Browsing by Subject "Randomized Controlled Trials as Topic"
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Item Open Access 5-α reductase inhibitors and prostate cancer prevention: where do we turn now?(BMC Med, 2011-09-15) Hamilton, Robert J; Freedland, Stephen JWith the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite decades of searching for such an agent, physicians still do not have an approved drug to offer their patients. In this article, we outline current strategies for preventing prostate cancer in general, with a focus on the 5-α-reductase inhibitors (5-ARIs) finasteride and dutasteride. We discuss the two landmark randomized, controlled trials of finasteride and dutasteride, highlighting the controversies stemming from the results, and address the issue of 5-ARI use, including reasons why providers may be hesitant to use these agents for chemoprevention. We further discuss the recent US Food and Drug Administration ruling against the proposed new indication for dutasteride and the change to the labeling of finasteride, both of which were intended to permit physicians to use the drugs for chemoprevention. Finally, we discuss future directions for 5-ARI research.Item Open Access A brief history of research synthesis.(Eval Health Prof, 2002-03) Chalmers, Iain; Hedges, Larry V; Cooper, HarrisScience is supposed to be cumulative, but scientists only rarely cumulate evidence scientifically. This means that users of research evidence have to cope with a plethora of reports of individual studies with no systematic attempt made to present new results in the context of similar studies. Although the need to synthesize research evidence has been recognized for well over two centuries, explicit methods for this form of research were not developed until the 20th century. The development of methods to reduce statistical imprecision using quantitative synthesis (meta-analysis) preceded the development of methods to reduce biases, the latter only beginning to receive proper attention during the last quarter of the 20th century. In this article, the authors identify some of the trends and highlights in this history, to which researchers in the physical, natural, and social sciences have all contributed, and speculate briefly about the "future history" of research synthesis.Item Open Access A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design.(Trials, 2014-01) Goswami, Neela D; Tsalik, Ephraim L; Naggie, Susanna; Miller, William C; Horton, John R; Pfeiffer, Christopher D; Hicks, Charles BBackground
The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves.Methods
We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition.Results
The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials.Conclusions
No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology.Item Open Access Adaptive intervention design in mobile health: Intervention design and development in the Cell Phone Intervention for You trial.(Clin Trials, 2015-12) Lin, Pao-Hwa; Intille, Stephen; Bennett, Gary; Bosworth, Hayden B; Corsino, Leonor; Voils, Corrine; Grambow, Steven; Lazenka, Tony; Batch, Bryan C; Tyson, Crystal; Svetkey, Laura PBACKGROUND/AIMS: The obesity epidemic has spread to young adults, and obesity is a significant risk factor for cardiovascular disease. The prominence and increasing functionality of mobile phones may provide an opportunity to deliver longitudinal and scalable weight management interventions in young adults. The aim of this article is to describe the design and development of the intervention tested in the Cell Phone Intervention for You study and to highlight the importance of adaptive intervention design that made it possible. The Cell Phone Intervention for You study was a National Heart, Lung, and Blood Institute-sponsored, controlled, 24-month randomized clinical trial comparing two active interventions to a usual-care control group. Participants were 365 overweight or obese (body mass index≥25 kg/m2) young adults. METHODS: Both active interventions were designed based on social cognitive theory and incorporated techniques for behavioral self-management and motivational enhancement. Initial intervention development occurred during a 1-year formative phase utilizing focus groups and iterative, participatory design. During the intervention testing, adaptive intervention design, where an intervention is updated or extended throughout a trial while assuring the delivery of exactly the same intervention to each cohort, was employed. The adaptive intervention design strategy distributed technical work and allowed introduction of novel components in phases intended to help promote and sustain participant engagement. Adaptive intervention design was made possible by exploiting the mobile phone's remote data capabilities so that adoption of particular application components could be continuously monitored and components subsequently added or updated remotely. RESULTS: The cell