Systematic review of randomized clinical trials on the use of hydroxyethyl starch for fluid management in sepsis

<p>Abstract</p> <p>Background</p> <p>Patients with sepsis typically require large resuscitation volumes, but the optimal type of fluid remains unclear. The aim of this systematic review was to evaluate current evidence on the effectiveness and safety of hydroxyethyl starch for fluid management in sepsis.</p> <p>Methods</p> <p>Computer searches of MEDLINE, EMBASE and the Cochrane Library were performed using search terms that included hydroxyethyl starch; hetastarch; shock, septic; sepsis; randomized controlled trials; and random allocation. Additional methods were examination of reference lists and hand searching. Randomized clinical trials comparing hydroxyethyl starch with other fluids in patients with sepsis were selected. Data were extracted on numbers of patients randomized, specific indication, fluid regimen, follow-up, endpoints, hydroxyethyl starch volume infused and duration of administration, and major study findings.</p> <p>Results</p> <p>Twelve randomized trials involving a total of 1062 patients were included. Ten trials (83%) were acute studies with observation periods of 5 days or less, most frequently assessing cardiorespiratory and hemodynamic variables. Two trials were designed as outcome studies with follow-up for 34 and 90 days, respectively. Hydroxyethyl starch increased the incidence of acute renal failure compared both with gelatin (odds ratio, 2.57; 95% confidence interval, 1.13–5.83) and crystalloid (odds ratio, 1.81; 95% confidence interval, 1.22–2.71). In the largest and most recent trial a trend was observed toward increased overall mortality among hydroxyethyl starch recipients (odds ratio, 1.35; 95% confidence interval, 0.94–1.95), and mortality was higher (p < 0.001) in patients receiving > 22 mL·kg^-1hydroxyethyl starch per day than lower doses.</p> <p>Conclusion</p> <p>Hydroxyethyl starch increases the risk of acute renal failure among patients with sepsis and may also reduce the probability of survival. While the evidence reviewed cannot necessarily be applied to other clinical indications, hydroxyethyl starch should be avoided in sepsis.</p

Awareness and use of home remedies in Italy's alps: a population-based cross-sectional telephone survey

Belief in complementary and alternative medicine practices is related to reduced preparedness for vaccination. This study aimed to assess home remedy awareness and use in South Tyrol, where vaccination rates in the coronavirus pandemic were lowest in Italy and differed between German- and Italian-speaking inhabitants.; A population-based survey was conducted in 2014 and analyzed using descriptive statistics, multiple logistic regression, and latent class analysis.; Of the representative sample of 504 survey respondents, 357 (70.8%) participants (43.0% male; primary language German, 76.5%) reported to use home remedies. Most commonly reported home remedies were teas (48.2%), plants (21.0%), and compresses (19.5%). Participants from rural regions were less likely (odds ratio 0.35, 95% confidence interval 0.19-0.67), while female (2.62, 1.69-4.10) and German-speaking participants (5.52, 2.91-9.88) were more likely to use home remedies. Latent classes of home remedies were "alcoholic home remedies" (21.4%) and "non-alcohol-containing home remedies" (78.6%). Compared to the "non-alcohol-containing home remedies" class, members of the "alcoholic home remedies" class were more likely to live in an urban region, to be male and German speakers.; In addition to residence and sex, language group membership associates with awareness and use of home remedies. Home remedies likely contribute to socio-cultural differences between the language groups in the Italian Alps. If the observed associations explain the lower vaccination rates in South Tyrol among German speakers requires further study

Reply to No evidence for individual blood-brain barrier phenylalanine transport to influence clinical outcome in typical phenylketonuria patients

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A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis

BACKGROUND: Meta-analysis of two randomised controlled trials in severe sepsis performed with recombinant human activated protein C may provide further insight as to the therapeutic utility of targeting the clotting cascade in this syndrome. METHODS: In search for relevant studies published, two randomized clinical trials were found eligible. RESULTS: The studies, PROWESS and ADDRESS, enrolled a total of 4329 patients with risk ratio (RR) and 95% confidence interval (CI) data for effect on 28-day mortality relative to control treatment of 0.92 (0.83–1.02) suggesting that recombinant human activated protein C is not beneficial in severe sepsis. In PROWESS, 873 of 1690 patients presented with low risk, and 2315 of 2639 patients in ADDRESS as defined by APACHE II score < 25. In this low-risk stratum, no effect of recombinant human activated protein C administration on 28-day mortality was observed. This observation appears to be consistent and homogenous. Heterogeneity between the two studies, however, was seen in patients with APACHE II score ≥ 25 in whom recombinant activated protein C was effective in PROWESS (n = 817; RR 0.71, CI 0.59–0.85) whereas a tendency toward harm was present in ADDRESS (n = 324; RR 1.21, CI 0.85–1.74). Even though the overall treatment effect in this high-risk population was still in favour of treatment with recombinant activated protein C (n = 1141; RR 0.80, CI 0.68–0.94), the observed heterogeneity suggests that the efficacy of recombinant human activated protein C is not robust. Not unlikely, the adverse tendency observed could have become significant with higher statistical power would ADDRESS not have been terminated prematurely. CONCLUSION: This meta-analysis, therefore, raises doubts about the clinical usefulness of recombinant activated protein C in patients with severe sepsis and an APACHE II score ≥ 25 which can only be resolved by another properly designed clinical trial

On the Executability of Interactive Computation

The model of interactive Turing machines (ITMs) has been proposed to characterise which stream translations are interactively computable; the model of reactive Turing machines (RTMs) has been proposed to characterise which behaviours are reactively executable. In this article we provide a comparison of the two models. We show, on the one hand, that the behaviour exhibited by ITMs is reactively executable, and, on the other hand, that the stream translations naturally associated with RTMs are interactively computable. We conclude from these results that the theory of reactive executability subsumes the theory of interactive computability. Inspired by the existing model of ITMs with advice, which provides a model of evolving computation, we also consider RTMs with advice and we establish that a facility of advice considerably upgrades the behavioural expressiveness of RTMs: every countable transition system can be simulated by some RTM with advice up to a fine notion of behavioural equivalence.Comment: 15 pages, 0 figure