Impact of 30-day prescribed opioid dose trajectory on fatal overdose risk: A population-based, statewide cohort study.

BACKGROUND: Both increases and decreases in patients' prescribed daily opioid dose have been linked to increased overdose risk, but associations between 30-day dose trajectories and subsequent overdose risk have not been systematically examined. OBJECTIVE: To examine the associations between 30-day prescribed opioid dose trajectories and fatal opioid overdose risk during the subsequent 15 days. DESIGN: Statewide cohort study using linked prescription drug monitoring program and death certificate data. We constructed a multivariable Cox proportional hazards model that accounted for time-varying prescription-, prescriber-, and pharmacy-level factors. PARTICIPANTS: All patients prescribed an opioid analgesic in California from March to December, 2013 (5,326,392 patients). MAIN MEASURES: Dependent variable: fatal drug overdose involving opioids. Primary independent variable: a 16-level variable denoting all possible opioid dose trajectories using the following categories for current and 30-day previously prescribed daily dose: 0-29, 30-59, 60-89, or ≥90 milligram morphine equivalents (MME). KEY RESULTS: Relative to patients prescribed a stable daily dose of 0-29 MME, large (≥2 categories) dose increases and having a previous or current dose ≥60 MME per day were associated with significantly greater 15-day overdose risk. Patients whose dose decreased from ≥90 to 0-29 MME per day had significantly greater overdose risk compared to both patients prescribed a stable daily dose of ≥90 MME (aHR 3.56, 95%CI 2.24-5.67) and to patients prescribed a stable daily dose of 0-29 MME (aHR 7.87, 95%CI 5.49-11.28). Patients prescribed benzodiazepines also had significantly greater overdose risk; being prescribed Z-drugs, carisoprodol, or psychostimulants was not associated with overdose risk. CONCLUSIONS: Large (≥2 categories) 30-day dose increases and decreases were both associated with increased risk of fatal opioid overdose, particularly for patients taking ≥90 MME whose opioids were abruptly stopped. Results align with 2022 CDC guidelines that urge caution when reducing opioid doses for patients taking long-term opioid for chronic pain.

Belimumab corticosteroid-sparing treatment in systemic lupus erythematosus: a real-life observational study (BESST study).

Data about the impact of Belimumab on corticosteroid sparing in real life are scarce. To assess the corticosteroid-sparing effect among patients with systemic lupus erythematosus (SLE) treated with Belimumab in real-life settings. Multicentric observational retrospective study including patients with SLE and having received Belimumab for at least 6 months between 2011 and 2020, in eight French hospitals. "Low dose" referred to patients receiving up to 7.5 mg of prednisone a day and "Very low dose" to those receiving strictly ≤ 5 mg prednisone a day The primary endpoint was the reduction of daily prednisone dose after six months of Belimumab. The secondary endpoint was a change in the proportion of patients with low or very low dose of prednisone as well as those without prednisone during the Belimumab course. Censoring occurred for patients who stopped Belimumab. Bivariate analyses were performed using the Wilcoxon signed-rank test. The threshold for statistical significance was set at p < 0.05. Thirty patients were included. All were female with a median age of 38 years. A significant reduction in prednisone dose was observed at month 6 (10 [7-20] vs 6.75 [2-9] mg, p < 0.0001), continued until month 12 (10 [7-20] mg vs 5 [0-7.12] mg, p < 0.001) and was sustained until month 24. The proportion of patients with very low dose of prednisone and those without prednisone progressively increased during the Belimumab course. Introducing Belimumab in patients with SLE, in real-life conditions, is associated with early and sustained corticosteroid-sparing effect.

Exploring TNFi drug-levels and anti-drug antibodies during tapering among patients with inflammatory arthritis: secondary analyses from the randomised BIODOPT trial.

