tag:blogger.com,1999:blog-53545530790529533852023-11-15T06:27:34.005-08:00CRITICAL CARE UPDATESUnknownnoreply@blogger.comBlogger12125tag:blogger.com,1999:blog-5354553079052953385.post-55271621742909084522018-05-29T04:15:00.001-07:002018-05-29T04:15:53.588-07:00APROCCHSS trial - Hydrocort plus Fludricort in septic shock <h2>
<span class="title_default" style="background-color: rgba(255, 255, 255, 0); border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><i>Hydrocortisone plus Fludrocortisone for Adults with Septic Shock</i></span></span></h2>
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<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">
<li style="border: 0px; box-sizing: inherit; display: inline; font-stretch: inherit; font-style: inherit; line-height: inherit; list-style-type: none; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Djillali Annane, et al. </li>
</span></span><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium; font-style: inherit;">for the CRICS-TRIGGERSEP Network</span><span style="background-color: rgba(255 , 255 , 255 , 0); border: 0px; box-sizing: inherit; color: rgb(0 , 0 , 0); font-family: sans-serif; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; position: relative; top: -0.4em; vertical-align: baseline;"><a data-behavior="ShowPopupTip" data-popup-content-ids="potcast_group" href="https://www.nejm.org/doi/10.1056/NEJMoa1705716#potcast_group" style="box-sizing: inherit; text-decoration: none; touch-action: inherit;">*</a></span></ul>
<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0); color: blue;"><b><i>N Engl J Med 2018; 378:809-818</i></b></span></span></ul>
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<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">BACKGROUND</span></span><br />
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);"><span style="-webkit-text-size-adjust: 100%; background-color: white; color: #4d4d4d; font-family: ff-quadraat-web-pro, "Times New Roman", serif; font-size: 17px;">Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock.</span></span></span><br />
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; margin-top: 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">HYPOTHESIS - </span></span></div>
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<span style="background-color: rgba(255, 255, 255, 0);">therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock.</span></div>
<br /><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">METHODS</span></span><br />
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;"> multicenter, double-blind, randomized trial with a 2-by-2 factorial design, </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">primary outcome - 90-day all-cause mortality. </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">Secondary outcomes - mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group).</span></li>
</ul>
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">RESULTS</span></span><ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">Mortality was significantly lower in the hydrocortisone-plus-fludrocortisone group than in the placebo group at ICU discharge (35.4% vs. 41.0%, P=0.04), hospital discharge (39.0% vs. 45.3%, P=0.02), and day 180 (46.6% vs. 52.5%, P=0.04) but not at day 28 (33.7% and 38.9%, respectively; P=0.06). </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">The number of vasopressor-free days to day 28 was significantly higher in the hydrocortisone-plus-fludrocortisone group than in the placebo group (17 vs. 15 days, P<0.001), as was the number of organ-failure–free days (14 vs. 12 days, P=0.003). </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">The number of ventilator-free days was similar in the two groups (11 days in the hydrocortisone-plus-fludrocortisone group and 10 in the placebo group, P=0.07). </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">The rate of serious adverse events did not differ significantly between the two groups, but hyperglycemia was more common in hydrocortisone-plus-fludrocortisone group.</span></li>
</ul>
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">CONCLUSIONS</span></span><br />
<br />
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo.</span></span><br />
<span style="background-color: rgba(255, 255, 255, 0);"><br /></span>
<span style="background-color: rgba(255, 255, 255, 0);">To read the article , </span><a href="https://www.nejm.org/doi/10.1056/NEJMoa1705716" style="background-color: rgba(255, 255, 255, 0);" target="_blank">click here</a>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-64738516649993576222018-05-29T04:05:00.001-07:002018-05-29T04:05:50.030-07:00SMART trial - Balanced Crystalloids vs Saline <h2>
<span class="title_default" style="background-color: rgba(255 , 255 , 255 , 0); border: 0px; box-sizing: inherit; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;">Balanced Crystalloids versus Saline in Critically Ill Adults</span></span></h2>
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<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">
<li style="border: 0px; box-sizing: inherit; display: inline; font-stretch: inherit; font-style: inherit; line-height: inherit; list-style-type: none; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Matthew W. Semler, et al. </li>
</span></span><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium; font-style: inherit;">for the SMART Investigators and the Pragmatic Critical Care Research Group</span></ul>
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<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="font-style: inherit; font-variant-caps: inherit;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0); color: blue;"><b>N Engl J Med 2018; 378:829-839</b></span></span></span></ul>
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<span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;"><br /></span></div>
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<span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;"><b>BACKGROUND: </b></span></div>
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<span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes.</span></div>
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">METHODS</span></span><br />
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">A pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">The primary outcome was a major adverse kidney event within 30 days — a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first.</span></li>
