Day: 08/19/2013

Does Air Pollution Increase the Risk for Acute Heart Failure?

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Certain types of air pollution have a significant temporal association with heart failure–related hospitalization and mortality.
Air pollution has been associated with increased risk for myocardial infarction To assess its potential association with risk for acute heart failure (HF), researchers systematically reviewed the literature and ultimately identified 35 relevant studies in 12 countries, published from 1995 to 2010. All 35 studies tracked levels of specific air pollutants (both gases and particulate matter) and rates of HF-related hospitalization and mortality. A random-effects model was used to estimate the overall risk from each pollutant.

The risk for HF-related hospitalization or death was temporally and significantly associated with exposure to carbon monoxide (3.5% greater risk per 1 part per million), sulphur dioxide (2.4% greater risk per 10 parts per billion), and nitrogen dioxide (1.7% greater risk per 10 parts per billion) — but not ozone. Increases in concentrations of particulate matter were also significantly associated with the risk for HF-related hospitalization or death (from 1.6% to 2.1% greater risk per 10 μg/m3, depending on the size of the particulate), predominantly on the day of exposure. A mean reduction of 3.9 μg/m3 in particulates that have a diameter <2.5 μm (PM2.5) was estimated to prevent nearly 8000 HF-related hospitalizations and save roughly $US300 million per year.

COMMENT

These data show that air pollution has a strong temporal association with heart failure–related hospitalization and death. Thirty-four of the 35 analyzed studies were conducted in developed countries, where even small improvements in air quality are likely to have major effects on population health and healthcare costs. We still need more studies from developing nations, where (as the authors note) cities often have PM2.5 levels up to 10-fold higher than U.S. National Ambient Air Quality Standards allow. Air quality must remain a key target for global health policy and research.

Source: NEJM

 

 

 

Interferon-Free Regimen for HCV Genotype 1 Infection: Closer Still.

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Despite promising findings, including higher response rates with inclusion of ribavirin in a triple-therapy regimen, response rates are still too low in this group to forgo interferon.
Interferon-free regimens should be available soon for hepatitis C virus (HCV) genotype 2 infection and probably genotype 3 infection. For now, the next-generation regimen for genotype 1 infection will be shorter and more tolerable but will still include interferon.

To continue the search for an effective, interferon-free regimen for HCV genotype 1 infection, researchers conducted an industry-funded, multicenter, randomized, open-label, phase IIb study in 362 treatment-naive patients. Patients received faldaprevir (120 mg once daily) plus deleobuvir (600 mg 2 or 3 times daily) with or without ribavirin (1000–1200 mg daily) for 16, 28, or 40 weeks. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12).

SVR12 did not differ by treatment duration (16 weeks, 59%; 28 weeks, 59%; 40 weeks, 52%) or by deleobuvir dose (69% for twice daily and 59% for three times daily). SVR12 was higher in ribavirin users versus nonusers (59% vs. 39%, P=0.03). SVR12 rates were numerically higher in patients with genotype 1b versus 1a (range across treatment groups, 56% to 85% vs. 11% to 47%) and in patients with IL28B genotype CC versus non-CC (range across treatment groups, 58% to 84% vs. 33% to 64%). Of 75 patients with virologic breakthrough, 73 had resistant HCV variant strains. Discontinuation rates ranged from 5% to 25% across treatment groups; the most common adverse events were rash, photosensitivity, nausea, vomiting, and diarrhea.

COMMENT

We are getting closer to an interferon-free regimen for genotype 1 hepatitis C virus infection, but we are not there yet. Ribavirin will likely still be needed as a part of the regimen. Also, multiple interferon-free regimens might be required, with choice of regimen based on predictors of response such as genotype 1 subtype and IL28B status. Finally, until their sustained virologic response rates approach 80%, interferon-free regimens will likely only be an option for patients for whom interferon-based regimens are intolerable or contraindicated.

 Source: NEJM

Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial .

