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1.
Eur J Endocrinol ; 181(4): C13-C15, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505455

RESUMO

A study has examined the rates of adrenal crises in patients treated with pituitary or adrenal surgery. Rates were substantial (approximately 9 per 100 patient years), perhaps representing suppression of corticotrope ACTH secretion and deprivation of normal corticotrope number postoperatively. Hormone withdrawal syndrome may have contributed to the rates of apparent adrenal crises given the definition used. Higher rates were seen in patients given relatively high dose glucocorticoids postoperatively in one of the two centres where patients were treated - perhaps some of the patients in the high dose centre had longer periods of corticotrope suppression from exogenous glucocorticoids, increasing the risk period for adrenal crises. The question of optimal glucocorticoid dose and weaning rate after cure of Cushing's syndrome remains a balance between weaning at a rate sufficiently rapid to allow resumption of normal corticotrope function thereby preventing adrenal crises and providing sufficient glucocorticoid support to avoid hormone withdrawal syndrome or even precipitating an adrenal crisis, in the vulnerable 4-6 month period after successful surgery. There is likely to be considerable inter-individual variability in optimum glucocorticoid dose and weaning rate so that close clinical and biochemical monitoring is currently a practical approach.


Assuntos
Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Síndrome de Cushing/metabolismo , Síndrome de Cushing/terapia , Glândulas Suprarrenais/efeitos dos fármacos , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Estudos Multicêntricos como Assunto/métodos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Resultado do Tratamento
2.
Medicine (Baltimore) ; 98(33): e16853, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415416

RESUMO

BACKGROUND: Low back pain is a common health problem worldwide, which also is a leading cause of long-term disability and has an important effect on the global economy and society. Usually, conservative therapies are used to treat low back pain. As a kind of Chinese patent medicine, Shujinjianyao pill (SJJYP) has a great curative effect on low back pain. However, its safety has not been studied yet. Therefore, we carried out this clinical trial to observe the safety of SJJYP in the real world. METHODS: First, participants need to meet the medication standards according to inclusion and exclusion criteria. Then, participants are conducted safety examination before taking SJJYP. After qualified screening, participants can be enrolled into the group. Second, all enrolled participants will receive SJJJYP for a period of 4 weeks. During the observation period, participants need to return to the hospital for a subsequent visit after 2 weeks of medication, and come to the hospital for safety check after 4 weeks of medication. Third, telephone follow-up is used to investigate any participants' physical discomfort after 6 to 8 weeks (2-4 weeks after medication withdrawal). After all these steps are completed, clinical observation is finished. If any adverse events occur during this process, we will record them in time. When serious adverse events occur, we will use nested case-control study to explore the causes and mechanisms. DISCUSSION: This study will obtain the safety results of SJJYP in clinical real world, which will offer a scientific basis for clinicians in the treatment of low back pain, and also provide a methodological basis for the safety study of other medicines. TRIAL REGISTRATION: ClinicalTrial.gov registration number is NCT03598153. This study was approved by the ethics committee of Wangjing hospital, China Academy of Chinese Medical Sciences (WJEC-KT-2018-012-P002).


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Dor Lombar/tratamento farmacológico , Ensaios Clínicos como Assunto , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Estudos Prospectivos , Projetos de Pesquisa
4.
Medicine (Baltimore) ; 98(31): e16680, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374049

RESUMO

BACKGROUND: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy. METHODS/DESIGN: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy. TRIAL REGISTRATION: NCT03616444.


Assuntos
Pólipos Adenomatosos/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Lesões Pré-Cancerosas/prevenção & controle , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Medicine (Baltimore) ; 98(26): e16176, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261551

