Occluding the proximal carotid artery with a balloon may confer better protection against cerebral embolization than a distal filter device during carotid stenting, a randomized trial found.

Compared with distal filter protection, proximal balloon occlusion significantly reduced the incidence of new ischemic lesions, according to Joachim Schofer, MD, from Hamburg University Cardiovascular Center in Hamburg, Germany, and colleagues.

The balloon occlusion strategy also resulted in a significant decrease in the number, as well as the volume, of new cerebral ischemic lesions, according to the study published in the Feb. 7 issue of Journal of the American College of Cardiology.

“These data are sensible, since in contrast to distal embolic protection devices, proximal embolic protection devices provide embolic protection prior to crossing the target lesion with a guidewire, and should be more efficient at capturing and removing debris since they are not dependent on filter pore size or particle dimensions,” wrote Robert D. Safian, MD, from the William Beaumont School of Medicine in Royal Oaks, Mich., in an accompanying editorial.

Although there are no restrictions for carotid endarterectomy reimbursement, the same is not true for carotid artery stenting (CAS), Safian pointed out.

The Centers for Medicare and Medicaid Services (CMS) will not reimburse carotid stenting for any standard-risk patients, Safian told MedPage Today. Reimbursement for stenting in high-risk patients is subject to certain restrictions, including: For symptomatic patients, the procedure must take place in a CMS-approved institution and the operators must use FDA-approved stents and embolic protection devices Both symptomatic and asymptomatic patients must be enrolled in an approved investigational device exemption trial or post-market approval registry.

There are several FDA-approved carotid stents, as well as approved embolic protection devices, including distal mesh filters and distal and proximal balloon occluding devices.

In his commentary, Safian listed the similarities in outcomes between surgery and carotid stenting, which include results from several seminal trials such as SAPPHIRE and CREST.

“Further [carotid artery stenting] trials are not needed to support reimbursement. It is time for CMS to align with professional guidelines and establish equipoise for carotid endarterectomy and CAS,” he concluded.

The trials comparing surgery with stenting used filters to stop emboli from causing periprocedural stroke. In the current study, Schofer and colleagues tested a proximal balloon occlusion device, which occludes the external and common carotid arteries to induce reversed flow before the lesion is crossed and stented.

“Whether this results in a more effective cerebral embolic protection than a filter device has never to our knowledge been studied in a randomized trial,” the investigators wrote.

They conducted the PROFI (Prevention of Cerebral Embolization by Proximal Balloon Occlusion Compared to Filter Protection During Carotid Artery Stenting) study, in which they randomized 62 consecutive patients (mean age 71, three-quarters men) equally to either filter or balloon occlusion.

The single-center trial employed diffusion-weighted MR imaging to identify new ischemic cerebral lesions. The stent operator was very experienced, the authors noted, and he used the same devices in each arm.

The primary endpoint was the incidence of new ischemic lesions between the two embolic strategies up to 24 hours post-procedure. The secondary endpoint was the number and volume of new lesions and major adverse cardiovascular and cerebral events (including death, stroke, myocardial infarction, and vascular complications) at 30 days, bleeding complications, and device crossover.

Baseline demographic, clinical, and lesion characteristics were similar between the two groups. Use of the balloon resulted in significantly more procedure time (30 min versus 22 min). One patient from each arm crossed over to the other.

The filter group had significantly more new lesions (87% versus 45%), which remained significant when broken down into symptomatic and asymptomatic patients, but not when those over the age of 80 were separated out.

The number of new lesions in the filter group was 3.6 compared with 1 in the balloon group (P=0.0001). Those in the filter arm also had significantly higher lesion volumes (0.59 cm3 versus 0.16 cm3).

There was one minor stroke in the filter group and no adverse events in the balloon group. There were no bleeding or vascular complications in any patients.

The MRI findings were mostly clinically unapparent, Schofer and colleagues said, yet “they are the tip of the iceberg of what is happening to the brain during [carotid artery stenting].”

They concluded that a randomized trial with clinical endpoints would be needed to show whether their findings translate to a lower stroke rate.

The study was limited because it involved one center with a small number of patients. Also, the endpoint demonstrated with MRI is a surrogate rather than a clinical event, and some differences in lesion characteristics may have introduced bias in favor of proximal balloon protection.

