&ast; Jiao Zeng,1,&ast; Xin Gu,1 Fan Zhang,1 Yongkai Han,1 Ping Zhang,1 Qun Wang,2,3 Renjun Gu1 1Department of Neurology, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renjun Gu, Department of Neurology, The Second Affiliated Hospital of Xinxiang Medical University, Qianjin Road, No. 207, Xinxiang, Henan, People’s Republic of China, Tel +86 0373-3373704, Email gurenjun1961@163.com Qun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Nansihuanxi Road, No. 119, Beijing, People’s Republic of China, Tel +86 010-59975052, Email wangq@ccmu.edu.cnBackground and Study Aims: Antiepileptic drugs are the first choice of treatment for patients with epilepsy. However, the withdrawal of antiepileptic drugs after seizure-free remains a significant focus for the majority of patients with epilepsy and their families. In this study, we evaluated the risk factors associated with relapse after drug withdrawal in patients with seizure free for 2 years. We aimed to guide patients in seizure-free to assess the risk of drug withdrawal.Patients and Methods: Through screening, 452 patients with epilepsy were included in the study.Patients were followed up for at least 2 years or more. Analyzed their clinical data by applying the χ 2-test, Kaplan-Meier survival analysis and multivariate Cox regression analysis.Results: 423 patients completed follow-up, of which 304 cases recurred (71.9%).Related recurrence factors include age of onset, type of seizure, number of AEDs, seizure-free time before withdrawal, and electroencephalogram (EEG) results before drug withdrawal (P< 0.05). The results of correlation analysis showed that age of onset, seizure frequency, seizure type, number of AEDs, the period from AEDs treatment to a seizure-free status, EEG results before drug withdrawal, and pre-medication course, were all significantly related to the recurrence of seizures after drug reduction and withdrawal (P< 0.05). We identified a range of independent risk factors, including onset age, seizure frequency, Multiple AEDs and the period from AEDs treatment to a seizure-free status.Conclusion: The overall recurrence rate of epilepsy in our patient cohort was high, and the peak recurrence period was within one-year of drug withdrawal. Patients with partial seizures, a short seizure-free time before withdrawal, severe EEG abnormalities before drug reduction, and a long course of the disease, are prone to relapse. Patients with an older age at onset and a high frequency of attack, those taking multi-drug combination therapy, and those that take a long time to gain control, should be managed carefully to AEDs withdrawal.Keywords: epilepsy, relapse, antiepileptic drugs, drug withdrawal

This review article offers an outlook on the use of opioids as therapeutics for treating several diseases, including cancer and non-cancer pain, and focuses the analysis on the opportunity to target opioid receptors for treating opioid use disorder (OUD), drug withdrawal, and addiction. Unfortunately, as has been well established, the use of opioids presents a plethora of side effects, such as tolerance and physical and physiological dependence. Accordingly, considering the great pharmacological potential in targeting opioid receptors, the identification of opioid receptor ligands devoid of most of the adverse effects exhibited by current therapeutic agents is highly necessary. To this end, herein, we analyze some interesting molecules that could potentially be useful for treating OUD, with an in-depth analysis regarding in vivo studies and clinical trials. [ABSTRACT FROM AUTHOR]

Drug addiction is at crisis level in the United States. Nurses caring for persons affected by substance use disorder (SUD) have a resource in Mr. Ming Ho Liu's testimony on Good TV (Taiwan)--translated and summarized in this article--of his addiction experiences and successful treatment at Operation Dawn, a Christian drug rehabilitation center. Recovery from SUD is possible by God's power. In Mr. Liu's case, his recovery was accomplished without medication. [ABSTRACT FROM AUTHOR]

Although digital cognitive behavior therapy for insomnia (D-CBTI) has been shown to be a viable treatment for insomnia, lacking flexibility of response and direct practitioner-to-patient contact and comfort potentially limited its efficacy. Integrating personalized telephone sessions into D-CBTI may overcome these obstacles, potentially providing additional clinical benefit to chronic insomnia patients. We evaluate the clinical effectiveness of telephone plus D-CBTI (TD-CBTI) versus D-CBTI alone. Insomnia patients were selected consecutively from the Sleep Medicine Center, West China Hospital from March 2020 to February 2021. Insomnia was defined by Diagnostic and Statistical Manual for Mental Disorders criteria with symptoms lasting ≥3 months. Standard D-CBTI was administered through the APP "SUMIAN," which provided fully automated, interactive and standard CBTI over six weekly treatments. TD-CBTI added weekly 10–15 min personalized telephone-based sessions to D-CBTI. One hundred and seven patients received D-CBTI and 465 patients received TD-CBTI. Pre-to posttreatment differences of ISI and most sleep diary reported sleep indexes were comparable between groups. However, TD-CBTI patients showed significantly increased odds of SE based remission (167%, OR = 2.67, 95% CI 1.34–5.23), and significantly increased odds of reduction of sleep medications (352%, OR = 4.52, 95% CI 1.27–10.05). This study demonstrates that integration of personalized telephone sessions into D-CBTI treatment, provides increased clinical benefit to insomnia patients, particularly for successful discontinuation of sleep medications. • Integration of telephone sessions with the automated D-CBTI protocol provide increased clinical benefit to insomnia patients. • TD-CBTI is particularly helpful for insomnia patients who regularly use sleep medications. • TD-CBTI can provide scalable, accessible, personalized, and effective remote treatment for insomnia. [ABSTRACT FROM AUTHOR]