RESUMO

INTRODUCTION: Re-irradiation after radiotherapy is a common treatment for locally recurrent esophageal cancer. However, the side effects of re-irradiation are serious. The most serious adverse reactions of re-irradiation include esophageal perforation and hemorrhage caused by esophageal perforation. Studies have shown that pulsed low-dose rate radiotherapy (PLDR) induces a hypersensitivity effect on tumor tissue and a hyper-repair effect on normal tissue, which can simultaneously reduce damage on the normal tissue and increase the therapeutic effect on the tumor. The objective of this study is to explore whether PLDR can reduce rate of esophageal perforation and improve efficacy in patients with recurrent esophageal squamous cell carcinoma (ESCC) after radiotherapy. METHODS AND ANALYSIS: This study is a prospective, multi-center, open, single-arm clinical trial designed to enroll 27 patients with locally recurrent ESCC after radiotherapy with or without chemotherapy. Re-irradiation will be performed using intensity modulated radiation therapy in 50 Gy/25 fractions. The strategy of PLDR includes dividing 2 Gy into 10 fractions, and administering each irradiating dose of 20 cGy at an interval of 3 minutes before the next low-dose irradiation. The actual dose rate of administration each time will be 16.67 cGy /minute. The primary endpoint in this study is the rate of esophageal perforation. The secondary endpoints are the objective remission rate, the palliative effect on quality of life and pain, and the time of disease progression. The observation time is 2 years after the end of the study. TRIAL REGISTRATION: Clinical trial number: ChiCTR1900020609.


Assuntos
Ensaios Clínicos Fase II como Assunto , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/radioterapia , Reirradiação , Quimiorradioterapia , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Seleção de Pacientes , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
6.
BMJ ; 365: l4223, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221622

RESUMO

The studyClare L, Kudlicka A, Oyebode J R, et al. Goal-oriented cognitive rehabilitation for early-stage Alzheimer's and related dementias: the GREAT RCT. Health Technol Assess 2019;23:1-242.The trial was funded by the NIHR Health Technology Assessment Programme (project number11/15/04).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000767/goal-setting-in-early-stage-dementia-can-improve-function.


Assuntos
Disfunção Cognitiva/economia , Disfunção Cognitiva/reabilitação , Demência/psicologia , Atividades Cotidianas , Disfunção Cognitiva/psicologia , Análise Custo-Benefício , Demência/economia , Demência/epidemiologia , Demência/reabilitação , Metas , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Autoeficácia , Avaliação da Tecnologia Biomédica , Resultado do Tratamento , Reino Unido
7.
Medicine (Baltimore) ; 98(24): e15850, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192915

RESUMO

BACKGROUND: The diabetic kidney disease (DKD) has become a seriously kidney disease that commonly caused by diabetes mellitus (DM). Oxidative stress response plays an essential role in the genesis and worsening of DKD and Coenzyme Q10 (CoQ10) has been reported the promising clinical effectiveness on DKD treatment. However, there is lack of relative evidence-based medical evidence currently. OBJECTIVE: The systematic review and meta-analysis was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, which conducted to evaluate the effectiveness of CoQ10 in combination with other western medicine for DKD therapy through the randomized controlled trials (RCTs) and experimental studies. METHODS: RCTs and experimental studies were searched based on standardized searching rules in 12 medical databases from the inception up to June 2018 and a total of 8 articles (4 RCTs and 4 experimental studies) were enrolled in the meta-analysis. RESULTS: The results revealed that CoQ10 combined with other western medicine show statistical differences in the laboratory parameters of fasting plasma glucose (FPG), Hemoglobin A1c (HbA1c), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), and malondialdehyde (MDA) amelioration after DKD therapy compared with control group. However, LDL-C and Urea level for RCTs and Urine output and Glucose for experimental studies on DKD was not superior to control group. CONCLUSION: We need to make conclusion cautiously for the effectiveness of CoQ10 application on DKD therapy. More standard, multicenter, double-blind RCTs, and formal experimental studies of CoQ10 treatment for DKD were urgent to be conducted for more clinical evidence providing in the future. The underlying pharmacological mechanism of CoQ10 needs to be researched and revealed for its future application on DKD therapy.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Ubiquinona/análogos & derivados , Vitaminas/uso terapêutico , Glicemia/metabolismo , Colesterol/metabolismo , Nefropatias Diabéticas/metabolismo , Medicina Baseada em Evidências , Hemoglobina A Glicada/metabolismo , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Ubiquinona/uso terapêutico
8.
J Stroke Cerebrovasc Dis ; 28(8): 2124-2131, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31147254

