Can we still consider treatment with colchicine effective in SARS-COV-2 infection? Systematic review, meta-analysis, and trial sequential analysis.

OBJECTIVE: To assess the effectiveness of colchicine, compared with standard of care, for reducing mortality, admission to intensive care, and use of mechanical ventilation. MATERIALS AND METHODS: We performed a systematic review, meta-analysis, and sequential trial analysis. The terms (SARS-CoV-2 OR COVID-19 OR coronavirus) AND (colchicine) were searched in MEDLINE, Scopus, Embase, Cochrane Central Register of Controlled Trials, and preprint repositories (February 2020 to April 2021, extended to June 2021). Risk of bias for randomised controlled trials and observational studies were assessed using the tools RoB 2.0 and ROBINS-I, respectively. We performed subgroup analyses based on study design and sensitivity analyses based on time of colchicine administration. RESULTS: We included six observational studies (1329 patients) and five clinical trials (16,048 patients). All studies but one were conducted in the hospital setting. Colchicine treatment was not associated with a significant decrease in mortality (RR 0.93, 95% CI 0.87 to 1; p=0.06, I2=72%) with a significant subgroup effect (p<0.001) depending on the design of the studies. The drug was effective in observational studies (RR 0.57, 95% CI 0.46 to 0.70, p<0.001, I2=50%) but not in clinical trials (RR 0.99, 95% CI 0.92 to 1.07, p=0.89, I2=21%). The effect of colchicine on intensive care admissions and the need for mechanical ventilation could not be confirmed. Trial sequential boundaries for cumulative meta-analyses of randomised controlled trials suggested no significant effect on mortality (p=0.182) beyond the optimal information size (13,107 patients). CONCLUSIONS: Our results suggest that colchicine treatment has no effect on mortality in hospitalised patients with SARS-CoV-2 infection, and that no further confirmatory clinical trials are needed owing to futility.

Clinical research in critical care. Difficulties and perspectives. / Investigación en el enfermo crítico. Dificultades y perspectivas.

In the field of Intensive Care Medicine, improved survival has resulted from better patient care, the early detection of clinical deterioration, and the prevention of iatrogenic complications, while research on new treatments has been followed by an overwhelming number of disappointments. The origins of these fiascos must be sought in the conjunction of methodological problems - common to other disciplines - and the particularities of critically ill patients. The present article discusses both aspects and suggests some options for progress.

Routine invasive strategy in acute coronary syndrome patients with renal dysfunction. Results of the ARIAM-SEMICYUC registry. / Estrategia invasiva de rutina en el síndrome coronario agudo sin elevación del segmento ST con disfunción renal. Resultados del registro ARIAM-SEMICYUC.

OBJECTIVE: To evaluate the use and effectiveness of a routine invasive strategy (RIS) in patients with acute coronary syndrome without persistent ST-segment elevation with renal dysfunction in the real world scenario. METHODS: A retrospective cohort study based on the ARIAM-SEMICYUC Registry (2011-2014) was carried out. Renal dysfunction was defined as GFR (Cockroft-Gault)<60ml/min (moderate dysfunction) or<30ml/min (severe dysfunction). Patients in which early angiography (<72h) was performed due to cardiogenic shock or recurrent myocardial ischemia were excluded. The primary endpoint was hospital mortality. Confounding factors were controlled using propensity score analysis. RESULTS: A total of 4,279 patients were analyzed, of which 26% had moderate renal dysfunction and 5% severe dysfunction. Patients with renal dysfunction had greater severity and comorbidity, higher hospital mortality (8.6 vs. 1.8%), and lesser use of the RIS (40 vs. 52%). The adjusted OR for mortality in patients without/with renal dysfunction were 0.38 (95% confidence interval [95%CI] 0.17 to 0.81) and 0.52 (95%CI 0.32 to 0.87), respectively (interaction P-value=.4779). The impact (adjusted risk difference) of RIS was higher in the group with renal dysfunction (-5.1%, 95%CI -8.1 to -2.1 vs. -1.6%, 95%CI -2.6 to -0.6; interaction P-value=.0335). No significant interaction was detected for the other endpoints considered (ICU mortality, 30-day mortality, myocardial infarction, acute renal failure or moderate/severe bleeding). CONCLUSIONS: The results suggest that the effectiveness of IRS is similar in patients with normal or abnormal renal function, and alert to the under-utilization of this strategy in such patients.

