Clinical Effectiveness Outcomes Research Articles

Clinical effectiveness and implementation outcomes of pMDI-to-DPI switch in children between 5 and 12 years of age: a scoping review protocol

IntroductionInhalers are critical in asthma treatment, and inappropriate inhaler use leads to poor asthma outcomes. In adults and adolescents, dry powder inhalers (DPIs) are safe and effective alternatives to mainstay...

P1151 6-month real-world results from the prospective FilgoColitis study on clinical effectiveness and psycho-social outcomes

Abstract Background Treatment options for patients with ulcerative colitis have increased considerably in recent years. Here, we present the 6-month results on clinical effectiveness and psycho-social outcomes of the ongoing FilgoColitis study in patients with ulcerative colitis (UC) starting new treatment with filgotinib (FIL) in a real-world setting. Methods FilgoColitis is a prospective, multicentre, non-interventional, 24-month observational study in patients with active UC and newly introduced FIL therapy. Disease activity (clinical response: reduction of pMayo by ≥3 points from baseline to month 6 and a reduction of at least 30% or reaching remission at month 6; clinical remission (CR): pMayo ≤ 1 plus a bleeding subscore=0; steroid-free remission: CR and no systemic use of steroids or oral budesonide), quality of life (QoL) (sIBDQ and EQ-5D), and fatigue level (FACIT-F) will be analyzed. In a subgroup, the daily step count was recorded using the SensMotion® thigh accelerometer for at least 3 days after each visit (n=21). Results 202 patients were enrolled in the study. After excluding missing outcomes, 164 patients were available for the 6-month analysis. Of these, 61.0% were male, and the median time since diagnosis was 8.0 years. Before treatment with FIL, 85.4% of patients had received biologic or small molecule therapies, and 57.3% had used immunosuppressants. Treatment persistence at month 6 was 87.2% (Fig. 1). After 6 months of treatment with FIL, the clinical response and remission rate were 59.2% and 41.7%, respectively (mITT (switchers=outcome failures), Table 1). There was no significant difference in clinical remission between biologic-naïve and biologic-experienced patients (41.7% vs 41.4%). Looking at week-10 responders only, the response rate at month 6 was 85.0%, and the remission rate was 58.8%. QoL improved significantly, with median EQ-VAS scores increasing from 64 to 80 at month 6 (p<0.001), and sIBDQ scores improving from 42.0 to 56.0 (p<0.001). Fatigue scores improved significantly from baseline to month 6 of FIL therapy (FACIT-F score part I: 8.0 vs 5.0, p<0.001). In patients who were in remission at month 6, the daily number of steps measured was higher than in patients who were not in remission (9918 (4861-11048) vs 5959 (4747-6323)). The steps measured during the night also differed between these two groups: 196 (142-559) vs 293 (164-479). This was consistent with asking the patients if they had nocturnal stools (0% vs 42.9%). Conclusion In this real-world study, FIL showed a clinical response rate of 59% and a clinical remission rate of 42% at month 6 in patients with active UC, demonstrating a further improvement compared to the induction phase. QoL was also significantly improved.

Transcatheter Left Ventricular Reconstruction in HeartFailure Patients With Prior Anterior Myocardial Infarction: The Prospective ALIVE Trial.

Left ventricular (LV) dilatation and extensive scar portend a poor prognosis in heart failure (HF). The Revivent TC system (BioVentrix Inc) is used either during a hybrid transcatheter-surgical or a surgical-only procedure to exclude transmural scar and reduce LV dimensions. The purpose of this study was to examine the safety and efficacy of the Revivent TC® anchor system in patients with HF. We conducted a prospective, multicenter, nonrandomized (2:1 device vs control) trial in patients with NYHA functional class III-IV symptoms, LV ejection fraction≤45%, LV end-systolic volume index≥50mL/m2, and transmural anterior LV scar. Patients with inadequate scar or previous sternotomy served as the control group. The primary safety endpoint was the composite of major adverse events in the device arm compared with a performance goal of 40.5%. The primary effectiveness endpoint was the hierarchical composite of cardiovascular mortality, HF hospitalization, change in 6-minute walk test, change in Minnesota Living With HeartFailure questionnaire score, and change in NYHA functional classification assessed at 12months as the win ratio in the device group compared with the control group. In total, 126 patients (84 device; 42 control) were enrolled at 28 sites. Mean LV ejection fraction was 29.6%±7.2%, and mean LV end-systolic volume index was 93.9 ± 35.5mm. The primary 30-day safety performance goal endpoint was met (major adverse events 15 of 84 [17.9%]; 1-sided 97.5% upper confidence limit 27.7%; P<0.0001). There was no significant difference in the primary 12-month hierarchical composite efficacy endpoint (win ratio 1.13; P = 0.32). In post hoc analysis, the surgical only approach (23 treated patients) had more favorable outcomes than the hybrid approach (60 treated patients). The Revivent TC® system safely reduced LV dimensions in HF patients caused by extensive anterior scar but did not improve clinical effectiveness outcomes at 1 year. A randomized trial is warranted to further define the risks and benefits of the surgical only approach. (BioVentrix Revivent TC™ System Clinical Study; NCT02931240).

