As uterine rupture may affect as many as 11/1000 women with 1 prior cesarean birth and 5/10.000 women with unscarred uterus undergoing labor induction, we intended to estimate the prevalence of such ...rare outcome when PGE2 is used for cervical ripening and labor induction.
We searched MEDLINE, ClinicalTrials.gov and the Cochrane library up to September 1st 2020. Retrospective and prospective cohort studies, as well as randomized controlled trials (RCTs) on singleton viable pregnancies receiving PGE2 for cervical ripening and labor induction were reviewed. Prevalence of uterine rupture was meta-analyzed with Freeman-Tukey double arcsine transformation among women with 1 prior low transverse cesarean section and women with unscarred uterus.
We reviewed 956 full text articles to include 69 studies. The pooled prevalence rate of uterine rupture is estimated to range between 2 and 9 out of 1000 women with 1 prior low transverse cesarean (5/1000; 95%CI 2-9/1000, 122/9000). The prevalence of uterine rupture among women with unscarred uterus is extremely low, reaching at most 0.7/100.000 (<1/100.000.000; 95%CI <1/100.000.000-0.7/100.000, 8/17.684).
Uterine rupture is a rare event during cervical ripening and labor induction with PGE2.
To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized ...patients with COVID19 not requiring Invasive Mechanical Ventilation IMV, are: a)more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: 1.Death2.Acute Myocardial Infarction AMI3.Objectively confirmed, symptomatic arterial or venous thromboembolism TE4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were receiving standard oxygen therapy5.IMV in patients who at randomisation were receiving non-invasive mechanical ventilationb)Similar in terms of major bleeding risk TRIAL DESIGN: Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study.
Inpatients will be recruited from 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit.
1. Age > 18 and < 80 years 2. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 3. Severe pneumonia defined by the presence of at least one of the following criteria: a.Respiratory Rate ≥25 breaths /minb.Arterial oxygen saturation≤93% at rest on ambient airc.PaO2/FiO2 ≤300 mmHg 4. Coagulopathy, defined by the presence of at least one of the following criteria: a.D-dimer >4 times the upper level of normal reference rangeb.Sepsis-Induced Coagulopathy (SIC) score >4 5. No need of IMV EXCLUSION CRITERIA: 1. Age <18 and >80 years 2. IMV 3. Thrombocytopenia (platelet count < 80.000 mm3) 4. Coagulopathy: INR >1.5, aPTT ratio > 1.4 5. Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min) 6. Known hypersensitivity to enoxaparin 7. History of heparin induced thrombocytopenia 8. Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations) 9. Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves) 10. Concomitant double antiplatelet therapy 11. Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed 12. Pregnancy or breastfeeding or positive pregnancy test 13. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 14. Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 UI subcutaneously once day). Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table. This dose is commonly used in Italy when a bridging strategy is required for the management of surgery or invasive procedures in patients taking anti-vitamin K oral anticoagulants Body Weight (kg)Enoxaparin dose every 12 hours (IU)<50200050-69400070-89600090-1108000>11010000 The treatment with Enoxaparin will be initiated soon after randomization (maximum allowed starting time 12h after randomization). The treatment will be administered every 12 hours in the intervention group and every 24 hours in the control group. Treatments will be administered in the two arms until hospital discharge or the primary outcomes detailed below occur.
Primary Efficacy Endpoint: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: 1.Death2.Acute Myocardial Infarction AMI3.Objectively confirmed, symptomatic arterial or venous thromboembolism TE4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces5.Need for IMV, in patients who at randomisation were in Cpap or NIV Time to the occurrence of each of these events will be recorded. Clinical worsening will be analysed as a binary outcome as well as a time-to-event one. Secondary Efficacy Endpoints: Any of the following events occurring within the hospital stay 1.Death2.Acute Myocardial Infarction AMI3.Objectively confirmed, symptomatic arterial or venous thromboembolism TE4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces5.Need for IMV in patients who at randomisation were in Cpap or NIV6.Improvement of laboratory parameters of disease severity, including: o D-dimer levelo Plasma fibrinogen levelso Mean Platelet Volumeo Lymphocyte/Neutrophil ratioo IL-6 plasma levels MORTALITY AT 30 DAYS: Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Primary safety endpoint: Major bleeding, defined as an acute clinically overt bleeding associated with one or more of the following: Decrease in haemoglobin of 2 g/dl or more;Transfusion of 2 or more units of packed red blood cells;Bleeding that occurs in at least one of the following critical sites intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal;Bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death);Bleeding that necessitates surgical intervention Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Secondary safety endpoint: Clinically Relevant non-major bleeding, defined as an acute clinically overt bleeding that does not meet the criteria for major and consists of: 1.Any bleeding compromising hemodynamic2.Spontaneous hematoma larger than 25 cm2, or 100 cm2 if there was a traumatic cause3.Intramuscular hematoma documented by ultrasonography4.Epistaxis or gingival bleeding requiring tamponade or other medical intervention5.Bleeding from venipuncture for >5 minutes6.Haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures7.Haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention8.Any other bleeding requiring temporary cessation of a study drug. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one.
