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1.
Ther Adv Cardiovasc Dis ; 14: 1753944720911329, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32168991

RESUMO

BACKGROUND: The objective of this review is to provide a practical update on endpoint selection for noninferiority (NI) studies in percutaneous coronary intervention studies. METHODS: A PubMed search was conducted for predefined terms to explore the use of NI designs and intrapatient comparisons to determine their current importance. Sample size calculations for the most frequently used endpoints with NI hypotheses were done to increase statistical awareness. RESULTS: Reported NI trials, with the most frequently chosen clinical endpoint of major adverse cardiac events (MACE), had NI margins ranging from 1.66% to 5.00%, resulting in patient populations of 400-1500 per treatment group. Clinical study endpoints comprising of MACE complemented with rates of bleeding complications and stent thrombosis (ST) are suggested to conduct a statistically and clinically meaningful NI trial. Study designs with surrogate endpoints amenable to intrapatient randomizations, are a very attractive option to reduce the number of necessary patients by about half. Comparative clinical endpoint studies with MACE and ST/bleeding rates to study a shortened dual antiplatelet therapy (DAPT) in coronary stent trials are feasible, whereas ST as the sole primary endpoint is not useful. CONCLUSIONS: Expanded composite clinical endpoints (MACE complemented by ST and bleeding rates and intrapatient randomization for selected surrogate endpoints) may be suitable tools to meet future needs in device approval, recertification and reimbursement.


Assuntos
Doença da Artéria Coronariana/terapia , Determinação de Ponto Final , Estudos de Equivalência como Asunto , Intervenção Coronária Percutânea , Projetos de Pesquisa , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Trombose Coronária , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Fatores de Risco , Tamanho da Amostra , Stents , Fatores de Tempo , Resultado do Tratamento
2.
Lancet Haematol ; 7(3): e196-e208, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32014125

RESUMO

BACKGROUND: The PROUD-PV and CONTINUATION-PV trials aimed to compare the novel monopegylated interferon ropeginterferon alfa-2b with hydroxyurea, the standard therapy for patients with polycythaemia vera, over 3 years of treatment. METHODS: PROUD-PV and its extension study, CONTINUATION-PV, were phase 3, randomised, controlled, open-label, trials done in 48 clinics in Europe. Patients were eligible if 18 years or older with early stage polycythaemia vera (no history of cytoreductive treatment or less than 3 years of previous hydroxyurea treatment) diagnosed by WHO's 2008 criteria. Patients were randomly assigned 1:1 to ropeginterferon alfa-2b (subcutaneously every 2 weeks, starting at 100 µg) or hydroxyurea (orally starting at 500 mg/day). After 1 year, patients could opt to enter the extension part of the trial, CONTINUATION-PV. The primary endpoint in PROUD-PV was non-inferiority of ropeginterferon alfa-2b versus hydroxyurea regarding complete haematological response with normal spleen size (longitudinal diameter of ≤12 cm for women and ≤13 cm for men) at 12 months; in CONTINUATION-PV, the coprimary endpoints were complete haematological response with normalisation of spleen size and with improved disease burden (ie, splenomegaly, microvascular disturbances, pruritus, and headache). We present the final results of PROUD-PV and an interim analysis at 36 months of the CONTINUATION-PV study (per statistical analysis plan). Analyses for safety and efficacy were per-protocol. The trials were registered on EudraCT, 2012-005259-18 (PROUD-PV) and 2014-001357-17 (CONTINUATION-PV, which is ongoing). FINDINGS: Patients were recruited from Sept 17, 2013 to March 13, 2015 with 306 enrolled. 257 patients were randomly assigned, 127 were treated in each group (three patients withdrew consent in the hydroxyurea group), and 171 rolled over to the CONTINUATION-PV trial. Median follow-up was 182·1 weeks (IQR 166·3-201·7) in the ropeginterferon alfa-2b and 164·5 weeks (144·4-169·3) in the standard therapy group. In PROUD-PV, 26 (21%) of 122 patients in the ropeginterferon alfa-2b group and 34 (28%) of 123 patients in the standard therapy group met the composite primary endpoint of complete haematological response with normal spleen size. In CONTINUATION-PV, complete haematological response with improved disease burden was met in 50 (53%) of 95 patients in the ropeginterferon alfa-2b group versus 28 (38%) of 74 patients in the hydroxyurea group, p=0·044 at 36 months. Complete haematological response without the spleen criterion in the ropeginterferon alfa-2b group versus standard therapy group were: 53 (43%) of 123 patients versus 57 (46%) of 125 patients, p=0·63 at 12 months (PROUD-PV), and 67 (71%) of 95 patients versus 38 (51%) of 74 patients, p=0·012 at 36 months (CONTINUATION-PV). The most frequently reported grade 3 and grade 4 treatment-related adverse events were increased γ-glutamyltransferase (seven [6%] of 127 patients) and increased alanine aminotransferase (four [3%] of 127 patients) in the ropeginterferon alfa-2b group, and leucopenia (six [5%] of 127 patients) and thrombocytopenia (five [4%] of 127 patients) in the standard therapy group. Treatment-related serious adverse events occurred in three (2%) of 127 patients in the ropeginterferon alfa-2b group and five (4%) of 127 patients in the hydroxyurea group. One treatment-related death was reported in the standard therapy group (acute leukaemia). INTERPRETATION: In patients with early polycythaemia vera, who predominantly presented without splenomegaly, ropeginterferon alfa-2b was effective in inducing haematological responses; non-inferiority to hydroxyurea regarding haematological response and normal spleen size was not shown at 12 months. However, response to ropeginterferon alfa-2b continued to increase over time with improved responses compared with hydroxyurea at 36 months. Considering the high and durable haematological and molecular responses and its good tolerability, ropeginterferon alfa-2b offers a valuable and safe long-term treatment option with features distinct from hydroxyurea. FUNDING: AOP Orphan Pharmaceuticals AG.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Policitemia Vera/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Idoso , Estudos de Equivalência como Asunto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Policitemia Vera/patologia , Prognóstico , Proteínas Recombinantes/uso terapêutico
3.
Lancet ; 395(10219): 212-224, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954466

