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2.
J Clin Neurosci ; 89: 1-7, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34119250

RESUMO

Robotic systems to assist with pedicle screw placement have recently emerged in the field of spine surgery. Here, the authors systematically reviewed the literature for evidence of these robotic systems and their utility. Thirty-four studies that reported the use of spinal instrumentation with robotic assistance and met inclusion criteria were identified. The outcome measures gathered included: pedicle screw accuracy, indications for surgery, rates of conversion to an alternative surgical method, radiation exposure, and learning curve. In our search there were five different robotic systems identified. All studies reported accuracy and the most commonly used accuracy grading scale was the Gertzbein Robbins scale (GRS). Accuracy of clinically acceptable pedicle screws, defined as < 2 mm cortical breech, ranged from 80% to 100%. Many studies categorized indications for robotic surgery with the most common being degenerative entities. Some studies reported rates of conversion from robotic assistance to manual instrumentation due to many reasons, with robotic failure as the most common. Radiation exposure data revealed a majority of studies reported less radiation using robotic systems. Studies looking at a learning curve effect with surgeon use of robotic assistance were not consistent across the literature. Robotic systems for assistance in spine surgery have continued to improve and the accuracy of pedicle screw placement remains superior when compared to free-hand technique, however rates of manual conversion are significant. Currently, these systems are successfully employed in various pathological entities where trained spine surgeons can be safe and accurate regardless of robotic training.


Assuntos
Procedimentos Neurocirúrgicos/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Doenças da Coluna Vertebral/cirurgia , Coluna Vertebral/cirurgia , Cirurgia Assistida por Computador/métodos , Humanos , Curva de Aprendizado , Procedimentos Neurocirúrgicos/instrumentação , Parafusos Pediculares , Estudos Prospectivos , Exposição à Radiação/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/instrumentação , Doenças da Coluna Vertebral/diagnóstico , Cirurgiões/tendências , Cirurgia Assistida por Computador/instrumentação
3.
J Clin Neurosci ; 89: 216-222, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34119270

RESUMO

BACKGROUND AND PURPOSE: In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. METHODS: The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1-4, 3) MBs 5-9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages. RESULTS: Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1-4, 48 (4%) had MBs 5-9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1-4, 94% in the MBs 5-9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1-4, MBs 5-9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10). CONCLUSIONS: MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.


Assuntos
Terapia Antiplaquetária Dupla/métodos , Microvasos , Estudos Multicêntricos como Assunto/métodos , Inibidores da Agregação Plaquetária/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/diagnóstico por imagem , Cilostazol/administração & dosagem , Cilostazol/efeitos adversos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Microvasos/diagnóstico por imagem , Microvasos/efeitos dos fármacos , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Resultado do Tratamento
4.
Eur Rev Med Pharmacol Sci ; 25(9): 3594-3606, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34002834

RESUMO

OBJECTIVE: Patients with 2019-nCoV infection have a high risk to develop venous thrombotic events. Several guidelines recommend the use of either unfractionated heparin or low molecular weight heparins in preventing thrombotic events in these patients. However, results from clinical studies, so far published, reached controversial conclusions on heparin efficacy in this kind of patients since the incidence of venous thromboembolism remains high despite prophylaxis. This narrative review aims to provide an overview of the antiviral and anti-inflammatory properties of heparins and their efficacy and safety in SARS-CoV-2 medical ward-patients. Moreover, anatomical findings and ongoing trials are also reported. Finally, this narrative review tries to explain why heparins fail to prevent venous thrombosis. MATERIALS AND METHODS: We searched for the most relevant published studies on heparins and 2019-nCoV infected patients using the MEDLINE electronic database in the period between January and December 2020. Articles were preliminarily defined as eligible if they: a) were in English language, b) enrolled 250 or more medical ward-patients and 100 or more ICU-patients, c) reported results on patients treated with heparins in a percentage of at least 70% and d) performed an objectively confirmed diagnosis of VTE. RESULTS: Data from medium to large scientific studies show that the incidence of venous thrombotic events in medical ward-patients with SARS-CoV-2 vary between 0% and 8.3%, while this rate is higher, from 6.2% to 49%, in Intensive Care Unit-patients. However, heparins reduce the mortality rate in these patients of about 50%. Histological findings show that thrombosis could affect capillaries, main and small-mid-sized vessels, and it is associated with diffuse alveolar damage. CONCLUSIONS: Heparins have anti-inflammatory and anti-viral properties, which may be of help in reducing mortality in SARS-CoV-2 patients. Failure of heparins at prophylactic dosages in preventing VTE, especially in ICU-patients, could be due to the severity of the disease. Data on the use of heparins in an early phase of the 2019-nCoV infection are still lacking.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/tratamento farmacológico , Heparina/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , COVID-19/epidemiologia , COVID-19/imunologia , Humanos , Mortalidade/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/imunologia
5.
J Pharm Pharm Sci ; 24: 237-245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34048669

