Background
Good neurological outcome after cardiac arrest is difficult to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. ...Experimental evidence suggests that therapeutic hypothermia is beneficial, and several clinical studies on this topic have been published. This review was originally published in 2009; updated versions were published in 2012 and 2016.
Objectives
We aimed to perform a systematic review and meta‐analysis to assess the influence of therapeutic hypothermia after cardiac arrest on neurological outcome, survival and adverse events.
Search methods
We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10); MEDLINE (1971 to May 2015); EMBASE (1987 to May 2015); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1988 to May 2015); and BIOSIS (1989 to May 2015). We contacted experts in the field to ask for information on ongoing, unpublished or published trials on this topic.The original search was performed in January 2007.
Selection criteria
We included all randomized controlled trials (RCTs) conducted to assess the effectiveness of therapeutic hypothermia in participants after cardiac arrest, without language restrictions. We restricted studies to adult populations cooled by any cooling method, applied within six hours of cardiac arrest.
Data collection and analysis
We entered validity measures, interventions, outcomes and additional baseline variables into a database. Meta‐analysis was performed only for a subset of comparable studies with negligible heterogeneity. We assessed the quality of the evidence by using standard methodological procedures as expected by Cochrane and incorporated the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.
Main results
We found six RCTs (1412 participants overall) conducted to evaluate the effects of therapeutic hypothermia ‐ five on neurological outcome and survival, one on only neurological outcome. The quality of the included studies was generally moderate, and risk of bias was low in three out of six studies. When we compared conventional cooling methods versus no cooling (four trials; 437 participants), we found that participants in the conventional cooling group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.18 to 3.21). The quality of the evidence was moderate.
Across all studies that used conventional cooling methods rather than no cooling (three studies; 383 participants), we found a 30% survival benefit (RR 1.32, 95% CI 1.10 to 1.65). The quality of the evidence was moderate.
Across all studies, the incidence of pneumonia (RR 1.15, 95% CI 1.02 to 1.30; two trials; 1205 participants) and hypokalaemia (RR 1.38, 95% CI 1.03 to 1.84; two trials; 975 participants) was slightly increased among participants receiving therapeutic hypothermia, and we observed no significant differences in reported adverse events between hypothermia and control groups. Overall the quality of the evidence was moderate (pneumonia) to low (hypokalaemia).
Authors' conclusions
Evidence of moderate quality suggests that conventional cooling methods provided to induce mild therapeutic hypothermia improve neurological outcome after cardiac arrest, specifically with better outcomes than occur with no temperature management. We obtained available evidence from studies in which the target temperature was 34°C or lower. This is consistent with current best medical practice as recommended by international resuscitation guidelines for hypothermia/targeted temperature management among survivors of cardiac arrest. We found insufficient evidence to show the effects of therapeutic hypothermia on participants with in‐hospital cardiac arrest, asystole or non‐cardiac causes of arrest.
Aims
This meta‐analysis aims to compare the diagnostic performance of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) in the assessment of liver fibrosis using ...liver biopsy (LB) as ‘gold‐standard’.
Methods
PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases were searched for all studies published until 31 May 2012 that evaluated the liver stiffness by means of ARFI, TE and LB. Information ed from each study according to a fixed protocol included study design and methodological characteristics, patient characteristics, interventions, outcomes and missing outcome data.
Results
Thirteen studies (11 full‐length articles and 2 s) including 1163 patients with chronic hepatopathies were included in the analysis. Inability to obtain reliable measurements was more than thrice as high for TE as that of ARFI (6.6% vs. 2.1%, P < 0.001). For detection of significant fibrosis, (F ≥ 2) the summary sensitivity (Se) was 0.74 (95% CI: 0.66–0.80) and specificity (Sp) was 0.83 (95% CI: 0.75–0.89) for ARFI, while for TE the Se was 0.78 (95% CI: 0.72–0.83) and Sp was 0.84 (95% CI: 0.75–0.90). For the diagnosis of cirrhosis, the summary Se was 0.87 (95% CI: 0.79–0.92) and Sp was 0.87 (95% CI: 0.81–0.91) for ARFI elastography, and, respectively, 0.89 (95% CI: 0.80–0.94) and 0.87 (95% CI: 0.82–0.91) for TE. The diagnostic odds ratio of ARFI and TE did not differ significantly in the detection of significant fibrosis mean difference in rDOR = 0.27 (95% CI: 0.69–0.14) and cirrhosis mean difference in rDOR = 0.12 (95% CI: 0.29–0.52).
