Withdrawal Of Medication Research Articles

Management of chronic myelogenous leukemia with COVID-19 and hepatitis B.

The application of immunosuppressive agents and targeted drugs has opened a novel approach for the treatment of hematological tumors, and the application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia is one of the landmark breakthroughs that has considerably improved the prognosis of CML patients. However, with the extensive use of TKI, the co-infection of CML patients has become increasingly apparent, especially regarding infectious diseases such as hepatitis B and COVID-19. The underlying mechanism may be related to the inhibition of the immune function by TKI. Poor management, including disease progression due to the infectious disease or TKI dose reduction or discontinuation, may lead to adverse clinical outcomes and can even be life-threatening. Therefore, this review principally provides an overview of the pathogenesis and standardized management principles of CML patients with comorbid COVID-19 or hepatitis B in order to improve clinicians' awareness of the risks so as to more effectively diagnose and treat CML and improve the survival rate and quality of life of patients. In the past two decades, owing to the advent of imatinib, chronic myeloid leukemia (CML) has transformed into a chronic controllable disease, and even treatment-free remission can be anticipated. Earlier studies have indicated that tyrosine kinase inhibitor (TKI) exerts a peculiar inhibitory effect on the body's immune function. Therefore, with the widespread application of TKI, more and more attention has been paid to the comorbidity of infectious diseases in CML patients, especially in patients with progressive disease or non-remission. Despite some studies revealing that the proportion and severity of SARS-CoV-2 infection in CML patients receiving TKI treatment are lower than in patients with other hematological malignancies, CML patients with stable disease are still recommended to be vaccinated against SARS-CoV-2, while TKI may or may not be discontinued. Meanwhile, the management of CML patients during the epidemic of coronavirus disease 2019 (COVID-19) still necessitates further discussion. This article also provides an overview of TKI-related hepatitis B reactivation. If not managed, patients may face adverse consequences such as hepatitis B reactivation-related hepatitis, liver failure, and progression of CML after forced withdrawal of medication. Therefore, this review aimed to comprehensively describe the management of CML patients with comorbid COVID-19, the pathogenesis of hepatitis B reactivation, the indicated population for prophylactic antiviral therapy, the time of antiviral drug discontinuation, and drug selection.

The effects of P2Y12 adenosine receptors' inhibitors on central and peripheral chemoreflexes.

Introduction: The most common side effect of ticagrelor is dyspnea, which leads to premature withdrawal of this life-saving medication in 6.5% of patients. Increased chemoreceptors' sensitivity was suggested as a possible pathophysiological explanation of this phenomenon; however, the link between oversensitization of peripheral and/or central chemosensory areas and ticagrelor intake has not been conclusively proved. Methods: We measured peripheral chemoreceptors' sensitivity using hypoxic ventilatory response (HVR), central chemoreceptors' sensitivity using hypercapnic hyperoxic ventilatory response (HCVR), and dyspnea severity before and 4 ± 1 weeks following ticagrelor initiation in 11 subjects with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI). The same tests were performed in 11 age-, sex-, and BMI-matched patients treated with clopidogrel. The study is registered at ClinicalTrials.com at NCT05080478. Results: Ticagrelor significantly increased both HVR (0.52 ± 0.46 vs. 0.84 ± 0.69 L min-1%-1; p < 0.01) and HCVR (1.05 ± 0.64 vs. 1.75 ± 1.04Lmin-1mmHg-1; p < 0.01). The absolute change in HVR correlated with the change in HCVR. Clopidogrel administration did not significantly influence HVR (0.63 ± 0.32 vs. 0.58 ± 0.33 L min-1%-1; p = 0.53) and HCVR (1.22 ± 0.67 vs. 1.2 ± 0.64Lmin-1mmHg-1; p = 0.79). Drug-related dyspnea was reported by three subjects in the ticagrelor group and by none in the clopidogrel group. These patients were characterized by either high baseline HVR and HCVR or excessive increase in HVR following ticagrelor initiation. Discussion: Ticagrelor, contrary to clopidogrel, sensitizes both peripheral and central facets of chemodetection. Two potential mechanisms of ticagrelor-induced dyspnea have been identified: 1) high baseline HVR and HCVR or 2) excessive increase in HVR or HVR and HCVR. Whether other patterns of changes in chemosensitivities play a role in the pathogenesis of this phenomenon needs to be further investigated.