phone intervention was delivered almost entirely via cell phone and was always-present, proactive, and interactive-providing passive and active reminders, frequent opportunities for knowledge dissemination, and multiple tools for self-tracking and receiving tailored feedback. The intervention changed over 2 years to promote and sustain engagement. The personal coaching intervention, alternatively, was primarily personal coaching with trained coaches based on a proven intervention, enhanced with a mobile application, but where all interactions with the technology were participant-initiated. CONCLUSION: The complexity and length of the technology-based randomized clinical trial created challenges in engagement and technology adaptation, which were generally discovered using novel remote monitoring technology and addressed using the adaptive intervention design. Investigators should plan to develop tools and procedures that explicitly support continuous remote monitoring of interventions to support adaptive intervention design in long-term, technology-based studies, as well as developing the interventions themselves.Item Open Access Advances in opioid antagonist treatment for opioid addiction.(The Psychiatric clinics of North America, 2012-06) Ling, Walter; Mooney, Larissa; Wu, Li-TzyItem Open Access Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials.(Psychosom Med, 2010-04) Smith, Patrick J; Blumenthal, James A; Hoffman, Benson M; Cooper, Harris; Strauman, Timothy A; Welsh-Bohmer, Kathleen; Browndyke, Jeffrey N; Sherwood, AndrewOBJECTIVES: To assess the effects of aerobic exercise training on neurocognitive performance. Although the effects of exercise on neurocognition have been the subject of several previous reviews and meta-analyses, they have been hampered by methodological shortcomings and are now outdated as a result of the recent publication of several large-scale, randomized, controlled trials (RCTs). METHODS: We conducted a systematic literature review of RCTs examining the association between aerobic exercise training on neurocognitive performance between January 1966 and July 2009. Suitable studies were selected for inclusion according to the following criteria: randomized treatment allocation; mean age > or =18 years of age; duration of treatment >1 month; incorporated aerobic exercise components; supervised exercise training; the presence of a nonaerobic-exercise control group; and sufficient information to derive effect size data. RESULTS: Twenty-nine studies met inclusion criteria and were included in our analyses, representing data from 2049 participants and 234 effect sizes. Individuals randomly assigned to receive aerobic exercise training demonstrated modest improvements in attention and processing speed (g = 0.158; 95% confidence interval [CI]; 0.055-0.260; p = .003), executive function (g = 0.123; 95% CI, 0.021-0.225; p = .018), and memory (g = 0.128; 95% CI, 0.015-0.241; p = .026). CONCLUSIONS: Aerobic exercise training is associated with modest improvements in attention and processing speed, executive function, and memory, although the effects of exercise on working memory are less consistent. Rigorous RCTs are needed with larger samples, appropriate controls, and longer follow-up periods.Item Open Access Assisted ambulation to improve health outcomes for older medical inpatients (AMBULATE): study protocol for a randomized controlled trial.(Trials, 2023-07) Johnson, Joshua K; Hamilton, Aaron C; Hu, Bo; Pack, Quinn R; Lindenauer, Peter K; Fox, Robert J; Hashmi, Ardeshir; Siegmund, Lee Anne; Burchill, Christian N; Taksler, Glen B; Goto, Toyomi; Stilphen, Mary; Rothberg, Michael BBackground
Hospitalized older adults spend as much as 95% of their time in bed, which can result in adverse events and delay recovery while increasing costs. Observational studies have shown that general mobility interventions (e.g., ambulation) can mitigate adverse events and improve patients' functional status. Mobility technicians (MTs) may address the need for patients to engage in mobility interventions without overburdening nurses. There is no data, however, on the effect of MT-assisted ambulation on adverse events or functional status, or on the cost tradeoffs if a MT were employed. The AMBULATE study aims to determine whether MT-assisted ambulation improves mobility status and decreases adverse events for older medical inpatients. It will also include analyses to identify the patients that benefit most from MT-assisted mobility and assess the cost-effectiveness of employing a MT.Methods