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Wiviott SD et al. – Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous coronary intervention; however, no clear benefit has been shown for patients managed first with drugs only. Authors assessed outcomes from the TRILOGY ACS trial based on whether or not patients had coronary angiography before treatment was chosen. Among patients who had angiography who took prasugrel there were fewer cardiovascular deaths, myocardial infarctions, or strokes than in those who took clopidogrel. This result needs to be corroborated, but it is consistent with previous trials of more versus less intensive antiplatelet treatment. When angiography is done for acute coronary syndrome and anatomic coronary disease confirmed, the benefits and risks of intensive antiplatelet treatment exist whether the patient is treated with drugs or percutaneous coronary intervention.

Methods

  • TRILOGY ACS (ClinicalTrials.gov number NCT00699998) was a randomised controlled trial, done at more than 800 sites worldwide.
  • Patients with non–ST–elevation acute coronary syndrome who were selected for management with revascularisation were randomly assigned to clopidogrel or prasugrel.
  • The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 months.
  • In the present analysis we assessed differences in the primary endpoint by angiography status and whether the effects of treatment on the primary endpoint differed between patients who had angiography before enrolment and those who had not.

Results

  • 7243 patients younger than 75 years were included in the TRILOGY ACS primary analysis.
  • 3085 (43%) had angiography at baseline, 4158 (57%) had not.
  • Fewer patients who had angiography reached the primary endpoint at 30 months compared with those who did not have angiography, according to Kaplan–Meier analysis (281/3085 [12•8%] vs 480/4158 [16•5%], adjusted hazard ratio [HR] 0•63, 95% CI 0•53—0•75; p<0•0001).
  • The proportion of patients who reached the primary endpoint was lower in the prasugrel group than in the clopidogrel group for those who had angiography (122/1524 [10•7%] vs 159/1561 [14•9%], HR 0•77, 95% CI 0•61—0•98; p=0•032) but did not differ between groups in patients who did not have angiography (242/2096 [16•3%] vs 238/2062 [16•7%], HR 1•01, 0•84—1•20; p=0•94; pinteraction=0•08).
  • Overall, TIMI major bleeding and GUSTO severe bleeding were rare.
  • Bleeding outcomes tended to be higher with prasugrel but did not differ significantly between treatment groups in either angiography cohort.

Source: Lancet

Gestational hypothyroxinemia associated with autism occurrence.

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Children born to mothers who had severe, early gestational hypothyroxinemia are nearly four times more likely to have autism, according to researchers. Although their results do not demonstrate causality, researchers said they lend support to the connection between low thyroid function and a child’s developing brain.

“It is increasingly apparent to us that autism is caused by environmental factors in most cases, not by genetics,” Gustavo C. Román, MD, neurologist at Houston Methodist Hospital, said in a press release. “That gives me hope that prevention is possible.”

The researchers used data from the Generation R Study to examine the relationship between thyroid function tests at 6 to 24 weeks of gestation in 5,100 women and parent-reported autistic symptoms in children aged 6 years. Autistic symptoms were measured by the Pervasive Development Problems (PDP) subscale (>98th percentile) and the Social Responsiveness Scale (SRS; the top 5%), according to researchers. Eighty children were defined as a “probable autistic child,” according to these scores.

Data indicate children born to mothers with early gestational hypothyroxinemia were four times more likely to have autism (adjusted OR=3.89; 95% CI, 1.83-8.20). However, no associations were made between maternal thyroid-stimulating hormone and free thyroxine during early pregnancy and children’s borderline and clinical PDP scores, the researchers wrote.

Children aged 6 years were twice as likely to demonstrate borderline PDP scores when their mothers had severe maternal hypothyroxinemia during early gestation (adjusted OR=2.02; 95% CI, 1.16-3.51), researchers added.

Furthermore, children of hypothyroxinemic mothers displayed higher odds for developing clinical PDP scores by age 6 years (adjusted OR=2.60; 95% CI, 1.30-5.18), according to data. No sex differences were observed.

