Current state of research on exercise for the treatment of myasthenia gravis: A scoping review.

OBJECTIVE: To provide a comprehensive overview of existing evidence, research gaps, and future research priorities concerning the treatment of myasthenia gravis (MG) using exercise therapies. METHOD: Clinical studies on exercise treatment for MG were searched in nine databases to conduct a scoping review. Two independent researchers screened the literature and comprehensively analyzed the characteristics and limitations of the included articles. RESULTS: A total of 5725 studies were retrieved, of which 24 were included. The included studies were conducted in 16 different countries/regions and 456 patients were enrolled. Study designs included both interventional and observational studies. Exercise interventions included aerobic exercise, resistance exercise, balance training, and stretch training, and are typically administered in conjunction with medication, usual care, or some other interventions. The intensity, frequency, and duration of exercise interventions varied hugely among studies. Six-minute walk test, adverse events, muscle strength, MG quality of life-15 scale, forced vital capacity, quantitative MG scale, and MG activities of daily living scale were the most frequently used outcomes. All studies reported results in favor of the efficacy and safety of exercise in MG, and exercise-related adverse events were reported in two studies. CONCLUSION: This scoping review provides an overview of the evidence concerning exercise treatment for MG. Key gaps in evidence include a limited number of participants, complex interventions, variability in outcome selection, and insufficient reporting in publications. The promotion of exercise treatment for MG still encounters several obstacles. A larger population, rigorous study design and conduction, standardized interventions and outcomes, and standardized reporting are essential.

The severity and infection of acute pancreatitis may increase the risk of bleeding in patients undergoing EUS-guided drainage and endoscopic necrosectomy: a large retrospective cohort.

BACKGROUND: There has been great progress in the use of endoscopic ultrasound (EUS)-guided drainage in acute pancreatitis patients using a novel lumen-apposing metal stent (LAMS) in the last decade, but some patients experience bleeding. Our research analyzed the preprocedural risk factors for bleeding. METHODS: From July 13, 2016 to June 23, 2021, we retrospectively analyzed all patients who received endoscopic drainage by the LAMS in our hospital. Univariate and multivariate statistical analyses were used to identify the independent risk factors. We plotted ROC curves based on the independent risk factors. RESULTS: A total of 205 patients were analyzed and 5 patients were excluded. A total of 200 patients were included in our research. Thirty (15%) patients presented with bleeding. In the multivariate analysis, computed tomography severity index score (CTSI) score [odds ratio (OR), 2.66; 95% CI: 1.31-5.38; P = 0.007], positive blood cultures [odds ratio (OR), 5.35; 95% CI: 1.31-21.9; P = 0.02], and Acute Physiology and Chronic Health Evaluation II (APACHE II) score [odds ratio (OR), 1.14; 95% CI: 1. 01-1.29; P = 0.045] were associated with bleeding. The area under the ROC curve of the combined predictive indicator was 0.79. CONCLUSION: Bleeding in endoscopic drainage by the LAMS is significantly associated with the CTSI score, positive blood cultures, and APACHE II score. This result could help clinicians make more appropriate choices.

Mapping current trends and hotspots in myasthenia gravis from 2003 to 2022: a bibliometric analysis.

Introduction: Research on myasthenia gravis (MG) has undergone rapid development in recent years. This article aimed to elucidate the characteristics of MG publications over the past 20 years and analyze emerging trends using bibliometric methods. Methods: Information on MG articles was obtained from the Web of Science Core Collection and stored in Excel for quantitative analyses. Bibliometric analyses were performed using CiteSpace and VOSviewer to visualize publications according to countries/regions, institutions, journals, and authors. Results: A total of 3,610 publications were included in the analysis. The USA had the highest number of publications (NP) and H-index. Among the institutions, the University of Oxford had the highest NP, followed by the University of Toronto and Duke University. Close cooperation was observed among countries and institutions. The most productive author was Renato Mantegazza, followed by Jan J. Verschuuren, and Amelia Evoli. Muscle & Nerve published the most articles on MG, followed by the Journal of Neuroimmunology and Neuromuscular Disorders. The keyword with the highest strength is "neuromuscular transmission," followed by "safety" and "rituximab." Co-citation analysis includes 103 publications cited at least 65 times, categorized into four clusters. Additionally, 123 keywords cited more than 40 times were analyzed and divided into five clusters. Conclusion: This bibliometric analysis shows the framework of research over the past 20 years by mapping the scholarly contributions of various countries or regions, institutions, journals, and authors in MG. The analysis also explores future trends and prospective directions, emphasizing individualized treatment based on subtypes, novel immunotherapeutic approaches, and thymectomy.

