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2.
Yonsei Med J ; 61(8): 689-697, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32734732

RESUMO

PURPOSE: Exposure to particulate matter (PM) is a well-known risk factor in the triggering and exacerbation of allergic airway disease. Indoor environments, where people spend most of their time, are of utmost importance. To assess the effects of air purifiers [equipped with high-efficiency particulate air (HEPA) filters] on allergic rhinitis (AR) in adult patients, we performed a multicenter, randomized, double-blind, and placebo-controlled study. MATERIALS AND METHODS: Patients with house dust mite (HDM)-induced AR were randomly assigned to either active or mockup (placebo) air-purification groups. Two air purifiers (placed in living room and bedroom) were operated for 6 weeks in each home environment. The primary study endpoint was to achieve improvement in AR symptoms and medication scores. Secondary endpoints were to achieve improvement in the quality of life (QoL) and visual analog scale (VAS) scores, as well as in the indoor (bedroom and living room) concentrations of PM2.5 and PM10. RESULTS: After 6 weeks of air purifier use, medication scores improved significantly in the active (vs. placebo) group, although subjective measures (symptoms, VAS, and QoL scores) did not differ. Bedroom PM2.5 concentrations initially exceeded living room or outdoor levels, but declined (by up to 51.8%) following active purifier operation. Concentrations of PM2.5 in living room and PM10 in bedroom and living room were also significantly reduced through active purification. CONCLUSION: The use of air purifiers with HEPA filters significantly reduced medication requirements for patients with HDM-induced AR and significantly lowered indoor PM2.5 concentrations, regardless of room placement. Active intervention to reduce household air pollutants may help improve allergic airway disease (clinicaltrials.gov NCT03313453).


Assuntos
Filtros de Ar , Rinite Alérgica/terapia , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Material Particulado/análise , Placebos , Qualidade de Vida , Fatores de Risco , Fatores de Tempo
3.
Medicine (Baltimore) ; 99(30): e21315, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791721

RESUMO

INTRODUCTION: There is evidence that caesarean section (CS) is associated with increased risk of childhood obesity, asthma, and coeliac disease. The gut microbiota of CS-born babies differs to those born vaginally, possibly due to reduced exposure to maternal vaginal bacteria during birth. Vaginal seeding is a currently unproven practice intended to reduce such differences, so that the gut microbiota of CS-born babies is similar to that of babies born vaginally. Our pilot study, which uses oral administration as a novel form of vaginal seeding, will assess the degree of maternal strain transfer and overall efficacy of the procedure for establishing normal gut microbiota development. METHODS AND ANALYSIS: Protocol for a single-blinded, randomized, placebo-controlled pilot study of a previously untested method of vaginal seeding (oral administration) in 30 CS-born babies. A sample of maternal vaginal bacteria is obtained prior to CS, and mixed with 5 ml sterile water to obtain a supernatant. Healthy babies are randomized at 1:1 to receive active treatment (3 ml supernatant) or placebo (3 ml sterile water). A reference group of 15 non-randomized vaginal-born babies are also being recruited. Babies' stool samples will undergo whole metagenomic shotgun sequencing to identify potential differences in community structure between CS babies receiving active treatment compared to those receiving placebo at age 1 month (primary outcome). Secondary outcomes include differences in overall gut community between CS groups (24 hours, 3 months); similarity of CS-seeded and placebo gut profiles to vaginally-born babies (24 hours, 1 and 3 months); degree of maternal vaginal strain transfer in CS-born babies (24 hours, 1 and 3 months); anthropometry (1 and 3 months) and body composition (3 months). ETHICS AND DISSEMINATION: Ethics approval by the Northern A Health and Disability Ethics Committee (18/NTA/49). Results will be published in peer-reviewed journals and presented at international conferences. REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12618000339257).