Withdrawal of anti‐seizure medication (ASM) is challenging, especially in patients with recurrent seizures. Only limited evidence exists regarding the success rate and recurrence risk factors after withdrawal of ASM for a second time in patients with pediatric‐onset epilepsy. In this observational study, we evaluated 104 patients with recurrent pediatric‐onset epilepsy who had ASM withdrawn for a second time. The success rate was 41.3% after the second withdrawal of ASM. The absence of a self‐limiting epilepsy syndrome, shorter seizure‐free intervals before the second withdrawal of ASM, and relapse during tapering after the initial withdrawal of ASM were negative factors significantly associated with the success of ASM withdrawal for a second time. Even after a second seizure recurrence, all patients eventually became seizure‐free after restarting their previous ASM (78.7%) or readjusting the ASM (21.3%). Our findings that 40% of patients with recurrent pediatric‐onset epilepsy could achieve long‐term seizure freedom and that all patients with a second seizure recurrence remained seizure‐free suggest that ASM may be withdrawn for a second time after carefully stratifying clinical risk. [ABSTRACT FROM AUTHOR]

Objective: Guidelines suggest considering antiseizure medication (ASM) discontinuation in patients with epilepsy who become seizure‐free. Little is known about how discontinuation decisions are being made in practice. We measured the frequency of, and factors associated with, discussions and decisions surrounding ASM discontinuation. Methods: We performed a multicenter retrospective cohort study at the University of Michigan (UM) and two Dutch centers: Wilhelmina Children's Hospital (WCH) and Stichting Epilepsie Instellingen Nederland (SEIN). We screened all children and adults with outpatient epilepsy visits in January 2015 and included those with at least one visit during the subsequent 2 years where they were seizure‐free for at least one year. We recorded whether charts documented (1) a discussion with the patient about possible ASM discontinuation and (2) any planned attempt to discontinue at least one ASM. We conducted multilevel logistic regressions to determine factors associated with each outcome. Results: We included 1058 visits from 463 patients. Of all patients who were seizure‐free at least one year, 248/463 (53%) had documentation of any discussion and 98/463 (21%) planned to discontinue at least one ASM. Corresponding frequencies for patients who were seizure‐free at least 2 years were 184/285 (65%) and 74/285 (26%). The probability of discussing or discontinuing increased with longer duration of seizure freedom. Still, even for patients who were 10 years seizure‐free, our models predicated that in only 49% of visits was a discontinuation discussion documented, and in only 16% of visits was it decided to discontinue all ASMs. Provider‐to‐provider variation explained 18% of variation in whether patients discontinued any ASM. Significance: Only approximately half of patients with prolonged seizure freedom had a documented discussion about ASM discontinuation. Discontinuation was fairly rare even among low‐risk patients. Future work should further explore barriers to and facilitators of counseling and discontinuation attempts. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the risk factors for recurrence in pediatric patients with epilepsy following normal antiseizure medication (ASM) treatment and drug withdrawal. We retrospectively analyzed 80 pediatric patients who received treatment at the Qilu Hospital of Shandong University between January 2009 and December 2019 after at least 2 years of seizure-free and normal electroencephalography (EEG) before the regular drug reduction. Patients were followed-up for at least 2 years and divided into the recurrence and nonrecurrence groups based on whether relapse occurred. Clinical information was gathered, and the risk variables for recurrence were statistically analyzed. Post 2 years of drug withdrawal, 19 patients showed relapses. The recurrence rate was 23.75%, and the mean time of recurrence was 11.09 ± 7.57 months, where 7 (36.8%) were women and 12 (63.2%) were men. In all, 41 pediatric patients were followedup until the 3rd year, of which 2 (4.9%) patients experienced a relapse. Among the remaining 39 patients without relapse, 24 were followed-up until the 4th year, and no recurrence occurred. After being monitored for >4 years, 13 patients experienced no recurrence. The differences in the history of febrile seizures, combined use of ≥2 ASMs, and EEG abnormalities after drug withdrawal between the two groups were statistically significant (p < 0.05). Multivariate binary logistic regression analysis revealed that these factors are independent risk factors for recurrence after drug withdrawal in children with epilepsy: history of febrile seizures (OR = 4.322, 95% CI: 1.262-14.804), combined ASM use (OR = 4.783, 95% CI: 1.409-16.238), and EEG abnormalities after drug withdrawal (OR = 4.688, 95% CI: 1.154-19.050). In summary, our results suggest that the probability of seizure recurrence following drug cessation may be greatly increased by a history of febrile seizures, concomitant use of ≥2 ASMs, and EEG abnormalities after drug cessation. The majority of recurrences occurred in the first 2 years following drug discontinuation, whereas the rate of recurrence was minimal thereafter. [ABSTRACT FROM AUTHOR]