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

TORONTO, Oct. 16 — In an end run around a key barrier to developing a practical vaccine against highly pathogenic avian influenza, investigators have devised a “priming” strategy that could make sufficient doses available if a pandemic develops.

The problem with vaccines that have been developed so far is that they need two large doses per person to be effective, too much to be widely used in a pandemic. But vaccination with a non-pandemic strain virus may be enough to dramatically improve immune responses when people are later immunized a single dose.

This priming might be a way to ensure that there would be at least enough vaccine to protect key groups — health care workers or the military, for instance — in the event of a pandemic, said Nega Ali Goji, M.D., of the University of Rochester (N.Y.) Medical Center.

Current work on avian flu vaccines shows that they are immunogenic after two doses of 90 mcg each, Dr. Goji told a late-breaking symposium at Infectious Diseases Society of America meeting here.

But the world’s vaccine manufacturing capacity is limited, he said, so that strategies to work with lower or fewer doses will be essential in the event of an avian flu pandemic, which some experts fear is only a matter of time.

Dr. Goji and colleagues took advantage of an earlier randomized placebo-controlled study, conducted in 1998 at Rochester, that evaluated the effects of a vaccine against a clade 3 H5N1 vaccine isolated in Hong Kong.

They enrolled 37 members of the group that received the 1998 vaccine and 103 volunteers who had never been given an H5 vaccine, Dr. Goji said.

All volunteers were given 90 mcg of the clade 1 vaccine that was tested and found immunogenic earlier this year. The na??ve volunteers were then given a second dose 28 days later, and immune responses were compared then and again at day 56.

The researchers found:

When the first dose was given, immune responses were comparable in terms of geometric mean titers of both hemagglutination inhibition antibody (HAI) and serum neutralizing antibody.
At day 28, when they got their second dose, the na??ve volunteers had an HAI geometric mean titer of 13.3 and a serum neutralizing antibody titer of 16.6.
At the same point, the primed volunteers had HAI titers of 64.0 and 187.6, respectively.
Both measures increased at day 56 for the na??ve volunteers, but still remained lower than what was seen in the primed subjects.

Dr. Goji said the vaccine was well-tolerated in both study groups.

The finding opens the possibility that some workers might be immunized with an H5N1 variant and then boosted with a vaccine against a future pandemic strain, but Dr. Goji cautioned that the study needs to be replicated with larger numbers.

Nonetheless, the result is “very definitely a positive finding,” commented Kathleen Neuzil, M.D., or the University of Washington and the chair of the association’s pandemic influenza task force.

“We see that the virus is changing, and so the fact that you can prime ahead of time and there still is enough relatedness to give you a response, to me is a very positive outcome of the trial,” Dr. Neuzil said.

In a statement, Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, echoed Dr. Neuzil’s comments. The institute provided financial support for the Rochester trial.

“These preliminary findings need to be confirmed in larger studies, but they offer the intriguing possibility that pre-pandemic priming with existing H5N1 vaccines may boost the immune response to a different H5N1 vaccine tailor-made years later to thwart an emerging human influenza pandemic,” Dr. Fauci said.

EDINBURGH, Scotland, July 3 — Depression therapy sessions delivered by oncology nurses significantly lifted the moods of cancer patients, researchers here said.

Compared with 99 cancer patients who had physician-delivered usual care for depression, 97 patients given nurse-delivered intensive therapy along with usual care in the randomized trial gained an extra 0.34 points, on average ((95% CI 0.13 to 0.55), on the four-point Symptom Checklist-20 scale after three months.

The advantage was maintained for a full year, reported Michael Sharpe, M.D., of the University of Edinburgh, and colleagues in the July 5 issue of The Lancet.

The intensive therapy cost an extra $10,556 per quality-adjusted life-year gained, they estimated.

Dr. Sharpe and colleagues called it “a feasible, acceptable, and cost-effective way to improve patients’ quality of life.”

They wrote, “Supplementation of usual care with a nurse-delivered complex intervention improved the symptoms of depression more than did usual care alone.”

Usual care was the standard treatment available to everyone in Great Britain, received either from a primary-care doctor or a hospital specialist. It could involve psychotherapy and/or anti-depressant drug treatment, according to individual consultations between patients and physicians.

In addition to whatever depression treatment was given under this system, the intensive therapy included 10 individual sessions over three months with an oncology nurse.

These 45-minute sessions included problem-solving therapy to help patients overcome feelings of helplessness; education about depression and the available treatments; and counseling on talking about depression with oncologists and primary-care physicians.

