Effectiveness of pain medication tapering in chronic pain patients: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to inventory all outcome measures that are affected by tapering in chronic noncancer pain and to investigate the effectiveness of tapering. METHODS: A literature search was conducted from inception to April 2024 in MEDLINE via PubMed, Web of Science, SCOPUS, EMBASE, and PsycINFO. RESULTS: The initial database search identified 3969 articles, which were screened by two independent reviewers. Studies evaluating pain medication tapering in adults with chronic noncancer pain were eligible for inclusion. In total, 57 and 34 articles were included in the systematic review and meta-analysis, respectively. Risk of bias assessment demonstrated poor, fair, and good quality in 30, 24, and three studies, respectively. Pain intensity was the most reported outcome measure, as reported in 28 studies. Furthermore, a random-effect three-level meta-analysis was performed. An overall effect size of 0.917 (95% confidence interval 0.61-1.22; P<0.001) was found, indicating a beneficial effect of tapering. In addition, a statistically significant improvement was demonstrated after tapering for pain intensity, headache disability, the number of headache days per month, anxiety, depression, the number of pills consumed per month, the number of days with medication intake per month, pain catastrophising, and pain interference. No statistically significant effect was observed for physical functioning, mental health-related quality of life, opioid use, pain self-efficacy, and physical health-related quality of life. CONCLUSIONS: This systematic review revealed a broad range of outcome measures affected by tapering. Owing to the high risk of bias of the included articles, the results of this meta-analysis must be interpreted with caution. SYSTEMATIC REVIEW PROTOCOL: CRD42023416343 (PROSPERO).

Successful Rapid Benzodiazepine Detoxification in an Acute Care Hospital: A Case Report.

Introduction: Benzodiazepine (BZD) dependence and withdrawal are significant public health concerns, affecting 15-30% of regular users within 4-6 weeks of administration. Rapid BZD tapering protocols in acute care settings can mitigate withdrawal symptoms and facilitate rehabilitation, yet are challenging due to variability in patient responses. Case presentation: We report a case of a 67-year-old male with a history of high-dose BZD use for panic disorder and depression and recent mild ischemic stroke, presenting with worsening left lower limb paralysis. The patient's complex medication regimen included multiple BZDs and other psychotropic drugs. Given the risks associated with high-dose BZD use, particularly in the context of stroke rehabilitation, a rapid detoxification protocol was initiated, aiming to reduce BZD dosage by 25% every 4 days. This approach led to successful detoxification within 2 weeks without significant withdrawal symptoms, facilitating stroke rehabilitation and improving prognosis. Discussion: This case highlights the effectiveness of a collaborative, rapid BZD tapering approach in an acute care setting, emphasizing the importance of patient cooperation, interdisciplinary communication, and careful monitoring of withdrawal symptoms. The case also underscores the potential benefits of replacing short-acting BZDs with long-acting ones, such as diazepam, to minimize withdrawal symptoms and support rehabilitation processes. Conclusion: Rapid BZD detoxification is feasible and can be safely achieved within a short-term hospital stay, demonstrating significant benefits for patients with BZD dependence. This case contributes to the evolving strategies for managing BZD dependence in acute care settings, advocating for tailored, patient-centered approaches to detoxification.

The effects of opioid tapering on select endocrine measures in men and women with head and neck cancer-a longitudinal 12-month study.