“The next steps are interventional studies,” Román said. “We must look at a large nationwide population of women in early pregnancy to measure urine iodine and thyroid function. We must then correct thyroid deficiencies, if present, and provide prenatal vitamins with supplementary iodine. If autism cases fall precipitously compared with recent historical numbers, I think we will be able to conclude that thyroid function is critical.”

Disclosure: One of the researchers reports being remunerated contributing editor of the Achenbach System of Empirically Based Assessment.

PERSPECTIVE

 

  • This study’s findings, that severe hypothyroxinemia (maternal free T4 in the lowest 5th percentile with normal serum TSH) was associated with an almost fourfold increased risk for probable autism, add to the growing body of observational studies demonstrating that even mild maternal thyroid hypofunction in pregnancy is associated with adverse effects on child neurodevelopment. Dietary iodine deficiency is one potential cause of maternal hypothyroxinemia, but urinary iodine concentrations were not assessed in this study. The Controlled Antenatal Thyroid Screening (CATS) study is the only clinical trial to date to assess the effects of levothyroxine treatment for hypothyroxinemic pregnant women on child development; the CATS study found no effect of treatment on IQ at age 3 years. Prospective interventional studies are needed to better understand whether screening for and treatment of mild maternal thyroid hypofunction will improve IQ as well as risk for autism and attention deficit disorders.
  • Elizabeth N. Pearce, MD
  • Associate professor of medicine Boston University School of Medicine

Source: Endocrine Today

 

DHA Linked to Intelligence in Children.

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Story at-a-glance

  • Low levels of the omega-3 fat DHA were associated with poorer reading, memory and behavioral problems in healthy school-aged children
  • Children who consumed an omega-3 fat supplement as infants scored higher on rule learning, vocabulary and intelligence testing at ages 3-5
  • Previous studies have also found children with attention deficit hyperactivity disorder (ADHD) and related behavior/learning disabilities are more likely to have low omega-3 fat levels, as well as benefit from supplementation
  • I recommend supplementing with animal-based omega-3 fats like krill oil before and during pregnancy, and while breastfeeding (infants receive DHA through breast milk); as soon as your child can safely swallow a capsule, he or she can start taking a high-quality, animal-based omega-3 supplement
  • dha
  • If you want your child to reach his or her maximum intellectual potential, the research is clear that plentiful intake of the omega-3 fat DHA (docosahexaenoic acid) is essential.
  • In the US, most kids get hardly any of this healthful fat, found primarily in seafood, in their diets, and may be missing out on this simple opportunity to boost brain performance.
  • Most recently, two new studies have confirmed that boosting your child’s intake of DHA as an infant and into the school-age years may be a simple way to generate measurable improvements in their brain function.
  • The first study involved children aged 7-9 who had below-average reading scores. In these kids, low levels of DHA and other omega-3 fats were associated with poor reading, memory and behavioral problems.1
  • Previous studies have also found children with attention deficit hyperactivity disorder (ADHD) and related behavior/learning disabilities are more likely to have low omega-3 fat levels that could benefit from supplementation.
  • The new study was unique in that it looked at healthy children without learning disabilities, but with poor reading skills, and still found a link with low omega-3 levels.
  • “These findings require confirmation, but suggest that the benefits from dietary supplementation with Omega-3 LC-PUFA [long-chain polyunsaturated fatty acids] found for ADHD, Dyspraxia, Dyslexia, and related conditions might extend to the general school population,” the researchers concluded.
  • In the second study, a group of infants received either an omega-3 fat supplement or a placebo.2 Tests to evaluate their cognition were given every six months starting at age 18 months and continuing until they were 6 years old.
  • While no changes were noted in the early test done at 18 months, the study found that infants consuming omega-3 fats consistently outscored the placebo group later, between 3 and 5 years old.
  • Specifically, the omega-3 fat group scored higher on rule learning, vocabulary and intelligence testing, which suggests early omega-3 fat supplementation, during the key period when your child’s brain is still developing, may translate directly into greater intelligence in the pre-school and school-aged years. The researchers noted:
  • “ … although the effects of LCPUFAs [omega-3 fats] may not always be evident on standardized developmental tasks at 18 mo[nths], significant effects may emerge later on [for] more specific or fine-grained tasks.”
  • Sixty percent of your brain is made up of fat. DHA alone makes up about 15 percent to 20 percent of your brain’s cerebral cortex. It’s found in relatively high levels in your neurons – the cells of your central nervous system, where it provides structural support.
  • Because your brain is literally built from omega-3 fats, it makes sense that it would play an integral role in brain function (and even may help support healing after a brain injury).
  • Still more research found, for instance, that DHA supplementation might affect functional cortical brain activity in 8-10-year-old boys.3
  • The study included 33 healthy boys who were randomly assigned to receive a daily dose of either 400 milligrams (mg) of DHA, 1,200 mg of DHA, or a placebo, for two months. Researchers then measured the boys’ brain activation patterns, using functional magnetic resonance imaging (fMRI), while the boys were playing video games.
  • In the group receiving the highest daily dose, the DHA levels in the membrane of red blood cells (erythrocytes) increased by a whopping 70 percent. The lower dose group saw an increase of 47 percent, while the placebo group had an 11 percent reduction in DHA levels while performing this type of sustained attention task.
  • The fMRI data indicates that there were significant increases in the activation of the dorsolateral prefrontal cortex part of the brain in the groups receiving supplemental DHA. This is an area of your brain that is associated with working memory.

