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ETHNOPHARMACOLOGICAL RELEVANCE: Mouthwashes based on medicinal plants have demonstrated benefits in controlling plaque and inflammation, acting positively on the oral hygiene of patients with gingivitis. In traditional medicine, Punica granatum L. has been used to treat oral diseases in countries in Europe, Asia, North America, and Africa. AIM OF THE STUDY: The present study aimed to conduct a comprehensive review on the dental applications of Punica granatum L. for the treatment of gingivitis, including ethnomedicinal uses, analysis of randomized clinical trials, antibacterial activity against Porphyromonas gingivalis, mechanisms of action of phytochemicals isolated from this plant, and preclinical toxicity. MATERIALS AND METHODS: The literature was retrieved from Google Scholar, PubMed®, SciELO, and ScienceDirect®, since the first report published on the topic in 2001 until March 2024. RESULTS: Several clinical trials have demonstrated that mouthwashes containing P. granatum have equal or better efficacy than chlorhexidine in treating patients with gingivitis, confirming the indications for use of this plant by traditional communities. However, reports on the in vitro antibacterial activity of extracts from the fruits of this plant have not shown clinical relevance against the pathogen P. gingivalis. The ellagitannin punicalagin isolated from P. granatum has shown potential against several strains of Gram-positive and Gram-negative bacteria, but, to date, this compound has not yet been tested against P. gingivalis. It is likely that the mechanisms of action of flavonoids, such as quercetin, are involved in the inhibition of the activities of the RgpA, RgpB, and Kgp proteases of P. gingivalis. CONCLUSIONS: In summary, natural products obtained from P. granatum do not present toxic side effects and can be considered as possible substitutes of commercial products recommended for the treatment of gingivitis and other oral diseases.
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Antibacterianos , Gengivite , Extratos Vegetais , Porphyromonas gingivalis , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Gengivite/tratamento farmacológico , Porphyromonas gingivalis/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Punica granatum/química , Medicina Tradicional , Animais , FitoterapiaRESUMO
This chapter summarizes the epidemiological study design of natural immune epidemiology studies based on recent COVID-19-related research. The epidemiological studies on antiviral innate immunity have mainly included randomized controlled trials (RCTs) and observational studies. Importantly, this chapter will discuss how to use these methodologies to answer an epidemiological question of natural immunity in the viral infection process based on previous studies. An observational case- or cohort-based study of antiviral innate immunity may support this theoretical hypothesis but is not appropriate for clinical practice or treatment. RCTs are the gold standard for epidemiological studies and occupy a greater role in the hierarchy of evidence.
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COVID-19 , Imunidade Inata , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Epidemiológicos , Antivirais/uso terapêutico , Estudos Observacionais como AssuntoRESUMO
Background: No comprehensive meta-analysis has evaluated the efficacy and safety of ertugliflozin compared to a placebo in patients with Type 2 diabetes (T2D) until now. This meta-analysis fills this gap in knowledge. Methods: A systematic search was carried out in electronic databases to identify randomized controlled trials (RCTs) that included patients with T2D receiving ertugliflozin in the treatment group and placebo in the control group. The change in HbA1c from the baseline values was the primary outcome, whereas changes in plasma glucose and other metabolic parameters and adverse events (AEs), including hypoglycemia, were the secondary outcomes. Results: Seven RCTs involving 7283 subjects met the inclusion criteria. Ertugliflozin outperformed placebo in reducing HbA1c in both 5 mg (MD -0.62%, 95% CI [-0.80, -0.44], p < 0.00001, I 2 = 91%) and 15 mg (MD -0.69%, 95% CI [-0.91, -0.47], p < 0.00001, I 2 = 93%) doses. A higher proportion of patients achieved HbA1c < 7.0% with ertugliflozin than with placebo. Ertugliflozin was also superior to placebo in lowering fasting plasma glucose (FPG), body weight, and systolic and diastolic blood pressure (BP). Ertugliflozin and placebo had comparable AE profiles, including urinary tract infection (UTI) and hypoglycemia, except for the greater risk of genital mycotic infections (GMIs) with ertugliflozin. Ertugliflozin 5 and 15 mg have equivalent efficacy and safety profiles except for greater weight reduction with ertugliflozin 15 mg. Conclusion: Ertugliflozin has a good glycemic efficacy and a reassuring safety profile in managing T2D. Trial Registration: Registration number: CRD42023456450.