[Accessibility to health care of diabetic patients with acute coronary syndrome ST-segment elevation]. / Accesibilidad al sistema sanitario de los pacientes diabéticos con síndrome coronario agudo con elevación del segmento ST.

OBJECTIVES: To measure accessibility to health care among diabetic patients and analyze whether differences in delay explain differences in hospital mortality. METHODS: A retrospective cohort study was conducted in diabetic patients with acute coronary syndrome with ST-segment elevation included in the ARIAM-SEMICYUC registry (2010-2013). Crude and adjusted analyses were performed using unconditional logistic regression. RESULTS: A total of 4817 patients were analyzed, of whom 1070 (22.2%) were diabetics. No differences were found in access to health care between diabetic and non-diabetic patients. Diabetic patients presented with longer patient delay (90 min vs. 75 min; p=.004) and prehospital delay (150 min vs. 130 min; p=.002). Once the health system was contacted, diabetic patients had a lower reperfusion rate (50% vs. 57.7%; p<.001), but no longer delay in treatment was observed compared with the non-diabetic individuals. Diabetic patients have greater in-hospital mortality (12.5 vs. 6%; p <.001), though neither patient delay nor prehospital delay were identified as independent predictors of in-hospital mortality. CONCLUSIONS: Diabetic patients had a longer delay in access to health care, though such delay was not independently related to increased mortality.

[Predictors of the use of the early invasive strategy in women with non-ST-elevation acute coronary syndrome]. / Predictores del uso de la estrategia invasiva precoz en mujeres con síndrome coronario agudo sin elevación de ST.

OBJECTIVE: To identify determinants associated to an early invasive strategy in women with acute coronary syndromes without ST elevation (NSTE-ACS). DESIGN: A retrospective cohort study was made. Crude and adjusted analysis of the performance of the early invasive strategy using logistic regression. SETTING: Coronary Units enrolled in 2010 - 2011 in the ARIAM-SEMICYUC registry. PATIENTS: A total of 440 women with NSTE-ACS were studied. Sixteen patients were excluded due to insufficient data, together with 58 patients subjected to elective coronary angiography (> 72 h). VARIABLES ANALYZED: Demographic parameters, coronary risk factors, previous medication, comorbidity. Clinical, laboratory, hemodynamic and electrocardiographic data of the episode. RESULTS: Women treated conservatively were of older age, had oral anticoagulation, diabetes, previous coronary lesions, and heart failure (p<0.005), increased baseline bleeding and ischemic risk (p=0.05) and a higher heart rate upon admission (p<0.05). After adjustment, only age > 80 years (OR 0.48, 95% CI 0.27 to 0.82, p=0.009), known coronary lesions (OR 0.47, 95% CI 0.26-0.84, p=0.011), and heart rate (OR 0.98, 95% CI 0.97-0.99, p=0.003) were independently associated to conservative treatment. Smoking (OR 2.50, 95% CI 1.20 to 5.19, p=0.013) and high-risk electrocardiogram (OR 2.96, 95% CI 1.72 to 4.97, p<0.001) were associated to the early invasive strategy. The exclusion of early deaths (<24 h) did not alter these results. CONCLUSIONS: In women with NSTE ACS, smoking and a high-risk electrocardiogram upon admission were independent factors associated to the early invasive strategy. Previous coronary lesions, age > 80 years and increased heart rate were independent factors associated to conservative treatment.

[New recommendations on the use of human albumin solutions in patients with severe sepsis and septic shock. A critical evaluation of the literature]. / Nuevas recomendaciones sobre la utilización de soluciones de albúmina humana en pacientes con sepsis grave y shock séptico. Una evaluación crítica de la literatura.