Real-World Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With First-Line Nivolumab Plus Ipilimumab in the United States.

Nivolumab plus ipilimumab (NIVO + IPI) is a first-in-class combination immunotherapy for the treatment of intermediate- or poor (I/P)-risk advanced or metastatic renal cell carcinoma (mRCC). Currently, there are limited real-world data regarding clinical effectiveness beyond 12-24 months from treatment initiation. In this real-world study, treatment patterns and clinical outcomes were evaluated for NIVO + IPI in a community oncology setting. A retrospective analysis using electronic medical record data from The US Oncology Network examined patients with I/P-risk clear cell mRCC who initiated first-line (1L) NIVO + IPI between January 4, 2018, and December 31, 2019, with follow-up until June 30, 2022. Baseline demographics, clinical characteristics, treatment patterns, clinical effectiveness, and safety outcomes were assessed descriptively. Overall survival (OS) and real-world progression-free survival (rwPFS) were analyzed using Kaplan-Meier methods. Among 187 patients identified (median follow-up, 22.4 months), with median age 63 (range, 30-89) years, 74 (39.6%) patients had poor risk and 37 (19.8%) patients had Eastern Cooperative Oncology Group performance status score ≥2. Of 86 patients who received second-line therapy, 54.7% received cabozantinib and 10.5% received pazopanib. The median (95% CI) OS and rwPFS were 38.4 (24.7-46.1) months and 11.1 (7.5-15.0) months, respectively. Treatment-related adverse events (TRAEs) were reported in 89 (47.6%) patients, including fatigue (n = 25, 13.4%) and rash (n = 19, 10.2%). This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients with I/P-risk mRCC. TRAE rates were low relative to clinical trials.

Addressing Hypertension and Diabetes through Community-Engaged Systems (ANDES) in Puno, Peru: rationale and study protocol for a hybrid type 2 effectiveness and implementation randomized controlled trial

BackgroundHypertension is the most common cardiovascular disease in Peru despite the availability of cost-effective, evidence-based treatment. Here we describe the rationale and study design for a hybrid type 2 randomized controlled trial to test the implementation and effectiveness of a community health worker (CHW)-led hypertension control program within the national primary care system in Puno, Peru.MethodsWe will recruit 1068 adult participants with hypertension aged ≥ 18 years in Puno, Peru, via facility-based enrollment and community health fairs. Participants will be individually randomized (1:1) to either continue with usual care or participate in a 12-month CHW-led home-based hypertension control program consisting of blood pressure monitoring, medication adherence support, and healthy lifestyle counseling. Outcome development and reporting are guided by the Consolidated Framework for Implementation Research (CFIR), the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, and the Proctor et al. framework. Clinical effectiveness outcomes include mean change in systolic blood pressure (primary outcome), diastolic blood pressure, and HbA1C. Implementation outcomes include fidelity (i.e., CHW protocol adherence and dose), reach, adoption, sustainability, acceptability, and cost-effectiveness.DiscussionThe ANDES trial is testing the first CHW-led multicomponent strategy for hypertension and type 2 diabetes management in Peru. This type 2 hybrid trial will provide critical insights into the individual, community, and system-level factors necessary for successful implementation and effectiveness. These data can inform the future adaptation and scaling of the ANDES strategy in Peru and other LMICs, as well as influence policies at the system level to support this transition. Furthermore, by addressing both hypertension and diabetes, the ANDES strategy supports integrated care approaches advocated by the WHO HEARTS technical package, ultimately enhancing health outcomes and reducing morbidity and mortality in the region.Trial registrationClinicalTrials.gov, ID: NCT05524987, Addressing Hypertension and Diabetes through Community-Engaged Systems in Puno, Peru (ANDES study), prospectively registered on September 1, 2021.