Most sessions were conducted in person but could be done by telephone or at patients’ homes when circumstances required.

Patients also received monthly telephone calls to assess depression symptoms for three months after the individual sessions ended. Those with worsening signs of depression could receive one or two additional in-person therapy sessions.

The session content was adapted from a program first developed for use in primary care. The nurses delivering the therapy had no prior psychiatric experience. They followed a manual developed by the investigators and were supervised by a psychiatrist. All sessions were video-recorded and 10% were reviewed for adherence to the treatment manual.

At baseline, those in the usual-care group had mean depression scores of 2.25 while the mean score in the intervention group was 2.35.

After three months, these had declined to 1.55 and 1.20, respectively. Adjusting for baseline scores and confounding variables, the difference between groups amounted to 0.34 points.

At the end of six months, the advantage for the intervention group grew to 0.59 points (95% CI 0.37 to 0.81) after adjustments. The two groups began to converge again, but at one year the intervention still appeared to have been more effective (difference 0.42 points, 95% CI 0.17 to 0.67).

The intensive therapy also appeared to improve patients’ quality of life by secondary measures, such as anxiety and fatigue symptom scores and in the proportion who no longer met criteria for major depression on the Structured Clinical Interview for DSM-IV.

However, there was no difference in effects on pain or physical functioning, the researchers found.

They said the effectiveness of usual care may have been artificially enhanced because the study protocol required the investigators to inform patients’ primary care physicians that the patients had major depression.

In the ordinary course of cancer care, oncology clinic personnel who determine a patient is depressed might not pass that along to the primary care doctor.

Dr. Sharpe and colleagues said that antidepressant use in both groups was more common than they had previously seen in depressed cancer patients.

One limitation of the study is that it focused on patients who were relatively well. About 66% were in clinical remission from their cancers, and those with other psychiatric diagnoses or a history of depression were excluded.

In an accompanying commentary, Gary Rodin, M.D., of the University Health Network in Toronto, said the study showed “that trained nurses with no previous psychiatric experience can deliver a cost-effective collaborative psychosocial intervention for cancer patients with major depressive disorder.”

He added, “Such multi-component interventions are potentially feasible in cancer treatment centers and can be perceived by patients as less stigmatizing than referral to a mental-health specialist.”

He noted that the study did not evaluate the efficacy of the intervention’s individual components, which could help in improving the approach.

Dr. Rodin also suggested that future studies address the inclusion of spouses in depression treatment programs.

“Spouses are most often identified as primary caregivers for cancer patients and might report depressive symptoms that are at least as severe as those of the patients themselves,” he wrote.

The study was funded by Cancer Research UK. No potential conflicts of interest were reported.

Primary source: The Lancet

Source reference:

Strong V, et al “Management of depression for people with cancer (SMaRT oncology 1): a randomised trial” Lancet 2008; 372: 40-48.

Additional source: The Lancet

Source reference:
Rodin G, “Treatment of depression in patients with cancer” Lancet 2008; 372: 8-10.

BALTIMORE, Dec. 21 – For older patients with acute illness, bringing hospital-level care into the family living room may be more beneficial than weathering a typical hospital visit, according to a multicenter study.

Investigators found that when elderly patients were treated at home for pneumonia, chronic heart failure, chronic obstructive pulmonary disease, or cellulitis, they had a shorter length of treatment (P=0.004), fewer complications, such as a lowered incidence of delirium and reduced need for sedatives, and lowered costs of care (P

Coordinated, regional care will help improve outcomes for individuals who suffer an out-of-hospital cardiac arrest, according to a policy statement from the American Heart Association.

Similar regional systems have been successful for treating ST-elevation myocardial infarction and life-threatening trauma, according to the authors, led by Graham Nichol, MD, MPH, of the University of Washington in Seattle.

“The time has come to develop and implement regional systems of care for patients resuscitated from out-of-hospital cardiac arrest to try to achieve similar improvements in outcomes,” they wrote online in Circulation: Journal of the American Heart Association.

Nichol and the other group members said integrating care at each step of the process — from resuscitation by emergency medical services teams, to triage at referral hospitals, to arrival at receiving centers specializing in postcardiac arrest care — would improve survival to discharge.

The median survival-to-discharge following EMS-treated, out-of-hospital cardiac arrest in North America is just 8.4%.