Opioid, sedative, preadmission medication and iatrogenic withdrawal risk in UK adult critically ill patients: a point prevalence study

BackgroundIatrogenic withdrawal syndrome, after exposure medication known to cause withdrawal is recognised, yet under described in adult intensive care.AimTo investigate, opioid, sedation, and preadmission medication practice in critically ill adults with focus on aspects associated with iatrogenic withdrawal syndrome.MethodOne-day point prevalence study in UK intensive care units (ICUs). We collected ICU admission medication and/or substances with withdrawal potential, sedation policy, opioid and sedative use, dose, and duration.ResultsThirty-seven from 39 participating ICUs contributed data from 386 patients. The prevalence rate for parenteral opioid and sedative medication was 56.1% (212 patients). Twenty-three ICUs (59%) had no sedation/analgesia policy, and no ICUs screened for iatrogenic withdrawal. Patient admission medications with withdrawal-potential included antidepressants or antipsychotics (43, 20.3%) and nicotine (41, 19.3%). Of 212 patients, 202 (95.3%) received opioids, 163 (76.9%) sedatives and 153 (72.2%) both. Two hundred and two (95.3%) patients received opioids: 167 (82.7%) by continuous infusions and 90 (44.6%) patients for longer than 96-h. One hundred and sixty-three (76.9%) patients received sedatives: 157 (77.7%) by continuous infusions and 74 (45.4%) patients for longer than 96-h.ConclusionOpioid sedative and admission medication with iatrogenic withdrawal syndrome potential prevalence rates were high, and a high proportion of ICUs had no sedative/analgesic policies. Nearly half of patients received continuous opioids and sedatives for longer than 96-h placing them at high risk of iatrogenic withdrawal. No participating unit reported using a validated tool for iatrogenic withdrawal assessment.

Safety and efficacy of rapid withdrawal of anti-seizure medication during long-term video-EEG monitoring.

Anti-seizure medications (ASMs) are often withdrawn during long-term video-EEG monitoring (LTM) to allow pre-surgical evaluation. Herein, we evaluated the safety and efficacy of ultra-rapid withdrawal (URW) and rapid withdrawal (RW) of ASMs in an epilepsy monitoring unit (EMU). This retrospective study examined all consecutive patients admitted to our EMU between May 2021 and October 2022. Patients were classified into the URW and RW groups according to the way ASMs were withdrawn. We compared the efficacy and safety of the procedures used in the groups in terms of duration of LTM, latency to the first seizure, and incidence of focal to bilateral tonic-clonic seizures (FBTCS), seizure clusters (SC), and status epilepticus (SE). Overall, 110 patients (38 women) were included. The mean age of patients at the time of LTM was 29 years. All medications were stopped on admission for monitoring in the URW group (n = 75), while in the RW group (n = 35) ASMs were withdrawn within 1 day. In both groups, the duration of LTM was approximately 3 days: URW group (2.9 ± 0.5 days) and RW group (3.1 ± 0.8 days). The latency to the first seizure was significantly different between the two groups; however, there were no differences between the two groups in terms of the distribution of FBTCS, SC, or SE, number of seizures, and the requirement for intravenous rescue medication was low. The rapid withdrawal of ASMs to provoke seizures during monitoring for pre-surgical evaluation following the URW protocol was as effective and safe as with RW. Ultra-rapid ASM withdrawal has the benefits of reducing LTM duration and shortening the time to first seizure compared to rapid medication tapering.