Objective To explore whether the abnormality of ambulatory electroencephalogram (AEEG) prior to postoperative drug withdrawal is related to the recurrence of epilepsy after drug discontinuation in patients with glioma related epilepsy (GRE). Methods The clinical data and AEEG of 68 GRE patients who underwent surgical treatment in our hospital with long-term follow-up from January 2014 to June 2020 were collected and retrospectively analyzed. The patients were subsequently divided into seizure group (seizure recurrence after withdrawal of antiepileptic drugs, n=31) and control group (no seizure after withdrawal, n=37). The differences in the occurrence rate and number of spike waves and paroxysmal slow wave events (PSWEs) were analyzed and compared between the 2 groups. The factors affecting the prognosis of epilepsy were discussed through analyzing the data of 47 patients who presented epileptic discharge on AEEG before drug discontinuation. Results ① In the seizure group, 29 patients (93.5%) had epileptic discharges on AEEG before drug withdrawal and 11 (35.5%) showed PSWEs, while there were only 18 (48.6%) and 5 (13.5%) patients correspondingly in the control group, indicating a significant difference in the occurrence rate between the 2 groups (P < 0.05). ② The number of spike and slow waves was significantly larger in the seizure group than the control group. In the seizure group, medium to large number of spike waves (25/29, 86.2%) as well as large number of paroxysmal slow waves (8/11, 72.7%) were predominant, whereas the control group mainly had small amount of spike waves (14/18, 77.8%) and small to medium amount of paroxysmal slow waves (4/5, 80.0%). ③ With epileptic discharge of AEEG, the extent of tumor removal and involvement of cortex were related to the epilepsy prognosis (P < 0.05). Conclusion When the tumor is sub-radical resected or the tumor involves the cortex, and the pre-discontinuation AEEG shows moderate to large number of epileptic discharge and PSWEs, it is necessary to consider suspending drug withdrawal and extending the interval between seizures to reduce the risk of seizure recurrence.

Background: Consultation-liaison psychiatry (C-LP) is an interface between physical and psychological health where the psychiatrists become a part of the medical team for a holistic approach in the treatment of the patient. Aims: Our study aimed to see the pattern and utility of C-LP services among inpatient referrals to the department of psychiatry. Settings and Design: This observational descriptive study recorded inpatient referrals to the department of psychiatry of a tertiary care hospital for 2 months. Subjects and Methods: The Mini-International Neuropsychiatric Interview (M. I. N. I.) was administered for identifying the comorbid psychiatric diagnoses. Results: Most of the received inpatient referrals were for male patients (73.7%) in the age group of 30–60 years (58%). Overall, the referral rate was significantly higher from the emergency department and intensive care units (ICU) (50%), followed by specialty (medicine and surgery) wards (20%) and super specialty (cardiology, gastroenterology, and oncology) wards (16%). Altered sensorium and restlessness were the most common reasons for referral (42%), followed by alcohol/drug withdrawal (21.6%), somatic complaints (7.3%), sadness of mood, disturbed sleep, and deliberate self-harm (6% each). Substance use disorders, including alcohol and opioid (32%), delirium (25%), and depression (19%), were among the most common psychiatric diagnoses seen in the referred patients. Conclusions: The pattern observed indicates that most inpatient referrals for psychological evaluation are received for altered sensorium from emergency and ICU than wards. The utility of C-LP helps to understand the reciprocal interdependence between the medical illness and the psychiatric comorbidity. [ABSTRACT FROM AUTHOR]

Non-human primate (NHP) renal transplantation models are widely used vivo models for researching new immunosuppressive therapies including allograft tolerance strategies. To enroll animals into a tolerance study, an immunosuppressive regimen that efficiently establishes stable renal function in NHPs is needed. Here, we assessed the effect of triple therapy comprising 2.0 mg/kg tacrolimus, mycophenolate mofetil and a steroid and its success rate for achieving stable renal function. In addition, to predict the pathophysiological consequences of withdrawing immunosuppressants, an indispensable process after induction of tolerance, we also assessed changes in the stable renal state maintained by triple therapy after drug withdrawal. Six cynomolgus monkeys were used. The median survival time was >176 days over the dosing period and 45 days after drug withdrawal. The triple therapy successfully induced stable graft function without calcineurin inhibitor nephrotoxicity in three of six recipients, although adopting trough-dependent tacrolimus dose adjustment rather than a preset dose regimen could improve on the present strategy. Further, drug withdrawal led to deterioration of renal function, de novo donor specific antibody production and increased the memory/naïve T cell ratio within two weeks post drug withdrawal. We expect that these findings contribute to establish one of the choices for animal model for evaluating future tolerance therapy for renal transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Strengthening self-efficacy is an alternative to prevent drug withdrawal in patients with pulmonary TB. Autogenic relaxation, movement and affirmation (RIMA) therapy can help strengthen self-efficacy in patients with pulmonary TB so as to prevent drug withdrawal. The general objective of this study was to determine the role of RIMA therapy in strengthening the self-efficacy of pulmonary TB patients. Methods: The design of this research is a quasi-experimental using pre-test and post-test with control group design. The Respondents were patients with pulmonary TB in the work area of the Puskesmas Pakis, Malang Regency, a total of 60 people were determined using purposive sampling. RIMA therapy was carried out for 2 weeks, and data collection was carried out using a questionnaire. Data analysis used Wilcoxon Signed Rank test and Mann-Whitney test with α = 0.05%. Results: The results of this study indicate that there is an effect of RIMA therapy on self-efficacy in the experimental group, which is indicated by a p value = 0.000 (< 0.05). In addition, there is a significant difference in self-efficacy between the experimental group and the comparison group, which is indicated by the p value = 0.000 (< 0.05). Conclusion: RIMA therapy influences increasing self-efficacy of pulmonary TB patients. Therefore, it is recommended that patients with pulmonary TB carry out RIMA therapy independently at home to support their treatment.

