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1.
Swiss Med Wkly ; 149: w20116, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31476244

RESUMO

AIMS OF THE STUDY: Physician shortage is problematic, but the percentage of physicians who left patient care in Switzerland is unclear. We set out to describe this percentage and determine whether gender or language region was associated with leaving patient care. METHODS: We analysed the National Registry (Medreg) of all physicians who graduated between 1980 and 2009 in Switzerland. Based on the last known working status noted in Medreg, physicians were classified as “probably involved in patient care” or “potentially left patient care”. We drew an unrestricted random sample of 250 from each category. We searched professional directories / social media to classify each sample. Those with undetermined status received a questionnaire that asked their working status. We quantified the percentage of physicians who left patient care and used Poisson and Cox regression to determine rates and the association of leaving patient care with gender, language region, and year of graduation. RESULTS: We identified 23,112 living physicians in Medreg in 2015. Of these, 18,406 (79.6%) were probably involved in patient care and 4706 (20.4%) had potentially left patient care. In the random sample of 250 physicians probably involved in patient care, 237 were involved in patient care, 11 had left and the status of 2 was undetermined (0.8%). In the random sample of 250 physicians who had potentially left patient care, 109 were involved in patient care, 109 had left, and the status of 32 was undetermined (12.8%). We estimated that 13.6% of physicians had left patient care (95% confidence interval [CI] 11.1–16.1%). According to the most realistic scenario, the rate of physicians who had left patient care was 1.2 per 100 physicians/year (95% CI 0.9–1.6) for those who had graduated between 1980 and 1994, and 1.8 per 100 physicians/year (95% CI 1.4–2.3) for those who graduated between 1995 and 2009 (adjusted hazard ratio 1.74, 95% CI 1.12–2.71). There was no evidence that the risk of leaving patient care was associated with gender or language region. CONCLUSIONS: Approximately one in seven physicians in Switzerland who graduated between 1980 and 2009 left patient care. Leaving patient care was not associated with gender, but the probability of leaving patient care was increased considerably in physicians who graduated more recently. Interventions that aim at keeping physicians in the work force and encourage their return to practice are sorely needed.

3.
Lancet ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31488372

RESUMO

BACKGROUND: Newer-generation drug-eluting stents that combine ultrathin strut metallic platforms with biodegradable polymers might facilitate vascular healing and improve clinical outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI) compared with contemporary thin strut second-generation drug-eluting stents. We did a randomised clinical trial to investigate the safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting stents versus thin strut durable polymer everolimus-eluting stents in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. METHODS: The BIOSTEMI trial was an investigator-initiated, multicentre, prospective, single-blind, randomised superiority trial at ten hospitals in Switzerland. Patients aged 18 years or older with acute STEMI who were referred for primary PCI were eligible to participate. Patients were randomly allocated (1:1) to either biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Central randomisation was done based on a computer-generated allocation sequence with variable block sizes of 2, 4, and 6, which was stratified by centre, diabetes status, and presence or absence of multivessel coronary artery disease, and concealed using a secure web-based system. Patients and treating physicians were aware of group allocations, whereas outcome assessors were masked to the allocated stent. The experimental stent (Orsiro; Biotronik; Bülach, Switzerland) consisted of an ultrathin strut cobalt-chromium metallic stent platform releasing sirolimus from a biodegradable polymer. The control stent (Xience Xpedition/Alpine; Abbott Vascular, Abbott Park, IL, USA) consisted of a thin strut cobalt-chromium stent platform that releases everolimus from a durable polymer. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial reinfarction (Q-wave and non-Q-wave), and clinically-indicated target lesion revascularisation, within 12 months of the index procedure. All analyses were done with the individual participant as the unit of analysis and according to the intention-to-treat principle. The trial was registered with ClinicalTrials.gov, number NCT02579031. FINDINGS: Between April 26, 2016, and March 9, 2018, we randomly assigned 1300 patients (1623 lesions) with acute myocardial infarction to treatment with biodegradable polymer sirolimus-eluting stents (649 patients and 816 lesions) or durable polymer everolimus-eluting stents (651 patients and 806 lesions). At 12 months, follow-up data were available for 614 (95%) patients treated with biodegradable polymer sirolimus-eluting stents and 626 (96%) patients treated with durable polymer everolimus-eluting stents. The primary composite endpoint of target lesion failure occurred in 25 (4%) of 649 patients treated with biodegradable polymer sirolimus-eluting stents and 36 (6%) of 651 patients treated with durable polymer everolimus-eluting stents (difference -1·6 percentage points; rate ratio 0·59, 95% Bayesian credibility interval 0·37-0·94; posterior probability of superiority 0·986). Cardiac death, target vessel myocardial reinfarction, clinically-indicated target lesion revascularisation, and definite stent thrombosis were similar between the two treatment groups in the 12 months of follow-up. INTERPRETATION: In patients with acute STEMI undergoing primary PCI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 1 year. This difference was driven by reduced ischaemia-driven target lesion revascularisation in patients treated with biodegradable polymer sirolimus-eluting stents compared with durable polymer everolimus-eluting stents. FUNDING: Biotronik.