RESUMO

PURPOSE: To evaluate the safety and efficacy of remdesivir in adult patients with COVID-19. METHODS: PubMed, Embase, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, and medRxiv databases were searched using a search strategy tailored to each database. The Consolidated Standards of Reporting Trials (CONSORT) and Strengthening the reporting of observational studies in epidemiology (STROBE) checklists were used for the studies' qualitative assessment. The outcomes studied were mortality, all adverse events, serious adverse events, and clinical improvement. The quantitative synthesis was conducted using fixed and random effects models in the CMA 2.2. Heterogeneity was tested using the I-squared (I2) measure. RESULTS: In general, six studies, including five randomized controlled trials and one cohort study were found eligible. Comparison of the findings related to both groups receiving remdesivir (10-day remdesivir group) and placebo/control group showed that remdesivir treatment had no significant effect on mortality at day 14 of the treatment (RR=0.769; 95% CI :0.563-1.050; p=0.098), and all adverse events (RR= 1.078; 95% CI: 0.908-1.279; p= 0.392). However, remdesivir had a significant effect on clinical improvement at day 14 compared to placebo/control (OR= 1.447; 95% CI: 1.005-2.085; p= 0.047) and reduced serious adverse events (RR= 0.736; 95% CI: 0.611-0.887; p= 0.001). CONCLUSION: Remdesivir has positive effects on clinical improvement, and reduction of the risk of serious adverse events. However, it does not influence the mortality at day 14 of treatment.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , COVID-19/diagnóstico , COVID-19/epidemiologia , Humanos , Hipoalbuminemia/induzido quimicamente , Hipopotassemia/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento
6.
J Pharm Pharm Sci ; 24: 246-257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34048671

RESUMO

PURPOSE: To provide the latest evidence on the efficacy and safety of lopinavir/ritonavir compared to other treatment options for COVID-19. METHODS: We searched PubMed, Cochran Library, Embase, Scopus, and Web of Science for the relevant records up to April 2021. Moreover, we scanned MedRxiv, Google Scholar, and clinical registry databases to identify additional records. We have used the Newcastle-Ottawa Scale and Cochrane risk of bias tools to assess the quality of studies. This Meta-analysis was conducted using RevMan software (version 5.3). RESULTS: Fourteen studies were included. No significant difference was observed between lopinavir/ritonavir and non-antiviral treatment groups in terms of negative rate of PCR (polymerase chain reaction) on day 7 (risk ratio [RR]: 0.83; 95% CI: 0.63 to 1.09; P=0.17), and day 14 (RR: 0.93; 95% CI: 0.81 to 1.05; P=0.25), PCR negative conversion time (mean difference [MD]: 1.09; 95% CI: -0.10 to 2.29; P=0.07), secondary outcomes, and adverse events (P>0.05). There was no significant difference between lopinavir/ritonavir and chloroquine as well as lopinavir/ritonavir and hydroxychloroquine regarding the efficacy outcomes (P>0.05). However, lopinavir/ritonavir showed better efficacy than arbidol for the same outcomes (P<0.05). Lopinavir/ritonavir plus arbidol was effective compared to arbidol alone in terms of the negative rate of PCR on day 7 (P=0.02). However, this difference was not significant regarding other efficacy outcomes (P>0.05). CONCLUSION: Lopinavir/ritonavir has no more treatment effects than other therapeutic agents used herein in COVID-19 patients.