Herbal medicine and acupuncture relieved progressive bulbar palsy for more than 3 years: A case report.

RATIONALE: Progressive bulbar palsy (PBP) is a type of motor neuron disease (MND). The main symptoms include dysarthria, dysphagia, tongue muscle atrophy and fasciculations. This disease is generally severe and develops rapidly. Due to the lack of effective treatment, many patients with MND in China turn to traditional Chinese medicine treatment for help. We successfully relieved dysphagia and sialorrhea in a patient with PBP for 3 years with herbal medicine and acupuncture. PATIENT CONCERNS: The patient was a 68-years-old woman with PBP and suffered from severe dysphagia and sialorrhea. DIAGNOSES: Progressive bulbar palsy. INTERVENTIONS: Chinese herbal medicine and acupuncture. OUTCOMES: After 4 months of herbal medicine and acupuncture treatment, dysphagia and sialorrhea were relieved considerably. The patient's condition has been stable for more than 3 years and continues to be treated with Chinese herbal medicine and acupuncture. LESSONS: Our case suggests that alternative therapies such as herbal medicine and acupuncture may be effective in alleviating the symptoms of MND/PBP. However, standardized clinical studies are still required to verify the effectiveness and safety.

Current state of research on acupuncture for the treatment of amyotrophic lateral sclerosis: A scoping review.

Objective: To provide an overview of the range and characteristics of existing evidence, research gaps, and future research priorities in treating amyotrophic lateral sclerosis (ALS) with acupuncture. Method: Clinical studies on acupuncture treatment for ALS were searched in 9 databases and two websites. Two independent researchers screened the literature according to the inclusion and exclusion criteria; extracted the demographic data, interventions, and significant findings of the studies; and comprehensively analyzed the characteristics and limitations of the included articles. Results: A total of 2,326 studies were retrieved, of which 92 were included. Most of the studies were conducted in China, with the number increasing over time. Study designs included case reports, case series, randomized controlled trials (RCTs), and before-and-after studies, among which case reports were the most frequently used. A total of 1,388 patients were enrolled, of whom 1,031 had ALS, 274 had progressive bulbar palsy (PBP), 60 had progressive muscle atrophy (PMA), and 23 had primary lateral sclerosis (PLS). Acupuncture interventions included body acupuncture, electroacupuncture, acupoint injection, scalp acupuncture, acupoint massage, Sa-am acupuncture, needle-embedding therapy, auricular acupuncture, venom pharmacopuncture therapy, plum blossom needling, acupoint paste, electroacupuncture, and needle warming through moxibustion. The most frequently used acupoints were ST36, LI4, SP6, and LI11. Acupuncture is often applied in combination with other treatments, such as herbal or Western medicine. The frequency of treatment ranged from once a month to three times a day, and the duration of treatment ranged from 5 days to 3 years. Clinical symptoms, muscle strength, and effective rates were the most frequently used outcomes. Most studies reported significant efficacy, and only a few studies reported adverse events explicitly. Conclusion: Evidence gaps include poor study design, complex interventions, limited significance of the selected outcomes, and limited study reporting. The promotion of acupuncture treatment for ALS still faces several obstacles. Rigorous study design and conduct, standardized intervention and outcome measurements, and normative reporting are needed to investigate the efficacy and safety of acupuncture treatment for ALS.

Effectiveness of acupuncture at acupoint BL1 (Jingming) in comparison with artificial tears for moderate to severe dry eye disease: a randomized controlled trial.

BACKGROUND: The global incidence of dry eye disease (DED) is very high. DED seriously affects the quality of life of patients; however, the current curative effect of medicine for moderate to severe DED is poor. This randomized clinical trial was planned to investigate the effect of acupuncture compared with artificial tears (AT) on moderate to severe DED. METHODS: A randomized clinical trial was performed at 2 hospitals in China. 120 DED patients were randomly equally divided into an acupuncture and an artificial tear group. Either acupuncture or artificial tears was performed for an 8-week period, and a 24-week follow-up was performed. The primary outcome measure was the Schirmer-I test (SIT) change from baseline. The secondary outcome measures included the numerical rating scale (NRS) change from baseline for improvement in ocular symptoms, the ocular surface disease index (OSDI), the tear-film break-up time (TBUT), corneal fluorescein staining (CFS), and acupuncture acceptability. Adverse events also were monitored and documented. RESULTS: For the primary outcome, the mean changes from baseline in the SIT values were significantly different between the acupuncture (5.75 [2.53-9.75]) and AT (0.52 [- 1.18-2.46]) groups at week 8 with a between difference of 5.23 (P < 0.05). Between-group differences of 8.49 in OSDI score change from baseline differed significantly at week 8 (P < 0.05). However, between-group differences of the changes in the average symptom NRS score, TBUT, and CFS did not differ significantly at week 8. Five cases experienced acupuncture-related adverse events. CONCLUSIONS: This randomized clinical trial found that acupuncture at BL1 significantly promoted tear secretion. Acupuncture showed greater benefits than AT for moderate to severe DED. However, the study findings warrant verification. TRIAL REGISTRATION: Registration number: ChiCTR1800015831. Name of trial registry: Efficacy and safety of acupuncture in the treatment of moderate to severe dry eye disease: a randomized controlled trial. Registered on 23 April 2018 ( https://clinicaltrials.gov/ ).