4.
Lancet ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31488373

RESUMO

BACKGROUND: The Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease, and reported results up to 5 years. We now report 10-year all-cause death results. METHODS: The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to the PCI group or CABG group. Patients with a history of PCI or CABG, acute myocardial infarction, or an indication for concomitant cardiac surgery were excluded. The primary endpoint of the SYNTAXES study was 10-year all-cause death, which was assessed according to the intention-to-treat principle. Prespecified subgroup analyses were performed according to the presence or absence of left main coronary artery disease and diabetes, and according to coronary complexity defined by core laboratory SYNTAX score tertiles. This study is registered with ClinicalTrials.gov, NCT03417050. FINDINGS: From March, 2005, to April, 2007, 1800 patients were randomly assigned to the PCI (n=903) or CABG (n=897) group. Vital status information at 10 years was complete for 841 (93%) patients in the PCI group and 848 (95%) patients in the CABG group. At 10 years, 244 (27%) patients had died after PCI and 211 (24%) after CABG (hazard ratio 1·17 [95% CI 0·97-1·41], p=0·092). Among patients with three-vessel disease, 151 (28%) of 546 had died after PCI versus 113 (21%) of 549 after CABG (hazard ratio 1·41 [95% CI 1·10-1·80]), and among patients with left main coronary artery disease, 93 (26%) of 357 had died after PCI versus 98 (28%) of 348 after CABG (0·90 [0·68-1·20], pinteraction=0·019). There was no treatment-by-subgroup interaction with diabetes (pinteraction=0·66) and no linear trend across SYNTAX score tertiles (ptrend=0·30). INTERPRETATION: At 10 years, no significant difference existed in all-cause death between PCI using first-generation paclitaxel-eluting stents and CABG. However, CABG provided a significant survival benefit in patients with three-vessel disease, but not in patients with left main coronary artery disease. FUNDING: German Foundation of Heart Research (SYNTAXES study, 5-10-year follow-up) and Boston Scientific Corporation (SYNTAX study, 0-5-year follow-up).