Introduction: Opioid treatment may affect endocrine measures in humans either through centrally or peripherally mediated mechanisms. There is a general lack of longitudinal studies examining endocrine measures in opioid-treated patients. Objectives: To longitudinally follow the levels of select endocrine measures in men and women with head and neck cancer for 1 year, who after having completed radiotherapy began tapering opioids. Methods: This was a prospective, longitudinal, observational study. Testosterone and estradiol were measured in men and women, respectively. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), and prolactin were measured in both sexes. Women were grouped based on if premenopausal or postmenopausal. Samples were collected when opioid tapering started and at 1, 3, 6, and 12 months after tapering start. Daily opioid doses at the same time points were registered. Results: Twenty-five men and 12 women were followed for 12 months. In men, testosterone levels increased significantly during the first month after opioid tapering started (P < 0.001). Levels of testosterone, FSH, DHEAS, and prolactin changed significantly in men during the study period. A moderate correlation between opioid dose reduction and testosterone level increase in men aged ≤60 years was found (r s = -0.577, 95% CI -0.854 to -0.044, P = 0.039). In postmenopausal women (n = 10), levels of FSH and LH changed significantly during the study period. Conclusion: Previously known effects of opioids on endocrine measures in humans seem to be reversible as select endocrine measures changed significantly in men and postmenopausal women after opioid tapering was initiated.

Verification of successful maintenance by serum drug level during a guided antipsychotic reduction to reach minimum effective dose (GARMED) trial.

BACKGROUND: Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages. METHODS: A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC-MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups. RESULTS: A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL. CONCLUSIONS: The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Research on Dual-Phase Composite Forming Process and Platform Construction of Radial Gradient Long Bone Scaffold.

The structure and composition of natural bone show gradient changes. Most bone scaffolds prepared by bone tissue engineering with single materials and structures present difficulties in meeting the needs of bone defect repair. Based on the structure and composition of natural long bones, this study proposed a new bone scaffold preparation technology, the dual-phase composite forming process. Based on the composite use of multiple biomaterials, a bionic natural long bone structure bone scaffold model with bone scaffold pore structure gradient and material concentration gradient changes along the radial direction was designed. Different from the traditional method of using multiple nozzles to achieve material concentration gradient in the scaffold, the dual-phase composite forming process in this study achieved continuous 3D printing preparation of bone scaffolds with gradual material concentration gradient by controlling the speed of extruding materials from two feed barrels into a closed mixing chamber with one nozzle. Through morphological characterization and mechanical property analysis, the results showed that BS-G (radial gradient long bone scaffolds prepared by the dual-phase composite forming process) had obvious pore structure gradient changes and material concentration gradient changes, while BS-T (radial gradient long bone scaffolds prepared by printing three concentrations of material in separate regions) had a discontinuous gradient with obvious boundaries between the parts. The compressive strength of BS-G was 1.00 ± 0.19 MPa, which was higher than the compressive strength of BS-T, and the compressive strength of BS-G also met the needs of bone defect repair. The results of in vitro cell culture tests showed that BS-G had no cytotoxicity. In a Sprague-Dawley rat experimental model, blood tests and key organ sections showed no significant difference between the experimental group and the control group. The prepared BS-G was verified to have good biocompatibility and lays a foundation for the subsequent study of the bone repair effect of radial gradient long bone scaffolds in large animals.

Impact of concomitant methotrexate on disease activity in patients with rheumatoid arthritis tapering abatacept: results from KOBIO registry.

Objectives: Tapering biologic agents can be considered for patients with stable disease activity in rheumatoid arthritis (RA). However, the specific strategy for abatacept is uncertain. This study aimed to examine the impact of tapering abatacept on disease activity in RA patients and assess the potential influence of concomitant methotrexate (MTX) treatment. Methods: Using data from the KOBIO registry, we included 505 1 year intervals from 176 patients with RA that initiated abatacept with concomitant MTX at baseline. The intervals were divided into two groups based on the dose quotient (DQ) of abatacept during each period (i.e., the tapering group (DQ < 1) and control group (DQ = 1)). The primary outcome was achieving DAS28-remission at 1 year intervals. Marginal structural models (MSM) were used to minimize confounding caused by an imbalance in time-varying variables. Results: Abatacept was tapered at 146 (28.9%) intervals, and the mean DQ was 0.68. DAS28-remission was achieved in 207 (41.8%) intervals. Tapering abatacept did not affect the odds of achieving DAS28-remission compared with the control group (OR 1.04 [0.67-1.62]). The odds remained unaffected in the subgroup that continued MTX (OR 1.42 [0.88-2.30]) but not in the subgroup that discontinued MTX (OR 0.26 [0.10-0.57]). The effects of interaction between tapering abatacept and concomitant MTX use on DAS28 and patient's functional status showed consistent results. The incidence of adverse events within a 1 year interval was comparable between the two groups. Conclusion: Withdrawal of MTX while tapering abatacept may compromise meeting the treatment goal for patients with RA.