The third edition of the Surviving Sepsis Campaign guidelines opens the door to the use of albumin for fluid resuscitation in patients with severe sepsis and septic shock. This recommendation is based on a recent meta-analysis that included studies with evidence of insufficient plasma expansion in the control group and studies performed in children with malaria with clear statistical heterogeneity (P for interaction=.02). After excluding pediatric studies, the confidence interval of the effect estimate was consistent with a mortality excess in the group treated with albumin (OR=.87 [95%CI: .71 to 1.07]). Two new randomized studies reported after publication of the meta-analysis found no benefit in patients treated with albumin. Given the uncertainty about the true effect of albumin (due to the existence of indirectness and imprecision) and its cost considerations, it is suggested not to use albumin in the initial resuscitation of patients with severe sepsis and septic shock (GRADE2C).

[Thrombolysis in acute ischemic stroke in centers lacking a stroke unit: referral to reference center or on-site treatment?]. / Trombolisis en el ictus isquémico agudo en centros sin unidad de ictus: ¿derivación a centro de referencia o tratamiento in situ?

OBJECTIVE: To assess the clinical impact of on-site thrombolysis versus referral to another hospital in patients with ischemic stroke attended in a hospital lacking a stroke unit. DESIGN: Expected value decision analysis and Monte Carlo simulation. PATIENTS AND SETTING: Decision analysis based on a cohort study (SIT-MOST) and a meta-analysis of randomized trials of thrombolysis versus placebo in patients with acute ischemic stroke. INTERVENTIONS: On-site thrombolysis (in hospitals lacking a stroke unit) versus delayed thrombolysis in a reference hospital. MAIN OUTCOMES: Neurological outcome (modified Rankin scale) three months after admission according to the delay in the administration of thrombolysis. RESULTS: At baseline (initial delay of 135 min, travel time 60 minutes), on-site treatment was more effective than referral to another hospital (number of patients with favorable neurological outcome 45.3% versus 41.3%). In patients seen within 45 minutes of the onset of symptoms, for every 10 patients transferred there was an additional case with an unfavorable neurological outcome that could have been avoided with on-site thrombolysis. In the Monte Carlo analysis, biased against on-site treatment by a reduction in effectiveness of 30%, on-site treatment was superior to patient referral in 77.2% of the cases. CONCLUSIONS: The available evidence does not support the recommendations of the national stroke strategy or some regional plans that discourage the administration of thrombolysis in hospitals without stroke units.

[Early invasive strategy in non-ST-segment elevation acute coronary syndrome. The paradox continues]. / Uso de la estrategia invasiva precoz en el síndrome coronario agudo sin elevación de ST. La paradoja continúa.

OBJECTIVE: Observational studies have reported a paradoxical inverse relationship between the use of an early invasive strategy (EIS) and the risk of events in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS). The study objectives are: 1) to examine the association between baseline risk in patients with NSTE ACS and the use of EIS; and 2) to identify some of the factors independently associated to the use of EIS. DESIGN: Retrospective cohort study. SETTING: Intensive care units participating in the SEMICYUC ARIAM Registry. PATIENTS: Consecutive patients admitted with a diagnosis of NSTE-ACS within 48 hours of evolution between the months of April-July 2010. INTERVENTIONS: None. MAIN OUTCOMES: Coronary angiography with or without angioplasty within 72 hours, risk stratification using the GRACE scale. RESULTS: We analyzed 543 patients with NSTE-ACS, of which 194 were of low risk, 170 intermediate risk and 179 high risk. The EIS was used in 62.4% of the patients at low risk, in 60.2% of those with intermediate risk, and in 49.7% of those at high risk (p for tendency 0.0144). The EIS was used preferentially in patients with low severity and comorbidity. In the logistic regression model, EIS was independently associated to the availability of a catheterization laboratory (OR 2.22 [CI 95% 1.55 to 3.19]), the presence of ST changes on ECG (OR 1.80 [1.23 to 2.64]), or the existence of a low risk of bleeding (OR 0.76 [0.66 to 0.88)]. Conversely, EIS was less prevalent in patients with diabetes (OR 0.60 [0.41 to 0.88]) or tachycardia upon admission (OR 0.54 [0 36 to 0.82]). CONCLUSIONS: In 2010 there remained a lesser relative use of EIS in patients at high risk, due in part to an increased risk of bleeding in these patients.