    They also noticed changes in other parts of the brain, including the occipital cortex (the visual processing center) and the cerebellar cortex (which plays a role in motor control). The researchers noted:

  • “These findings suggest that this imaging paradigm could be useful for elucidating neurobiological mechanisms underlying deficits in cortical activity in psychiatric disorders associated with DHA deficiencies, including ADHD and major depression.”
  • A high-quality, animal-based omega-3 supplement is something that I recommend for virtually everyone, especially if you’re pregnant, as the benefits likely begin in utero. Research has, in fact, linked inadequate intake of omega-3 fats in pregnant women to premature birth and low birth weight, in addition to hyperactivity in children. So not only is this one healthful fat your children should be consuming, but you should likely be consuming as well – and this includes in later life, too.
  • It is a point well worth emphasizing that omega-3 fats are considered essential because your body cannot produce them, and must get them from your daily diet. DHA-rich foods include wild fish, liver, and brain—all of which are no longer consumed in great amounts by most Americans. When your omega-3 intake is inadequate, your nerve cells become stiff and more prone to inflammation as the missing omega-3 fats are substituted with cholesterol and omega-6 instead. Once your nerve cells become rigid and inflamed, proper neurotransmission from cell to cell and within cells become compromised.
  • It’s thought that the unsaturated fatty acid composition of normal brain tissue is age-specific, which could imply that in addition to their importance during brain development, the older you get, the greater your need for animal-based omega-3 fat to prevent mental decline and brain degeneration becomes.4
  • For example, low DHA levels have been linked to memory loss and Alzheimer’s disease, and research suggests degenerative conditions can not only be prevented but also potentially reversed. For example, in one study, 485 elderly volunteers suffering from memory deficits saw significant improvement after taking 900 mg of DHA per day for 24 weeks, compared with controls.5 The point is, consuming omega-3 fats is a lifelong habit you should get into, just as important as drinking plenty of pure water and eating vegetables…
  • While a helpful form of omega-3 (ALA) can be found in flaxseed, chia, hemp, and a few other foods, the most beneficial form of omega-3 — containing the two fatty acids, DHA and EPA, which are essential to brain function — can only be found in fish and krill. While your body can convert ALA into DHA/EPA, it does so at a very low ratio, and only when sufficient enzymes (that many people are deficient in) are present.
  • Unfortunately, nearly all EPA- and DHA-rich fish are now severely contaminated with toxic mercury, which is why I generally don’t recommend consuming fish on a regular basis. About the only exception to this rule is wild-caught Alaskan salmon or very small fish, like sardines. Alaskan salmon is really the ONLY fish I eat regularly, and the only one I feel comfortable recommending as a good source of healthful fats. AVOID farmed salmon, as it contains only about half of the omega-3 levels of wild salmon. Farmed salmon may also contain a range of harmful contaminants, including environmental toxins, synthetic astaxanthin, and dangerous metabolic byproducts and agrichemical residues of genetically engineered organisms from the corn- and soy-based feed they’re given.
  • My latest recommendation for a source of high-quality omega-3 fats is krill oil. The omega-3 in krill is attached to phospholipids that increase its absorption, which means you need less of it, and it won’t cause belching or burping like many other fish oil products. Additionally, it contains naturally occurring astaxanthin, a potent antioxidant—almost 50 times morethan is present in fish oil.
  • This prevents the highly perishable omega-3 fats from oxidizing before you are able to integrate them into your cellular tissue. In laboratory tests, krill oil remained undamaged after being exposed to a steady flow of oxygen for 190 hours. Compare that to fish oil, which went rancid after just one hour. That makes krill oil nearly 200 times more resistant to oxidative damage (i.e. rancidity) compared to fish oil! When purchasing krill oil, you’ll want to read the label and check the amount of astaxanthin it contains. The more the better, but anything above 0.2 mg per gram of krill oil will protect it from rancidity.
  • As for your kids, I recommend supplementing with krill oil before and during pregnancy, and while breastfeeding. Infants receive vital DHA through your breast milk, so if you can continue breastfeeding through the first year, you will give your child a great head start for success in life.
  • Then, as soon as your child can safely swallow a capsule, he or she can start taking a high-quality krill oil supplement. The capsules should be kid-sized – about half the size of a regular capsule – and odor-free, making them easy and palatable for kids to swallow.