Evaluating the Implementation and Clinical Effectiveness of an Innovative Digital First Care Model for Behavioral Health Using the RE-AIM Framework: Quantitative Evaluation.

In the United States, innovation is needed to address the increasing need for mental health care services and widen the patient-to-provider ratio. Despite the benefits of digital mental health interventions (DMHIs), they have not been effective in addressing patients' behavioral health challenges as stand-alone treatments. This study evaluates the implementation and effectiveness of precision behavioral health (PBH), a digital-first behavioral health care model embedded within routine primary care that refers patients to an ecosystem of evidence-based DMHIs with strategically placed human support. Patient demographic information, triage visit outcomes, multidimensional patient-reported outcome measure, enrollment, and engagement with the DMHIs were analyzed using data from the electronic health record and vendor-reported data files. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework was used to evaluate the implementation and clinical effectiveness outcomes of PBH. PBH had a 47.58% reach rate, defined as patients accepting the PBH referral from their behavioral health integrated clinician. PBH patients had high DMHI registration rates (79.62%), high activation rates (76.54%), and high retention rates at 15 days (57.69%) and 30 days (44.58%) compared to literature benchmarks. In total, 74.01% (n=168) of patients showed clinical improvement, 22.47% (n=51) showed no clinical change, and 3.52% (n=8) showed clinical deterioration in symptoms. PBH had high adoption rates, with behavioral health integrated clinicians referring on average 4.35 (SD 0.46) patients to PBH per month and 90%-100% of clinicians (n=12) consistently referring at least 1 patient to PBH each month. A third (32%, n=1114) of patients were offered PBH as a treatment option during their triage visit. PBH as a care model with evidence-based DMHIs, human support for patients, and integration within routine settings offers a credible service to support patients with mild to moderate mental health challenges. This type of model has the potential to address real-life access to care problems faced by health care settings.

Development and Implementation of a Multicenter Registry for Resuscitation-Focused Transesophageal Echocardiography

To evaluate the clinical effect, safety, and clinical outcomes of focused transesophageal echocardiography (TEE) in the evaluation of critically ill patients in the emergency department (ED) and ICUs. We established a prospective, multicenter, observational registry involving adult critically ill patients in whom focused TEE was performed for evaluation of out-of-hospital cardiac arrest (OHCA), inhospital cardiac arrest, evaluation of undifferentiated shock, hemodynamic monitoring, and/or procedural guidance in the ED, ICU, or operating room setting. The primary objective of the current investigation was to evaluate the clinical influence and safety of focused, point-of-care TEE in critically ill patients. Data elements included patient and procedure characteristics, laboratory values, timing of interventions, clinical outcomes, and TEE video images. A total of 1,045 focused TEE studies were collected among 916 patients from 28 hospitals, including 585 (64%) intraarrest and postarrest OHCA and inhospital cardiac arrest, 267 (29%) initial evaluation of undifferentiated shock, 101 (11%) procedural guidance, and 92 (10%) hemodynamic monitoring. TEE changed management in 85% of patients with undifferentiated shock, 71% of patients with inhospital cardiac arrest, and 62% of patients with OHCA. There were no reported esophageal perforations or oropharyngeal injuries, and other procedural complications were rare. A prospective, multicenter, and multidisciplinary TEE registry was successfully implemented, and demonstrated that focused TEE is safe and clinically impactful across multiple critical care applications. Further studies from this research network will accelerate the development of outcome-oriented research and knowledge translation on the use of TEE in emergency and critical care settings.

GnRH-a-based fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients: a multicenter, open-label, randomized designed clinical trial protocol

BackgroundAround 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes.MethodsThis study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence.Ethics and disseminationThe protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association’s Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal.ConclusionsProspective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH.Trial registration numberChinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.