The AMBULATE study is a multicenter, single-blind, parallel control design, individual-level randomized trial. It will include patients admitted to a medical service in five hospitals in two regions of the USA. Patients over age 65 with mild functional deficits will be randomized using a block randomization scheme. Those in the intervention group will ambulate with the MT up to three times daily, guided by the Johns Hopkins Mobility Goal Calculator. The intervention will conclude at hospital discharge, or after 10 days if the hospitalization is prolonged. The primary outcome is the Short Physical Performance Battery score at discharge. Secondary outcomes are discharge disposition, length of stay, hospital-acquired complications (falls, venous thromboembolism, pressure ulcers, and hospital-acquired pneumonia), and post-hospital functional status.Discussion
While functional decline in the hospital is multifactorial, ambulation is a modifiable factor for many patients. The AMBULATE study will be the largest randomized controlled trial to test the clinical effects of dedicating a single care team member to facilitating mobility for older hospitalized patients. It will also provide a useful estimation of cost implications to help hospital administrators assess the feasibility and utility of employing MTs.Trial registration
Registered in the United States National Library of Medicine clinicaltrials.gov (# NCT05725928). February 13, 2023.Item Open Access Auriculotherapy for pain management: a systematic review and meta-analysis of randomized controlled trials.(J Altern Complement Med, 2010-10) Asher, Gary N; Jonas, Daniel E; Coeytaux, Remy R; Reilly, Aimee C; Loh, Yen L; Motsinger-Reif, Alison A; Winham, Stacey JOBJECTIVES: Side-effects of standard pain medications can limit their use. Therefore, nonpharmacologic pain relief techniques such as auriculotherapy may play an important role in pain management. Our aim was to conduct a systematic review and meta-analysis of studies evaluating auriculotherapy for pain management. DESIGN: MEDLINE,(®) ISI Web of Science, CINAHL, AMED, and Cochrane Library were searched through December 2008. Randomized trials comparing auriculotherapy to sham, placebo, or standard-of-care control were included that measured outcomes of pain or medication use and were published in English. Two (2) reviewers independently assessed trial eligibility, quality, and abstracted data to a standardized form. Standardized mean differences (SMD) were calculated for studies using a pain score or analgesic requirement as a primary outcome. RESULTS: Seventeen (17) studies met inclusion criteria (8 perioperative, 4 acute, and 5 chronic pain). Auriculotherapy was superior to controls for studies evaluating pain intensity (SMD, 1.56 [95% confidence interval (CI): 0.85, 2.26]; 8 studies). For perioperative pain, auriculotherapy reduced analgesic use (SMD, 0.54 [95% CI: 0.30, 0.77]; 5 studies). For acute pain and chronic pain, auriculotherapy reduced pain intensity (SMD for acute pain, 1.35 [95% CI: 0.08, 2.64], 2 studies; SMD for chronic pain, 1.84 [95% CI: 0.60, 3.07], 5 studies). Removal of poor quality studies did not alter the conclusions. Significant heterogeneity existed among studies of acute and chronic pain, but not perioperative pain. CONCLUSIONS: Auriculotherapy may be effective for the treatment of a variety of types of pain, especially postoperative pain. However, a more accurate estimate of the effect will require further large, well-designed trials.Item Open Access Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child.(Addiction (Abingdon, England), 2016-12) Zedler, Barbara K; Mann, Ashley L; Kim, Mimi M; Amick, Halle R; Joyce, Andrew R; Murrelle, E Lenn; Jones, Hendrée EAims
To assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder.Methods
We searched PubMed, Embase and the Cochrane Library from inception to February 2015 for randomized controlled trials (RCT) and observational cohort studies (OBS) that compared buprenorphine with methadone for treating opioid-dependent pregnant women. Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events. We ascertained each study's risk of bias using validated instruments and assessed the strength of evidence for each outcome using established methods. We computed effect sizes using random-effects models for each outcome with two or more studies.Results
Three RCTs (n = 223) and 15 cohort OBSs (n = 1923) met inclusion criteria. In meta-analyses using unadjusted data and methadone as comparator, buprenorphine was associated with lower risk of preterm birth [RCT risk ratio (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.91; OBS RR = 0.67, 95% CI = 0.50, 0.90], greater birth weight [RCT weighted mean difference (WMD) = 277 g, 95% CI = 104, 450; OBS WMD = 265 g, 95% CI = 196, 335] and larger head circumference [RCT WMD = 0.90 cm, 95% CI = 0.14, 1.66; OBS WMD = 0.68 cm, 95% CI = 0.41, 0.94]. No treatment differences were observed for spontaneous fetal death, fetal/congenital anomalies and other fetal growth measures, although the power to detect such differences may be inadequate due to small sample sizes.Conclusions