RESUMO

BACKGROUND: Cataract surgery is one of the most common operations in health care. Femtosecond laser-assisted cataract surgery (FLACS) enables more precise ocular incisions and lens fragmentation than does phacoemulsification cataract surgery (PCS). We hypothesised that FLACS might improve outcomes in cataract surgery compared with PCS despite having higher costs. METHODS: We did a participant-masked randomised superiority clinical trial comparing FLACS and PCS in two parallel groups (permuted block randomisation stratified on centres via a centralised web-based application, allocation ratio 1:1, block size of 2 or 4 for unilateral cases and 2 or 6 for bilateral cases). Five French University Hospitals enrolled consecutive patients aged 22 years or older who were eligible for unilateral or bilateral cataract surgery. Participants, outcome assessors, and technicians carrying out examinations were masked to the surgical treatment allocation until the last follow-up visit and a sham laser procedure was set up for participants randomly assigned to the PCS arm. The primary clinical endpoint was the success rate of surgery, defined as a composite of four outcomes at a 3-month postoperative visit: absence of severe perioperative complication, a best-corrected visual acuity (BCVA) of 0·0 LogMAR (logarithm of the minimum angle of resolution) or better, an absolute refractive error of 0·75 dioptres or less, and unchanged postoperative corneal astigmatism power (≤0·5 dioptres) and axis (≤20°). The primary economic endpoint was the incremental cost per additional patient who had treatment success at 3 months. Primary outcomes were assessed in all randomly assigned patients who met all eligibility criteria (missing data considered as failure). We used mixed logistic regression models or mixed linear regression models for statistical comparisons, adjusted on centres and whether cataract surgery was bilateral or unilateral. The study is registered with ClinicalTrials.gov, NCT01982006. FINDINGS: Of the 907 patients (1476 eyes) randomly assigned between Oct 9, 2013, and Oct 30, 2015, 870 (704 eyes in FLACS group and 685 eyes in the PCS group) were analysed. We identified no significant difference in the success rate of surgery between the FLACS and PCS groups (FLACS: 41·1% [289 eyes]; PCS: 43·6% [299 eyes]); adjusted odds ratio 0·85, 95% CI 0·64-1·12, p=0·250). The incremental cost-effectiveness ratio was €10 703 saved per additional patient who had treatment success with PCS compared with FLACS. We observed no severe adverse events during the femtosecond laser procedure, and most of the complications in the FLACS group related to the primary outcome measures occurred during the phacoemulsification phase or postoperatively. INTERPRETATION: Despite its advanced technology, femtosecond laser was not superior to phacoemulsification in cataract surgery and, with higher costs, did not provide an additional benefit over phacoemulsification for patients or health-care systems. FUNDING: French Ministry of Social Affairs and Health.


Assuntos
Extração de Catarata/economia , Extração de Catarata/métodos , Análise Custo-Benefício , Terapia a Laser/economia , Facoemulsificação/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Extração de Catarata/efeitos adversos , Estudos de Equivalência como Asunto , Feminino , Humanos , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Masculino , Pessoa de Meia-Idade , Facoemulsificação/efeitos adversos , Facoemulsificação/métodos , Resultado do Tratamento
4.
Lancet ; 395(10219): 191-199, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31879028

