The Doctor's Channel - Critical Care

3-pronged treatment improves outcomes in neonatal post-bleeding ventricular dilatation

2010-03-12T20:56:51+00:00

NEW YORK (Reuters Health) - A treatment called DRIFT (Drainage, Irrigation, and Fibrinolytic Therapy) may improve developmental outcomes and survival in preterm infants with posthemorrhagic cerebral ventricular dilatation, new research suggests.

Definitive conclusions can't be drawn as the trial was stopped early, partly due to a higher risk of secondary intraventricular bleeding with DRIFT. But clinically speaking, infants treated with DRIFT were better off two years later than those given standard therapy.

"Premature infants with posthemorrhagic ventricular dilatation have a high rate of severe cognitive and motor disabilities, but no intervention has been shown to improve outcome," lead author Dr. Andrew Whitelaw, from the University of Bristol Medical School, U.K., and colleagues note.

"Secondary cerebral injury may be caused by free radicals, inflammation, and pressure," the authors explain. Drainage, irrigation, and fibrinolysis address all these mechanisms and could potentially improve patient outcomes.

As they report in the April issue of Pediatrics, the researchers randomized 77 preterm infants with posthemorrhagic ventricular dilatation to receive DRIFT (n = 39) or standard treatment (n = 38), which included drainage of cerebrospinal fluid to control ventricular expansion.

By two years of corrected age, 3 children in the DRIFT group and 5 in the control group had died, and 18 and 22 in the DRIFT and control groups, respectively, were severely disabled.

Therefore, rates of the primary endpoint - death or severe disability - were 54% with DRIFT versus 71% with standard care (adjusted OR, 0.25).

"Severe cognitive disability was nearly halved" with DRIFT, the authors report. Specifically, 11 survivors in the DRIFT group (31%) had severe cognitive impairment, versus 19 of 33 (58%) in the control group (aOR, 0.17), as measured by the Bayley Mental Development Index. The median Mental Development Index score in the DRIFT group was also better: 68 vs. <50.

DRIFT did not improve rates of sensorimotor disability, however.

The research team comments that their results "raise a difficult dilemma in trial management." Given that the interim analysis showed increased intracerebral bleeding and no decrease in the need for shunts with DRIFT, "few would have taken responsibility in 2007 for continuing to recruit" to this trial. But today, the authors continue, the two study groups have a difference of more than 18 points on the Mental Development Index score, "which most families and clinicians would rate as important."

With the caveat that their population was small and the trial was stopped early, the researchers still conclude: "Despite an increase in secondary intraventricular bleeding, DRIFT reduced severe cognitive disability in survivors and overall death or severe disability."

Reference:
Pediatrics 2010;125:e852-e858.

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Cardiac catheterization has low diagnostic yield

2010-03-11T22:49:39+00:00

NEW YORK (Reuters Health) – Just 38% of patients with suspected cardiac disease are found to have obstructive coronary disease on elective cardiac catheterization, new research shows. This low diagnostic yield suggests that clinical assessments and noninvasive tests are not doing their job in selecting patients for cardiac catheterization.

“Guidelines recommend continued observation in the case of patients who are at very low risk, noninvasive stress testing to determine the need for cardiac catheterization in the case of patients at intermediate risk, and direct referral for catheterization in the case of patients at high risk,” lead author Dr. Manesh R. Patel and colleagues note.

But whether these recommendations help limit the number of patients without coronary disease who undergo cardiac catheterization was unclear, according to the report in The New England Journal of Medicine for March 11.

To investigate, Dr. Patel, from Duke University Medical Center, Durham, North Carolina, and colleagues analyzed national registry data on nearly 400,000 patients without known coronary disease who had elective cardiac catheterization at 663 hospitals in the U.S.

Obstructive coronary disease was defined as stenosis of at least 50% of the diameter of the left main coronary artery or stenosis of at least 70% of the diameter of a major epicardial vessel.

The median patient age was 61 years and 52.7% of patients were male. Twenty-six percent of subjects had diabetes and 69.6% had hypertension. Roughly 84% had noninvasive tests before cardiac catheterization.

Only 37.6% of patients had obstructive coronary disease at catheterization, the report indicates. Moreover, 39.2% of patients had no coronary disease (stenosis <20% in all vessels).

A positive noninvasive test result slightly increased the likelihood of finding obstructive disease: 41.0% vs. 35.0% (adjusted odds ratio, 1.28, p < 0.001).