</ul>
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">RESULTS</span></span><ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">7942 patients in the balanced-crystalloids group - 1139 (14.3%) had a major adverse kidney event, </span><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04).</span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;"> In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P=0.06). </span></li>
</ul>
<ul>
<li><span style="background-color: rgba(255 , 255 , 255 , 0); color: rgb(0 , 0 , 0); font-family: sans-serif; font-size: medium;">The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P=0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P=0.60).</span></li>
</ul>
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<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">CONCLUSIONS</span></span><br />
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; margin-top: 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. </span></span></div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; margin-top: 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">To read the article <a href="https://www.nejm.org/doi/10.1056/NEJMoa1711584" target="_blank">Click here </a></span></span></div>
</div>
<div>
<span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%;"><br /></span></span></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-86779891798676202292018-05-26T07:53:00.001-07:002018-05-26T07:53:57.140-07:00WAKE-UP study : MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset <h1 class="m-article-header__title f-h1" style="border: 0px; box-sizing: inherit; font-stretch: inherit; font-weight: 400; line-height: 36px; margin-bottom: -2px; margin-top: 16px; outline: 0px; padding: 2px 16px 0px; vertical-align: baseline;">
<span class="title_default" style="background-color: rgba(255 , 255 , 255 , 0); border: 0px; box-sizing: inherit; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;">MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset</span></span></h1>
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<span class="title_default" style="border: 0px; box-sizing: inherit; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"></span><br>
<ul class="m-article-header__authors f-ui" style="background-color: rgba(255 , 255 , 255 , 0); border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;">
<li style="border: 0px; box-sizing: inherit; display: inline; font-stretch: inherit; font-style: inherit; line-height: inherit; list-style-type: none; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="title_default" style="border: 0px; box-sizing: inherit; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;">Götz Thomalla, et al. WAKE-UP investigators. </span></span></li>
</ul>
<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;">
<li style="background-color: rgba(255 , 255 , 255 , 0); border: 0px; box-sizing: inherit; display: inline; font-stretch: inherit; font-style: inherit; line-height: inherit; list-style-type: none; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="title_default" style="border: 0px; box-sizing: inherit; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;">BACKGROUND:<br>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
- Under current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. </div>
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We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase.</div>
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METHODS<br>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
- <span style="background-color: rgba(255 , 255 , 255 , 0); font-style: inherit;">multicenter trial, </span></div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span style="background-color: rgba(255 , 255 , 255 , 0); font-style: inherit;">- randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. </span></div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span style="background-color: rgba(255 , 255 , 255 , 0); font-style: inherit;">- All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. </span></div>
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<span style="background-color: rgba(255 , 255 , 255 , 0); font-style: inherit;">- excluded patients for whom thrombectomy was planned. </span></div>
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<span style="background-color: rgba(255 , 255 , 255 , 0); font-style: inherit;">- The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days. </span></div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span style="background-color: rgba(255 , 255 , 255 , 0); font-style: inherit;">- A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo (shift analysis).</span></div>
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<span style="background-color: rgba(255 , 255 , 255 , 0); font-style: inherit;"><br></span></div>
RESULTS<br>
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- The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients.</div>
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- Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. </div>
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- A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02). </div>
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- The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 to 2.23; P=0.003). </div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
- There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P=0.07). </div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
- The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P=0.15).</div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br></div>
CONCLUSIONS<br>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days. </div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br></div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
To read the full text of the article <a href="https://www.nejm.org/doi/10.1056/NEJMoa1804355" target="_blank">Click here</a></div>
</span></span></li>
</ul>
</div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-16754901850874256842018-05-24T11:57:00.005-07:002018-05-24T12:02:42.067-07:00SAFE study - Albumin vs Saline for fluid resuscitation in ICU<h1 class="m-article-header__title f-h1" style="border: 0px; box-sizing: inherit; font-stretch: inherit; font-weight: 400; line-height: 36px; margin-bottom: -2px; margin-top: 16px; outline: 0px; padding: 2px 16px 0px; vertical-align: baseline;">