Purpose: To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death. Methods: This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of − 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal. Results: The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI − 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population. Conclusions: Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering. [ABSTRACT FROM AUTHOR]

Objective: The 1991 Medical Research Council (MRC) Study compared seizure relapse for seizure‐free patients randomized to withdraw vs continue of antiseizure medications (ASMs). We re‐analyzed this trial to account for crossover between arms using contamination‐adjusted intention to treat (CA ITT) methods, to explore dose‐response curves, and to validate predictions against external data. ITT assesses the effect of being randomized to withdraw, as‐treated analysis assesses the confounded effect of withdrawing, but CA ITT assesses the unconfounded effect of actually withdrawing. Methods: CA ITT involves two stages. First, we used randomized arm to predict whether patients withdrew their ASM (logistic) or total daily ASM dose (linear). Second, we used those values to predict seizure occurrence (logistic). Results: The trial randomized 503 patients to withdraw and 501 patients to continue ASMs. We found that 316 of 376 patients (88%) who were randomized to withdraw decreased their dose at every pre‐seizure visit, compared with 35 of 424 (8%) who were randomized to continue (p <.01). Adjusted odds ratios of a 2‐year seizure for those who withdrew vs those who did not was 1.3 (95% confidence interval [CI] 0.9–1.9) in the as‐treated analysis, 2.5 (95% CI 1.9–3.4) comparing those randomized to withdraw vs continue for ITT, and 3.1 (95% CI 2.1–4.5) for CA ITT. Probabilities (withdrawal vs continue) were 28% vs 24% (as‐treated), 40% vs 22% (ITT), and 43% vs 21% (CA ITT). Differences between ITT and CA ITT were greater when varying the predictor (reaching zero ASMs) or outcome (1‐year seizures). As‐treated dose‐response curves demonstrated little to no effects, but larger effects in CA ITT analysis. MRC data overpredicted risk in Lossius data, with moderate discrimination (areas under the curve ~0.70). Significance: CA ITT results (the effect of actually withdrawing ASMs on seizures) were slightly greater than ITT effects (the effect of recommend withdrawing ASMs on seizures). How these findings affect clinical practice must be individualized. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to identify the post-marketing withdrawal of medicines due to their adverse drug reactions (ADRs)-related abuse effects and to examine the types of evidence, mechanisms and patterns for the withdrawal decisions after their approval across different geographical regions. Methods By searching through different databases that focused on withdrawn drugs due to their ADRs-related abuse effects between 1930 and 2021 that could provide findings of evidence used in making withdrawal decisions based on the tools of the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria alongside sources derived from authorities based on their withdrawal. The outcomes were categorized, and the average time between the launch date of exposure and withdrawal was calculated and stratified. Key findings A total of 33 abused withdrawn drugs. The withdrawals occurred between 1961 and 2007. Psychostimulant drugs accounted for most of the abuse withdrawals (42.4%). Most of the withdrawals occurred between 1981 and 1990 (n = 18, 54.5%). Most withdrawn drugs were in Europe (41, 46.6%) with a minimum withdrawal period of 5 years and an average time of withdrawal of 28.8 years. Conclusions Psychostimulant drugs presented the most abuse withdrawals based on the evidence of case–control studies, and the most withdrawals were in Europe. The duration of withdrawn drugs was different from region to region in different continents. More intensive research is required to further reduce the time duration between drug marketing and withdrawal, which will help improve decision-making processes with favourable benefit-risk ratio outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Numerous cases with ocular toxicity secondary to tamoxifen have been reported, and became more apparent with keratopathy, cataract, optic neuritis, macular holes, crystalline retinopathy with or without cystoid macular edema (CME). Withdrawing tamoxifen with the approval of the oncologist is the major treatment for cases with tamoxifen-induced retinopathy. Case presentation We herein reported a patient with a two-year history of painless and reduced visual acuity in both eyes who received tamoxifen therapy for 6 years. Tamoxifen-induced rentinopathy with CME showed significant development even though the patient has already discontinued tamoxifen treatment for 6 months. Anatomic improvements after intravitreal ranibizumab injection in both eyes were significant but were temporary. Surprisingly, CME in both eyes has been resolved spontaneously after 10 months in the penultimate visit without any therapy. Conclusion Intravitreal ranibizumab injection temporarily improved the anatomy of the eyes in a case with tamoxifen-induced CME, and only tamoxifen withdrawal can bring a sustained effect.

Background: Few studies have focused on the treatment of tuberculosis (TB) during pregnancy. This study aimed to evaluate the risk of adverse events, particularly liver toxicity, in pregnant women during treatment for active TB. Methods: We conducted a retrospective study on pregnant and age-matched non-pregnant women receiving treatment for active TB at four hospitals in Western Sweden between 1992 and 2017. Results: A total of 135 women were included, 40 pregnant and 95 non-pregnant. The frequency of severe hepatotoxicity was 40% in pregnant women and 6% among non-pregnant women (p < 0.001) (odds ratio 9.9; 95% confidence interval 3.5–28.0). Temporary drug withdrawal due to elevated transaminase levels was more frequent for pregnant than non-pregnant women (40% vs 9.5%; p < 0.001) (odds ratio 6.4; 95% confidence interval 2.5–16.2). There was one fatal case of hepatotoxicity in a pregnant woman. Conclusion: Severe hepatotoxicity was significantly more frequent in pregnant women compared to non-pregnant women. Careful monitoring of liver transaminases while receiving TB treatment during pregnancy is mandatory, as well as ensuring adequate measures with adjustment of drug regimen and temporary drug withdrawals when a rise in liver enzymes is noted.