5.
Eur J Anaesthesiol ; 36(9): 695-704, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31368907

RESUMO

BACKGROUND: Failed back surgery syndrome (FBSS) is a pain condition refractory to therapy, and is characterised by persistent low back pain after spinal surgery. FBSS is associated with severe disability, low quality of life and high unemployment. We are currently unable to identify patients who are at risk of developing FBSS. Patients with chronic low back pain may display signs of central hypersensitivity as assessed by quantitative sensory tests (QST). This can contribute to the risk of developing persistent pain after surgery. OBJECTIVE: We tested the hypothesis that central hypersensitivity as assessed by QST predicts FBSS. DESIGN: Prospective cohort study. SETTING: Three tertiary care centres. PATIENTS: 141 patients scheduled for up to three segment spinal surgery for chronic low back pain (defined as at least 3 on a numerical rating scale on most days during the week and with a minimum duration of 3 months) due to degenerative changes. OUTCOMES: We defined FBSS as persistent pain, persistent disability or a composite outcome defined as either persistent pain or disability. The primary outcome was persistent pain 12 months after surgery. We applied 14 QST using electrical, pressure and temperature stimulation to predict FBSS and assessed the association of QST with FBSS in multivariable analyses adjusted for sociodemographic, psychological and clinical and surgery-related characteristics. RESULTS: None of the investigated 14 QST predicted FBSS, with 95% confidence intervals of crude and adjusted associations of all QST including one as a measure of no association. Results remained robust in all sensitivity and secondary analyses. CONCLUSION: The study indicates that assessment of altered central pain processing using current QST is unlikely to identify patients at risk of FBSS and is therefore unlikely to inform clinical decisions.

8.
Circulation ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31434508

RESUMO

BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors lower cardiovascular events in type 2 diabetes (T2DM) but whether they promote direct cardiac effects remains unknown. We sought to determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with T2DM and coronary artery disease (CAD). METHODS: Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5 to 10.0%, known CAD and estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed (LVMi) to body surface area (BSA) from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to BSA (LVEDVi and LVESVi), ejection fraction (LVEF), 24-h ambulatory blood pressure, hematocrit and N-terminal pro b-type natriuretic peptide (NT-proBNP). RESULTS: Among the 97 participants (90 men [93%], mean [SD] age 62.8 [9.0] years, T2DM duration 11.0 [8.2] years, eGFR 88.4 [16.9] mL/min/1.73m2, LVMi 60.7 [11.9] g/m2) 90 had evaluable imaging at follow-up. Mean LVMi regression over 6 months was 2.6 g/m2 and 0.01 g/m2 for those assigned empagliflozin and placebo, respectively (adjusted difference -3.35 g/m2, 95% CI -5.9 to -0.81g/m2, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference -6.8mmHg, 95% CI -11.2 to -2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference -3.2mmHg, 95% CI -5.8 to -0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003). CONCLUSIONS: Among people with T2DM and CAD, SGLT2 inhibition with empagliflozin was associated with significant reduction in LVMi after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME trial. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT02998970.

9.
Eur Heart J ; 40(31): 2595-2604, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31397487

RESUMO

AIMS : To evaluate the impact of an experimental strategy [23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT)] vs. a reference regimen (12-month aspirin monotherapy following 12-month DAPT) after complex percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the present post hoc analysis of the Global Leaders trial, the primary endpoint [composite of all-cause death or new Q-wave myocardial infarction (MI)] at 2 years was assessed in patients with complex PCI, which includes at least one of the following characteristics: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents, or total stent length >60 mm. In addition, patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, or any revascularization) and net adverse clinical events (NACE) [composite of POCE or Bleeding Academic Research Consortium (BARC) Type 3 or 5 bleeding] were explored. Among 15 450 patients included in this analysis, 4570 who underwent complex PCI had a higher risk of ischaemic and bleeding events. In patients with complex PCI, the experimental strategy significantly reduced risks of the primary endpoint [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.48-0.85] and POCE (HR: 0.80, 95% CI: 0.69-0.93), but not in those with non-complex PCI (Pinteraction = 0.015 and 0.017, respectively). The risk of BARC Type 3 or 5 bleeding was comparable (HR: 0.97, 95% CI: 0.67-1.40), resulting in a significant risk reduction in NACE (HR: 0.80, 95% CI: 0.69-0.92; Pinteraction = 0.011). CONCLUSION : Ticagrelor monotherapy following 1-month DAPT could provide a net clinical benefit for patients with complex PCI. However, in view of the overall neutral results of the trial, these findings of a post hoc analysis should be considered as hypothesis generating.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31410968