Intensity of continuous renal replacement therapies in patients with severe sepsis and septic shock: a systematic review and meta-analysis.

The purpose of this study was to assess the efficacy of continuous renal replacement therapies in patients with severe sepsis or septic shock, with or without acute kidney injury. We performed a systematic search in Medline, Embase, Web of Knowledge, Cochrane Library and Clinicaltrials.gov and a hand search of the retrieved studies. We included both randomised controlled clinical trials and subgroups of randomised trials that assessed the effect of continuous renal replacement therapies (at traditional or high doses) and reported clinical outcomes in adult patients with severe sepsis or septic shock. The study selection and data extraction were performed by duplicate. Analysis of heterogeneity and meta-analysis was performed according to the Cochrane Collaboration guidelines for conducting systematic reviews of interventions. Twelve studies (1895 patients) met the inclusion criteria. Pooling of all studies resulted in a mortality risk ratio of 0.96 (95% confidence interval 0.83 to 1.12). The studies showed moderate statistical heterogeneity (I2 statistic 52%, P = 0.02). The effect on mortality was not modified (interaction P values non significant) by the dose of continuous renal replacement therapies, the severity of illness or the risk of bias. The available evidence suggests that these therapies in patients with severe sepsis or septic shock are not associated with an improvement in other outcomes such as haemodynamics, pulmonary gas exchange, multiple organ dysfunction syndrome or length of stay. The best available evidence does not support the routine use of continuous renal replacement therapies (at traditional or high doses) in patients with severe sepsis or septic shock.

[Quality indicators in the acute coronary syndrome for the analysis of the pre- and in-hospital care process]. / Indicadores de calidad en el síndrome coronario agudo para el análisis del proceso asistencial pre e intrahospitalario.

We present a map of 27 indicators to measure the care quality given to patients with acute coronary syndrome attended in the pre- and hospital area. This includes technical process indicators (registration of care intervals, performance of electrocardiogram, monitoring and vein access, assessment of prognostic risk, hemorrhage and in-hospital mortality, use of reperfusion techniques and performance of echocardiograph), pharmacological process indicators (platelet receptors inhibition, anticoagulation, thrombolysis, beta-blockers, angiotensin converting inhibitors and lipid lowering drugs) and outcomes indicators (quality scales of the care given and mortality).

[Prognostic value of the sTREM-1 plasma values in patients with sepsis: a cohort study]. / Valor pronóstico de los niveles plasmáticos de sTREM-1 en pacientes con sepsis: un estudio de cohortes.

OBJECTIVE: To evaluate the association between plasma levels of soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) and mortality of patients with sepsis. DESIGN: Prospective cohort study. SETTING: Two general Intensive Care Units. PATIENTS: Patients with sepsis in whom sTREM-1 plasma levels were determined daily in the first 3 days of their presentation. VARIABLES OF INTEREST: Mortality at 28 days. RESULTS: We analyzed 121 patients (23% severe sepsis, 44% septic shock, 33% non-severe sepsis). Mortality at 28 days was 24.8%. The initial sTREM-1 levels were slightly higher in nonsurvivors than in survivors (median 366.9 versus 266.5 pg/ml, p=0.2668). An increase in sTREM-1 levels higher than 90 pg/ml within the first 3 days (delta-TREM) was associated with an excess of mortality (hazard ratio [HR] 2.68, p=0.0047), with a sensitivity of 47% and a specificity of 78%. This excess of mortality disappeared after adjusting for severity by Cox analysis (adjusted HR 1.07, p=0.8665). CONCLUSIONS: The increase in the levels of sTREM-1 during the first 3 days of evolution is associated with an excess of mortality in critically ill patients with sepsis. This is explained by the greater initial severity of these patients. The discriminative capacity of this finding is insufficient to be clinically useful.