But in areas with regional care systems, survival is much better. In Seattle, for example, the survival rate after any initial rhythm was 16.3%, and it reached nearly 40% after arrests caused by ventricular fibrillation.

Unfortunately, the authors asserted, most regions lack this coordinated approach, with barriers that include lack of experience, knowledge about effective interventions, personnel, resources, and infrastructure.

“The time to implement these systems of care is now,” they wrote.

Nichol and his colleagues noted that guidelines for improving care for victims of out-of-hospital cardiac arrest have been released, but they said uptake has been slow.

For example, they noted, therapeutic hypothermia after patients reach the hospital has been shown to improve outcomes, but the practice is applied infrequently.

Also, postresuscitation care should include percutaneous coronary intervention when ischemia is suspected, early hemodynamic stabilization, a reliable prediction of long-term outcome, and an evaluation of the need for an implantable cardioverter-defibrillator before discharge.

“ICDs decrease mortality rates in survivors of cardiac arrest with good neurological recovery when treatable causes of arrest are not determined, in patients with underlying coronary disease without myocardial ischemia as the cause of arrest, and in patients with a low ejection fraction (i.e., <30% to 35%) in combination with medical therapy,” the authors wrote.

Regional systems of care will better enable the administration of care according to evidence-based guidelines, they said.

“As with trauma centers, burn centers, STEMI centers, and stroke centers, national criteria should be developed to enable the categorization, verification, and designation of centers for the treatment of patients with restoration of circulation after out-of-hospital cardiac arrest,” they wrote.

They said specialized care centers, limited in number to ensure sufficient volumes of patients and keep costs down, should be certified by an external agency.

“Some may argue that the costs or charges associated with this multifaceted approach are likely to be excessive,” the authors added, “but resuscitation interventions that are associated with increased rates of survival are also associated with improved quality of life and acceptable cost to society.”

They asserted that the additional funding needed to establish these systems could be achieved through shared reimbursement for care among various levels of the system, from EMS to the centers specializing in postcardiac arrest care.

Nichol reported receiving research grants from the NIH, the Asmund S. Laerdal Foundation for Acute Medicine, and the National Heart, Lung, and Blood Institute.

He also reported relationships with the Canadian Institutes of Health Research, Medtronic, the U.S. Department of Defense, the Heart and Stroke Foundation of Canada, Laerdal, Physio-Control, and Channing Bete.

The other members of the writing group reported relationships with numerous pharmaceutical and medical device companies.

NEW YORK, March 26 — Tobacco-industry money has been revealed as the funding source of a widely publicized study that reported annual CT-screening of smokers and former smokers could save lives by detecting lung cancer at its earliest stage.

The money, $3.6 million, was funneled through a charity called the Foundation for Lung Cancer: Early Detection, Prevention & Treatment, according to a front page article in today’s New York Times.

Claudia I. Henschke, M.D., Ph.D., of Weill Cornell Medical Center who was principal investigator for the I-ELCAP (International Early Lung Cancer Action Program), served as president of the foundation. Her co-investigator, David Yankelevitz, M.D., was its secretary-treasurer, Antonio Gotto, M.D., dean of Weill Cornell, and Arthur J. Mahon, vice-chairman of the Weill Cornell board of overseers, were listed as directors.

The tobacco money came in the form of four grants from the Vector Group, which is the parent company of the Liggett Group, maker of Liggett Select, Eve, Grand Prix, Quest, and Pyramid cigarettes.

As reported in the Oct. 26 issue of the New England Journal of Medicine, I-ELCAP screened more than 31,000 persons at risk for lung cancer from smoking or environmental exposure to carcinogens.

The annual low-dose CT spiral scans picked up 484 lung cancers, 85% of which were clinical stage I, with an estimated 10-year survival rate of 88%.

Dr. Henschke said that the results suggested that annual screening could prevent 80% of lung cancer deaths, an extrapolation that was disputed almost as soon as it was published. (See: Spiral CT Screening for Lung Cancer Detects Early Curable Disease)

The Times uncovered the tobacco link by investigating the tax records of the foundation. When told about the funding, Jeffrey M. Drazen, M.D., editor-in-chief of the NEJM, said that during his seven-year tenure, the journal had never knowingly published any tobacco-funded research.