Assuntos
COVID-19/tratamento farmacológico , Lopinavir/administração & dosagem , Ritonavir/administração & dosagem , COVID-19/diagnóstico , Quimioterapia Combinada , Inibidores da Protease de HIV/administração & dosagem , Humanos , Hidroxicloroquina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Estudos Retrospectivos
7.
Paediatr Drugs ; 23(4): 349-359, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34036532

RESUMO

Lidocaine is an amino amide with a well-established role as a local anesthetic agent. Systemic intravenous administration expands its clinical use to include acute and chronic pain circumstances, such as postoperative pain, neuropathic pain, postherpetic neuralgia, hyperalgesia, visceral pain, and centrally mediated pain. For refractory pain that has not responded to conventional therapy or if further escalation of treatment is prevented by contraindications or side effects to standard therapies, a continuous infusion of lidocaine may be considered as a single intervention or as a sequence of infusions. Here, we review and evaluate published data reflecting the use of lidocaine continuous infusions for pain management in the pediatric population.


Assuntos
Anestésicos Locais/administração & dosagem , Lidocaína/administração & dosagem , Manejo da Dor/métodos , Pediatria/métodos , Adolescente , Anestesia Local/métodos , Criança , Dor Crônica/diagnóstico , Dor Crônica/tratamento farmacológico , Feminino , Humanos , Infusões Intravenosas , Masculino , Neuralgia/diagnóstico , Neuralgia/tratamento farmacológico , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
9.
Clin Trials ; 18(4): 391-397, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34041932

RESUMO

BACKGROUND: Although several COVID-19 vaccines have been found to be effective in rigorous evaluation and have emerging availability in parts of the world, their supply will be inadequate to meet international needs for a considerable period of time. There also will be continued interest in vaccines that are more effective or have improved scalability to facilitate mass vaccination campaigns. Ongoing clinical testing of new vaccines also will be needed as variant strains continue to emerge that may elude some aspects of immunity induced by current vaccines. Randomized clinical trials meaningfully enhance the efficiency and reliability of such clinical testing. In clinical settings with limited or no access to known effective vaccines, placebo-controlled randomized trials of new vaccines remain a preferred approach to maximize the reliability, efficiency and interpretability of results. When emerging availability of licensed vaccines makes it no longer possible to use a placebo control, randomized active comparator non-inferiority trials may enable reliable insights. METHODS: In this article, "hybrid" methods are proposed to address settings where, during the conduct of a placebo-controlled trial, a judgment is made to replace the placebo arm by a licensed COVID-19 vaccine due to emerging availability of effective vaccines in regions participating in that trial. These hybrid methods are based on proposed statistics that aggregate evidence to formally test as well as to estimate the efficacy of the experimental vaccine, by combining placebo-controlled data during the first period of trial conduct with active-controlled data during the second period. RESULTS: Application of the proposed methods is illustrated in two important scenarios where the active control vaccine would become available in regions engaging in the experimental vaccine's placebo-controlled trial: in the first, the active comparator's vaccine efficacy would have been established to be 50%-70% for the 4- to 6-month duration of follow-up of its placebo-controlled trial; in the second, the active comparator's vaccine efficacy would have been established to be 90%-95% during that duration. These two scenarios approximate what has been seen with adenovirus vaccines or mRNA vaccines, respectively, assuming the early estimates of vaccine efficacy for those vaccines would hold over longer-term follow-up. CONCLUSION: The proposed hybrid methods could readily play an important role in the near future in the design, conduct and analysis of randomized clinical trials performed to address the need for multiple additional vaccines reliably established to be safe and have worthwhile efficacy in reducing the risk of symptomatic disease from SARS-CoV-2 infections.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Grupos Controle , Humanos , Placebos , SARS-CoV-2
10.
BMC Cancer ; 21(1): 389, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836710

RESUMO

BACKGROUND: The fragility index (FI) of trial results can provide a measure of confidence in the positive effects reported in randomized controlled trials (RCTs). The aim of this study was to calculate the FI of RCTs supporting HCC treatments. METHODS: A methodological systematic review of RCTs in HCC treatments was conducted. Two-arm studies with randomized and positive results for a time-to-event outcome were eligible for the FI calculation. RESULTS: A total of 6 trails were included in this analysis. The median FI was 0.5 (IQR 0-10). FI was ≤7 in 4 (66.7%) of 6 trials; in those trials the fragility quotient was ≤1%. CONCLUSION: Many phase 3 RCTs supporting HCC treatments have a low FI, which challenges the confidence in concluding the superiority of these drugs over control treatments.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Modelos Estatísticos , Avaliação de Resultados em Cuidados de Saúde/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas
11.
Postgrad Med ; 133(5): 565-571, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33821768