<span class="title_default" style="background-color: rgba(255, 255, 255, 0); border: 0px; box-sizing: inherit; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;">A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit</span></span></h1>
<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">
<li style="border: 0px; box-sizing: inherit; display: inline; font-stretch: inherit; line-height: inherit; list-style-type: none; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><i>The SAFE Study Investigators</i></li>
<span style="border: 0px; box-sizing: inherit; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; position: relative; top: -0.4em; vertical-align: baseline;"><a data-behavior="ShowPopupTip" data-popup-content-ids="potcast_group" href="https://www.nejm.org/doi/full/10.1056/NEJMoa040232#potcast_group" style="box-sizing: inherit; text-decoration: none; touch-action: inherit;">*</a></span></span></span></ul>
<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="background-color: rgba(255 , 255 , 255 , 0); color: blue;"><b>N Engl J Med 2004; 350:2247-2256</b></span></span></ul>
<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);"><section class="o-article-body__section section-in-viewport" data-article-section-title="Abstract" id="article_abstract" style="border-top-color: rgb(226 , 226 , 226); border-top-style: solid; border-width: 1px 0px 0px; box-sizing: inherit; font-stretch: inherit; line-height: inherit; margin: 24px 0px 0px; outline: 0px; padding: 23px 0px 0px; vertical-align: baseline;"><span style="font-weight: normal;">BACKGROUND</span><br />
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival. We conducted a multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU.</div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br /></div>
METHODS<br />
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
We randomly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days. The primary outcome measure was death from any cause during the 28-day period after randomization.</div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br /></div>
RESULTS<br />
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and 3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 percent confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups (P=0.85). There were no significant differences between the groups in the mean (±SD) numbers of days spent in the ICU (6.5±6.6 in the albumin group and 6.2±6.2 in the saline group, P=0.44), days spent in the hospital (15.3±9.6 and 15.6±9.6, respectively; P=0.30), days of mechanical ventilation (4.5±6.1 and 4.3±5.7, respectively; P=0.74), or days of renal-replacement therapy (0.5±2.3 and 0.4±2.0, respectively; P=0.41).</div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br /></div>
CONCLUSIONS<br />
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days.</div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br /></div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
To read the full text of the article <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa040232" target="_blank">click here</a></div>
</section><section class="
o-article-body__section o-article-body__section--collapsible o-article-body__section--collapsible-open@medium+ o-article-body__section--hide-title@medium+
" data-article-section-title="Introduction" data-behavior="CollapsibleArea" id="article_introduction" style="border-top-color: rgb(226 , 226 , 226); border-top-style: solid; border-width: 1px 0px 0px; box-sizing: inherit; font-stretch: inherit; line-height: inherit; margin: 20px 0px 0px; outline: 0px; padding: 23px 0px 0px; vertical-align: baseline;"></section></span></span></ul>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-22605692289220592012018-05-24T11:47:00.000-07:002018-05-24T11:48:50.971-07:00ARDS Network - Low tidal volume vs Traditional tidal volume<h3>
<span class="title_mid" style="background-color: rgba(255 , 255 , 255 , 0); border: 0px; box-sizing: inherit; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;">Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome</span></span></h3>
<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">
<li style="border: 0px; box-sizing: inherit; display: inline; font-stretch: inherit; line-height: inherit; list-style-type: none; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><i>The Acute Respiratory Distress Syndrome Network</i></li>
<span style="border: 0px; box-sizing: inherit; font-stretch: inherit; font-style: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; position: relative; top: -0.4em; vertical-align: baseline;"><a data-behavior="ShowPopupTip" data-popup-content-ids="potcast_group" href="https://www.nejm.org/doi/full/10.1056/NEJM200005043421801#potcast_group" style="box-sizing: inherit; text-decoration: none; touch-action: inherit;">*</a></span></span></span></ul>
<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0); color: blue;"><b>N Engl J Med 2000; 342:1301-1308</b></span></span></ul>
<ul class="m-article-header__authors f-ui" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; list-style: none; margin: 20px 0px 0px; outline: 0px; padding: 0px 16px; vertical-align: baseline;"><span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);">BACKGROUND-<br>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients.</div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br></div>
METHODS<br>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The first primary outcome was death before a patient was discharged home and was breathing without assistance. The second primary outcome was the number of days without ventilator use from day 1 to day 28.</div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br></div>
RESULTS<br>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [±SD], 12±11 vs. 10±11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2±0.8 and 11.8±0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25±6 and 33±8 cm of water (P<0.001), respectively.</div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br></div>
CONCLUSIONS<br>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.</div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
<br></div>
<div class="f-body" style="border: 0px; box-sizing: inherit; font-stretch: inherit; line-height: 24px; outline: 0px; padding: 0px; vertical-align: baseline;">