RESUMO

BACKGROUND: The aim of this study was to investigate the impact of ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for bifurcation lesions. METHODS: GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing 1-month DAPT with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. The primary endpoint was a composite of all-cause death or new Q-wave myocardial infarction (MI) at 2 years. RESULTS: Among the 15,845 patients included in this subgroup analysis, 2,498 patients (15.8%) underwent PCI for at least one bifurcation lesion. The incidence of the primary endpoint was similar between the bifurcation and nonbifurcation groups (4.7 vs. 4.0%, p = .083). The experimental treatment had no significant effect on the primary endpoint according to the presence/absence of a bifurcation lesion (bifurcation: hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.51-1.07; nonbifurcation: HR: 0.90, 95% CI: 0.76-1.07, p for interaction = .343), but was associated with significant reduction in definite or probable stent thrombosis (p for interaction = .022) and significant excess of stroke (p for interaction = .018) when compared with the reference treatment. CONCLUSIONS: After PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial.

11.
Eur Heart J ; 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31329852

RESUMO

AIMS : Owing to new evidence from randomized controlled trials (RCTs) in low-risk patients with severe aortic stenosis, we compared the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the entire spectrum of surgical risk patients. METHODS AND RESULTS : The meta-analysis is registered with PROSPERO (CRD42016037273). We identified RCTs comparing TAVI with SAVR in patients with severe aortic stenosis reporting at different follow-up periods. We extracted trial, patient, intervention, and outcome characteristics following predefined criteria. The primary outcome was all-cause mortality up to 2 years for the main analysis. Seven trials that randomly assigned 8020 participants to TAVI (4014 patients) and SAVR (4006 patients) were included. The combined mean STS score in the TAVI arm was 9.4%, 5.1%, and 2.0% for high-, intermediate-, and low surgical risk trials, respectively. Transcatheter aortic valve implantation was associated with a significant reduction of all-cause mortality compared to SAVR {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.78-0.99], P = 0.030}; an effect that was consistent across the entire spectrum of surgical risk (P-for-interaction = 0.410) and irrespective of type of transcatheter heart valve (THV) system (P-for-interaction = 0.674). Transcatheter aortic valve implantation resulted in lower risk of strokes [HR 0.81 (95% CI 0.68-0.98), P = 0.028]. Surgical aortic valve replacement was associated with a lower risk of major vascular complications [HR 1.99 (95% CI 1.34-2.93), P = 0.001] and permanent pacemaker implantations [HR 2.27 (95% CI 1.47-3.64), P < 0.001] compared to TAVI. CONCLUSION : Compared with SAVR, TAVI is associated with reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of THV system.

12.
N Engl J Med ; 381(1): 36-46, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31269364

RESUMO

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).


Assuntos
Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclosporina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Indução de Remissão , Rituximab/efeitos adversos , Falha de Tratamento , Adulto Jovem
13.
Eur. heart j ; 40(25)Jul. 1, 2019. ilus
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1009597

RESUMO

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.(AU)


Assuntos
Adesão à Medicação
14.
World J Surg ; 43(10): 2379-2392, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31197439

RESUMO

BACKGROUND: Adverse events occur commonly in the operating room (OR) and often contribute to morbidity, mortality, and increased healthcare spending. Validated frameworks to measure and report postoperative outcomes have long existed to facilitate exchanges of structured information pertaining to postoperative complication rates in order to improve patient safety. However, systematic evidence regarding measurement and reporting of intraoperative adverse events (iAE) is still lacking. METHODS: We searched Ovid Medline, Embase, and Cochrane databases for articles published up to June 2016 that measured and reported iAE. We presented the terms and definitions used to describe iAE. We identified the types of reported iAE and summarized them into discrete categories. We reported frequencies of iAE by detection methods. RESULTS: Of the 47 included studies, 30 were cross-sectional, 14 were case-series, and 3 were cohort studies. The studies used 16 different terms and 22 unique definitions to describe 74 types of iAE. Frequencies of iAE appeared to vary depending on the detection methods, with higher numbers reported when direct observation in the OR was used to detect iAE. Twenty studies assessed severity of iAE, which were mostly based on whether they resulted in postoperative outcomes. CONCLUSIONS: This study systematically reviewed the current evidence on prevalence and characteristics of iAE that were detected by direct observation, reviews of patient charts, administrative data and incident reports, and surveys and interviews of healthcare providers. Our findings suggest that direct observation method has the most potential to identify and characterize iAE in detail.

