To analyze the effects of a short course of methyl-prednisolone pulses (MP) during the second week of disease (week-2) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia.
...Comparative observational study using data collected from routine care at Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain in patients with COVID-19 pneumonia. We compared patients who received week-2-MP (125-250 mg/d x3) with those who did not, with the end-points time to death and time to death or endotracheal intubation.
We included 242 patients with COVID-19 pneumonia and elevated inflammatory markers at admission. Sixty-one patients (25%) received week-2-MP. Twenty-two patients (9%) died and 31 (12.8%) suffered death or intubation. The adjusted HRs for death and death or intubation for patients in the week-2-MP group were 0.35 (95%CI 0.11 to 1.06, p = 0.064) and 0.33 (95%CI 0.13 to 0.84, p = 0.020), respectively. These differences were specifically seen in the subcohort of patients with a SpO2/FiO2 at day 7 lower than 353 (adjusted HR 0.31, 95% CI 0.08 to 1.12, p = 0.073 and HR 0.34, 95%CI 0.12 to 0.94, p = 0.038, respectively) but not in patients with higher SpO2/FiO2. Patients receiving out-of-week-2-MP, non-pulse glucocorticoids or no glucocorticoids had an increased adjusted risk for both outcomes compared with week-2-MP group: HR 5.04 (95% CI 0.91-27.86), HR 10.09 (95% CI 2.14-47.50), HR 4.14 (95% CI 0.81-21.23), respectively, for death; HR 7.38 (95% CI 1.86-29.29), HR 13.71 (95% CI 3.76-50.07), HR 3.58 (95% CI 0.89-14.32), respectively, for death or intubation. These differences were significant only in the subgroup with low SpO2/FiO2.
Week-2-MP are effective in improving the prognosis of patients with COVID-19 pneumonia with features of inflammatory activity and respiratory deterioration entering the second week of disease. The recognition of this high-risk population should prompt early use of MP at this point.
To describe the development of a novel on-line database aimed to serve as a source of information concerning healthcare interventions appraised for their clinical value and appropriateness by several ...initiatives worldwide, and to present a retrospective analysis of the appraisals already included in the database.
Database development and a retrospective analysis. The database DianaHealth.com is already on-line and it is regularly updated, independent, open access and available in English and Spanish. Initiatives are identified in medical news, in article references, and by contacting experts in the field. We include appraisals in the form of clinical recommendations, expert analyses, conclusions from systematic reviews, and original research that label any health care intervention as low-value or inappropriate. We obtain the information necessary to classify the appraisals according to type of intervention, specialties involved, publication year, authoring initiative, and key words. The database is accessible through a search engine which retrieves a list of appraisals and a link to the website where they were published. DianaHealth.com also provides a brief description of the initiatives and a section where users can report new appraisals or suggest new initiatives. From January 2014 to July 2015, the on-line database included 2940 appraisals from 22 initiatives: eleven campaigns gathering clinical recommendations from scientific societies, five sets of conclusions from literature review, three sets of recommendations from guidelines, two collections of articles on low clinical value in medical journals, and an initiative of our own.
We have developed an open access on-line database of appraisals about healthcare interventions considered of low clinical value or inappropriate. DianaHealth.com could help physicians and other stakeholders make better decisions concerning patient care and healthcare systems sustainability. Future efforts should be focused on assessing the impact of these appraisals in the clinical practice.
The therapeutic approach is crucial to prostate cancer prognosis. We describe treatments and outcomes for a Spanish cohort of patients with prostate cancer during the first 12 months after diagnosis ...and identify the factors that influenced the treatment they received.This multicenter prospective cohort study included patients with prostate cancer followed up for 12 months after diagnosis. Treatment was stratified by factors such as hospital, age group (<70 and ≥70 years), and D'Amico cancer risk classification. The outcomes were Eastern Cooperative Oncology Group (ECOG) performance status, adverse events (AEs), and mortality. The patient characteristics associated with the different treatment modalities were analyzed using multivariate logistic regression.We included 470 men from 7 Spanish tertiary hospitals (mean (standard deviation) age 67.8 (7.6) years), 373 (79.4%) of which received treatment (alone or in combination) as follows: surgery (n = 163; 34.7%); radiotherapy (RT) (n = 149; 31.7%); and hormone therapy (HT) (n = 142; 30.2%). The remaining patients (n = 97) were allocated to no treatment, that is, watchful waiting (14.0%) or active surveillance (5.7%). HT was the most frequently administered treatment during follow-up and RT plus HT was the most common therapeutic combination. Surgery was more frequent in patients aged <70, with lower histologic tumor grades, Gleason scores <7, and lower prostate-specific antigen levels; while RT was more frequent in patients aged ≥70 with histologic tumor grade 4, and higher ECOG scores. HT was more frequent in patients aged ≥70, with histologic tumor grades 3 to 4, Gleason score ≥8, ECOG ≥1, and higher prostate-specific antigen levels. The number of fully active patients (ECOG score 0) decreased significantly during follow-up, from 75.3% at diagnosis to 65.1% at 12 months (P < .001); 230 (48.9%) patients had at least 1 AE, and 12 (2.6%) patients died.Surgery or RT were the main curative options. A fifth of the patients received no treatment. Palliative HT was more frequently administered to older patients with higher tumor grades and higher Gleason scores. Close to half of the patients experienced an AE related to their treatment.
