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1.
BMJ Open ; 10(5): e036829, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32444433

RESUMO

INTRODUCTION: Shoulder pain due to irreparable rotator cuff tears can cause substantial disability, but treatment options are limited. A balloon spacer is a relatively simple addition to a standard arthroscopic debridement procedure, but it is costly and there is no current randomised trial evidence to support its use. This trial will evaluate the clinical and cost-effectiveness of a subacromial balloon spacer for individuals undergoing arthroscopic debridement for irreparable rotator cuff tears.New surgical procedures can provide substantial benefit to patients. Good quality randomised controlled trials (RCTs) are needed, but trials in surgery are typically long and expensive, exposing patients to risk and the healthcare system to substantial costs. One way to improve the efficiency of trials is with an adaptive sample size. Such methods are well established in drug trials but have rarely, if ever, been used in surgical trials. METHODS AND ANALYSIS: Subacromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS) is a participant and assessor blinded, adaptive, multicentre RCT comparing arthroscopic debridement with the InSpace balloon (Stryker, USA) to arthroscopic debridement alone for people with a symptomatic irreparable rotator cuff tear. It uses a group sequential adaptive design where interim analyses are performed using all of the 3, 6 and 12-month data that are available at each time point. A maximum of 221 participants will be randomised (1:1 ratio), this will provide 90% power (at the 5% level) for a 6 point difference in the primary outcome; the Oxford Shoulder Score at 12 months. A substudy will use deltoid-active MRI scans in 56 participants to assess the function of the balloon. Analysis will be on an intention-to-treat basis and reported according to principles established in the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: NRES number 18/WM/0025. The results will be disseminated via peer-reviewed publications, presentations at conferences, lay summaries and social media. TRIAL REGISTRATION NUMBER: ISRCTN17825590.

2.
BMC Pulm Med ; 20(1): 143, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429969

RESUMO

BACKGROUND: Supervised cardio-pulmonary rehabilitation may be safe and beneficial for people with pulmonary hypertension (PH) in groups 1 (pulmonary arterial hypertension) and 4 (chronic thromboembolic disease), particularly as a hospital in-patient. It has not been tested in the most common PH groups; 2 (left heart disease), 3 (lung disease), or 5 (other disorders). Further it has not been evaluated in the UK National Health Service (NHS) out-patient setting, or with long-term follow-up. The aim of this randomised controlled trial (RCT) is to test the clinical and cost-effectiveness of a supervised exercise rehabilitation intervention with psychosocial support compared to best practice usual care for people with PH in the community/outpatient setting. METHODS: This multi-centre, pragmatic, two-arm RCT with embedded process evaluation aims to recruit 352 clinically stable adults with PH (groups 1-5) and WHO functional class II-IV. Participants will be randomised to either the Supervised Pulmonary Hypertension Exercise Rehabilitation (SPHERe) intervention or control. The SPHERe intervention consists of 1) individual assessment and familiarisation sessions; 2) 8-week, twice-weekly, supervised out-patient exercise training; 3) psychosocial/motivational support and education; 4) guided home exercise plan. The control intervention consists of best practice usual care with a single one-to-one practitioner appointment, and general advice on physical activity. Outcomes will be measured at baseline, 4 months (post-intervention) and 12 months by researchers blinded to treatment allocation. The primary outcome is the incremental shuttle walk test at 4 months. Secondary outcomes include health-related quality of life (HRQoL), time to clinical worsening and health and social care use. A purposive sample of participants (n = 20 intervention and n = 20 control) and practitioners (n = 20) will be interviewed to explore experiences of the trial, outcomes and interventions. DISCUSSION: The SPHERe study is the first multi-centre clinical RCT to assess the clinical and cost effectiveness of a supervised exercise rehabilitation intervention compared to usual care, delivered in the UK NHS, for people in all PH groups. Results will inform clinicians and commissioners as to whether or not supervised exercise rehabilitation is effective and should be routinely provided for people with PH. TRIAL REGISTRATION: ISRCTN no. 10608766, prospectively registered on 18th March 2019.