In an editorial, Dr. David J. Brenner from Columbia University Medical Center in New York agrees with the authors that a better “gatekeeper” test is needed to select the best candidate for cardiac catheterization. “Ironically,” he notes, “there is evidence that, in many situations, a better gatekeeper test may be yet another radiographic imaging technique—namely, multidetector-row computed-tomographic angiography.”

Reference:
N Engl J Med 2010;362:886-895,943-945.

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Women benefit as much as men from statins for primary prevention of CVD

2010-03-11T22:44:28+00:00

NEW YORK (Reuters Health) - Statin use by women cuts their risk of primary cardiovascular disease (CVD) events by roughly a third, which is similar to the risk reduction seen in men, research shows.

"Statin therapy in women without CVD is controversial, given the insufficient evidence of benefit," Dr. Samia Mora, from Brigham and Women's Hospital, Boston, and colleagues note in the March 9th issue of Circulation.

Dr. Mora and colleagues analyzed gender-specific outcomes from the randomized JUPITER trial and performed a meta-analysis of statin trials that focused on women.

JUPITER included 6801 women at least 60 years of age, and 11,001 men at least 50 years of age. All had high C-reactive protein levels (at least 2 mg/L) and normal to low levels of low density lipoprotein cholesterol (no higher than 130 mg/dL). Participants took either rosuvastatin or placebo daily.

The meta-analysis included 7 primary prevention trials, with 13,154 women who had 240 CVD events and 216 deaths.

Compared to the men in the JUPITER trial, the women had lower absolute CVD rates per 100 person-years (0.57 vs. 0.88 for rosuvastatin groups and 1.04 vs. 1.54 for placebo groups) - but both genders had relative risk reductions of roughly 44%.

Further analysis showed that statin therapy significantly reduced revascularization and unstable angina in women, but did not affect other CVD events.

In the meta-analysis, statin use by women cut primary CVD events by 37% (p < 0.001), but did not significantly affect total mortality.

When the results of JUPITER and the meta-analysis are taken together, the researchers conclude, "statin therapy resulted in about a one-third relative reduction in primary CVD in women, a benefit similar to that seen in previous meta-analyses of men."

Reference:
Circulation 2010;121:1069-1077.

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Longer follow-up confirms advantage of sirolimus-eluting vs bare metal stents

2010-03-10T16:43:41+00:00

NEW YORK (Reuters Health) – Three years after ST-segment elevation myocardial infarction (STEMI), sirolimus-eluting stents still provide better protection against major adverse cardiovascular events compared to bare metal stents, new research shows.

The findings are based on 3 years of data from the randomized SESAMI trial. The 1-year results from SESAMI indicated superior outcomes with sirolimus-eluting stents.

Until now, however, long-term safety and efficacy data for sirolimus-eluting stents in STEMI patients came only from registries, according to author Dr. Carmine Musto, from San Camillo Hospital, Rome, and colleagues.

As reported in the February 23rd Journal of the American College of Cardiology, SESAMI included 320 patients, with long-term data available for more than 97% in each group.

The primary outcome – the incidence of major adverse cardiovascular events at 3 years – was 12.7% with sirolimus-eluting stents vs 21% with bare metal stents (p = 0.034). The endpoint was a composite of cardiac and noncardiac death, Q-wave and non-Q-wave infarction, coronary artery bypass graft surgery, or target lesion revascularization.

Patients with sirolimus-eluting stents also had significantly lower rates of target lesion revascularization (7% vs. 13.5%, p = 0.048), target vessel revascularization (8% vs. 16%, p = 0.027), and target vessel failure (11.5% vs. 20.5%, p = 0.028) compared to patients with bare metal stents.

In addition, significantly more sirolimus-treated patients were alive and free from these adverse outcomes (87% to 93%, depending on the event) compared to patients with bare metal stents (79% to 86.5%; p < 0.05). Prevention of target lesion revascularization drove the benefit of the drug-eluting stents, and this was first apparent in the first year of follow-up.

After clopidogrel was discontinued, the two groups had similar cumulative rates of death and recurrent myocardial infarction, the report indicates.

The study had two principal limitations, the authors note. First, it examined only clinical endpoints. Second, it was not powered to detect differences in cardiac event rates between 12 and 36 months.

Reference:
J Am Coll Cardiol 2010;55:810-814.

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Tenofovir-related renal dysfunction can't always be reversed

2010-03-09T16:55:19+00:00

NEW YORK (Reuters Health) - Tenofovir nephrotoxicity can't always be fully reversed in HIV-infected men, according to a new study.