RESUMO

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used in revascularisation of patients with left main coronary artery disease in place of the standard treatment, coronary artery bypass grafting (CABG). The NOBLE trial aimed to evaluate whether PCI was non-inferior to CABG in the treatment of left main coronary artery disease and reported outcomes after a median follow-up of 3·1 years. We now report updated 5-year outcomes of the trial. METHODS: The prospective, randomised, open-label, non-inferiority NOBLE trial was done at 36 hospitals in nine northern European countries. Patients with left main coronary artery disease requiring revascularisation were enrolled and randomly assigned (1:1) to receive PCI or CABG. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, repeat revascularisation, and stroke. Non-inferiority of PCI to CABG was defined as the upper limit of the 95% CI of the hazard ratio (HR) not exceeding 1·35 after 275 MACCE had occurred. Secondary endpoints included all-cause mortality, non-procedural myocardial infarction, and repeat revascularisation. Outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were enrolled and allocated to PCI (n=598) or CABG (n=603), with 17 subsequently lost to early follow-up. 592 patients in each group were included in this analysis. At a median of 4·9 years of follow-up, the predefined number of events was reached for adequate power to assess the primary endpoint. Kaplan-Meier 5-year estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG (HR 1·58 [95% CI 1·24-2·01]); the HR exceeded the limit for non-inferiority of PCI compared to CABG. CABG was found to be superior to PCI for the primary composite endpoint (p=0·0002). All-cause mortality was estimated in 9% after PCI versus 9% after CABG (HR 1·08 [95% CI 0·74-1·59]; p=0·68); non-procedural myocardial infarction was estimated in 8% after PCI versus 3% after CABG (HR 2·99 [95% CI 1·66-5·39]; p=0·0002); and repeat revascularisation was estimated in 17% after PCI versus 10% after CABG (HR 1·73 [95% CI 1·25-2·40]; p=0·0009). INTERPRETATION: In revascularisation of left main coronary artery disease, PCI was associated with an inferior clinical outcome at 5 years compared with CABG. Mortality was similar after the two procedures but patients treated with PCI had higher rates of non-procedural myocardial infarction and repeat revascularisation. FUNDING: Biosensors.


Assuntos
Ponte de Artéria Coronária , Estenose Coronária/cirurgia , Intervenção Coronária Percutânea , Idoso , Causas de Morte , Ponte de Artéria Coronária/efeitos adversos , Reestenose Coronária/cirurgia , Stents Farmacológicos , Estudos de Equivalência como Asunto , Oclusão de Enxerto Vascular , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Complicações Pós-Operatórias , Estudos Prospectivos , Acidente Vascular Cerebral , Resultado do Tratamento
5.
Bone Joint J ; 101-B(12): 1472-1475, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31787004

RESUMO

The Ankle Injury Management (AIM) trial was a pragmatic equivalence randomized controlled trial conducted at 24 hospitals in the United Kingdom that recruited 620 patients aged more than 60 years with an unstable ankle fracture. The trial compared the usual care pathway of early management with open reduction and internal fixation with initially attempting non-surgical management using close contact casting (CCC). CCC is a minimally padded cast applied by an orthopaedic surgeon after closed reduction in the operating theatre. The intervention groups had equivalent functional outcomes at six months and longer-term follow-up. However, potential barriers to using CCC as an initial form of treatment for these patients have been identified. In this report, the results of the AIM trial are summarized and the key issues are discussed in order to further the debate about the role of CCC. Evidence from the AIM trial supports surgeons considering conservative management by CCC as a treatment option for these patients. The longer-term follow-up emphasized that patients treated with CCC need careful monitoring in the weeks after its application to monitor maintenance of reduction. Cite this article: Bone Joint J 2019;101-B:1472-1475.


Assuntos
Fraturas do Tornozelo/cirurgia , Traumatismos do Tornozelo/cirurgia , Moldes Cirúrgicos , Redução Fechada/métodos , Tratamento Conservador/métodos , Fixação Interna de Fraturas/métodos , Idoso , Idoso de 80 Anos ou mais , Redução Fechada/instrumentação , Tratamento Conservador/instrumentação , Estudos de Equivalência como Asunto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Ensaios Clínicos Pragmáticos como Assunto , Resultado do Tratamento
7.
Cancer Radiother ; 23(6-7): 503-509, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471253

RESUMO

There are many treatment options for localized prostate cancers, including active surveillance, brachytherapy, external beam radiotherapy, and radical prostatectomy. Quality of life remains a primary objective in the absence of superiority of one strategy over another in terms of specific survival with similar long-term biochemical control rates. Despite a significant decrease in digestive and urinary toxicities thanks to IMRT and IGRT, external radiotherapy remains a treatment that lasts approximately 2 months or 1.5 months, when combined with a brachytherapy boost. Given the specific radiosensitivity of this tumor, several randomized studies have shown that a hypofractionated scheme is not inferior in terms of biochemical control and toxicities, allowing to divide the number of fractions by a factor 2 to 8. Given that SBRT becomes a validated therapeutic option for a selected population of patients with localized prostate cancer, extreme hypofractionation is becoming a strong challenger of conventional external radiotherapy or brachytherapy.