3.
J Thorac Cardiovasc Surg ; 159(6): 2512-2520.e1, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32087959

RESUMO

OBJECTIVE: Diffuse chest wall invasion (DCWI) is a common finding in patients undergoing intended resection for malignant pleural mesothelioma. We sought to determine the incidence and preoperative predictors of this finding, and to test our anecdotal impression that contraction of the ipsilateral hemithorax is associated with DCWI. METHODS: This was a single-institution retrospective study of 170 patients undergoing intended macroscopic complete resection for malignant pleural mesothelioma from 2014-2018. A novel metric of thoracic cage volume was calculated by preoperative chest computed tomography. Univariable analyses were performed to determine associations of preoperative variables with DCWI. RESULTS: Macroscopic complete resection was achieved by pleurectomy/decortication in 104 patients (61%) and by extrapleural pneumonectomy in 39 patients (23%). Unresectable disease was discovered at thoracotomy in 27 (16%) of patients; 24 (14%) by DCWI and 3 (2%) by intrathoracic organ invasion. In univariable analysis, decreased ipsilateral thoracic cage volume demonstrated the strongest association with unresectability by DCWI (P = .009) with >5% decrease in thoracic cage volume representing the optimal cutoff (P = .014; area under the curve, 0.67). Other preoperative variables associated with DCWI included preoperative chest pain requiring opioids (P = .028), prior pleurodesis (P = .036), decreased forced vital capacity (P = .023), decreased ipsilateral lung perfusion by ventilation/perfusion lung scan (P = .007), and magnetic resonance imaging findings of chest wall invasion (P = .035). CONCLUSIONS: Preoperative identification of DCWI will avoid unnecessary thoracotomy and accelerate initiation of nonsurgical therapy in malignant pleural mesothelioma. Our data suggest that contraction of thoracic cage volume has merit in predicting malignant pleural mesothelioma unresectability and should be validated in prospective studies.

4.
J Am Chem Soc ; 142(6): 2876-2888, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31990532

RESUMO

The signal transducer and activator of transcription 3 (STAT3) protein is a master regulator of most key hallmarks and enablers of cancer, including cell proliferation and the response to DNA damage. G-Quadruplex (G4) structures are four-stranded noncanonical DNA structures enriched at telomeres and oncogenes' promoters. In cancer cells, stabilization of G4 DNAs leads to replication stress and DNA damage accumulation and is therefore considered a promising target for oncotherapy. Here, we designed and synthesized novel quinazoline-based compounds that simultaneously and selectively affect these two well-recognized cancer targets, G4 DNA structures and the STAT3 protein. Using a combination of in vitro assays, NMR, and molecular dynamics simulations, we show that these small, uncharged compounds not only bind to the STAT3 protein but also stabilize G4 structures. In human cultured cells, the compounds inhibit phosphorylation-dependent activation of STAT3 without affecting the antiapoptotic factor STAT1 and cause increased formation of G4 structures, as revealed by the use of a G4 DNA-specific antibody. As a result, treated cells show slower DNA replication, DNA damage checkpoint activation, and an increased apoptotic rate. Importantly, cancer cells are more sensitive to these molecules compared to noncancerous cell lines. This is the first report of a promising class of compounds that not only targets the DNA damage cancer response machinery but also simultaneously inhibits the STAT3-induced cancer cell proliferation, demonstrating a novel approach in cancer therapy.