Integrating a Polygenic Risk Score for Coronary Artery Disease as a Risk-Enhancing Factor in the Pooled Cohort Equation: A Cost-Effectiveness Analysis Study.

Background Cardiovascular diseases are the leading cause of death in the United States, yet a significant proportion of adults at high risk remain undetected by standard screening practices. Polygenic risk score for coronary artery disease (CAD-PRS) improves precision in determining the 10-year risk of atherosclerotic cardiovascular disease but health benefits and health care costs associated with CAD-PRS are unknown. We examined the cost-effectiveness of including CAD-PRS as a risk-enhancing factor in the pooled cohort equation (PCE)-the standard of care for determining the risk of atherosclerotic cardiovascular disease-versus PCE alone. Methods and Results We applied a Markov model on a cohort of 40-year-old individuals with borderline or intermediate 10-year risk (5% to <20%) for atherosclerotic cardiovascular disease to identify those in the top quintile of the CAD-PRS distribution who are at high risk and eligible for statin prevention therapy. Health outcomes examined included coronary artery disease (CAD; ie, myocardial infarction) and ischemic stroke. The model projected medical costs (2019 US$) of screening for CAD, statin prevention therapy, treatment, and monitoring patients living with CAD or ischemic stroke and quality-adjusted life-years for PCE+CAD-PRS versus PCE alone. Deterministic and probabilistic sensitivity analyses and scenario analyses were performed to examine uncertainty in parameter inputs. PCE+CAD-PRS was dominant compared with PCE alone in the 5- and 10-year time horizons. We found that, respectively, PCE+CAD-PRS had 0.003 and 0.011 higher mean quality-adjusted life-years and $40 and $181 lower mean costs per person screened, with 29 and 50 fewer events of CAD and ischemic stroke in a cohort of 10 000 individuals compared with PCE alone. The risk of developing CAD, the effectiveness of statin prevention therapy, and the cost of treating CAD had the largest impact on the cost per quality-adjusted life-year gained. However, this cost remained below the $50 000 willingness-to-pay threshold except when the annual risk of developing CAD was <0.006 in the 5-year time horizon. Results from Monte Carlo simulation indicated that PCE+CAD-PRS would be cost-effective. with the probability of 94% and 99% at $50 000 willingness-to-pay threshold in the 5- and 10-year time horizon, respectively. Conclusions Implementing CAD-PRS as a risk-enhancing factor in the PCE to determine the risk of atherosclerotic cardiovascular disease reduced the mean cost per individual, improved quality-adjusted life-years, and averted future events of CAD and ischemic stroke when compared with PCE alone.

Effects of Indwelling Pleural Catheter on Severe Acute Pancreatitis: A Retrospective Study.

BACKGROUND: Pleural effusion (PE) is an important predictor for severity and prognosis of severe acute pancreatitis (SAP). However, there are few studies focused on the effects and timing of indwelling pleural catheter (IPC) on SAP. Considering this, we designed a retrospective study to verify the relationship between PE and severity of SAP and observe the effects and timing of IPC in SAP. METHODS: A total of 309 SAP patients were enrolled. Based on the presence or absence of PE and IPC and IPC time, the enrolled patients were divided into 6 groups. Then, baseline parameters, disease severity, critical complications, ventilator supporting time (VST), length of stay (LOS), and 60-day mortality were compared between each two groups. RESULTS: PE was a risk factor for death of SAP, but not an independent risk factor. SAP patients with PE rather without PE had higher critical complication rates (p < 0.001), along with longer VST (p < 0.001) and LOS (p < 0.001). And the critical complication rates were lower in group 1 (IPC within 1 week of onset) than group 2 (IPC after 1 week of onset). Further, patients in group 1 also had shorter LOS (p = 0.042) and VST (p = 0.001) than those in group 2. In addition, the survival analysis showed the risk of death in the PE group was higher than the non-PE group (HR 6.6, 95% CI, 3.67-11.86, and p < 0.001). And the risk of death in group 1 was lower than group 2 (HR 0.26, 95% CI, 0.08-0.84, and p = 0.025). CONCLUSIONS: PE is a risk factor for death of SAP, but not an independent risk factor. IPC, especially IPC within 1 week of onset, has clinical practical value in SAP.