15.
BMJ Open ; 9(6): e026769, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31164366

RESUMO

INTRODUCTION: Multimorbidity and polypharmacy are important risk factors for drug-related hospital admissions (DRAs). DRAs are often linked to prescribing problems (overprescribing and underprescribing), as well as non-adherence with drug regimens for different reasons. In this trial, we aim to assess whether a structured medication review compared with standard care can reduce DRAs in multimorbid older patients with polypharmacy. METHODS AND ANALYSIS: OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people is a European multicentre, cluster randomised, controlled trial. Hospitalised patients ≥70 years with ≥3 chronic medical conditions and concurrent use of ≥5 chronic medications are included in the four participating study centres of Bern (Switzerland), Utrecht (The Netherlands), Brussels (Belgium) and Cork (Ireland). Patients treated by the same prescribing physician constitute a cluster, and clusters are randomised 1:1 to either standard care or Systematic Tool to Reduce Inappropriate Prescribing (STRIP) intervention with the help of a clinical decision support system, the STRIP Assistant. STRIP is a structured method performing customised medication reviews, based on Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment criteria to detect potentially inappropriate prescribing. The primary endpoint is any DRA where the main reason or a contributory reason for the patient's admission is caused by overtreatment or undertreatment, and/or inappropriate treatment. Secondary endpoints include number of any hospitalisations, all-cause mortality, number of falls, quality of life, degree of polypharmacy, activities of daily living, patient's drug compliance, the number of significant drug-drug interactions, drug overuse and underuse and potentially inappropriate medication. ETHICS AND DISSEMINATION: The local Ethics Committees in Switzerland, Ireland, The Netherlands and Belgium approved this trial protocol. We will publish the results of this trial in a peer-reviewed journal. MAIN FUNDING: European Union's Horizon 2020 programme. TRIAL REGISTRATION NUMBER: NCT02986425 , SNCTP000002183 , NTR6012, U1111-1181-9400.

16.
EuroIntervention ; 15(6): e539-e546, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31217143

RESUMO

AIMS: The aim of this study was the external validation of the updated logistic clinical SYNTAX score for two-year all-cause mortality after PCI in the GLOBAL LEADERS trial. METHODS AND RESULTS: The GLOBAL LEADERS trial was an investigator-initiated, prospective randomised, multicentre, open-label trial comparing two strategies of antiplatelet therapy in 15,991 patients undergoing PCI. As a predefined analysis, we studied the first 4,006 consecutive patients enrolled between July 2013 and April 2014 for whom the anatomic SYNTAX scores were calculated by an independent core lab. The updated logistic clinical SYNTAX score was available in 3,271 patients. Patients were divided into quintiles according to the score. The C-statistic of the updated logistic clinical SYNTAX score for two-year all-cause mortality was 0.71 (95% confidence interval [CI]: 0.64-0.77). The updated logistic clinical SYNTAX score identified patients at very high risk for two-year all-cause mortality after PCI. Although it systematically overestimated two-year all-cause mortality, predicted and observed two-year all-cause mortality in the majority of the patients (four out of five quintiles) were in agreement. CONCLUSIONS: Overall discrimination for two-year all-cause mortality of the updated logistic clinical SYNTAX score is either borderline acceptable or possibly helpful. Calibration in the majority of patients is appropriate. The score is potentially useful in selecting enriched high-risk populations.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas , Humanos , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
19.
Lancet ; 393(10190): 2503-2510, 2019 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-31056295