To read the full text of the article <a href="https://www.nejm.org/doi/full/10.1056/NEJM200005043421801" target="_blank">click here</a></div>
</span></span></ul>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-47728740788407068472018-05-23T10:49:00.000-07:002018-05-24T00:58:45.054-07:00ADRENAL trial - Adjunctive Glucocorticoid Therapy in Patients with Septic ShockAdjunctive Glucocorticoid Therapy in Patients with Septic Shock<br>
<br>
<i>B. Venkatesh, S. Finfer, et al</i>.<br>
<br>
<span style="-webkit-text-size-adjust: 100%; background-color: white; font-family: ff-scala-sans-web-pro, Helvetica, Arial, sans-serif; font-size: 16px;"><b><span style="color: blue;">N Engl J Med 2018; 378:797-808</span></b></span><br>
<br>
BACKGROUND:<br>
Whether hydrocortisone reduces mortality among patients with septic shock is unclear.<br>
<br>
METHODS:<br>
We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days.<br>
<br>
RESULTS:<br>
Hi From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P = 0.50). The effect of the trial regimen was similar in six prespecified subgroups.<br>
Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001).<br>
Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation.<br>
Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P = 0.004).<br>
There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renalreplacement therapy, and the incidence of new-onset bacteremia or fungemia.<br>
CONCLUSIONS:<br>
Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo.<br>
(Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109.)<br>
<br>
To read the article <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1705835" target="_blank">Click here</a><br>
<br>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-57408326323598709812018-05-22T18:48:00.000-07:002018-05-24T00:57:41.041-07:00Colistin vs Colistin plus meropenem in MDR GNB<div>
<b>Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial.</b></div>
<div>
<br></div>
<div>
Mical Paul, George L Daikos, et al.<br></div><div><br></div>
<div>
<span style="color: blue;"><b>The Lancet <span style="color: black; font-family: sans-serif; font-size: small;"><span style="-webkit-tap-highlight-color: rgba(26, 26, 26, 0.301961); -webkit-text-size-adjust: 100%; background-color: rgba(255, 255, 255, 0);"><a href="https://www.thelancet.com/journals/laninf/issue/vol18no4/PIIS1473-3099(18)X0004-8" style="text-align: center; text-decoration: none;">Volume 18, No. 4</a><span style="text-align: center;">, p391–400, April 2018</span></span></span></b></span></div>
<div>
<br></div>
<div>
<div>
Background: </div>
<div>
Colistin–carbapenem combinations are synergistic in vitro against carbapenem-resistant Gram-negative bacteria. We aimed to test whether combination therapy improves clinical outcomes for adults with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria.</div>
<div>
<br></div>
<div>
Methods: </div>
<div>
A randomised controlled superiority trial was done in six hospitals in Israel, Greece, and Italy. We included adults with bacteraemia, ventilator-associated pneumonia, hospital-acquired pneumonia, or urosepsis caused by carbapenem-non-susceptible Gram-negative bacteria. Patients were randomly assigned (1:1) centrally, by computer- generated permuted blocks strati ed by centre, to intravenous colistin (9-million unit loading dose, followed by 4·5 million units twice per day) or colistin with meropenem (2-g prolonged infusion three times per day). </div>
<div>
The trial was open-label, with blinded outcome assessment. Treatment success was defined as survival, haemodynamic stability, improved or stable Sequential Organ Failure Assessment score, stable or improved ratio of partial pressure of arterial oxygen to fraction of expired oxygen for patients with pneumonia, and microbiological cure for patients with bacteraemia. The primary outcome was clinical failure, defined as not meeting all success criteria by intention- to-treat analysis, at 14 days after randomisation. This trial is registered at ClinicalTrials.gov, number NCT01732250, and is closed to accrual.</div>
<div>
<br></div>
<div>
Findings: </div>
<div>
Between Oct 1, 2013, and Dec 31, 2016, we randomly assigned 406 patients to the two treatment groups. Most patients had pneumonia or bacteraemia (355/406, 87%), and most infections were caused by Acinetobacter baumannii (312/406, 77%). </div>
<div>
No significant difference between colistin monotherapy (156/198, 79%) and combination therapy (152/208, 73%) was observed for clinical failure at 14 days after randomisation (risk difference –5·7%, 95% CI –13·9 to 2·4; risk ratio [RR] 0·93, 95% CI 0·83–1·03). </div>
<div>
Results were similar among patients with A baumannii infections (RR 0·97, 95% CI 0·87–1·09). Combination therapy increased the incidence of diarrhoea (56 [27%] vs 32 [16%] patients) and decreased the incidence of mild renal failure (37 [30%] of 124 vs 25 [20%] of 125 patients at risk of or with kidney injury).</div>
<div>
<br></div>
<div>
Interpretation: </div>
<div>
Combination therapy was not superior to monotherapy. The addition of meropenem to colistin did not improve clinical failure in severe A baumannii infections. The trial was unpowered to specifically address other bacteria.</div>
</div>
<div>
<br>
To read the article <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30099-9/fulltext" target="_blank">Click here </a></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-18890318439577114132018-05-22T05:39:00.003-07:002018-05-24T00:56:26.593-07:00TICH-2 : Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage<div style="-webkit-text-stroke-width: 0px; color: black; font-family: "Times New Roman"; font-size: medium; font-style: normal; font-variant-caps: normal; font-variant-ligatures: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-decoration-color: initial; text-decoration-style: initial; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px;"><span style="font-size: large; -webkit-text-size-adjust: 100%; background-color: white; font-family: "source sans pro", helvetica, sans-serif;">Tranexamic acid for hyperacute primary IntraCerebral
Haemorrhage (TICH-2): an international randomised,
placebo-controlled, phase 3 superiority trial</span><br></div>
<div>
<span style="background-color: white;"><br></span></div>