RESUMO

OBJECTIVES: An ibuprofen (IBU)/acetaminophen (APAP) fixed-dose combination (FDC) for over-the-counter (OTC) use was developed with the goal of providing the same effective analgesic activity as full doses of the individual monocomponents, while reducing individual monocomponent drug exposures. Here, the safety and tolerability of the FDC is characterized using pooled safety data from phase 1-3 clinical trials in the FDC development program. METHODS: We conducted a pooled safety analysis of data from 7 clinical trials: three phase 1 pharmacokinetic trials, a phase 2 proof-of-concept trial, and three phase 3 trials (a single- and a multiple-dose trial in a dental pain model and a single-dose trial in an induced-fever model). Safety and tolerability of the FDC were assessed by adverse events (AEs) for the total group and subgroups (age, sex, race). RESULTS: A total of 1,477 participants were enrolled in the 7 trials; 715 were treated with FDC IBU/APAP, 432 with IBU monotherapy, 330 with APAP monotherapy, and 156 with placebo. Most subjects were white (86.5%), and 44% were female. Two trials enrolling 195 adolescents accounted for 13.2% of the overall study population. All-causality treatment-emergent AEs (TEAEs) occurred in 19.7% of the 1477 participants. Nausea (13.5%), vomiting (7.4%), dizziness (4.5%), headache (1.2%), and feeling hot (1.0%) were the only TEAEs reported in ≥1% of subjects. Treatment-related AEs occurred in 1.8% of the subjects in the overall population. The incidence of AEs, including treatment-related AEs, was consistently lower in all active treatment groups than in the placebo group; this also applied to subgroups according to sex, race, and age, including adolescents aged 12-17 years. The higher rate of AEs with placebo was likely due to lack of pain/fever control. CONCLUSION: Single-dose or short-course FDC IBU/APAP OTC use was well tolerated, with an AE profile similar to its IBU and APAP monocomponents. CLINICALTRIALS.GOV REGISTRATION: NCT01559259; NCT02912650; NCT02837952; NCT02761980. The pharmacokinetic studies (n = 3) did not require registration.


Assuntos
Acetaminofen/administração & dosagem , Ensaios Clínicos Fase I como Assunto/métodos , Ensaios Clínicos Fase II como Assunto/métodos , Ensaios Clínicos Fase III como Assunto/métodos , Tolerância a Medicamentos , Ibuprofeno/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Adulto , Analgésicos não Narcóticos/administração & dosagem , Anti-Inflamatórios não Esteroides , Distúrbios do Sono por Sonolência Excessiva , Quimioterapia Combinada , Feminino , Humanos , Masculino , Adulto Jovem
12.
Methods Mol Biol ; 2249: 193-211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33871845

RESUMO

Today's clinical practice relies on the application of well-designed clinical research, the gold standard test of an intervention being the randomized controlled trial. Principles of the randomized control trial include emphasis on the principal research question, randomization, blinding; definitions of outcome measures, of inclusion and exclusion criteria, and of co-morbid and confounding factors; enrolling an adequate sample size; planning data management and analysis; preventing challenges to trial integrity such as drop-out, drop-in, and bias. The application of pre-trial planning is stressed to ensure the proper application of epidemiological principles resulting in clinical studies that are feasible and generalizable. In addition, funding strategies and trial team composition are discussed.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Viés , Humanos , Modelos Teóricos , Avaliação de Resultados em Cuidados de Saúde , Tamanho da Amostra
13.
Methods Mol Biol ; 2249: 213-227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33871846

RESUMO

When analyzing the results of a trial, the primary outcome variable must be kept in clear focus. In the analysis plan, consideration must be given to comparing the characteristics of the subjects, taking account of differences in these characteristics, intention-to-treat analysis, interim analyses and stopping rules, mortality comparisons, composite outcomes, research design including run-in periods, factorial, stratified and crossover designs, number needed to treat, power issues, multivariate modeling, subgroup analysis, competing risks, and hypothesis-generating analyses.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Estudos Cross-Over , Humanos , Análise de Intenção de Tratamento , Análise Multivariada , Projetos de Pesquisa
14.
Methods Mol Biol ; 2249: 229-245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33871847