Effects of immediate or early oral feeding on acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND: The timing of oral refeeding can affect length of stay (LOS) and recovery of acute pancreatitis (AP). However, the optimal timing for oral refeeding is still controversial for AP. This meta-analysis investigated the effects of immediate or early versus delayed oral feeding on mild and moderate AP, regardless of improvement in clinical signs or laboratory indicators. METHODS: This systematic review and meta-analysis of randomized controlled trials (RCTs) based on data from Embase, Cochrane Library, PubMed, Web of science, and CBM before August 2021. Two researchers independently used Stata16 to extract and analyse study data. Random effect model was performed for meta-analysis to calculate the risk ratio (RR) and standardized mean difference (SMD). RESULTS: 8 RCTs were selected, including 748 patients with mild to moderate AP. Patients in IOR (Immediate or early Oral Refeeding) group had less costs [SMD -0.83, 95%CI (-1.17, -0.5), P < 0.001] and shorter LOS [SMD -1.01, 95%CI (-1.17, -0.85), P < 0.001] than the DOR (Delayed Oral Refeeding) group patients. However, there was no difference in mortality [RR 0.54, 95%CI (0.11, 2.62), P = 0.44], pain relapse rate [RR 0.58, 95%CI (0.25, 1.35), P = 0.27], feeding intolerance rate [RR 0.61, 95%CI (0.28, 1.3), P = 0.2], AP progression rate [RR 0.21, 95%CI (0.04, 1.07), P = 0.06] and overall complications rate [RR 0.41, 95%CI (0.17, 1.01), P = 0.05] between the IOR and DOR groups. CONCLUSIONS: Limited data suggest that IOR could reduce LOS and costs without increasing adverse events in mild to moderate AP.

The safety of COVID-19 vaccines in patients with myasthenia gravis: A scoping review.

Background: COVID-19 vaccines are required for individuals with myasthenia gravis (MG), as these patients are more likely to experience severe pneumonia, myasthenia crises, and higher mortality rate. However, direct data on the safety of COVID-19 vaccines in patients with MG are lacking, which results in hesitation in vaccination. This scoping was conducted to collect and summarize the existing evidence on this issue. Methods: PubMed, Cochrane Library, and Web of Science were searched for studies using inclusion and exclusion criteria. Article titles, authors, study designs, demographics of patients, vaccination information, adverse events (AEs), significant findings, and conclusions of included studies were recorded and summarized. Results: Twenty-nine studies conducted in 16 different countries in 2021 and 2022 were included. Study designs included case report, case series, cohort study, cross-sectional study, survey-based study, chart review, and systemic review. A total of 1347 patients were included. The vaccines used included BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, inactivated vaccines, and recombinant subunit vaccines. Fifteen case studies included 48 patients reported that 23 experienced new-onset, and five patients experienced flare of symptoms. Eleven other types of studies included 1299 patients reported that nine patients experienced new-onset, and 60 participants experienced flare of symptoms. Common AEs included local pain, fatigue, asthenia, cephalalgia, fever, and myalgia. Most patients responded well to treatment without severe sequelae. Evidence gaps include limited strength of study designs, type and dose of vaccines varied, inconsistent window of risk and exacerbation criteria, limited number of participants, and lack of efficacy evaluation. Conclusion: COVID-19 vaccines may cause new-onset or worsening of MG in a small proportion of population. Large-scale, multicenter, prospective, and rigorous studies are required to verify their safety.

Economic impact of using maternal plasma cell-free DNA testing to guide further workup in recurrent pregnancy loss.

OBJECTIVE: We have previously demonstrated that maternal-plasma cell-free DNA (cfDNA)-testing can detect chromosomal anomalies in recurrent pregnancy loss (RPL) with 81.8% sensitivity and 90.3% specificity. Here we assess whether this is cost effective in guiding further workup in RPLs. METHOD: A decision-analytic model was developed to compare the cost of various RPL management pathways: (1) current American Society for Reproductive Medicine (ASRM) RPL workup; (2) microarray or karyotyping analysis of products of conception (POCs) and RPL workup only for euploid cases; and (3) cfDNA testing and RPL workup only for euploid cases. Sample accessibility, failure rates, and sensitivity were specified for each test. Costs of sample collection, genetic tests, and RPL workup were considered. Analysis outcomes included detection rate of chromosomal anomaly and cost per patient tested. RESULTS: In comparison to existing cytogenetic testing on POCs, cfDNA testing pathway allowed for better sample accessibility with a lower cost per patient. In addition, using cfDNA to guide further workup significantly increases the number of causative fetal chromosome anomalies detected, reducing the number of patients undergoing unnecessary workup resulting in an overall cost savings. CONCLUSION: Our study showed that inclusion of cfDNA testing is a cost-effective approach to guide RPL workup.