Assuntos
Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Braquiterapia , Ensaios Clínicos Fase III como Assunto , Estudos de Equivalência como Asunto , Humanos , Irradiação Linfática/métodos , Masculino , Seleção de Pacientes , Cuidados Pós-Operatórios , Qualidade de Vida , Hipofracionamento da Dose de Radiação/normas , Tolerância a Radiação , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Maturitas ; 129: 23-29, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31547909

RESUMO

BACKGROUND: Menopause syndrome generally includes psychological problems. Group treatment delivered via the Internet and mobile phone (imGT) may improve women's physiological and psychological conditions. OBJECTIVE: To investigate the efficacy of group cognitive behavioural therapy of menopause-related mood swings and quality of life, delivered face to face or via the Internet and mobile phone. METHODS: This protocol is for a randomized controlled clinical trial with a sample of 140 menopausal women divided into 2 groups: imGT and face-to-face group treatment (ffGT). The primary outcome will be the improvement in the menopausal symptoms of the two groups, as assessed by the Greene Climacteric Scale. The secondary outcomes will be: quality of life, assessed by the Short Form 36 Health Survey Questionnaire; insomnia, assessed by the Pittsburgh Sleep Quality Inventory; anxiety, assessed by the Hamilton Anxiety Rating Scale; and therapeutic alliance, assessed by the Working Alliance Inventory-Short Revised and Client Sat-is-fac-tion Qes-tion-naire-8. imGT will be performed once a week for 1.5 h for 10 weeks with a daily 'Punched-in' on the WeChat app; ffGT will be performed once a week for 1.5 h for 10 weeks. All outcomes will be assessed at baseline, at a post-intervention evaluation (week 10), and at a follow-up evaluation (week 22). DISCUSSION: This study will be the first clinical trial to examine the effects of imGT on menopausal women in China. If imGT is found to be non-inferior to ffGT, it will facilitate access to menopausal health services.


Assuntos
Sintomas Afetivos/terapia , Telefone Celular , Terapia Cognitivo-Comportamental/métodos , Internet , Menopausa/psicologia , Psicoterapia de Grupo/métodos , Adulto , Ansiedade/terapia , China , Estudos de Equivalência como Asunto , Feminino , Humanos , Pessoa de Meia-Idade , Aplicativos Móveis , Qualidade de Vida/psicologia , Distúrbios do Início e da Manutenção do Sono/terapia , Inquéritos e Questionários , Síndrome
9.
BMC Musculoskelet Disord ; 20(1): 357, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31387574

RESUMO

BACKGROUND: Scaphoid fractures are the most common carpal fractures. They often need to be treated by surgery, where the use of a compression screw is the globally accepted gold standard. Surgeons may choose between different implant materials including titanium alloys, which remain in the body or are removed after healing. An alternative are biodegradable magnesium-based implants. Properties of magnesium alloys include high stability, osteoconductivity, potential reduction of infections and few artifacts in magnetic resonance imaging (MRI). The aim of this trial is to demonstrate non-inferiority of magnesium-based compression screws compared with titanium Herbert screws for scaphoid fractures. METHODS: The trial is designed as a multicenter, blinded observer, randomized controlled parallel two-group post market trial. Approximately 190 patients will be randomized (1:1) with stratification by center either to titanium or magnesium-based compression screws. Follow-up is 1 year per patient. Surgical procedures and aftercare will be performed according to the German treatment guideline for scaphoid fractures. The first primary endpoint is the patient-rated wrist evaluation (PRWE) score after 6 months. The second primary endpoint is a composite safety endpoint including bone union until 6 months, no adverse device effect (ADE) during surgery or wound healing and no serious ADE or reoperation within 1 year. The third primary endpoint is the difference in change MRI artifacts over time. Non-inferiority will be investigated for primary endpoints 1 (t-test confidence interval) and 2 (Wilson's score interval) using both the full analysis set (FAS) and the per protocol population at the one-sided 2.5% test-level. Superiority of magnesium over titanium screws will be established using the FAS at the two-sided 5% test-level (Welch test) only if non-inferiority has been established for both primary endpoints. Secondary endpoints include quality of life. DISCUSSION: This study will inform care providers whether biodegradable magnesium-based implants are non-inferior to standard titanium Herbert screws for the treatment of scaphoid fractures in terms of wrist function and safety. Furthermore, superiority of magnesium-based implants may be demonstrated using MRI, which is used as surrogate endpoint for screw degradation. TRIAL REGISTRATION: DRKS, DRKS00013368 . Registered Dec 04, 2017.


Assuntos
Implantes Absorvíveis/efeitos adversos , Parafusos Ósseos/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Osso Escafoide/lesões , Traumatismos do Punho/cirurgia , Adolescente , Adulto , Ensaios Clínicos Fase IV como Assunto , Estudos de Equivalência como Asunto , Fixação Interna de Fraturas/efeitos adversos , Humanos , Magnésio/efeitos adversos , Imagem por Ressonância Magnética , Masculino , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação/estatística & dados numéricos , Osso Escafoide/diagnóstico por imagem , Osso Escafoide/cirurgia , Titânio/efeitos adversos , Resultado do Tratamento , Traumatismos do Punho/diagnóstico por imagem , Traumatismos do Punho/fisiopatologia , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/fisiopatologia , Adulto Jovem
10.
Pediatrics ; 144(3)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31416827