RESUMO

BACKGROUND: New-generation drug-eluting stents (DES) have mostly been investigated in head-to-head non-inferiority trials against early-generation DES and have typically shown similar efficacy and superior safety. How the safety profile of new-generation DES compares with that of bare-metal stents (BMS) is less clear. METHODS: We did an individual patient data meta-analysis of randomised clinical trials to compare outcomes after implantation of new-generation DES or BMS among patients undergoing percutaneous coronary intervention. The primary outcome was the composite of cardiac death or myocardial infarction. Data were pooled in a one-stage random-effects meta-analysis and examined at maximum follow-up and a 1-year landmark. Risk estimates are reported as hazard ratios (HRs) with 95% CIs. This study is registered in PROSPERO, number CRD42017060520. FINDINGS: We obtained individual data for 26 616 patients in 20 randomised trials. Mean follow-up was 3·2 (SD 1·8) years. The risk of the primary outcome was reduced in DES recipients compared with BMS recipients (HR 0·84, 95% CI 0·78-0·90, p<0·001) owing to a reduced risk of myocardial infarction (0·79, 0·71-0·88, p<0·001) and a possible slight but non-significant cardiac mortality benefit (0·89, 0·78-1·01, p=0·075). All-cause death was unaffected (HR with DES 0·96, 95% CI 0·88-1·05, p=0·358), but risk was lowered for definite stent thrombosis (0·63, 0·50-0·80, p<0·001) and target-vessel revascularisation (0·55, 0·50-0·60, p<0·001). We saw a time-dependent treatment effect, with DES being associated with lower risk of the primary outcome than BMS up to 1 year after placement. While the effect was maintained in the longer term, there was no further divergence from BMS after 1 year. INTERPRETATION: The performance of new-generation DES in the first year after implantation means that BMS should no longer be considered the gold standard for safety. Further development of DES technology should target improvements in clinical outcomes beyond 1 year. FUNDING: Bern University Hospital.


Assuntos
Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/instrumentação , Stents/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Stents Farmacológicos/efeitos adversos , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Razão de Chances , Intervenção Coronária Percutânea/mortalidade , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Resultado do Tratamento
20.
Cochrane Database Syst Rev ; 5: CD005522, 2019 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-31132298