To evaluate tumour necrosis factor inhibitor (TNFi) drug-levels and presence of anti-drug antibodies (ADAb) in patients with inflammatory arthritis who taper TNFi compared to TNFi continuation. Patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis on stable TNFi dose and in low disease activity ≥ 12 months were randomised (2:1) to disease activity-guided tapering or control. Blood samples at baseline, 12- and 18-months were evaluated for TNFi drug-levels and ADAb. In total, 129 patients were randomised to tapering (n = 88) or control (n = 41). Between baseline and month 18, a significant shift in TNFi drug-levels were observed in the tapering group resulting in fewer patients with high drug-levels (change: - 14% [95% CI - 27 to - 1%]) and more with low drug-levels (change: 18% [95% CI 5-31%]). Disease activity was equivalent between groups at 18 months, mean difference: RA - 0.06 (95% CI - 0.44 to 0.33), PsA 0.03 (95% CI - 0.36 to 0.42), and axSpA 0.16 (- 0.17 to 0.49), equivalence margins ± 0.5 disease activity points. ADAb were detected in eight patients, all from the tapering group. TNFi drug-level category or ADAb were not predictive for achieving successful tapering at 18 months. TNFi drug-levels decreased during tapering which indicate adherence to the tapering algorithm. Despite the difference in TNFi drug-levels at 18 months, disease activity remained equivalent, and only few tapering patients had detectable ADAb. These data do not support using TNFi drug-level and/or ADAb to guide the tapering decision but future research with larger trials is needed.Trial registration: EudraCT: 2017-001970-41, December 21, 2017.

Outcomes of the second withdrawal of anti-seizure medication in patients with pediatric-onset epilepsy.

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.

Disentangling pharmacological and expectation effects in antidepressant discontinuation among patients with fully remitted major depressive disorder: study protocol of a randomized, open-hidden discontinuation trial.

BACKGROUND: Antidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence. METHODS: To disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be manipulated by varying verbal instructions using an open-hidden paradigm. Within the open trial arms, participants will receive full information about treatment, i.e., high expectation. Within the hidden trial arms, participants will be informed about a 50% chance of discontinuing versus remaining on their antidepressant, i.e., moderate expectation. A total of N = 196 participants will be randomly assigned to either of the four experimental groups: open discontinuation (OD; n = 49), hidden discontinuation (HD; n = 49), open continuation (OC; n = 49), or hidden continuation (HC; n = 49). Discontinuation symptom load during the 13-week experimental phase will be our primary outcome measure. Secondary outcome measures include discontinuation symptom load during the subsequent 39-week clinical observation phase, recurrence during the 13-week experimental period, recurrence over the course of the complete 52-week trial evaluated in a time-to-event analysis, and stress, anxiety, and participants' attentional and emotional processing at 13 weeks post-baseline. Blood and saliva samples will be taken as objective markers of antidepressant blood serum level and stress. Optional rsfMRI measurements will be scheduled. DISCUSSION: Until today, no study has explored the interplay of pharmacological effects and patients' expectations during antidepressant discontinuation. Disentangling their effects has important implications for understanding mechanisms underlying adverse discontinuation symptoms. Results can inform strategies to manage discontinuation symptoms and optimize expectations in order to help patients and physicians discontinue antidepressants more safely and effectively. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05191277), January 13, 2022.

Psychiatric Deprescribing: A Narrative Review.

OBJECTIVE: Psychiatric deprescribing is an intervention where psychiatric medications are reduced or discontinued with the goal to improve health and reduce unnecessary risks. The purpose of this study was to synthesize the literature related to psychiatric deprescribing to discuss practice and research implications. METHODS: A structured search of the literature was conducted from May to September 2022, yielding 29 articles meeting inclusion criteria. Articles were reviewed and synthesized. RESULTS: Psychiatric deprescribing is a complex process with many potential facilitators and barriers. The extant literature provides insight into current gaps in knowledge and implications for clinical practice and research. CONCLUSIONS: In current clinical practice, psychiatric deprescribing is a priority but there are significant barriers. Several areas of future research could be pursued to better support evidence-based practice in this area.

Deprescribing: An umbrella review.

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.

