Wednesday, March 26, 2014

Current Use of Proton Pump Inhibitors Increases Risk of Developing Acute Interstitial Nephritis

Current use of a proton pump inhibitor (omeprazole, pantoprazole, or lansoprazole) was linked with a fivefold increased risk of acute interstitial nephritis, relative to past use, in a Kidney International study of 572,661 patients without a history of renal disease who started a new episode of proton pump inhibitor use between 2005 and 2009. The crude incidence rates of acute interstitial nephritis per 100,000 person-years were 11.98 for current proton pump inhibitor use and 1.68 for past use. Greater caution concerning the use of proton pump inhibitors is warranted considering the extremely large number of patients using the drugs.

High Protein Intake Linked with Kidney Function Decline

A cross-sectional analysis of 1522 men and women aged 45 to 64 years showed that each 1 g/day increment in protein intake was associated with a 4.7 mL/min/1.73 m² increment in eGFR. However, longitudinal analyses demonstrated that after 12 years of follow-up, each 1 g/day increment in protein intake was associated with a 4.1 mL/min/1.73 m² decline in eGFR and a 78% increased likelihood of having an eGFR <60 mL/min/1.73 m². TheNephrology Dialysis Transplantation findings agree with studies demonstrating short-term GFR stimulation by protein intake but unfavorable effects of high protein intake in patients with CKD.

Tuesday, March 25, 2014

Fauci: Cause of 20-30% of adult common colds still unidentified.

On the front of its Personal Journal section, the Wall Street Journal (3/25, D1, Reddy, Subscription Publication) reports that according to the National Institutes of Health, the number one cause of visits to a physician is the common cold. Colds, which may be caused by any of some 200 known viruses, may last for up to two weeks. It is possible for people to get colds back-to-back, particularly during cold weather when people are stuck inside, or to confuse symptoms of a sinus infection or allergies with those of a cold. Some cold symptoms may be also caused by respiratory syncytial virus, the coronavirus and the enterovirus. The piece quotes Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, who said, “The most confounding thing of all is that we still haven’t identified the cause of 20% to 30% of adult common colds.”

Study: E-cigarette use not tied to greater rates of smoking cessation.

The Washington Post (3/25, Millman) “Wonkblog” reports that a research letter published March 24 in “JAMA Internal Medicine found that use of e-cigarettes was not associated with ‘greater rates of quitting cigarettes or reduced cigarette consumption’ after one year.” The study “authors reached the conclusion based on self-reported data from 949 smokers, which included 88 who used e-cigarettes.”

        The Los Angeles Times (3/25, MacVean) “Science Now” blog reports that “researchers from the Center for Tobacco Control Research and Education and the Department of Medicine at” the University of California-San Francisco “noted that e-cigarettes are ‘aggressively promoted as smoking cessation aids.’” But, given the findings of the study, “‘regulations should prohibit advertising, claiming or suggesting that e-cigarettes are effective smoking cessation devices until claims are supported by scientific evidence,’ the researchers...wrote.”

        Still, the Boston Globe (3/25, Kotz) points out that the study’s “small sample size makes it difficult to draw firm conclusions, admits study leader Dr. Pamela Ling, an associate professor of medicine at” UCSF.

        Newsday (3/25, Ricks) points out that “earlier this month,” researchers “found in a study of thousands of youths that the addictive nicotine in e-cigs may lure teens to more potent sources of the substance.”

        According to MedPage Today (3/25, Phend), an accompanying editorial written by JAMA Internal Medicine editor Mitchell Katz, MD, “further advocated FDA regulation” of e-cigarettes “as drug-delivery devices.” MedPage Today added that the FDA “has regulations in the works that are expected to generally bring the same kind of restrictions to e-cigarettes as to other tobacco products.” Some of the data for the study came from National Cancer Institute-funded research.

        Also covering the story are Reuters (3/25, Seaman), theMinneapolis Star Tribune (3/25, Stoxen) “Health Check” blog, the CBS News (3/25, Jaslow) website, Time (3/25, Sifferlin), HealthDay (3/25, Reinberg), Medscape (3/25, Cassels), and a Modern Healthcare (3/25, Johnson, Subscription Publication) blog.

Hepatitis C Linked with Immune-Mediated Glomerulonephritis

Occult hepatitis C (HCV)–RNA (detectable viral RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) was found in 34 of 87 patients with immune-mediated glomerulonephritis vs. 1 of 26 control patients with hereditary glomerular nephropathies. In theKidney International study serum creatinine levels were higher in patients with immune-mediated glomerulonephritis with occult HCV than in those without occult HCV (1.5 vs. 1.1 mg/dL). After adjustments, patients with immune-mediated glomerulonephritis were over 13 times more likely to have occult HCV than controls. Progression to ESRD was faster in patients with immune-mediated glomerulonephritis and occult HCV than in negative cases.

