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1.
Med Decis Making ; : 272989X211003880, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33813933

RESUMO

Economic evaluations conducted alongside randomized controlled trials are a popular vehicle for generating high-quality evidence on the incremental cost-effectiveness of competing health care interventions. Typically, in these studies, resource use (and by extension, economic costs) and clinical (or preference-based health) outcomes data are collected prospectively for trial participants to estimate the joint distribution of incremental costs and incremental benefits associated with the intervention. In this article, we extend the generalized linear mixed-model framework to enable simultaneous modeling of multiple outcomes of mixed data types, such as those typically encountered in trial-based economic evaluations, taking into account correlation of outcomes due to repeated measurements on the same individual and other clustering effects. We provide new wrapper functions to estimate the models in Stata and R by maximum and restricted maximum quasi-likelihood and compare the performance of the new routines with alternative implementations across a range of statistical programming packages. Empirical applications using observed and simulated data from clinical trials suggest that the new methods produce broadly similar results as compared with Stata's merlin and gsem commands and a Bayesian implementation in WinBUGS. We highlight that, although these empirical applications primarily focus on trial-based economic evaluations, the new methods presented can be generalized to other health economic investigations characterized by multivariate hierarchical data structures.

2.
Trials ; 22(1): 8, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407804

RESUMO

OBJECTIVES: The primary objective is to determine which of two interventions: 1) an eight week, online, home-based, supervised, group rehabilitation programme (REGAIN); or 2) a single online session of advice (best-practice usual care); is the most clinically and cost-effective treatment for people with ongoing COVID-19 sequelae more than three months after hospital discharge. TRIAL DESIGN: Multi-centre, 2-arm (1:1 ratio) parallel group, randomised controlled trial with embedded process evaluation and health economic evaluation. PARTICIPANTS: Adults with ongoing COVID-19 sequelae more than three months after hospital discharge Inclusion criteria: 1) Adults ≥18 years; 2) ≥ 3 months after any hospital discharge related to COVID-19 infection, regardless of need for critical care or ventilatory support; 3) substantial (as defined by the participant) COVID-19 related physical and/or mental health problems; 4) access to, and able/supported to use email and internet audio/video; 4) able to provide informed consent; 5) able to understand spoken and written English, Bengali, Gujarati, Urdu, Punjabi or Mandarin, themselves or supported by family/friends. EXCLUSION CRITERIA: 1) exercise contraindicated; 2) severe mental health problems preventing engagement; 3) previous randomisation in the present study; 4) already engaged in, or planning to engage in an alternative NHS rehabilitation programme in the next 12 weeks; 5) a member of the same household previously randomised in the present study. INTERVENTION AND COMPARATOR: Intervention 1: The Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) programme: an eight week, online, home-based, supervised, group rehabilitation programme. Intervention 2: A thirty-minute, on-line, one-to-one consultation with a REGAIN practitioner (best-practice usual care). MAIN OUTCOMES: The primary outcome is health-related quality of life (HRQoL) - PROMIS® 29+2 Profile v2.1 (PROPr) - measured at three months post-randomisation. Secondary outcomes include dyspnoea, cognitive function, health utility, physical activity participation, post-traumatic stress disorder (PTSD) symptom severity, depressive and anxiety symptoms, work status, health and social care resource use, death - measured at three, six and 12 months post-randomisation. RANDOMISATION: Participants will be randomised to best practice usual care or the REGAIN programme on a 1:1.03 basis using a computer-generated randomisation sequence, performed by minimisation and stratified by age, level of hospital care, and case level mental health symptomatology. Once consent and baseline questionnaires have been completed by the participant online at home, randomisation will be performed automatically by a bespoke web-based system. BLINDING (MASKING): To ensure allocation concealment from both participant and REGAIN practitioner at baseline, randomisation will be performed only after the baseline questionnaires have been completed online at home by the participant. After randomisation has been performed, participants and REGAIN practitioners cannot be blind to group allocation. Follow-up outcome assessments will be completed by participants online at home. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 535 participants will be randomised: 263 to the best-practice usual care arm, and 272 participants to the REGAIN programme arm. TRIAL STATUS: Current protocol: Version 3.0 (27th October 2020) Recruitment will begin in December 2020 and is anticipated to complete by September 2021. TRIAL REGISTRATION: ISRCTN:11466448 , 23rd November 2020 FULL PROTOCOL: The full protocol Version 3.0 (27th October 2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interests of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.