·         Low DHA Levels May Impact Reading, Memory and Behavior

·         DHA Supplementation Early in Life Increases Intelligence as Older Children

·         Omega-3s Found to Alter and Boost Brain Function

·         Omega-3 Fats Are Essential During Pregnancy (and Later in Life) Too

·         What’s the Optimal Source of Omega-3 Fats?

·         Tips for Giving Omega-3 Fats to Kids

Source: mercola.com

 

 

Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation.

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Abstract

BACKGROUND:

Anticoagulant treatment with vitamin K antagonists (VKAs) is aimed at preventing thromboembolic complications and has been the therapy of choice for most people with non-valvular atrial fibrillation (AF) for many decades. A new class of anticoagulants, the factor Xa inhibitors, appear to have several pharmacological and practical advantages over VKAs.

OBJECTIVES:

To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for the prevention of cerebral or systemic embolic events in people with AF.

SEARCH METHODS:

We searched the trials registers of the Cochrane Stroke Group and the Cochrane Heart Group (June 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10), MEDLINE (1950 to April 2013) and EMBASE (1980 to April 2013). In an effort to identify further published, unpublished and ongoing trials we searched trials registers and Google Scholar (July 2012). We also screened reference lists and contacted pharmaceutical companies, authors and sponsors of relevant published trials.

SELECTION CRITERIA:

Randomised controlled trials that directly compared the effects of long-term treatment (more than four weeks) with factor Xa inhibitors and VKAs for the prevention of cerebral and systemic embolism in patients with AF. We included patients with and without a previous stroke or TIA.

DATA COLLECTION AND ANALYSIS:

The primary efficacy outcome was the composite endpoint of all strokes and other systemic embolic events. Two authors independently assessed trial quality and the risk of bias, and extracted data. We calculated a weighted estimate of the typical treatment effect across trials using the odds ratio (OR) with 95% confidence interval (CI) by means of a fixed-effect model. However, in the case of moderate or high heterogeneity of treatment effects, we used a random-effects model to compare the overall treatment effects and performed a pre-specified sensitivity analysis excluding any fully open-label studies.