Can edoxaban be used at extremes of bodyweight and in patients with a creatinine clearance ≥95 ml/min? – A population pharmacokinetic analysis

BackgroundClinical evidence surrounding edoxaban use in patients weighing <50 kg and >120 kg is lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee suggests avoiding edoxaban in patients >120 kg. Additionally, concerns exist regarding decreased efficacy in patients prescribed edoxaban for atrial fibrillation with a creatinine clearance (CrCl) >95 ml/min, a finding of the ENGAGE AF-TIMI 48 trial when edoxaban was compared to warfarin. ObjectiveTo derive a population pharmacokinetic (PopPK) model using clinical practice data, to understand the impact of bodyweight and renal function on edoxaban pharmacokinetics. MethodEdoxaban plasma concentrations and patient characteristics were collated from King's College Hospital anticoagulation clinics between 11/2016 and 08/2022. A PopPK model was developed using non-linear mixed effects modelling and used to simulate edoxaban concentrations at the extremes of bodyweight and with varying renal function. ResultsData from 409 patients (46 < 50 kg, 34 > 120 kg and 123 with a CrCl > 95 ml/min) provided 455 edoxaban plasma concentrations. A one-compartment model with between-subject variability on clearance with a proportional error model best described the data. The most significant covariates impacting on edoxaban exposure were CrCl and bodyweight. Our work suggests that edoxaban exposure in patients weighing up to 140 kg is comparable to those weighing 75 kg. Edoxaban exposure is reduced in patients weighing <50 kg due to the recommended dose reductions. There is also a reduction in AUCss when CrCl > 95 ml/min compared to CrCl 80 ml/min. ConclusionsOur population PK model for edoxaban suggests that renal function is a key driver for overall edoxaban exposure. Further clinical outcome data is required to understand clinical effectiveness and adverse outcomes.

Real-world Clinical Effectiveness and Safety of Vedolizumab and Adalimumab in Biologic-naive Patients With Crohn's Disease: Results From the EVOLVE Study.

This study evaluated the real-world effectiveness and safety of vedolizumab versus adalimumab over 12 months of treatment in biologic-naive patients with Crohn's disease (CD), using data from the EVOLVE study. A comparison of vedolizumab and adalimumab may help to better position them in the therapeutic algorithm for moderate-to-severe CD. Data were collected from medical records of patients with CD aged ≥18 years initiating treatment with adalimumab or vedolizumab between May 2014 and July 2017. Adjusted analyses were performed using inverse probability weighting to account for differences in baseline characteristics. Cumulative rates for clinical effectiveness outcomes and treatment persistence were estimated using Kaplan-Meier analyses. Disease-related exacerbations, serious adverse events (SAEs), and serious infections (SIs) were also assessed. Data from 218 vedolizumab- and 144 adalimumab-treated patients were analyzed. Adjusted cumulative rates of clinical remission were greater with vedolizumab than with adalimumab (66.3% vs. 46.4%; P=0.006). Probability of treatment persistence was higher with vedolizumab (89.3% vs. 77.5%; P=0.024); probabilities of clinical response (68.5% vs. 61.1%; P=0.586) and mucosal healing (67.7% vs. 56.0%; P=0.562) were similar. SAEs were less likely to occur with vedolizumab [hazard ratio, 0.45 (95% confidence interval, 0.22-0.93)]; however, the likelihood of SIs [0.27 (0.06-1.20)], CD exacerbations [0.91 (0.56-1.47)], and CD-related surgeries [1.55 (0.21-11.15)] was comparable between the 2 groups. In a real-world setting, biologic-naive patients with CD treated with vedolizumab demonstrated a greater likelihood of drug persistence and achieving clinical remission, with equivalent rates of response and mucosal healing versus adalimumab-treated patients.

Therapeutic sequencing in inflammatory bowel disease: Determining the optimal position of vedolizumab for long-term Crohn's disease control using real-world evidence.