Effectiveness of Bundled Hyperpolypharmacy Deprescribing Compared With Usual Care Among Older Adults

Older patients using many prescription drugs (hyperpolypharmacy) may be at increased risk of adverse drug effects. To test the effectiveness and safety of a quality intervention intended to reduce hyperpolypharmacy. This randomized clinical trial allocated patients 76 years or older who used 10 or more prescription medications to a deprescribing intervention or to usual care (1:1 ratio) at an integrated health system with multiple preexisting deprescribing workflows. Data were collected from October 15, 2020, to July 29, 2022. Physician-pharmacist collaborative drug therapy management, standard-of-care practice recommendations, shared decision-making, and deprescribing protocols administered by telephone over multiple cycles for a maximum of 180 days after allocation. Primary end points were change in the number of medications and in the prevalence of geriatric syndrome (falls, cognition, urinary incontinence, and pain) from 181 to 365 days after allocation compared with before randomization. Secondary outcomes were use of medical services and adverse drug withdrawal effects. Of a random sample of 2860 patients selected for potential enrollment, 2470 (86.4%) remained eligible after physician authorization, with 1237 randomized to the intervention and 1233 to usual care. A total of 1062 intervention patients (85.9%) were reached and agreed to enroll. Demographic variables were balanced. The median age of the 2470 patients was 80 (range, 76-104) years, and 1273 (51.5%) were women. In terms of race and ethnicity, 185 patients (7.5%) were African American, 234 (9.5%) were Asian or Pacific Islander, 220 (8.9%) were Hispanic, 1574 (63.7%) were White (63.7%), and 257 (10.4%) were of other (including American Indian or Alaska Native, Native Hawaiian, or >1 race or ethnicity) or unknown race or ethnicity. During follow-up, both the intervention and usual care groups had slight reductions in the number of medications dispensed (mean changes, -0.4 [95% CI, -0.6 to -0.2] and -0.4 [95% CI, -0.6 to -0.3], respectively), with no difference between the groups (P = .71). There were no significant changes in the prevalence of a geriatric condition in the usual care and intervention groups at the end of follow-up and no difference between the groups (baseline prevalence: 47.7% [95% CI, 44.9%-50.5%] vs 42.9% [95% CI, 40.1%-45.7%], respectively; difference-in-differences, 1.0 [95% CI, -3.5 to 5.6]; P = .65). No differences in use of medical services or adverse drug withdrawal effects were observed. In this randomized clinical trial from an integrated care setting with various preexisting deprescribing workflows, a bundled hyperpolypharmacy deprescribing intervention was not associated with reduction in medication dispensing, prevalence of geriatric syndrome, utilization of medical services, or adverse drug withdrawal effects. Additional research is needed in less integrated settings and in more targeted populations. ClinicalTrials.gov Identifier: NCT05616689.

People with lived and living experience of methamphetamine use and admission to hospital: what harm reduction do they suggest needs to be addressed?

People who use substances may access hospital services for treatment of infections and injuries, substance use disorder, mental health issues and other reasons. Our aim was to identify the experiences, issues and recommendations of people who use methamphetamine and have accessed hospital services. Of the 114 people with lived and living experience of methamphetamine use recruited for a mixed-methods study conducted in southwestern Ontario, Canada, 104 completed the qualitative component. Interviews were conducted from October 2020 to April 2021. Participants were asked open-ended questions and the responses were analyzed using an ethnographic thematic approach. Negative patient-staff interactions included stigma and a lack of understanding of addiction and methamphetamine use, leading to distrust, avoidance of hospital care and reduced help-seeking and health care engagement. The consequences can be infections, unsafe needle use, discharge against medical advice and withdrawal. Almost all participants were in favour of in-hospital harm reduction strategies including safe consumption services, provision of sterile equipment and sharps containers, and withdrawal support. Clinical implications include education to reduce knowledge gaps about methamphetamine use and addiction and address stigma, which could facilitate the introduction of harm reduction strategies. Although the strategies identified by participants could promote a safer care environment, improving therapeutic relationships through education of health care providers and hospital staff is an essential first step. The addition of in-hospital harm reduction strategies requires attention as the approach remains uncommon in hospitals in Canada.