MAIN RESULTS:

We included data from 42,084 participants randomised into 10 trials. All participants had a confirmed diagnosis of AF (or atrial flutter) and were deemed by the randomising physician to be eligible for long-term anticoagulant treatment with a VKA (warfarin) with a target International Normalised Ratio (INR) of 2.0 to 3.0 in most patients. The included trials directly compared dose-adjusted warfarin with either apixaban, betrixaban, darexaban, edoxaban, idraparinux or rivaroxaban. Four trials were double-masked, five partially-masked (that is different doses of factor Xa inhibitor administered double-masked and warfarin administered open-label) and one was open-label. Median duration of follow-up ranged from 12 weeks to 1.9 years.The composite primary efficacy endpoint of all strokes (both ischaemic and haemorrhagic) and non-central nervous systemic embolic events was reported in nine of the included studies (40,777 participants). Treatment with a factor Xa inhibitor significantly decreased the number of strokes and systemic embolic events compared with dose-adjusted warfarin (OR 0.81, 95% CI 0.72 to 0.91). We also analysed both components of this composite endpoint separately: treatment with a factor Xa inhibitor significantly decreased both the number of ischaemic and haemorrhagic strokes (OR 0.78, 95% CI 0.69 to 0.89) and the number of systemic embolic events (OR 0.53, 95% CI 0.32 to 0.87).All of the included studies (42,078 participants) reported the number of major bleedings. Treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.89, 95% CI 0.81 to 0.98). There was, however, statistically significant and high heterogeneity (I² = 81%) and an analysis using a random-effects model did not show a statistically significant decrease in the number of major bleedings (OR 0.92, 95% CI 0.63 to 1.34). The pre-specified sensitivity analysis excluding open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.84, 95% CI 0.76 to 0.92) but moderate heterogeneity was still observed (I² = 65%). A similar sensitivity analysis using a random-effects model did not show a statistically significant decrease in the number of major bleedings in patients treated with factor Xa inhibitors (OR 0.78, 95% CI 0.57 to 1.05). Part of the observed heterogeneity can thus be explained by the increased risk of major bleedings in the factor Xa treatment arm in the single included open-label study, which studied idraparinux. Other heterogeneity might be explained by differences in baseline bleeding risks in the two largest trials of apixaban and rivaroxaban that we included in this review.Data on intracranial haemorrhages (ICHs) were reported in eight studies (39,638 participants). Treatment with a factor Xa inhibitor significantly reduced the risk of ICH compared with warfarin (OR 0.56, 95% CI 0.45 to 0.70). Again, we observed statistically significant heterogeneity (I² = 60%). The pre-specified sensitivity analysis excluding the open-label study showed that treatment with a factor Xa inhibitor significantly reduced the number of ICHs compared with warfarin (OR 0.51, 95% CI 0.41 to 0.64), without any sign of statistical heterogeneity (I² = 0%).The number of patients who died from any cause was reported in six studies (38,924 participants). Treatment with a factor Xa inhibitor significantly reduced the number of all-cause deaths compared with warfarin (OR 0.88, 95% 0.81 to 0.97).

AUTHORS’ CONCLUSIONS:

Factor Xa inhibitors significantly reduced the number of strokes and systemic embolic events compared with warfarin in patients with AF. Factor Xa inhibitors also seem to reduce the number of major bleedings and ICHs compared with warfarin, though the evidence for a reduction of major bleedings is somewhat less robust. There is currently no conclusive evidence to determine which factor Xa inhibitor is more effective and safer for long-term anticoagulant treatment of patients with AF as head-to-head studies of the different factor Xa inhibitors have not yet been performed.

Source: PMID

 

Effects of Vascular Endothelial Growth Factor Signaling Inhibition on Human Erythropoiesis.