Assuntos
Cesárea/efeitos adversos , Microbiota/fisiologia , Placebos/administração & dosagem , Vagina/microbiologia , Adulto , Antropometria/métodos , Asma/epidemiologia , Asma/etiologia , Fenômenos Fisiológicos Bacterianos , Composição Corporal , Estudos de Casos e Controles , Doença Celíaca/epidemiologia , Doença Celíaca/etiologia , Parto Obstétrico/tendências , Fezes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Metagenômica/métodos , Microbiota/genética , Nova Zelândia/epidemiologia , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/etiologia , Gravidez
4.
Medicine (Baltimore) ; 99(31): e21447, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756163

RESUMO

BACKGROUND: The comparative efficacy and safety of small molecule and biological agents in the treatment of psoriatic arthritis (PsA) remain unknown. OBJECTIVES: To compare the efficacy and safety of 14 small molecule and biological agents by network meta-analysis (NMA). METHODS: Relevant randomized controlled trials involving biological treatments for PsA were identified by searching PubMed, Cochrane Library, EMBASE, Web of Science, and Clinicaltrials.gov and by manual retrieval, up to June 2018. NMA was conducted with Stata 14.0 based on the frequentist method. Effect measures were odds ratios (ORs) with 95% confidence intervals (CIs). Intervention efficacy and safety were ranked according to the surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 30 studies involving 10,191 adult subjects were included. According to NMA, ≥ 20% improvement in modifed American College of Rheumatology response criteria (ACR20) response, Psoriasis Area and Severity Index 75 (PASI75) response, and serious adverse events rate (SAEs) were observed. In direct comparisons, most of the biologics performed better than placebo in terms of ACR20 response rate and PASI75 response rate. Additionally, all medicines were comparable to placebo in terms of SAEs except secukinumab. In terms of mixed comparisons, with regard to the ACR20 response, etanercept (ETN) and infliximab (IFX) were more effective than golimumab (GOL), with ORs of 3.33 (95% CI: 1.17-9.48) and 1.24 (95% CI: 0.61-2.52), respectively. For PASI75 response, IFX was superior to certolizumab pegol (OR = 10.08, 95% CI: 1.54-75.48). In addition, these medicines were comparable to each other in terms of SAEs. ETN and IFX were shown to have the most favorable SUCRA for achieving improved ACR20 and PASI75 responses, respectively, while ABT-122 exhibited the best safety according to the SUCRA for SAEs. Considering both the efficacy (ACR20, PASI75) and safety (SAEs), GOL, ETN, and IFX are the top 3 treatments. CONCLUSIONS AND IMPLICATIONS: Direct and indirect comparisons and integrated results suggested that the 3 anti- tumor necrosis factor -α biologics (GOL, ETN, and IFX) can be considered the best treatments for PsA after comprehensive consideration of efficacy and safety.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fatores Biológicos/efeitos adversos , Estudos de Casos e Controles , Certolizumab Pegol/uso terapêutico , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Placebos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(29): e20735, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702819

RESUMO

BACKGROUND: Type 2 diabetes mellitus is one of the most common chronic diseases, which endangers peoples health and life qualities. Sodium-Glucose Transporter 2 (SGLT2) inhibitors have been widely recognized since their clinical application in blood glucose control. While, dyslipidemia caused by SGLT2 inhibitors has been identified that affected the prognosis of this disease. METHODS: We will retrieve 8 databases including English and Chinese. After multiple screening, all randomized controlled trials (RCTs) related to SGLT2 inhibitors will be included by the 2 authors and data will be extracted. After completion of the risk of bias assessment, we will use these effect values including risk ratio (RR), weighted mean difference (WMD) and 95% confidence interval (CI) to conduct data analysis. Chi-Squared test and I test will be used to assess heterogeneity between studies. The robustness of meta-analysis results will be determined by sensitivity analysis. It will be assessed that evidence quality of the outcomes on the GRADE. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The purpose of this systematic review and meta-analysis is to evaluate the association and degree of association between different doses of SGLT2 inhibitors and changes on blood lipid levels in patients with type 2 diabetes mellitus, in order to provide a reliable basis for clinical medication. INPLASY REGISTRATION NUMBER: INPLASY202040201.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Glicemia/efeitos dos fármacos , Estudos de Casos e Controles , Protocolos Clínicos/normas , Feminino , Humanos , Masculino , Placebos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
6.
Int Heart J ; 61(4): 799-805, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32728000

