Summary Background If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple ...therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with clopidogrel plus aspirin. Methods We did an open-label, multicentre, randomised, controlled trial in 15 centres in Belgium and the Netherlands. From November, 2008, to November, 2011, adults receiving oral anticoagulants and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00769938. Findings 573 patients were enrolled and 1-year data were available for 279 (98·2%) patients assigned double therapy and 284 (98·3%) assigned triple therapy. Mean ages were 70·3 (SD 7·0) years and 69·5 (8·0) years, respectively. Bleeding episodes were seen in 54 (19·4%) patients receiving double therapy and in 126 (44·4%) receiving triple therapy (hazard ratio HR 0·36, 95% CI 0·26–0·50, p<0·0001). In the double-therapy group, six (2·2%) patients had multiple bleeding events, compared with 34 (12·0%) in the triple-therapy group. 11 (3·9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9·5%) patients in the triple-therapy group (odds ratio from Kaplan-Meier curve 0·39, 95% CI 0·17–0·84, p=0·011). Interpretation Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events. Funding Antonius Ziekenhuis Foundation, Strect Foundation.
Summary Background In critically ill patients, antibiotic therapy is of great importance but long duration of treatment is associated with the development of antimicrobial resistance. Procalcitonin ...is a marker used to guide antibacterial therapy and reduce its duration, but data about safety of this reduction are scarce. We assessed the efficacy and safety of procalcitonin-guided antibiotic treatment in patients in intensive care units (ICUs) in a health-care system with a comparatively low use of antibiotics. Methods We did a prospective, multicentre, randomised, controlled, open-label intervention trial in 15 hospitals in the Netherlands. Critically ill patients aged at least 18 years, admitted to the ICU, and who received their first dose of antibiotics no longer than 24 h before inclusion in the study for an assumed or proven infection were eligible to participate. Patients who received antibiotics for presumed infection were randomly assigned (1:1), using a computer-generated list, and stratified (according to treatment centre, whether infection was acquired before or during ICU stay, and dependent on severity of infection ie, sepsis, severe sepsis, or septic shock) to receive either procalcitonin-guided or standard-of-care antibiotic discontinuation. Both patients and investigators were aware of group assignment. In the procalcitonin-guided group, a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80% or more of its peak value or to 0·5 μg/L or lower. In the standard-of-care group, patients were treated according to local antibiotic protocols. Primary endpoints were antibiotic daily defined doses and duration of antibiotic treatment. All analyses were done by intention to treat. Mortality analyses were completed for all patients (intention to treat) and for patients in whom antibiotics were stopped while being on the ICU (per-protocol analysis). Safety endpoints were reinstitution of antibiotics and recurrent inflammation measured by C-reactive protein concentrations and they were measured in the population adhering to the stopping rules (per-protocol analysis). The study is registered with ClinicalTrials.gov , number NCT01139489 , and was completed in August, 2014. Findings Between Sept 18, 2009, and July 1, 2013, 1575 of the 4507 patients assessed for eligibility were randomly assigned to the procalcitonin-guided group (761) or to standard-of-care (785). In 538 patients (71%) in the procalcitonin-guided group antibiotics were discontinued in the ICU. Median consumption of antibiotics was 7·5 daily defined doses (IQR 4·0–12·7) in the procalcitonin-guided group versus 9·3 daily defined doses (5·0–16·6) in the standard-of-care group (between-group absolute difference 2·69, 95% CI 1·26–4·12, p<0·0001). Median duration of treatment was 5 days (3–9) in the procalcitonin-guided group and 7 days (4–11) in the standard-of-care group (between-group absolute difference 1·22, 0·65–1·78, p<0·0001). Mortality at 28 days was 149 (20%) of 761 patients in the procalcitonin-guided group and 196 (25%) of 785 patients in the standard-of-care group (between-group absolute difference 5·4%, 95% CI 1·2–9·5, p=0·0122) according to the intention-to-treat analysis, and 107 (20%) of 538 patients in the procalcitonin-guided group versus 121 (27%) of 457 patients in the standard-of-care group (between-group absolute difference 6·6%, 1·3–11·9, p=0·0154) in the per-protocol analysis. 1-year mortality in the per-protocol analysis was 191 (36%) of 538 patients in the procalcitonin-guided and 196 (43%) of 457 patients in the standard-of-care groups (between-group absolute difference 7·4, 1·3–13·8, p=0·0188). Interpretation Procalcitonin guidance stimulates reduction of duration of treatment and daily defined doses in critically ill patients with a presumed bacterial infection. This reduction was associated with a significant decrease in mortality. Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial, leading to more adequate diagnosis and treatment, the cornerstones of antibiotic stewardship. Funding Thermo Fisher Scientific.