[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.

Tapering and Sustained Remission of Thrombopoietin Receptor Agonists (TPO-RAs): Is it Time for Paediatric ITP?

Thrombopoietin receptor agonists (TPO-Ras; romiplostim/eltrombopag/avatrombopag) have demonstrated high efficacy rates (59-88%) and a good safety profile in clinical trials with adult patients with immune thrombocytopenia (ITP). Similar efficacy and safety results have been observed with romiplostim and eltrombopag in paediatric cohorts. Continuous treatment with TPO-RAs has shown durable responses with long-term use, up to 3 years. The effect of TPO-RAs was generally considered transient, as platelet counts tended to drop to baseline values after a short period of time (about 2 weeks), unless treatment was maintained. Several groups have reported successful discontinuation of TPO-RAs without the need for concomitant treatments. This is referred to as sustained remission off treatment (SROT). Both short- and medium-term treatment with TPO-RAs may reduce costs to our healthcare systems and, more importantly, may reduce the potential side effects that may be associated with continuous TPO-RA treatment. The issue of tapering and discontinuation of TPO-RAs in paediatric patients with ITP has received little attention to date. Given that paediatric ITP has much higher rates of spontaneous remission than ITP in adults, we consider that the possibility of SROT of TPO-RAs in paediatric patients with ITP is a neglected but very relevant issue in this subtype of the disease.

Immunosuppressives discontinuation after renal response in lupus nephritis: predictors of flares, time to withdrawal and long-term outcomes.

OBJECTIVES: The optimal duration of immunosuppressive (IS) treatment for lupus nephritis (LN) remains uncertain. We assessed the prevalence and predictors of IS tapering and discontinuation (D/C) in LN patients. METHODS: Data from 137 inception cohort LN patients were analyzed. We examined determinants of flares during tapering and after IS D/C, D/C achievement and time to D/C, and adverse long-term outcomes applying logistic and linear regression models. RESULTS: IS tapering was attempted in 111 (81%) patients, and D/C was achieved in 67.5%. Longer time to achieve complete renal response (CR) (OR : 1.07, p= 0.046) and higher SLEDAI-2K at tapering initiation (OR : 2.57, p= 0.008) were correlated with higher risk of renal flares during tapering. Persistent hydroxychloroquine use (≥2/3 of follow-up) (OR : 0.28, p= 0.08) and lower SLEDAI-2K 12 months before IS D/C (OR : 1.70, p= 0.013) decreased the risk of post-D/C flares. Adverse outcomes (>30% eGFR decline, chronic kidney disease, end-stage renal disease, death) at the end of follow-up (median124 months) were more frequent in patients with flares during IS tapering (53% vs 16%, p< 0.0038) but did not differ between IS D/C achievers and non-achievers. In proliferative LN, differences mirrored those in entire cohort, except for time to D/C, which occurred 20 months earlier in membranous vs proliferative LN (ß-coef=-19.8, p= 0.014). CONCLUSION: Earlier CR achievement and lower SLEDAI-2K at tapering initiation prevent flares during IS tapering, while persistent hydroxychloroquine use and lower SLEDAI-2K 12 months before IS D/C prevent post-D/C flares. Flares during tapering increase the risk of unfavorable long-term outcomes. Earlier IS D/C is feasible in membranous LN.

Mindfulness-Oriented Recovery Enhancement: Implementing an evidence-based intervention for chronic pain, opioid use, and opioid addiction in clinical settings.