RESUMO

BACKGROUND: Orthostatic hypotension (OH) has been independently associated with increased risk of stroke and other cardiovascular events. We sought to investigate the relationship between OH at follow-up and recurrent stroke risk in SPS3 (Secondary Prevention of Small Subcortical Strokes) trial patient cohort. This is a retrospective cohort analysis. METHODS: We included all SPS3 trial participants with blood pressure measurements in both sitting and standing position per protocol at baseline, with at least 1 follow-up visit to establish the relationship between OH at follow-up and recurrent stroke risk (primary outcome). Secondary outcomes included major vascular events, myocardial infarction, all-cause mortality, and, ischemic and hemorrhagic stroke subtypes. Participants were classified as having OH at baseline and at each follow-up visit based on a systolic BP decline ≥20 mm Hg or a diastolic BP decline ≥10 mm Hg on position change from sitting to standing. We used Cox proportional hazards regression modeling to compare the risk of outcomes among those with and without OH. RESULTS: A total of 2275 patients were included with a mean follow up time 3.2 years (standard deviation = 1.6 years). 39% (881/2275) had OH at some point during their follow-up. Of these, 41% (366/881) had orthostatic symptoms accompanying the BP drop. In a fully adjusted model, those with OH had a 1.8 times higher risk of recurrent stroke than those without OH (95% confidence interval: 1.1-3.0). The risk of ischemic stroke, major vascular events, and all-cause mortality was similarly elevated among the OH group. CONCLUSION: OH was associated with increased recurrent stroke risk, vascular events, and all-cause death in this large cohort of lacunar stroke patients. Whether minimizing OH in the management of poststroke hypertension in patients with lacunar stroke reduces recurrent stroke risk deserves further study.


Assuntos
Pressão Sanguínea , Hipotensão Ortostática/complicações , Prevenção Secundária/métodos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Causas de Morte , Feminino , Humanos , Hipotensão Ortostática/mortalidade , Hipotensão Ortostática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
9.
Medicine (Baltimore) ; 98(19): e15570, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083229

RESUMO

BACKGROUND: Intradialytic resistance training (IRT) protects patients' muscle mass and functions against protein-energy wasting, malnutrition and cachexia. However, the evidence of the effects of such an intervention in haemodialysis patients is limited and not conclusive. To improve the applicability of such interventions, we need a better understanding of molecular, functional and psycho-social adaptation in dialysed patients following a physical training. Therefore, the aim of this study is to investigate the effects of IRT on lower extremity muscle functions, quality of life, and anxiety and depression, clinical outcomes and circulatory micro-ribonucleic acid (miRNA) profiles in patients on chronic haemodialysis therapy. METHODS: We will perform a quasi-experimental study in 3 dialysis centres. Patients will be recruited via their nephrologists and will be allocated to an experimental and a control group based on the location of the patients' dialysis centre. Patients allocated to the experimental group will undergo a 12-week IRT, while the control group will remain physically inactive during dialysis. The primary outcome is the change in the maximal force produced during an isometric contraction of lower extremity muscles. Secondary outcomes regard quality of life, anxiety and depression, clinical outcomes and circulatory miRNA profiles. Patients' level of health literacy defined as the ability to get and understand health information will be also measured in the study as a potential modifier of effects. DISCUSSION: This quasi-experimental study can add in an important way to our understanding of the effects of resistance training on dialysis patients' muscle strength, quality of life and disease-specific outcomes.


Assuntos
Estudos Clínicos como Assunto , Falência Renal Crônica/terapia , Diálise Renal , Treinamento de Resistência , Ansiedade/terapia , Depressão/terapia , Humanos , Contração Isométrica , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/psicologia , MicroRNAs/sangue , Estudos Multicêntricos como Assunto , Força Muscular , Qualidade de Vida , Treinamento de Resistência/métodos , Resultado do Tratamento
10.
BMC Health Serv Res ; 19(1): 286, 2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31054578