<h1 class="articleTitle" style="-webkit-text-stroke-width: 0px; color: black; font-family: "source sans pro", helvetica, sans-serif; font-style: normal; font-variant-caps: normal; font-variant-ligatures: normal; letter-spacing: normal; line-height: normal; margin: 0px; orphans: 2; text-align: start; text-decoration-color: initial; text-decoration-style: initial; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px;">
<span style="font-size: small; font-weight: normal;"><span style="background-color: white;">Nikola Sprigg, Katie Flaherty, et </span><span style="background-color: white;">al.</span></span></h1>
<div>
<span style="font-weight: normal;"><br></span></div>
<div>
<span style="color: blue;"><b>The Lancet, Published Online
May 16, 2018.</b></span></div>
<div>
<span style="font-weight: normal;"><br></span></div>
<div>
<b>Abstract:</b></div>
<div>
<span style="font-weight: normal;"><br></span></div>
<div>
<span style="font-weight: normal;">Background: </span></div>
<div>
<span style="font-weight: normal;">Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We
aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke
due to intracerebral haemorrhage. </span></div>
<div>
<span style="font-weight: normal;"><br></span></div>
<div>
<span style="font-weight: normal;">Methods:</span></div>
<div>
<span style="font-weight: normal;">We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from
acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g
intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within
8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by
country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome
assessors, and all other health-care workers involved in the trial. </span></div>
<div>
<span style="font-weight: normal;">The primary outcome was functional status at day 90,
measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification
and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the
ISRCTN registry, number ISRCTN93732214. </span></div>
<div>
<span style="font-weight: normal;"><br></span></div>
<div>
<span style="font-weight: normal;">Findings:</span></div>
<div>
<span style="font-weight: normal;">We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic
acid and 1164 received placebo; the treatment groups were well balanced at baseline. </span></div>
<div>
<span style="font-weight: normal;">The primary outcome was
assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly
between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76–1·03, p=0·11). </span></div>
<div>
<span style="font-weight: normal;">Although there were fewer deaths
by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo
group; aOR 0·73, 0·53–0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%];
adjusted hazard ratio 0·92, 95% CI 0·77–1·10, p=0·37). </span></div>
<div>
<span style="font-weight: normal;">Fewer patients had serious adverse events after tranexamic
acid than after placebo by days 2 (379 [33%] patients vs 417 [36%] patients), 7 (456 [39%] vs 497 [43%]), and 90 (521 [45%]
vs 556 [48%]). </span></div>
<div>
<span style="font-weight: normal;"><br></span></div>
<div>
<span style="font-weight: normal;">Interpretation:</span></div>
<div>
<span style="font-weight: normal;">Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients
who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse
events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect.</span></div>
<div>
<span style="font-weight: normal;"><br></span></div>
<div>
<span style="font-weight: normal;">To read, the full article <a href="https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(18)31033-X.pdf">Click here</a> </span></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-54286807723734793092018-05-22T05:07:00.000-07:002018-05-24T00:55:00.915-07:00ICU-ROX - results of the pilot phase<h1 style="font-family: arial, helvetica, clean, sans-serif; font-size: 1.4em; line-height: 1.25em; margin: 0.5em 0px;">
<span style="background-color: #990000;">
I<span style="color: white;">ntensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX): results of the pilot phase.</span></span></h1>
<div class="auths" style="font-family: arial, helvetica, clean, sans-serif; font-size: 0.923em;">
<span style="background-color: #990000; color: white;">Young PJ, Mackle DM, et al.; The ICU-ROX pilot investigators; The Australian and New Zealand Intensive Care Society Clinical Trials Group.</span></div>
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<span style="background-color: #990000;"><br></span></div>
<div class="auths" style="font-family: arial, helvetica, clean, sans-serif;">
<i><span style="color: blue;"><b style="background-color: #990000;"><span role="menubar">Crit Care Resusc.</span> 2017 Dec;19(4):344-354.</b></span></i></div>
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<span style="background-color: #990000; font-size: 11.0045px;"><br></span></div>
<div class="afflist" style="font-family: arial, helvetica, clean, sans-serif; zoom: 1;">
<div>
<span style="background-color: #990000; color: white; font-size: large;">Abstract:</span></div>
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OBJECTIVE:</span></h4>
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<span style="background-color: #990000; color: white;">The objective of the intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX) pilot phase, which included the first 100 patients of an overall sample of 1000, was to examine feasibility.</span></div>
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<span style="background-color: #990000; color: white;">
DESIGN:</span></h4>
<div style="font-size: 1.04em; margin-bottom: 0.5em;">
<span style="background-color: #990000; color: white;">Investigator-initiated, prospective, parallel-group, pilot randomised controlled trial.</span></div>
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SETTING:</span></h4>
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<span style="background-color: #990000; color: white;">Six medical-surgical intensive care units (ICUs) in Australia and New Zealand, with participants recruited from September 2015 through June 2016.</span></div>
<h4 style="float: left; font-size: 1em; margin: 0px 0.25em 0px 0px; text-transform: uppercase;">
<span style="background-color: #990000; color: white;">
PARTICIPANTS:</span></h4>
<div style="font-size: 1.04em; margin-bottom: 0.5em;">
<span style="background-color: #990000; color: white;">100 patients ≥ 18 years of age who required invasive mechanical ventilation in the ICU and were expected to be receiving it beyond the next calendar day at the time of randomisation.</span></div>