Up to 2% of patients have adverse renal effects from the nucleotide reverse transcriptase inhibitor, and reportedly, kidney function rapidly normalizes when tenofovir is stopped. But "because of the few cases, limited follow-up and the insensitive measure used" (serum creatinine) in the previous reports, it's not known how reversible the nephrotoxicity really is, note senior author Dr. Andrew Carr, from St. Vincent's Hospital, Sydney, Australia, and colleagues.

In a paper published online February 19th in the Journal of Acquired Immune Deficiency Syndromes, Dr. Carr and his associates describe 24 men who discontinued tenofovir because their estimated glomerular filtration rate (eGFR) was less than 60 ml/minute/1.73 m2.

During a median of 30 months between start of tenofovir and drug cessation, median eGFR fell from 74 to 51 ml/min/1.73 m2 - a reduction about 10 times greater than expected with normal aging.

During the median period of 13 months after tenofovir discontinuation, eGFR rose by a median of 19 ml/min/1.73 m2. Most improvement occurred in the first month.

In only 10 (42%) patients did eGFR return to pre-tenofovir levels, and only two exceeded 90 ml/min/1.73 m2.

Twelve patients had eGFR increases above the median; this group had a more rapid monthly decline while on tenofovir compared to those with less improvement (1.9 vs 0.7 ml/min/1.73 m2, p = 0.009) and a shorter duration of tenofovir therapy (21 vs 51 months, p = 0.08), suggesting that "more acute renal damage is less likely to be permanent."

These patients were also more likely to have received protease inhibitors (100% vs 54%, p = 0.02). The authors explain that protease inhibitors can increase tenofovir levels in plasma and renal tubular epithelium. Therefore, the greater improvement was likely due to cessation of higher tenofovir exposure.

The single-center study was retrospective, relatively small and had a variable duration of follow-up, and so prospective validation in a larger, more heterogeneous population is needed, the researchers say.

Nevertheless, they conclude, earlier discontinuation of tenofovir might have led to greater improvements in renal function, "which underlines the importance of regular assessment and perhaps of earlier intervention."

Specifically, they advise, even gradual deterioration in eGFR to levels above 60 ml/min/1.73 m2 might be cause enough to discontinue tenofovir.

Reference:
J Acquir Immune Defic Syndr 2010.

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Emboli filters during PCI lead to higher risk of stent thrombosis

2010-03-09T16:49:30+00:00

NEW YORK (Reuters Health) - Using a distal filter to protect against emboli during coronary stent implantation increases long-term rates of stent thrombosis and target vessel revascularization, investigators in Denmark report.

Randomized trials have shown no benefit of distal protection in the short or intermediate term after percutaneous coronary intervention (PCI), Dr. Anne Kaltoft from Aarhus University Hospital, Skejby, and her associates note. Their article in the Journal of the American College of Cardiology for March 2 reports their 15-month follow-up of patients treated for ST-elevation myocardial infarction in the DEDICATION trial.

Patients received aspirin, clopidogrel, and unfractionated heparin in advance of the procedure. If a cardiologist believed that a wire filter could be advanced (based on pre-dilation and initial visualization of the peripheral vascular bed), the researchers then randomized the patient either to distal protection (n = 312) or conventional treatment (n = 314).

In the distal protection group, filter placement was attempted in 304 patients (97%) and was successful in 254 patients (81%).

But filter protection afforded no benefit at either 30 days, 6 months, or 15 months later, the researchers said.

Nine cases of definite stent thrombosis occurred in the protection group and one in the control group (2.9% vs 0.3%, p = 0.01).

The rate of target lesion revascularization was also significantly increased in the distal protection group (12.5% vs 7%, p = 0.05), as was the rate of target vessel revascularization (15.4% vs 8.3%, p < 0.01).

The two groups had similar rates of myocardial infarction and mortality.

Dr. Kaltoft's team suggests that vessel spasm in response to filter placement could lead "to an underestimation of the vessel diameter and to undersizing of the implanted stent, a known predictor of early stent thrombosis." Other possibilities include damage to the vessel wall at the site of filter deployment or stent apposition during filter retrieval.

Similarly, damage to the vessel wall from pre-dilation or during placement of the filter could increase restenosis rates and the need for repeat revascularization.

Whatever the cause, the authors conclude, "Routine use of a filter wire in its present form cannot be advocated and probably should be avoided with primary PCI for ST-elevation myocardial infarction."