Advanced heart failure (HF) is a complex entity with a clinical course difficult to predict. However, most patients have a poor prognosis. This document addresses the modification of cardiovascular drugs in patients with advanced HF that are not candidates to heart transplantation or ventricular assist device and are in need of palliative care. The adjustment of cardiovascular drugs is frequently needed in these patients. The shift in emphasis from life-prolonging to symptomatic treatments should be a progressive one. We establish a series of recommendations with the aim of adjusting drugs in these patients, in order to adapt treatment to the needs and wishes of each patient. This is frequently a difficult process for patients and professionals, as drug discontinuing needs to balance treatment benefit with the psychological adaption to having a terminal illness. We encourage the use of validated assessment tools to assess prognosis and to use this information to take clinical decisions regarding drug withdrawal and therapeutic changes. The golden rule is to stop drugs that are harmful or non-essential and to continue the ones that provide symptomatic improvement.

Intrathecal morphine is associated with the complication of catheter tip granuloma which causes symptoms of decreased pain control, increased required dose, and neurological deficit. Catheter tip granulomas from intrathecal baclofen are thought to never occur because of the mechanism by which intrathecal morphine causes granulomas. We present a case of an intrathecal baclofen induced scarring of a catheter tip with clinical characteristics similar to some symptoms of granuloma. A 66-year-old woman with multiple sclerosis induced spasticity was partially controlled with intrathecal baclofen delivery at an extremely high dose of 1638 micrograms per day. She presented in the hospital with symptoms of withdrawal from intrathecal baclofen and required an emergency revision of her baclofen pump. Replacement of the catheter demonstrated complete occlusion of the catheter tip by scar tissue. Following surgery, her spasticity was well-controlled at the much lower dose of 200 micrograms per day. Intrathecal baclofen delivery can cause catheter tip scarring which causes some symptoms similar to catheter tip granuloma. Early recognition of these signs of catheter tip occlusion could help prevent progression to withdrawal., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Inova Fairfax Hospital IRB issued approval N/A. Retrospective, deidentified case report with waived consent. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Leiphart et al.)

Gilteritinib is a tyrosine kinase inhibitor (TKI) that treats acute myeloid leukemia (AML) by inhibiting FMS-like tyrosine kinase 3 (FLT3). This is a report on hypopituitarism induced by gilteritinib and its resolution following withdrawal. A 54-year-old woman was treated with gilteritinib for AML. She subsequently developed general fatigue. Blood tests showed low levels of anterior pituitary hormone. After 10 months of gilteritinib withdrawal, the levels of anterior pituitary hormones returned to normal values. When nonspecific symptoms such as fatigue in patients treated with gilteritinib are coupled with electrolyte abnormalities, a close checkup for hypopituitarism is recommended., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hori et al.)

Little is known about the impact of dose, duration, and timing of prenatal prescription opioid exposure on the risk of neonatal opioid withdrawal syndrome (NOWS). Using a cohort of 18,869 prepregnancy chronic opioid users nested within the 2000–2014 Medicaid Analytic eXtract, we assessed average opioid dosage within biweekly gestational age intervals, created group-based trajectory models, and evaluated the association between trajectory groups and NOWS risk. Women were grouped into 6 distinct opioid use trajectories which, based on observed patterns, were categorized as 1) continuous very low-dose use, 2) continuous low-dose use, 3) initial moderate-dose use with a gradual decrease to very low-dose/no use, 4) initial high-dose use with a gradual decrease to very low-dose use, 5) continuous moderate-dose use, and 6) continuous high-dose use. Absolute risk of NOWS per 1,000 infants was 7.7 for group 1 (reference group), 28.8 for group 2 (relative risk (RR) = 3.7, 95% confidence interval (CI): 2.8, 5.0), 16.5 for group 3 (RR = 2.1, 95% CI: 1.5, 3.1), 64.9 for group 4 (RR = 8.4, 95% CI: 5.6, 12.6), 77.3 for group 5 (RR = 10.0, 95% CI: 7.5, 13.5), and 172.4 for group 6 (RR = 22.4, 95% CI: 16.1, 31.2). Trajectory models—which capture information on dose, duration, and timing of exposure—are useful for gaining insight into clinically relevant groupings to evaluate the risk of prenatal opioid exposure. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to analyze the characteristics of brain function and microstructure linked to epilepsy relapse after drug withdrawal in patients with focal epilepsy. Methods: Resting-state functional magnetic resonance imaging and high-resolution T1-weighted images were acquired within 1 month prior to drug withdrawal from 15 patients who did not have epilepsy relapse (PER − group) and 16 patients who subsequently had epilepsy relapse (PER + group). Additionally, 23 healthy participants undergoing the same scanning protocol were included as controls. Fractional amplitude of low-frequency fluctuation (fALFF) and gray matter density (GMD) were compared among groups. Subgroup and correlation analyses were also performed. Results: There were no significant differences in fALFF between patient groups, but the PER + group showed lower GMD in the bilateral calcarine, left precuneus, and right superior temporal gyrus than the PER − group (Gaussian random field correction, voxel-level P < 0.001 and cluster-level P < 0.05). Both increased seizure number and polytherapy were associated with lower GMD; also, patients using other antiseizure medications showed lower GMD than those using only levetiracetam (Gaussian random field correction, voxel-level P < 0.001, and cluster-level P < 0.05). The active period and disease duration showed both positive and negative correlations with GMD, while the seizure-free period mainly showed positive correlations with GMD (uncorrected, P < 0.001). Conclusion: Gray matter microstructure, but not local functional activity, showed distinct characteristics between patients with and without epilepsy relapse and may serve as a potential biomarker for predicting seizure recurrence upon drug withdrawal. [ABSTRACT FROM AUTHOR]