<h4 style="float: left; font-size: 1em; margin: 0px 0.25em 0px 0px; text-transform: uppercase;">
<span style="background-color: #990000; color: white;">
INTERVENTIONS:</span></h4>
<div style="font-size: 1.04em; margin-bottom: 0.5em;">
<span style="background-color: #990000; color: white;">Conservative oxygen therapy or standard care.</span></div>
<h4 style="float: left; font-size: 1em; margin: 0px 0.25em 0px 0px; text-transform: uppercase;">
<span style="background-color: #990000; color: white;">
MAIN OUTCOME MEASURES:</span></h4>
<div style="font-size: 1.04em; margin-bottom: 0.5em;">
<span style="background-color: #990000; color: white;">Eligibility, recruitment rate, and separation in oxygen exposure (fraction of inspired oxygen [FiO<span style="bottom: -0.25em; font-size: 0.8461em; line-height: 1.6363em; position: relative; top: 0.25em; vertical-align: baseline;">2</span>] and oxygen saturation measured by pulse oximetry [SpO<span style="bottom: -0.25em; font-size: 0.8461em; line-height: 1.6363em; position: relative; top: 0.25em; vertical-align: baseline;">2</span>Z]).</span></div>
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RESULTS:</span></h4>
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<span style="background-color: #990000; color: white;">94 of 99 participants (94.9%) were confirmed by study monitors to fulfil the study eligibility criteria. 3.6 patients per site per month were enrolled (95% confidence interval [CI], 2.5-4.7). Patients allocated to conservative oxygen therapy spent significantly more time on an FiO<span style="bottom: -0.25em; font-size: 0.8461em; line-height: 1.6363em; position: relative; top: 0.25em; vertical-align: baseline;">2</span> of 0.21 in the ICU; median, 31.5 hours (interquartile range [IQR], 7-63.5) for conservative oxygen therapy patients v 0 hours for standard oxygen therapy patients (IQR, 0-10; midpoint difference, 21.5 hours; 95% CI, 9-34; P < 0.0001). Patients allocated to conservative oxygen therapy spent less time in the ICU with an SpO<span style="bottom: -0.25em; font-size: 0.8461em; line-height: 1.6363em; position: relative; top: 0.25em; vertical-align: baseline;">2</span>Z of ≥ 97% than patients allocated to standard oxygen therapy; median, 18.5 hours (IQR, 5-46) for conservative oxygen therapy patients v 32 hours for standard oxygen therapy (IQR, 17-80; midpoint difference, 13.5 hours; 95% CI, 2-25; P = 0.02).</span></div>
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<span style="background-color: #990000; color: white;">
CONCLUSIONS:</span></h4>
<div style="font-size: 1.04em; margin-bottom: 0.5em;">
<span style="background-color: #990000; color: white;">Our findings confirm the feasibility of completing the ICU-ROX trial without the need for substantive changes to the study protocol for the remaining 900 trial participants.</span></div>
<div style="font-size: 1.04em; margin-bottom: 0.5em;">
<span style="background-color: #990000; color: white;">To find the article - <a href="https://www.ncbi.nlm.nih.gov/pubmed/29202261">Click here</a></span></div>
</div>
</div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-35392762410743049712011-11-04T23:43:00.000-07:002011-11-04T23:43:56.867-07:00Xigris succumbs to PROWESS-SHOCK<div dir="ltr" style="text-align: left;" trbidi="on"><span class="Apple-style-span" style="font-family: inherit; font-size: large;">The U.S. Food and Drug Administration (FDA) is informing healthcare professionals and the public that on October 25, 2011, Eli Lilly and Company announced a world wide voluntary market withdrawal of Xigris [drotrecogin alfa (activated)].</span><br />
<span class="Apple-style-span" style="font-family: inherit; font-size: large;"><br />
</span><br />
<b><span class="Apple-style-span" style="font-family: inherit; font-size: large;">Xigris treatment should not be started in new patients. Xigris treatment should be stopped in patients being treated with Xigris.</span></b><br />
<b><span class="Apple-style-span" style="font-family: inherit; font-size: large;"><br />
</span></b><br />
<b><span class="Apple-style-span" style="font-family: inherit; font-size: large;">All remaining Xigris should be returned to the supplier from whom it was purchased.</span></b><br />
<b><span class="Apple-style-span" style="font-family: inherit; font-size: large;"><br />
</span></b><br />
<span class="Apple-style-span" style="font-family: inherit; font-size: large;">In a recently completed clinical trial (PROWESS-SHOCK trial), Xigris failed to meet the primary endpoint of a statistically significant reduction in 28-day all cause mortality in patients treated with Xigris compared with placebo. The study also fails its secondary endpoint of a reduction of mortality in the population of patients with severe protein C deficiency.</span><br />
<span class="Apple-style-span" style="font-family: inherit; font-size: large;"><br />
</span><br />
<span class="Apple-style-span" style="font-family: inherit; font-size: large;">In this trial of 1696 patients, 851 patients were enrolled in the Xigris arm and 845 patients were enrolled in the placebo arm. Results based on preliminary analyses done by Eli Lilly and Company, that were submitted to the FDA, showed a 28-day all cause mortality rate of 26.4% (223/846) in Xigris-treated patients compared to 24.2% (202/834) in placebo-treated patients, for a relative risk of 1.09; 95% CI (0.92,1.28), and P-value = 0.31 (not statistically significant).</span><br />
<span class="Apple-style-span" style="font-family: inherit; font-size: large;"><br />
</span><br />
<span class="Apple-style-span" style="font-family: inherit; font-size: large;">These questions call into question the overall benefit-risk balance of Xigris for the indicated patient population (severe sepsis). Eli Lilly has thus decided to withdraw the prduct from the market worldwide.</span><br />
<span class="Apple-style-span" style="font-family: inherit; font-size: large;"><br />
</span><br />