Several biologics are available for the treatment of moderate to severe Crohn's disease, but data to optimize their use are scarce. Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking monoclonal antibody that was approved in 2014 for the treatment of moderate to severe Crohn's disease. Based on real-world evidence, a model was developed to examine the effect of VDZ's position in the treatment sequence on clinical outcomes. The aim of this study was to develop a model using real-world data to investigate how the positioning of VDZ in a sequence of biologic therapies for CD affects clinical effectiveness outcomes of quality-adjusted life-years (QALYS), patient-reported disease activity, and surgery rates. A semi-Markov sequential model was developed to identify the optimal position of VDZ in a treatment sequence that included corticosteroids (CS), two biologics, and best supportive care (BSC). Using real-world data, three sequences were compared: VDZ as first (position), second, and last biologic (with anti-tumor necrosis factor alpha agents adalimumab (ADA) and infliximab (IFX) and the anti-interleukin-12 and -23 agent ustekinumab (UST) as alternative biologic treatments). Published real-world evidence informed model inputs. Vedolizumab sequences were compared and ranked based on QALYS, patient-reported outcomes from Crohn's disease activity index scores, or proportion of patients undergoing surgery by the 10-year time horizon for model simulation. Sensitivity analyses were used to evaluate the impact of model input uncertainty. Vedolizumab as the first biologic was the optimal position for this treatment according to all criteria, including yielding the highest QALYs (5.09) versus VDZ in second (4.97) and third (4.96) biologic sequence positions in sequences containing CS, anti-TNFα (aggregated data), UST, and BSC; 1780/2000 (89%) probabilistic simulations. In sequences containing ADA, VDZ, and UST biologics, ADA and VDZ in the first-line biologic position yielded QALYs of 5.09 versus 5.07, respectively. Adalimumab as the first biologic was best for clinical remission. This simulation model using real-world evidence indicates that positioning VDZ or ADA as the first biologic is likely to lead to improved long-term patient outcomes when compared to administering these treatments later or starting with IFX monotherapy.

Family cascade screening for equitable identification of familial hypercholesterolemia: study protocol for a hybrid effectiveness-implementation type III randomized controlled trial

BackgroundFamilial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap. In pilot work, we leveraged best practices from behavioral economics and implementation science—including mixed-methods contextual inquiry with clinicians, patients, and health system constituents—to co-design two patient-facing implementation strategies to address this care gap: (a) an automated health system-mediated strategy and (b) a nonprofit foundation-mediated strategy with contact from a foundation-employed care navigator. This trial will test the comparative effectiveness of these strategies on completion of cascade screening for relatives of individuals with FH, centering equitable reach.MethodsWe will conduct a hybrid effectiveness-implementation type III randomized controlled trial testing the comparative effectiveness of two strategies for implementing cascade screening with 220 individuals with FH (i.e., probands) per arm identified from a large northeastern health system. The primary implementation outcome is reach, or the proportion of probands with at least one first-degree biological relative (parent, sibling, child) in the USA who is screened for FH through the study. Our secondary implementation outcomes include the number of relatives screened and the number of relatives meeting the American Heart Association criteria for FH. Our secondary clinical effectiveness outcome is post-trial proband cholesterol level. We will also use mixed methods to identify implementation strategy mechanisms for implementation strategy effectiveness while centering equity.DiscussionWe will test two patient-facing implementation strategies harnessing insights from behavioral economics that were developed collaboratively with constituents. This trial will improve our understanding of how to implement evidence-based cascade screening for FH, which implementation strategies work, for whom, and why. Learnings from this trial can be used to equitably scale cascade screening programs for FH nationally and inform cascade screening implementation efforts for other genetic disorders.Trial registrationClinicalTrials.gov, NCT05750667. Registered 15 February 2023—retrospectively registered, https://clinicaltrials.gov/study/NCT05750667.

Impact of Local Tailoring on Acute Stroke Care in 21 Disparate Emergency Departments: A Prospective Stepped Wedge Type III Hybrid Effectiveness-Implementation Study.

Faster delivery of tPA (tissue-type plasminogen activator) results in better health outcomes for eligible patients with stroke. Standardization of stroke protocols in emergency departments (EDs) has been difficult, especially in nonstroke centers. We measured the effectiveness of a centrally led implementation strategy with local site tailoring to sustain adherence to an acute stroke protocol to improve door-to-needle (DTN) times across disparate EDs in a multihospital health system. Prospective, type III hybrid effectiveness-implementation cohort study measuring performance at 21 EDs in Utah and Idaho (stroke centers [4]/nonstroke centers [17]) from January 2018 to February 2020 using a nonrandomized stepped-wedge design, monthly repeated site measures and multilevel hierarchical modeling. Each site received the implementation strategies in 1 of 6 steps providing control and intervention data. Co-primary outcomes were percentage of DTN times ≤60 minutes and median DTN time. Secondary outcomes included percentage of door-to-activation of neurological consult times ≤10 minutes and clinical effectiveness outcomes. Results were stratified between stroke and nonstroke centers. A total of 855 474 ED patient encounters occurred with 5325 code stroke activations (median age, 69 [IQR, 56-79] years; 51.8% female patients]. Percentage of door-to-activation times ≤10 minutes increased from 47.5% to 59.9% (adjusted odds ratio, 1.93 [95% CI, 1.40-2.67]). A total of 615 patients received tPA of ≤3 hours from symptom onset (median age, 71 [IQR, 58-80] years; 49.6% female patients). The percentage of DTN times ≤60 minutes increased from 72.5% to 86.1% (adjusted odds ratio, 3.38, [95% CI, 1.47-7.78]; stroke centers (77.4%-90.0%); nonstroke centers [59.3%-72.1%]). Median DTN time declined from 46 to 38 minutes (adjusted median difference, -9.68 [95% CI, -17.17 to -2.20]; stroke centers [41-35 minutes]; nonstroke centers [55-52 minutes]). No differences were observed in clinical effectiveness outcomes. A centrally led implementation strategy with local site tailoring led to faster delivery of tPA across disparate EDs in a multihospital system with no change in clinical effectiveness outcomes including rates of complication. Disparities in performance persisted between stroke and nonstroke centers.