Moderately strong evidence indicates lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of maternal opioid use disorder during pregnancy compared with methadone treatment, and no greater harms.Item Open Access Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial.(J Policy Anal Manage, 2015) Albert, Dustin; Belsky, Daniel W; Crowley, D Max; Latendresse, Shawn J; Aliev, Fazil; Riley, Brien; Group, Conduct Problems Prevention Research; Dick, Danielle M; Dodge, Kenneth AEarly interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era.Item Open Access Caveat emptor: the combined effects of multiplicity and selective reporting.(Trials, 2018-09-17) Li, Tianjing; Mayo-Wilson, Evan; Fusco, Nicole; Hong, Hwanhee; Dickersin, KayClinical trials and systematic reviews of clinical trials inform healthcare decisions. There is growing concern, however, about results from clinical trials that cannot be reproduced. Reasons for nonreproducibility include that outcomes are defined in multiple ways, results can be obtained using multiple methods of analysis, and trial findings are reported in multiple sources ("multiplicity"). Multiplicity combined with selective reporting can influence dissemination of trial findings and decision-making. In particular, users of evidence might be misled by exposure to selected sources and overly optimistic representations of intervention effects. In this commentary, drawing from our experience in the Multiple Data Sources in Systematic Reviews (MUDS) study and evidence from previous research, we offer practical recommendations to enhance the reproducibility of clinical trials and systematic reviews.Item Open Access Changing CHANGE: adaptations of an evidence-based telehealth cardiovascular disease risk reduction intervention.(Translational behavioral medicine, 2018-03) Zullig, Leah L; McCant, Felicia; Silberberg, Mina; Johnson, Fred; Granger, Bradi B; Bosworth, Hayden BRelatively few successful medication adherence interventions are translated into real-world clinical settings. The Prevention of Cardiovascular Outcomes in African Americans with Diabetes (CHANGE) intervention was originally conceived as a randomized controlled trial to improve cardiovascular disease-related medication adherence and health outcomes. The purpose of the study was to describe the translation of the CHANGE trial into two community-based clinical programs. CHANGE 2 was available to Medicaid patients with diabetes and hypertension whose primary care homes were part of a care management network in the Northern Piedmont region of North Carolina. CHANGE 3 was available to low-income patients receiving care in three geographical areas with multiple chronic conditions at low or moderate risk for developing cardiovascular disease. Adaptations were made to ensure fit with available organizational resources and the patient population's health needs. Data available for evaluation are presented. For CHANGE 2, we evaluated improvement in A1c control using paired t test. For both studies, we describe feasibility measured by percentage of patients who completed the curriculum. CHANGE 2 involved 125 participants. CHANGE 3 had 127 participants. In CHANGE 2, 69 participants had A1c measurements at baseline and 12-month follow-up; A1c improved from 8.4 to 7.8 (p = .008). In CHANGE 3, interventionists completed 47% (n = 45) of calls to enroll participants at the 4-month encounter, and among those eligible for a 12-month call (n = 52), 21% of 12-month calls were completed with participants. In CHANGE 2, 40% of participants (n = 50) completed all 12 encounters. Thoughtful adaptation is critical to translate clinical trials into community-based clinic settings. Successful implementation of adapted evidence-based interventions may be feasible and can positively affect patients' disease control.Item Open Access Chronic Lyme disease: the controversies and the science.(Expert Rev Anti Infect Ther, 2011-07) Lantos, Paul MThe diagnosis of chronic Lyme disease has been embroiled in controversy for many years. This is exacerbated by the lack of a clinical or microbiologic definition, and the commonality of chronic symptoms in the general population. An accumulating body of evidence suggests that Lyme disease is the appropriate diagnosis for only a minority of patients in whom it is suspected. In prospective studies of Lyme disease, very few patients go on to have a chronic syndrome dominated by subjective complaints. There is no systematic evidence that Borrelia burgdorferi, the etiology of Lyme disease, can be identified in patients with chronic symptoms following treated Lyme disease. Multiple prospective trials have revealed that prolonged courses of antibiotics neither prevent nor alleviate such post-Lyme syndromes. Extended courses of intravenous antibiotics have resulted in severe adverse events, which in light of their lack of efficacy, make them contraindicated.Item Open Access Clinical trials registration.(PLoS Med, 2006-03) Rockhold, Frank W; Krall, Ronald LItem Open Access Comparison of methods that combine multiple randomized trials to estimate heterogeneous treatment effects.