5.
Nat Commun ; 11(1): 400, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964864

RESUMO

Circulating cell-free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, cf-mRNA composition and its potential clinical applications remain largely unexplored. Here we show, using Next Generation Sequencing-based profiling, that cf-mRNA is enriched in transcripts derived from the bone marrow compared to circulating cells. Further, longitudinal studies involving bone marrow ablation followed by hematopoietic stem cell transplantation in multiple myeloma and acute myeloid leukemia patients indicate that cf-mRNA levels reflect the transcriptional activity of bone marrow-resident hematopoietic lineages during bone marrow reconstitution. Mechanistically, stimulation of specific bone marrow cell populations in vivo using growth factor pharmacotherapy show that cf-mRNA reflects dynamic functional changes over time associated with cellular activity. Our results shed light on the biology of the circulating transcriptome and highlight the potential utility of cf-mRNA to non-invasively monitor bone marrow involved pathologies.


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Medula Óssea/patologia , Ácidos Nucleicos Livres/isolamento & purificação , Leucemia Mieloide Aguda/diagnóstico , Mieloma Múltiplo/diagnóstico , RNA Mensageiro/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Medula Óssea/efeitos dos fármacos , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Estudos de Viabilidade , Perfilação da Expressão Gênica/métodos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Estudos Longitudinais , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , RNA Mensageiro/sangue , RNA Mensageiro/genética , Análise de Sequência de RNA/métodos , Resultado do Tratamento , Adulto Jovem
6.
J Bone Joint Surg Am ; 102(2): 119-127, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31725123

RESUMO

BACKGROUND: There is evidence to support the use of highly cross-linked polyethylene (HXLPE) in patients undergoing total hip arthroplasty. However, the benefits for those undergoing total knee arthroplasty are uncertain, with conflicting reports based on previous cohort analyses. The purpose of the present study was to compare the revision rates following primary total knee arthroplasty with use of HXLPE as compared with conventional polyethylene (CPE) using data from the National Joint Registry (NJR) for England, Wales and Northern Ireland. METHODS: We performed a retrospective analysis of primary total knee arthroplasties recorded in the NJR from 2003 to 2014. Cobalt-chromium (CoCr)-CPE and CoCr-HXLPE bearing surfaces were compared using all-cause revision, aseptic revision, and septic revision as end points. Survival analyses were conducted using rates per 100 years observed, Kaplan-Meier survival estimates, and Cox regression hazard ratios (HRs) adjusted for age, sex, American Society of Anesthesiologists (ASA) classification, body mass index (BMI), lead surgeon grade, and implant constraint. Secondary analyses compared the most commonly used HXLPEs (Zimmer Prolong, DePuy XLK, and Stryker X3) against CPE for the 3 most common total knee arthroplasty systems (NexGen, PFC Sigma, and Triathlon). RESULTS: In the present study of 550,658 total knee arthroplasties, the unadjusted aseptic revision rates were significantly lower following procedures performed with CPE (n = 513,744) as compared with those performed with HXLPE total knee replacements (n = 36,914) (0.29 [95% confidence interval (CI), 0.28 to 0.30] compared to 0.38 [95% CI, 0.35 to 0.42], p < 0.01). The 10-year HR associated with CPE was 0.4 (95% CI, 0.1 to 0.8, p = 0.03). There were no significant differences between the adjusted revision rates of HXPLE compared with CPE in individual analyses of the most common total knee arthroplasty systems. However, for the subset of patients who were both <60 years of age and had a BMI of >35 kg/m, the "second-generation" Stryker X3 HXLPE demonstrated significantly better survival than its respective CPE, with CPE having an HR of 2.6 (95% CI, 1.2 to 5.9) (p = 0.02). CONCLUSIONS: Alternative bearings are marketed as having improved wear properties over traditional CoCr-CPE. This registry-based analysis demonstrated no overall survival benefit of HXLPE after a maximum duration of follow-up of 12 years. Because of their increased cost, the routine use of HXLPE bearings may not be justified. However, they may have a role in specific "higher demand" groups such as patients <60 years of age and/or those with a BMI of >35 kg/m. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete list of levels of evidence.