RESUMO

The study of patient-reported outcomes, now common in clinical research, had its origins in social and scientific developments during the latter twentieth century. Patient-reported outcomes comprise functional and health status, health-related quality of life, and quality of life. The terms overlap and are used inconsistently, and these terms should be distinguished from expressions of preference regarding health states. Regulatory standards from the USA and European Union provide some guidance regarding reporting of patient-reported outcomes. Determining that patient-reported outcomes measurement is important depends in part on the balance between subjective and objective outcomes of the health problem under study. Instrument selection depends to a large extent on practical considerations. A number of instruments can be identified that are frequently used in particular clinical situations. The domain coverage of commonly used generic short forms varies substantially. Individualized measurement of quality of life is possible, but resource intensive. Focus groups are useful, not only for scale development but also to confirm the appropriateness of existing instruments.Under classical test theory, validity and reliability are the critical characteristics of tests. Under item response theory, validity remains central, but the focus moves from the reliability of scales to the relative levels of traits in individuals and items' relative difficulty. Plans for clinical studies should include an explicit model of the relationship of patient-reported outcomes to other parameters, as well as define the magnitude of difference in patient-reported outcomes that will be considered important. It is particularly important to minimize missing patient-reported outcome data; to a limited extent, a variety of statistical techniques can mitigate the consequences of missing data.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Guias como Assunto , Nível de Saúde , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Reprodutibilidade dos Testes , Inquéritos e Questionários
15.
Methods Mol Biol ; 2249: 247-259, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33871848

RESUMO

Quality-of-life (QoL) outcomes are important elements of randomized controlled trials. The instruments for measurement of QoL vary but usually multiple comparisons are possible, a concern that can be offset by prespecifying the outcomes of interest. Missing data may threaten the validity of QoL assessments in trials. Therefore, familiarity with the strategies used to account for missing data is necessary. Measures that incorporate both survival and QoL are helpful for treatment decisions. The definition of minimal clinically important differences in QoL scores is important and often derived using inadequate methods.


Assuntos
Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Nível de Saúde , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários
16.
Methods Mol Biol ; 2249: 261-280, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33871849

RESUMO

Biomarkers are characteristics that are measured as indicators of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Biomarkers may serve a number of important uses, particularly in diagnosis and prognosis of disease, and as surrogates for clinical outcomes of disease (i.e., outcomes that measure how patient survives, functions, or feels). Establishing the validity of a given biomarker for a specific role requires the conduct of carefully designed clinical studies in which the biomarker and the outcome of interest are measured independently. The design and analysis of such studies is discussed. Surrogate outcomes in clinical trials consist of events or biomarkers intended to reflect important clinical outcomes. Surrogate outcomes may offer advantages in providing statistically robust estimates of treatment effects with smaller sample sizes. However, to be useful, surrogate outcomes have to be validated to ensure that the effect of therapy on them truly reflects the effect of therapy on the important clinical outcomes of interest.


Assuntos
Biomarcadores/análise , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Humanos , Modelos Estatísticos , Prognóstico , Projetos de Pesquisa , Tamanho da Amostra , Resultado do Tratamento
17.
Methods Mol Biol ; 2249: 281-305, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33871850

RESUMO

Performing well-powered, randomized, controlled trials is of fundamental importance in clinical research. The goal of sample size calculations is to assure that statistical power is sufficiently high when the probability of falsely rejecting a true null hypothesis (type I error) is kept acceptably small. This chapter overviews the fundamental of sample size calculation for standard types of outcomes for 2-group studies. It also considers (1) the problem of determining the size of the treatment effect that a study should be designed to detect, (2) modifications to sample size calculations to account for loss to follow-up and nonadherence, (3) options that can be used when initial calculations indicate that the feasible sample size is insufficient to provide adequate power, (4) implications of using multiple primary end points. In addition, a discussion of cluster randomized trials is provided. Sample size estimates for longitudinal cohort studies must take account of confounding by baseline factors.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Estudos de Coortes , Interpretação Estatística de Dados , Humanos , Modelos Estatísticos , Tamanho da Amostra
18.
Anesth Analg ; 133(1): 58-67, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33886521