(Statistics in medicine, 2024-03) Brantner, Carly Lupton; Nguyen, Trang Quynh; Tang, Tengjie; Zhao, Congwen; Hong, Hwanhee; Stuart, Elizabeth AIndividualized treatment decisions can improve health outcomes, but using data to make these decisions in a reliable, precise, and generalizable way is challenging with a single dataset. Leveraging multiple randomized controlled trials allows for the combination of datasets with unconfounded treatment assignment to better estimate heterogeneous treatment effects. This article discusses several nonparametric approaches for estimating heterogeneous treatment effects using data from multiple trials. We extend single-study methods to a scenario with multiple trials and explore their performance through a simulation study, with data generation scenarios that have differing levels of cross-trial heterogeneity. The simulations demonstrate that methods that directly allow for heterogeneity of the treatment effect across trials perform better than methods that do not, and that the choice of single-study method matters based on the functional form of the treatment effect. Finally, we discuss which methods perform well in each setting and then apply them to four randomized controlled trials to examine effect heterogeneity of treatments for major depressive disorder.Item Open Access Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--The BRACE CORONA Trial.(American heart journal, 2020-08) Lopes, Renato D; Macedo, Ariane Vieira Scarlatelli; de Barros E Silva, Pedro Gabriel Melo; Moll-Bernardes, Renata Junqueira; Feldman, Andre; D'Andréa Saba Arruda, Guilherme; de Souza, Andrea Silvestre; de Albuquerque, Denilson Campos; Mazza, Lilian; Santos, Mayara Fraga; Salvador, Natalia Zerbinatti; Gibson, C Michael; Granger, Christopher B; Alexander, John H; de Souza, Olga Ferreira; BRACE CORONA investigatorsAngiotensin-converting enzyme-2 (ACE2) expression may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. DESIGN: BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 34 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from cardiovascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, and troponin, B-type natriuretic peptide (BNP), N-terminal-proBNP, and D-dimer levels. SUMMARY: BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19.Item Open Access Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial.(Trials, 2022-05) Turner, Nicholas A; Zaharoff, Smitha; King, Heather; Evans, Scott; Hamasaki, Toshimitsu; Lodise, Thomas; Ghazaryan, Varduhi; Beresnev, Tatiana; Riccobene, Todd; Patel, Rinal; Doernberg, Sarah B; Rappo, Urania; Fowler, Vance G; Holland, Thomas L; Antibacterial Resistance Leadership Group (ARLG)Background
Staphylococcus aureus bacteremia is a life-threatening infection and leading cause of infective endocarditis, with mortality rates of 15-50%. Treatment typically requires prolonged administration of parenteral therapy, itself associated with high costs and potential catheter-associated complications. Dalbavancin is a lipoglycopeptide with potent activity against Staphylococcus and a long half-life, making it an appealing potential therapy for S. aureus bacteremia without the need for durable central venous access.Methods
DOTS is a phase 2b, multicenter, randomized, assessor-blinded, superiority, active-controlled, parallel-group trial. The trial will enroll 200 adults diagnosed with complicated S. aureus bacteremia, including definite or possible right-sided infective endocarditis, who have been treated with effective antibiotic therapy for at least 72 h (maximum 10 days) and with subsequent clearance of bacteremia prior to randomization to study treatment. Subjects will be randomized 1:1 to complete their antibiotic treatment course with either two doses of dalbavancin on days 1 and 8, or with a total of 4-8 weeks of standard intravenous antibiotic therapy. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at day 70 for patients randomized to dalbavancin versus standard of care. Key secondary endpoints include quality of life outcomes and pharmacokinetic analyses of dalbavancin.Discussion
The DOTS trial will establish whether dalbavancin is superior to standard parenteral antibiotic therapy for the completion of treatment of complicated S. aureus bacteremia.Trial registration
US National Institutes of Health ClinicalTrials.gov NCT04775953 . Registered on 1 March 2021.Item Open Access Does distance modify the effect of self-testing in oral anticoagulation?(The American journal of managed care, 2016-01) Rose, Adam J; Phibbs, Ciaran S; Uyeda, Lauren; Su, Pon; Edson, Robert; Shih, Mei-Chiung; Jacobson, Alan; Matchar, David BObjectives
Patient self-testing (PST) improves anticoagulation control and patient satisfaction. It is unknown whether these effects are more pronounced when the patient lives farther from the anticoagulation clinic (ACC). If the benefits of PST are limited to a subset of patients (those living farther from care), selectively providing PST to that subset could enhance cost-effectiveness.Study design