Evidence-based guidelines have been developed outlining the concomitant use of anti-tumor necrosis factor alpha (anti-TNF) agents and immunomodulators including azathioprine (AZA) and methotrexate (MTX) in both adult and pediatric populations. However, there exists a paucity of data guiding evidence-based strategies for their withdrawal in pediatric patients in sustained remission. This narrative review focuses on the available pediatric evidence on this question in the context of what is known from the larger body of evidence available from adult studies. The objective is to provide clarity and practical guidance around who, what, when, and how to step down pediatric patients with inflammatory bowel disease (IBD) from combination immunotherapy. Outcomes following withdrawal of either of the two most commonly used anti-TNF therapies [infliximab (IFX) or adalimumab (ADA)], or immunomodulator therapies, from a combination regimen are examined. Essentially, a judicious approach must be taken to identify a significant minority of patients who would benefit from treatment rationalization. We conclude that step-down to anti-TNF (rather than immunomodulator) monotherapy after at least 6 months of sustained clinical remission is a viable option for a select group of pediatric patients. This group includes those with good indicators of mucosal healing, low or undetectable anti-TNF trough levels, lack of predictors for severe disease, and no prior escalation of anti-TNF therapy. Transmural healing and specific human leukocyte antigen (HLA) typing are some of the emerging targets and tools that may help facilitate improved outcomes in this process. We also propose a simplified evidence-based schema that may assist in this decision-making process. Further pediatric clinical studies are required to develop the evidence base for decision-making in this area.

Timothy H Harries,1 Gill Gilworth,1 Christopher J Corrigan,2 Patrick B Murphy,3 Nicholas Hart,3 Mike Thomas,4 Patrick T White1 1Department of Public Health and Primary Care, School of Population Health and Environmental Sciences, King’s College London, London, UK; 2Department of Asthma Allergy and Respiratory Science, King’s College London, London, UK; 3Lane Fox Respiratory Unit, Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London, London, UK; 4Primary Care and Population Medicine, University of Southampton, Southampton, UKCorrespondence: Timothy H HarriesDepartment of Public Health and Primary Care, School of Population Health and Environmental Sciences, King’s College London 3rd Floor Addison House, Guys Campus, London SE1 1UL, UKTel +44 20 7836 5454Email timothy.harries@kcl.ac.ukAbstract: COPD patients prescribed inhaled corticosteroids (ICS) outside guidelines should be targeted for ICS withdrawal. Within a primary care population of 209,618 we used a combination of digital search algorithm, individual record review, and clinical review to identify COPD patients suitable for a trial of ICS withdrawal. At most, 39% of COPD patients with mild or moderate airflow limitation prescribed ICS were suitable for withdrawal according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Recurrent exacerbations and reversible airway obstruction were the main reasons for patients’ unsuitability for withdrawal. Identifying COPD patients in whom ICS withdrawal should be considered presents a challenge to primary care clinicians.Keywords: pulmonary disease, chronic obstructive, inhaled corticosteroids, drug withdrawal, mild airflow limitation, moderate airflow limitation

Abstract Introduction Although non-melanoma skin cancers (NMSCs) are associated with a very low mortality risk, they have been reported to have a major impact on patients’ health-related quality of life (HRQoL). Vismodegib is a therapy for patients who are affected by locally advanced basal cell carcinoma (BCC) or metastatic BCC who are ineligible for surgery and/or radiotherapy. The aim of the present clinical study was to assess the long-term efficacy of vismodegib after its withdrawal by evaluating the recurrence rate of advanced BCC, assessing also patients’ HRQoL after 3 and 6 months from drug withdrawal. Methods A retrospective study was performed to analyze patients with advanced and/or multiple BCCs that had been treated with vismodegib (150 mg daily) at the Non-Melanoma Skin Cancer Unit of the University of Naples Federico II (Italy) and had obtained a complete regression in 6 months. At the end of the 6-month treatment cycle, patients that reported total remission of the skin tumor were visited monthly in order to assess their therapeutic response. Moreover, to assess the specific impact of vismodegib on HRQoL, DLQI was administered before vismodegib treatment (baseline), at the end of the therapy cycle (6 months), as well as after 3 and 6 months from vismodegib discontinuation. Results Thirty-five patients (27 male, 8 female), with a complete regression of their advanced BCC after vismodegib treatment, were included in the study. The duration of treatment for all patients was 6 months as set by study inclusion criteria. A BCC recurrence rate of 31% (11/35) was reported after a 6-month follow-up. The average reported Dermatology Life Quality Index (DLQI) score increased from a value of 0 at the end of the 6-month vismodegib treatment to a mean value of 2.4 after 3 months from drug withdrawal and 3.6 after 6 months from treatment discontinuation. Conclusion The results of this exploratory analysis of vismodegib withdrawal are consistent with a substantial link between treatment response and patients’ HRQoL. Furthermore, 11 out of 35 (31%) patients that reported a complete remission of the disease after 6 months of vismodegib treatment reported BCC recurrence. These data highlight the importance of continuous follow-up and perhaps different regimens of treatment, such as an alternate dose regimen to maintain disease control and reduce the adverse events as previously described in the literature.