Effects of the Traditional Chinese Medicine Tang Luo Ning on Intestinal Flora and Oxidative Stress in Diabetic Rats.

OBJECTIVE: To determine the effects of TLN on glycolipid metabolism, oxidative stress, and intestinal flora in diabetic rat. MATERIALS AND METHODS: Thirty-five male Sprague-Dawley (SD) rats (180-200 g) were divided into two groups. The normal group was fed a standard-chow diet, whereas, in the model group, diabetes was induced by intraperitoneal administration of streptozotocin (STZ) combined with a high-fat sucrose diet. Then, the model group was randomly allocated to four groups: DM (diabetes model) and TLNH (TLN high dose), TLNL (TLN low dose), and NAC (N-acetylcysteine). Rats in the TLNH, TLNL, and NAC groups were intragastrically administered TLN and NAC for 12 weeks. Subsequently, their weights, fasting glucose levels, serum lipids, serum insulin, serum ROS, and intestinal flora were determined. RESULTS: The weight and intestinal flora abundance of the DM group were significantly lower than those of the normal group, whereas their total serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), serum reactive oxygen species (ROS), and serum insulin (INS) levels were significantly higher than those of the normal group. TC and LDL-C levels in the TLNL group and DM group were similar, whereas FBG, INS, and ROS levels in the TLNL group were obviously lower than those in the DM group. Compared with the DM group, there was a significant increase in intestinal flora abundance in the TLNL group. At the phylum level, the ratio of Firmicutes to Bacteroidetes (core microbiota) varied in all groups. However, in the DM group, Firmicutes abundance decreased, whereas that of Bacteroidetes increased. An opposite trend was observed in the TLN-treated groups. CONCLUSIONS: TLN, which showed a dose-dependent therapeutic effect, can effectively decrease serum lipid, serum insulin, blood glucose, and serum ROS levels. It can also rebalance the ratio of Firmicutes to Bacteroidetes. Furthermore, the low-dose TLN treatment was most efficacious.

Improvement of long-term risks of cardiovascular events associated with community-based disease management in Chinese patients of the Xinjiang autonomous region of China.

BACKGROUND: A recent community-based disease management (CBDM) pilot study reported a 20.5% prevalence of hypertension and a 0.5 and 3.6% prevalence of stroke and coronary heart disease (CHD), respectively, in an elderly population (mean age 65 years) in the Xin Jiang autonomous region of China. The CBDM was initiated in 2013 as an essential public health service; however, the potential long-term impact of CBDM on cardiovascular (CV: CHD and stroke) events is unknown. The objective of the study was to understand the long-term impact of CBDM interventions on CV risk factors using disease-model simulation based on a single-arm experimental study. METHODS: A discrete event simulation was developed to evaluate the impact of CBDM on the long-term CV risk among patients with hypertension, in China's Xin Jiang autonomous region. The model generated pairs of identical patients; one receives CBDM and one does not (control group). Their clinical courses were simulated based on time to CV events (CHD and strokes), which are estimated using published risk equations. The impact of CBDM was incorporated as improvement in systolic blood pressure (SBP) based on observations from the CBDM study. The simulation estimated the number of CV events over patients' lifetimes. RESULTS: During a 2-year follow up, the CBDM led to an average reduction of 8.73 mmHg in SBP from baseline, and a 42% reduction in smoking. The discrete event simulation showed that, in the control group, the model estimated incidence rates of 276, 1789, and 616 per 100,000 individuals for lifetime CHD, stroke, and CV-related death, respectively. The impact of CBDM on SBP translated into reductions of 8, 28, and 23% in CHD, stroke, and CV-related deaths, respectively. Taking into account CBDM's reduction of both SBP and smoking, deaths from CHD, stroke, and CV-related deaths were reduced by 12, 30, and 26%, respectively. CONCLUSIONS: The implementation of CBDM in China's Xinjiang autonomous region is expected to significantly reduce incidences of CHD, strokes, and CV-related deaths.

Cost-effectiveness analysis of dabigatran versus rivaroxaban for stroke prevention in patients with non-valvular atrial fibrillation using real-world evidence in elderly US Medicare beneficiaries.