The effects of antipsychotic discontinuation or maintenance on the process of recovery in remitted first-episode psychosis patients - A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The optimal duration of antipsychotic treatment following remission of first-episode psychosis (FEP) is uncertain, considering potential adverse effects and individual variability in relapse rates. This study aimed to investigate the effect of antipsychotic discontinuation compared to continuation on recovery in remitted FEP patients. METHODS: CENTRAL, MEDLINE (Ovid), Embase, and PsycINFO databases were searched on November 2, 2023, with no language restrictions. RCTs evaluating antipsychotic discontinuation in remitted FEP patients were selected. The primary outcome was personal recovery, and secondary outcomes included functional recovery, global functioning, hospital admission, symptom severity, quality of life, side effects, and employment. Risk of bias was assessed using the Cochrane risk-of-bias tool 2, and the certainty of evidence was evaluated with GRADE. Meta-analysis used a random-effect model with an inverse-variance approach. RESULTS: Among 2185 screened studies, 8 RCTs (560 participants) were included. No RCTs reported personal recovery as an outcome. Two studies measured functional recovery, and discontinuation group patients were more likely to achieve functional recovery (RR 2.19; 95% CIs: 1.13, 4.22; I2 = 0%; n = 128), although evidence certainty was very low. No significant differences were found in hospital admission, symptom severity, quality of life, global functioning, or employment between the discontinuation and continuation groups. CONCLUSIONS: Personal recovery was not reported in any antipsychotic discontinuation trial in remitted FEP. The observed positive effect of discontinuation on functional recovery came from an early terminated trial and an RCT followed by an uncontrolled period. These findings should be interpreted cautiously due to very low certainty of evidence.

[Adverse effects of the tezacaftor/ivacaftor/elexacaftor combination that may lead to discontinuation: About a series of 10 cases]. / Effets indésirables de l'association tezacaftor/ivacaftor/elexacaftor pouvant mener à un arrêt de traitement : à propos d'une série de 10 cas.

INTRODUCTION: Cystic fibrosis transmembrane regulator (CFTR) channel modulators (ivacaftor, lumacaftor, tezacaftor and elexacaftor) represent a major advance in the management of cystic fibrosis. However, few data are available on the real-life safety profile of these medications, in particular on adverse events that may lead to their discontinuation. The aim of this study is to describe the characteristics and evolution of adverse reactions to the tezacaftor/ivacaftor/elexacaftor combination that led to discontinuation and were reported to the Centre régional de pharmacovigilance (CRPV) in Rennes (France). MATERIALS AND METHODS: A retrospective study was conducted from December 2021 to May 2023, focusing on cases of discontinuation of the tezacaftor/ivacaftor/elexacaftor combination due to the occurrence of one or more adverse effects, and reported to the CRPV of Rennes, France. RESULTS: Ten cases of drug discontinuation were reported to the Rennes CRPV (6 women/4 men). Adverse effects mainly involved neuropsychiatric disorders (n=6), followed by liver disorders (n=2), ear, nose and throat disorders (n=1), and digestive disorders (n=1). The average duration of treatment at discontinuation was 339.8 [39-668] days. The drug was reintroduced in 7 patients on average 48.7 [7-123] days after discontinuation, with a dosage adjustments (n=4) consisting of changes in dosing times or a reduction in daily doses, with varying success in alleviating adverse symptoms depending on the case. CONCLUSION: This small case series suggests that neuropsychiatric adverse effects may occur more frequently than initially described after initiation of tezacaftor/ivacaftor/elexacaftor, and should be carefully screened and monitored. Dosage or administration schedule modifications may be considered for patients experiencing these adverse effects. Further pharmacovigilance studies are needed to better understand the adverse effect profiles of "caftors", their possible risk factors, and the impact of adjusting dosing modalities.

Minimal effective dose of maintenance steroid therapy for relapse of cryptogenic organizing pneumonia.

BACKGROUND: Long-term maintenance steroid therapy (MST) is frequently required for repeated relapses of cryptogenic organizing pneumonia (COP); however, the optimal minimal dose has not been clarified. Therefore, this study evaluated the minimal MST dose required to prevent repeated relapses and identify relapse predictors. METHODS: We retrospectively reviewed the medical records of patients with steroid-treated COP and compared background factors between the non-relapse and relapse groups. We also reviewed the treatment course in the relapse group and determined the minimal effective steroid dose based on the MST dose at relapse events and the current relapse prevention dose. RESULTS: In total, 48 patients were identified, including 27 (56%) in the non-relapse group and 21 (44%) in the relapse group. Receiver operating characteristic curve analysis identified prednisolone at 5 mg/day as the optimal cut-off value in the relapse group. Relapse-free time in patients with relapsed COP was significantly longer in the MST dose ≥5 mg/day group than in the <5 mg/day group (log-rank P = 0.003; hazard ratio, 0.19; 95% confidence interval [CI], 0.04-0.60). Multivariate logistic regression analysis demonstrated that a high eosinophil percentage and CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) were predictors of relapse (odds ratio [OR], 1.12; 95% CI, 1.02-1.23; P = 0.008 and OR, 3.87; 95% CI, 1.29-11.6; P = 0.008, respectively). CONCLUSIONS: Our results indicate that 5 mg/day of prednisolone may be the minimal effective dose for preventing repeated relapses, and a high BALF eosinophil percentage and CD4/CD8 ratio are independent predictors of relapse.