RESUMO

Therapeutic strategies for pulmonary arterial hypertension (PAH) have made remarkable progress over the last two decades. Currently, 3 types of drugs can be used to treat PAH; prostacyclins, phosphodiesterase 5 inhibitors, and endothelin receptor antagonists (ERA). In Japan, the first generation ERA bosentan was reimbursed in 2005, following which the 2nd generation ERAs ambrisentan and macitentan were reimbursed in 2009 and 2015, respectively. The efficacy of each ERA on hemodynamics in PAH patients remains to be elucidated. The aims of this study were to evaluate the hemodynamic effects of ERAs and compare these effects among each generation of ERAs.We retrospectively examined the clinical parameters of 42 PAH patients who were prescribed an ERA (15 bosentan, 12 ambrisentan, and 15 macitentan) and who underwent a hemodynamic examination before and after ERA introduction at our institution from January 2007 to July 2019.In a total of 42 patients, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were significantly decreased and cardiac index was significantly increased after ERA introduction (P < 0.001) and the World Health Organization-Functional class (WHO-Fc) was significantly improved after ERA introduction (P = 0.005). Next, in a comparison between 1st and 2nd generation ERAs, 2nd generation ERAs were found to have brought about greater improvements in hemodynamic parameters (mPAP and PVR. P < 0.01), heart rate, brain natriuretic peptide, arterial oxygen saturation, and mixed venous oxygen saturation than the 1st generation ERA bosentan.We conclude that all ERAs could successfully improve the hemodynamics of PAH patients and that the newer generation ERAs, ambrisentan and macitentan, seemed to be preferable to bosentan.


Assuntos
Bosentana/uso terapêutico , Antagonistas dos Receptores de Endotelina/uso terapêutico , Fenilpropionatos/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Piridazinas/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Administração Oral , Adulto , Idoso , Bosentana/administração & dosagem , Estudos de Casos e Controles , Antagonistas dos Receptores de Endotelina/administração & dosagem , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenilpropionatos/administração & dosagem , Inibidores da Fosfodiesterase 5/uso terapêutico , Placebos/administração & dosagem , Prostaglandinas I/uso terapêutico , Hipertensão Arterial Pulmonar/fisiopatologia , Pressão Propulsora Pulmonar/efeitos dos fármacos , Piridazinas/administração & dosagem , Pirimidinas/administração & dosagem , Estudos Retrospectivos , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacos
7.
N Engl J Med ; 383(1): 24-34, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32609980

RESUMO

BACKGROUND: The World Health Organization (WHO) recommends oral amoxicillin for patients who have pneumonia with tachypnea, yet trial data indicate that not using amoxicillin to treat this condition may be noninferior to using amoxicillin. METHODS: We conducted a double-blind, randomized, placebo-controlled noninferiority trial involving children at primary health care centers in low-income communities in Karachi, Pakistan. Children who were 2 to 59 months of age and who met WHO criteria for nonsevere pneumonia with tachypnea were randomly assigned to a 3-day course of a suspension of amoxicillin (the active control) of 50 mg per milliliter or matched volume of placebo (the test regimen), according to WHO weight bands (500 mg every 12 hours for a weight of 4 to <10 kg, 1000 mg every 12 hours for a weight of 10 to <14 kg, or 1500 mg every 12 hours for a weight of 14 to <20 kg). The primary outcome was treatment failure during the 3-day course of amoxicillin or placebo. The prespecified noninferiority margin was 1.75 percentage points. RESULTS: From November 9, 2014, through November 30, 2017, a total of 4002 children underwent randomization (1999 in the placebo group and 2003 in the amoxicillin group). In the per-protocol analysis, the incidence of treatment failure was 4.9% among placebo recipients (95 of 1927 children) and 2.6% among amoxicillin recipients (51 of 1929 children) (between-group difference, 2.3 percentage points; 95% confidence interval [CI], 0.9 to 3.7). Results were similar in the intention-to-treat analysis. The presence of fever and wheeze predicted treatment failure. The number needed to treat to prevent one treatment failure was 44 (95% CI, 31 to 80). One patient (<0.1%) in each group died. Relapse occurred in 40 children (2.2%) in the placebo group and in 58 children (3.1%) in the amoxicillin group. CONCLUSIONS: Among children younger than 5 years of age with nonsevere pneumonia, the frequency of treatment failure was higher in the placebo group than in the amoxicillin group, a difference that did not meet the noninferiority margin for placebo. (Funded by the Joint Global Health Trials Scheme [of the Department for International Development, Medical Research Council, and Wellcome] and others; RETAPP ClinicalTrials.gov number, NCT02372461.).


Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Pneumonia/tratamento farmacológico , Administração Oral , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Pré-Escolar , Método Duplo-Cego , Duração da Terapia , Feminino , Humanos , Lactente , Masculino , Paquistão , Placebos/uso terapêutico , Pneumonia/fisiopatologia , Recidiva , Taquipneia , Falha de Tratamento
9.
Medicine (Baltimore) ; 99(27): e21071, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629738

RESUMO

BACKGROUND: Only few studies have yet investigated whether perioperative administration of pregabalin can reduce the incidence of postoperative chronic neuropathic pain after total hip arthroplasty (THA). This prospective, randomized study compared placebo with pregabalin in the hope that a lower pregabalin dose would improve analgesia without increasing side-effects after THA. METHODS: This study was a prospective randomized blinded study, with a parallel design and an allocation ratio of 1:1 for the treatment groups. The study was approved by the Institutional Review Board in Weifang People's Hospital and written informed consent was obtained from all subjects before enrolment. A total of 120 patients who meet inclusion criteria are randomized to either pregabalin or placebo group. The primary objective of the study was visual analog scale score. As secondary outcomes, opioid consumption measurement, Harris Hip Score, hip range of motion, patient satisfaction, and complications were made at different time points throughout the study for comparison. RESULTS: The null hypothesis of this study was that pregabalin would reduce pain after THA. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5669).


Assuntos
Analgésicos/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Pregabalina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/administração & dosagem , Estudos de Casos e Controles , China/epidemiologia , Método Duplo-Cego , Humanos , Incidência , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Manejo da Dor/métodos , Dor Pós-Operatória/epidemiologia , Satisfação do Paciente/estatística & dados numéricos , Assistência Perioperatória/métodos , Placebos/administração & dosagem , Pregabalina/administração & dosagem , Estudos Prospectivos , Amplitude de Movimento Articular/efeitos dos fármacos , Escala Visual Analógica , Adulto Jovem
10.
Lancet Gastroenterol Hepatol ; 5(9): 839-849, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32682494

RESUMO

BACKGROUND: Glecaprevir-pibrentasvir results in high rates of sustained virological response in patients with chronic hepatitis C virus (HCV) genotype 1-6 infection. Data for glecaprevir-pibrentasvir in non-Japanese Asian patients have been minimal. The aim of these studies was to assess the efficacy and safety of glecaprevir-pibrentasvir in treatment-naive and treatment-experienced Asian patients with chronic HCV genotype 1-6 infection without cirrhosis (VOYAGE-1) and with compensated cirrhosis (VOYAGE-2). METHODS: We did two phase 3 studies in treatment-naive and treatment-experienced patients with chronic HCV genotype 1-6 infection. VOYAGE-1 was a randomised, double-blind, placebo-controlled study that recruited patients without cirrhosis at 47 sites across China, South Korea, and Singapore. Randomisation was 2:1 with a fixed block size of three and stratified by geographical region and HCV genotype. Investigators, study site personnel, the study sponsor, and patients were masked to treatment allocation. VOYAGE-2 was a single-arm, open-label study that recruited patients with compensated cirrhosis at 34 sites across China and South Korea. Glecaprevir (300 mg) and pibrentasvir (120 mg) or placebo (VOYAGE-1, 2:1 ratio), administered as three tablets daily, was given for 8 weeks in patients without cirrhosis and for 12 weeks in those with cirrhosis (and for 16 weeks in treatment-experienced patients with genotype 3). The primary efficacy endpoint was the proportion of patients with a sustained virological response, defined as HCV RNA below the lower limit of quantification 12 weeks after the last dose of glecaprevir-pibrentasvir. We analysed efficacy and safety in all patients who received at least one dose of the study drug. These trials are registered with ClinicalTrials.gov, NCT03222583 (VOYAGE-1) and NCT03235349 (VOYAGE-2); both trials have been completed. This Article reports the results of the primary analysis for each study, undertaken when all patients who received glecaprevir-pibrentasvir (during the double-blind period in VOYAGE-1) had been followed up for 12 weeks following their last dose of study drug. Data from the double-blind period for placebo patients in VOYAGE-1 are also summarised. FINDINGS: Between Oct 4, 2017, and April 20, 2018, 546 patients with chronic HCV without cirrhosis were randomly assigned to treatment (363 to glecaprevir-pibrentasvir, 183 to placebo) in VOYAGE-1. One patient withdrew consent and did not receive treatment with glecaprevir-pibrentasvir. 352 of 362 patients who received glecaprevir-pibrentasvir achieved SVR12 (97·2% [95% CI 95·5-98·9]). Of 160 patients with compensated cirrhosis who were enrolled in VOYAGE-2 between Sept 29, 2017, and June 14, 2018, 159 of 160 achieved SVR12 (99·4%, 95% CI 98·2-100·0). 20 patients with HCV genotype 3b across both trials received glecaprevir-pibrentasvir; six of these patients were among the 11 patients who did not achieve SVR12. Upper respiratory tract infection was the most common adverse event (35 [10%] of 362 receiving glecaprevir-pibrentasvir and 18 [10%] of 183 receiving placebo in VOYAGE-1; 19 [12%] of 160 in VOYAGE-2). For patients receiving glecaprevir-pibrentasvir, serious adverse events occurred in three (<1%) of 362 patients in VOYAGE-1 and five (3%) of 160 patients in VOYAGE-2. Grade 3-4 adverse events in patients receiving glecaprevir-pibrentasvir occurred in five (1%) of 362 patients in VOYAGE-1 and six (4%) of 160 patients in VOYAGE-2; each type of event was experienced by at most one patient within a study. One patient with cirrhosis discontinued study drug because of an adverse event. INTERPRETATION: Glecaprevir-pibrentasvir showed high efficacy and an acceptable safety profile in these studies although responses were less common in the few patients with HCV genotype 3b. The results support the use of glecaprevir-pibrentasvir in these Asian populations. FUNDING: AbbVie.


