Apomorphine titration with and without anti-emetic pretreatment in patients with Parkinson’s disease experiencing OFF episodes: A modified Delphi panel
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SUBMITTER: Isaacson S
PROVIDER: S-EPMC11338955 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundOn-demand treatments can treat OFF episodes in Parkinson's disease, however, there is limited information regarding when to prescribe them.ObjectiveDevelop expert consensus to determine appropriate clinical factors for considering on-demand treatments.MethodsUsing a RAND/UCLA modified Delphi panel method, a panel developed consensus on the use of on-demand treatments for OFF episodes.ResultsThe panel agreed on-demand treatments were appropriate when OFF episodes were associated with greater functional impact and interfered with basic daily activities. The panel also agreed on-demand treatment may be appropriate for patients with morning akinesia and/or delayed ON of first levodopa dose and >1 type of OFF episode (eg, early morning OFF or wearing OFF regardless of frequency).ConclusionsExperts agreed on-demand treatment is appropriate for many patients with OFF episodes. The greater the functional impact of OFF episodes, the more likely experts agreed that on-demand treatment is appropriate to prescribe.
| S-EPMC10105118 | biostudies-literature
Project description:BackgroundApomorphine sublingual film (SL-APO) and subcutaneous apomorphine (SC-APO) have been used for the treatment of OFF episodes in Parkinson's disease (PD). No study has prospectively compared efficacy and safety of these formulations.ObjectiveTo compare SL-APO with SC-APO for treatment of OFF episodes in PD.MethodsAn open-label, randomized, crossover study assessed SL-APO versus SC-APO in patients with PD and OFF episodes (N = 113). Doses were optimized in randomly assigned order. SL-APO dose initiation (10 mg) occurred in clinic; further dose optimization (15-30 mg; 5-mg increments) occurred primarily at home. SC-APO dosing (2-6 mg; 1-mg increments) occurred entirely in clinic. After a 3-7-day washout, patients were randomized 1 : 1 to 4 weeks of treatment with their optimized dose of SL-APO or SC-APO, followed by washout and 4 weeks of crossover treatment.ResultsPropensity score matching applied on 159 patients (STN-DBS n = 75, MED n = 84) resulted in 40 patients in each treatment group. At 36-month follow-up, STN-DBS led to significantly better PDSS and PDQ-8 change scores, which were significantly correlated. We observed no significant effects for HADS and no significant correlations between change scores in PDSS, HADS, and LEDD.ConclusionsWe report Class IIb evidence of beneficial effects of STN-DBS on quality of sleep at 36-month follow-up, which were associated with QoL improvement independent of depression and dopaminergic medication. Our study highlights the importance of sleep for assessments of DBS outcomes.ResultsNo difference was observed between SL-APO and SC-APO for change from predose to 90 minutes postdose in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score at week 4 (primary endpoint), assessed by a blinded rater (-13.6 vs. -13.8, respectively; p = NS). Overall, 72.2% of patients preferred SL-APO compared with SC-APO/no preference (p = 0.0002) per the Treatment Preference Questionnaire (secondary endpoint). Patients reported greater satisfaction with SL-APO compared with SC-APO, per mean scores of convenience (73.7 vs. 53.5) and global satisfaction (63.9 vs. 57.6) on the Treatment Satisfaction Questionnaire for Medication (other endpoint). The safety profiles of both treatments were generally comparable and were well-tolerated.ConclusionsPatients reported overall preference for and greater satisfaction with SL-APO over SC-APO.