Withdrawal of antiseizure medications after MRI–Guided laser interstitial thermal therapy in extra-temporal lobe epilepsy

PurposeThis study investigated the success rate of antiseizure medications (ASMs) withdrawal following MRI Guided Laser Interstitial Thermal Therapy (MRg-LITT) for extra-temporal lobe epilepsy (ETLE), and identified predictors of seizure recurrence. MethodsWe retrospectively assessed 27 patients who underwent MRg-LITT for ETLE. Patients’ demographics, disease characteristics, and post-surgical outcomes were evaluated for their potential to predict seizure recurrence associated with ASMs withdrawal. ResultsThe median period of observation post MRg-LITT was 3 years (range 18 - 96 months) and the median period to initial ASMs reduction was 0.5 years (range 1–36 months). ASMs reduction was attempted in 17 patients (63%), 5 (29%) of whom had seizure recurrence after initial reduction. Nearly all patient who relapsed regained seizure control after reinstitution of their ASMs regimen. Pre-operative seizure frequency (p = 0.002) and occurrence of acute post-operative seizures (p = 0.01) were associated with increased risk for seizure recurrence post ASMs reduction. At the end of the observation period, 11% of patients were seizure free without drugs, 52% were seizure free with drugs and 37% still experienced seizures despite ASMs. Compared with pre-operative status, the number of ASMs was reduced in 41% of patients, unchanged in 55% of them and increased in only 4% of them. ConclusionsSuccessful MRg-LITT for ETLE allows for ASMs reduction in a significant portion of patients and complete ASMs withdrawal in a subset of them. Patients with higher pre-operative seizure frequency or occurrence of acute post operative seizures exhibit higher chances relapse post ASMs reduction.

Medical withdrawals in elite tennis in reference to playing standards, court surfaces and genders.

To examine the relationships between medical withdrawals, playing standards, court surfaces and genders in tennis players participating in all elite tours. Descriptive epidemiology study. Medical withdrawals of men and women tennis players from Association of Tennis Professionals, Women Tennis Association, Challengers and International Tennis Federation Futures tours' matches have been identified considering the court surfaces (fast vs. slow). Proportion comparison and the binomial regression model were used to determine the influence of playing standards, court surfaces and genders on tennis players' likelihoods to withdraw. A higher proportion of withdrawals was found for men in Challengers and Futures vs. Association of Tennis Professionals (4.8 %, 5.9 % vs 3.4 %; p < 0.001), but without difference between court surfaces (0.1 %, p > 0.05) whatever the playing standards. Women reported higher proportion of medical withdrawals sustained on slow surfaces (0.4 %, p < 0.001), but without different withdrawal rates between playing standards (3.9 %, p > 0.05). After adjustment, the odds of medical withdrawals were higher for Challengers (1.18, p < 0.001) and Futures (1.34, p < 0.001), with a higher likelihood to withdraw (1.04, p < 0.001) when playing on slow surfaces and with a gender-dependent effect indicating higher odds (1.29, p < 0.001) to withdraw for medical reasons in men in reference to women. These findings demonstrated a gender-dependent effect on medical withdrawals from an elite tennis tournament with higher likelihood for men participating in Challengers/Futures tours and for women playing on slow surfaces.

Severe lichenoid eruption due to concomitant medications following nivolumab administration

AbstractRecently, immune checkpoint inhibitors have been administered for several cancers and have shown great efficacy. However, they are associated with various immune‐related adverse events. Here, we report a case with severe lichenoid eruption following nivolumab administration that improved after the withdrawal of concomitant medications and the patient could continue nivolumab therapy. While nivolumab has been reported to cause severe skin reactions, the current case suggests that severe cutaneous manifestations after nivolumab administration could also be caused by the acquisition of immunogenicity of concomitant medications, including the one that was safely administered before nivolumab treatment and discontinuation of them may enable the patient to continue nivolumab therapy.