This is a secondary analysis of a randomized trial of PST versus usual ACC care, which involved 2922 patients of the Veterans Health Administration (VHA).Methods
Our 3 outcomes were the primary composite clinical end point (stroke, major hemorrhage, or death), anticoagulation control (percent time in therapeutic range), and satisfaction with anticoagulation care. We measured the driving distance between the patient's residence and the nearest VHA facility. We divided patients into quartiles by distance and looked for evidence of an interaction between distance and the effect of the intervention on the 3 outcomes.Results
The median driving distance was 12 miles (interquartile range = 6-21). Patients living in the farthest quartile had higher rates of the primary composite clinical end point in both groups compared with patients living in the nearest quartile. For PST, the hazard ratio (HR) was 1.77 (95% CI, 1.18-2.64), and for usual care, the HR was 1.81 (95% CI, 1.19-2.75). Interaction terms did not suggest that distance to care modified the effect of the intervention on any outcome.Conclusions
The benefits of PST were not enhanced among patients living farther from care. Restricting PST to patients living more than a certain distance from the ACC is not likely to improve its cost-effectiveness.Item Open Access Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.(The New England journal of medicine, 2017-06) PRISM Investigators; Rowan, Kathryn M; Angus, Derek C; Bailey, Michael; Barnato, Amber E; Bellomo, Rinaldo; Canter, Ruth R; Coats, Timothy J; Delaney, Anthony; Gimbel, Elizabeth; Grieve, Richard D; Harrison, David A; Higgins, Alisa M; Howe, Belinda; Huang, David T; Kellum, John A; Mouncey, Paul R; Music, Edvin; Peake, Sandra L; Pike, Francis; Reade, Michael C; Sadique, M Zia; Singer, Mervyn; Yealy, Donald MBACKGROUND:After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. METHODS:We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. RESULTS:We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. CONCLUSIONS:In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158 .).Item Open Access Efficacy of BETTER transitional care intervention for diverse patients with traumatic brain injury and their families: Study protocol of a randomized controlled trial.(PloS one, 2024-01) Oyesanya, Tolu O; Ibemere, Stephanie O; You, HyunBin; Emerson, Maralis Mercado; Pan, Wei; Palipana, Anushka; Kandel, Melissa; Ingram, Darius; Soto, Mayra; Pioppo, Anne; Albert, Brittany; Walker-Atwater, Tamia; Hawes, Jodi; Komisarow, Jordan; Ramos, Katherine; Byom, Lindsey; Gonzalez-Guarda, Rosa; Van Houtven, Courtney H; Agarwal, Suresh; Prvu Bettger, JanetObjective
The purpose of this study is to examine the efficacy of BETTER (Brain Injury, Education, Training, and Therapy to Enhance Recovery) vs. usual transitional care management among diverse adults with traumatic brain injury (TBI) discharged home from acute hospital care and families.Methods
This will be a single-site, two-arm, randomized controlled trial (N = 436 people, 218 patient/family dyads, 109 dyads per arm) of BETTER, a culturally- and linguistically-tailored, patient- and family-centered, TBI transitional care intervention for adult patients with TBI and families. Skilled clinical interventionists will follow a manualized protocol to address patient/family needs. The interventionists will co-establish goals with participants; coordinate post-hospital care, services, and resources; and provide patient/family education and training on self- and family-management and coping skills for 16 weeks following hospital discharge. English- and Spanish-speaking adult patients with mild-to-severe TBI who are discharged directly home from the hospital without inpatient rehabilitation or transfer to other settings (community discharge) and associated family caregivers are eligible and will be randomized to treatment or usual transitional care management. We will use intention-to-treat analysis to determine if patients receiving BETTER have a higher quality of life (primary outcome, SF-36) at 16-weeks post-hospital discharge than those receiving usual transitional care management. We will conduct a descriptive, qualitative study with 45 dyads randomized to BETTER, using semi-structured interviews, to capture perspectives on barriers and facilitators to participation. Data will be analyzed using conventional content analysis. Finally, we will conduct a cost/budget impact analysis, evaluating differences in intervention costs and healthcare costs by arm.Discussion
Findings will guide our team in designing a future, multi-site trial to disseminate and implement BETTER into clinical practice to enhance the standard of care for adults with TBI and families. The new knowledge generated will drive advancements in health equity among diverse adults with TBI and families.Trial registration
NCT05929833.