Cost-effectiveness of prehabilitation of elderly frail or pre-frail patients prior to elective surgery (PRAEP-GO) versus usual care – Protocol for a health economic evaluation alongside a randomized controlled trial

BackgroundPrehabilitation aims to improve patients' functional capacity before surgery to reduce perioperative complications, promote recovery and decrease probability of disability. The planned economic evaluation is performed alongside a large German multi-centre pragmatic, two-arm parallel-group, randomized controlled trial on prehabilitation for frail elderly patients before elective surgery compared to standard care (PRAEP-GO RCT). The aim is to determine the cost-effectiveness and cost-utility of prehabilitation for frail elderly before an elective surgery.MethodsThe planned health economic evaluation comprises cost-effectiveness, and cost-utility analyses. Analyses are conducted in the German context from different perspectives including the payer perspective, i.e. the statutory health insurance, the societal perspective and the health care provider perspective. Data on outcomes and costs, are collected alongside the ongoing PRAEP-GO RCT. The trial population includes frail or pre-frail patients aged ≥70 years with planned elective surgery. The intervention consists of frailty screening (Fried phenotype), a shared decision-making conference determining modality (physiotherapy and unsupervised physical exercises, nutrition counselling, etc.) and setting (inpatient, day care, outpatient etc.) of a 3-week individual multimodal prehabilitation prior to surgery. The control group receives standard preoperative care.Costs include the intervention costs, the costs of the index hospital stay for surgery, and health care resources consumed during a 12-month follow-up. Clinical effectiveness outcomes included in the economic evaluation are the level of care dependency, the degree of disability as measured by the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), quality-adjusted life years (QALY) derived from the EQ-5D-5L and the German utility set, and complications occurring during the index hospital stay. Each adopted perspective considers different types of costs and outcomes as outlined in the protocol. All analyses will feature Intention-To-Treat analysis. To explore methodological and parametric uncertainties, we will conduct probabilistic and deterministic sensitivity analyses. Subgroup analyses will be performed as secondary analyses.DiscussionThe health economic evaluation will provide insights into the cost-effectiveness of prehabilitation in older frail populations, informing decision-making processes and contributing to the evidence base in this field. Potential limitation includes a highly heterogeneous trial population.Trial registrationPRAEP-GO RCT: NCT04418271; economic evaluation: OSF (https://osf.io/ecm74).

Pharmacological Considerations during Percutaneous Treatment of Heart Failure.

Heart Failure (HF) remains a global health challenge, marked by its widespread prevalence and substantial resource utilization. Although the prognosis has improved in recent decades due to the treatments implemented, it continues to generate high morbidity and mortality in the medium to long term. Interventional cardiology has emerged as a crucial player in HF management, offering a diverse array of percutaneous treatments for both acute and chronic HF. This article aimed to provide a comprehensive review of the role of percutaneous interventions in HF patients, with a primary focus on key features, clinical effectiveness, and safety outcomes. Despite the growing utilization of these interventions, there remain critical gaps in the existing body of evidence. Consequently, the need for high-quality randomized clinical trials and extensive international registries is emphasized to shed light on the specific patient populations and clinical scenarios that stand to benefit most from these innovative devices.

Design and selection of drug properties to increase the public health impact of next-generation seasonal malaria chemoprevention: a modelling study.

