Withdrawal In Patients Research Articles

Relapse After Drug Withdrawal in Patients with Epilepsy After Two Years of Seizure-Free: A Cohort Study.

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. 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 χ2-test, Kaplan-Meier survival analysis and multivariate Cox regression analysis. 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. 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.

A Retrospective Study of Time to Relapse following Guselkumab Withdrawal in Patients with Psoriasis

Background. Psoriasis is a chronic immune‐mediated skin disease requiring long‐term management. However, for various reasons such as financial issues, treatment cessation is common among psoriasis patients who have achieved clinical remission. Currently, only few studies have assessed the time to relapse after guselkumab withdrawal in the real‐world setting. Objective. The study aimed at assessing the time to relapse after remission following guselkumab discontinuation in patients with moderate‐to‐severe plaque psoriasis in the real‐world setting. Materials and Methods. Eligible adult moderate‐to‐severe plaque psoriasis patients received at least 2 doses of administration of guselkumab treatment between March 2020 and March 2022 were enrolled. The study included patients who achieved PASI &lt; 3 at week 12. Relapse was defined as restart of systemic therapy upon guselkumab withdrawal. Time to relapse was defined as the time interval between the last guselkumab administration and restart of systemic therapy. Results. Totally, 76 patients were enrolled. Relapse was found in 60.5% of patients, with a median PASI score at relapse of 4.6 (IQR: 1.6, 8.4) and median time to relapse was 201 (IQR: 159, 314) days. The proportion of patients with comorbidities significantly differed between the relapse and nonrelapse groups at baseline (P &lt; 0.05). Compared with patients with PASI &lt; 3, those with PASI ≥ 3 at relapse had longer time to relapse (P &lt; 0.001). Conclusions. Guselkumab provides durable maintenance of response after discontinuation of therapy in the real‐world setting. Higher PASI score at relapse was associated with longer time to relapse. This trial is registered with Chinese Clinical Trial Registry: ChiCTR2000041398.

Electrocardiographic Abnormalities During and After Withdrawal in Patients Diagnosed with Opioid Use Disorder

Electrocardiographic Abnormalities During and After Withdrawal in Patients Diagnosed with Opioid Use Disorder

Social isolation after chronic unpredictable mild stress perpetuates depressive-like behaviors, memory deficits and social withdrawal via inhibiting ERK/KEAP1/NRF2 signaling

BackgroundSocial withdrawal in patients with depression can aggravate depressive symptoms. However, few studies focus on the behavioral changes of social isolation after CUMS. NRF2 had been reported to be down-regulated after CUMS. But whether NRF2 participates in behavioral changes induced by social isolation after CUMS remains unclear. This study aims to develop a new model combined social isolation with CUMS, and investigate whether such behavioral changes are related to NRF2 signaling. MethodsThis study included two stages. In Stage 1, rats were subjected to 4-week CUMS and CUMS-susceptible rats were selected. In Stage 2, the CUMS-susceptible rats received 4-week social isolation or social support. Behavioral tests were carried out to observe behavioral changes, including sucrose preference test, forced swimming test, open field test, novel object recognition and social interaction test. QRT-PCR, western blot and immunofluorescence staining detected the ERK/KEAP1/NRF2 signaling. ResultsCUMS-susceptible rats exhibited depressive-like behaviors accompanied by the down-regulated ERK/KEAP1/NRF2 signaling in hippocampus. In Stage 2, compared with 4-week social support (group CUMSG), 4-week social isolation (group CUMSI) perpetuated the depressive-like behaviors, memory deficits and social withdrawal in CUMS-susceptible rats, as well as lower levels of p-ERK, NRF2, p-NRF2, HO-1 and NQO1, and the higher levels of KEAP1 in hippocampus. ConclusionThese findings suggested that social isolation after CUMS perpetuated depressive-like behaviors, memory deficits and social withdrawal via inhibiting ERK/KEAP1/NRF2 signaling. This study provided molecular evidence for the effects of post-stress social isolation on mental health, and the antioxidant stress signaling might be a target to rescue these.