The International Vitreomacular Traction Study (IVTS) Group was convened to develop an optical coherence tomography (OCT)-based anatomic classification system for diseases of the vitreomacular ...interface (VMI).
The IVTS applied their clinical experience, after reviewing the relevant literature, to support the development of a strictly anatomic OCT-based classification system.
A panel of vitreoretinal disease experts was the foundation of the International Classification System.
Before the meeting, panel participants were asked to review 11 articles and to complete 3 questionnaires. The articles were preselected based on searches for comprehensive reviews covering diseases of the VMI. Responses to questionnaires and the group's opinions on definitions specified in the literature were used to guide the discussion.
Optical coherence tomography-based anatomic definitions and classification of vitreomacular adhesion, vitreomacular traction (VMT), and macular hole.
Vitreomacular adhesion is defined as perifoveal vitreous separation with remaining vitreomacular attachment and unperturbed foveal morphologic features. It is an OCT finding that is almost always the result of normal vitreous aging, which may lead to pathologic conditions. Vitreomacular traction is characterized by anomalous posterior vitreous detachment accompanied by anatomic distortion of the fovea, which may include pseudocysts, macular schisis, cystoid macular edema, and subretinal fluid. Vitreomacular traction can be subclassified by the diameter of vitreous attachment to the macular surface as measured by OCT, with attachment of 1500 μm or less defined as focal and attachment of more than 1500 μm as broad. When associated with other macular disease, VMT is classified as concurrent. Full-thickness macular hole (FTMH) is defined as a foveal lesion with interruption of all retinal layers from the internal limiting membrane to the retinal pigment epithelium. Full-thickness macular hole is primary if caused by vitreous traction or secondary if directly the result of pathologic characteristics other than VMT. Full-thickness macular hole is subclassified by size of the hole as determined by OCT and the presence or absence of VMT.
This classification system will support systematic diagnosis and management by creating a clinically applicable system that is predictive of therapeutic outcomes and is useful for the execution and analysis of clinical studies.