Randomisation (with a 1:1 randomisation ratio) will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (<75/≥75 years); 3) BMI (<30/≥30); 4) Comorbidities (0-1/>2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment. Blinding (masking) The study is conceived as open-label: patients and all health-care personnel involved in the study will be aware of the assigned group.
The target sample size is based on the hypothesis that LMWH administered at high doses versus low doses will significantly reduce the risk of clinical worsening. The overall sample size in this study is expected to be 300 with 150 in the Low-Dose LMWH control group and 150 in the High-Dose LMWH intervention group, recruited over 10-11 months. Assuming an alpha of 5% (two tailed) and a percentage of patients who experience clinical worsening in the control group being between 25% and 30%, the study will have 80% power to detect at least 50% relative reduction in the risk of death between low and high doses of heparin.
Protocol version 1.2 of 11/05/2020. Recruitment start (expected): 08/06/2020 Recruitment finish (expected): 30/04/2021 Trial registration EudraCT 2020-001972-13, registered on April 17th, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in 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.
A transparent and evidence-based priority-setting process promotes the optimal use of resources to improve health outcomes. Decision-makers and funders have begun to increasingly engage ...representatives of patients and healthcare consumers to ensure that research becomes more relevant. However, disadvantaged groups and their needs may not be integrated into the priority-setting process since they do not have a "political voice" or are unable to organise into interest groups. Equitable priority-setting methods need to balance patient needs, values, experiences with population-level issues and issues related to the health system.
Objective Transcatheter aortic valve implantation is an emerging technique for the treatment of aortic valve stenosis in high-risk patients. Detailed knowledge of aortic root anatomy, including ...specific information on the extent of native cusp calcifications, is required. The aim of this study was to evaluate whether echocardiographic assessment of aortic stenosis using a calcification score is useful to predict outcomes of transcatheter aortic valve implantation in elderly high-risk patients. Methods Detailed preoperative digitalized transesophageal echocardiographic images were available from 103 patients treated by transapical transcatheter aortic valve implantation between February 2006 and February 2009. On the basis of a previously published study, an index score was developed to describe the extent of valve calcification ranging from 0 to 8 (normal to diffuse calcification). Results The median age of patients was 82.2 ± 5.9 years. The mean logistic European System for Cardiac Operative Risk Evaluation was 33.0% ± 16.3%. Mild paravalvular leak was present in 43 patients (42.2%), and a moderate paravalvular leak was observed in 5 patients (4.9%). Severe regurgitation was not observed in any patient. Logistic regression analysis revealed that the transcatheter aortic valve implantation echocardiographic calcification score is associated with the presence of moderate paravalvular aortic regurgitation (odds ratio, 8.5; 95% confidence interval, 1.2–58.9; P = .0001) and overall moderate aortic regurgitation (odds ratio, 3.6; 95% confidence interval, 1.2–10.4; P = .0006). Conclusions Transesophageal echocardiography demonstrates detailed anatomic information of the calcification patterns of the aortic valve and root and thus plays an important role in the screening of patients undergoing transcatheter aortic valve implantation. The transcatheter aortic valve implantation echocardiographic calcification score allowed prediction of the risk of postoperative paravalvular and overall aortic regurgitation.
Coronary artery bypass grafting (CABG) is the commonest major operation in most developed countries. A single internal mammary artery (IMA) graft has proven survival benefits, but the additional ...survival advantage of a second graft is unknown. We systematically reviewed published studies of bilateral versus single IMA grafts in CABG to assess any differences in survival.
We identified from Medline all studies in which single and bilateral IMA grafts were compared. We included studies in which at least 100 patients in each group had been followed up for at least 4 years. We assessed study quality on the basis of patient selection, comparability of intervention groups (especially for age, sex, ventricular function, and diabetes status), outcome assessment, and completeness of follow-up. Our primary outcome was survival. Estimates of treatment effect (single versus bilateral) expressed as hazard ratios were pooled across studies.