Otis Brawley, M.D., chief medical officer for the American Cancer Society, told the newspaper that the ACS would not have given Dr. Henschke more than $100,000 in research grants if it had known that she was “using blood money.”

The Times said Drs. Henschke and Yankelevitz denied any wrong-doing. In an email, the investigators pointed out that the grants were “announced publicly [and] the advocacy and public health community knew about it.”

Here are some of the latest health and medical news developments, compiled by the editors of HealthDay:

FDA Updates Kidney Failure Warning on Bone-Building Drug

The U.S. Food and Drug Administration on Thursday issued an updated warning that doctors should screen patients for kidney problems before prescribing Reclast, a bone-building drug that has been linked to an increased risk of kidney failure in certain patients.

In a statement posted on its website, the agency said kidney failure “was a rare but serious condition associated with the use of Reclast in patients with a history of or risk factors for [kidney] impairment.”

The agency said it has added instructions to the medication’s labeling that tell doctors to test patient’s kidney function with a blood test and to monitor patients who already take Reclast (zoledronic acid). Patients who have acute kidney impairment should not be prescribed Reclast, the FDA noted.

A warning about possible kidney failure was first added to the drug’s labeling back in 2009, after the FDA received five reports of kidney failure, some of which were fatal, following Reclast infusion. Since then, the agency has received 11 reports of fatal kidney failure and nine reports of non-fatal kidney injury in similar patient settings.

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New Laws Forcing Florida Pill Mills to Close

With new laws at their disposal, Florida officials this year have taken aggressive action against so-called “pill mills” in the state.

The state has long been the hub of illegal sales of prescription drugs in the United States. For example, doctors in Florida last year bought 89 percent of all oxycodone (an often-abused prescription painkiller) sold in the U.S. and at one point the state had more than 1,000 pain clinics, The New York Times reported.

But in the past year, more than 400 clinics were either shut down or closed, prosecutors have indicted dozens of pill mill operators, and nearly 80 doctors have had their licenses suspended for prescribing large amounts of pills without verified medical need.

A new law that took effect in July forbids Florida doctors, with some exceptions, from dispensing narcotics and addictive medicines in their clinics, The Times reported.

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ER Visits Due to Air Gun, Paintball Injuries Declining

Air and paintball gun injuries accounted for more than 20,000 emergency department visits in the United States in 2008, a federal government report says.

While a large number, it’s a 20 percent decrease from 2006, according to the latest News and Numbers from the Agency for Healthcare Research and Quality.

Children and teens 17 and younger accounted for about 60 percent of air and paintball gun injury emergency department visits in 2008, and more than 25 of the visits were for children ages 10 to 14.

Males accounted for five times more visits than females. Visits for air and paintball gun injuries were higher in rural areas (92 per 1 million population) than in urban areas (61 per 1 million), and were nearly three times higher among low-income children (93 visits per 1 million people) than among children from higher income families (34 per 1 million).

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U.S. Ranks 41st in Newborn Survival: Study

Newborn babies in countries such as Cuba, Poland and Malaysia now have a better chance of survival than newborns in the United States, according to a study that looked at 20 years of data from all 193 member nations of the World Health Organization.

The figures also show that newborns in Qatar, Croatia and the United Arab Emirates now die at about the same rate as newborns in the United States, the Associated Press reported.

With a newborn death rate of 4.3 per 1,000 live births, the United States now trails 40 other countries in terms of newborn death risk. The U.S. had the 28th lowest risk in 1990.

“It’s not that things are worse in the United States than before, it’s that the U.S. isn’t making progress like other countries,” Dr. Joy Lawn, a pediatrician who works for Save the Children, told the AP.

Lawn conducted the study with researchers from WHO and the London School of Hygiene and Tropical Medicine in England. They found that babies under 4 weeks old account for 41 percent of child deaths worldwide and that the three leading causes of newborn death are preterm delivery, asphyxia and severe infections.

Proper care can prevent all three problems, Lawn told the AP.

The study was published Tuesday in the journal PLoS Medicine.

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Heart disease. Cancer. Lung disease. Diabetes.

All these scourges loom large as global killers and, unlike infectious illnesses, all are largely preventable, experts say.

But the truth is that these “non-communicable diseases” (NCDs) are now the leading cause of death worldwide by a wide margin. That’s why health experts and leaders from 193 nations plan to meet next week at the United Nations in New York City to discuss strategies to lower the death toll.