RESUMO

OBJECTIVES: The use of either prednisolone or low-dose dexamethasone in the treatment of childhood croup lacks a rigorous evidence base despite widespread use. In this study, we compare dexamethasone at 0.6 mg/kg with both low-dose dexamethasone at 0.15 mg/kg and prednisolone at 1 mg/kg. METHODS: Prospective, double-blind, noninferiority randomized controlled trial based in 1 tertiary pediatric emergency department and 1 urban district emergency department in Perth, Western Australia. Inclusions were age >6 months, maximum weight 20 kg, contactable by telephone, and English-speaking caregivers. Exclusion criteria were known prednisolone or dexamethasone allergy, immunosuppressive disease or treatment, steroid therapy or enrollment in the study within the previous 14 days, and a high clinical suspicion of an alternative diagnosis. A total of 1252 participants were enrolled and randomly assigned to receive dexamethasone (0.6 mg/kg; n = 410), low-dose dexamethasone (0.15 mg/kg; n = 410), or prednisolone (1 mg/kg; n = 411). Primary outcome measures included Westley Croup Score 1-hour after treatment and unscheduled medical re-attendance during the 7 days after treatment. RESULTS: Mean Westley Croup Score at baseline was 1.4 for dexamethasone, 1.5 for low-dose dexamethasone, and 1.5 for prednisolone. Adjusted difference in scores at 1 hour, compared with dexamethasone, was 0.03 (95% confidence interval -0.09 to 0.15) for low-dose dexamethasone and 0.05 (95% confidence interval -0.07 to 0.17) for prednisolone. Re-attendance rates were 17.8% for dexamethasone, 19.5% for low-dose dexamethasone, and 21.7% for prednisolone (not significant [P = .59 and .19]). CONCLUSIONS: Noninferiority was demonstrated for both low-dose dexamethasone and prednisolone. The type of oral steroid seems to have no clinically significant impact on efficacy, both acutely and during the week after treatment.


Assuntos
Crupe/tratamento farmacológico , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Administração Oral , Pré-Escolar , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Serviço Hospitalar de Emergência , Estudos de Equivalência como Asunto , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Lactente , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Prospectivos , Austrália Ocidental
11.
Trials ; 20(1): 496, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409421

RESUMO

BACKGROUND: HIV-testing coverage remains below the targeted 90% despite efforts and resources invested. Home-based HIV-testing is a key approach endorsed by the World Health Organization (WHO), especially to reach individuals who might not seek testing otherwise. Although acceptance of testing during such campaigns is high, coverage remains low due to absent household members. This cluster-randomized trial aims to assess increase in testing coverage using oral HIV self-testing (HIVST) among individuals who are absent or decline testing during home-based HIV-testing. METHODS: The HOSENG (HOme-based SElf-testiNG) trial is a cluster-randomized, parallel-group, superiority trial in two districts of Lesotho, Southern Africa. Clusters are stratified by district, village size, and village access to the nearest health facility. Cluster eligibility criteria include: village is in catchment area of one of the study facilities, village authority provides consent, and village has a registered, capable, and consenting village health worker (VHW). In intervention clusters, HIV self-tests are provided for eligible household members who are absent or decline HIV-testing in the presence of the campaign team. In control clusters, standard of care for absent and refusing individuals applies, i.e., referral to a health facility. The primary outcome is HIV-testing coverage among individuals aged 12 years or older within 120 days after enrollment. Secondary objectives include HIV-testing coverage among other age groups, and uptake of the different testing modalities. Statistical analyses will be conducted and reported in line with CONSORT guidelines. The HOSENG trial is linked to the VIBRA (Village-Based Refill of ART) trial. Together, they constitute the GET ON (GETting tOwards Ninety) research project. DISCUSSION: The HOSENG trial tests whether oral HIVST may be an add-on during door-to-door testing campaigns towards achieving optimal testing coverage. The provision of oral self-test kits, followed up by VHWs, requires little additional human resources, finances and logistics. If cost-effective, this approach should inform home-based HIV-testing policies not only in Lesotho, but in similar high-prevalence settings. TRIAL REGISTRATION: ClinicalTrials.gov, (ID: NCT03598686 ). Registered on 25 July 2018. More information is available at www.getonproject.wordpress.com .


Assuntos
Agentes Comunitários de Saúde/organização & administração , Infecções por HIV/diagnóstico , Promoção da Saúde/organização & administração , Visita Domiciliar , Programas de Rastreamento/organização & administração , Aceitação pelo Paciente de Cuidados de Saúde , Serviços de Saúde Rural/organização & administração , Autocuidado , Adolescente , Adulto , Criança , Estudos de Equivalência como Asunto , Feminino , Infecções por HIV/terapia , Humanos , Lesoto , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Adulto Jovem
12.
Trials ; 20(1): 500, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412913