Optimising the prescribing of drugs that may cause dependency: An evidence and gap map of systematic reviews.

We set out to map the quantitative and qualitative systematic review evidence available to inform the optimal prescribing of drugs that can cause dependency (benzodiazepines, opioids, non-benzodiazepine hypnotics, gabapentinoids and antidepressants). We also consider how this evidence can be used to inform decision-making in the patient care pathway for each type of medication. Eight bibliographic databases were searched for the period 2010 to 2020. All included reviews were initially appraised using four items from the Collaboration for Environmental Evidence Synthesis Assessment Tool, with reviews that scored well on all items proceeding to full quality appraisal. Key characteristics of the reviews were tabulated, and each review was incorporated into an evidence and gap map based on a patient care pathway. The care pathway was based upon an amalgamation of existing NICE guidelines and feedback from clinical and patient stakeholders. We identified 80 relevant reviews and displayed them in an evidence and gap map. The evidence included in these reviews was predominantly of low overall quality. Areas where systematic reviews have been conducted include barriers and facilitators to the deprescribing of drugs that may cause dependency, although we identified little evidence exploring the experiences or evaluations of specific interventions to promote deprescribing. All medications of interest, apart from gabapentinoids, were included in at least one review. The evidence and gap map provides an interactive resource to support (i) policy developers and service commissioners to use evidence in the development and delivery of services for people receiving a prescription of drugs that may cause dependency, where withdrawal of medication may be appropriate, (ii) the clinical decision-making of prescribers and (iii) the commissioning of further research. The map can also be used to inform the commissioning of further systematic reviews. To address the concerns regarding the quality of the existing evidence based raised in this report, future reviews should be conducted according to best-practice guidelines. Systematic reviews focusing on evaluating interventions to promote deprescribing would be particularly beneficial, as would reviews focusing on addressing the paucity of evidence regarding the deprescription of gabapentinoids.

Vogt-Koyanagi-Harada-like Syndrome Induced by Checkpoint Inhibitor Cemiplimab.

Checkpoint inhibition targeting programmed cell-death protein 1 has demonstrated efficacy for a wide range of indications including cutaneous malignancy. However, immune-related adverse events (irAEs), including infrequent but visually impactful ocular irAEs, require careful consideration of treatment options, including medication withdrawal, local corticosteroids, or rarely immunomodulation. This case presents a 53-year-old woman who developed uveitis and mucous membrane ulcers after treatment for numerous cutaneous neoplasms, primarily squamous cell carcinoma, with the programmed cell-death protein 1 inhibitor cemiplimab. Ophthalmic examination revealed diffuse choroidal depigmentation consistent with a Vogt-Koyanagi-Harada-like syndrome. Topical and periocular steroids were used to treat the intraocular inflammation, and cemiplimab was discontinued. Because of ongoing severe uveitis, systemic corticosteroids and corticosteroid-sparing immunosuppression were initiated. Specifically, azathioprine and methotrexate were introduced, but each was stopped due to side effects, prompting the initiation of adalimumab (ADA) treatment. While ADA controlled intraocular inflammation, the squamous cell carcinomas were noted to progress, resulting in the discontinuation of ADA. However, a uveitis recurrence was observed. After a discussion of risks and benefits of biologic immunosuppressive therapy, including the risk of vision loss, ADA was restarted with successful disease quiescence at a 16-month follow-up. The cutaneous neoplasms were managed with topical and intralesional therapies, such as 5-fluorouracil. Recent dermatologic examinations suggested no new cutaneous lesions. This scenario presents the effective use of ADA in an ocular irAE that balances the management of sight-threatening ocular inflammation with the risk of promoting recurrent or de novo neoplastic disease.