U-Shaped Association of BMI and Outcomes in Patients with CKD, Study Finds

New research reveals a relatively consistent U-shaped association between BMI and clinical outcomes, with the best outcomes observed in overweight and mildly obese patients. Among a nationally representative cohort of 453,946 US veterans with eGFR <60 mL/min/1.73 m², BMI levels <25 kg/m² were associated with worse outcomes in all patients, independent of severity of CKD. BMI levels ≥35 kg/m² were associated with worse outcomes in patients with earlier stages of CKD, but this association was attenuated in those patients with eGFR <30 mL/min/1.73 m². The findings are published in JASN.

E-Cigs: No Help in Quitting, Smoking Less

Medpage link:

Published: Mar 24, 2014


Electronic cigarettes didn't help smokers quit or even smoke less, according to a longitudinal study that may quash some public health hopes for the nicotine-delivery devices.

Smokers who also reported any e-cigarette use at baseline in the web-based studyweren't significantly more likely to have quit tobacco 1 year later (odds ratio 0.71, P=0.35), said Pamela Ling, MD, MPH, of the University of California San Francisco.

The same was true for prior 30-day e-cigarette use after accounting for baseline intent to quit, cigarette consumption, and dependence (OR 0.76, P=0.46), the group reported in a research letter online in JAMA Internal Medicine.

Action Points

  • Electronic cigarettes didn't help smokers quit or even smoke less, according to a longitudinal study that may quash some public health hopes for the nicotine-delivery devices.
  • Note that while the U.S. Supreme court struck down FDA attempts to regulate e-cigarettes as drugs or devices in 2010, the agency has pending regulations that are expected to generally bring the same kind of restrictions to e-cigarettes as to other tobacco products.

Among people who didn't quit, "vaping" wasn't associated with smoking fewer cigarettes over time either (P=0.25).

These findings from analysis of 949 smokers in a nationally representative panel followed from 2011 through 2012 by web-based market research firm Knowledge Networks (now GfK) add to similar findings from population-based and Quitline studies.

"Although electronic cigarettes are aggressively promoted as smoking cessation aids, studies of their effectiveness for cessation have been unconvincing," Ling's group wrote.

For example, one placebo-controlled but underpowered trial suggested e-cigarettes were at least as good as nicotine patches in helping smokers quit, but quit rates were dismal either way at 6% to 7%.

"Regulations should prohibit advertising claiming or suggesting that e-cigarettes are effective smoking cessation devices until claims are supported by scientific evidence," Ling's group argued.

The top reason for regular e-cigarette usecited in surveys has been kicking the tobacco habit, and some public health experts have been cautiously supporting that harm-reduction strategy.

"As a harm reduction proponent, I would be willing to put aside the fact that any product with the name 'cigarette' (e- or otherwise) causes me reflex tachycardia and support electronic cigarettes ... if there were good data indicating that they helped smokers to stop," JAMA Internal Medicine editorMitchell Katz, MD, wrote in a note accompanying Ling's letter.

However, he agreed with their conclusion and further advocated FDA regulation as drug-delivery devices.

While the U.S. Supreme court struck down FDA attempts to regulate e-cigarettes as drugs or devices in 2010, the agency has regulations in the works that are expected to generally bring the same kind of restrictions to e-cigarettes as to other tobacco products.

"The bottom line is e-cigarettes are not a good way to quit," commented Brian Tiep, MD, director of smoking cessation at City of Hope in Duarte, Calif.

The devices may not have all the carcinogenic compounds found in burning tobacco, but that doesn't mean they're entirely safe, he told MedPage Today, pointing to FDA analyses finding carcinogenic nitrosamines and the antifreeze component diethylene glycol in e-cigarette nicotine solutions.

However, he noted that Ling's study population wasn't actively trying to quit and that an adequately-powered study is still needed to assess e-cigarettes' performance in a smoking cessation program.

Ling's group also cautioned about limited statistical power, as smoking cessation was self-reported and included only nine of the 88 e-cigarette users.

Their study lacked data on how frequently the population used e-cigarettes and motivation for use as well.

The data came from a study funded by the National Cancer Institute.

The researchers disclosed no relevant financial relationships with industry.

Tiep disclosed no relevant financial relationships with industry.