Assuntos
COVID-19/reabilitação , Terapia por Exercício/métodos , Intervenção Baseada em Internet/economia , Sistemas de Apoio Psicossocial , Encaminhamento e Consulta/economia , Adulto , COVID-19/diagnóstico , COVID-19/psicologia , COVID-19/virologia , Análise Custo-Benefício , Terapia por Exercício/economia , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Resultado do Tratamento , Reino Unido
3.
BMJ Open ; 11(1): e041398, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514577

RESUMO

OBJECTIVE: To compare clinical and health economic outcomes after manubrium-limited mini-sternotomy (intervention) and conventional median sternotomy (usual care). DESIGN: A single-blind, randomised controlled trial. SETTING: Single centre UK National Health Service tertiary hospital. PARTICIPANTS: Adult patients undergoing aortic valve replacement (AVR) surgery. INTERVENTIONS: Intervention was manubrium-limited mini-sternotomy performed using a 5-7 cm midline incision. Usual care was median sternotomy performed using a midline incision from the sternal notch to the xiphisternum. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of patients who received a red cell transfusion postoperatively and within 7 days of index surgery. Secondary outcomes included proportion of patients receiving a non-red cell blood component transfusion and number of units transfused within 7 days and during index hospital stay, quality of life and cost-effectiveness analyses. RESULTS: 270 patients were randomised, received surgery and contributed to the intention to treat analysis. No difference between mini and conventional sternotomy in red-cell transfusion within 7 days was found; 23/135 patients in each arm received a transfusion, OR 1.0 (95% CI 0.5 to 2.0) and risk difference 0.0 (95% CI -0.1 to 0.1). Mini-sternotomy reduced chest drain losses (mean 181.6 mL (SD 138.7) vs conventional, mean 306·9 mL (SD 348.6)); this did not reduce red-cell transfusions. Mean valve size and postoperative valve function were comparable between mini-sternotomy and conventional groups; 23 mm vs 24 mm and 6/134 moderate or severe aortic regurgitation vs 3/130, respectively. Mini-sternotomy resulted in longer bypass (82.7 min (SD 23.5) vs 59.6 min (SD 15.1)) and cross-clamp times (64.1 min (SD 17.1) vs 46·3 min (SD 10.7)). Conventional sternotomy was more cost-effective with only a 5.8% probability of mini-sternotomy being cost-effective at a willingness to pay of £20 000/QALY (Quality Adjusted Life Years). CONCLUSIONS: AVR via mini-sternotomy did not reduce red blood cell transfusion within 7 days following surgery when compared with conventional sternotomy. TRIAL REGISTRATION NUMBER: ISRCTN29567910; Results.


Assuntos
Valva Aórtica , Implante de Prótese de Valva Cardíaca , Adulto , Valva Aórtica/cirurgia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Qualidade de Vida , Estudos Retrospectivos , Método Simples-Cego , Medicina Estatal , Esternotomia , Resultado do Tratamento
4.
Bone Jt Open ; 1(6): 205-213, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33225291