RESUMO

BACKGROUND: Topical pharmacological agents typically used to treat postoperative sore throat (POST) after tracheal intubation include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, lidocaine, Glycyrrhiza (licorice), and N-methyl-d-aspartate (NMDA) receptor antagonists (including ketamine and magnesium). However, the optimal prophylactic drug remains elusive. METHODS: The literature published before September 8, 2019 was searched on the PubMed, the Embase, the Web of Science, and the Cochrane Library. Randomized controlled trials (RCTs) covering topical prophylactic medications for patients with POST were included. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the quality of evidence. The primary outcome is the risk of POST. Combining both direct and indirect evidence, a network meta-analysis was performed to assess odds ratios (ORs) between the topical pharmacological agents and surface under the cumulative ranking (SUCRA) curve for the treatment-based outcomes. This study is registered with PROSPERO, number CRD42020158985. RESULTS: Sixty-two RCTs (at least 73% of which were double blinded) that included a total of 6708 subjects and compared 6 categories of drugs and/or placebos were ultimately enrolled. All preventive interventions except lidocaine were more effective than placebo at the 4 time intervals. Lidocaine (OR: 0.35, 95% credible interval [CrI], 0.16-0.79) has a greater POST preventative intervention effect than the placebo at a time interval of only 2 to 3 hours after surgery. Relative to lidocaine, the risk of POST except 2 to 3 hours was lower for the following treatments: corticosteroids, ketamine, magnesium, NSAIDs, and Glycyrrhiza. The NMDA receptor antagonists studied here included ketamine and magnesium. Magnesium generally demonstrated greater benefit than ketamine at 24 hours postsurgery/extubation (OR: 0.41, 95% CrI, 0.18-0.92). Compared with ketamine, corticosteroids were associated with a reduced risk of POST during the 4 to 6 hours (OR: 0.40, 95% CrI, 0.19-0.83) and 24 hours (OR: 0.34, 95% CrI, 0.16-0.72) time intervals. During the 2 to 3 hours time interval, Glycyrrhiza (OR: 0.38, 95% CrI, 0.15-0.97) was more efficacious than magnesium. CONCLUSIONS: Our analysis shows that, among the 6 topical medications studied, lidocaine is not optimal for topical use to prevent POST. Glycyrrhizin, corticosteroids, NSAIDs, and NMDA receptor antagonists (ketamine and magnesium) are associated with a reduced postoperative pharyngeal pain across the 4 postsurgical time intervals studied, all of which can be chosen according to the clinical experience of the anesthesiologists and the patient preferences and are recommended for the reduction of postoperative throat pain.


Assuntos
Anestésicos Locais/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Intubação Intratraqueal/efeitos adversos , Dor Pós-Operatória/prevenção & controle , Faringite/prevenção & controle , Administração Tópica , Extubação/efeitos adversos , Extubação/tendências , Humanos , Intubação Intratraqueal/tendências , Metanálise em Rede , Dor Pós-Operatória/etiologia , Faringite/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento
19.
Lancet Glob Health ; 9(5): e691-e700, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33865474

RESUMO

In global health research, short-term, small-scale clinical trials with fixed, two-arm trial designs that generally do not allow for major changes throughout the trial are the most common study design. Building on the introductory paper of this Series, this paper discusses data-driven approaches to clinical trial research across several adaptive trial designs, as well as the master protocol framework that can help to harmonise clinical trial research efforts in global health research. We provide a general framework for more efficient trial research, and we discuss the importance of considering different study designs in the planning stage with statistical simulations. We conclude this second Series paper by discussing the methodological and operational complexity of adaptive trial designs and master protocols and the current funding challenges that could limit uptake of these approaches in global health research.


Assuntos
Saúde Global , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Projetos de Pesquisa , Humanos
20.
Lancet Glob Health ; 9(5): e701-e710, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33865475

RESUMO

Evaluating whether an intervention works when trialled in groups of individuals can pose complex challenges for clinical research. Cluster randomised controlled trials involve the random allocation of groups or clusters of individuals to receive an intervention, and they are commonly used in global health research. In this paper, we describe the potential reasons for the increasing popularity of cluster trials in low-income and middle-income countries. We also draw on key areas of global health research for an assessment of common trial planning practices, and we address their methodological shortcomings and pitfalls. Lastly, we discuss alternative approaches for population-level intervention trials that could be useful for research undertaken in low-income and middle-income countries for situations in which the use of cluster randomisation might not be appropriate.


Assuntos
Saúde Global , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Análise por Conglomerados , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos
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