Conclusion
Acoustic radiation force impulse elastography seems to be a good method for assessing liver fibrosis, and shows higher rate of reliable measurements and similar predictive value to TE for significant fibrosis and cirrhosis.
Good neurologic outcome after cardiac arrest is hard to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence ...suggests that therapeutic hypothermia is beneficial, and a number of clinical studies on this subject have been published. This review was originally published in 2009.
We performed a systematic review and meta-analysis to assess the effectiveness of therapeutic hypothermia in patients after cardiac arrest. Neurologic outcome, survival and adverse events were our main outcomes. We aimed to perform individual patient data analysis, if data were available, and to form subgroups according to the cardiac arrest situation.
We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2001, Issue 7); MEDLINE (1971 to July 2011); EMBASE (1987 to July 2011); CINAHL (1988 to July 2011); PASCAL (2000 to July 2011); and BIOSIS (1989 to July 2011). The original search was performed in January 2007.
We included all randomized controlled trials assessing the effectiveness of therapeutic hypothermia in patients after cardiac arrest, without language restrictions. Studies were restricted to adult populations cooled with any cooling method, applied within six hours of cardiac arrest.
Validity measures, the intervention, outcomes and additional baseline variables were entered into a database. Meta-analysis was only done for a subset of comparable studies with negligible heterogeneity. For these studies, individual patient data were available.
We included four trials and one abstract reporting on 481 patients in the systematic review. The updated search resulted in no new studies to include. Quality of the included studies was good in three out of five studies. For the three comparable studies on conventional cooling methods all authors provided individual patient data. With conventional cooling methods, patients in the hypothermia group were more likely to reach a best cerebral performance categories (CPC) score of one or two (five point scale: 1 = good cerebral performance, to 5 = brain death) during the hospital stay (individual patient data; RR 1.55; 95% CI 1.22 to 1.96) and were more likely to survive to hospital discharge (individual patient data; RR 1.35; 95% CI 1.10 to 1.65) compared to standard post-resuscitation care. Across all studies, there was no significant difference in reported adverse events between hypothermia and control.
Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines.
Background
Perioperative subcutaneous tissue oxygen tension (PsqO
2
) is substantially reduced in obese surgical patients. Goal-directed fluid therapy optimizes cardiac performance and thus tissue ...perfusion and oxygen delivery. We therefore tested the hypothesis that intra- and postoperative PsqO
2
is significantly reduced in obese patients undergoing standard fluid management compared to goal-directed fluid administration.
Methods
We randomly assigned 60 obese patients (BMI ≥ 30 kg/m
2
) undergoing laparoscopic bariatric surgery to receive either esophageal Doppler-guided goal-directed fluid management or conventional fluid treatment. Our primary outcome parameter was intra- and postoperative PsqO
2
measured with a polarographic electrode in the subcutaneous tissue of the upper arm. A random effects linear regression model was used to analyze the effect of intervention.
Results
Overall, mean (± SD) PsqO
2
was significantly higher in obese patients receiving goal-directed therapy compared to conventional fluid therapy (65.8 ± 28.0 mmHg vs. 53.7 ± 21.7, respectively; repeated measures design adjusted difference: 13.0 mmHg 95% CI 2.3 to 23.7;
p
= 0.017). No effect was seen intraoperatively (69.6 ± 27.9 mmHg vs. 61.4 ± 28.8, difference: 9.7 mmHg 95% CI -3.8 to 23.2;
p
= 0.160); however, goal-directed fluid management improved PsqO
2
in the early postoperative phase (63.1 ± 27.9 mmHg vs. 48.4 ± 12.5, difference: 14.5 mmHg 95% CI 4.1 to 24.9;
p
= 0.006). Intraoperative fluid requirements did not differ between the two groups.