“This will be the first time that the U.N. has actually focused on the major killer of most people,” said Dr. Otis Brawley, chief medical officer for the American Cancer Society, and a professor of oncology and epidemiology at Emory University in Atlanta.

“We need this,” he added. “We need a chronic disease movement. We need to drive attention toward overall health. Because cancer, for example, kills more people in the world than HIV/AIDS, malaria and tuberculosis combined.”

As analyzed in a new report issued this week by the World Health Organization (WHO), non-infectious diseases are responsible for roughly 36 million fatalities worldwide every year. The loss in terms of life-years and productivity is staggering, since about 9 million of these deaths occur among men and women under the age of 60.

According to Dr. Gordon Tomaselli, president of the American Heart Association, “if current trends continue, well before the middle of this century [non-communicable diseases] will be responsible for more than three-quarters of the deaths around the world.”

Heart disease currently accounts for the lion’s share of these deaths, with WHO saying that 48 percent of non-communicable disease fatalities are attributable to cardiac illness. A little more than one in five non-communicable disease deaths are due to cancer, while respiratory illness is linked to slightly more than one in 10 fatalities. These are followed by diabetes, which claims the lives of 3 percent of non-communicable disease patients.

Poorer countries are often hardest hit by such diseases, the report noted, and by some measures their citizens bear a three times greater risk for dying from a non-communicable disease before the age of 60, compared with residents of richer nations.

“And the impact of the growing prevalence of non-communicable diseases is not only on the medical health, but the economic health of all nations, in direct care costs and that of lost productivity,” Tomaselli said

Experts note that this health trend is occurring not only in poorer nations but also in the developed world, which has hardly proven immune to the ravages of non-communicable diseases.

The WHO report found, for example, that non-communicable diseases account for 87 percent of all deaths in the United States. Not coincidentally, the United States is increasingly weighted down by an obesity epidemic, a largely inactive population (with a 43 percent sedentary rate), a 16 percent smoking rate, and markedly rising blood pressure and glucose levels.

Solving problems like that are the U.N. summit’s principle goal: to identify those steps that countries can take to promote healthful behaviors, blunting the impact of non-communicable diseases.

“This summit is a once-in-a-generation opportunity,” the American Diabetes Association (ADA) said in a statement.

In fact, it’s only the second time the U.N. has taken up a health issue — the first, in 2001, created the Global Fund to Fight AIDS, Tuberculosis and Malaria.

The ADA noted that non-communicable diseases share many preventable risk factors, such as poor diet, insufficient exercise habits, smoking and alcohol abuse.

The ADA said those attending the upcoming summit will be shooting to achieve an ambitious but tangible goal: to curtail unhealthful behaviors and shave 25 percent off the global death rate from non-communicable diseases by 2025.

But Brawley emphasized that the U.N. effort to reach such goals will aim to build on existing public health initiatives, rather than usurp them.

“This is not a disease Olympics,” he said. “And we are not in a competition. So the summit’s aim is to focus the world on overall health. Not to the exclusion of infectious disease, but with the inclusion of non-infectious disease.”

More information

For more on non-communicable diseases, visit the World Health Organization.

CHICAGO — The timing of postoperative chemotherapy for colorectal cancer may be as meaningful as what regimen is used, a meta-analysis affirmed.

Each four weeks of delay in adjuvant chemotherapy after colorectal cancer resection predicted 14% poorer overall and disease-free survival (DFS), James J. Biagi, MD, of Queen’s University in Kingston, Ontario, and colleagues found.

The significant risks seen in the meta-analysis were reported online in the Journal of the American Medical Association in advance of presentation at the American Society of Clinical Oncology meeting here.

Delaying chemotherapy to eight weeks or 12 weeks would reduce expected five-year survival from 60% to 54% or 48% for a typical 65-year old man in good health, aside from T3N2 colorectal cancer.

That’s as much difference as oxaliplatin (Eloxatin) makes atop a fluoropyrimidine regimen, the group pointed out.

There can be legitimate reasons to hold off on chemotherapy, such as postoperative complications, the researchers noted.

But because there is sufficient evidence that delay is causal in potential harm, the researchers urged physicians to avoid delays in referral and treatment as much as possible.

“The implication that time to adjuvant chemotherapy may be as relevant to patient outcome as access to modern chemotherapy should encourage [cancer services providers] to streamline and coordinate the delivery of adjuvant chemotherapy,” they wrote in the JAMA paper.