Assuntos
Benzimidazóis/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Pirrolidinas/uso terapêutico , Quinoxalinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Ásia/epidemiologia , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Estudos de Casos e Controles , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Prevalência , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , Quinoxalinas/administração & dosagem , Quinoxalinas/efeitos adversos , Infecções Respiratórias/induzido quimicamente , Infecções Respiratórias/epidemiologia , Segurança , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento
11.
Lancet HIV ; 7(7): e463-e471, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32621874

RESUMO

BACKGROUND: Observational data suggest that low vitamin D status is associated with an increased incidence of pulmonary tuberculosis and mortality among people living with HIV. The primary aims of this study were to assess the effect of vitamin D3 supplementation on the risk of mortality and incidence of pulmonary tuberculosis among adults initiating antiretroviral therapy (ART). METHODS: This was a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation among adults living with HIV who initiated ART and had serum 25-hydroxyvitamin D concentrations of less than 30 ng/mL at four large HIV care and treatment centres in Dar es Salaam, Tanzania. Patients were excluded if they were younger than 18 years, pregnant at the time of randomisation, or were enrolled in any other clinical trial. Patients were randomly assigned 1:1 to receive either weekly oral 50 000 IU vitamin D3 supplements (cholecalciferol) for the first month of ART followed by daily 2000 IU vitamin D3 supplements or a matching weekly and daily placebo regimen. The randomisation list was computer-generated by a non-study statistician with sequence blocks of ten that were stratified by study clinic. Complete allocation concealment was ensured and patients, field team, and investigators were masked to group assignment. The trial follow-up duration was 1 year and the primary efficacy outcomes were death and incident pulmonary tuberculosis. An intention-to-treat analysis was followed for all-cause mortality; participants diagnosed with or receiving treatment for pulmonary tuberculosis at randomisation, or suspected to have tuberculosis at randomisation and who later had that diagnosis confirmed, were excluded from analyses of pulmonary tuberculosis incidence. Safety was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT01798680, and is completed. FINDINGS: Between Feb 24, 2014, and Feb 24, 2017, 6250 adults initiating ART had serum 25-hydroxyvitamin D screening, 4000 of whom were enrolled in the trial and followed up for 1 year (follow-up of all participants was completed on March 7, 2018). 2001 patients were randomly assigned to the vitamin D3 supplementation group, and 1999 to the placebo group. 415 deaths were recorded: 211 in the vitamin D3 group and 204 in the placebo group. Among all randomly assigned participants, there was no overall effect of vitamin D3 supplementation on the risk of mortality (hazard ratio [HR] 1·04, 95% CI 0·85-1·25; p=0·73). There was also no difference in the overall incidence of pulmonary tuberculosis between the vitamin D3 (50 events in 1812 patients analysed) and placebo groups (64 events in 1827 patients; HR 0·78, 0·54-1·13; p=0·19). The vitamin D3 regimen did not increase the risk of hypercalcaemia (three events in the vitamin D3 group and two events in the placebo group; relative risk 1·25, 95% CI 0·43-3·66; Fisher's exact p=1·00). 101 hospital admissions were reported in the vitamin D3 group and 94 in the placebo group (incidence rate ratio 1·06, 95% CI 0·80-1·41; p=0·66). INTERPRETATION: Additional research is needed before vitamin D3 supplementation should be considered for implementation in HIV care and treatment programmes for the prevention of pulmonary tuberculosis or mortality. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.