RESUMO

BACKGROUND: Persons with mild to borderline intellectual disabilities generally show dysfunctions in mentalization and stress regulation, resulting in problematic social relationships and personal distress. Intervention programs may improve mentalizing abilities. The aim of this study is to examine the effectiveness of the serious game 'You & I' in changing mentalizing abilities and stress regulation in adults with mild to borderline intellectual disabilities. METHODS: A two-arm, parallel, superiority randomized controlled trial will be used with 172 adults with mild to borderline intellectual disabilities. Participants will be randomly assigned to either the experimental group to play the serious game 'You & I' or a waitlist control group. Participants will be assessed at baseline, post intervention (5 weeks after baseline), and follow-up (6-8 weeks after post intervention). They also will fill in questionnaires for personal factors, personal development, personal well-being, social validity, autism spectrum quotient (demographic variables), mentalizing abilities (primary outcome measure), and stress regulation (secondary outcome measure). DISCUSSION: The serious game 'You & I' aims to improve mentalizing abilities in adults with mild to borderline intellectual disabilities, which is expected to lead to improved regulation of stress in social relationships. The study's unique feature is the use of a serious game to improve mentalizing abilities. If the intervention is effective, the serious game can be implemented on a broad scale in Dutch care organizations for people with intellectual disabilities as an effective preventive tool to improve mentalizing abilities. TRIAL REGISTRATION: Netherlands Trial Register, NTR7418 . Registered on 2 August 2018.


Assuntos
Deficiência Intelectual/reabilitação , Mentalização , Pessoas com Deficiência Mental/reabilitação , Estresse Psicológico/prevenção & controle , Jogos de Vídeo , Adaptação Psicológica , Estudos de Equivalência como Asunto , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/psicologia , Pessoas com Deficiência Mental/psicologia , Países Baixos , Comportamento Social , Estresse Psicológico/diagnóstico , Estresse Psicológico/psicologia , Fatores de Tempo , Resultado do Tratamento
14.
Trials ; 20(1): 522, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439004

RESUMO

BACKGROUND: There is a need for evaluating community-based antiretroviral therapy (ART) delivery models to improve overall performance of HIV programs, specifically in populations that may have difficulties to access continuous care. This cluster-randomized clinical trial aims to evaluate the effectiveness of a multicomponent differentiated ART delivery model (VIBRA model) after home-based same-day ART initiation in remote villages in Lesotho, southern Africa. METHODS/DESIGN: The VIBRA trial (VIllage-Based Refill of ART) is a cluster-randomized parallel-group superiority clinical trial conducted in two districts in Lesotho, southern Africa. Clusters (i.e., villages) are randomly assigned to either the VIBRA model or standard care. The clusters are stratified by district, village size, and village access to the nearest health facility. Eligible individuals (HIV-positive, aged 10 years or older, and not taking ART) identified during community-based HIV testing campaigns are offered same-day home-based ART initiation. The intervention clusters offer a differentiated ART delivery package with two features: (1) drug refills and follow-ups by trained and supervised village health workers (VHWs) and (2) the option of receiving individually tailored adherence reminders and notifications of viral load results via SMS. The control clusters will continue to receive standard care, i.e., collecting ART refills from a clinic and no SMS notifications. The primary endpoint is viral suppression 12 months after enrolment. Secondary endpoints include linkage to and engagement in care. Furthermore, safety and cost-effectiveness analyses plus qualitative research are planned. The minimum target sample size is 262 participants. The statistical analyses will follow the CONSORT guidelines. The VIBRA trial is linked to another trial, the HOSENG (HOme-based SElf-testiNG) trial, both of which are within the GET ON (GETing tOwards Ninety) research project. DISCUSSION: The VIBRA trial is among the first to evaluate the delivery of ART by VHWs immediately after ART initiation. It assesses the entire HIV care cascade from testing to viral suppression. As most countries in sub-Saharan Africa have cadres like the VHW program in Lesotho, this model-if shown to be effective-has the potential to be scaled up. The system impact evaluation will provide valuable cost estimations, and the qualitative research will suggest how the model could be further modified to optimize its impact. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03630549 . Registered on 15 August 2018.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Assistência à Saúde/organização & administração , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Adesão à Medicação , Serviços de Saúde Rural/organização & administração , Fármacos Anti-HIV/efeitos adversos , Prescrições de Medicamentos , Estudos de Equivalência como Asunto , HIV/crescimento & desenvolvimento , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Humanos , Lesoto , Estudos Multicêntricos como Assunto , Fatores de Tempo , Resultado do Tratamento , Carga Viral
15.
BMC Musculoskelet Disord ; 20(1): 351, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366332