That message may not come as a surprise because early initiation of adjuvant chemotherapy in colorectal cancer is widely considered clinically important, the group noted.

That timing makes a difference is biologically plausible, they explained.

Early initiation of chemotherapy may eradicate micrometastases and the circulating tumor cells stirred up by surgery and its pro-tumor healing response. Preclinical studies also suggest that chemotherapy is most effective when tumor burden is low.

The meta-analysis included 15,410 patients in 10 studies, which reported the time to standard forms of adjuvant chemotherapy for colorectal cancer, without concurrent or sequential additional therapies, such as radiation or hormonal treatments.

Nine of these studies were cohort or population-based; one was a secondary analysis from a randomized chemotherapy trial.

Time to adjuvant chemotherapy ranged from three to 26 weeks across the studies.

In the pooled analysis, each four weeks of waiting time from surgery to initiation of adjuvant chemotherapy was associated with an identical hazard ratio of 1.14 for overall survival (95% confidence interval 1.10 to 1.17) and for DFS (95% CI 1.10 to 1.18).

Neither outcome showed evidence of heterogeneity. Excluding the largest studies didn’t change the results.

However, the study didn’t support the “commonly used, and arguably arbitrary” three-month limit beyond which adjuvant chemotherapy is often no longer recommended, Biagi’s group noted.

They pointed back to the hypothetical patient, whose chance of overall survival at five years would be 60% with adjuvant chemotherapy started four weeks after surgery.

While delay would drop that prognosis, giving chemotherapy at 12 weeks would still be better than no chemotherapy alone (48% versus 45% projected overall survival at five years).

“It is possible that a reasonable limit may be more in the order of four to five months,” the investigators concluded in the paper.

They cautioned, though, that the meta-analysis was biased, as were all the studies, because poor postoperative performance status may independently predict prolonged wait times.

Extrapolating the hazard ratios outside the time periods covered by the studies may be problematic, they noted. The results came predominantly from trials in the era of fluoropyrimidine adjuvant chemotherapy without oxaliplatin, making it unclear whether the results can be generalized to the current oxaliplatin era.

The meta-analysis was supported in part by a grant from the Canadian Institutes of Health Research.

Biagi reported having no conflicts of interest to disclose.

No progress has been made in the past decade toward abolishing state-level restrictions on local anti-smoking policies, one of the goals of the national Healthy People 2020 project, researchers said.

Whereas 28 states in 2000 preempted at least some types of local effort to discourage smoking, such restrictions were still in place last year in 27 states, according to Michelle Griffin, MPH, of the University of Washington in Seattle, and three CDC researchers.

They reported findings from the CDC’s State Tobacco Activities Tracking and Evaluation database in the Aug. 26 issue of Morbidity and Mortality Weekly Report.

Although eight states have dropped laws that prevent localities from adopting ordinances and administrative rules that limit smoking in workplaces and public gathering spots, states have been reluctant to allow local restrictions on tobacco advertising or vending methods that make tobacco products available to minors.

“Like smoke-free laws, restrictions on advertising and youth access are components of a comprehensive approach to tobacco control,” Griffin and colleagues wrote, citing studies that these are effective in reducing tobacco use.

Many communities have sought to adopt such policies, but have found that they are forbidden to implement regulations that are more restrictive than those in place at the state level.

The Healthy People 2020 initiative called for abolition of such state-level preemption of local regulation.

“State preemptive provisions that prevent local action in any of these three areas impede local and state efforts to reduce tobacco use,” Griffin and colleagues asserted.

In 2000, the study found, 18 states had laws blocking local regulation of smoking at work or in public places, which had fallen to 12 by 2010.

Eight states “completely rescinded preemptive provisions or had such provisions overturned by state courts” during the decade, the researchers wrote.

But in two states, litigation produced rulings that “ambiguous provisions” in statutes preempted local action.

Local advertising restrictions were preempted in 18 states both in 2000 and 2010. And, states thwarting local-level policies to block youth access to tobacco (primarily by banning vending machine sales) actually increased by one, to 22, when Pennsylvania adopted a preemptive provision in 2002.

Seven states retained preemptions on all three categories of anti-smoking policies in 2010: Michigan, North Carolina, Oklahoma, South Dakota, Tennessee, Utah, and Washington. But that number was down from the 11 with comprehensive preemptions in 2000.