RESUMO

BACKGROUND: Advanced care planning (ACP) is a process that involves thinking about what medical care one would like should individuals be seriously ill and cannot communicate decisions about treatment for themselves. The literature indicates that ACP leads to increased satisfaction from both patients and healthcare professionals. Despite the well-known benefits of ACP, it is still underutilised in Australia. METHODS: The aim of this study is to investigate the effects of normalising ACP in acute and community settings with the use of specially trained normalisation agents. This is a quasi-experimental study, involving 16 sites (8 intervention and 8 control) in two health districts in Australia. A minimum of total 288 participants will be recruited (144 intervention, 144 control). We will train four registered nurses as normalisation agents in the intervention sites, who will promote and facilitate ACP discussions with adult patients with chronic conditions in hospital and community settings. An audit of the prevalence of ACP and Advanced Care Directives (ACDs) will be conducted before and after the 6-month intervention period at the 16 sites to assess the effects of the ACP service delivered by these agents. We will also collect interview and survey data from patients and families who participate, and healthcare professionals who are involved in this service to capture their experiences with ACP. DISCUSSION: This study will potentially contribute to better patient outcomes with their health care services. Completion of ACDs will allow patients to express their wishes for care and receive the care that they wish for, as well as ease their family from the burden of making difficult decisions. The study will contribute to development of a new best practice model to normalise ACP that is sustainable and transferable in the processes of: 1) initiation of conversation; 2) discussion of important issues; 3) documentation of the wishes; 4) storage of the documented wishes; and 5) access and execution of the documented wishes. The study will generate new evidence on the challenges, strategies and benefits of normalising ACP into practice in acute and community settings. TRIAL REGISTRATION: This project has been approved by the Hunter New England Human Research Ethics Committee (Approval No. 17/12/13/4.16). It has also been retrospectively registered on 3 October 2018 with the Australian New Zealand Clinical Trials Registry (Trial ID: ACTRN12618001627246 ). This study will operate in accordance with the National Health and Medical Research Council's National Statement on Ethical Conduct in Human Research (2007) and the CPMP/ICH Note for Guidance on Good Clinical Practice.


Assuntos
Planejamento Antecipado de Cuidados/normas , Doença Crônica/terapia , Adulto , Diretivas Antecipadas , Austrália , Tomada de Decisão Clínica , Ensaios Clínicos como Assunto , Comunicação , Serviços de Saúde Comunitária/normas , Humanos , Estudos Multicêntricos como Assunto , Projetos de Pesquisa , Estudos Retrospectivos , Inquéritos e Questionários
11.
BMC Cancer ; 19(1): 420, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060544

RESUMO

BACKGROUND: At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy. METHODS: In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3-4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression. DISCUSSION: The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only. TRIAL REGISTRATION: clinicaltrials.gov NCT03348150 ; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Cuidados Paliativos/métodos , Neoplasias Peritoneais/terapia , Neoplasias Gástricas/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante/economia , Quimioterapia Adjuvante/métodos , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Procedimentos Cirúrgicos de Citorredução/economia , Intervalo Livre de Doença , Feminino , Gastrectomia/economia , Gastrectomia/métodos , Humanos , Hipertermia Induzida/economia , Estimativa de Kaplan-Meier , Masculino , Estudos Multicêntricos como Assunto , Países Baixos/epidemiologia , Cuidados Paliativos/economia , Neoplasias Peritoneais/economia , Neoplasias Peritoneais/secundário , Peritônio/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/economia , Neoplasias Gástricas/patologia
12.
BMC Health Serv Res ; 19(1): 237, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014343