The therapeutic approach of bladder cancer strongly determines its prognosis. We describe the treatments and outcomes for a Spanish cohort of patients with bladder cancer for the first 12 months ...after diagnosis and identify the factors that influenced the decision to undergo the treatment received. We conducted a multicenter, prospective, cohort study including primary bladder cancer patients during the first 12 months after diagnosis. The clinical outcomes were performance status (ECOG), adverse events and any cause of mortality. We stratified the analysis by factors that might influence the treatments received. We conducted univariate and multivariable logistic regression models to assess which patient and tumor characteristics were associated with receiving adjuvant treatment in the subgroup of noninvasive bladder cancer patients. In total, 314 patients were included (85% men; 53.8% >70 years) in 7 tertiary Spanish hospitals; 82.2% had a noninvasive urothelial bladder cancer (NMIBC). Patients received mostly surgery plus adjuvant therapy (67.7%). BCG (32.8% patients) was the most frequently administered adjuvant therapy, followed by intravesical chemotherapy (17.8% patients) and radiotherapy (10.8%). The variability of administered treatments among hospitals was low. Patients with NMIBC were more likely to receive adjuvant therapy if they had a higher educational level, some comorbidities and a high-grade tumor. The number of fully active patients (ECOG 0) significantly decreased during the first year of follow-up from 58% to 36 % (OR: 2.41, 95%CI 1.82–3.20); at 12-month follow-up 10.8% patients had died from any cause. In conclusion, most of the patients had a NMIBC. Surgery alone or plus adjuvant therapy were the commonest curative options of bladder cancer. BCG therapy was the adjuvant therapy most frequently administered. Higher educational level, presence of comorbidities and a high-grade tumor were associated with adjuvant therapy. Patient performance status was worsening over time. Almost 1 of 10 patients died during the first year of follow-up.
Transplantation of human cultured limbal epithelial stem/progenitor cells (LESCs) has demonstrated to restore the integrity and functionality of the corneal surface in about 76% of patients with ...limbal stem cell deficiency. However, there are different protocols for the expansion of LESCs, and many of them use xenogeneic products, being a risk for the patients' health. We compared the culture of limbal explants on the denuded amniotic membrane in the culture medium-supplemental hormone epithelial medium (SHEM)-supplemented with FBS or two differently produced human sera. Cell morphology, cell size, cell growth rate, and the expression level of differentiation and putative stem cell markers were examined. Several bioactive molecules were quantified in the human sera. In a novel approach, we performed a multivariate statistical analysis of data to investigate the culture factors, such as differently expressed molecules of human sera that specifically influence the cell phenotype. Our results showed that limbal cells cultured with human sera grew faster and contained similar amounts of small-sized cells, higher expression of the protein p63α, and lower of cytokeratin K12 than FBS cultures, thus, maintaining the stem/progenitor phenotype of LESCs. Furthermore, the multivariate analysis provided much data to better understand the obtaining of different cell phenotypes as a consequence of the use of different culture methodologies or different culture components.
Controlled donation after circulatory death (cDCD) has been associated with a high incidence of ischemic cholangiopathy and other perioperative complications. In an attempt to avoid these ...complications, we implemented an active protocol of cDCD liver transplant (LT) with normothermic regional perfusion (NRP) preservation.
This is a descriptive analysis of data collected from a prospective date base of cDCD LT preserved with NRP from January 2015 to June 2017 with a minimum follow up of 9 months.
Fifty-seven potential cDCD donors were connected to the NRP system. Of these, 46 livers were transplanted over a 30-month period (80% liver recovery rate). The median posttransplant peak in alanine transaminase was 1136 U/L (220-6683 U/L). Seven (15%) patients presented postreperfusion syndrome and 11 (23%) showed early allograft dysfunction. No cases of ischemic cholangiopathy were diagnosed, and no graft loss was observed over a medium follow-up period of 19 months. Of note, 13 donors were older than 65 years, achieving comparable perioperative and midterm results to younger donors.
As far as we know, this represents the largest published series of cDCD LT with NRP preservation. Our results demonstrate that cDCD liver grafts preserved with NRP appear far superior to those obtained by the conventional rapid recovery technique.
To assess the repeatability and reliability of the most important tomographic parameters for characterising keratoconus measured with a Pentacam HR (high resolution).