| S-EPMC10741320 | biostudies-literature
Project description:Background: "On-demand" treatments approved in the United States (US) for "OFF" episodes in Parkinson's disease (PD) include apomorphine hydrochloride injection (SC-APO), apomorphine sublingual film (APL), and levodopa inhalation powder (CVT-301). APL received US approval in 2020, and its cost-effectiveness has not been compared with SC-APO and CVT-301. Objective: To develop a cost-effectiveness analysis model comparing APL versus SC-APO and CVT-301 for treatment of patients with PD experiencing "OFF" episodes from a US payer perspective. Methods: The model estimated total costs and effectiveness for each comparator arm, informed from the treatments' pivotal studies or literature, over a 10-year horizon. Total and incremental patient costs (in 2020 US dollars), total time spent without "OFF" episode symptoms, and quality-adjusted life years (QALY) gained were summarized and compared. Incremental cost-effectiveness ratios for APL versus SC-APO and CVT-301 were estimated and expressed as incremental patient costs per patient QALY gained and incremental cost per "OFF" hour avoided. Scenario analyses varying inputs and including caregiver costs were also conducted. Results: In the base case, APL had the lowest total "on-demand" treatment costs ($42,095) compared with SC-APO ($276,320; difference: -$234,225) and CVT-301 ($69,577; difference: -$27,482) over the 10-year horizon. APL was also associated with the highest utility, with incremental QALYs of 0.019 versus SC-APO and 0.235 versus CVT-301. APL was dominant over CVT-301 in terms of incremental cost per "OFF" hour, and dominant over both CVT-301 and SC-APO in terms of incremental cost per QALY gained. In all scenario analyses, APL was dominant against both SC-APO and CVT-301, confirming the robustness of the base-case results. Discussion: APL was dominant compared with both comparator arms, being less costly and more effective on average than SC-APO and CVT-301 in terms of QALYs. For SC-APO, cost-effectiveness of APL was driven by lower "on-demand" treatment costs and adverse event-related disutilities. For CVT-301, cost-effectiveness of APL was driven by lower "on-demand" treatment costs and substantially higher efficacy. Conclusions: From a US payer perspective, APL represents a cost-effective option compared with SC-APO and CVT-301 for treatment of "OFF" episodes in patients with PD.
| S-EPMC8809356 | biostudies-literature
Project description:BackgroundNausea is common upon initiating dopamine agonists in patients with Parkinson's disease (PD); however, pretreatment with an antiemetic is recommended only when initiating apomorphine formulations.ObjectiveEvaluate the need for prophylactic antiemetic use during dose optimization of apomorphine sublingual film (SL-APO).MethodsA post hoc analysis of a Phase III study evaluated nausea and vomiting treatment-emergent adverse events in patients with PD who underwent SL-APO dose optimization (10-35 mg; 5-mg increments) to achieve a tolerable FULL ON. Frequencies of nausea and vomiting were described for patients who did versus did not use an antiemetic during dose optimization and by patient subgroups based on extrinsic and intrinsic factors.ResultsOverall, 43.7% (196/449) of patients did not use an antiemetic during dose optimization; most of these patients (86.2% [169/196]) achieved an effective and tolerable SL-APO dose. In patients who did not use an antiemetic, nausea (12.2% [24/196]) and vomiting (0.5% [1/196]) were uncommon. An antiemetic was used in 56.3% (253/449) of patients, with 17.0% (43/253) and 2.4% (6/253) experiencing nausea and vomiting, respectively. All events of nausea (14.9% [67/449]) and vomiting (1.6% [7/449]) were of mild-to-moderate severity except for 1 event each. Irrespective of antiemetic use, among patients without baseline dopamine agonist use, nausea and vomiting rates were 25.2% (40/159) and 3.8% (6/159); in those already using dopamine agonists, rates were 9.3% (27/290) and 0.3% (1/290).ConclusionProphylactic treatment with an antiemetic is not necessary for most patients who initiate SL-APO for the treatment of OFF episodes in PD.