RESUMO

BACKGROUND: A comprehensive in-hospital patient management with reasonable and economic resource allocation is arguably the major challenge of health-care systems worldwide, especially in elderly, frail, and polymorbid patients. The need for patient management tools to improve the transition process and allocation of health care resources in routine clinical care particularly for the inpatient setting is obvious. To address these issues, a large prospective trial is warranted. METHODS: The "Integrative Hospital Treatment in Older patients to benchmark and improve Outcome and Length of stay" (In-HospiTOOL) study is an investigator-initiated, multicenter effectiveness trial to compare the effects of a novel in-hospital management tool on length of hospital stay, readmission rate, quality of care, and other clinical outcomes using a time-series model. The study aims to include approximately 35`000 polymorbid medical patients over an 18-month period, divided in an observation, implementation, and intervention phase. Detailed data on treatment and outcome of polymorbid medical patients during the in-hospital stay and after 30 days will be gathered to investigate differences in resource use, inter-professional collaborations and to establish representative benchmarking data to promote measurement and display of quality of care data across seven Swiss hospitals. The trial will inform whether the "In-HospiTOOL" optimizes inter-professional collaboration and thereby reduces length of hospital stay without harming subjective and objective patient-oriented outcome markers. DISCUSSION: Many of the current quality-mirroring tools do not reflect the real need and use of resources, especially in polymorbid and elderly patients. In addition, a validated tool for optimization of patient transition and discharge processes is still missing. The proposed multicenter effectiveness trial has potential to improve interprofessional collaboration and optimizes resource allocation from hospital admission to discharge. The results will enable inter-hospital comparison of transition processes and accomplish a benchmarking for inpatient care quality.


Assuntos
Benchmarking/normas , Múltiplas Afecções Crônicas/terapia , Adolescente , Adulto , Idoso , Ensaios Clínicos como Assunto , Pesquisa Comparativa da Efetividade , Assistência à Saúde/estatística & dados numéricos , Prestação Integrada de Cuidados de Saúde/normas , Hospitalização/estatística & dados numéricos , Humanos , Relações Interprofissionais , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Alta do Paciente/normas , Readmissão do Paciente/normas , Transferência de Pacientes/normas , Ensaios Clínicos Pragmáticos como Assunto , Estudos Prospectivos , Qualidade da Assistência à Saúde , Alocação de Recursos , Adulto Jovem
13.
Trials ; 20(1): 197, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953543

RESUMO

BACKGROUND: Sepsis accounts for 30% to 50% of all in-hospital deaths in the United States. Other than antibiotics and source control, management strategies are largely supportive with fluid resuscitation and respiratory, renal, and circulatory support. Intravenous vitamin C in conjunction with thiamine and hydrocortisone has recently been suggested to improve outcomes in patients with sepsis in a single-center before-and-after study. However, before this therapeutic strategy is adopted, a rigorous assessment of its efficacy is needed. METHODS: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial. It will enroll patients with sepsis causing respiratory or circulatory compromise or both. Patients will be randomly assigned (1:1) to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 h or matching placebos until a total of 16 administrations have been completed or intensive care unit discharge occurs (whichever is first). Patients randomly assigned to the comparator group are permitted to receive open-label stress-dose steroids at the discretion of the treating clinical team. The primary outcome is consecutive days free of ventilator and vasopressor support (VVFDs) in the 30 days following randomization. The key secondary outcome is mortality at 30 days. Sample size will be determined adaptively by using interim analyses with pre-stated stopping rules to allow the early recognition of a large mortality benefit if one exists and to refocus on the more sensitive outcome of VVFDs if an early large mortality benefit is not observed. DISCUSSION: VICTAS is a large, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial that will test the efficacy of vitamin C, thiamine, and hydrocortisone as a combined therapy in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. Because the components of this therapy are inexpensive and readily available and have very favorable risk profiles, demonstrated efficacy would have immediate implications for the management of sepsis worldwide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03509350 . First registered on April 26, 2018, and last verified on December 20, 2018. Protocol version: 1.4, January 9, 2019.


Assuntos
Ácido Ascórbico/administração & dosagem , Hidrocortisona/administração & dosagem , Sepse/tratamento farmacológico , Tiamina/administração & dosagem , Administração Intravenosa , Ácido Ascórbico/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Mortalidade Hospitalar , Humanos , Hidrocortisona/efeitos adversos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra , Sepse/diagnóstico , Sepse/mortalidade , Sepse/fisiopatologia , Tiamina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
14.
Trials ; 20(1): 198, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953556