Covid-19 Challenges: Socio-Legal Issues Concerning the Patient Rights and Privacy During the Pandemic Era

Patient privacy is a right guaranteed by law that allows patient to conceal their medical records. However, this rights only applies in normal conditions and does not apply during a pandemic. It is often being misunderstood that broad society decided to close their medical records during this pandemic. The closing of the medical record will potentially cause the difficulty in detecting the virus’ transmission. Moreover, the status of a patient recognized as pandemic-suspected is often being ignored by their family and ultimately brought home assuming that their family is in good condition. This fact has immense potential to generate a wider spread of the pandemic virus. According to the previous subject, the study will further discuss the Indonesian regulations concerning the protection of patient confidentiality during the pandemic and the legal status for those responsible for taking the pandemic-suspected patient in force. This study hopefully will be contributing to the prevention of such actions mentioned above. This study uses a normative legal approach with secondary data research. The study results show that the broad society merely understands that the confidentiality of patient privacy only applies in normal circumstances and does not apply during the pandemic situation. Moreover, the forced withdrawal of pandemic-suspected patients occurs due to society's general prejudice towards the suspected patient. Therefore, this study argues that social awareness regarding the protection of patient confidentiality is necessary to increase social knowledge about patients' rights.

Autogenic Relaxation, Movement, and Affirmation (RIMA) Therapy: Efforts to Strengthen Self-Efficacy to Prevent Drug Withdrawal in Aggregate Patients with Pulmonary TB

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.&#x0D; 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%.&#x0D; 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 (&lt; 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 (&lt; 0.05).&#x0D; 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.

Etanercept Withdrawal and Retreatment in Nonradiographic Axial Spondyloarthritis: Results of RE-EMBARK, an Open-Label Phase IV Trial.

RE-EMBARK investigated etanercept (ETN) withdrawal and retreatment in patients with nonradiographic axial spondyloarthritis (nr-axSpA) achieving inactive disease. Patients received ETN and a background nonsteroidal antiinflammatory drug for 24 weeks in period 1 (P1); those achieving inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] with C-reactive protein [CRP] < 1.3) discontinued ETN for 40 weeks or less (period 2 [P2]). Patients who flared (ASDAS with erythrocyte sedimentation rate [ESR] ≥ 2.1) were retreated for 12 weeks in period 3 (P3). The primary endpoint was the proportion of patients with inactive disease who flared within 40 weeks of ETN withdrawal. Baseline characteristics were analyzed post hoc as predictors of maintenance and regaining of inactive disease, respectively, using univariate logistic and stepwise multivariable logistic regression models. The proportion of patients experiencing flare following ETN withdrawal (P2) increased from 22.3% (25/112) after 4 weeks to 67% (77/115) after 40 weeks; 74.8% (86/115) experienced flare at any time during P2. Median time to flare was 16.1 weeks. Most patients (54/87, 62.1%) who were retreated with ETN in P3 reachieved inactive disease. Absence of both sacroiliitis detected on magnetic resonance imaging (MRI) and high-sensitivity CRP (hs-CRP) > 3 mg/L at baseline predicted inactive disease maintenance in P2 following ETN withdrawal in multivariable analysis; male sex and age younger than 40 years predicted regaining of inactive disease in P3 after flare/retreatment. There were no unexpected safety signals. Approximately 25% of patients maintained inactive disease for 40 weeks after discontinuing ETN. Absence of both MRI sacroiliitis and high hs-CRP at baseline predicted response maintenance after ETN withdrawal. (ClinicalTrials.gov: NCT02509026).

Pharmacoeconomic analysis of fixed-duration targeted therapy regimens for chronic lymphocytic leukemia compared with therapy used until progression or intolerable toxicity

Background. Chronic lymphocytic leukemia (CLL) is a b-cell tumor of small b-lymphocytes. In CLL, significant lymphocytosis (5000 monoclonal b-lymphocytes) is observed in the blood, there are no morphological signs of bone marrow involvement. The 2020 Russian Clinical Guidelines “Chronic lymphocytic leukemia/Small lymphocyte lymphoma” approved several main chemotherapy regimens for the treatment of CLL patients.Aim. To perform a pharmacoeconomic analysis of the feasibility of fixed therapy regimens based on venetoclax in comparison with other targeted drugs registered in Russia, from the class of bruton kinase inhibitors, used until CLL progression or unacceptable toxicity.Materials and methods. A list of direct costs in the health care system was compiled. To assess the change in the cost structure and budget impact analyze, 4 mathematical models were constructed from a health care system perspective. Model 1 analyzed the direct costs of the health care system over 5 years, without taking into account the addition of new patients to the model. At the beginning of the modeling, the patients were equally divided between the strategies; later, there was a natural withdrawal of patients from the cycle. Models 2–4 analyze the economic impact of increasing the proportion of venetoclax-based fixed regimens.Results. with venetoclax + rituximab and venetoclax + obinutuzumab combinations used in 65 % of new patients, a cost reduction of 6.97 % would be observed in 2nd year of the budget impact analysis. In the case of an increase in the use of venetoclax in combination with rituximab or obinutuzumab to 80 % for new patients in the 5th year of the budget impact analysis, direct costs will decrease by 31.17 %, to 9,077,299,932 rubles.Conclusion. Increasing the proportion of fixed-dose venetoclax-based combinations compared to regimens prior to CLL progression or unacceptable toxicity in all models demonstrates cost-effectiveness.