Video-EEG-monitoring to guide antiseizure medication withdrawal

BackgroundDiscontinuing anti-seizure medication (ASM) should be considered in persons with epilepsy with long-term seizure freedom. Clinicians should also pursue ASM withdrawal in persons with one-time seizures without increased recurrence risk and those with suspected non-epileptic events. However, ASM withdrawal is associated with the risk of recurring seizures. Monitored ASM withdrawal in an epilepsy monitoring unit (EMU) could help better evaluate the risk of seizure recurrence. Here, we investigate the practice of EMU-guided ASM withdrawal, assess its indications, and aim to determine positive and negative predictors for successful withdrawal.MethodsWe screened the medical records of all patients admitted to our EMU between November 1, 2019, and October 31, 2021, and included patients of at least 18 years admitted with the aim of permanent ASM withdrawal. We defined four groups of withdrawal indications: (1) long-term seizure freedom; (2) suspected non-epileptic events; (3) history of epileptic seizures but not fulfilling diagnostic criteria of epilepsy; and (4) seizure-freedom after epilepsy surgery. Successful withdrawal was defined according to the following criteria: no recoding of (sub)clinical seizure activity during VEM (groups 1, 2, and 3), patients did not meet the International League Against Epilepsy (ILAE) definition of epilepsy (groups 2 and 3) [14], and patients were discharged without ongoing ASM treatment (all groups). We also evaluated the prediction model by Lamberink et al. (LPM) for the risk of seizure recurrence in groups 1 and 3.Results55/651 (8.6%) patients fulfilled the inclusion criteria. Withdrawal indications were distributed as follows; group 1: 2/55 (3.6%); group 2: 44/55 (80%); group 3: 9/55 (16,4%); group 4: 0/55. Overall, ASM withdrawal was successful in 90.9%. The sensitivity of the LPM for a 2-year 50% relapse risk threshold was 75%, the specificity 33.3%; for a 5-year relapse risk respectively 12.5% and 33.3%, suggesting that the model is not suitable for risk assessment in patients with one-time seizures or acute-symptomatic seizures, who constituted most of the evaluated patients.ConclusionsOur study suggests that EMU-guided ASM withdrawal could be a helpful tool to support clinical decision-making and improve patient safety. Prospective, randomized trials should further evaluate this method in the future.

Clinical assessment and management of patients with multimorbidity.

Internal medicine specialists, also known as general internal medicine specialists are specialist physicians trained to manage particularly complex or multisystem disease conditions that single-organ-disease specialists may not be trained to deal with. The management of multimorbidity, however, is often complex, and requires specific clinical skills and corresponding experience in appropriate diagnostic and therapeutic procedures. Multimorbidity is associated with a decline in many aspects of health and in consequence with an increase in hospital admissions, polypharmacy, and use of health care and social resouces. When prescribing medicine to patients with multimorbidity, all the risks and benefits, as well as possible interactions should be carefully considered. The prescription appropriateness can be assessed by validated tools like STOPP-START criteria. Beneficial part of good prescribing is deprescribing - planned and supervised process of dose reduction or withdrawal of medications that are no longer needed in the circumstances of the patient.

Safety Profile of Medicines Used for the Treatment of Drug-Resistant Tuberculosis: A Descriptive Study Based on the WHO Database (VigiBase®).