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Glicemia , Compostos Bicíclicos Heterocíclicos com Pontes , Diabetes Mellitus Tipo 2 , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Resultado do Tratamento , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemia/induzido quimicamenteRESUMO
Background: The first-line treatment for advanced hepatocellular carcinoma has evolved significantly. This study aimed to identify the most beneficial regimen. Methods: A systematic search was conducted from July 2012 to August 2024 across the following four databases: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. This search focused on phase III prospective randomized controlled trials that compared first-line treatment for advanced hepatocellular carcinoma. Results: Seventeen studies involving 10322 patients were included in this network meta-analysis. Of the studies we included, twelve studies were global multicenter clinical studies, four were initiated in China, and one was initiated in Korea. The results of our statistical analysis suggest that Hepatic artery infusion chemotherapy with oxaliplatin plus fluorouracil (HAIC-FO) demonstrated significant overall survival (OS) benefits compared with most treatments, including various immune checkpoint inhibitors (ICIs) and anti-vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs). In terms of OS, HAIC had shown similar efficacy with sorafenib plus FOLFOX (HR, 0.88; 95% CI: 0.37-2.09) and transcatheter arterial chemoembolization (TACE) combined with lenvatinib (HR, 0.69; 95% CI: 0.30-1.56). Notably, immune-related treatments, such as ICIs combined with anti-VEGF therapies, also showed improved OS compared with anti-VEGF-TKIs alone. In terms of progression-free survival (PFS), HAIC-FO outperformed anti-VEGF-TKI monotherapy, ICI monotherapy, and several ICI combinations. However, it was not superior to lenvatinib plus TACE or lenvatinib plus pembrolizumab. Based on the Surface Under the Cumulative Ranking Curve (SUCRA) values, HAIC-FO was ranked the most effective in terms of OS (SUCRA = 0.961) and objective response rate (ORR) (SUCRA = 0.971). The results of the subgroup analysis suggested that HAIC-FO achieved the best OS benefit in the macrovascular invasion (MVI) and extrahepatic spread (EHS) subgroup (SUCRA = 0.99) and that tremelimumab combined with durvalumab achieved the best OS benefit in the Asian subgroup (SUCRA = 0.88). Conclusion: This systematic review and network meta-analysis suggest that HAIC-based therapies may become a potential first-line treatment option for advanced HCC, especially for patients in Mainland China with MVI and EHS. Additionally, immune-related treatments may be more suitable for Asian populations.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Metanálise em Rede , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversosRESUMO
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, particularly when diagnosed at an unresectable stage. Traditional treatments for advanced HCC have limited efficacy, prompting the exploration of combination therapies. This systematic review and meta-analysis evaluate the effectiveness and safety of combining PD-1/PD-L1 inhibitors with anti-angiogenic agents in patients with unresectable HCC. Methods: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, including studies up to June 2024. Randomized controlled trials (RCTs) comparing combination therapy (PD-1/PD-L1 inhibitors with anti-angiogenic agents) to monotherapy or standard treatments in unresectable HCC patients were included. Data were synthesized using random-effects models, with pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and risk ratios (RRs) for objective response rate (ORR) and adverse events (AEs). Results: Five Phase III RCTs involving 1515 patients were included. Combination therapy significantly improved OS (HR: 0.71, 95% CI: 0.60-0.85) and PFS (HR: 0.64, 95% CI: 0.53-0.77) compared to monotherapy or standard treatments. The pooled OR for ORR was 1.27 (95% CI: 1.57-2.11), indicating a higher response rate with combination therapy. However, the risk of AEs was also higher in the combination therapy group (RR: 1.04, 95% CI: 1.02-1.06). Subgroup analyses revealed consistent benefits across different types of PD-1/PD-L1 inhibitors and anti-angiogenic agents, with no significant publication bias detected. Conclusions: The combination of PD-1/PD-L1 inhibitors with anti-angiogenic agents offers significant benefits in improving OS and PFS in patients with unresectable HCC, although it is associated with an increased risk of adverse events.
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Inibidores da Angiogênese , Antígeno B7-H1 , Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Platelet-rich plasma (PRP) has shown positive effects on enhancing erectile function in animal studies. Human clinical trials are limited and provide contradictory results. This review aims to conduct a meta-analysis of the available Randomized controlled trials (RCT) to assess the efficacy of PRP in males with ED. METHODS: A systematic review was carried out following the Cochrane Handbook of Intervention and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in PROSPERO (CRD42023441655). RESULTS: A total of three RCTs were included in the analysis for a total of 221 patients with mild to moderate ED. The patients receiving PRP reported significantly better improvement of IIEFEF score during 1,3- and 6-months follow-up compared to the placebo group (mean difference [MD] 2.66, 95% confidence interval [CI] 1.48 to 3.83, p < 0.01; MD 2.11, 95%CI 0.13 to 4.09, p = 0.04; MD 2.99, 95%CI 1.79 to 4.19, p < 0.01). The pooled analysis indicated that attainment of minimally clinical important difference (MCID) was significantly higher in patients receiving PRP compared to the placebo group during one and 6-month follow-up (odds ratio [OR] 5.51, 95%CI 1.2 to 254, p = 0.03; OR 5.64, 95%CI 2.05 to 15.55, p < 0.01; respectively). Encouragingly, no major AEs were reported in all three trials in the PRP and placebo groups (p = 0.99). CONCLUSIONS: This review highlights the potential role of PRP in providing short-term improvement of erectile function parameters for up to 6 months in mild to moderate ED patients. Future RCTs with longer-duration follow-ups and more standardized treatment protocols are necessary to gain sufficient details on PRP's long-term effectiveness and safety.