Agoraphobic avoidance in patients with psychosis: Severity and response to automated VR therapy in a secondary analysis of a randomised controlled clinical trial

BackgroundThe social withdrawal of many patients with psychosis can be conceptualised as agoraphobic avoidance due to a range of long-standing fears. We hypothesised that greater severity of agoraphobic avoidance is associated with higher levels of psychiatric symptoms and lower levels of quality of life. We also hypothesised that patients with severe agoraphobic avoidance would experience a range of benefits from an automated virtual reality (VR) therapy that allows them to practise everyday anxiety-provoking situations in simulated environments. Methods345 patients with psychosis in a randomised controlled trial were categorised into average, moderate, high, and severe avoidance groups using the Oxford Agoraphobic Avoidance Scale. Associations of agoraphobia severity with symptom and functioning variables, and response over six months to brief automated VR therapy (gameChange), were tested. ResultsGreater severity of agoraphobic avoidance was associated with higher levels of persecutory ideation, auditory hallucinations, depression, hopelessness, and threat cognitions, and lower levels of meaningful activity, quality of life, and perceptions of recovery. Patients with severe agoraphobia showed the greatest benefits with gameChange VR therapy, with significant improvements at end of treatment in agoraphobic avoidance, agoraphobic distress, ideas of reference, persecutory ideation, paranoia worries, recovering quality of life, and perceived recovery, but no significant improvements in depression, suicidal ideation, or health-related quality of life. ConclusionsPatients with psychosis with severe agoraphobic avoidance, such as being unable to leave the home, have high clinical need. Automated VR therapy can deliver clinical improvement in agoraphobia for these patients, leading to a number of wider benefits.

Early Eculizumab Withdrawal in Patients With Atypical Hemolytic Uremic Syndrome in Native Kidneys Is Safe and Cost-Effective: Results of the CUREiHUS Study

Early Eculizumab Withdrawal in Patients With Atypical Hemolytic Uremic Syndrome in Native Kidneys Is Safe and Cost-Effective: Results of the CUREiHUS Study

Early Eculizumab Withdrawal in Patients With Atypical Hemolytic Uremic Syndrome in Native Kidneys Is Safe and Cost-Effective: Results of the CUREiHUS Study

The introduction of eculizumab has improved the outcome in patients with atypical hemolytic uremic syndrome (aHUS). The optimal treatment strategy is debated. Here, we report the results of the CUREiHUS study, a 4-year prospective, observational study monitoring unbiased eculizumab discontinuation in Dutch patients with aHUS after 3 months of therapy. All pediatric and adult patients with aHUS in native kidneys and a first-time eculizumab treatment were evaluated. In addition, an extensive cost-consequence analysis was conducted. A total of 21 patients were included in the study from January 2016 to October 2020. In 17 patients (81%), a complement genetic variant or antibodies against factor H were identified. All patients showed full recovery of hematological thrombotic microangiopathy (TMA) parameters after the start of eculizumab. A renal response was noted in 18 patients. After a median treatment duration of 13.6 weeks (range 2.1-43.9), eculizumab was withdrawn in all patients. During follow-up (80.7 weeks [0.0-236.9]), relapses occurred in 4 patients. Median time to first relapse was 19.5 (14.3-53.6) weeks. Eculizumab was reinitiated within 24 hours in all relapsing patients. At last follow-up, there were no chronic sequelae, i.e., no clinically relevant increase in serum creatinine (sCr), proteinuria, and/or hypertension in relapsing patients. The low sample size and event rate did not allow to determine predictors of relapse. However, relapses only occurred in patients with a likely pathogenic variant. The cost-effectiveness analysis revealed that the total medical expenses of our population were only 30% of the fictive expenses that would have been made when patients received eculizumab every fortnight. It is safe and cost-effective to discontinue eculizumab after 3 months of therapy in patients with aHUS in native kidneys. Larger data registries are needed to determine factors associated with suboptimal kidney function recovery during eculizumab treatment, factors to predict relapses, and long-term outcomes of eculizumab discontinuation.