Background: The adverse effects of long-term maternal exposure of labetalol on neonates have been recognized clinically. But there are few systematic studies on their clinical demonstrations and potential mechanisms.Methods: A death case of an infant with long-term maternal labetalol exposure was reported and compared with two case reports from the literature. A systematic literature review was carried out followed by a retrospective analysis on neonatal labetalol withdrawal effects.Results: It was discovered that labetalol withdrawal effects initially cause various degrees of hypotension, hypoglycemia, and bradycardia among exposed neonates. Some life-threatening cases can also occur within 1 week after birth. Long-term maternal exposure of labetalol, preterm infants with birth asphyxia, acidosis, hypoalbuminemia, and cardiac defects are their primary features. Possible mechanisms were concluded as labetalol-induced effects on the vascular and sympathetic nervous system as well as tissue oxygen extraction.Conclusions: Neonatal labetalol withdrawal effects include early-onset and late-onset demonstrations, the latter can be life-threatening. A possible mechanism is multiple factors induced imbalance of sympathetic homeostasis increases neonatal vulnerability to common stresses. Long-term exposed preterm infants complicated with asphyxia, acidosis, hypoalbuminemia and cardiac defects, should be provided with intense care during the first week after birth. Further work is necessary to enrich this hypothesis. [ABSTRACT FROM AUTHOR]

Background: Numerous cases with ocular toxicity secondary to tamoxifen have been reported, and became more apparent with keratopathy, cataract, optic neuritis, macular holes, crystalline retinopathy with or without cystoid macular edema (CME). Withdrawing tamoxifen with the approval of the oncologist is the major treatment for cases with tamoxifen-induced retinopathy.Case Presentation: We herein reported a patient with a two-year history of painless and reduced visual acuity in both eyes who received tamoxifen therapy for 6 years. Tamoxifen-induced rentinopathy with CME showed significant development even though the patient has already discontinued tamoxifen treatment for 6 months. Anatomic improvements after intravitreal ranibizumab injection in both eyes were significant but were temporary. Surprisingly, CME in both eyes has been resolved spontaneously after 10 months in the penultimate visit without any therapy.Conclusion: Intravitreal ranibizumab injection temporarily improved the anatomy of the eyes in a case with tamoxifen-induced CME, and only tamoxifen withdrawal can bring a sustained effect. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to evaluate the risk factors on seizure recurrence after antiepileptic drug withdrawal in children with idiopathic epilepsy. Material and Methods: The treatment is withdrawn within 4-6 months in all patients who had normal magnetic resonance imaging and electroencephalogram results on at least 24 months of antiepileptic drug treatment. After drug withdrawal 72 patients had seizure recurrence in whom labeled as relapse group. Eighty-two patients had no seizure recurrence are labeled as remission group. Results: The age of diagnosis with epilepsy and remission time were observed as risk factors on seizure recurrence. It is determined that after drug withdrawal seizure recurrence is occurred within the first 2 years of follow-up in 95,9 % of the relapse group's patients. Conclusion: In patients, who had more than 3 months of seizure remission time have more seizure recurrence risk after drug withdrawal. Furthermore, it is observed that in patients older than 12 years old the risk of recurrence is higher. Besides, we suggest 2 years of close follow-up in all patients whose antiepileptic drug is withdrawn. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to evaluate the self-reported impact of mandatory confinement occurring in the first wave of the SARS-CoV-2 pandemic in Portuguese patients with rheumatoid arthritis (RA), as a means to improve care during this and in future pandemics. Material and methods. The web-based survey COVIDRA was developed to assess 5 domains including RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through email and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Results. We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%) with a mean age of 58 years. The majority had disease lasting >10 years and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23.7%). Over 40% experienced symptom worsening during confinement, almost half considered moderate or severe. Mobility restriction and increased stress, anxiety or depression were responsible for this worsening. Only 2.5% reduced or withheld their immunosuppressive medication due to fear of becoming infected with SARSCoV-2. After confinement, 16.2% of those previously employed were in a lay-off regime and 3% lost their jobs. Most employed RA patients practiced telework during confinement. The majority of patients decreased or did not practice any physical exercise (80.5%). Symptoms of anxiety and depression developed or worsened in 67.3% and 51.9% respectively, approximately one third were considered moderate or severe. Conclusions. Portuguese RA patients experienced significant symptom worsening, anxiety and depression during the first wave confinement. Only a minority changed their immunosuppressive treatment for fear of SARS-CoV-2 infection. Published literature on these matters shows results very similar to ours. [ABSTRACT FROM AUTHOR]