Summary Background Previously, we assessed selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) on survival and prevention of bacteraemia in patients in ...intensive-care units. In this analysis, we aimed to assess effectiveness of these interventions for prevention of respiratory tract colonisation and bacteraemia with highly resistant microorganisms acquired in intensive-care units. Methods We did an open-label, clustered group-randomised, crossover study in 13 intensive-care units in the Netherlands between May, 2004, and July, 2006. Participants admitted to intensive-care units with an expected duration of mechanical ventilation of more than 48 h or an expected stay of more than 72 h received SOD (topical tobramycin, colistin, and amphotericin B in the oropharynx), SDD (SOD antibiotics in the oropharynx and stomach plus 4 days' intravenous cefotaxime), or standard care. The computer-randomised order of study regimens was applied by an independent clinical pharmacist who was masked to intensive-care-unit identity. We calculated crude odds ratios (95% CI) for rates of bacteraemia or respiratory tract colonisation with highly resistant microorganisms in patients who stayed in intensive-care units for more than 3 days (ie, acquired infection). This trial is registered at http://isrctn.org , number ISRCTN35176830. Findings Data were available for 5927 (>99%) of 5939 patients, of whom 5463 (92%) were in intensive-care units for more than 3 days. 239 (13%) of 1837 patients in standard care acquired bacteraemia after 3 days, compared with 158 (9%) of 1758 in SOD (odds ratio 0·66, 95% CI 0·53–0·82), and 124 (7%) of 1868 in SDD (0·48, 0·38–0·60). Eight patients acquired bacteraemia with highly resistant microorganisms during SDD, compared with 18 patients (with 19 episodes) during standard care (0·41, 0·18–0·94; rate reduction RR 59%, absolute risk reduction ARR 0·6%) and 20 during SOD (0·37, 0·16–0·85; RR 63%, ARR 0·7%). Of the patients staying in intensive-care units for more than 3 days, we obtained endotracheal aspirate cultures for 881 (49%) patients receiving standard care, 886 (50%) receiving SOD, and 828 (44%) receiving SDD. 128 (15%) patients acquired respiratory tract colonisation with highly resistant microorganisms during standard care, compared with 74 (8%) during SDD (0·58, 0·43–0·78; RR 38%, ARR 5·5%) and 88 (10%) during SOD (0·65, 0·49–0·87; RR 32%, ARR 4·6%). Acquired respiratory tract colonisation with Gram-negative bacteria or cefotaxime-resistant and colistin-resistant pathogens was lowest during SDD. Interpretation Widespread use of SDD and SOD in intensive-care units with low levels of antibiotic resistance is justified. Funding None.
Microsurgery of the retina would be dramatically improved by instruments that offer supra-human precision. Here, we report the results of a first-in-human study of remotely controlled robot-assisted ...retinal surgery performed through a telemanipulation device. Specifically, 12 patients requiring dissection of the epiretinal or inner limiting membrane over the macula were randomly assigned to either undergo robot-assisted-surgery or manual surgery, under general anaesthesia. We evaluated surgical success, duration of surgery and amount of retinal microtrauma as a proxy for safety. Surgical outcomes were equally successful in the robotic-surgery and manual-surgery groups. Differences in the amount of retinal microtrauma between the two groups were statistically insignificant, yet dissection took longer with robotic surgery (median time, 4 min 5 s) than with manual surgery (1 min 20 s). We also show the feasibility of using the robot to inject recombinant tissue plasminogen activator under the retina to displace sight-threatening haemorrhage in three patients under local anaesthesia. A safe and viable robotic system for intraocular surgery would enable precise and minimally traumatic delivery of gene therapy or cell therapy to the retina.
Abstract Objective Endovascular treatment of a significant stenosis in an infrainguinal autologous bypass prevents bypass occlusion and improves bypass patency. Drug-eluting balloons (DEBs) have been ...proven to possess antirestenotic features in the treatment of femoropopliteal stenoses and occlusions. This study evaluated the effects of DEB angioplasty vs uncoated balloon (UCB) angioplasty to rescue infrainguinal autologous bypass grafts at risk (BAR). Methods The study included all consecutive patients treated endovascularly for BAR from December 1, 2012, to July 31, 2015. As of April 1, 2014, the primary treatment of BAR was changed from UCBs to DEBs. Patients treated with DEBs were prospectively recorded in a database and retrospectively analyzed. Patients treated with UCBs were retrospectively collected from a historical cohort with a similar inclusion period length as the DEB cohort. The follow-up scheme did not differ between the two groups. The primary end point was the combined end point of freedom from recurrent stenosis or bypass occlusion. Secondary end points were primary assisted patency, secondary patency, technical success, major amputation, and mortality. Results Twenty-one patients were treated in the DEB group and 18 were treated in the UCB group. The two groups were evenly distributed in demographics, bypass, treatment, and lesion characteristics. No statistically significant differences were found in the combined end point of freedom from recurrent stenosis and the occlusion rate after 1 year between the UCB group (77.8%) and the DEB group (80.0%; P = .76). After 1 year, the primary assisted patency rate was 88.2% in the UCB group vs 95.2% in the DEB group ( P = .47), and the secondary patency rate was 94.1% in the UCB group vs 95.2% in the DEB group ( P = .91). During follow-up, restenosis developed in four patients (22.2%) in the UCB group and in four patients (19.0%) in the DEB group ( P = .80). One bypass (5.6%) in the UCB group and one bypass (4.8%) in the DEB group occluded during follow-up ( P = .884). Conclusions DEBs and UCBs perform equally in the treatment of significant stenosis in infrainguinal autologous bypasses with regard to freedom from restenosis or bypass occlusion, primary assisted patency, and secondary patency at 1 year. We suggest using a less expensive UCB in the treatment of BAR.