7.
J Econ Entomol ; 113(2): 887-895, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-31880307

RESUMO

Flea beetles, are common pests of cabbage Brassica oleracea L. (Brassicales: Brassicaceae) and eggplant Solanum melongena L. (Solanales: Solanaceae), but little is known about the flea beetle populations in Virginia, their impact on yield, or the most effective control methods. This research investigates flea beetle populations and the impact of their feeding injury on cabbage and eggplant in Southwest Virginia and determines the most efficacious control methods. In Whitethorne, VA, cabbage and eggplant crops were vacuum sampled weekly throughout two summers (2015, 2016). Crucifer flea beetle, Phyllotreta cruciferae (Goeze) (Coleoptera: Chrysomelidae), and striped flea beetle, Phyllotreta striolata Fabr. (Coleoptera: Chrysomelidae) were found on cabbage; whereas, eggplant flea beetle, Epitrix fucula (Crotch) (Coleoptera: Chrysomelidae), and the tobacco flea beetle, Epitrix hirtipennis (Melsheimer) (Coleoptera: Chrysomelidae) were found on eggplant. To evaluate the impact of flea beetle feeding on these plants flea beetle densities and defoliation were assessed weekly and individual plant, as well as whole plot yields, assessed at harvest. For cabbage, significant yield reductions were observed between 1 and 20% and >60% defoliation. Similarly, significant yield reductions were observed between 41 and 60% and >60% defoliation for eggplant. The efficacy of various insecticides was also evaluated. Soil application of the systemic neonicotinoid dinotefuran, imidacloprid, and the foliar-applied bifenthrin resulted in the fewest beetles, the least amount of leaf defoliation, and the highest yield in cabbage and eggplant. This research helps vegetable growers to better understand the severity of these pests and how to effectively combat them.

8.
Trials ; 20(1): 694, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31815651

RESUMO

BACKGROUND: There is widespread concern across the clinical and research communities that clinical trials, powered for patient-reported outcomes, testing new surgical procedures are often expensive and time-consuming, particularly when the new intervention is shown to be no better than the standard. Conventional (non-adaptive) randomised controlled trials (RCTs) are perceived as being particularly inefficient in this setting. Therefore, we have developed an adaptive group sequential design that allows early endpoints to inform decision making and show, through simulations and a worked example, that these designs are feasible and often preferable to conventional non-adaptive designs. The methodology is motivated by an ongoing clinical trial investigating a saline-filled balloon, inserted above the main joint of the shoulder at the end of arthroscopic debridement, for treatment of tears of rotor cuff tendons. This research question and setting is typical of many studies undertaken to assess new surgical procedures. METHODS: Test statistics are presented based on the setting of two early outcomes, and methods for estimation of sequential stopping boundaries are described. A framework for the implementation of simulations to evaluate design characteristics is also described. RESULTS: Simulations show that designs with one, two and three early looks are feasible and, with appropriately chosen futility stopping boundaries, have appealing design characteristics. A number of possible design options are described that have good power and a high probability of stopping for futility if there is no evidence of a treatment effect at early looks. A worked example, with code in R, provides a practical demonstration of how the design might work in a real study. CONCLUSIONS: In summary, we show that adaptive designs are feasible and could work in practice. We describe the operating characteristics of the designs and provide guidelines for appropriate values for the stopping boundaries for the START:REACTS (Sub-acromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery) study. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN17825590. Registered on 5 March 2018.