The effect of intranasal oxytocin on processing emotional stimuli during alcohol withdrawal: A randomized placebo-controlled double-blind clinical trial

Alcohol dependence is associated with difficulties in processing emotional stimuli, which can lead to interpersonal problems. The neuropeptide oxytocin has been shown to modulate the processing of emotional stimuli, however, oxytocin treatment has not yet been examined in patients with withdrawal symptoms during alcohol detoxification. The aim of the present study was to investigate the effect of oxytocin on the reading the mind in the eyes test (RMET), which indexes theory of mind ability, during a three-day period of alcohol detoxification at an addiction treatment centre in Norway. We performed a randomized, double-blind, placebo-controlled trial in 39 patients fulfilling criteria for ICD-10 diagnosis of alcohol dependence admitted for alcohol detoxification and withdrawal treatment. Participants were randomized to receive either intranasal oxytocin (24 IU) or placebo, twice daily for three days. We evaluated RMET performance on day 2 and day 3 of detoxification and differences in RMET scores between day 2 and day 3 of detoxification. Frequentist and Bayesian statistical inference suggested that oxytocin administration during alcohol withdrawal in alcohol-dependent patients did not improve RMET performance. However, exploratory analyses provided preliminary evidence that oxytocin might improve performance on the RMET negative emotion subscale (uncorrected p value = 0.038), and that oxytocin treatment might show the most promise for those with high levels of alcohol consumption (i.e., ≥20 alcohol units per day; uncorrected p value = 0.023). Moreover, alcohol consumption levels significantly predicted RMET performance on day 2, but not on day 3, of withdrawal.

Analysis of withdrawal status and influencing factors in patients receiving methadone maintenance treatment in Hubei province

Objective: To analyze the withdrawal in patients receiving methadone maintenance treatment (MMT) and its related influencing factors in Hubei province. Methods: The patients receiving MMT in clinics in Hubei province were selected from June 2006 to December 2021. The general demographic data, drug abuse history, and MMT information were collected. The survival data of patients with MMT were analyzed by the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analysis. Results: A total of 26 716 patients receiving MMT were included in this study, and the gender ratio between men and women was 3.34∶1(20 557∶6 159). The duration of MMT was 0.01-15.72 years, and the median duration was 2.21 (95%CI: 2.16-2.26) years. At the end of the follow-up, the withdrawal proportion was 86.75% (23 175/26 716). MMT's 0-year, 2-year, 4-year, 9-year and 14-year cumulative probabilities appeared as 67.61%, 40.24%, 30.03%, 15.49% and 6.56%, respectively. Results from the Cox proportional hazards regression model showed that the factors of the withdrawal risk were higher in patients receiving MMT, including minority nationality (HR=1.66,95%CI:1.52-1.82), having jobs (HR=1.05, 95%CI:1.01-1.08), no history of compulsory isolation or detoxification (HR=1.04, 95%CI:1.01-1.09) and the enrollment in 2016-2021 (HR=1.46,95%CI:1.35-1.58). The factors of the withdrawal risk were lower in patients receiving MMT, including 60-year-olds or above (HR=0.56,95%CI:0.42-0.75), college degree or above education level (HR=0.83, 95%CI:0.75-0.91), outpatient services of other cities (HR=0.90, 95%CI:0.87-0.93), drug use for 20 years or more (HR=0.72, 95%CI:0.66-0.80), 90 mg or more per daily dosage (HR=0.73,95%CI:0.69-0.78) and the enrollment in 2011-2015 (HR=0.93,95%CI:0.89-0.97). Conclusions: The withdrawal proportions of patients receiving MMT were high in Hubei province. The withdrawal influencing factors were complex. The daily dose was an essential factor that can be intervened under the safe MMT condition, and a higher dose should be appropriately prescribed.

Withdrawal of MTX in rheumatoid arthritis patients on bDMARD/tsDMARD plus methotrexate at target: a systematic review and meta-analysis.