<span class="Apple-style-span" style="font-family: inherit; font-size: large;">Xigris - RIP</span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-59823807538668409352010-01-28T00:06:00.001-08:002011-06-18T14:56:17.262-07:00Clinical Practice Guideline: Red Blood Cell Transfusion in Adult Trauma and Critical Care<p><font size="3" face="Segoe Print"><strong>Lena M. Napolitano, MD; Stanley Kurek, DO; Fred A. Luchette, MD; Howard L. Corwin, MD; Philip S. Barie, MD; Samuel A. Tisherman, MD; Paul C. Hebert, MD, MHSc; Gary L. Anderson, DO; Michael R. Bard, MD; William Bromberg, MD; William C. Chiu, MD; Mark D. Cipolle, MD, PhD; Keith D. Clancy, MD; Lawrence Diebel, MD; William S. Hoff, MD; K. Michael Hughes, DO; Imtiaz Munshi, MD; Donna Nayduch, RN, MSN, ACNP; Rovinder Sandhu, MD; Jay A. Yelon, MD</strong></font></p> <p><font color="#00ffff" size="3" face="Segoe Print"><strong>Ref: Crit Care Med. 2009;37(12):3134-57. © 2009 Lippincott Williams & Wilkins</strong></font></p> <p><font color="#ffff00" size="3" face="Segoe Print"><em><strong>Recommendations Regarding Indications for RBC Transfusion in the General Critically Ill Patient</strong></em></font></p> <ol> <li><font size="3" face="Segoe Print"><strong>RBC transfusion is indicated for patients with evidence of hemorrhagic shock. (Level 1) </strong></font> <li><font size="3" face="Segoe Print"><strong>RBC transfusion may be indicated for patients with evidence of acute hemorrhage and hemodynamic instability or inadequate oxygen delivery. (Level 1) </strong></font> <li><font size="3" face="Segoe Print"><strong>A "restrictive" strategy of RBC transfusion (transfuse when Hb < 7 g/dL) is as effective as a "liberal" transfusion strategy (transfusion when Hb < 10 g/dL) in critically ill patients with hemodynamically stable anemia, except possibly in patients with acute myocardial ischemia. (Level 1) </strong></font> <li><font size="3" face="Segoe Print"><strong>The use of only Hb level as a "trigger" for transfusion should be avoided. Decision for RBC transfusion should be based on an individual patient's intravascular volume status, evidence of shock, duration and extent of anemia, and cardiopulmonary physiologic parameters. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>In the absence of acute hemorrhage RBC, transfusion should be given as single units. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>Consider transfusion if Hb < 7 g/dL in critically ill patients requiring mechanical ventilation (MV). There is no benefit of a "liberal" transfusion strategy (transfusion when Hb < 10 g/dL) in critically ill patients requiring MV. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>Consider transfusion if Hb < 7 g/dL in resuscitated critically ill trauma patients. There is no benefit of a "liberal" transfusion strategy (transfusion when Hb < 10 g/dL) in resuscitated critically ill trauma patients. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>Consider transfusion if Hb < 7 g/dL in critically ill patients with stable cardiac disease. There is no benefit of a "liberal" transfusion strategy (transfusion when Hb < 10 g/dL) in critically ill patients with stable cardiac disease. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>RBC transfusion should not be considered as an absolute method to improve tissue oxygen consumption in critically ill patients. (Level 2) </strong></font> <li><font face="Segoe Print"><strong><font size="3">RBC transfusion may be beneficial in patients with acute coronary syndromes (ACS) who are anemic (Hb < 8 g/dL) on hospital admission. (Level 3)</font> </strong></font></li></ol> <p><font color="#ffff00" size="3" face="Segoe Print"><em><strong>Recommendations Regarding RBC Transfusion in Sepsis</strong></em></font></p> <ol> <li><font size="3" face="Segoe Print"><strong>There are insufficient data to support Level 1 recommendations on this topic. </strong></font> <li><font face="Segoe Print"><strong><font size="3">The transfusion needs for each septic patient must be assessed individually since optimal transfusion triggers in sepsis patients are not known and there is no clear evidence that blood transfusion increases tissue oxygenation. (Level 2)</font> </strong></font></li></ol> <p><font size="3"><em><font color="#ffff00" face="Segoe Print"><strong>Recommendations Regarding RBC Transfusion in Patients at Risk for or With Acute Lung Injury (ALI) and ARDS</strong></font></em></font></p> <p><font size="3" face="Segoe Print"><strong>ALI and ARDS are common clinical sequelae of massive transfusion. Prior studies have suggested that RBC transfusion is associated with respiratory complications, including ALI and ARDS that remains even after adjusting for potential confounders. </strong></font></p> <ol> <li><font size="3" face="Segoe Print"><strong>There are insufficient data to support Level 1 recommendations on this topic. </strong></font> <li><font size="3" face="Segoe Print"><strong>All efforts should be initiated to avoid RBC transfusion in patients at risk for ALI and ARDS after completion of resuscitation. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>All efforts should be made to diagnose and report transfusion-related ALI (TRALI) to the local blood bank because it has emerged as a leading cause of transfusion-associated morbidity and mortality, despite underdiagnosis and underreporting. (Level 2) </strong></font> <li><font face="Segoe Print"><strong><font size="3">RBC transfusion should not be considered as a method to facilitate weaning from MV. (Level 2)</font> </strong></font></li></ol> <p><font color="#ffff00" size="3" face="Segoe Print"><em><strong>Recommendations Regarding RBC Transfusion in Patients With Neurologic Injury and Diseases</strong></em></font></p> <ol> <li><font size="3" face="Segoe Print"><strong>There are insufficient data to support Level 1 Recommendations on this topic. </strong></font> <li><font size="3" face="Segoe Print"><strong>There is no benefit of a "liberal" transfusion strategy (transfusion when Hb < 10 g/dL) in patients with moderate-to-severe traumatic brain injury. (Level 2) </strong></font> <li><font face="Segoe Print"><strong><font size="3">Decisions regarding blood transfusion in patients with subarachnoid hemorrhage (SAH) must be assessed individually since optimal transfusion triggers are not known and there is no clear evidence that blood transfusion is associated with improved outcome. (Level 3)</font> </strong></font></li></ol> <p><font color="#ffff00" size="3" face="Segoe Print"><em><strong>Recommendations Regarding RBC Transfusion Risks</strong></em></font></p> <ol> <li><font size="3" face="Segoe Print"><strong>There are insufficient data to support Level 1 Recommendations on this topic. </strong></font> <li><font size="3" face="Segoe Print"><strong>RBC transfusion is associated with increased nosocomial infection (wound infection, pneumonia, sepsis) rates independent of other factors. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>RBC transfusion is an independent risk factor for MOF and SIRS. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>There is no definitive evidence that prestorage leukocyte depletion of RBC transfusion reduces complication rates, but some studies have shown a reduction in infectious complications. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>RBC transfusions are independently associated with longer ICU and hospital length of stay, increased complications, and increased mortality. (Level 2) </strong></font> <li><font face="Segoe Print"><strong><font size="3">There is a relationship between transfusion and ALI and ARDS. (Level 2)</font> </strong></font></li></ol> <p><font color="#ffff00" size="3" face="Segoe Print"><em><strong>Recommendations Regarding Alternatives to RBC Transfusion</strong></em></font></p> <ol> <li><font size="3" face="Segoe Print"><strong>There are insufficient data to support Level 1 recommendations on this topic. </strong></font> <li><font size="3" face="Segoe Print"><strong>Recombinant human erythropoietin (rHuEpo) administration improves reticulocytosis and hematocrit and may decrease overall transfusion requirements. (Level 2) </strong></font> <li><font face="Segoe Print"><strong><font size="3">Hemoglobin-based oxygen carriers (HBOCs) are undergoing investigation for use in critically ill and injured patients but are not yet approved for use in the United States. (Level 2)</font> </strong></font></li></ol> <p><font color="#ffff00" size="3" face="Segoe Print"><em><strong>Recommendations Regarding Strategies to Reduce RBC Transfusion</strong></em></font></p> <ol> <li><font size="3" face="Segoe Print"><strong>There are insufficient data to support Level 1 recommendations on this topic. </strong></font> <li><font size="3" face="Segoe Print"><strong>The use of low-volume adult or pediatric blood sampling tubes is associated with a reduction in phlebotomy volumes and a reduction in blood transfusion. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>The use of blood conservation devices for reinfusion of waste blood with diagnostic sampling is associated with a reduction in phlebotomy volume. (Level 2) </strong></font> <li><font size="3" face="Segoe Print"><strong>Intraoperative and postoperative blood salvage and alternative methods for decreasing transfusion may lead to a significant reduction in allogeneic blood usage. (Level 2) </strong></font> <li><font face="Segoe Print"><strong><font size="3">Reduction in diagnostic laboratory testing is associated with a reduction in phlebotomy volumes and a reduction in blood transfusion. (Level 2)</font> </strong></font></li></ol> Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-5354553079052953385.post-22930314698774388132010-01-04T22:45:00.001-08:002011-06-18T14:54:48.671-07:00New FDA Alert on Clopidogrel-PPI Interaction<p align="justify"><font size="3" face="Segoe Print"><strong>The FDA has today issued a new public-health warning on the possible interaction between clopidogrel and the proton-pump inhibitor (PPI) omeprazole. The alert states: "New data show that when clopidogrel and omeprazole are taken together, the effectiveness of clopidogrel is reduced. Patients at risk for heart attacks or strokes who use clopidogrel to prevent blood clots will not get the full effect of this medicine if they are also taking omeprazole."</strong></font></p> <p align="justify"><font size="3" face="Segoe Print"><strong>The FDA alert says the new information on which its warning is based comes from new studies that compared the amount of clopidogrel's active metabolite in the blood and its effect on platelets in people who took clopidogrel plus omeprazole vs those who took clopidogrel alone. A reduction in active metabolite levels of about 45% was found in people who received clopidogrel with omeprazole compared with those taking clopidogrel alone. The effect of clopidogrel on platelets was reduced by as much as 47% in people receiving clopidogrel and omeprazole together. These reductions were seen whether the drugs were given at the same time or 12 hours apart, the statement adds.</strong></font></p> <p align="justify"><font size="3" face="Segoe Print"><strong>Based on the current scientific information, the clopidogrel label has been updated with new warnings on omeprazole and other drugs that inhibit the CYP2C19 enzyme that could interact with clopidogrel in the same way. In addition, the manufacturer of clopidogrel is conducting follow-up studies to explore this and other drug interactions.</strong></font></p> <p align="justify"><font size="3" face="Segoe Print"><strong>It adds that patients who use clopidogrel and need a medication to reduce stomach acid can use antacids or H2 antagonists such as ranitidine, famotidine, or nizatidine, because the FDA does not believe that these medicines will interfere with the anti-clotting activity of clopidogrel. However,cimetidine should not be used, it says.</strong></font></p> <p align="justify"><font size="3" face="Segoe Print"><strong>It also says that other drugs that are potent inhibitors of the CYP2C19 enzyme would be expected to have a similar effect and should be avoided in combination with clopidogrel. These include: cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, and ticlopidine. "Since the level of inhibition among other PPIs varies, it is unknown to what amount other PPIs may interfere with clopidogrel. However, esomeprazole, a PPI that is a component of omeprazole, inhibits CYP2C19 and should also be avoided in combination with clopidogrel," it adds.</strong></font></p> <p align="justify"><font size="3" face="Segoe Print"><strong></strong></font></p> <p align="justify"><font size="3" face="Segoe Print"><strong>Ref: Food and Drug Adminstration. Public-health advisory: Updated safety information about a drug interaction between clopidogrel bisulfate (marketed as Plavix) and omeprazole (marketed as Prilosec and Prilosec OTC). November 17, 2009. [</strong></font><a href="http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm190825.htm"><font color="#ffa4a4" size="3" face="Segoe Print"><strong>http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm190825.htm</strong></font></a><font size="3" face="Segoe Print"><strong>]</strong></font></p> <p align="justify"><font size="3" face="Kristen ITC"></font></p> Unknownnoreply@blogger.com0