10.
Bone Joint J ; 101-B(11): 1331-1347, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31674244

RESUMO

AIMS: Antibiotic-loaded bone cements (ALBCs) may offer early protection against the formation of bacterial biofilm after joint arthroplasty. Use in hip arthroplasty is widely accepted, but there is a lack of evidence in total knee arthroplasty (TKA). The objective of this study was to evaluate the use of ALBC in a large population of TKA patients. MATERIALS AND METHODS: Data from the National Joint Registry (NJR) of England and Wales were obtained for all primary cemented TKAs between March 2003 and July 2016. Patient, implant, and surgical variables were analyzed. Cox proportional hazards models were used to assess the influence of ALBC on risk of revision. Body mass index (BMI) data were available in a subset of patients. RESULTS: Of 731 214 TKAs, 15 295 (2.1%) were implanted with plain cement and 715 919 (97.9%) with ALBC. There were 13 391 revisions; 2391 were performed for infection. After adjusting for other variables, ALBC had a significantly lower risk of revision for any cause (hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77 to 0.93; p < 0.001). ALBC was associated with a lower risk of revision for all aseptic causes (HR 0.85, 95% CI 0.77 to 0.95; p < 0.001) and revisions for infection (HR 0.84, 95% CI 0.67 to 1.01; p = 0.06). The results were similar when BMI was added into the model, and in a subanalysis where surgeons using only ALBC over the entire study period were excluded. Prosthesis survival at ten years for TKAs implanted with ALBC was 96.3% (95% CI 96.3 to 96.4) compared with 95.5% (95% CI 95.0 to 95.9) in those implanted with plain cement. On a population level, where 100 000 TKAs are performed annually, this difference represents 870 fewer revisions at ten years in the ALBC group. CONCLUSION: After adjusting for a range of variables, ALBC was associated with a significantly lower risk of revision in this registry-based study of an entire nation of primary cemented knee arthroplasties. Using ALBC does not appear to increase midterm implant failure rates. Cite this article: Bone Joint J 2019;101-B:1331-1347.


Assuntos
Antibacterianos/administração & dosagem , Artroplastia do Joelho/métodos , Cimentos para Ossos , Prótese do Joelho/efeitos adversos , Adulto , Idoso , Anticoagulantes/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Infecções Relacionadas à Prótese/prevenção & controle , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Tromboembolia/prevenção & controle , Resultado do Tratamento
12.
BMJ Open ; 9(8): e028201, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391190

RESUMO

OBJECTIVES: To assess the impact of both the Committee on Safety of Medicines (CSM) warning (December 2003) and the National Institute for Health and Care Excellence (NICE) guidance (September 2005) on antidepressant prescription rates in children and adolescents within the UK primary care service. SETTING: Population based study of primary care antidepressant prescribing using the Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Under-18s presenting to primary care with a depressive disorder or related diagnostic code recorded in the CPRD. PRIMARY OUTCOME MEASURE: Antidepressant prescription rates per month per 100 000 depressed 4-17 year olds. RESULTS: Following the CSM warning, the prior trend towards increased prescribing rates for selective serotonin reuptake inhibitors (SSRIs) in children was significantly reversed (ß for change in trend -12.34 (95% CI -18.67 to -6.00, p<0.001)). However, after the publication of the NICE guidelines the prior trend towards increased prescribing resumed for those SSRIs mentioned as potential treatments in the guidance (fluoxetine, citalopram and sertraline) (ß for change in trend 11.52 (95% CI 5.32 to 17.73, p<0.001)). Prescribing of other SSRIs and tricyclics remained low. CONCLUSIONS: Despite a strong emphasis on psychosocial interventions for child and adolescent depression, it may be that the NICE guidelines inadvertently encouraged further antidepressant prescribing, at least for those SSRIs cited. Although the guidelines gave cautions and caveats for the use of antidepressants, practitioners may have interpreted these recommendations as endorsing their use in young people with depression and related conditions. However, more accurate prevalence trend estimates for depression in this age group, and information on the use of psychosocial interventions would be needed to rule out other reasons underlying this increase in prescribing.