The opioid crisis emerged in part due to the overprescribing of opioid analgesics for chronic pain. Although not the only source of the current epidemic of opioid use disorder (OUD), the prescription of opioids for chronic pain remains one vector for the development of opioid misuse and OUD. However, opioid tapering is not appropriate for all patients, and some patients may need to remain on opioid therapy for the long term. To reduce the risk of opioid-related harm among people with chronic pain and to treat incipient or entrenched addictive behaviours, new interventions are needed. This review discusses the clinical outcomes, biobehavioural mechanisms and implementation considerations for a novel, evidence-based intervention for chronic pain, opioid use and OUD called Mindfulness-Oriented Recovery Enhancement (MORE). MORE unites complementary aspects of mindfulness training, cognitive behavioural therapy and principles from positive psychology to simultaneously address addictive behaviour, emotion dysregulation and chronic pain by targeting brain reward and stress systems. MORE has been tested in 13 completed randomized clinical trials, including over 1300 patients, and has demonstrated efficacy against a range of active control conditions for reducing opioid dosing, opioid misuse, illicit drug use, depression, post-traumatic stress symptoms and chronic pain. Opportunities for implementing MORE include facilitating opioid tapering and promoting safe opioid use in primary care and specialty pain clinics, decreasing opioid misuse and enhancing medication-assisted treatment for OUD. Given evidence of MORE's efficacy, it is now time to consider disseminating this evidence-based treatment in the United States, the United Kingdom and worldwide.

Long-Term Safety and Performance of BioMime™ Morph Sirolimus-Eluting Coronary Stent System for Very Long Coronary Lesions.

Background: The use of multiple overlapping stents for long lesions in tapered coronary arteries has been associated with poor outcomes. This study was conducted to evaluate the 3-year safety and performance of the BioMime™ Morph sirolimus-eluting stent (SES) in very long (length 30 to ≤ 56 mm) coronary lesions in native coronary arteries with a reference vessel diameter of 2.25 to 3.50 mm. Methods: This was a prospective, single-center, observational, real-world, post-marketing surveillance study. Eligible patients were implanted with BioMime™ Morph SES. Patients were followed up at 6, 12, 24, and 36 months. Results: A total of 88 patients were enrolled in the study. The mean age was 58.72 ± 10.10 years and 82.95% were male. Most patients had angina (81.82%) and ischemic heart disease (78.41%), and there was a high prevalence of comorbidities like diabetes mellitus (59.09%), and hypertension (54.55%). A total of 92 long coronary de novo lesions were treated with BioMime™ Morph SES with an average stent length of 45.54 ± 10.20 mm. Device and procedural success rates were 100%. One patient died at 30 days and one case of myocardial infarction was recorded. The cumulative rates of major adverse cardiovascular events (MACEs) at 6, 12, 24, and 36 months were 3.41%, 6.82%, 7.95%, and 7.95%, respectively. There were no cases of stent thrombosis (ST), ischemia-driven target vessel revascularization, or ischemia-driven target lesion revascularization until 36 months of follow-up. Conclusion: BioMime™ Morph SES showed favorable outcomes up to 3 years in treating very long coronary lesions in native coronary arteries, as demonstrated by an acceptable rate of MACEs and absence of ST, based on clinical outcomes up to 3 years.

Taper versus discontinuation of tocilizumab in patients with giant cell arteritis: Real-world experience from a tertiary center.