RESUMO

BACKGROUND: In the treatment of Lateral Epicondylitis (LE) no single intervention concerning injection therapies has been proven to be the most effective with regard to pain reduction. In this trial 3 injection therapies (perforation with application of autologous blood, perforation with application of dextrose and perforation only) will be compared in a standardized and ultrasound guided way. The objective is to assess the effectiveness of these 3 injection therapies on pain, quality of life and functional recovery. By conducting this study, we hope to make a statement on the effectiveness of injection therapy in the treatment of LE. Hereby, unnecessary treatments can be avoided, a more universal method of treatment can be established and the quality of the treatment can be improved. METHODS/DESIGN: A multicenter, randomized controlled trial with a superiority design and 12 months follow-up will be conducted in four Dutch hospitals. One hundred sixty five patients will be recruited in the age of 18 to 65 years, with chronic symptomatic lateral epicondylitis lasting longer than 6 weeks, which have concordant pain during physical examination. Patients will be randomized by block randomization to one of the three treatment arms. The treatment will be blinded for patients and outcome assessors. The following three injection therapies are compared: perforation with application of autologous blood, perforation with application of dextrose and perforation only. Injections will be performed ultrasound guided in a standardized and automated way. The primary endpoint is: pain (change in 'Visual Analogue Scale'). Secondary endpoints are quality of life and functional recovery. These measurements are collected at baseline, 8 weeks, 5 months and 1 year after treatment. DISCUSSION: When completed, this trial will provide evidence on the effectiveness of injection therapy in the treatment of lateral epicondylitis on pain, quality of life and functional recovery. In current literature proper comparison of the effectiveness of injectables for LE is questionable, due to the lack of standardization of the treatment. This study will overcome bias due to manually performed injection therapy. TRIAL REGISTRATION: This study is registered in the Trial Register ( www.trialregister.nl ) of the Dutch Cochrane centre. Trial ID; NTR4569. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4569.


Assuntos
Transfusão de Sangue Autóloga/métodos , Glucose/administração & dosagem , Dor Musculoesquelética/terapia , Manejo da Dor/métodos , Cotovelo de Tenista/terapia , Adolescente , Adulto , Idoso , Estudos de Equivalência como Asunto , Feminino , Humanos , Injeções/instrumentação , Injeções/métodos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/etiologia , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Cotovelo de Tenista/complicações , Cotovelo de Tenista/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia de Intervenção , Adulto Jovem
16.
Trials ; 20(1): 540, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464617

RESUMO

BACKGROUND: In Hong Kong, one of six couples is affected by subfertility problems. Male infertility contributes to half of the infertility cases. In male infertility, there is no effective treatment for patients with idiopathic infertility/poor semen parameters. Recent meta-analysis results suggest that a traditional Chinese medicine (TCM) formula - Wuzi Yanzong pill - showed a curative effect on male fertility. However, the heterogeneity of the studies could not draw a definitive conclusion on the therapeutic effect of this formula. The aim of this study is to conduct a well-designed randomized controlled trial to investigate the effect of TCM formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters. METHODS: This study is a double-blinded, randomized placebo-controlled trial conducted in a public hospital in Hong Kong. Participants will be randomized, using computer-generated random numbers, with a 1:1 ratio to either the Wuzi Yanzong pill formula group or the placebo group. Both groups will be administered the drugs for 12 weeks. Participants will have a total of four visits for their semen and blood assessments for a 6-month period, and we will follow up for another 6 months to record their conception outcome. The primary outcome is to compare the total motile sperm count, natural conception rate, and pregnancy outcome to those under placebo treatment. Secondary objectives are sperm functions and assisted reproductive technology outcome. DISCUSSION: To date, there are no studies using the disclosed Wuzi Yanzong formula or double-blinded, randomized trials. The Wuzi Yanzong TCM formula may provide a good clinical solution for subfertile males for which contemporary western medicine has no cure. Therefore, a well-designed randomized trial for evaluating the effect of Wuzi Yanzong TCM formula is urgently needed. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-INR-17010790 . Registered on 27 February 2017. Centre for Clinical Research and Biostatistics - Clinical Trials Registry, CUHK_CCRB00548 . Registered on 27 February 2017.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Fármacos para a Fertilidade Masculina/administração & dosagem , Fertilidade/efeitos dos fármacos , Infertilidade Masculina/tratamento farmacológico , Sêmen/efeitos dos fármacos , Administração Oral , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Estudos de Equivalência como Asunto , Fármacos para a Fertilidade Masculina/efeitos adversos , Hong Kong , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/fisiopatologia , Masculino , Estudos Prospectivos , Análise do Sêmen , Comprimidos , Fatores de Tempo , Resultado do Tratamento
17.
Lancet ; 394(10202): 919-928, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31451207

RESUMO

BACKGROUND: In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting ß-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting ß-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide-formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline. METHODS: We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18-75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 µg-formoterol 6 µg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 µg Turbuhaler (one inhalation twice daily) plus terbutaline 250 µg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437. FINDINGS: Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide-formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide-formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48-1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide-formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed. INTERPRETATION: In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid-formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma. FUNDING: Health Research Council of New Zealand.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Adolescente , Adulto , Idoso , Antiasmáticos/administração & dosagem , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Esquema de Medicação , Estudos de Equivalência como Asunto , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Índice de Gravidade de Doença , Terbutalina/administração & dosagem , Terbutalina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
18.
Trials ; 20(1): 519, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429792