Assuntos
Colecalciferol/farmacologia , Suplementos Nutricionais/análise , Infecções por HIV/tratamento farmacológico , Tuberculose Pulmonar/prevenção & controle , Adulto , Método Duplo-Cego , Feminino , Infecções por HIV/mortalidade , Humanos , Incidência , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Placebos , Tanzânia , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue
12.
Lancet ; 396(10246): 239-254, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711800

RESUMO

BACKGROUND: Tenofovir alafenamide shows high antiviral efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate when used for HIV treatment. Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir alafenamide versus emtricitabine and tenofovir disoproxil fumarate for HIV prevention. METHODS: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both. We enrolled adult cisgender men who have sex with men and transgender women who have sex with men, both with a high risk of acquiring HIV on the basis of their self-reported sexual behaviour in the past 12 weeks or their recent history (within 24 weeks of enrolment) of bacterial sexually transmitted infections. Participants with current or previous use of PrEP with emtricitabine and tenofovir disoproxil fumarate were not excluded. We used a computer-generated random allocation sequence to randomly assign (1:1) participants to receive either emtricitabine (200 mg) and tenofovir alafenamide (25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). As such, all participants were given two tablets. The trial sponsor, investigators, participants, and the study staff who provided the study drugs, assessed the outcomes, and collected the data were masked to group assignment. The primary efficacy outcome was incident HIV infection, which was assessed when all participants had completed 48 weeks of follow-up and half of all participants had completed 96 weeks of follow-up. This full analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug and had at least one post-baseline HIV test. Non-inferiority of emtricitabine and tenofovir alafenamide to emtricitabine and tenofovir disoproxil fumarate was established if the upper bound of the 95·003% CI of the HIV incidence rate ratio (IRR) was less than the prespecified non-inferiority margin of 1·62. We prespecified six secondary bone mineral density and renal biomarker safety endpoints to evaluate using the safety analysis set. This analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02842086, and is no longer recruiting. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5387 (92%) of 5857 participants were randomly assigned and received emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693). At the time of the primary efficacy analysis (ie, when all participants had completed 48 weeks and 50% had completed 96 weeks) emtricitabine and tenofovir alafenamide was non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the IRR, was less than the prespecified non-inferiority margin of 1·62 (IRR 0·47 [95% CI 0·19-1·15]). After 8756 person-years of follow-up, 22 participants were diagnosed with HIV, seven participants in the emtricitabine and tenofovir alafenamide group (0·16 infections per 100 person-years [95% CI 0·06-0·33]), and 15 participants in the emtricitabine and tenofovir disoproxil fumarate group (0·34 infections per 100 person-years [0·19-0·56]). Both regimens were well tolerated, with a low number of participants reporting adverse events that led to discontinuation of the study drug (36 [1%] of 2694 participants in the emtricitabine and tenofovir alafenamide group vs 49 [2%] of 2693 participants in the emtricitabine and tenofovir disoproxil fumarate group). Emtricitabine and tenofovir alafenamide was superior to emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarker safety endpoints. INTERPRETATION: Daily emtricitabine and tenofovir alafenamide shows non-inferior efficacy to daily emtricitabine and tenofovir disoproxil fumarate for HIV prevention, and the number of adverse events for both regimens was low. Emtricitabine and tenofovir alafenamide had more favourable effects on bone mineral density and biomarkers of renal safety than emtricitabine and tenofovir disoproxil fumarate. FUNDING: Gilead Sciences.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Método Duplo-Cego , Emtricitabina/efeitos adversos , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/efeitos adversos , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , HIV-1/efeitos dos fármacos , Homossexualidade Masculina/etnologia , Humanos , Masculino , América do Norte/epidemiologia , Placebos/administração & dosagem , Profilaxia Pré-Exposição/métodos , Prevalência , Segurança , Minorias Sexuais e de Gênero , Tenofovir/efeitos adversos , Resultado do Tratamento
13.
Lancet ; 396(10246): 255-266, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711801