Several studies have highlighted the prognostic role of preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow in the infarct-related artery (IRA) in patients with ST-segment elevation ...myocardial infarction (STEMI). However, the impact of preprocedural IRA occlusion in patients with diabetes with STEMI has been insufficiently studied. The aim of this study was to evaluate the effects of baseline IRA occlusion and diabetic status in patients with STEMI who underwent primary percutaneous coronary intervention by using data from a pooled analysis of randomized trials comparing intracoronary with intravenous abciximab bolus administration. A total of 3,046 patients with STEMI who underwent primary percutaneous coronary intervention were included. Diabetes was present in 578 patients (19%). The primary outcome was mortality after a median follow-up period of 375 days. Secondary end points were reinfarction and stent thrombosis. In patients without diabetes, IRA occlusion versus no occlusion was not associated with increased rates of mortality (4.3% vs 2.7%, p = 0.051) and reinfarction (3.3% vs 2.5%, p = 0.33). Patients with diabetes with IRA occlusion compared with those without occlusion showed higher rates of mortality (10.6% vs 4.6%, p = 0.01) and reinfarction (5.6% vs 2.1%, p = 0.03). Baseline IRA occlusion increased the rate of stent thrombosis in the nondiabetic (2.1% vs 1.0%, p = 0.04) and diabetic (3.2% vs 0.8%, p = 0.05) cohorts. Interaction analysis demonstrated that the risk for death and reinfarction was significantly increased when diabetes and IRA occlusion occurred concomitantly. In conclusion, patients with STEMI with diabetes and baseline IRA occlusion had disproportionately higher rates of death and reinfarction. Preprocedural IRA occlusion increased the risk for stent thrombosis, irrespective of diabetic status.
Introduction This study was designed to determine the effect of 2 different potassium regulation strategies with different targets (within the reference range) on atrial fibrillation (AF) or atrial ...flutter (AFL) in a cohort of intensive care unit patients after cardiac surgery. Methods The GRIP-COMPASS study was a prospective double-blinded interventional study in 910 patients after cardiac surgery (coronary artery bypass grafting and/or valvular surgery). Patients were assigned to either the normal-low potassium target (nLP group, 4.0 mmol/L) or the normal-high potassium target (nHP group, 4.5 mmol/L) in alternating blocks of 50 patients. Potassium levels were regulated using a validated computer-assisted potassium replacement protocol (GRIP-II). The primary end point was the incidence of AF/AFL on a 12-lead electrocardiogram during the first postoperative week. Results Of the 910 patients, 447 were assigned to the nLP group; and 463, to the nHP group, with no baseline differences between the 2 groups. The mean daily administered dose of potassium was 30 ± 23 mmol (nLP) versus 52 ± 27 mmol (nHP) ( P < .001), which resulted in mean intensive care unit potassium concentration of 4.22 ± 0.36 mmol/L and 4.33 ± 0.34 mmol/L, respectively ( P < .001). The incidence of AF/AFL after cardiac surgery did not differ: 38% in the nLP group and 41% in the nHP group. Also in several subgroups (eg, patients not known with prior AF/AFL or with valve surgery), there were no differences. Conclusions There were no differences in incidence of AF/AFL with 2 potassium regulation strategies with different potassium targets and different amounts of potassium administered in patients after cardiac surgery.