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Inhibition of vascular endothelial growth factor (VEGF) signaling increases red blood cell (RBC) counts, and erythropoiesis markers have been proposed to guide antiangiogenic therapy in humans. We analyzed RBC measurements in patients enrolled in three studies: a phase II trial of axitinib in thyroid cancer; a study of sorafenib in advanced solid tumors; and a randomized trial of fluorouracil, hydroxyurea, and radiation with and without bevacizumab for head and neck cancer. In the sorafenib trial, plasma erythropoietin concentrations were measured at baseline, day 8, and day 35. Over the first 84 days of treatment, RBC counts increased for each day on sorafenib (2.7 M/μ L [95% confidence interval (CI), 1.5–3.9]) and axitinib (4.3 M/μ L [95% CI, 2.2–6.5]). RBCs declined over the first 68 days of cytotoxic chemoradiotherapy alone (−12.8 M/μ L per day [95% CI, −15.7 to −9.8]) but less so with added bevacizumab (−7.2 M/μ L per day [95% CI, −9.5 to −4.9]). Erythropoietin levels increased, on average, by 9.5 mIU/mL between day 8 and day 35 of sorafenib exposure. No significant relationships between elevations in RBCs and changes in volume status or blood pressure or between elevations in erythropoietin and smoking status were found. VEGF signaling inhibition is associated with increased RBC and erythropoietin production in humans. The effects of these changes are subtle at physiologic doses and are unlikely to be clinically useful biomarkers for guiding the administration of or predicting treatment responses to VEGF pathway inhibitors.

  • Source: the Oncologist

 

Ultrasonographically guided peripheral intravenous cannulation of children and adults: a systematic review and meta-analysis. .

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Peripheral intravenous cannulation is procedurally challenging and painful. We perform a systematic review to evaluate ultrasonographic guidance as an aid to peripheral intravenous cannulation.

METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, ClinicalTrials.gov, and Google.ca. We included randomized trials evaluating ultrasonographically guided peripheral intravenous cannulation and reporting risk of peripheral intravenous cannulation failure, number of attempts, procedure time, or time from randomization to peripheral intravenous cannulation. We separately analyzed pediatric and adult data and emergency department (ED), ICU, and operating room data. Quality assessment used the Cochrane Risk of Bias Tool.
RESULTS: We identified 4,664 citations, assessed 403 full texts for eligibility, and included 9 trials. Five had low risk, 1 high risk, and 3 unclear risk of bias. A pediatric ED trial found that ultrasonography decreased mean difference (MD) in the number of attempts (MD -2.00; 95% confidence interval [CI] -2.73 to -1.27) and procedure time (MD -8.10 minutes; 95% CI -12.48 to -3.72 minutes). In an operating room pediatric trial, ultrasonography decreased risk of first-attempt failure (risk ratio 0.23; 95% CI 0.08 to 0.69), number of attempts (MD -1.50; 95% CI -2.52 to -0.48), and procedure time (MD -5.95; 95% CI -10.21 to -1.69). Meta-analysis of adult ED trials suggests that ultrasonography decreases the number of attempts (MD -0.43; 95% CI -0.81 to -0.05). Ultrasonography decreased risk of failure (risk ratio 0.47; 95% CI 0.26 to 0.87) in an adult ICU trial.
CONCLUSION: Ultrasonography may decrease peripheral intravenous cannulation attempts and procedure time in children in ED and operating room settings. Few outcomes reached statistical significance. Larger well-controlled trials are needed.

Source: Annals of Emergency Medicine.

 

A randomized, open-label study of sirolimus versus cyclosporine in primary de novo renal allograft recipients. .

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Despite a decreased incidence of acute rejection and early renal allograft loss due to calcineurin inhibitors (CNIs) in transplant recipients, nephrotoxicity associated with long-term CNI use remains an important issue. This study evaluated whether a CNI-free regimen, including sirolimus, mycophenolate mofetil, corticosteroids, and anti-interleukin-2 receptor antibody induction, results in improved long-term renal function.