OBJECTIVE: Dabigatran and rivaroxaban have been approved by the US FDA to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients. Newly published real-world evidence based on the US population found that elderly Medicare patients with NVAF treated with rivaroxaban experienced statistically significant increases in intracranial hemorrhage (ICH) and major extracranial bleeding, and statistically nonsignificant decreases in thromboembolic stroke and acute myocardial infarction (AMI) compared with dabigatran. This study assessed the cost-effectiveness of dabigatran vs. rivaroxaban for the treatment of US Medicare NVAF patients. METHODS: A previously published Markov model was adapted to compare dabigatran and rivaroxaban. The model considered thromboembolic stroke, bleeding events, and AMI based on the published real-world event risks. Model outputs included clinical event rates, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Dabigatran patients experienced fewer ICH and major extracranial bleeding events than rivaroxaban patients, but more stroke and AMI events. Dabigatran was found to yield lower costs and higher QALYs than rivaroxaban, with incremental costs of -$3534 and incremental QALYs of 0.004. Results remained consistent in sensitivity analyses, with a positive net monetary benefit (willingness-to-pay thresholds of $50,000 and $100,000 per QALY) for dabigatran over rivaroxaban for all model inputs tested. CONCLUSIONS: In this study using US Medicare real-world data, dabigatran was found to dominate rivaroxaban. The analyses were limited by the short follow-up period of the real-world data and results may not be generalizable to other patient populations.

Cost-effectiveness of DTG + ABC/3TC versus EFV/TDF/FTC for first-line treatment of HIV-1 in the United States.

OBJECTIVE: Data from the SINGLE trial demonstrated that 88% of treatment-naïve HIV-1 patients treated with dolutegravir and abacavir/lamivudine (DTG + ABC/3TC) achieved viral suppression at 48 weeks compared with 81% of patients treated with efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC). It is unclear how this difference in short-term efficacy impacts long-term cost-effectiveness of these regimens. This study sought to evaluate long-term cost-effectiveness of DTG + ABC/3TC vs EFV/TDF/FTC from a US payer perspective. METHODS: This study is an individual discrete-event simulation which tracked the disease status and treatment pathway of HIV-1 patients. The model simulated treatment over a lifetime horizon by tracking change in patients' CD4 count, clinical events occurrence (opportunistic infections, cancer, and cardiovascular events), treatment switch, and death. The model included up to four lines of treatment. Baseline patient characteristics, efficacy, and safety of DTG + ABC/3TC and EFV/TDF/FTC were informed by data from the SINGLE trial. The efficacy of subsequent treatment lines, clinical event risks, mortality, cost, and utility inputs were based on literature and expert opinion. Outcomes were lifetime discounted medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: Compared with EFV/TDF/FTC, DTG + ABC/3TC increased lifetime costs by $19,153 and per person survival by 0.12 QALYs, resulting in an ICER of $158,890/QALY. ICERs comparing DTG + ABC/3TC to EFV/TDF/FTC remained above the traditional, US willingness-to-pay threshold of $50,000/QALY gained in all scenarios, and above $100,000 or $150,000/QALY gained in most scenarios. LIMITATIONS: Due to data limitations, the treatment patterns, CD4 count during viral rebound and treatment switch, viral rebound after trial end, and long-term adverse event-related treatment discontinuation were based on assumptions, presented to and approved by clinical experts. CONCLUSIONS: Compared with EFV/TDF/FTC, DTG + ABC/3TC resulted in higher cost and only slightly increased QALYs over a lifetime, with an ICER that exceeded the standard cost-effectiveness threshold. This indicates that the incremental benefit in effectiveness associated with DTG + ABC/3TC may not be worth the incremental increase in costs.

Cost-effectiveness of DTG+ABC/3TC versus EFV/TDF/FTC for first-line treatment of HIV-1 in the United States.