| S-EPMC10200146 | biostudies-literature
Project description:IntroductionIn a pivotal study, apomorphine sublingual film (APL; KYNMOBI®) was an effective and generally well-tolerated on-demand treatment of "OFF" episodes in patients with Parkinson's disease (PD), approved across the dose range of 10-30 mg. Pharmacokinetics and comparative bioavailability of APL and two subcutaneous (SC) apomorphine formulations (SC-APO [APOKYN®] and SC-APO-GO [APO-go® PEN]) were evaluated in a randomized, three-way crossover, open-label study (NCT03292016).MethodsPatients with PD and "OFF" episodes received an open-label randomized sequence of single doses of SC-APO and SC-APO-GO at the currently prescribed dose (2/3/4/5 mg) and APL doses with similar plasma exposure (15/20/25/30 mg) with ≥ 1-day washout between formulations. Plasma pharmacokinetics of apomorphine and apomorphine sulfate (major inactive metabolite) were measured 0-6 h postdose.ResultsMedian time to maximum plasma concentration (tmax) of apomorphine was 0.63-0.75 h for APL and 0.25-0.38 h for SC-APO and SC-APO-GO. Geometric mean maximum plasma concentration (Cmax) of apomorphine was 4.31-11.2 ng/ml across APL doses and was generally lower compared with SC apomorphine formulations within dose groups. Area under the concentration-time curve from time 0 to infinity (AUC∞) was similar across apomorphine formulations within most dose groups. Relative bioavailability of APL was ~ 17% of SC apomorphine by AUC∞; SC-APO and SC-APO-GO had similar bioavailability (98% and 83% by AUC∞ and Cmax, respectively). Apomorphine sulfate exposure was ~ three-fold higher for APL versus SC-APO and SC-APO-GO by AUC∞ and Cmax.ConclusionIn patients with PD and "OFF" episodes, APL demonstrated lower Cmax and relative bioavailability but similar exposures (AUCs) versus SC apomorphine within the approved dose range.Trial registrationClinicalTrials.gov, NCT03292016.
| S-EPMC8571442 | biostudies-literature
Project description:Expert consensus on the potential benefits of early cancer detection does not exist for most cancer types. We convened 10 practicing oncologists using a RAND/UCLA modified Delphi panel to evaluate which of 20 solid tumors, representing >40 American Joint Committee on Cancer (AJCC)-identified cancer types and 80% of total cancer incidence, would receive potential clinical benefits from early detection. Pre-meeting, experts estimated how long cancers take to progress and rated the current curability and benefit (improvement in curability) of an annual hypothetical multi-cancer screening blood test. Post-meeting, experts rerated all questions. Cancers had varying estimates of the potential benefit of early cancer detection depending on estimates of their curability and progression by stage. Cancers rated as progressing quickly and being curable in earlier stages (stomach, esophagus, lung, urothelial tract, melanoma, ovary, sarcoma, bladder, cervix, breast, colon/rectum, kidney, uterus, anus, head and neck) were estimated to be most likely to benefit from a hypothetical screening blood test. Cancer types rated as progressing quickly but having comparatively lower cure rates in earlier stages (liver/intrahepatic bile duct, gallbladder, pancreas) were estimated to have medium likelihood of benefit from a hypothetical screening blood test. Cancer types rated as progressing more slowly and having higher curability regardless of stage (prostate, thyroid) were estimated to have limited likelihood of benefit from a hypothetical screening blood test. The panel concluded most solid tumors have a likelihood of benefit from early detection. Even among difficult-to-treat cancers (e.g., pancreas, liver/intrahepatic bile duct, gallbladder), early-stage detection was believed to be beneficial. Based on the panel consensus, broad coverage of cancers by screening blood tests would deliver the greatest potential benefits to patients.