Reference:
J Am Coll Cardiol 2010;55:867-871.

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Cardiac vegetations don't rule out percutaneous ICD lead extraction

2010-03-08T19:26:08+00:00

NEW YORK (Reuters Health) - Percutaneous extraction of pacemaker or implantable cardioverter-defibrillator (ICD) leads is safe in patients with cardiac vegetations, investigators report. And as long as blood cultures remain sterile, permanent devices can be reimplanted within a week or two.

Eradication of device-related infection requires complete system removal, the authors note in the March 2nd Journal of the American College of Cardiology. Traditionally, patients with vegetations larger than 1 cm in diameter have had their leads removed via thoracotomy, in order to avoid septic emboli -- but the surgery itself increases patients' risks for serious complications and for prolonged recovery.

Senior author Dr. Steven P. Kutalek and associates at Drexel University College of Medicine, Philadelphia, studied 100 patients (mean age, 67 years) who had 1838 leads extracted percutaneously despite echocardiographic evidence of vegetations. This group accounted for roughly 10% of all the percutaneous lead extraction cases at the authors' center between 1991 and 2007.

The vegetations ranged from 0.2 to 4.0 cm in largest diameter (mean 1.6 cm). Implants had been in place for an average of 51 months. The median extraction time (4 min per lead) was not significantly different from the median in a reference group consisting of all 66 patients without vegetations who underwent extraction in 2004.

Five patients had complications during lead extraction, including embolized vegetation in two. However, all 5 were discharged in stable condition and recovered uneventfully.

In 54 patients, surgeons reimplanted new devices during the same hospitalization, at a median of 7 days after extraction. None of these second devices had to be extracted due to relapsing infection.

Twenty-nine patients were lost to follow-up. In the remaining 71, the average follow-up was 438 days.

Nineteen patients died - 11 of persistent septicemia, 1 of sudden cardiac death, and the other 7 of unknown causes with no evidence of ongoing infection (including 4 who had received a new device).

Ten patients died within 30 days of lead extraction. "These unfortunate outcomes occurred in a critically ill subset of patients who often have extensive comorbidities," the researchers note. They attribute the operative mortality to disease severity rather than the mode of lead extraction.

Also, "given the frequent ambiguity of initial culture data," the authors recommend transesophageal ultrasonography before device extraction in order to identify patients at high risk for endocarditis.

This study demonstrates that "percutaneous lead extraction with vegetations of all sizes is possible and seemingly appropriate," Dr. James D. Maloney at Heartland Spine and Specialty Hospital, Overland Park, Kansas, and Dr. James D. Maloney III at the University of Wisconsin, Madison, write in a related editorial.

Still, they're concerned that residual infected inflammatory tissue needs to be debrided after the leads are removed.

"The question remains... if a nidus of chronic infection sometimes remains, does that cause refractory sepsis and congestive heart failure?" they ask. "Can and should it be removed surgically?"

Reference:
J Am Coll Cardiol 2010;55:886-897.

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Aspirin prophylaxis not useful for asymptomatic vascular disease

2010-03-05T21:36:50+00:00

NEW YORK (Reuters Health) – Asymptomatic patients with a low ankle brachial index don’t seem to get cardiovascular protection from aspirin, randomized trial results suggest.

The subjects came from a cohort of nearly 29,000 men and women ages 50 to 75 years enrolled in a community health registry in Scotland. All were free of clinical cardiovascular disease at baseline, and each agreed to ankle brachial index screening. The 3350 individuals with an index of no more than 0.95 took either 100 mg of aspirin daily, or placebo, for the next 8.2 years, on average.

In the Journal of the American Medical Association for March 3, lead author Dr. F. Gerald R. Fowkes, from the University of Edinburgh and colleagues report that 357 subjects met the main endpoint (a composite of coronary events, stroke, or revascularization). Rates per 1000 person-years were similar with aspirin (13.7) and placebo (13.3).

Rates of a secondary outcome – a composite of the main endpoint plus angina, intermittent claudication, or transient ischemic attack – were also comparable: 22.8 vs. 22.9 per 1000 person-years with aspirin vs placebo, respectively.

All-cause mortality was similar as well, with 12.8 deaths per 1000 person-years in the aspirin group and 13.5 in the placebo group.

Subjects treated with aspirin were 71% more likely than those given placebo to experience major hemorrhage requiring admission to the hospital: 2.5 vs. 1.5 per 1000 person-years.