RESUMO

Aims: Torus fractures of the distal radius are the most common fractures in children. The NICE non-complex fracture guidelines recently concluded that bandaging was probably the optimal treatment for these injuries. However, across the UK current treatment varies widely due to a lack of evidence underpinning the guidelines. The Forearm Fracture Recovery in Children Evaluation (FORCE) trial evaluates the effect of a soft bandage and immediate discharge compared with rigid immobilization. Methods: FORCE is a multicentre, parallel group randomized controlled equivalence trial. The primary outcome is the Wong-Baker FACES pain score at three days after randomization and the primary analysis of this outcome will use a multivariate linear regression model to compare the two groups. Secondary outcomes are measured at one and seven days, and three and six-weeks post-randomization and include the Patient Reported Outcome Measurement Information System (PROMIS) upper extremity limb score, EuroQoL EQ-5D-Y, analgesia use, school absence, complications, and healthcare resource use. The planned statistical and health economic analyses for this trial are described here. The FORCE trial protocol has been published separately. Conclusion: This paper provides details of the planned analyses for this trial, and will reduce the risks of outcome reporting bias and data driven results.Cite this article: Bone Joint Open 2020;1-6:205-213.

5.
Bone Jt Open ; 1(6): 214-221, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33225292

RESUMO

Aims: Torus fractures are the most common childhood fracture, accounting for 500,000 UK emergency attendances per year. UK treatment varies widely due to lack of scientific evidence. This is the protocol for a randomized controlled equivalence trial of 'the offer of a soft bandage and immediate discharge' versus 'rigid immobilization and follow-up as per the protocol of the treating centre' in the treatment of torus fractures . Methods: Children aged four to 15-years-old inclusive who have sustained a torus/buckle fracture of the distal radius with/without an injury to the ulna are eligible to take part. Baseline pain as measured by the Wong Baker FACES pain scale, function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb, and quality of life (QoL) assessed with the EuroQol EQ-5D-Y will be collected. Each patient will be randomly allocated (1:1, stratified by centre and age group (four to seven years and ≥ eight years) to either a regimen of the offer of a soft bandage and immediate discharge or rigid immobilization and follow-up as per the protocol of the treating centre. Results: At day one, three, and seven, data on pain, function, QoL, immobilization, and analgesia will be collected. Three and six weeks after injury, the main outcomes plus data on complications, resource use, and school absence will be collected. The primary outcome is the Wong-Baker FACES pain scale at three days post-randomization. All data will be obtained through electronic questionnaires completed by the participants and/or parents/guardian.Cite this article: Bone Joint Open 2020;1-6:214-221.

6.
Mov Disord ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32960456

RESUMO

BACKGROUND: Lewy body dementia, comprising both dementia with Lewy bodies and Parkinson's disease dementia, is challenging to manage because of a complex symptom profile and lack of clear evidence-based management guidelines. OBJECTIVES: We assessed the feasibility of undertaking a cluster randomized study of the introduction of an evidence-based management toolkit for Lewy body dementia, assessing the outcomes for patients and carers as secondary measures. METHODS: We randomized 23 memory/dementia, movement disorder, or nonspecialist secondary care services to the management toolkit or usual care. People with dementia with Lewy bodies or Parkinson's disease dementia underwent assessments of cognition, motor and neuropsychiatric symptoms, and global outcome at baseline and 3 and 6 months. Healthcare, personal and social care costs, and carer-related outcomes of carer stress, depression, and anxiety were also examined. RESULTS: A total of 131 participants were recruited (target 120), for whom 6-month data were available on 108 (83%). There was a benefit of being in the intervention arm for carers (reduced Zarit Burden Scale [P < 0.01], reduced depressive symptoms [P < 0.05]), who also reported less marked patient deterioration on the global outcome measure (P < 0.05). There were no significant differences in other outcomes or in costs between groups. CONCLUSIONS: The introduction of an evidence-based management toolkit for Lewy body dementia was feasible and associated with some benefits, especially for carers. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

7.
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.