[Gender bias in women with myocardial infarction: ten years after]. / Desigualdad de esfuerzo terapéutico en mujeres con infarto agudo de miocardio: 10 años después.

OBJECTIVE: Previous studies show that the women with acute myocardial infarction (AMI) receive less fibrinolitic treatment than the men. The objective of this study is to analyze if it exists any difference in fibrinolysis related to gender and to compare the results with those obtained 10 years ago. DESIGN: Retrospective descriptive study that compare patients with AMI of less than 24 hours of evolution of studies Analysis of Delay in Acute Infarct of Myocardium (ARIAM) in 2003-2004 and Project of Analysis Epidemiologist of Critical Patient (PAEEC) of 1992-1993. SETTING: ICUs from 86 hospitals in Spain that participated in the PAEEC study and 120 ICUs in the ARIAM. PATIENTS: We compared data of 9,981 patients including in study ARIAM in 2003-2004 with 1,668 of the PAEEC of 1992-1993. RESULTS: Women were less likely to receive thrombolytic therapy than men (odds ratio= 0.82, p < 0.01), after adjusting for age, origin, size of the hospital and antecedents. The probability of fibrynolisis is lower in elderly, patients referred from the general ward, in hospitals of more than 1,000 beds and patients with arterial hypertension, stroke, diabetes or peripheral vascular disease. The probability of fibrinólisis is higher when patient is transferred from another hospital (followed by those of Emergencies Room), in the hospitals by less than 300 beds (followed by those of 300-1,000) and when history of prior ischemic heart disease exists. Comparing the two periods, has increased the frequency of fibrynolisis in both genders, although the increment has been greater in the women. CONCLUSIONS: The women with AMI continue receiving less fibrynolisis, although exists an increase in the number of treatments superior to register in the men.

[High PEEP vs. conventional PEEP in the acute respiratory distress syndrome: a systematic review and meta-analysis]. / PEEP alta frente a PEEP convencional en el síndrome de distrés respiratorio agudo. Revisión sistemática y metaanálisis.

OBJECTIVE: To perform a systematic review and meta-analysis of the literature to evaluate the effects of high PEEP versus conventional PEEP on mortality and on the risk of barotrauma in patients with the acute respiratory distress syndrome (ARDS). SOURCE OF DATA: Computer search of Medline, Embase, CINAHL, CANCERLIT, Pascal-Biomed, ACP Journal Club, Cochrane library (CDSR, DARE, CCTR), ISI Proceedings, Current Contents, and Web of Science, as well as manual search of selected references. SELECTION OF STUDIES: Controlled random clinical trials published after NAECC (1994) that evaluated the effect of two levels of PEEP and that reported the mortality and incidence of barotrauma in the series. DATA EXTRACTION: By two investigators working independently, with discrepancies resolved by group consensus. Contingency tables were elaborated and the RRs with corresponding confidence intervals were obtained for each study. RESULTS: Four articles were selected for the meta-analysis of mortality and three for the meta-analysis of barotrauma. No effects of PEEP level on mortality were found (RR 0.73, 95% CI: 0.49 to 1.10) or on the incidence of barotrauma (RR 0.50, 95% CI: 0.14 to 1.73). However, an analysis of the studies in which PEEP was individualized in function of Pflex showed a significant decrease in mortality (RR 0.59, 95% CI: 0.43 to 0.82) (p=0.001) CONCLUSIONS: The use of high or conventional PEEP in function of oxygenation does not affect mortality or the incidence of barotrauma in patients with ARDS. However, there might be a decrease in mortality associated to high PEEP individualized in function of the pulmonary mechanics of each patient.