| S-EPMC9770338 | biostudies-literature
Project description: Not available
| S-EPMC10548076 | biostudies-literature
Project description:Individuals seek help to stop their use of e-cigarettes from their healthcare practitioners. However, there is a paucity of published work addressing e-cigarette cessation methods empirically, and what evidence that is available is weak. Therefore, we developed an expert informed clinical resource to guide practitioners helping their clients quit using e-cigarettes. We conducted a modified Delphi process between September and December 2021 to reach consensus on clinical recommendations for e-cigarette cessation. Expert and Peer Panel members (n = 28) voted and provided feedback on the recommendations through three rounds of structured surveys, a discussion board, and one intermediate survey. The penultimate knowledge products underwent usability testing and were finalized based on user feedback. The Expert Panel maintained a 100% response rate for rounds 1 and 2 and 96% for round 3; the Peer Panel achieved a 100% response rate for all three rounds of the modified Delphi process. Consensus was reach on 24 recommendations and 2 statements spanning eight domains: severity and dependence; general approaches; treatment approaches; dual use; pharmacotherapy strategies; behavioural therapy strategies; harm reduction; and relapse prevention. Two additional 'no agreement' statements that did not reach consensus are included in the guidance resource. The recommendations were also contextualized for the following groups: adults; youth; people who are pregnant, breastfeeding and/or chestfeeding; and people with mental illness and/or substance use issues. The recommendations listed in the resource provide general clinical guidance on e-cigarette cessation to assist healthcare practitioners in the treatment planning process.
| S-EPMC10466900 | biostudies-literature
Project description:Limited guidance exists to support investigators in the choice, adaptation, validation and use of implementation measures for global mental health implementation research. Our objectives were to develop consensus on best practices for implementation measurement and identify strengths and opportunities in current practice. We convened seven expert panelists. Participants rated approaches to measure adaptation and validation according to appropriateness and feasibility. Follow-up interviews were conducted and a group discussion was held. We then surveyed investigators who have used quantitative implementation measures in global mental health implementation research. Participants described their use of implementation measures, including approaches to adaptation and validation, alongside challenges and opportunities. Panelists agreed that investigators could rely on evidence of a measure's validity, reliability and dimensionality from similar contexts. Panelists did not reach consensus on whether to establish the pragmatic qualities of measures in novel settings. Survey respondents (n = 28) most commonly reported using the Consolidated Framework for Implementation Research Inner Setting Measures (n = 9) and the Program Assessment Sustainability Tool (n = 5). All reported adapting measures to their settings; only two reported validating their measures. These results will support guidance for implementation measurement in support of mental health services in diverse global settings.
| S-EPMC10663693 | biostudies-literature
Project description:BackgroundFever of unknown origin (FUO) and inflammation of unknown origin (IUO) are syndromes commonly used as medical diagnoses. Since the existing literature has a mixture of diagnostic approaches, developing consensus-based recommendations would be helpful for clinicians, researchers, and patients.MethodsA modified Delphi process was performed from October 2022 to July 2023, involving 4 rounds of online surveys and 2 live video conferences. The panel comprised international experts recruited based on peer-reviewed published publications and studies.ResultsAmong 50 invited experts, 26 (52.0%) agreed to participate. Twenty-three panelists completed round 1 of the survey, 21 completed rounds 2 and 3, 20 completed round 4, and 7 participated in round 5 live video discussions. Of the participants, 18 (78.3%) were academic-based clinicians and researchers, 5 (21.7%) practiced in a community-based hospital, and 6 (26.1%) were female. Consensus was reached on 5 themes: (1) incorporating epidemiologic factors, such as geographic location and travel history; (2) updated criteria for classifying FUO or IUO; (3) initial evaluation approaches; (4) a classification system for diagnoses; and (5) recommendations for judicious limitation of empiric therapies. Experts strongly disagreed with using 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography as part of the diagnostic criteria for FUO. There were mixed opinions about the importance of the temperature measurement site, the 3-week minimum illness criterion, the need for a standard definition of relapsing fevers, and the use of similar evaluation strategies for FUO and IUO.ConclusionsThese Delphi-generated consensus-based recommendations offer potential improvements compared with earlier definitions and a guide for clinical practice and future research.
| S-EPMC11222709 | biostudies-literature