RESUMO

BACKGROUND: Tramadol is often prescribed to treat pain and is associated physical disability in osteoarthritis (OA). Due to the pharmacologic mechanism of tramadol, it may lead to fewer associated adverse effects (i.e. gastrointestinal bleeding or renal problems) compared to non-steroidal anti-inflammatory drugs (NSAIDs). This is an update of a Cochrane Review originally published in 2006. OBJECTIVES: To determine the benefits and harms of oral tramadol or tramadol combined with acetaminophen or NSAIDs in people with osteoarthritis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases, as well as the US National Institutes of Health and World Health Organization trial registries up to February 2018. We searched the LILACS database up to August 2015. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated the effect of tramadol, or tramadol in combination with acetaminophen (paracetamol) or NSAIDs versus placebo or any comparator in people with osteoarthritis. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. MAIN RESULTS: We included 22 RCTs (11 more than the previous review) of which 21 RCTs were included in meta-analyses for 3871 participants randomized to tramadol alone or tramadol in combination with another analgesic and 2625 participants randomized to placebo or active control. Seventeen studies evaluated tramadol alone and five evaluated tramadol plus acetaminophen. Thirteen studies used placebo controls and eleven studies used active controls (two trials had both placebo and active arms). The dose of tramadol ranged from 37.5 mg to 400 mg daily; all doses were pooled. Most trials were multicenter with a mean duration of two months. Participants were predominantly women with hip or knee osteoarthritis, with a mean age of 63 years and moderate to severe pain. There was a high risk of selection bias as only four trials reported both adequate sequence generation and allocation concealment. There was a low risk for performance bias as most studies blinded participants. There was a high risk of attrition bias as 10/22 trials showed incomplete outcome data. Most of the trials were funded by the pharmaceutical industry.Moderate quality evidence (downgraded due to risk of bias) indicated that tramadol alone and in combination with acetaminophen had no important benefit on pain reduction compared to placebo control (tramadol alone: 4% absolute improvement, 95% confidence interval (CI) 3% to 5%; 8 studies, 3972 participants; tramadol in combination with acetaminophen: 4% absolute improvement, 95% CI 2% to 6%; 2 studies, 614 participants).Fifteen out of 100 people in the tramadol group improved by 20% (which corresponded to a clinically important difference in pain) compared to 10/100 in the placebo group (5% absolute improvement). Twelve out of 100 people improved by 20% in the tramadol in combination with acetaminophen group compared to 7/100 in the placebo group (5% absolute improvement).Moderate quality evidence (downgraded due to risk of bias) indicated that tramadol alone and in combination with acetaminophen led to no important benefit in physical function compared to placebo (tramadol alone: 4% absolute improvement, 95% CI 2% to 6%; 5 studies, 2550 participants; tramadol in combination with acetaminophen: 4% absolute improvement, 95% CI 2% to 7%; 2 studies, 614 participants).Twenty-one out of 100 people in the tramadol group improved by 20% (which corresponded to a clinically important difference in physical function) compared to 16/100 in the placebo group (5% absolute improvement). Fifteen out of 100 people improved by 20% in the tramadol in combination with acetaminophen group compared to 10/100 in the placebo group (5% absolute improvement).Moderate quality evidence (downgraded due to risk of bias) indicated that, compared to placebo, there was a greater risk of developing adverse events with tramadol alone (risk ratio (RR) 1.34, 95% CI 1.24 to 1.46; 4 studies, 2039 participants) and tramadol in combination with acetaminophen compared to placebo (RR 1.91, 95% CI 1.32 to 2.76; 1 study, 308 participants). This corresponded to a 17% increase (95% CI 12% to 23%) with tramadol alone and 22% increase (95% CI 8% to 41%) with tramadol in combination with acetaminophen.The three most frequent adverse events were nausea, dizziness and tiredness. Moderate quality evidence (downgraded due to risk of bias) indicated that there was a greater risk of withdrawing from the study because of adverse events with tramadol alone compared to placebo (RR 2.64, 95% CI 2.17 to 3.20; 9 studies, 4533 participants), which corresponded to a 12% increase (95% CI 9% to 16%).Low quality evidence (downgraded due to risk of bias and inconsistency) indicated that there was a greater risk of withdrawing from the study because of adverse events with tramadol in combination with acetaminophen compared to placebo (RR 2.78, 95% CI 1.50 to 5.16; 2 studies, 614 participants), which corresponded to a 8% absolute improvement (95% CI 2% to 19%).Low quality evidence (downgraded due to risk of bias and imprecision) indicated that there was a greater risk of developing serious adverse events with tramadol alone compared to placebo (110/2459 participants with tramadol compared to 22/1153 participants with placebo; RR 1.78, 95% CI 1.11 to 2.84; 7 studies, 3612 participants), which corresponded to a 1% increase (95% CI 0% to 4%). There were no serious adverse events reported in one small study (15 participants) of tramadol with acetaminophen compared to placebo. AUTHORS' CONCLUSIONS: Moderate quality evidence indicates that compared to placebo, tramadol alone or in combination with acetaminophen probably has no important benefit on mean pain or function in people with osteoarthritis, although slightly more people in the tramadol group report an important improvement (defined as 20% or more). Moderate quality evidence shows that adverse events probably cause substantially more participants to stop taking tramadol. The increase in serious adverse events with tramadol is less certain, due to the small number of events.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Osteoartrite/complicações , Dor/tratamento farmacológico , Tramadol/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Dor/etiologia , Dor/prevenção & controle , Manejo da Dor , Medição da Dor
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