INTRODUCTION: Following the approval of tocilizumab (TCZ) for giant cell arteritis (GCA), recent studies have shown a high relapse frequency after abrupt discontinuation of TCZ. However, a thorough exploration of TCZ tapering compared to abrupt discontinuation has never been undertaken. Likewise, adverse events have only been scarcely investigated in routine care. This study aimed to compare the incidence of relapses in GCA patients undergoing TCZ tapering compared to abrupt discontinuation. METHODS: We performed a single-center retrospective cohort study from 2012 to 2022. Data from GCA patients treated with TCZ was obtained from the Electronic Patients Record. Relapse-free survival is reported in Kaplan-Meier plots and tapering versus abrupt discontinuation were compared using a Wilcoxon-Brewlos-Gehan test. RESULTS: We included 155 patients receiving TCZ treatment for GCA, of which 104 discontinued TCZ. Among the 104 patients discontinuing TCZ, 42 (40 %) experienced a relapse within the first year. A total of 57 patients underwent taper with 6/38 (16 %) and 2/19 (11 %) relapsing while receiving TCZ every second or third week, respectively. In comparison, 59 patients underwent abrupt discontinuation with 27 (46 %) relapsing during follow-up. The patients undergoing abrupt TCZ discontinuation demonstrated a significantly shorter time to relapse compared to all tapered patients (p = 0.02) as well as patients tapered from weekly TCZ treatment to every second week (p < 0.01). Furthermore, 15 % of patients discontinued TCZ due to adverse events. CONCLUSION: This is the first study indicating that TCZ taper induced longer relapse-free survival than abrupt discontinuation, implying that taper may be favored over discontinuation in patients with GCA.

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.

Incidence of Fatigue Following Dexamethasone Administration for Supportive Therapy and Efficacy of Tapering in Perioperative Chemotherapy for Breast Cancer: A Retrospective Observational Study.

In perioperative chemotherapy for breast cancer, dexamethasone (DEX) is administered at high dose to prevent adverse effects. Abrupt cessation of high-dose DEX treatment induces fatigue, but the incidence of the fatigue is uncertain. In this study, we retrospectively evaluated the incidence of fatigue following DEX administration for supportive therapy and the improvement of fatigue with DEX tapering, a gradual reduction of the daily dose, in breast cancer patients. The subjects were 124 patients with breast cancer receiving epirubicin- or docetaxel-based regimens as perioperative chemotherapy. Of all patients, 16.1% of patients experienced fatigue after cessation of DEX administration. The severity of fatigue was grade 1 in 6.5% of patients, grade 2 in 8.1% of patients, and grade 3 in 1.6% of patients. There were no significant differences in dose and duration of DEX administration between the group with fatigue and the group without fatigue. In almost all patients with fatigue, DEX tapering was performed from the next cycle. The efficacy of DEX tapering was evaluated by comparing the grade and subjective symptoms. Following DEX tapering, the severity of fatigue was significantly reduced (p < 0.05), and the subjective symptom was improved in 94.7% of patients. Therefore, fatigue is occasionally induced after the cessation of DEX administration for supportive therapy in breast cancer patients. The tapering of DEX may be effective for fatigue.

A pilot multicentre randomised clinical trial to determine the effect of a pharmacist-partnered opioid tapering intervention before total hip or knee arthroplasty.

BACKGROUND: Opioid analgesic use before total hip or knee arthroplasty has been associated with worse postoperative outcomes. This pilot study aimed to examine the feasibility of a telehealth-based pharmacist-partnered opioid tapering intervention before elective primary hip or knee arthroplasty and its potential effectiveness compared with usual care. METHODS: This study was conducted at seven hospitals in New South Wales, Australia. Eligible patients were those aged ≥ 18 years, scheduled to undergo primary hip or knee arthroplasty for osteoarthritis and taking opioid analgesics pre-operatively. The intervention group participated in an opioid tapering telehealth service, a partnership between a pharmacist and general practitioner, for 3 months pre-operatively up to the day of surgery, while the control group received usual care. The primary outcomes of the study were to investigate the feasibility of the intervention (i.e. adherence to treatment) and potential effectiveness in decreasing baseline daily opioid dose by > 50% before surgery. RESULTS: Between December 2021 and June 2023, 70 patients were recruited and assigned randomly to the intervention group (n = 35) or control group (n = 35). Baseline characteristics were similar between groups. Thirty patients in each group completed their allocated treatment. All patients allocated to the intervention group completed at least one appointment with a pharmacist, with the median (IQR [range]) being 2 (1-4 [1-6]) appointments. The number of patients who successfully decreased their baseline daily opioid dose by ≥ 50% before surgery was 27/30 in the intervention group compared with 5/30 in the usual care group (p < 0.001). CONCLUSIONS: The findings of this pilot study support the feasibility of a telehealth-delivered, pharmacist-partnered opioid tapering service for patients scheduled for primary hip or knee arthroplasty. A broader multicentre study to examine the effectiveness of this intervention on clinical outcomes is warranted.