RESUMO

BACKGROUND: Chronic mesenteric ischemia (CMI) is the result of insufficient blood supply to the gastrointestinal tract and is caused by atherosclerotic stenosis of one or more mesenteric arteries in > 90% of cases. Revascularization therapy is indicated in patients with a diagnosis of atherosclerotic CMI to relieve symptoms and to prevent acute-on-chronic mesenteric ischemia, which is associated with high morbidity and mortality. Endovascular therapy has rapidly evolved and has replaced surgery as the first choice of treatment in CMI. Bare-metal stents (BMS) are standard care currently, although retrospective studies suggested significantly higher patency rates for covered stents (CS). The Covered stents versus Bare-metal stents in chronic atherosclerotic Gastrointestinal Ischemia (CoBaGI) trial is designed to prospectively assess the patency of CS versus BMS in patients with atherosclerotic CMI. METHODS/DESIGN: The CoBaGI trial is a randomized controlled, parallel-group, patient- and investigator-blinded, superiority, multicenter trial conducted in six centers of the Dutch Mesenteric Ischemia Study group (DMIS). Eighty-four patients with a consensus diagnosis of atherosclerotic CMI are 1:1 randomized to either a balloon-expandable BMS (Palmaz Blue with rapid-exchange delivery system, Cordis Corporation, Bridgewater, NJ, USA) or a balloon-expandable CS (Advanta V12 over-the-wire, Atrium Maquet Getinge Group, Hudson, NH, USA). The primary endpoint is the primary stent-patency rate at 24 months assessed with CT angiography. Secondary endpoints are primary stent patency at 6 and 12 months and secondary patency rates, freedom from restenosis, freedom from symptom recurrence, freedom from re-intervention, quality of life according the EQ-5D-5 L and SF-36 and cost-effectiveness at 6, 12 and 24 months. DISCUSSION: The CoBaGI trial is designed to assess the patency rates of CS versus BMS in patients treated for CMI caused by atherosclerotic mesenteric stenosis. Furthermore, the CoBaGI trial should provide insights in the quality of life of these patients before and after stenting and its cost-effectiveness. The CoBaGI trial is the first randomized controlled trial performed in CMI caused by atherosclerotic mesenteric artery stenosis. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02428582 . Registered on 29 April 2015.


Assuntos
Angioplastia com Balão/instrumentação , Aterosclerose/terapia , Materiais Revestidos Biocompatíveis , Isquemia Mesentérica/terapia , Oclusão Vascular Mesentérica/terapia , Metais , Stents , Angioplastia com Balão/efeitos adversos , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Doença Crônica , Método Duplo-Cego , Estudos de Equivalência como Asunto , Humanos , Isquemia Mesentérica/diagnóstico por imagem , Isquemia Mesentérica/fisiopatologia , Oclusão Vascular Mesentérica/diagnóstico por imagem , Oclusão Vascular Mesentérica/fisiopatologia , Estudos Multicêntricos como Assunto , Países Baixos , Placa Aterosclerótica , Intervalo Livre de Progressão , Desenho de Prótese , Recidiva , Circulação Esplâncnica , Fatores de Tempo , Grau de Desobstrução Vascular
19.
Ann Surg Oncol ; 26(11): 3510-3516, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31297674

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a highly accurate method for staging the axilla in early breast cancer. Superparamagnetic iron oxide mapping agents have been explored to overcome the disadvantages of the standard SLNB technique, which uses a radioisotope tracer with or without blue dye. One such agent, Sienna+, was shown to be non-inferior to the standard technique for SLNB in a number of studies. The SentimagIC trial was designed to establish the non-inferiority of a new formulation of this magnetic tracer, Magtrace (formerly SiennaXP). METHODS: Patients with clinically node-negative early-stage breast cancer were recruited from six centers in the US. Patients received radioisotope and isosulfan blue dye injections, followed by an intraoperative injection of magnetic tracer, prior to SLNB. The sentinel node identification rate was compared between the magnetic and standard techniques to evaluate non-inferiority and concordance. RESULTS: Data were collected for 146 procedures in 146 patients. The per patient detection rate was 99.3% (145/146) when using the magnetic tracer and 98.6% (144/146) when using the standard technique, while the nodal detection rate was 94.3% (348/369 nodes) when using the magnetic tracer and 93.5% (345/369) when using the standard technique (difference 0.8%, 95% binomial confidence interval lower bound - 2.1%). Of the 22 patients with positive sentinel lymph nodes (SLNs), 21 (95.4%) were detected by both the magnetic tracer and the standard technique. All malignant nodes detected by standard technique were also identified by the magnetic technique. CONCLUSION: The magnetic technique is non-inferior to the standard technique of radioisotope and blue dye for axillary SLN detection in early-stage breast cancer. The magnetic technique is therefore a viable alternative.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Compostos Férricos , Nanopartículas de Magnetita , Corantes de Rosanilina , Linfonodo Sentinela/patologia , Tecnécio , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/cirurgia , Estudos de Equivalência como Asunto , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
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