None of the studies was a randomised trial, but nine cohort studies met our inclusion criteria. Seven studies yielded survival data for meta-analysis, and included 15 962 patients: 11 269 single and 4693 bilateral IMA grafts. The bilateral group had significantly better survival than the single group (hazard ratio for death 0·81; 95% Cl 0·70–0·94). Exclusion of methodologically weak studies improved survival rates with bilateral IMA grafts.
Because no study was a randomised trial, our results are more uncertain than is indicated by the 95% Cl. Nevertheless, bilateral IMA grafts seem to give better survival rates than single grafts.
By contrast, Filippini and colleagues examined only attack-free status; the use of complimentary (confirmatory) outcomes—for example, MRI—would have provided convergent validity4 to the clinical ...findings. ...because attack-free status is the same irrespective of whether a patient has one attack or ten, the use of an outcome—eg, attack rate—that captures such clinically relevant information, might be preferable. ...although drop-out bias is an important consideration, the sensitivity analysis used by Filippini and coworkers is problematic. ...even in the face overwhelming evidence, this worst-case method1would cast doubt on the efficacy of drug X. Such a method seems far too stringent to be of any practical use in the assessment of studies.
The spurious precision of the NNT is a statistical artefact which derives not from clinical knowledge but from the illegitimate pooling of the large amounts of qualitatively unlike and clinically ...irrelevant data that are incorporated in almost all megatrials and meta-analyses Unless trials incorporate patients with the same characteristics and the same prognosis and who are being given the same treatment as those to which the trial results will apply, then statistical summary is inevitably misleading. 2 It is somewhat galling that mega-epidemiologists and biostatisticians so routinely take credit for the act of creating spurious analytic tools, and then for belatedly dismantling them-but so it goes. 4 Moreover, we have been able to use large amounts of data from individual patients and clinical trials to investigate the effect of chance on baseline and experimental event rates. 5 Because individual clinical trials are set up to investigate the direction of treatment effect (treatment better than control), we need to know how much information is needed to overcome random effects in estimating the magnitude of the clinical effect of an intervention-or when an NNT becomes clinically valid. 5 NNT is a tool.
The 6 minute walk test has been recently chosen as the primary outcome measure in international multicenter clinical trials in Duchenne muscular dystrophy ambulant patients. The aim of the study was ...to assess the spectrum of changes at 3 years in the individual measures, their correlation with steroid treatment, age and 6 minute walk test values at baseline. Ninety-six patients from 11 centers were assessed at baseline and 12, 24 and 36 months after baseline using the 6 minute walk test and the North Star Ambulatory Assessment. Three boys (3%) lost the ability to perform the 6 minute walk test within 12 months, another 13 between 12 and 24 months (14%) and 11 between 24 and 36 months (12%). The 6 minute walk test showed an average overall decline of -15.8 (SD 77.3) m at 12 months, of -58.9 (SD 125.7) m at 24 months and -104.22 (SD 146.2) m at 36 months. The changes were significantly different in the two baseline age groups and according to the baseline 6 minute walk test values (below and above 350 m) (p<0.001). The changes were also significantly different according to steroid treatment (p = 0.01). Similar findings were found for the North Star Ambulatory Assessment. These are the first 36 month longitudinal data using the 6 minute walk test and North Star Ambulatory Assessment in Duchenne muscular dystrophy. Our findings will help not only to have a better idea of the progression of the disorder but also provide reference data that can be used to compare with the results of the long term extension studies that are becoming available.
The aim of the study was to establish 24 month changes in upper limb function using a revised version of the performance of upper limb test (PUL 2.0) in a large cohort of ambulant and non-ambulant ...boys with Duchenne muscular dystrophy and to identify possible trajectories of progression. Of the 187 patients studied, 87 were ambulant (age range: 7-15.8 years), and 90 non-ambulant (age range: 9.08-24.78). The total scores changed significantly over time (p<0.001). Non-ambulant patients had lower total scores at baseline (mean 19.7) when compared to the ambulant ones (mean 38.4). They also had also a bigger decrease in total scores over 24 months compared to the ambulant boys (4.36 vs 2.07 points). Multivariate model analysis showed that the Performance of Upper Limb changes reflected the entry level and ambulation status, that were independently associated to the slope of Performance of Upper Limb changes. This information will be of help both in clinical practice and at the time of designing clinical trials.
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