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Disfunção Erétil , Plasma Rico em Plaquetas , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Disfunção Erétil/terapia , Masculino , Índice de Gravidade de Doença , Injeções , Resultado do Tratamento , PênisRESUMO
BACKGROUND: Asthma is one of the most common reasons for hospital admission among children, with significant economic burden and impact on quality of life. Non-invasive positive pressure ventilation (NPPV) is increasingly used in the care of children with acute asthma, although the evidence supporting it is weak, and clinical guidelines do not offer any recommendations on its routine use. However, NPPV might be an effective way to improve outcomes for some children with asthma. A previous review did not demonstrate a clear benefit, but was limited by few studies with small sample sizes. This is an update of the previous review. OBJECTIVES: To assess the benefits and harms of NPPV as an add-on therapy to usual care (e.g. bronchodilators and corticosteroids) in children (< 18 years) with acute asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, and Embase. We also conducted a search of ClinicalTrials.gov and the WHO ICTRP. We searched all databases from their inception to March 2023, with no restrictions on language of publication. SELECTION CRITERIA: We included randomised clinical trials (RCTs) assessing NPPV as add-on therapy to usual care versus usual care for children hospitalised for acute asthma exacerbations. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. MAIN RESULTS: We included three RCTs randomising 60 children with acute asthma to NPPV and 60 children to control. All included trials assessed the effects of bilevel positive airway pressure (BiPAP) for acute asthma in a paediatric intensive care unit (PICU) setting. None of the trials used continuous positive airway pressure (CPAP). The controls received standard care. The median age of children ranged from three to six years, and asthma severity ranged from moderate to severe. Our primary outcome measures were all-cause mortality, serious adverse events, and asthma symptom score. Secondary outcomes were non-serious adverse events, health-related quality of life, arterial blood gases and pH, pneumonia, cost, and PICU length of stay. None of the trials reported any deaths or serious adverse events (except one trial that reported intubation rate). Two trials reported asthma symptom score, each demonstrating reductions in asthma symptoms in the BiPAP group. In one trial, the asthma symptom score was (mean difference (MD) -2.50, 95% confidence interval (CI) -4.70 to -0.30, P = 0.03; 19 children) lower in the BiPAP group. In the other trial, a cross-over trial, BiPAP was associated with a lower mean asthma symptom score (MD -3.7; 16 children; very low certainty evidence) before cross-over, but investigators did not report a standard deviation, and it could not be estimated from the first phase of the trial before cross-over. The reduction in both trials was above our predefined minimal important difference. Overall, NPPV with standard care may reduce asthma symptom score compared to standard care alone, but the evidence is very uncertain. The only reported serious adverse event was intubation rate in one trial. The trial had an intubation rate of 40% and showed that BiPAP may result in a large reduction in intubation rate (risk ratio 0.47, 95% CI 0.23 to 0.95; 78 children), but the evidence is very uncertain. Post hoc analysis showed that BiPAP may result in a slight decrease in length of PICU stay (MD -0.87 day, 95% CI -1.52 to -0.22; 100 children), but the evidence is very uncertain. Meta-analysis or Trial Sequential Analysis was not possible because of insufficient reporting and different scoring systems. All three trials had high risk of bias with serious imprecision of results, leading to very low certainty of evidence. AUTHORS' CONCLUSIONS: The currently available evidence for NNPV is uncertain. NPPV may lead to an improvement in asthma symptom score, decreased intubation rate, and slightly shorter PICU stay; however, the evidence is of very low certainty. Larger RCTs with low risk of bias are warranted.