RESUMO

BACKGROUND: Suicide amongst Australian Aboriginal and Torres Strait Islander communities occurs at twice the rate of the general population and, with significant barriers to treatment, help-seeking prior to a suicide attempt is low. This trial aims to test the effectiveness of an app (iBobbly) designed with Aboriginal and Torres Strait Islander people for reducing suicidal ideation. METHODS/DESIGN: This is a two-arm randomised controlled trial that will compare iBobbly to a wait-list control condition. The trial aims to recruit Aboriginal and Torres Strait Islander participants aged 16 years and over to test iBobbly, which is a self-help app delivering content based on acceptance and commitment therapy. The primary outcome for the study is suicidal ideation, and secondary outcomes include depression, hopelessness, distress tolerance, perceived burdensomeness and thwarted belonging, and help-seeking intentions. Data will be collected for both groups at baseline, post-intervention (after 6 weeks of app use), and at 6 months post-baseline (with a final 12-month follow-up for the iBobbly group). Primary analysis will compare changes in suicidal ideation for the intervention condition relative to the wait-list control condition using mixed models. An examination of the cost-effectiveness of the intervention compared to the control condition will be conducted. DISCUSSION: If effective, iBobbly could overcome many barriers to help-seeking amongst a group of people who are at increased risk of suicide. It may provide a low-cost, accessible intervention that can reach more people. This trial will add to a sparse literature on indigenous suicide prevention and will increase our knowledge about the effectiveness of e-health interventions for suicide prevention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12614000686606 . Registered on 30 June 2014.


Assuntos
Terapia de Aceitação e Compromisso/instrumentação , Telefone Celular , Saúde Mental , Aplicativos Móveis , Grupo com Ancestrais Oceânicos/psicologia , Ideação Suicida , Suicídio/prevenção & controle , Telemedicina/instrumentação , Terapia de Aceitação e Compromisso/métodos , Austrália , Feminino , Acesso aos Serviços de Saúde , Humanos , Masculino , Estudos Multicêntricos como Assunto , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Suicídio/etnologia , Suicídio/psicologia , Telemedicina/métodos , Fatores de Tempo , Resultado do Tratamento
15.
Trials ; 20(1): 203, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961658

RESUMO

BACKGROUND: CADENCE-BZ is a multi-centre, parallel-group, double-blind randomized controlled trial designed to examine the clinical efficacy and safety of an accessible food preservative, sodium benzoate, as an add-on treatment for patients with early psychosis. The original study protocol was published in 2017. Here, we describe the updated protocol along with the Statistical Analysis Plan (SAP) for the CADENCE-BZ trial prior to study completion. METHODS AND MATERIALS: Two important changes were made to the original protocol: (1) improvements to our statistical analysis plan permitted a reduction in sample size; and (2) a revision in the secondary outcomes with the intent of reducing redundancy and excluding those measures that were not appropriate as outcomes. CONCLUSIONS: We provide the updated SAP prior to the completion of the study with the intent of increasing the transparency of the data analyses for CADENCE-BZ. The final participants are currently completing the study and the results will be published in the near future. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12615000187549 ). Registered on 26th February 2015.


Assuntos
Antipsicóticos/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Benzoato de Sódio/uso terapêutico , Antipsicóticos/efeitos adversos , Austrália , Interpretação Estatística de Dados , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra , Benzoato de Sódio/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
16.
BMC Pulm Med ; 19(1): 75, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30971235

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease, with a median survival of 2-3 years and variable natural history, characterized by gradual and progressive deterioration. Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication, associated with poor survival and a mortality > 50%. To date, no treatment has proven effective in AE-IPF, with cyclophosphamide (CYC) the only therapy suggested to be effective on survival, primarily based on retrospective series. Considering the high fatality rates of AE-IPF, evaluating the efficacy of immunosuppressive agents in a randomized controlled trial proves crucial, as the results could significantly impact treatment and prognosis of AE-IPF. METHODS: The EXAFIP study is a French national multicenter double-blind placebo-controlled randomized trial. Its primary objective is to evaluate the efficacy of CYC compared to placebo on early survival in patients treated with corticosteroids. We hypothesize that adding CYC to high-dose corticosteroids would reduce 3-month mortality in AE-IPF patients. The primary outcome is all-cause mortality rate at Month 3; secondary objectives are to evaluate the efficacy of CYC compared to placebo on overall survival at Months 6 and 12, respiratory disease-specific mortality, respiratory morbidity, and chest high-resolution computed tomography features, and to determine prognostic factors in AE-IPF and compare the safety of the two treatment arms during 6 months' follow-up. DISCUSSION: There is an urgent unmet clinical need for effective AE-IPF treatment. The EXAFIP study is the first large Phase III placebo-controlled randomized trial evaluating the efficacy and safety of CYC added to corticosteroids in treating AE-IPF. The results of this study could significantly impact treatment strategy and prognosis of AE-IPF. TRIAL REGISTRATION: Clinical trials, NCT02460588 ; Date: June 2, 2015, prospectively; Issue date: 14/11/2017; Protocole Amendment Number: 03.