Seasonal malaria chemoprevention (SMC) is recommended for disease control in settings with moderate to high Plasmodium falciparum transmission and currently depends on the administration of sulfadoxine-pyrimethamine plus amodiaquine. However, poor regimen adherence and the increased frequency of parasite mutations conferring sulfadoxine-pyrimethamine resistance might threaten the effectiveness of SMC. Guidance is needed to de-risk the development of drug compounds for malaria prevention. We aimed to provide guidance for the early prioritisation of new and alternative SMC drugs and their target product profiles. In this modelling study, we combined an individual-based malaria transmission model that has explicit parasite growth with drug pharmacokinetic and pharmacodynamic models. We modelled SMC drug attributes for several possible modes of action, linked to their potential public health impact. Global sensitivity analyses identified trade-offs between drug elimination half-life, maximum parasite killing effect, and SMC coverage, and optimisation identified minimum requirements to maximise malaria burden reductions. Model predictions show that preventing infection for the entire period between SMC cycles is more important than drug curative efficacy for clinical disease effectiveness outcomes, but similarly important for impact on prevalence. When children younger than 5 years receive four SMC cycles with high levels of coverage (ie, 69% of children receiving all cycles), drug candidates require a duration of protection half-life higher than 23 days (elimination half-life >10 days) to achieve reductions higher than 75% in clinical incidence and severe disease (measured over the intervention period in the target population, compared with no intervention across a range of modelled scenarios). High coverage is crucial to achieve these targets, requiring more than 60% of children to receive all SMC cycles and more than 90% of children to receive at least one cycle regardless of the protection duration of the drug. Although efficacy is crucial for malaria prevalence reductions, chemoprevention development should select drug candidates for their duration of protection to maximise burden reductions, with the duration half-life determining cycle timing. Explicitly designing or selecting drug properties to increase community uptake is paramount. Bill & Melinda Gates Foundation and the Swiss National Science Foundation.

Long-term follow-up of inpatients with meniscus tears who received integrative Korean medicine treatment: A retrospective analysis and follow-up survey.

Evidence regarding the use of Korean medicine (KM) for the conservative treatment of meniscus tears remains lacking. We aimed to evaluate clinical effectiveness and long-term follow-up outcomes in patients undergoing integrative KM treatment for meniscus tears. We analyzed the electronic medical records (EMRs) of 86 patients with meniscus tears and administered a follow-up survey. Patients treated at 1 of 4 KM hospitals between June 1, 2015, and June 30, 2020, were reviewed. KM treatment comprised herbal medicine, acupuncture, pharmacopuncture, bee venom pharmacopuncture, Chuna therapy, and KM physiotherapy. The primary outcome was the numeric rating scale (NRS) score for knee pain; secondary outcomes were the Western Ontario and McMaster Universities Arthritis Index (WOMAC), EuroQol 5-dimension (EQ-5D) score, range of motion, and patient global impression of change. The NRS for knee pain was reduced by an average of 2.49 (95% confidence interval [CI]: 2.03-2.95) at discharge and 1.97 (95% CI: 2.03-2.95) at follow-up. The WOMAC decreased by an average of 15.52 (95% CI: 10.14-20.89) during hospital stay and 30.72 (95% CI: 24.58-36.87) at follow-up. The EQ-5D score increased by an average of 0.06 (95% CI: -0.14 to 0.02) at discharge and 0.19 (95% CI: -0.29 to -0.09) at follow up. KM treatment effectively reduced knee pain, improved knee joint function, and enhanced the quality of life in patients with a meniscus tear for a relatively long period after treatment.

Safety and Quality Within the Healthcare Supply Chain: A Great Unknown.

Quality and safety in healthcare have emerged as key factors impacting on both clinical effectiveness and clinical outcomes. While improving the healthcare supply chain has been extensively researched, the impact of the healthcare supply chain on clinical safety has received little attention in the literature, largely due to the complexity of such studies and the involvement of multiple stakeholders. This research proposes an evaluation model using key performance measurements for an electronic procurement system that enables digital transformation of the healthcare supply chain. The model will be tested before and after the introduction of an electronic procurement system in the healthcare supply chain for small and medium sized healthcare providers to provide evidence of both the usefulness of the model itself within industry and to further contribute to the knowledge base. Future use of the model may provide benchmarking and important data and insights to enable enhanced clinical safety in the healthcare supply chain.

Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: A systematic review and meta-analysis.