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Asma , Ventilação não Invasiva , Respiração com Pressão Positiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Criança , Asma/terapia , Doença Aguda , Respiração com Pressão Positiva/métodos , Ventilação não Invasiva/métodos , Pré-Escolar , Adolescente , Viés , Qualidade de Vida , Broncodilatadores/uso terapêuticoRESUMO
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the leading inherited cause of kidney disease. Clinical management has historically focused on symptom control and reducing associated complications. Improved understanding of the molecular and cellular mechanisms involved in kidney cyst growth and disease progression has resulted in new pharmaceutical agents targeting disease pathogenesis and preventing disease progression. However, the role of disease-modifying agents for all people with ADPKD is unclear. This is an update of a review first published in 2015. OBJECTIVES: We aimed to evaluate the benefits and harms of interventions to prevent the progression of ADPKD and the safety based on patient-important endpoints, defined by the Standardised Outcomes in NephroloGy-Polycystic Kidney Disease (SONG-PKD) core outcome set, and general and specific adverse effects. SEARCH METHODS: We searched the Cochrane Kidney and Transplants Register of Studies up to 13 August 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any interventions for preventing the progression of ADPKD with other interventions, placebo, or standard care were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study risks of bias and extracted data. Summary estimates of effects were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 57 studies (8016 participants) that investigated 18 pharmacological interventions (vasopressin 2 receptor (V2R) antagonists, antihypertensive therapy, mammalian target of rapamycin (mTOR) inhibitors, somatostatin analogues, antiplatelet agents, eicosapentaenoic acids, statins, kinase inhibitors, diuretics, anti-diabetic agents, water intake, dietary intervention, and supplements) in this review. Compared to placebo, the V2R antagonist tolvaptan probably preserves eGFR (3 studies, 2758 participants: MD 1.26 mL/min/1.73 m2, 95% CI 0.73 to 1.78; I2 = 0%) and probably slows total kidney volume (TKV) growth in adults (1 study, 1307 participants: MD -2.70 mL/cm, 95% CI -3.24 to -2.16) (moderate certainty evidence). However, there was insufficient evidence to determine tolvaptan's impact on kidney failure and death. There may be no difference in serious adverse events; however, treatment probably increases nocturia, fatigue and liver enzymes, may increase dry mouth and thirst, and may decrease hypertension and urinary and upper respiratory tract infections. Data on the impact of other therapeutic interventions were largely inconclusive. Compared to placebo, somatostatin analogues probably decrease TKV (6 studies, 500 participants: SMD -0.33, 95% CI -0.51 to -0.16; I2 = 11%), probably have little or no effect on eGFR (4 studies, 180 participants: MD 4.11 mL/min/1.73 m3, 95% CI -3.19 to 11.41; I2 = 0%) (moderate certainty evidence), and may have little or no effect on kidney failure (2 studies, 405 participants: RR 0.64, 95% CI 0.16 to 2.49; I2 = 39%; low certainty evidence). Serious adverse events may increase (2 studies, 405 participants: RR 1.81, 95% CI 1.01 to 3.25; low certainty evidence). Somatostatin analogues probably increase alopecia, diarrhoea or abnormal faeces, dizziness and fatigue but may have little or no effect on anaemia or infection. The effect on death is unclear. Targeted low blood pressure probably results in a smaller per cent annual increase in TKV (1 study, 558 participants: MD -1.00, 95% CI -1.67 to -0.33; moderate certainty evidence) compared to standard blood pressure targets, had uncertain effects on death, but probably do not impact other outcomes such as change in eGFR or adverse events. Kidney failure was not reported. Data comparing antihypertensive agents, mTOR inhibitors, eicosapentaenoic acids, statins, vitamin D compounds, metformin, trichlormethiazide, spironolactone, bosutinib, curcumin, niacinamide, prescribed water intake and antiplatelet agents were sparse and inconclusive. An additional 23 ongoing studies were also identified, including larger phase III RCTs, which will be assessed in a future update of this review. AUTHORS' CONCLUSIONS: Although many interventions have been investigated in patients with ADPKD, at present, there is little evidence that they improve patient outcomes. Tolvaptan is the only therapeutic intervention that has demonstrated the ability to slow disease progression, as assessed by eGFR and TKV change. However, it has not demonstrated benefits for death or kidney failure. In order to confirm the role of other therapeutic interventions in ADPKD management, large RCTs focused on patient-centred outcomes are needed. The search identified 23 ongoing studies, which may provide more insight into the role of specific interventions.
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Progressão da Doença , Rim Policístico Autossômico Dominante , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Taxa de Filtração Glomerular , Tolvaptan/uso terapêuticoRESUMO
BACKGROUND: Older adults are at high risk for toxicity due to cancer treatment and increased risk for adverse events related to chemotherapy-induced nausea and vomiting (CINV). Unfortunately, older adults report multiple treatment-related symptoms but use few strategies to self-manage these symptoms due to erroneous beliefs related to the effectiveness of commonly taught self-management strategies. We developed a novel serious game, Managing at Home (MAH), to help older adults learn how to effectively self-manage CINV at home. OBJECTIVE: This study has 2 aims. Aim 1 is to examine changes in CINV severity, self-management behaviors, functioning, quality of life, cognitive representation, and health care use within the intervention group from baseline (T1) to completion of the study (T6). Aim 2 is to determine the efficacy of the MAH intervention by comparing differences in primary outcomes (CINV severity and health care use) and secondary outcomes (self-management behaviors, functioning, and quality of life) between the intervention and control groups at each follow-up visit (T2-T6) and completion of the study (T6). METHODS: This is a longitudinal randomized clinical trial. We will collect data from 500 older adults receiving cancer-related chemotherapy at baseline (T1) and at each treatment cycle until cycle 6 (T6). Participants will be enrolled if they are 60 years or older of age, are newly diagnosed with cancer, being treated with any chemotherapy agent with moderate or high emetic potential, are on a 2-, 3-, or 4-week treatment cycle, are proficient in English, and have a telephone. Previous diagnosis or treatment for cancer, end-stage disease with less than 6 months to live, and uncorrected visual or hearing impairment are exclusion criteria. RESULTS: This study was funded in September 2022 and received institutional review board approval in October 2022. As of July 2023, the enrollment of participants is ongoing and currently has 130 enrolled participants. Data collection and analysis will be complete in 2027. CONCLUSIONS: This study addresses self-management of CINV in older adults using an innovative serious game. The MAH intervention uses simulation and gaming technology to engage older adults in active learning in order to reframe erroneous perceptions about symptom self-management. If shown to be effective, it can easily be adapted to include other cancer-related symptoms or other chronic illnesses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05838638; https://clinicaltrials.gov/study/NCT05838638. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64673.