“Based on the trial conducted by Fowkes et al and other similar studies, aspirin appears to have marginal benefits for reducing initial cardiovascular events when used for patients without clinically evident cardiovascular disease and is associated with higher rates of bleeding in these patients,” Dr. Jeffrey S. Berger, from New York University School of Medicine, comments in a related editorial.

Dr. Fowkes and colleagues conclude that “given the increased level of risk among those with a low ankle brachial index, the use of alternative therapies, such as statins or more potent antiplatelet agents without attendant hemorrhagic risks may usefully be considered.”

Reference:
JAMA 2010;303:841-848,880-882.

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After hip replacement, mobile compression device cuts VTE without bleeding risk

2010-03-05T19:51:51+00:00

NEW YORK (Reuters Health) - A new battery-operated compression device is at least as effective as low-molecular weight heparin in preventing venous thromboembolism (VTE) after hip arthroplasty, but with a lower risk of major bleeding, new research suggests.

As reported in the March 1st issue of The Journal of Bone and Joint Surgery (American Volume), no patient who used the device had major bleeding, whereas 6% of those treated with enoxaparin (Lovenox) did.

The ActiveCare + Synchronized Flow Technology (S.F.T.) system offers several advantages over earlier compression devices, lead author Dr. Clifford W. Colwell, from the Scripps Clinic, La Jolla, California, told Reuters Health.

The device is portable enough for the patient to use after discharge, Dr. Colwell said. Another benefit is that the device "measures blood flow and can synchronize compression with a person's respirations." Also, it has "an LCD screen that can track a patient's compliance."

Dr. Colwell and his colleagues randomized 410 patients (who had 414 hips replaced) to 10 days of treatment with either ActiveCare+S.F.T. or enoxaparin (30 mg twice daily until discharge, then 40 mg once daily). Patients in the compression device group could take aspirin (81 mg/day) at the discretion of the treating clinician.

The authors screened patients for venous thromboembolism in the calf and thigh with duplex ultrasonography between postoperative days 10 to 12, and again at 12 weeks during a clinical exam.

Distal and proximal deep venous thrombosis rates were 3% and 2%, respectively, in the compression group -- not significantly different from the corresponding 3% and 1% rates seen in the enoxaparin group. Rates of pulmonary embolism, as confirmed by spiral CT lung scans, were 1% in each group.

One patient in the compression group with a negative ultrasound exam on day 12 had one deep venous thrombosis and one pulmonary embolism during the 12-week follow-up.

"I think there is going to be a paradigm shift in how we prevent venous thromboembolism," Dr. Colwell said. "I hope that once these findings come out, it will motivate other companies to produce similar devices."

The study was funded by Medical Compression Systems, Or Akiva, Israel, which manufactures the ActiveCare+S.F.T. system.

Reference:
J Bone Joint Surg Am 2010;92:527-535.

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Without thrombolysis, women fare worse than men after stroke

2010-03-04T15:20:25+00:00

NEW YORK (Reuters Health) – Thrombolysis is a must for female stroke patients if they are to achieve the same outcomes as men, according to a March 2nd report in the Neurology.

“Women need to be treated for stroke as soon as possible,” senior author Dr. Michael D. Hill, from the University of Calgary, Alberta, Canada, said in a statement. “We found that women who weren’t treated had a worse quality of life after stroke than men. However, the good news is that women who were treated responded just as well as men to the treatment.”

The findings are drawn from registry data on 2113 stroke patients treated all across Canada, from June 2001 to February 2002 and from June to December 2002. Women accounted for 43.5% of the cohort.

The primary outcomes were the score on the Stroke Impact Scale-16 score and mortality at 6 months.

Without tissue plasminogen activator (tPA), 70% of men but only 58% of had good outcomes, defined as a score of at least 75 on the Stroke Impact Scale-16 (p < 0.001). With tPA thrombolysis, however, women were just as likely as men to have good outcomes.

Mortality was comparable for men and women whether or not tPA was used.

After adjusting for age, stroke severity, and the time from symptom onset to arrival in the emergency department, gender was found to influence the Stroke Impact Scale-16 score, but not mortality.

Exactly why untreated women fare worse than untreated men is unclear, Dr. Hill said in the statement.

Biologic reasons could explain the difference, he noted. Or older women might be less likely than older men to have a surviving spouse who can assist them in their stroke recovery. In addition, post-stroke depression, which can slow recovery, is more common in women.

Reference:
Neurology 2010;74:767-771.

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