Assuntos
Corticosteroides/uso terapêutico , Ciclofosfamida/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Causas de Morte , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , França , Humanos , Estudos Multicêntricos como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento
17.
Trials ; 20(1): 189, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940164

RESUMO

BACKGROUND: Early adolescence is a period of dynamic neurobiological change. Converging lines of research suggest that regular physical activity (PA) and improved aerobic fitness have the potential to stimulate positive brain changes, improve cognitive function and boost academic attainment in this age group, but high-quality studies are needed to substantiate these findings. The primary aim of the Fit to Study trial is to investigate whether short infusions of vigorous PA (VPA) delivered during secondary school physical education (PE) can improve attainment in maths, as described in a protocol published by NatCen Social Research. The present protocol concerns the trial's secondary outcome measures, which are variables thought to moderate or mediate the relationship between PA and attainment, including the effect of the intervention on cardiorespiratory fitness, cognitive performance, mental health and brain structure and function. METHOD: The Fit to Study project is a cluster-randomised controlled trial that includes Year 8 pupils (aged 12-13) from secondary state schools in South/Mid-England. Schools were randomised into an intervention condition in which PE teachers delivered an additional 10 min of VPA per PE lesson for one academic year, or a 'PE as usual' control condition. Intervention and control groups were stratified according to whether schools were single-sex or co-educational. Assessments take place at baseline (end of Year 7, aged 11-12) and after 12 months (Year 8). Secondary outcomes are cardiorespiratory fitness, objective PA during PE, cognitive performance and mental health. The study also includes exploratory measures of daytime sleepiness, attitudes towards daily PA and PE enjoyment. A sub-set of pupils from a sub-set of schools will also take part in a brain imaging sub-study, which is embedded in the trial. DISCUSSION: The Fit to Study trial could advance our understanding of the complex relationships between PA and aerobic fitness, the brain, cognitive performance, mental health and academic attainment during adolescence. Further, it will add to our understanding of whether school PE is an effective setting to increase VPA and fitness, which could inform future PA interventions and education policy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03286725 . Retrospectively registered on 18 September 2017. ClinicalTrials.gov, NCT03593863 . Retrospectively registered on 19 July 2018.


Assuntos
Desempenho Acadêmico , Comportamento do Adolescente , Encéfalo/fisiologia , Comportamento Infantil , Cognição , Saúde Mental , Educação Física e Treinamento/métodos , Aptidão Física , Serviços de Saúde Escolar , Adolescente , Fatores Etários , Encéfalo/diagnóstico por imagem , Criança , Inglaterra , Exercício , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
18.
Trials ; 20(1): 188, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940201