INTRODUCTION: Data from the SINGLE trial demonstrated that 88% of treatment-naive HIV-1 patients treated with dolutegravir and abacavir/lamivudine (DTG+ABC/3TC) achieved viral suppression at 48 weeks compared with 81% of patients treated with efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC). It is unclear how this difference in short-term efficacy impacts long-term cost-effectiveness of these regimens. This study sought to evaluate the long-term cost-effectiveness of DTG+ABC/3TC versus EFV/TDF/FTC from a US payer perspective. MATERIALS AND METHODS: An individual discrete-event simulation model tracked the disease status and treatment pathway of HIV-1 patients. The model simulated treatment over a lifetime horizon by tracking change in patients' CD4 count, occurrence of clinical events (opportunistic infections, cancer and cardiovascular events), treatment switch and death. The model included up to four lines of treatment. Baseline patient characteristics, efficacy and safety of DTG+ABC/3TC and EFV/TDF/FTC were informed by data from the SINGLE trial. The efficacy of subsequent lines of treatment, clinical event risks, mortality, cost and utility inputs were based on literature and expert opinion. Outcomes were lifetime medical costs, quality-adjusted life-years (QALYs) (both discounted at 3% per annum) and the incremental cost-effectiveness ratio (ICER). RESULTS: Compared with EFV/TDF/FTC, DTG+ABC/3TC increased lifetime costs by $58,188 and per-person survival by 0.12 QALYs, resulting in an ICER of $482,717/QALY. In sensitivity analyses testing conservative assumptions about EFV/TDF/FTC's efficacy beyond the trial period, ICERs comparing DTG+ABC/3TC to EFV/TDF/FTC remained high (lowest reported ICER of $365,662/QALY). In a scenario in which the price of EFV/TDF/FTC was reduced by 10% to reflect the potential for price reduction as EFV goes off patent, DTG+ABC/3TC's ICER compared to EFV/TDF/FTC was $600,916/QALY. When DTG+ABC/3TC's price was reduced by 10%, the resulting ICER comparing DTG+ABC/3TC to EFV/TDF/FTC was $302,171/QALY. CONCLUSIONS: Compared with EFV/TDF/FTC, DTG+ABC/3TC resulted in substantially higher cost, slightly better QALY over lifetime, and ICERs far exceeding standard cost-effectiveness thresholds, indicating that the incremental benefit in efficacy associated with DTG+ABC/3TC may not be worth the incremental increase in costs.

Efficacy and cost-effectiveness of dabigatran etexilate versus warfarin in atrial fibrillation in different age subgroups.

This study aims to estimate the cost-effectiveness of dabigatran 150 mg twice daily versus warfarin for stroke and systemic embolism risk reduction in patients with nonvalvular atrial fibrillation initiating treatment before age 75 (<75), at or after age 75 (≥ 75), and the overall population (All) from a US Medicare payer perspective. Clinical event rates by age cohort with dabigatran or warfarin for safety-on-treatment and intent-to-treat populations were estimated from Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY). An economic model was adapted using these data to evaluate the impact of starting age on clinical and economic outcomes. Costs were obtained from Medicare payment schedules and utilities from publications. Model outputs included event rates, costs, quality-adjusted life-years, and incremental cost-effectiveness ratios. The RE-LY analysis shows that the <75 cohort has lower rates of all events than the ≥ 75 cohort; versus warfarin, dabigatran performed better in main efficacy and safety in all age cohorts with the exception of extracranial hemorrhage in the ≥ 75 cohort. The clinical event costs avoided per patient for dabigatran were $1,100, $135, and $713 for cohorts <75, ≥ 75, and All, respectively. Extrapolating over a lifetime horizon, the model found that dabigatran resulted in lower rates of stroke and intracranial hemorrhage and higher rates for extracranial hemorrhage versus warfarin for all age cohorts. Lifetime quality-adjusted life-years and costs were higher for dabigatran than warfarin, resulting in incremental cost-effectiveness ratios of $52,773, $65,946, and $56,131 for cohorts <75, ≥ 75, and All, respectively. In conclusion, dabigatran was cost-effective versus warfarin in US patients with atrial fibrillation regardless of age of treatment initiation.

A comparative analysis of models used to evaluate the cost-effectiveness of dabigatran versus warfarin for the prevention of stroke in atrial fibrillation.