The introduction of new drugs that increase the usage of repurposed medicines for managing drug-resistant tuberculosis (DR-TB) comes with challenges of understanding, properly managing, and predicting adverse drug reactions (ADRs). In addition to the health consequences of ADRs for the individual, ADRs can reduce treatment adherence, thus contributing to resistance. This study aimed to describe the magnitude and characteristics of DR-TB-related ADRs through an analysis of ADRs reported to the WHO database (VigiBase) in the period from January 2018 to December 2020. A descriptive analysis was performed on selected reports from VigiBase on the basis of medicine-potential ADR pairs. The ADRs were stratified by sex, age group, reporting country, seriousness, outcome of the reaction, and dechallenge and rechallenge. In total, 25 medicines reported to be suspected individual medicines or as a fixed-dose combination in the study period were included the study. Pyrazinamide (n = 836; 11.2%) was the most commonly reported medicine associated with ADRs, followed by ethionamide (n = 783; 10.5%) and cycloserine (n = 696; 9.3%). From the report included in this analysis, 2334 (31.2%) required complete withdrawal of the suspected medicine(s), followed by reduction of the dose (77; 1.0%) and an increased dose (4; 0.1%). Almost half of the reports were serious ADRs mainly caused by bedaquiline, delamanid, clofazimine, linezolid, and cycloserine that are the backbone of the DR-TB treatment currently in use. A third of the reports required medication withdrawal, which impacts treatment adherence and ultimately leads to drug resistance. Additionally, more than 40% of the reports indicated that ADRs appeared two months after the commencement of treatment, thus it's important to remain alert for the potential ADRs for the entire duration of the treatment.

Teaching NeuroImages: Sleep-onset REM period during routine EEG

A 76-year-old incarcerated man presented with word-finding difficulties and underwent a routine EEG. Shortly after reaching stage N2 sleep, EEG showed brisk lateral eye movements with concurrent sawtooth waves (figure), indicating sleep-onset REM period (SOREMP). Normal REM sleep is reached 90–120 minutes after sleep onset. SOREMP is an abnormal EEG finding thought to be suggestive of narcolepsy. However, it may also be present in 3.9% of the general population1 and is normal in infants. It is also associated with severe sleep deprivation, obstructive sleep apnea, and alcohol or medication (selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors) withdrawal. In the inpatient setting, it is usually caused by sleep deprivation.2

Factors Associated With Maintenance of Remission Following Change From Combination Therapy to Monotherapy in Patients With Rheumatoid Arthritis.

Some patients with rheumatoid arthritis (RA) who persist in remission may decide to stop their therapy. We evaluated baseline characteristics associated with remaining in remission or low disease activity (LDA) following medication withdrawal. The Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis (SEAM-RA) was a phase III, multicenter, randomized withdrawal, double-blind, controlled study in patients with RA on methotrexate (MTX) + etanercept (ETN). If remission (Simplified Disease Activity Index [SDAI] ≤ 3.3) was sustained through a 24-week run-in period, patients then entered a 48-week double-blind period and were randomized 2:2:1 to receive MTX monotherapy, ETN monotherapy, or continue combination therapy. Multivariate logistic regression analysis was performed to identify baseline factors associated with remission or LDA at the end of both periods. Of 371 patients enrolled, 253 entered the double-blind period. After adjusting for other factors, covariates associated with achieving SDAI remission at the end of the run-in period included younger age, longer duration of MTX treatment, and less severe clinical disease variables. Covariates associated with maintaining remission/LDA at the end of the 48-week double-blind period included lower patient global assessment of disease activity (PtGA), lower C-reactive protein, rheumatoid factor (RF) negativity, longer RA duration in the MTX arm, shorter duration of ETN treatment, and lower magnesium. These findings indicate patients with overall lower disease activity are more likely to remain in SDAI remission/LDA after switching from combination therapy to monotherapy. RF-negative status and lower PtGA scores were strongly associated with increased likelihood of remaining in remission/LDA with MTX or ETN monotherapy. (SEAM-RA; ClinicalTrials.gov: NCT02373813).

Sustained Response to Eculizumab in a Patient With COVID-19–Associated Acute Thrombotic Microangiopathy of the Allograft Kidney: A Case Report

Acute thrombotic microangiopathy (TMA) developing in association with SARS-CoV-2 infection is a rare but recognized phenomenon in native kidneys. In the allograft kidney, a diagnosis of TMA has a broad etiologic differential, including antibody-mediated rejection and recurrent and de novo causes of TMA that affect the native kidney. Prior case reports have described plasma exchange or eculizumab use in patients with COVID-19-associated TMA. Herein, we describe the course of a kidney transplant patient with COVID-19-associated TMA with response to eculizumab that was sustained after medication withdrawal and review the literature on COVID-19-associated TMA of the allograft kidney.