Opioid exit plans for tapering postoperative pain control in noncancer patients: a systematic review.

BACKGROUND: A growing number of countries have reported sharp increases in the use and harm of opioid analgesics. High rates of new opioid initiation are observed in postoperative patients. In response, various tertiary care institutions have developed opioid exit plans (OEPs) to curb potential opioid-related harm. METHODS: PubMed and Embase were systematically searched to identify, summarize, and compare the interventional elements of OEPs for postoperative patient populations published from January 1, 2000, to June 4, 2024. Two researchers independently screened the articles for eligibility following the PRISMA 2020 guidelines, extracted the data, and assessed the study quality and risk of bias. Data synthesis was performed for study characteristics, intervention details, efficacy, and development. RESULTS: A total of 2,585 articles were screened, eight of which met the eligibility criteria. All studies were conducted in North America and focused on orthopedic surgery patients following total hip or knee arthroplasty (n = 5) or neurosurgery (n = 3). Most studies (n = 7) included a pre-post (n = 4) or randomized clinical design (n = 3). Three studies were of good quality, and none had a low risk of bias. The interventions varied and ranged from educational sessions (n = 1) to individualized tapering protocols (n = 4) or a combination of the two (n = 2). Key elements were instructions on how to anticipate patients' postoperative need for opioid analgesics and tapering strategies based on 24-h predischarge opioid consumption. Six studies included efficacy as an endpoint in their analysis, of which four assessed statistical significance, with all four identifying that the OEPs were successful in reducing postoperative opioid use. CONCLUSION: Despite differences in design and implementation, the identified OEPs suggest that they are efficacious in reducing outpatient opioid consumption. They provide a robust estimate of postoperative analgesic requirements and a rationale for tapering duration and rate. However, more rigorous studies are needed to evaluate their real-world effectiveness.

Efficacy and safety of an early response-based tapering regimen of tocilizumab in children with systemic juvenile idiopathic arthritis.

INTRODUCTION: Systemic juvenile idiopathic arthritis (sJIA) is a distinct disease subset, with a poorer prognosis compared with other JIA subsets. Tocilizumab has an important role in the management of sJIA refractory to standard initial therapy. However, no specific guidelines exist for the tapering of tocilizumab therapy in sJIA, which could have implications on the overall cost and side effects of treatment. METHODS: This was an observational study which included 21 children with refractory sJIA, who were initially put on injection tocilizumab every 2 weekly, with subsequent dosing tapered to 4 weekly and 6 weekly intervals based on JIA ACR 70 responses at 12 and 24 weeks, respectively. The primary outcome at week 36 included JIA ACR 30, 50, 70, and 90 response rates with other efficacy and safety measures as secondary outcomes. RESULTS: At 36 weeks, JIA ACR 30, 50, 70, and 90 responses were observed in 90.5%, 90.5%, 71.4%, and 52.4% patients respectively along with significant improvement in hematological and inflammatory parameters. The mean prednisolone dose could be reduced from 0.54 to 0.13 mg/kg/day and around 29% patients were able to discontinue steroids altogether. No serious adverse events were recorded. With drug tapering, we could curtail on 26% of the total tocilizumab dose that would have been otherwise required on the continuous 2 weekly protocol. CONCLUSIONS: Tocilizumab, used in an early response-based tapering regimen, was both safe and efficacious in children with sJIA refractory to standard therapy. Larger and longer duration studies are required to further validate our observations.

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.