RESUMO

BACKGROUND: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis. METHODS: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060. FINDINGS: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported. INTERPRETATION: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis. FUNDING: Pfizer.


Assuntos
Dermatite Atópica/tratamento farmacológico , Eczema/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Canadá/epidemiologia , Estudos de Casos e Controles , Criança , Dermatite Atópica/patologia , Método Duplo-Cego , Eczema/patologia , Grupos Étnicos , Europa (Continente)/epidemiologia , Feminino , Humanos , Janus Quinase 1/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Segurança , Índice de Gravidade de Doença , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Estados Unidos/epidemiologia
14.
Eur J Endocrinol ; 183(4): E7-E9, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32688333

RESUMO

The validity of clinical research is potentially threatened by missing data. Any variable measured in a study can have missing values, including the exposure, the outcome, and confounders. When missing values are ignored in the analysis, only those subjects with complete records will be included in the analysis. This may lead to biased results and loss of power. We explain why missing data may lead to bias and discuss a commonly used classification of missing data.


Assuntos
Viés , Reprodutibilidade dos Testes , Projetos de Pesquisa/normas , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Terapia de Reposição Hormonal , Humanos , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Modelos Logísticos , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Tamanho da Amostra , Tiroxina/uso terapêutico
15.
BMJ ; 370: m1668, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690477

RESUMO

Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this review examines the effect of placebo treatment under three distinct frameworks: double blind, deception, and open label honestly prescribed. These specific conditions do not necessarily differentially modify placebo outcomes. Psychological, clinical, and neurological theories of placebo effects are scrutinized. In chronic pain, conscious expectation does not reliably predict placebo effects. A supportive patient-physician relationship may enhance placebo effects. This review highlights "predictive coding" and "bayesian brain" as emerging models derived from computational neurobiology that offer a unified framework to explain the heterogeneous evidence on placebos. These models invert the dogma of the brain as a stimulus driven organ to one in which perception relies heavily on learnt, top down, cortical predictions to infer the source of incoming sensory data. In predictive coding/bayesian brain, both chronic pain (significantly modulated by central sensitization) and its alleviation with placebo treatment are explicated as centrally encoded, mostly non-conscious, bayesian biases. The review then evaluates seven ways in which placebos are used in clinical practice and research and their bioethical implications. In this way, it shows that placebo effects are evidence based, clinically relevant, and potentially ethical tools for relieving chronic pain.


Assuntos
Dor Crônica/tratamento farmacológico , Relações Médico-Paciente/ética , Placebos/efeitos adversos , Padrões de Prática Médica/ética , Teorema de Bayes , Dor Crônica/psicologia , Decepção , Método Duplo-Cego , Ética Médica , Humanos , Efeito Placebo , Placebos/administração & dosagem , Padrões de Prática Médica/estatística & dados numéricos
16.
Medicine (Baltimore) ; 99(29): e21181, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702878