Withdrawal of antiseizure medications – for whom, when, and how?

ABSTRACT Introduction Epilepsy is a chronic disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. Most patients can achieve complete seizure control (seizure freedom) with antiseizure medications (ASMs). In some of them, the withdrawal of ASMs can be considered. Guidance is required to identify patients in whom drug discontinuation can be safely attempted and to inform when and how ASM withdrawal can be done. Areas covered In this perspective, the authors discuss the evidence on ASM withdrawal in epilepsy patients who are seizure-free and provide some suggestions on how to do it effectively in clinical practice, minimizing the risk of seizure recurrence. Expert opinion The decision of discontinuing ASMs in epilepsy patients should rely on an accurate estimate of seizure recurrence risk. Whenever possible, such a risk should be assessed on an individual basis. The decision should also consider the psychosocial and personal consequences of seizure relapse. No robust evidence is available on the safest tapering regimen.

The Use of Medication for Challenging Behaviors in People with Intellectual Disabilities: The Direct Care Providers’ Perspective

ABSTRACT Background Overmedication of people with intellectual disabilities, particularly when psychotropic medications are used for challenging behavior (CB) in the absence of a psychiatric disorder, is a significant public health concern. Support staff play a pivotal role in influencing the prescribing process. Staff views and attitudes toward medication use for CB are therefore of paramount importance. Method We have conducted four focus groups involving support staff (n = 8), home managers (n = 5) and trainers (n = 3), two of which primarily explored participants’ experiences and views on using medication for CB and medication withdrawal. Results Some participants felt medication use was justified, but others saw that as a form of chemical restraint. Most agreed that polypharmacy of psychotropics might lead to side effects. Some acknowledged the lack of shared decision-making involving people with intellectual disabilities and their families. There was universal anxiety about withdrawing the medication. Conclusions All agreed on the need for more medication-related information.

Long-Term Pharmacological and Psychosocial Outcomes of Adolescent-Onset Epilepsy: A Single-Center Experience

Purpose: Despite the high incidence of epilepsy during adolescence, little attention has been paid to the outcomes and prognosis of adolescent-onset epilepsy. The aim of this study was to investigate the long-term pharmacological and psychosocial outcomes of adolescent-onset epilepsy.Methods: From 1993 to 2019, the electronic medical records of adolescent-onset epilepsy patients were retrieved from Asan Medical Center Children’s Hospital. Seizure outcomes were evaluated based on the seizure-free period at last contact. Possible predictors of remission, relapse, and intractability were investigated. Neuropsychiatric comorbidities, socioeconomic status, and transition outcomes were also assessed. Results: In total, 137 patients were enrolled in this study. The median age at diagnosis of epilepsy was 14 years and the mean duration of therapy was 13.0 years. During follow-up, 93 patients (67.9%) achieved terminal remission, of which 27 cases (19.7%) resolved. Relapse after withdrawal of medication occurred in 74 patients (54.0%), and the presence of electroencephalographic abnormalities (odds ratio [OR], 8.23; 95% confidence interval [CI], 1.39 to 48.87; P=0.020), poor adherence (OR, 4.84; 95% CI, 2.13 to 11.02; P=0.000), and history of febrile seizures (OR, 4.10; 95% CI, 1.21 to 13.93; P=0.024) were risk factors for relapse. Neurodevelopmental and psychological comorbidities were documented in 17 (12.4%) and 12 (8.8%) patients, respectively. Thirty-six (26.3%) patients transferred to adult clinics, at a mean age of 21.9 years. Conclusion: This study showed overall favorable seizure outcomes with a high rate of remission, but with frequent relapse after withdrawal.