Background: Many Juvenile Idiopathic Arthritis (JIA) patients reach inactivity while medicated, but there are no guidelines to determine the moment or method for discontinuing medications. We present the flare rates and remission and possible influencing factors after therapy discontinuation in children with JIA. Methods: Data was collected from charts of JIA patients in remission on medication, who had their drugs withdrawn. Results: Seventy patients fulfilled inclusion criteria and were included for analysis. The mean time of inactive disease on medication until tapering or withdrawal was 15.6±6.7 months; 45 (64.3%) patients remained in remission and 25 (35.7%) flared. There was no diffe rence between groups regarding sex, age, JIA subtype, disease duration, time in remission on medication and scheme of therapy withdrawal. Patients who fulfilled Wallace criteria for remission off medication had lower flare rates than those who did not achieve 12 months of remission after the medication withdrawal (p<0.0001). Patients who used biologic disease-modifying anti-rheumatic drugs (DMARDs) plus synthetic DMARDs appeared to flare more (77.8% vs 29.5% respectively, p=0.008) and presented shorter periods of inactivity off medication (15.3±24.7 vs 32.3 ± 31.7 months respectively, p=0.049) compared to those who used only synthetic DMARDs. Conclusion: It is possible that gradual drug tapering is not necessary for JIA patients, but caution must be exerted in those patients using biologic DMARDs, weighing carefully the decision to withdraw medication, due to their higher flare rates and shorter times of inactive disease after the medication withdrawal. [ABSTRACT FROM AUTHOR]

Background: Medication overuse headache (MOH) is one of the highly disabling headache disorder and affects about 1% of the population of the world. It is associated with the development of headache for 15 days or more, with consumption of acute symptomatic medications for 10-15 days (depending on the class of drug, like, simple analgesics, triptans, and opioids) in a month, used for relief of headache for three or more months, in a known patient of primary headache disorder.Objective: The aim of this study was to review the topic of MOH and present the details of this disorder with an emphasis on recent updates in the field of pathophysiology and treatment.Material and Methods: Literature search was performed in the PubMed/MEDLINE and Cochrane database with appropriate keywords and relevant full-text articles were reviewed for writing this article.Results: Over the years, the concept of MOH has evolved, although the exact pathophysiology is still being explored. In a susceptible individual interplay of genetics, change in pain pathways, changes in areas of the brain associated with the perception of pain, and changes in the neurotransmitters have been implicated. It has to be differentiated from other secondary chronic daily headache disorders, by a careful history, targeted examination, details of intake of medications. Treatment predominantly involves patient education, removal of the offending agent, and initiation of prophylactic medications for primary headache disorder in the outpatient or inpatient services.Conclusions: MOH is a secondary headache disorder, which should be considered in any chronic headache patient. There are various pathophysiological mechanisms attributed to its development. Management includes educating the patients about the disorder, detoxification, and prophylactic therapy. [ABSTRACT FROM AUTHOR]

Background: Inhaled corticosteroid (ICS) therapy has been demonstrated to reduce the risk of COPD exacerbations. It should only be prescribed to COPD patients who are not adequately controlled by dual long-acting bronchodilator therapy and who have ≥2 exacerbations per year and a blood eosinophil count ≥300cells/µL. ICS therapy is widely prescribed outside guidelines to COPD patients, making ICS withdrawal an important consideration. This systematic review aims to provide an up-to-date analysis of the effect of ICS withdrawal on exacerbation frequency, change in lung function (FEV 1 ) and to determine the proportion of COPD patients who resume ICS therapy following withdrawal., Methods: Randomised controlled trials (RCTs) and observational studies which compared ICS withdrawal with ICS continuation treatment were included. Cochrane Central, Web of Science, CINHAL, Embase and OVID Medline were searched. Risk of bias was assessed using the Cochrane RoB2 tool and the Newcastle-Ottawa Scale. Quality assessment of RCTs was conducted using GRADE. Meta-analysis of post-hoc analyses of RCTs of ICS withdrawal, stratified by blood eosinophil count (BEC), was undertaken., Results: Ten RCTs (6642 patients randomised) and 6 observational studies (160,029 patients) were included in the results. When ICS was withdrawn and long-acting bronchodilator therapy was maintained, there was no consistent difference in exacerbation frequency or lung function change between the ICS withdrawal and continuation trial arms. The evidence for these effects was of moderate quality. There was insufficient evidence to draw a firm conclusion on the proportion of patients who resumed ICS therapy following withdrawal (estimated range 12-93% of the participants)., Discussion: Withdrawal of ICS therapy from patients with COPD is safe and feasible but should be accompanied by maintenance of bronchodilation therapy for optimal outcomes., Competing Interests: THH and PW were co-authors of the study Harries TH, Gilworth G, Corrigan CJ, et al. Withdrawal of inhaled corticosteroids from patients with COPD with mild or moderate airflow limitation in primary care: a feasibility randomised trial. BMJ Open Respir Res. 2022;9(1):e001311. doi:10.1136/bmjresp-2022-001311. They have recused themselves from any involvement in the assessment of the risk of bias in this study. The authors report no other conflicts of interest in this work., (© 2024 Georgiou et al.)