Comparing Two Naloxone Tapering Methods in Management of Methadone Intoxication; a Quasi-experimental Study.

Introduction: Even though naloxone is the main treatment for methadone poisoning treatment there are controversies about the proper method of its tapering. This study aimed to compare two methods in this regard. Method: This study was a prospective, single-blind pilot quasi-experimental study on non-addicted adult patients poisoned with methadone. Patients were randomly divided into 2 groups. In one group, after stabilization of respiratory conditions and consciousness, naloxone was tapered using the half-life of methadone and in the other group, naloxone was tapered using the half-life of naloxone. Recurrence of symptoms and changes in venous blood gas parameters were compared between groups as outcome. Results: 52 patients were included (51.92% female). 31 cases entered Group A (tapering based on methadone's half-life) and 21 cases entered Group B (tapering based on naloxone's half-life). The two groups were similar regarding mean age (p = 0.575), gender distribution (p = 0.535), the cause of methadone use (p = 0.599), previous medical history (p = 0.529), previous methadone use (p = 0.654), drug use history (p = 0.444), and vital signs on arrival to emergency department (p = 0.054). The cases of re-decreasing consciousness during tapering (52.38% vs. 25.81%; p = 0.049) and after discontinuation of naloxone (72.73% vs. 37.50%; p = 0.050) were higher in the tapering based on naloxone half-life group. The relative risk reduction (RRR) for naloxone half-life group was -1.03 and for methadone half-life group was 0.51. The absolute risk reduction (ARR) was 0.27 (95% confidence interval (CI) = 0.01-0.53) and the number needed to treat (NNT) was 3.7 (95% CI= 1.87- 150.53). There was not any statistically significant difference between groups regarding pH, HCO3, and PCO2 changes during tapering and after naloxone discontinuation (p > 0.05). However, repeated measures analysis of variance (ANOVA), showed that in the tapering based on methadone's half-life group, the number of changes and stability in the normal range were better (p < 0.001). Conclusion: It seems that, by tapering naloxone based on methadone's half-life, not only blood acid-base disorders are treated, but they also remain stable after discontinuation and the possibility of symptom recurrence is reduced.

Appropriate use of tapentadol: focus on the optimal tapering strategy.

OBJECTIVE: Due to its opioid and non-opioid mechanism of action, tapentadol is considered an atypical opioid with improved gastrointestinal tolerability versus traditional opioids. As for all opioid analgesics it is important to understand how to discontinue a treatment when it is not needed anymore. The aim of this article was to provide an overview of opioid therapy in non-cancer pain, with a specific focus on tapering of tapentadol in patients with chronic non-cancer pain, and suggestions on how to achieve tapering. METHODS: Studies for this narrative review were identified via PubMed using a structured search strategy, focusing on management of chronic non-cancer pain with opioids, and the efficacy, tolerability, and pharmacology of tapentadol prolonged release. Publications were limited to English-language articles published within the last ∼10 years. RESULTS: The review discusses the use and discontinuation of opioids in general, as well clinical data on discontinuation of tapentadol specifically. We provide a flow chart, which can be used by clinicians in the context of their own clinical experience to appropriately taper tapentadol in patients with chronic non-cancer pain. The flow chart can be easily tailored to individual patient characteristics, duration of tapentadol treatment, response to progressive dosage reduction, and likelihood of withdrawal symptom occurrence. CONCLUSIONS: While tapentadol is associated with a low frequency of opioid withdrawal symptoms after abrupt discontinuation, use of a tapering strategy is prudent. Tapering strategies developed for opioids in general can potentially be safely individualized in tapentadol-treated patients, although research on tapering strategies for tapentadol is required.