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Antineoplásicos , Náusea , Neoplasias , Vômito , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Náusea/tratamento farmacológico , Náusea/terapia , Neoplasias/tratamento farmacológico , Qualidade de Vida/psicologia , Autogestão/métodos , Jogos de Vídeo , Vômito/induzido quimicamente , Vômito/prevenção & controle , Vômito/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoAssuntos
Abdome , Sede , Humanos , Abdome/cirurgia , Xerostomia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Clinical research is conducted to investigate physicians' clinical questions and to clarify research hypotheses. When conducting clinical research, it is important to carefully consider the research design in advance. An optimal design that meets the objectives of the study and addresses practical implementation issues is desirable. Randomized comparisons during the final confirmatory phase may be the best tool for comparing treatments. However, not all clinical questions can be answered through randomized controlled trials. This article summarizes the basics of clinical study design and explains the role of randomization. It also introduces a propensity score-based method that has gained attention as a statistical method for comparing treatment groups when randomization is not feasible, and is increasingly being utilized in clinical research.
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Projetos de Pesquisa , Humanos , Pesquisa Biomédica , Ensaios Clínicos Controlados Aleatórios como Assunto , Pontuação de PropensãoRESUMO
This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433-0.973) and 0.682 (95% CI: 0.464-0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511-1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14-3.4) and PFS 2.13 (95% CI: 1.28-3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Inibidores de Proteínas Quinases , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Progressão , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagemRESUMO
PURPOSE: To compare the efficacy of first-line regimens based on programmed cell death (or ligand) [PD-(L)1] blockade in extensive-stage small-cell lung cancer (ES-SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. METHODS: Network meta-analysis of randomized controlled trials (RCTs) comparing chemo-immunotherapy (CIT) and chemotherapy (CT) in ES-SCLC patients stratified by LM. Overall survival (OS) and progression-free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Seven RCTs involving 3658 ES-SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti-PD-1 + CT (HR, 0.67; 95% CI, 0.54%-0.82%; p < 0.001) and anti-PD-L1 + CT + anti-angiogenesis (HR, 0.84; 95% CI, 0.71%-0.99%; p = 0.042) demonstrated superior efficacy in prolonging OS compared to CT alone. The anti-PD-1 + CT regimen had the highest cumulative probability of 91.6% for extending OS in patients with LM. For patients without LM, all CIT regimens resulted in improved OS compared to CT alone, with the regimen of anti-angiogenesis + anti-PD-L1 + CT ranking first and having the highest cumulative probability of 95.5% for prolonging OS. CONCLUSIONS: CIT is effective for ES-SCLC patients regardless of LM status. For patients with LM, PD-1 blockade combined with CT is the best option. For patients without LM, the most beneficial regimen is the combination of anti-angiogenesis, PD-L1 blockade, and CT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Hepáticas , Neoplasias Pulmonares , Metanálise em Rede , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estadiamento de Neoplasias , Intervalo Livre de ProgressãoRESUMO
OBJECTIVE: Patients with breast cancer experience decreased quality of life due to various physical and psychological challenges. Web-based interventions are accessible, cost-effective, and convenient for improving their quality of life. This study evaluated whether web-based interventions improve quality of life and included only randomized controlled trials (RCTs) with clear evidence. METHODS: PubMed, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO were searched for articles published until October 16, 2023. Inclusion criteria were RCTs evaluating the effect of web-based interventions on quality of life in patients with breast cancer. The risk of bias was assessed with Cochrane's Risk of Bias Tool 2.0. Standardized mean differences were calculated with a random effects model using R version 4.0.3, and subgroup and moderator analyses were performed. RESULTS: Since quality of life was measured using two different instruments in two studies, 21 comparisons were analyzed from 19 RCTs. As a result, the findings suggest that web-based interventions have a small effect size on improving the quality of life for patients with breast cancer (SMD = 0.27, 95% confidence intervals [CIs]: 0.15-0.38, p = 0.03). Heterogeneity was found to be low (I2 = 40%). The quality-of-life subdomain results showed a moderate effect size on the physical functioning and a small effect size on the cognitive and emotional functioning of patients with breast cancer but no significant impact on their role or social functioning. CONCLUSIONS: Web-based interventions are effective in improving patients' quality of life with breast cancer; they also improve physical, cognitive, and emotional functioning. However, evidence regarding intervention methods remains inconclusive due to the limited number of RCTs, necessitating further research.