Background Vascular access is a necessity for patients with end-stage renal disease who need chronic intermittent hemodialysis. According to Kidney Disease Outcomes Quality Initiative (KDOQI) ...guidelines, radial-cephalic (RC) and brachial-cephalic (BC) arteriovenous fistulas (AVF) are the first and second choice for vascular access, respectively. If these options are not possible, an autogenous brachial-basilic fistula in the upper arm (BBAVF) or a prosthetic brachial-antecubital forearm loop (PTFE loop) may be considered. Until now, it was not clear which access type was preferable. We have performed a randomized study comparing BBAVF and prosthetic implantation in patients without the possibility for RCAVF or BCAVF. Methods Patients with failed primary/secondary access or inadequate arterial and/or venous vessels were randomized for either BBAVF or PTFE loop creation. The numbers of complications and interventions were recorded. Kaplan-Meier method was used to calculate primary, assisted-primary and secondary patency rates. The patency rates were compared with the log-rank test. Complication and intervention rates were compared with the Mann-Whitney test. Results A total of 105 patients were randomized for a BBAVF or PTFE loop (52 vs 53, respectively). Primary and assisted-primary 1-year patency rates were significantly higher in the BBAVF group: 46% ± 7.4% vs 22% ± 6.1% ( P = .005) and 87% ± 5.0% vs 71% ± 6.7% ( P = .045) for the BBAVF and PTFE group, respectively. Secondary patencies were comparable for both groups; 89% ± 4.6% vs 85% ± 5.2% for the BBAVF and PTFE group, respectively. The incidence rate of complications was 1.6 per patient-year in the BBAVF group vs 2.7 per patient-year in the PTFE group. Patients in the BBAVF group needed a total of 1.7 interventions per patient-year vs 2.7 per patient-year for the PTFE group. Conclusion These data show a significantly better primary and assisted-primary patency in the BBAVF group compared with the PTFE group. Furthermore, in the BBAVF group, fewer interventions were needed. Therefore, we conclude that BBAVF is the preferred choice for vascular access if RCAVF or BCAVF creation is impossible, or when these types of access have already failed.
Background
Carotid intima-media thickness (CIMT) is increasingly used as a prognostic indicator for early atherosclerosis and the development of cardiovascular disease. The objective of this study is ...to assess the exact effects of bariatric surgery on CIMT reduction in different age groups.
Methods
CIMT was measured just proximal to the bifurcation of the carotid artery in 166 patients with mean body mass index of 43.4 kg/m
2
before and at 6 and 12 months after bariatric surgery. Preoperative CIMT and Framingham Risk Score (FRS) were compared to measurements at 6 and 12 months, postoperatively. Impact of age on CIMT change and cardiovascular risk reduction was analyzed.
Results
Median follow-up was 12 months; 12% were lost to follow-up. Mean CIMT values at 12 months after bariatric surgery were significantly lower compared to baseline (0.619 vs. 0.587 mm,
p
= 0.005 in women and 0.675 vs. 0.622 mm,
p
= 0.037 in men, respectively), and these effects were statistically significant in all age groups. The mean reduction of CIMT for patients < 50 years at 12 months was 0.043 mm (− 7.0%), while CIMT was reduced with 0.013 mm for patients ≥ 50 years (− 1.9%,
p
= 0.022). At 12 months after bariatric surgery, FRS had decreased with 52% in patients < 50 years as compared with 35% in patients ≥ 50 years (
p
= 0.025).
Conclusions
Bariatric surgery resulted in a significant CIMT decrease in patients with morbid obesity in all evaluated age categories. These beneficial effects of bariatric surgery were more pronounced in younger patients, while cardiovascular risk reduction by bariatric surgery appeared inferior in patients of 50 years and older.
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