RESUMO

BACKGROUND: Symptomatic hemorrhoids are one of the most common anorectal disorders. Many surgeons use tamponades after open hemorrhoidectomy to manage postoperative bleeding. The question of whether a tamponade is necessary and beneficial after hemorrhoidectomy has not yet been conclusively answered. A previously conducted single-center pilot trial included 100 patients after Milligan-Morgan hemorrhoidectomy. The data indicated that insertion of an anal tamponade after hemorrhoidectomy does not reduce postoperative bleeding but causes significantly more pain. The findings of this pilot trial are now to be verified by means of a multicenter randomized clinical study called NoTamp. METHODS: We plan to include 953 patients after Milligan-Morgan or Parks hemorrhoidectomy in the NoTamp study. The aim is to demonstrate that using no tamponade dressing after open hemorrhoidectomy is not inferior to using tamponades with respect to postoperative bleeding, and that the patients report less pain. Primary endpoints of the trial are the maximum postoperative pain within 48 h and the incidence of severe postoperative bleeding that requires surgical revision within 7 days after the surgical procedure. Secondary endpoints of the study are the use of analgesics in the postoperative course, the lowest hemoglobin documented within 7 days, quality of life and patient satisfaction. Safety analysis includes all adverse and serious adverse events in relation to the study treatment. Further information can be found in the registration at the German Registry of Clinical Studies (DRKS00011590) and on the study webpage ( https://notamp.de/en-GB/trial/main/setLocale/en_GB/ ). The study is financed by the HELIOS research funding. DISCUSSION: The study received full ethics committee approval. The first patient was enrolled on 3 May 2017. This trial will finally answer the question whether the insertion of a tamponade after open hemorrhoidectomy is necessary and beneficial. TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinischer Studien (DRKS), DRKS00011590 . Registered on 12 April 2017.


Assuntos
Bandagens , Hemorroidectomia , Hemorroidas/cirurgia , Técnicas Hemostáticas/instrumentação , Hemorragia Pós-Operatória/prevenção & controle , Tampões Cirúrgicos , Analgésicos/uso terapêutico , Estudos de Equivalência como Asunto , Alemanha , Hemorroidectomia/efeitos adversos , Hemorroidas/diagnóstico , Técnicas Hemostáticas/efeitos adversos , Humanos , Estudos Multicêntricos como Assunto , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente , Hemorragia Pós-Operatória/etiologia , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento
19.
Trials ; 20(1): 192, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944022

RESUMO

BACKGROUND: Multicentre randomised trials provide some of the key evidence underpinning healthcare practice around the world. They are also hard work and generally expensive. Some of this work and expense are devoted to sites that fail to recruit as many participants as expected. Methods to identify sites that will recruit to target would be helpful. METHODS: We asked trial managers at the Centre for Healthcare Randomised Trials (CHaRT), University of Aberdeen to predict whether a site would recruit to target. Predictions were made after a site initiation visit and were collected on a form comprising a simple 'Yes/No' prediction and a reason for the prediction. We did not provide guidance as to what trial managers might want to think about when making predictions. After a minimum of eight months of recruitment at each site for which a prediction had been made, all trial mangers in CHaRT were invited to a group discussion where predictions were presented together with sites' actual recruitment performance over that period. Individual trial managers reflected on their predictions and there was a general discussion about predicting site recruitment. The prediction reasons from the forms and the content of the group discussion were used to identify features linked to correct predictions of recruitment failure. RESULTS: Ten trial managers made predictions for 56 site visits recruiting to eight trials. Trial managers' sensitivity was 82% and their specificity was 32%, correctly identifying 65% of sites that would hit their recruitment target and 54% of those that did not. Eight 'red flags' for recruitment failure were identified: previous poor site performance; slow approvals process; strong staff/patient preferences; the site recruitment target; the trial protocol and its implementation at the site; lack of staff engagement; lack of research experience among site staff; and busy site staff. We used these red flags to develop a guided prediction form. CONCLUSIONS: Trial managers' unguided recruitment predictions were not bad but were not good enough for decision-making. We have developed a modified prediction form that includes eight flags to consider before making a prediction. We encourage anyone interested in contributing to its evaluation to contact us.


Assuntos
Técnicas de Apoio para a Decisão , Estudos Multicêntricos como Assunto/métodos , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Pesquisadores/psicologia , Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Tamanho da Amostra
20.
Trials ; 20(1): 191, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944040

RESUMO

BACKGROUND: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer's disease compared to those who are receiving placebo. METHODS/DESIGN: ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer's dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Cooperative Study-Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. DISCUSSION: Alzheimer's disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer's treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01843075 . Registration 30 April 2013.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucose/metabolismo , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Atividades Cotidianas , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Ensaios Clínicos Fase II como Assunto , Cognição/efeitos dos fármacos , Método Duplo-Cego , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Liraglutida/efeitos adversos , Memória/efeitos dos fármacos , Estudos Multicêntricos como Assunto , Fármacos Neuroprotetores/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Reino Unido
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