Assuntos
Neoplasias da Mama , Intervenção Baseada em Internet , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , FemininoRESUMO
Background: A multitude of randomized controlled trials (RCTs) conducted in both the initial and subsequent treatment settings for patients diagnosed with metastatic colorectal cancer (mCRC) have provided clinical evidence supporting the efficacy of immunotherapy with the use of immune checkpoint inhibitors (ICIs). In light of these findings, the U.S. Food and Drug Administration (FDA) has authorized the use of several ICIs in specific subpopulations of mCRC patients. Nevertheless, there remains a dearth of direct comparative RCTs evaluating various treatment options. Consequently, the most effective ICI therapeutic strategy for microsatellite-stable (MSS) subgroup and microsatellite instability (MSI) subgroup in the first- and second-line therapies remains undefined. To address this gap, the present study employs a Bayesian network meta-analysis to ascertain the most effective first- and second-line ICI therapeutic strategies. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, with the retrieval date ranging from the databases' inception to August 20, 2024. A total of 875 studies were identified, and seven were ultimately included in the analysis after a screening process. A systematic review and network meta-analysis were conducted on the basis of the search results. Results: This comprehensive analysis, comprising seven RCTs, evaluated first-line and second-line immunotherapy regimens in 1,358 patients diagnosed with mCRC. The treatments under investigation consisted of five initial treatments, including three focusing on MSS patients and two on MSI patients, as well as two secondary immunotherapy regimens, both focusing on MSS patients. A total of 1051 individuals underwent first-line treatment, while 307 received second-line treatment. The application of ICIs proved to offer varying degrees clinical benefits when compared to standard-of-care therapy alone, both in two subgroups of the first and the second treatment phases. Of particular note is the performance of Nivolumab combination with ipilimumab, which demonstrated superior efficacy in improving progression-free survival (PFS) (HR=0.21; 95% CI, 0.13-0.34),. Moreover, the treatment demonstrated an optimal safety profile, with a relatively low risk of adverse events (OR = 0.33; 95% CI, 0.19-0.56), compared to other first-line treatment modalities for MSI subgroup. Regarding MSS subgroup, the improvement of PFS by Nivolumab plus standard-of-care (SOC) was relatively significant (HR = 0.74; 95% CI, 0.53-1.02). In the realm of second-line therapies for MSS subgroup, the administration of Atezolizumab plus SOC has proven to be an effective approach for prolonging PFS, exhibiting an HR of 0.66 (95% CI, 0.44-0.99). These findings underscore the clinical benefits and safety profiles of ICIs in the treatment of mCRC across various treatment lines. Conclusions: The clinical application of ICIs in both first- and second-line treatment strategies for patients with mCRC yields substantial therapeutic benefits. A detailed assessment in this study indicates that first-line treatment with Nivolumab combination with ipilimumab may represent an efficacious and well-tolerated therapeutic approach for MSI subgroup. In terms of MSS subgroup in first-line therapy, Nivolumab plus SOC may be a relative superior choice. In the context of second-line therapy for MSS subgroup, it is evident that a combination of Atezolizumab and SOC represents a preferable option for enhancing PFS. Furthermore, it is noteworthy that other ICIs treatment regimens also exhibit great value in various aspects, with the potential to inform the development of future clinical treatment guidelines and provide a stronger rationale for the selection of ICIs in both first- and second-line therapeutic strategies for mCRC. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024543400.
Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Imunoterapia , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/métodos , Resultado do Tratamento , Metástase Neoplásica , Instabilidade de Microssatélites , Teorema de BayesRESUMO
Objective: This study aimed to assess and visually depict the clinical evidence landscape of traditional Chinese exercises and identify any research gaps and future research needs. Methods: We comprehensively searched seven Chinese and English databases to identify randomized controlled trials (RCTs) and systematic reviews (SRs) evaluating the effects of traditional Chinese exercises from their inception until May 2023. The quality of evidence was assessed via the GRADE approach, and the research topics, intervention effects, and strength of evidence were graphically displayed. Results: This evidence map includes 2,017 studies, comprising 1,822 RCTs and 195 SRs. These studies were conducted globally in various countries. Among the traditional Chinese exercises, Tai Chi and Baduanjin have received the most research attention, with a growing number of publications. When traditional Chinese exercises were compared with the control groups, 88.2% of the included SRs reported significantly positive effects, 4.1% reported unclear effects, and 7.7% reported no significant differences. The findings suggested that traditional Chinese exercises could benefit patients with osteoarthritis, osteoporosis, hypertension, coronary heart disease, diabetes, chronic obstructive pulmonary disease, stroke, Parkinson's disease, anxiety, and depression. However, the overall quality of the evidence was suboptimal, with 11.3% rated as moderate, 45.6% as low, and 43.1% as critically low. Conclusion: This evidence map visually represents valuable information on traditional Chinese exercises. While most studies have reported significant benefits, the overall quality of evidence is low.