8.
BMJ Open ; 10(5): e036829, 2020 05 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.

9.
J Thorac Cardiovasc Surg ; 159(6): 2512-2520.e1, 2020 06.
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.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Mesotelioma/diagnóstico por imagem , Neoplasias Pleurais/diagnóstico por imagem , Parede Torácica/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Feminino , Humanos , Imageamento Tridimensional , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Invasividade Neoplásica , Seleção de Pacientes , Neoplasias Pleurais/patologia , Neoplasias Pleurais/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Parede Torácica/patologia , Parede Torácica/cirurgia , Toracotomia , Procedimentos Desnecessários
10.
J Am Chem Soc ; 142(6): 2876-2888, 2020 02 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.

11.
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
12.
Clin Teach ; 17(4): 455-456, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31799797
13.
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.


Assuntos
Artroplastia do Joelho/instrumentação , Prótese do Joelho , Polietileno/uso terapêutico , Idoso , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Irlanda do Norte , Desenho de Prótese , Falha de Prótese , Sistema de Registros , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/etiologia , País de Gales
15.
J Econ Entomol ; 113(2): 887-895, 2020 04 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.


Assuntos
Brassica , Besouros , Inseticidas , Sifonápteros , Solanum melongena , Animais , Controle de Insetos , Virginia
16.
BMJ Open ; 10(11): e040623, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33444204

RESUMO

INTRODUCTION: First-time traumatic anterior shoulder dislocation (TASD) is predominantly managed non-operatively. People sustaining TASD have ongoing pain, disability and future risk of redislocation. There are no published randomised controlled trials (RCTs) comparing different non-operative rehabilitation strategies to ascertain the optimum clinically effective approach after TASD. METHODS AND ANALYSIS: In this multicentre adaptive RCT, with internal pilot, adults with a radiologically confirmed first time TASD treated non-surgically will be screened at a minimum of 30 sites. People with neurovascular complications, bilateral dislocations or are unable to attend physiotherapy will be excluded.Randomisation will be on a 1:1 treatment allocation, stratified by age, hand dominance and site. Participants will receive a single session of advice; or a single session of advice plus offer of further physiotherapy (maximum 4 months). The primary analysis will be the difference in Oxford Shoulder Instability Score at 6 months. A sample size of a minimum of 478 participants will allow us to show a four point difference with 90% power.An embedded qualitative study will explore the participants' experiences of the trial interventions. ETHICS, REGISTRATION AND DISSEMINATION: Funded by NIHR HTA (16/167/56), 1 June 2018; National Research Ethic Committee approved (18/WA/0236), 26 July 2018. First site opened 5 November 2018 and final results will be updated on trial registries and submitted to a peer-reviewed journal and will inform rehabilitation strategies after a TASD. Study Within A Trial (SWAT) funded by MRC (MR/R013748/1), 1 May 2019; registered on the MRC-HTMR All-Ireland Hub (reference number SWAT 121). TRIAL REGISTRATION NUMBER: ISRCTN63184243. (Trial stage: Pre-results).


Assuntos
Instabilidade Articular , Luxação do Ombro , Atividades Cotidianas , Adulto , Idoso , Humanos , Irlanda , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários
17.
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.


Assuntos
Ensaios Clínicos como Assunto/métodos , Tomada de Decisões , Projetos de Pesquisa , Lesões do Manguito Rotador/cirurgia , Acrômio/cirurgia , Humanos
18.
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 Ósseos , 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
19.
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.


Assuntos
Comitês Consultivos , Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Uso de Medicamentos/tendências , Atenção Primária à Saúde/tendências , Adolescente , Criança , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Modelos Lineares , Masculino , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/tendências , Atenção Primária à Saúde/estatística & dados numéricos , Reino Unido
20.
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.


Assuntos
Mapeamento Potencial de Superfície Corporal/métodos , Ablação por Cateter/métodos , Átrios do Coração/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Imageamento Tridimensional , Taquicardia Supraventricular/fisiopatologia , Idoso , Feminino , Seguimentos , Humanos , Período Intraoperatório , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Taquicardia Supraventricular/cirurgia
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