Two case reports of tapering sedative-hypnotic drugs through classical conditioning using herbal medicine (CARE-compliant).

RATIONALE: Sedative-hypnotic drugs (SHDs) used for insomnia are recommended for short-term use owing to concerns regarding abuse and dependence. Nevertheless, drug discontinuation is challenging owing to rebound insomnia that occurs when the SHD is ceased. Therefore, a strategy is required to reduce or discontinue SHDs, while minimizing rebound insomnia. PATIENT CONCERNS: The present report discusses the cases of a 72-year-old man and 27-year-old man with insomnia. Both patients had been taking SHDs for more than 2 months. DIAGNOSES: Both patients were diagnosed with primary insomnia. INTERVENTIONS AND OUTCOMES: After 2 weeks of classical conditioning (CC) using Hwangryunhaedok-tang (HHT), both patients succeeded in tapering SHD; the Korean version of the insomnia severity index of patient 1 dropped from 14 to 5, and that of patient 2 dropped from 28 to 11. In the final follow-up, the index dropped to 2 and 3, respectively. LESSONS: The CC, a concept emerging in psychology, could be a new strategy for tapering drugs. In this case, SHDs, which had been taken for a long time, were successfully reduced or discontinued through CC using HHT. Herbal medicine such as HHT is selected as a neutral stimulus for CC because the risk of rebound phenomenon is low as the compounds of herbal medicine have high structural similarities with human metabolites. Both patients in this study reported no particular challenges when HHT was discontinued. However, further studies are needed that will assist in tapering anticonvulsants or steroids as well as SHDs.

Optimizing treatment for older adults with depression.

This review presents a comprehensive guide for optimizing medication management in older adults with depression within an outpatient setting. Medication optimization involves tailoring the antidepressant strategy to the individual, ensuring the administration of appropriate medications at optimal dosages. In the case of older adults, this process necessitates not only adjusting or changing antidepressants but also addressing the concurrent use of inappropriate medications, many of which have cognitive side effects. This review outlines various strategies for medication optimization in late-life depression: (1) Utilizing the full dose range of a medication to maximize therapeutic benefits and strive for remission. (2) Transitioning to alternative classes (such as a serotonin and norepinephrine reuptake inhibitor [SNRI], bupropion, or mirtazapine) when first-line treatment with selective serotonin reuptake inhibitors [SSRIs] proves inadequate. (3) Exploring augmentation strategies like aripiprazole for treatment-resistant depression. (4) Implementing measurement-based care to help adjust treatment. (5) Sustaining an effective antidepressant strategy for at least 1 year following depression remission, with longer durations for recurrent episodes or severe presentations. (6) Safely discontinuing anticholinergic medications and benzodiazepines by employing a tapering method when necessary, coupled with counseling about the benefits of stopping them. Additionally, this article explores favorable medications for depression, as well as alternatives for managing anxiety, insomnia, allergy, overactive bladder, psychosis, and muscle spasm in order to avoid potent anticholinergics and benzodiazepines.

Antidepressant Tapering Is Not Routine But Could Be.

INTRODUCTION: When antidepressants are discontinued, severe withdrawal symptoms are possible. Some patients have few or no problems stopping, whereas others struggle. That struggle can be minimized or prevented with careful dose tapering. How often is that done? METHODS: Using 7 years of medical records, we determined the percentage of patients who received a prescription for the lowest available dose of their antidepressant before it was discontinued, as an indicator of a deliberate taper. RESULTS: Over that period, 8.9% of patients had evidence of tapering. The percentage increased from 4.9% in 2014 to a plateau around 10% in the past 4 years. DISCUSSION: While reports of severe withdrawal are increasingly recognized and must be addressed, our data suggest that many patients can discontinue their antidepressants without a taper through the lowest dose. However, it is difficult to identify which patients will struggle without a careful taper. A "one-size-fits-all" taper approach is recommended, balancing the need for withdrawal prevention with the need to avoid unnecessary complexity for the majority of patients. The first decrement is key for all patients: it must go well. Thereafter many patients may accelerate but all should receive a prescription for the lowest available dose of their antidepressant.