BACKGROUND: A number of models exploring the cost-effectiveness of dabigatran versus warfarin for stroke prevention in atrial fibrillation have been published. These studies found dabigatran was generally cost-effective, considering well-accepted willingness-to-pay thresholds, but estimates of the incremental cost-effectiveness ratios (ICERs) varied, even in the same setting. The objective of this study was to compare the findings of the published economic models and identify key model features accounting for differences. METHODS: All aspects of the economic evaluations were reviewed: model approach, inputs, and assumptions. A previously published model served as the reference model for comparisons of the selected studies in the US and UK settings. The reference model was adapted, wherever possible, using the inputs and key assumptions from each of the other published studies to determine if results could be reproduced in the reference model. Incremental total costs, incremental quality-adjusted life years (QALYs), and ICERs (cost per QALY) were compared between each study and the corresponding adapted reference model. The impact of each modified variable or assumption was tracked separately. RESULTS: The selected studies were in the US setting (2), the Canadian setting (1), and the UK setting (2). All models used the Randomized Evaluation of Long-Term Anticoagulation study (RE-LY) as the main source for clinical inputs, and all used a Markov modelling approach, except one that used discrete event simulation. The reference model had been published in the Canadian and UK settings. In the UK setting, the reference model reported an ICER of UK£4,831, whereas the other UK-based analysis reported an ICER of UK£23,082. When the reference model was modified to use the same population characteristics, cost inputs, and utility inputs, it reproduced the results of the other model (ICER UK£25,518) reasonably well. Key reasons for the different results between the two models were the assumptions on the event utility decrement and costs associated with intracranial haemorrhage, as well as the costs of warfarin monitoring and disability following events. In the US setting, the reference model produced an ICER similar to the ICER from one of the US models (US$15,115/QALY versus US$12,386/QALY, respectively) when modelling assumptions and input values were transferred into the reference model. Key differences in results could be explained by the population characteristics (age and baseline stroke risk), utility assigned to events and specific treatments, adjustment of stroke and intracranial haemorrhage risk over time, and treatment discontinuation and switching. The reference model was able to replicate the QALY results, but not the cost results, reported by the other US cost-effectiveness analysis. The parameters driving the QALY results were utility values by disability levels as well as utilities assigned to specific treatments, and event and background mortality rates. CONCLUSIONS: Despite differences in model designs and structures, it was mostly possible to replicate the results published by different authors and identify variables responsible for differences between ICERs using a reference model approach. This enables a better interpretation of published findings by focusing attention on the assumptions underlying the key model features accounting for differences.

Dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in atrial fibrillation in Canada. Comparative efficacy and cost-effectiveness.

Canadian patients with atrial fibrillation (AF) in whom anticoagulation is appropriate have two new choices for anticoagulation for prevention of stroke and systemic embolism--dabigatran etexilate (dabigatran) and rivaroxaban. Based on the RE-LY and ROCKET AF trial results, we investigated the cost-effectiveness of dabigatran (twice daily dosing of 150 mg or 110 mg based on patient age) versus rivaroxaban from a Canadian payer perspective. A formal indirect treatment comparison (ITC) of dabigatran versus rivaroxaban was performed, using dabigatran clinical event rates from RE-LY for the safety-on-treatment population, adjusted to the ROCKET AF population. A previously described Markov model was modified to simulate anticoagulation treatment using ITC results as inputs. Model outputs included total costs, event rates, and quality-adjusted life-years (QALYs). The ITC found when compared to rivaroxaban, dabigatran had a lower risk of intracranial haemorrhage (ICH) (relative risk [RR] = 0.38; 95% confidence interval [CI] 0.21 - 0.67) and stroke (RR = 0.62; 95%CI 0.45-0.87). Over a lifetime horizon, the model found dabigatran-treated patients experienced fewer ICHs (0.33 dabigatran vs. 0.71 rivaroxaban) and ischaemic strokes (3.40 vs. 3.96) per 100 patient-years, and accrued more QALYs (6.17 vs. 6.01). Dabigatran-treated patients had lower acute care and long-term follow-up costs per patient ($52,314 vs. $53,638) which more than offset differences in drug costs ($7,299 vs. $6,128). In probabilistic analysis, dabigatran had high probability of being the most cost-effective therapy at common thresholds of willingness-to-pay (93% at a $20,000/QALY threshold). This study found dabigatran is economically dominant versus rivaroxaban for prevention of stroke and systemic embolism among Canadian AF patients.

Cost-effectiveness of a fourth-generation combination immunoassay for human immunodeficiency virus (HIV) antibody and p24 antigen for the detection of HIV infections in the United States.

PURPOSE: The US Food and Drug Administration recently approved the first 4th-generation HIV test. This study evaluated the cost-effectiveness of the 4th-generation assay versus a 3rd-generation test in screening for HIV infections in the United States. METHODS: An exploratory microsimulation model was developed that follows hypothetical individuals and simulates the course of HIV/AIDS, treatment with highly active antiretroviral therapy, and transmissions. RESULTS: With a 1% HIV prevalence, screening 1.5 million individuals with the 4th- versus 3rd-generation assay resulted in detection of 266 additional HIV cases at an incremental cost per additional HIV case detected of $63,763, an additional 489 life years and 395 quality-adjusted life years (QALYs), and 26 HIV transmissions prevented. Although lifetime costs were increased by $33.6 million, the incremental cost/QALY gained was $85,206. The 4th-generation test was more cost-effective in high incidence settings. The number needed to screen to detect one additional HIV case was 5,635. CONCLUSIONS: Screening using the 4th-generation assay may be cost-effective for HIV detection in appropriate settings, resulting in increased case identification, fewer transmissions, extended life, and increased quality of life. With early and accurate detection, this 4th-generation test may provide a suitable alternative to current 3rd-generation tests.