Iron deficiency anaemia (IDA) during pregnancy is treated with oral and parenteral iron. The objective of this review was to compare the clinical effectiveness, safety, pregnancy and neonatal outcomes of intravenous (iv) ferric carboxymaltose (FCM) and iv iron sucrose (IS) in treating IDA in pregnancy. The Department of Health Research funded this study. PubMed, Cochrane Library, EMBASE and Scopus were searched to include studies published till November 2022. The protocol was registered in PROSPERO (CRD42022306092). Pregnant women (15-49 yr) in second and third trimesters, diagnosed with moderate-to-severe iron deficiency anaemia, treated with either of the drugs were included. The included studies were critically assessed using appropriate tools. We conducted a qualitative synthesis of the studies and meta-analysis for improvement in haematological parameters and incidence of adverse events. A total of 18 studies were included. The risk of bias was low to moderate. A rise in haemoglobin up to four weeks was higher with FCM than IS by 0.57 (0.24, 0.9) g/dl. Intravenous FCM is associated with fewer adverse events than IS [pooled odds ratio: 0.5 (0.32, 0.79)]. The included studies had limited evidence on pregnancy and neonatal outcomes after iv iron treatment. Intravenous FCM is effective and safer than intravenous IS in terms of haematological parameters, in treating IDA in pregnancy. Further research is required on the effects of iv FCM and iv IS on the pregnancy and neonatal outcomes when used for treating IDA in pregnancy.

Special contoured pelvic brim reconstruction titanium plate combined with trans-plate buttress screws (quadrilateral screws) for acetabular fractures with quadrilateral plate involvement through the anterior ilioinguinal approach.

Managing complicated acetabular fractures involving the quadrilateral plate (QLP) can be challenging for surgeons, especially when complicated by comminution and osteoporosis. Traditional implants do not provide sufficient fixed strength or a proper match. The new-type pre-contoured infrapectineal buttress plates may have drawbacks, such as inaccurate fitting on the medial surface of QLP and an inability to apply reversed compression force to resist medial displacement of femoral head. Therefore, the primary purpose of this study is to introduce a novel technique that utilizes a special contoured pelvic brim reconstruction titanium plate combined with quadrilateral screws to reduce and stabilize acetabular fractures involving the QLP through the ilioinguinal approach. Additionally, the secondary purpose is to evaluate both clinical effectiveness and radiological outcomes of this technique for QLP fractures. We conducted a retrospective analysis of prospectively collected data from 48 patients (31 males and 17 females) who suffered from acute displaced fractures of the QLP and were treated between January 2012 and December 2019 using a special contoured plate combined with quadrilateral screws. The patients' mean age was 47.56 ± 11.31 years (range: 19-73 years). Fracture patterns included 20 both-column fractures, 12 anterior column and posterior hemitransverse fractures, eight T-type fractures, five transverse fractures and three anterior column fractures with the QLP affected, all of which had femoral head protrusion. Immediate postoperative reduction quality was evaluated according to Matta's criteria. Final clinical functions were assessed during follow-up using the modified Merle d'Aubigné and Harris Hip scores (HHS). The patients were followed up for an average of 48.36 ± 12.94 months (ranging from 24 to 84 months). The mean operative time was 246.08 ± 54.30 min (ranging from 178 to 397 min), and the average blood loss was 715.16 ± 263.84 ml (ranging from 400 to 2000ml). The radiological grading at postoperative stage showed anatomical reduction in 30 patients (62.50%), satisfactory reduction in 14 patients (29.17%), and poor reduction in four patients (8.33%). At the final follow-up, no re-protrusion of the femoral head was observed. In terms of functional outcome, the mean modified Merle d'Aubigné-Postel score was excellent in 26 patients (54.17%), good in 17 patients (35.42%), fair in four patients (8.33%), and poor in one patient (2.08%). The HHS was excellent in 23 patients (47.92%), good in 20 patients (41.67%), fair in four patients (8.33%), and poor in one patient (2.08%). The average HHS was 87.38 ± 7.86 (ranging from 52 to 98). Postoperative complications included lateral femoral cutaneous nerve injury in two patients, delayed wound healing and subsequent development of an inguinal hernia in one patient. Late complications were observed in two patients, with one case of heterotopic ossification and another case of post-traumatic osteoarthritis underwent hip arthroplasty within two years after surgery. Our results indicate that employing the contoured plate specifically designed for QLP injuries, in conjunction with quadrilateral screws through the ilioinguinal approach, can lead to positive outcomes in the treatment of displaced acetabular fractures involving the QLP. This straightforward and efficient technique offers a viable option for surgeons who are managing complex acetabular fractures.