13.
Circ Arrhythm Electrophysiol ; 12(8): e007394, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31394921

RESUMO

BACKGROUND: Ripple mapping (RM) is an alternative approach to activation mapping of atrial tachycardia (AT) that avoids electrogram annotation. We tested whether RM is superior to conventional annotation based local activation time (LAT) mapping for AT diagnosis in a randomized and multicenter study. METHODS: Patients with AT were randomized to either RM or LAT mapping using the CARTO3v4 CONFIDENSE system. Operators determined the diagnosis using the assigned 3D mapping arm alone, before being permitted a single confirmatory entrainment manuever if needed. A planned ablation lesion set was defined. The primary end point was AT termination with delivery of the planned ablation lesion set. The inability to terminate AT with this first lesion set, the use of more than one entrainment manuever, or the need to crossover to the other mapping arm was defined as failure to achieve the primary end point. RESULTS: One hundred five patients from 7 centers were recruited with 22 patients excluded due to premature AT termination, noninducibility or left atrial appendage thrombus. Eighty-three patients (pts; RM=42, LAT=41) completed mapping and ablation within the 2 groups of similar characteristics (RM versus LAT: prior ablation or cardiac surgery n=35 [83%] versus n=35 [85%], P=0.80). The primary end point occurred in 38/42 pts (90%) in the RM group and 29/41pts (71%) in the LAT group (P=0.045). This was achieved without any entrainment in 31/42 pts (74%) with RM and 18/41 pts (44%) with LAT (P=0.01). Of those patients who failed to achieve the primary end point, AT termination was achieved in 9/12 pts (75%) in the LAT group following crossover to RM with entrainment, but 0/4 pts (0%) in the RM group crossing over to LAT mapping with entrainment (P=0.04). CONCLUSIONS: RM is superior to LAT mapping on the CARTO3v4 CONFIDENSE system in guiding ablation to terminate AT with the first lesion set and with reduced entrainment to assist diagnosis. CLINICAL TRIALS REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT02451995.

14.
Urology ; 133: 222-228, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401219

RESUMO

OBJECTIVE: To determine the long-term outcome of transobturator sling for male stress urinary incontinence (SUI) clustered according to preoperative SUI severity, and to identify predictors of treatment success durability and failure occurrence in long-term follow-up. METHOD: A nonconcurrent study was conducted on all transobturator male sling cases performed from August 2006 to June 2012 by a single surgeon. Preoperative SUI severity was clustered into mild (≤2 ppd), moderate (3-4 ppd) or severe (≥5 ppd). Success was defined as complete dryness with 0 pads used (cured), and a patient with ≥50% improvement, satisfied without further procedures needed. Otherwise it was considered a treatment failure. Clinical variables significantly associated with long-term treatment success were determined. Time-to-event (Kaplan-Meier) and Multiple-Cox regression analysis were performed to determine predictors of long-term treatment outcome. RESULTS: A total of 215 patients (mild-59, moderate-94, and severe-62) with a mean follow-up of 56.4 ± 41.6 months were included. On long-term follow-up, 150 (69.8%) patients-maintained treatment success and 96 (44.7%) were dry. The long-term outcome success clustered according to SUI severity as mild, moderate, and severe was 84.7%, 72.3%, and 51.6%, respectively. Kaplan-Meier with Log-rank test and Multiple Cox-regression determined that both concomitant urge incontinence and preoperative SUI severity were independent predictors of long-term durability of treatment success and failure occurrence. Preoperative SUI severity was the only predictor of long-term cure sustainability. CONCLUSION: The time to event analysis with an average of ∼5 years postoperative follow-up has determined that the preoperative severity and presence of concomitant urge incontinence were independent predictors for long-term outcome.