Overall, 230 eyes in 158 ...patients with keratoconus were analysed. We performed five consecutive corneal tomography examinations for each eye with a Pentacam HR in patients with keratoconus. Study eyes were classified into three groups depending on the maximum posterior elevation (max_BFS_post): grade 1 for cases of keratoconus with a max_BFS_post of 40 µm; grade 2 for those with a max_BFS_post of between 41 and 75 µm and grade 3 for those with a max_BFS_post of over 75 µm. We calculated the intraclass correlation coefficients (ICCs) and repeatability limits of parameters from tomography and aberrometry.
All the parameters were found to have excellent ICCs (0.9). The repeatability limits for the key parameters were higher than 0.5D for the power parameters, 20° for the axis of corneal astigmatism and 10 µm for the thinnest corneal thickness. Further, we obtained repeatability limits of above 0.1 µm for the aberrometry values and overall greater than 15° for the coma axis. All the values increase with the severity of keratoconus, except for that of the coma axis which falls with keratoconus grade.
The reliability indicated by ICCs supports the view that the Pentacam HR is useful for the diagnosis of keratoconus. The repeatability limits suggest that new criteria should be established for monitoring progression taking into account the real measurements that can be made using this system.
Background
The decision of whether frozen embryo transfer (FET) should be performed in the cycle immediately after OPU or at least one cycle later is controversial. FET could improve pregnancy rates ...in IVF; however, how much time is needed for the endometrium to return to optimal receptivity after ovarian stimulation is not known.
Methods
Electronic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies providing data on the influence of the interval between embryo freezing (or OPU) and FET in FET cycles published between January 1, 2007, and February 1, 2020.
Main findings
Data analyzed indicated that in the immediate FET cycles, there was a trend to an increased biochemical pregnancy rate (RR = 1.08; CI = 1.00‐1.18), whereas the clinical pregnancy rate was somewhat higher, but without reaching statistical significance (RR = 1.07; CI = 0.99‐1.15). The live birth rate was similar in the two groups (RR = 1.05; CI = 0.95‐1.15), as was the implantation rate (RR = 0.98; CI = 0.83‐1.16). Stratifying by embryo stage or FET type (freeze‐all or FET after failed fresh transfer) showed no differences.
Conclusion
Systematically delaying FET does not offer benefits to IVF outcomes. In addition, immediate transfer is associated with a nonsignificant trend to better clinical pregnancy rate and it also avoids the psychological effects of prolonging the stress on prospective parents.
These meta‐analysis showed that systematically delaying FET does not offer benefits to IVF outcomes. In addition, immediate transfer is associated with a non‐significant trend to better clinical PR and it also avoids the psychological effects of prolonging the stress on prospective parents.
To assess the reliability and repeatability of the parameters obtained using a Scheimpflug system (Pentacam HR-high resolution) for monitoring progression in eyes with keratoconus.
A prospective ...study was conducted based on measurements taken with the Pentacam HR in 82 eyes with keratoconus. We calculated the intraclass correlation coefficient (ICC) and the repeatability limit for topographic and aberrometric parameters.
All the parameters analyzed had excellent ICCs, above 0.95 in all cases, except for the measurement of the anterior best-fit sphere, for which the ICC was 0.873. The key repeatability limits for the parameters analyzed were as follows: 1.54 diopters (D) for the maximum keratometry in the central cornea, 1.08 D for maximum keratometry, 32.6 degrees for the axis of corneal astigmatism, 11.9 degrees for the coma axis, and 14.2 μm for thinnest corneal thickness.
The level of repeatability of the measurements obtained with a Pentacam HR confirms the usefulness of this system for the diagnosis of keratoconus. Nevertheless, it has certain limitations for monitoring individual progression of keratoconus and planning intrastromal corneal ring segment insertion.
The estimation of the Sample Size Requirement (SSR) when using a binary composite endpoint (i.e. two or more outcomes combined in a unique primary endpoint) is not trivial. Besides information about ...the rate of events for each outcome, information about the strength of association between the outcomes is crucial, since it can determine an increase or decrease of the SSR. Specifically, the greater the strength of association between outcomes the higher the SSR. We present Bin-CE, a free tool to assist clinicians for computing the SSR for binary composite endpoints. In a first step, the user enters a set of candidate outcomes, the assumed rate of events for each outcome and the assumed effect of therapy on each outcome. Since the strength of the association between outcomes is usually unknown, a semi-parametric approach linking the a priori clinical knowledge of the potential degree of association between outcomes with the exact values of these parameters was programmed with Bin-CE. Bin-CE works with a recursive algorithm to choose the best combination of outcomes that minimizes the SSR. In addition, Bin-CE computes the sample size using different algorithms and shows different figures plotting the magnitude of the sample size reduction, and the effect of different combinations of outcomes on the rate of the primary endpoint. Finally, Bin-CE is programmed to perform sensitivity analyses. This manuscript presents the mathematic bases and introduces the reader to the use of Bin-CE using a real example.
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