Blended care to discontinue benzodiazepine receptor agonists use in patients with chronic insomnia disorder: a pragmatic cluster randomized controlled trial in primary care.

STUDY OBJECTIVES: International guidelines recommend using benzodiazepine receptor agonists (BZRA) for maximally four weeks. Nevertheless, long-term use for chronic insomnia disorder remains a common practice. This study aimed to test the effectiveness of blended care for discontinuing long-term BZRA use in general practice. METHODS: A pragmatic cluster randomized controlled superiority trial compared blended care to usual care through urine toxicology screening. In the intervention, care by the general practitioner (GP) was complemented by an interactive e-learning program, based on cognitive behavioral therapy for insomnia. Adults using BZRA daily for minimally 6 months were eligible. Participants were clustered at the level of the GP surgery for allocation (1:1). Effectiveness was measured as the proportion of patients who had discontinued at one-year follow-up. Data analysis followed intention-to-treat principles. RESULTS: In total, 916 patients in 86 clusters, represented by 99 GPs, were randomized. Primary outcome data was obtained from 727 patients (79%). At one-year follow-up, 82 patients (18%) in blended care, compared to 91 patients (20%) in usual care, had discontinued. There was no statistically significant effect for the intervention (OR: 0.924; 95% CI: 0.60; 1.43). No adverse events were reported to the research team. CONCLUSIONS: The findings did not support the superiority of blended care over usual care. Both strategies showed clinical effectiveness, with an average of 19% of patients having discontinued at one-year follow-up. Further research is important to study the effect of structurally implementing digital interventions in general practice. CLINICAL TRIAL: Big Bird trial; KCE-17016. This trial is registered at clinicaltrials.gov (NCT03937180).

A Survey on Opioid Tapering Practices, Policies, and Perspectives by Pain and Palliative Care Pharmacists.

Opioid tapering is an essential clinical tool to utilize for a variety of reasons, including safety and analgesic optimization. The need for individualized regimens reveals a corresponding need for healthcare providers who can actively manage patients throughout the process. Pharmacists have taken on an integral role for achieving success in opioid tapering. This survey was conducted to describe the current opioid tapering practices of pain and palliative care pharmacists. A Qualtrics survey was offered to the Society of Pain and Palliative Care Pharmacist members. The majority (87%) indicated they specialized in pain management. Almost all respondents (98%) reported providing tapering recommendations and 82% reported being involved with patient monitoring throughout the taper. The majority (multiple responses could be chosen) noted that the indication for initiating an opioid taper was due to abuse/misuse (91%), reduced overall efficacy (89%), and adverse drug reactions (78%). The most common follow-up intervals during tapering were weekly (15%), every 2 weeks (22%), and every 4 weeks (44%). This practice-based survey, though small, showed that pharmacists in pain management and palliative care are actively involved in opioid tapering. This survey will hopefully serve as a foundation for continuing research into opioid tapering and the pharmacist's role therein.

Antiepileptic-drug tapering and seizure recurrence: Correlation with serum drug levels and biomarkers in persons with epilepsy.

OBJECTIVES: Antiepileptic-drug (AED) serum level and inflammatory biomarkers are primarily monitored/assessed during epilepsy treatment for effective seizure control; however, their correlation with seizure recurrence (SR) following AED-tapering has not been established, and this is being investigated in this study. MATERIALS AND METHODS: This prospective observational study enrolled persons with epilepsy (PWE) on AED monotherapy and going to start tapering after being seizure-free for ≥2 years. Data regarding seizure episodes, AED-treatment, and adverse events (using Liverpool Adverse Event profile [LAEP]-score) were recorded. Serum AED levels using high-performance liquid chromatography and biomarkers levels through enzyme-linked immunosorbent assay kits were estimated at AED-tapering commencement and at 6 months/SR time. RESULTS: Among 129 enrolled PWE (levetiracetam [n = 52], valproate [n = 34], carbamazepine [n = 29], and phenytoin [n = 14]), SR occurred in 23.3% during follow-up (range 12-44 months). PWE with subtherapeutic serum AED level at the onset of tapering had higher SR (P = 0.004) than those with therapeutic or higher levels. Levetiracetam-treated PWEs with SR have significantly low AED levels than PWE with no-SR (P < 0.001). PWE had significantly raised inflammatory biomarkers (interleukin [IL]-1 ß, tumor necrosis factor [TNF]-α, IL-6, and high-mobility group box protein 1) and decreased IL-10 than healthy control subjects. SR and no-SR groups did not differ significantly in inflammatory markers except for higher IL-1 ß and TNF-α levels in SR group (P = 0.001, 0.02, respectively). Improvement in LAEP score was observed in follow-up visits without any difference between SR and no-SR groups. CONCLUSION: Low serum AED levels (especially levetiracetam) and raised levels of TNF-α and IL-1 ß during tapering commencement had a higher association with SR following AED-tapering.