To evaluate the effect of MTX withdrawal on disease activity and remission rate in patients at target after treatment with biologic DMARDs (bDMARDs)/targeted synthetic DMARDs (tsDMARDs) plus MTX. We searched the PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials (RCTs) on MTX withdrawal in patients with RA at target after combination therapy from inception to 7 March 2022 in order to extract data, including: the change from withdrawal in DAS28 at the endpoint; proportion of low disease activity (LDA) assessed by DAS28, Simplified Disease Activity Index (SDAI) or Clinical Disease Activity Index (CDAI); proportion of remission assessed by DAS28, SDAI CDAI or ACR/EULAR Boolean remission. The Cochrane Q test and I2 test were used to assess heterogeneity, and random-effects models were used for data synthesis. This study is registered with PROSPERO (CRD42022303891). Six articles were included for qualitative and quantitative analysis, all of which were noninferior RCTs involving 1430 patients (734 in the withdrawal group and 696 in the continuation group). Compared with continuing combination therapy, tapering off or discontinuing MTX increased DAS28 by 0.20 (95% CI 0.09, 0.32, I2 = 0%) and decreased the percentage of patients with LDA assessed by DAS28 to <3.2 [risk ratio (RR) 0.88 (0.80, 0.97), I2 = 0%]. However, MTX withdrawal did not decrease remission rates assessed by DAS28, SDAI, CDAI or ACR/EULAR Boolean remission [RR 0.90 (0.81, 1.01), 0.93 (0.77, 1.11), 0.90 (0.74, 1.11), 0.95 (0.70, 1.29), respectively]. Withdrawing MTX slightly increases the RA disease activity in patients treated at target with bDMARDs/tsDMARDs plus MTX and has limited effects for patients with deep remission.

Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B.

When patients with chronic hepatitis B (CHB) stop nucleos(t)ide analogue (NA) therapy before achieving HBsAg loss, flares often ensue which are challenging to predict early. We determined the incidence, severity, outcome and predictors of flares after NA withdrawal. Forty-five patients enrolled in an RCT were included; 107 patients from an external, prospective cohort were used for validation. Retreatment criteria were pre-defined. Pre- and post-treatment predictors of alanine aminotransferase (ALT) flare (>5× ULN) were evaluated by Cox proportional-hazards regression. Seventy-two weeks after NA withdrawal, 23/45 (51%) patients had developed >5× ULN and 14 (31%) >20× ULN. Median time to develop ALT >5× ULN was 12 weeks after NA withdrawal. Independent predictors of ALT >5× ULN were male sex (HR [95% CI] 3.2 [1.2-8.9]; p=0.03) and serum HBV DNA (1.2 [1.0-1.8]; p=0.03) at Week 6 off-therapy. Specifically, week 6 HBV DNA >10,000 IU/ml predicted ALT >5× ULN (3.4 [1.4-8.4]; p=0.01), which was externally validated. In conclusion, this study on post-treatment flares revealed a high cumulative incidence in CHB. Week 6 HBV DNA >10,000 IU/ml independently predicted flares. The proposed threshold enables prediction of imminent flares in patients who may benefit from closer monitoring and earlier retreatment.

Clinical and Economic Impact of Long-Term Inhaled Corticosteroid Withdrawal in Patients with Chronic Obstructive Pulmonary Disease Treated with Triple Therapy in Spain.

PurposeTo determine the clinical and economic impact of inhaled corticosteroid (ICS) withdrawal in Spanish patients with COPD receiving triple therapy (TT) with ICS, long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA).Patients and MethodsThis was an observational, retrospective study of BIG-PAC database medical records. Patients aged ≥40 years receiving TT from 2016 to 2018 were followed for 1 year. Two cohorts were identified: patients continuing TT (ICS+LABA+LAMA), and patients receiving TT with ICS withdrawn (LABA+LAMA). Variables included medication, exacerbations (moderate and severe), pneumonia, mortality, health resource use (HRU), and cost per patient/year. Cohorts were compared using propensity score matching (PSM). Multivariate statistical analysis using analysis of covariance and Cox proportional risks was conducted.ResultsOf 6541 patients included, 5740 (87.8%) continued TT and 801 (12.2%) had ICS withdrawn. Patients with ICS withdrawal were younger, had lower disease burden, higher ICS doses, and more exacerbations compared with those continuing ICS. PSM matched 795 patients in each cohort. Mean age was 68.5 years (SD: 11.2), 69.9% were male, and mean Charlson index was 2.0. Patients with ICS withdrawal had more total exacerbations in the 12 months following withdrawal compared with patients continuing TT (36.6% vs 31.4%; p=0.030). No significant differences were found for pneumonia (3.3% vs 3.6%; p=0.583) and mortality (9.9% vs 7.5%; p=0.092). Median time to first exacerbation was shorter in patients with ICS withdrawal compared with those continuing ICS (HR: 0.69, 95% CI: 0.57–0.83; p<0.001). Mean health cost per patient/year among patients with ICS withdrawal was higher than those continuing TT (€2993 vs €2130; p<0.001).ConclusionICS withdrawal in patients with COPD receiving TT was associated with increased exacerbations, HRU, and costs compared with continuing TT, with health and economic impacts on patients and the Spanish National Healthcare System, respectively. Pneumonia and mortality rates were similar between groups.