Assuntos
Falha de Prótese , Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Idoso , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/instrumentação
15.
Trials ; 20(1): 463, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358032

RESUMO

BACKGROUND: Differentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP) trial tests the hypothesis that a PCT-based algorithm to guide initiation, continuation and discontinuation of antibiotics will lead to reduced antibiotic use in patients with acute pancreatitis and without an adverse effect on outcome. METHODS: This is a single-centre, randomised, controlled, single-blind, two-arm pragmatic clinical and cost-effectiveness trial. Patients with a clinical diagnosis of acute pancreatitis will be allocated on a 1:1 basis to intervention or standard care. Intervention will involve the use of a PCT-based algorithm to guide antibiotic use. The primary outcome measure will be the binary outcome of antibiotic use during index admission. Secondary outcome measures include: safety non-inferiority endpoint all-cause mortality; days of antibiotic use; clinical infections; new isolates of multiresistant bacteria; duration of inpatient stay; episode-related mortality and cause; quality of life (EuroQol EQ-5D); and cost analysis. A 20% absolute change in antibiotic use would be a clinically important difference. A study with 80% power and 5% significance (two-sided) would require 97 patients in each arm (194 patients in total): the study will aim to recruit 200 patients. Analysis will follow intention-to-treat principles. DISCUSSION: When complete, PROCAP will be the largest randomised trial of the use of a PCT algorithm to guide initiation, continuation and cessation of antibiotics in acute pancreatitis. PROCAP is the only randomised trial to date to compare standard care of acute pancreatitis as defined by the International Association of Pancreatology/American Pancreatic Association guidelines to patients having standard care but with all antibiotic prescribing decisions based on PCT measurement. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number, ISRCTN50584992. Registered on 7 February 2018.


Assuntos
Algoritmos , Antibacterianos/uso terapêutico , Técnicas de Apoio para a Decisão , Monitoramento de Medicamentos/métodos , Pancreatite/tratamento farmacológico , Pró-Calcitonina/sangue , Antibacterianos/efeitos adversos , Antibacterianos/economia , Biomarcadores/sangue , Tomada de Decisão Clínica , Ensaios Clínicos Fase III como Assunto , Redução de Custos , Análise Custo-Benefício , Custos de Medicamentos , Monitoramento de Medicamentos/economia , Inglaterra , Humanos , Pancreatite/sangue , Pancreatite/diagnóstico , Pancreatite/economia , Ensaios Clínicos Pragmáticos como Assunto , Valor Preditivo dos Testes , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento
17.
Eur J Gastroenterol Hepatol ; 31(6): 653-660, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31009400

RESUMO

OBJECTIVES: Sacral nerve stimulation (SNS) may provide long-term symptom relief to patients suffering from chronic constipation. Patients are currently selected for SNS using a 2-week peripheral nerve evaluation (PNE) comprising stimulation by temporary leads. However, only 40% of test responders receive long-term benefit from treatment meaning that healthcare costs per successfully treated patient are too high. The primary objective was to assess tined-lead testing to predict benefit from SNS for chronic constipation. PATIENTS AND METHODS: A randomized double-blind sham-controlled cross-over design evaluated enhanced PNE (ePNE) using tined quadripolar electrode leads over 6 weeks. The design differentiated between patients with discriminate and indiscriminate responses to testing. A score improvement of 25% or more was considered to be a positive response within a stimulation period. The primary outcome was the proportion of patients showing a reduction of at least 0.5 in constipation symptom score at 6 months. RESULTS: A total of 45 patients were randomized, of whom 29 (64.4%) were test-phase responders. Of these, 27 were implanted providing permanent SNS. During ePNE, seven (18%) were discriminate responders, 22 (56%) were indiscriminate responders and 10 (26%) were nonresponders. Six patients were withdrawn during the test phase because of infection or noncompliance. At 6 months, there was no significant difference in primary outcome between discriminate and indiscriminate responders (60 vs. 57%, P=0.76). The study was terminated prematurely because of a persistent infection rate of 10 (22%) during ePNE of which nine (20%) were severe. CONCLUSION: ePNE is a poor predictor of treatment response at 6 months. This suggests a strong and persistent placebo response during both SNS PNE and treatment. An extended 6-week PNE poses a high risk of infection.

18.
Pharmacoeconomics ; 37(6): 869, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30778866

RESUMO

Open Access This article is distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/ ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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