Assuntos
Tai Chi Chuan , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicina Tradicional Chinesa , Terapia por Exercício/métodos , População do Leste AsiáticoRESUMO
Endometriosis is a common gynecological disease affecting 5-10% of women resulting in several psychological impacts. Regarding the high prevalence as well as extensive somatic symptoms, this has become a growing issue of psychological research in recent years. Thanks to its rising importance the negative effect on quality of life, mood, and anxiety symptoms has been proven. Thus we aimed to organize psychological interventions affecting the mentioned constructs and also examine their efficiency and scientific standards. Our inclusion criteria referred to studies based on randomized controlled trials, systematic reviews, and meta-analyses. We selected seven types of interventions, such as psychoeducation, cognitive behavioural therapy, mindfulness-based methods, progressive muscle relaxation, yoga, physical activity, and complex programs. Regarding the quality of life, mood, and anxiety cognitive behavioural therapy and progressive muscle relaxation were the most effective methods, however, other interventions had promising results either. Besides, there is a growing demand for psychological and mind-body interventions, which should get a more important place in the primary care of endometriosis next to medical treatment. We find inevitable further high-quality examinations, and from the point of practice, we consider it crucial to implement current evidence-based methods in the psychological care of endometriosis. Keywords: , , , , , , , , , , , .
Assuntos
Ansiedade , Terapia Cognitivo-Comportamental , Endometriose , Atenção Plena , Qualidade de Vida , Yoga , Humanos , Endometriose/psicologia , Endometriose/terapia , Feminino , Terapia Cognitivo-Comportamental/métodos , Atenção Plena/métodos , Ansiedade/terapia , Ansiedade/etiologia , Ansiedade/psicologia , Terapia de Relaxamento/métodos , Exercício Físico , Afeto , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervenção Psicossocial/métodosRESUMO
BACKGROUND: Older adults are at increased risk of both falls and fall-related injuries. Falls have multiple causes and many interventions exist to try and prevent them, including educational and psychological interventions. Educational interventions aim to increase older people's understanding of what they can do to prevent falls and psychological interventions can aim to improve confidence/motivation to engage in activities that may prevent falls. This review is an update of previous evidence to focus on educational and psychological interventions for falls prevention in community-dwelling older people. OBJECTIVES: To assess the benefits and harms of psychological interventions (such as cognitive behavioural therapy; with or without an education component) and educational interventions for preventing falls in older people living in the community. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, four other databases, and two trials registries to June 2023. We also screened reference lists and conducted forward-citation searching. SELECTION CRITERIA: We included randomised controlled trials of community-dwelling people aged 60 years and older exploring the effectiveness of psychological interventions (such as cognitive behavioural therapy) or educational interventions (or both) aiming to prevent falls. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcome was rate of falls. We also explored: number of people falling; people with fall-related fractures; people with falls that required medical attention; people with fall-related hospital admission; fall-related psychological outcomes (i.e. concerns about falling); health-related quality of life; and adverse events. MAIN RESULTS: We included 37 studies (six on cognitive behavioural interventions; three on motivational interviewing; three on other psychological interventions; nine on multifactorial (personalised) education; 12 on multiple topic education; two on single topic education; one with unclear education type; and one psychological plus educational intervention). Studies randomised 17,478 participants (71% women; mean age 73 years). Most studies were at high or unclear risk of bias for one or more domains. Cognitive behavioural interventions Cognitive behavioural interventions make little to no difference to the number of fallers (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.82 to 1.02; 4 studies, 1286 participants; low-certainty evidence), and there was a slight reduction in concerns about falling (standardised mean difference (SMD) -0.30, 95% CI -0.42 to -0.19; 3 studies, 1132 participants; low-certainty evidence). The evidence is very uncertain or missing about the effect of cognitive behavioural interventions on other outcomes. Motivational interviewing The evidence is very uncertain about the effect of motivational interviewing on rate of falls, number of fallers, and fall-related psychological outcomes. No evidence is available on the effects of motivational interviewing on people experiencing fall-related fractures, falls requiring medical attention, fall-related hospital admission, or adverse events. Other psychological interventions The evidence is very uncertain about the effect of health coaching on rate of falls, number of fallers, people sustaining a fall-related fracture, or fall-related hospital admission; the effect of other psychological interventions on these outcomes was not measured. The evidence is very uncertain about the effect of health coaching, guided imagery, and mental practice on fall-related psychological outcomes. The effect of other psychological interventions on falls needing medical attention or adverse events was not measured. Multifactorial education Multifactorial (personalised) education makes little to no difference to the rate of falls (rate ratio 0.95, 95% CI 0.77 to 1.17; 2 studies, 777 participants; low-certainty evidence). The effect of multifactorial education on people experiencing fall-related