Conclusions
Goal-directed fluid therapy improved subcutaneous tissue oxygenation in obese patients. This effect was more pronounced in the early postoperative period.
Clinical Trial Number and Registry
The study was registered at
ClinicalTrials.gov
(NCT 01052519).
To investigate the influence of various factors on the two outcome parameters "procedure - specific complication" (femoral head necrosis, infection, nonunion, femoral neck shortening, screw ...loosening, implant penetration) and "functional outcome" in patients with displaced and undisplaced femoral neck fracture treated by cannulated screw fixation. All cases of a femoral neck fracture, operated by cannulated screw fixation, in the period from December 2014 to December 2017 were included. The observation period of the included patients was 12 months. Information on their outcome was collected after evaluation of current x-ray images and on request from the responsible further treatment physician. Continuous data were presented as mean value ± standard deviation, categorical data as absolute and relative frequency. The effect of potential factors on endpoints was estimated with a multivariable logistic regression analysis and 95% confidence intervals calculated. The null hypothesis Odds Ratio = 1 was checked by the Wald test. The likelihood ratio test was used to test for deviation from linearity. The mean age of the 56 included patients was 72 years (36 min, 96 max), 44.5% (n = 25) were male and 55.5% (n = 25) female. The femoral neck fractures were classified as follows: Garden I: 73%, Garden II: 16%, Garden III: 11%, Pauwels I: 73%, Pauwels II: 21%, Pauwels III: 5%, 31-B1: 73%, 31-B2: 27%, 31-B3: 0%. The factor patient age showed a statistically significant influence on the outcome parameter procedure-specific complication. None of the remaining factors examined showed a statistically significant influence on both outcome parameters procedure-specific complication and functional outcome. 69% of the patients from age 80 onwards suffered a procedure-specific complication. A rate of 41% procedure-specific complications as an outcome parameter in trauma surgery shows a necessity for improvement. The increasing risk of procedure-specific complications for patients with a femoral neck fracture treated by cannulated screw fixation is associated with rising patient age. A more stable head-perserving operative method or an endoprosthetic procedure should be considered in high-risk patients (≥80 y.o.).
Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized ...controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthritis. Primary outcomes of American College of Rheumatology (ACR) 20 responses were compared by mixed-model logistic regression, including exploration of potential determinants of efficacy overestimation. In rheumatoid arthritis, phase 2 trial outcomes systematically overestimated subsequent phase 3 results (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.39, 95% confidence interval: 1.25-1.57, P < 0.001). Data for psoriatic arthritis trials were similar, but not statistically significant (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.35, 95% confidence interval: 0.94-1.94, P = 0.09). Differences in inclusion criteria largely explained the observed differences in efficacy findings. Our findings have implications for all stakeholders in new therapeutic development and testing, as well as potential ethical implications.
Standard blood laboratory parameters may have diagnostic potential, if polymerase-chain-reaction (PCR) tests are not available on time. We evaluated standard blood laboratory parameters of 655 ...COVID-19 patients suspected to be infected with SARS-CoV-2, who underwent PCR testing in one of five hospitals in Vienna, Austria. We compared laboratory parameters, clinical characteristics, and outcomes between positive and negative PCR-tested patients and evaluated the ability of those parameters to distinguish between groups. Of the 590 patients (20-100 years, 276 females and 314 males), 208 were PCR-positive. Positive compared to negative PCR-tested patients had significantly lower levels of leukocytes, neutrophils, basophils, eosinophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocytes, and thrombocytes; while significantly higher levels were detected with erythrocytes, hemoglobin, hematocrit, C-reactive-protein, ferritin, activated-partial-thromboplastin-time, alanine-aminotransferase, aspartate-aminotransferase, lipase, creatine-kinase, and lactate-dehydrogenase. From all blood parameters, eosinophils, ferritin, leukocytes, and erythrocytes showed the highest ability to distinguish between COVID-19 positive and negative patients (area-under-curve, AUC: 72.3-79.4%). The AUC of our model was 0.915 (95% confidence intervals, 0.876-0.955). Leukopenia, eosinopenia, elevated erythrocytes, and hemoglobin were among the strongest markers regarding accuracy, sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio, and post-test probabilities. Our findings suggest that especially leukopenia, eosinopenia, and elevated hemoglobin are helpful to distinguish between COVID-19 positive and negative tested patients.