Effect of treatment with Fufang Huangqi decoction on dose reductions and discontinuation of pyridostigmine bromide tablets, prednisone, and tacrolimus in patients with type I or II myasthenia gravis.

OBJECTIVE: To investigate the clinical efficacy of Fufang Huangqi decoction in combination with pyridostigmine bromide tablets, prednisone, and tacrolimus in the treatment of type I and II myasthenia gravis (MG) through changes in the clinical symptom scores of 100 patients with type I and II MG. This study also aimed to examine dose reductions and dis-continuation of these 3 Western medicines after administration of Fufang Huangqi decoction. METHODS: The clinical data on 100 patients with type I or II MG who were treated in the outpatient department of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China, between June 2017 and June 2020 were collected. The patients were divided into 4 groups based on whether they had taken pyridostigmine bromide tablets, prednisone, and/or tacrolimus at the time of their hospital visit: the Fufang Huangqi decoction group (group A), the pyridostigmine bromide tablets + Fufang Huangqi decoction group (group B), the pyridostigmine bromide tablets + prednisone + Fufang Huangqi decoction group (group C), and the pyridostigmine bromide tablets + tacrolimus + Fufang Huangqi decoction group (group D). The average treatment time was (15.6 ± 11.5) months (range: 0.5-55 months). Changes in the clinical symptom scores of the 4 groups of patients after medication administration and dose reductions and discontinuation of the 3 Western medicines were analyzed. RESULTS: An overall effectiveness rate of 86.00% was achieved in the 100 patients after treatment for (15.6 ± 11.5) months (range 0.5-55 months). The effectiveness rates were 85.71% in group A, 88.24% in group B, 76.92% in group C, and 80.00% in group D. The dosage of pyridostigmine bromide was reduced for 69.12% of the patients in group B for the first time after (4.2 ± 4.1) months, and 45.59% of the patients in group B discontinued pyridostigmine bromide after (8.8 ± 6.1) months. The dosage of pyridostigmine bromide was reduced for 46.15% of the patients in group C for the first time after (5.3 ± 3.4) months, and 23.08% of the patients in group C discontinued pyridostigmine bromide after (19.8 ± 11.0) months; 76.92% reduced hormone dosage after (2.8 ± 1.9) months, and 23.08% discontinued hormone treatment after (6.7 ± 2.9) months. The dosage of pyridostigmine bromide was reduced for 1 patient in group D after 1 month; this patient discontinued pyridostigmine bromide after 3 months and reduced tacrolimus dosage after 5 months. One patient in group D discontinued pyridostigmine bromide and tacrolimus on his own initiative at 0.5 months and took Fufang Huangqi decoction for 2 months without discontinuing Western medicine. CONCLUSION: Fufang Huangqi decoction is effective for the treatment of type I and II MG and improves the associated clinical symptoms. Moreover, this agent is conducive to dose reductions and discontinuation of basic Western medicines, thereby reducing the side effects experienced by patients.

Benzodiazepines and Related Sedatives.

Benzodiazepine and related sedative use has been increasing. There has been a growing number of unregulated novel psychoactive substances, including designer benzodiazepines. Benzodiazepines have neurobiological and pharmacologic properties that result in a high potential for misuse and physical dependence. Options for discontinuing long-term benzodiazepine use include an outpatient benzodiazepine taper or inpatient withdrawal management at a hospital or detoxification facility. The quality of evidence on medications for benzodiazepine discontinuation is overall low, whereas cognitive behavioral therapy has shown the most benefit in terms of behavioral treatments. Benzodiazepines may also have significant adverse effects, increasing the risk of overdose and death.