METHODS: This open-label, randomized, parallel group, comparative study in primary de novo renal transplant recipients was planned for 48 months but terminated early because of high acute rejection rates in the sirolimus arm.
RESULTS: Enrollment was stopped after approximately 12 months, with 475 transplanted patients randomized (2:1) to sirolimus (n=314) or cyclosporine A (CsA) treatment (n=161). Mean length of follow-up after transplantation was 190 days; this article focuses on available data through 6 months. Mean+/-SD on-therapy Nankivell-calculated glomerular filtration rate was not significantly different between the sirolimus (69.1+/-18.7 mL/min) and CsA (66.0+/-15.2 mL/min) treatment groups. Occurrence and length of delayed graft function was not significantly different between groups. Patients in the sirolimus group experienced numerically lower survival rates (96.9% vs. 99.4%; P=0.14), with nine deaths reported with sirolimus and one with CsA; higher rates of biopsy-confirmed acute rejection (21.4% vs. 6.1%; P<0.001); and higher rates of discontinuations due to adverse events (17.4% vs. 6.8%; P=0.001).
CONCLUSION: A sirolimus-based, CNI-free immunosuppressive regimen, when used with mycophenolate mofetil, corticosteroids, and anti-interleukin-2 receptor antibody induction, was associated with high rates of biopsy-confirmed acute rejection compared with CsA-based immunosuppression and is not recommended.

Source: Transplantation.

 

Mortality and causes of death in Crohn`s disease: results from 20 years of follow-up in the IBSEN study.

Population-based studies have shown a slightly decreased life expectancy in patients with Crohn`s disease (CD). The primary aim of the present study was to evaluate mortality and causes of death 20 years after the diagnosis in a well defined population-based cohort of CD patients in Norway.
DESIGN: The Inflammatory Bowel South-Eastern Norway study has prospectively followed all patients diagnosed with CD in the period between 1 January 1990 and 31 December 1993 in four geographically well-defined areas. All patients (n=237) were age and sex matched with 25 persons from the same county selected at random from the general population. Data on death and causes of deaths were collected from the Norwegian Causes of Death Register. All causes and cause-specific mortality (gastrointestinal cancer, cancer and heart disease) were modelled with Cox regression model stratified by matched sets. Results are expressed as HRs with 95% CIs.
RESULTS: There was no significant difference between CD patients and controls in overall mortality (HR=1.35, 95% CI 0.94 to 1.94, p=0.10). Furthermore, there were no marked differences in deaths from gastrointestinal cancer, other cancers or cardiovascular diseases in the CD group compared with the controls. In the CD group, 13.9% had died compared with 12.7% in the control group (p=0.578).
CONCLUSIONS: In our population-based inception cohort followed for 20 years, there was no increased mortality or more deaths from cancer compared with the general population.

Source: Gut

Increased risk of arthropathies and joint replacement surgery in patients with genetic hemochromatosis.

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Genetic hemochromatosis (GH) is an autosomal recessive disease in individuals of Northern and Western European descent. Heterozygosity for the C282Y mutation is common (6-20%). Arthropathy is one of the few complications of GH suggested not to be associated with iron body stores; synovial iron deposition remains in iron-depleted patients. Previous studies suggest an elevated prevalence of clinical and radiographic signs of arthropathy in patients with GH, and 2 smaller studies suggest a possibly elevated risk of joint replacement surgery, but more mixed results are shown regarding risks with HFE genotype. We therefore assessed the risks of arthropathy and joint replacement surgery in patients with GH and in their first-degree relatives (FDRs).

METHODS: We performed a population-based cohort study of 3,531 patients with GH and of their 11,794 FDRs (assumed to be heterozygous for the C282Y mutation) using nationwide Swedish population-based health and census registers. Hazard ratios (HRs) of arthropathies and joint replacement surgeries among patients and their FDRs (versus the general population) were assessed using Cox regression.
RESULTS: Between 1997 and 2005, 406 of 3,531 patients were reported/hospitalized with any noninfectious arthropathies, including osteoarthritis, corresponding to an HR of 2.38 (95% confidence interval [95% CI] 2.14-2.64). Patients were also at increased risk of hip replacement (HR 2.77, 95% CI 2.27-3.38) and knee replacement (HR 2.14, 95% CI 1.58-2.88) surgery. Among the 11,794 FDRs (patients excluded), we found no increased risk of any of the joint morbidities.
CONCLUSION: Patients with GH, but not their FDRs, are at increased risk of arthropathies, including the need for joint replacement surgery.