Elevated levels of thyroid-stimulating-hormone (TSH) are associated with reduced glomerular filtration rate (GFR) and increased risk of developing chronic kidney disease even in euthyroid patients. ...Thyroid hormone replacement therapy has been shown to delay progression to end-stage renal disease in sub-clinically hypothyroid patients with renal insufficiency. However, such associations after kidney transplantation were never investigated. In this study the association of thyroid hormones and estimated GFR (eGFR) in euthyroid patients after kidney transplantation was analyzed. In total 398 kidney transplant recipients were assessed retrospectively and association between thyroid and kidney function parameters at and between defined time points, 12 and 24 months after transplantation, was studied. A significant inverse association was shown for TSH changes and eGFR over time between months 12 and 24 post transplantation. For each increase of TSH by 1 µIU/mL, eGFR decreased by 1.34 mL/min 95% CI, -2.51 to -0.16; p = 0.03, corresponding to 2.2% eGFR decline, within 12 months. At selected time points 12 and 24 months post transplantation, however, TSH was not associated with eGFR. In conclusion, an increase in TSH between 12 and 24 months after kidney transplantation leads to a significant decrease in eGFR, which strengthens the concept of a kidney-thyroid-axis.
It is extremely difficult to compare studies investigating the frequency of anaphylaxis making it challenging to satisfactorily assess the worldwide incidence rate. Using a systematic review and ...meta-analysis, this publication aims to determine the current incidence of all-cause anaphylaxis worldwide. Additionally, we investigated whether the incidence of anaphylaxis has changed over time and which factors influence the rates determined by individual studies.
A literature search was performed in four databases. All articles that reported relevant information on population-based incidence rates of all-cause anaphylaxis were included. The protocol was published on INPLASY, the International Platform of Registered Systematic Review and Meta-analysis Protocols.
The database query and screening process resulted in 46 eligible articles on anaphylaxis. The current incidence worldwide was found to be approximately 46 cases per 100,000 population per year (95% CI 21-103). Evaluating confounding factors showed that studies using allergy clinics and hospitalizations as data source result in comparably low rates. Moreover, children are less prone to develop anaphylaxis compared to the general population. Using a random effects Poisson model we calculated a yearly increase of anaphylaxis incidence by 7.4% (95% CI 7.3-7.6,
< 0.05).
This seems to be the first approach to analyze every reported all-cause anaphylaxis incidence rate until 2017 for an at most accurate determination of its epidemiology. Based on these results, future research could investigate the underlying causes for the rising incidence in order find ways to decrease the condition's frequency.
inplasy.com, identifier INPLASY202330047.
The plasma soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker for focal segmental glomerulosclerosis (FSGS), but its value is under discussion because of ambiguous results ...arising from different ELISA methods in previous studies. The aim of this study was to compare diagnostic performance of two leading suPAR ELISA kits and examine four objectives in 146 subjects: (1) plasma suPAR levels according to glomerular disease (primary, secondary and recurrent FSGS after kidney transplantation, other glomerulonephritis) and in healthy controls; (2) suPAR levels based on glomerular filtration rate; (3) sensitivity and specificity of suPAR for FSGS diagnosis and determination of optimal cut-offs; (4) suPAR as prognostic tool. Patients with FSGS showed significant higher suPAR values than patients with other glomerulonephritis and healthy individuals. This applied to subjects with and without chronic kidney disease. Although both suPARnostic™ assay and Quantikine Human uPAR ELISA Kit exerted high sensitivity and specificity for FSGS diagnosis, their cut-off values of 4.644 ng/mL and 2.789 ng/mL were significantly different. Higher suPAR was furthermore predictive for progression to end-stage renal disease. In summary, suPAR values must be interpreted in the context of population and test methods used. Knowing test specific cut-offs makes suPAR a valuable biomarker for FSGS.
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