RESUMO

INTRODUCTION: Androgenetic alopecia is the most common form of hair loss in both sexes. In recent studies, low-level light therapy (LLLT) has been established as an effective treatment for alopecia. The purpose of this study was to evaluate the safety and efficacy of LLLT using a new helmet-type device for the treatment of androgenetic alopecia. METHOD: A randomized, sham device-controlled, double-blind clinical trial was conducted at 2 institutions. Sixty participants diagnosed with androgenetic alopecia aged from 19 to 65 years were recruited. LLLT was performed through a helmet-type device that emitted light with a mean output power of 2.36 mW/cm at a wavelength of 655 nm. Participants were divided into 2 groups, which respectively used the experimental device and a sham device. After tattooing at the central point of the vertex, phototrichograms at that point were obtained at 0, 8, and 16 weeks. The primary endpoint of the study was the difference in the rate of change of hair density between the test group and the control group. RESULTS: Comparing the results at baseline and week 16, the experimental group showed an increase in hair density of 41.90 hairs/cm and an increase in hair thickness of 7.50 µm, whereas the control group showed an increase of 0.72 hairs/cm and a decrease of 15.03 µm, respectively (P < .001). No adverse events or side effects occurred. CONCLUSION: LLLT showed a significant effect on increasing hair density in patients with androgenetic alopecia. LLLT could be a safe and effective treatment for androgenetic alopecia in both sexes.


Assuntos
Alopecia/urina , Dispositivos de Proteção da Cabeça/normas , Terapia com Luz de Baixa Intensidade/normas , Adulto , Idoso , Alopecia/fisiopatologia , Método Duplo-Cego , Desenho de Equipamento/métodos , Feminino , Dispositivos de Proteção da Cabeça/estatística & dados numéricos , Humanos , Terapia com Luz de Baixa Intensidade/métodos , Terapia com Luz de Baixa Intensidade/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Resultado do Tratamento
18.
Medicine (Baltimore) ; 99(28): e20907, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664084

RESUMO

BACKGROUND: The increasing prevalence of osteoarthritis among the old population worldwide is a great concern. Two of the biggest complaints of OA patients are joint pain and inflammation. Currently, people are relying on non-steroidal anti-inflammatory drugs (NSAIDs) and steroids to control pain and inflammation. However, long-term use of these pharmaceutical drugs has negative health consequences in the elderly, including gastro-intestinal, respiratory, and renal diseases. Natural products are receiving more attention than ever as alternative treatments against OA for their efficacies and safety. The root of Paeonia lactiflora Pal and the gum resin of Commiphora myrrha have been used as analgesics and anti-inflammatory agents since ancient time. A new herbal formula composed of P. lactiflora root and C. myrrha gum resin extracts, known as HT083, has shown promising antinociceptive and anti-inflammatory effects in a rodent model of OA. We design this study to investigate the safety and the efficacy of HT083 to prevent OA in patients with mild OA. METHODS: This is a randomized, double-blind, and placebo-controlled study. A total of 100 eligible participants will be divided into two groups and will be given HT083 and a placebo for 12 weeks in 1:1 ratio. Treatment results will be assessed using a visual analog scale (VAS), Korean-Short Form health survey-36 score (SF-36), personal evaluation, and laboratory analysis. DISCUSSION: This trial is expected to provide clinical evidence on the effectiveness and the safety of HT083 as a natural treatment for mild OA. TRIAL REGISTRATION: Korean Clinical Research Information Service (CRIS) number KCT0004925 Registered on 2020.04.16.


Assuntos
Artralgia/tratamento farmacológico , Indóis/uso terapêutico , Inflamação/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Osteoartrite do Joelho/tratamento farmacológico , Pirróis/uso terapêutico , Adulto , Idoso , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Commiphora/efeitos adversos , Commiphora/química , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/patologia , Paeonia/efeitos adversos , Paeonia/química , Placebos/administração & dosagem , República da Coreia/epidemiologia , Roedores , Segurança , Resultado do Tratamento , Escala Visual Analógica
20.
Lancet ; 395(10241): 1927-1936, 2020 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-32563378

RESUMO

BACKGROUND: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. METHODS: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. FINDINGS: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82-1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). INTERPRETATION: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.


Assuntos
Antifibrinolíticos/efeitos adversos , Hemorragia Gastrointestinal/tratamento farmacológico , Tromboembolia/induzido quimicamente , Ácido Tranexâmico/efeitos adversos , Doença Aguda , Adulto , Idoso , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/uso terapêutico , Estudos de Casos e Controles , Método Duplo-Cego , Feminino , Hemorragia Gastrointestinal/mortalidade , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Placebos/administração & dosagem , Valor Preditivo dos Testes , Embolia Pulmonar/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Tromboembolia/epidemiologia , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/uso terapêutico , Trombose Venosa/epidemiologia
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