fractures was very imprecise (RR 0.66, 95% CI 0.29 to 1.48; 2 studies, 510 participants; low-certainty evidence), and the evidence is very uncertain about its effect on the number of fallers. There was no evidence for other outcomes. Multiple component education Multiple component education may improve fall-related psychological outcomes (MD -2.94, 95% CI -4.41 to -1.48; 1 study, 459 participants; low-certainty evidence). However, the evidence is very uncertain about its effect on all other outcomes. Single topic education The evidence is very uncertain about the effect of single-topic education on rate of falls, number of fallers, and people experiencing fall-related fractures. There was no evidence for other outcomes. Psychological plus educational interventions Motivational interviewing/coaching combined with multifactorial (personalised) education likely reduces the rate of falls (although the size of this effect is not clear; rate ratio 0.65, 95% CI 0.43 to 0.99; 1 study, 430 participants; moderate-certainty evidence), but makes little to no difference to the number of fallers (RR 0.93, 95% CI 0.76 to 1.13; 1 study, 430 participants; high-certainty evidence). It probably makes little to no difference to falls-related psychological outcomes (MD -0.70, 95% CI -1.81 to 0.41; 1 study, 353 participants; moderate-certainty evidence). There were no adverse events detected (1 study, 430 participants; moderate-certainty evidence). There was no evidence for psychological plus educational intervention on other outcomes. AUTHORS' CONCLUSIONS: The evidence suggests that a combined psychological and educational intervention likely reduces the rate of falls (but not fallers), without affecting adverse events. Overall, the evidence for individual psychological interventions or delivering education alone is of low or very-low certainty; future research may change our confidence and understanding of the effects. Cognitive behavioural interventions may improve concerns about falling slightly, but this may not help reduce the number of people who fall. Certain types of education (i.e. multiple component education) may also help reduce concerns about falling, but not necessarily reduce the number of falls. Future research should adhere to reporting standards for describing the interventions used and explore how these interventions may work, to better understand what could best work for whom in what situation. There is a particular dearth of evidence for low- to middle-income countries.
Assuntos
Acidentes por Quedas , Terapia Cognitivo-Comportamental , Vida Independente , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Acidentes por Quedas/prevenção & controle , Idoso , Feminino , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Fraturas Ósseas/prevenção & controle , Qualidade de Vida , Idoso de 80 Anos ou mais , ViésRESUMO
Participation in a paediatric, complex randomized controlled trial (RCT) might add to the family burden when a child is diagnosed with a severe disease. Although important, there are only a limited number of papers describing this aspect of research from the family point of view. This study explored parents' and children's experiences of participation in a research study shortly after the child had been diagnosed with type 1 diabetes. Sixteen parents (nine mothers, seven fathers) and nine children were interviewed by an independent researcher about their inducement, the decision-making process within the family which led to their participation, and their experience of having done so. The result showed that the parents wanted to contribute to improve treatment for children with diabetes in general but also specifically for their own child. Older children were more involved in the decision making than the younger children. Study information needs to be communicated clearly and effectively since decision-making based on information of a clinical trial directly after the child's diabetes onset proved difficult. Being randomized to the intervention group in this specific study was considered somewhat burdensome. However, parental participants in both intervention and control group claimed that they would recommend participation in research studies to other parents in a similar situation, and so did the children. There was no difference between the mothers' and fathers' experiences.
Parents' expectations: A predominant driving force for the parents was the expectation that the study outcome could lead to something good for both their own child and other children with type 1 diabetes.Children's perspective on participation: Older children appreciated being involved in the decision-making process and valued their role in potentially helping others with diabetes. However, younger children were less involved and often relied on their parents for decision-making.Personal benefits: Both children and parents considered it important to gain something for themselves; by participating, they could benefit from more advanced technology and more rigorous follow-ups.Importance of control group: It was important for the families' motivation for completing the study that the researchers conveyed that the control group was as important for the outcome of the study as the intervention group.Future treatments: The parents felt that participation in the clinical trial could eventually lead to new treatments that could help their own child.Perceived safety: The fact that the clinical trial was considered well-planned and safe and implied no risk for the child made it easier to agree to participation.Effective communication: Since the onset of diabetes is emotionally stressful, and diabetes treatment itself is demanding, effective communication about the content of such a clinical trial is necessary, otherwise families may not understand what they are agreeing to.Burden on the intervention group: This clinical trial was somewhat burdensome for the intervention group to participate in; nevertheless, all of the families remained committed to their reasons for participating and completed the study.