Safety and impact of eculizumab withdrawal in patients with atypical haemolytic uraemic syndrome: protocol for a multicentre, open-label, prospective, single-arm study

IntroductionAtypical haemolytic uraemic syndrome (aHUS) is a rare, life-threatening disease caused by excessive activation of part of the immune system called complement. Eculizumab is an effective treatment, controlling aHUS in...

Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease

Discontinuation of anti-tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing. This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3-4) versus complete (Mayo 0/SES-CD 0-2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use. Among 81 patients (CD: n= 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6-2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43-7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01-0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months. The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse.

Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder: A double-blind, randomized, sham-controlled pilot study

BackgroundOpioid Use Disorder (OUD) is a serious public health problem, and the behavioral and physiological effects of opioid withdrawal can be a major impediment to recovery. Medication for OUD is currently the mainstay of treatment; however, it has limitations and alternative approaches are needed. ObjectiveThe purpose of this study was to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on behavioral and physiological manifestations of acute opioid withdrawal. MethodsPatients with OUD undergoing acute opioid withdrawal were randomly assigned to receive double blind active tcVNS (N = 10) or sham stimulation (N = 11) while watching neutral and opioid cue videos. Subjective opioid withdrawal, opioid craving, and anxiety were measured using a Visual Analogue Scale (VAS). Distress was measured using the Subjective Units of Distress Scale (SUDS), and pain was measured using the Numerical Rating Scale (NRS) for pain. Electrocardiogram signals were measured to compute heart rate. The primary outcomes of this initial phase of the clinical trial (ClinicalTrials.gov NCT04556552) were heart rate and craving. ResultstcVNS compared to sham resulted in statistically significant reductions in subjective opioid withdrawal (p = .047), pain (p = .045), and distress (p = .004). In addition, tcVNS was associated with lower heart rate compared to sham (p = .026). Craving did not significantly differ between groups (p = .11). ConclusionstcVNS reduces behavioral and physiological manifestations of opioid withdrawal, and should be evaluated in future studies as a possible non-pharmacologic, easily implemented approach for adjunctive OUD treatment.

Tryptophan-kynurenine metabolism during acute alcohol withdrawal in patients with alcohol use disorder: The role of immune activation.

Recent research has suggested that excessive alcohol consumption in patients with alcohol use disorder (AUD) is associated with chronic immune activation, which affects the metabolism of the neurotransmitter precursor amino acid tryptophan (TRP) and contributes to the complex pathophysiology of AUD. Our study investigated possible immune-associated alterations of TRP to kynurenine (KYN) metabolism in patients with AUD during acute alcohol withdrawal. We measured serum concentrations of TRP, KYN, quinolinic (QUIN), kynurenic acid (KYNA), and the immune activation marker neopterin (NEO) at the first, fifth and 10th day of alcohol withdrawal in patients with AUD, who attended a standardized in-patient treatment program and underwent a detailed clinical assessment. Data from these individuals were compared to data from a reference control group (RCG). The primary outcome measures were the differences in serum concentrations of metabolites between AUD patients and RCG and correlations between NEO and metabolites of the tryptophan-kynurenine pathway. r=0.695, p < 0.001) in the AUD group. Mixed models analysis showed that NEO concentrations were positively associated with QUIN but not with KYNA concentrations. Several behavioral symptoms correlated positively with QUIN concentrations and negatively with the KYNA/QUIN ratio. Our findings demonstrate that the changes in TRP catabolism in acute alcohol withdrawal resulting in increased KYN production could reflect the involvement of immune-associated activation of the enzyme indoleamine 2,3-dioxygenase, as NEO concentrations correlated with the KYN/TRP ratio. In addition, our data show that this low-grade immune activation may cause an imbalance in the production of neurotoxic and neuroprotective kynurenine metabolites in AUD.