Steroid Therapy for COPD Exacerbations: Getting By With Less

Medpage link:

Steroid Therapy for COPD Exacerbations: Getting By With Less

Treating exacerbations of chronic obstructive pulmonary disease (COPD) with corticosteroids for 5 days is no less effective than treating patients for 1 or 2 weeks or even longer. In fact, 5-day treatment should be considered the norm for most patients, including those with the most severe disease.

Findings from the Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) trial,1 published in June 2013, prompted the Global Initiative for Chronic Obstructive Lung Disease (GOLD) to revise its guidelines for the treatment of COPD flare-ups and call for the shorter course of steroid therapy instead of the 7 to 14 days of treatment that GOLD had previously recommended.

According to the 2014 GOLD guidelines, “A dose of 40 mg prednisone per day for 5 days is recommended (Evidence B), although there are insufficient data to provide firm conclusions concerning the optimal duration of corticosteroid therapy for acute exacerbations of COPD. Therapy with oral prednisolone is preferable. Nebulized budesonide alone may be an alternative (although more expensive) to oral corticosteroids in the treatment of exacerbations. Nebulized magnesium as an adjuvant to salbutamol treatment in the setting of acute exacerbations of COPD has no effect on FEV1.”2

Acute exacerbations of COPD are a major cause of hospitalization, lung function decline, and death. Treatment with corticosteroids can reduce the length of hospital stays and shorten recovery times, but long-term use has been associated with poorer patient outcomes and greater mortality.3,4 Even steroid use to treat COPD flare-ups for as short as a few weeks has been linked to adverse outcomes, including hyperglycemia, weight gain, and insomnia. And since the majority of patients experience at least 1 exacerbation a year, and as many as 10% experience 2 or more annually, the risk for cumulative exposures may be great.4,5

A 2011 Cochrane review of 7 studies including a total of 288 patients with COPD exacerbations showed no significant differences in clinical outcomes between patients treated with corticosteroids for more than 7 days and those treated for 7 days or less (5 studies used oral prednisolone and 2 used intravenous corticosteroids). But the Cochrane researchers concluded that the studies weren’t of sufficient quality to make firm recommendations regarding the duration of corticosteroid treatment during COPD exacerbations.6

“The beauty of the REDUCE trial is that it definitively told us whether we should be treating patients with a long or short course of therapy,” said Don D. Sin, MD, University of British Columbia professor of medicine and COPD researcher, in an interview. “In most cases, 5 days of prednisone at 40 mg per day is sufficient for acute exacerbation management. This is important to know because we don’t want to give these medications for longer periods or at higher doses than is necessary, because while they’re very effective, they also have severe toxicities.”

The REDUCE trial included 314 patients who presented with acute COPD exacerbations to 5 Swiss teaching hospital emergency departments between March 2006 and February 2011 and were randomized to treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The main outcome measure for the study was time to next exacerbation within 180 days.

A total of 289 patients (92%) were hospitalized after being seen in the ER; 311 were included in the intention-to-treat analysis and 296 were included in the per-protocol analysis. In the 5-day treatment group, 56 patients (35.9%) reached the main endpoint compared to 57 (36.8%) in the 14-day treatment group. Rates of re-exacerbation within 180 days were also similar in the 2 groups (37.2% [95% CI 29.5% to 44.9%] in the 5-day group and 38.4% [95% CI 30.6% to 46.3%] in the 14-day group, for a difference of -1.2% [95% CI -12.2% to 9.8%]).

Among patients with re-exacerbations, the median time to the event was 43.5 days (interquartile range [IQR], 13 to 118) in the 5-day treatment group and 29 days (IQR, 16 to 85) in the 14-day treatment group. No significant differences were seen among the 2 groups in time to death; the combined endpoint of exacerbation, death, or both; and recovery of lung function.

Not surprisingly, mean cumulative prednisone dose was significantly higher in the longer treatment group (793 mg [95% CI 710 to 876 mg] versus 379 mg [95% CI 311 to 446 mg], P<.001). Treatment-associated adverse reactions, however—including hyperglycemia and hypertension—were similar in both groups.

“Most of our patients had severe or very severe COPD: therefore, our results cannot necessarily be applied to less severe disease grades. However, it seems unlikely that patients with GOLD grades 1 and 2 would benefit from longer glucocorticoid treatment for COPD exacerbations,” lead researcher Jörg D. Leuppi, MD, PhD, and colleagues, wrote in the June 5, 2013 issue of JAMA.

Dr. Sin agrees. Although he wasn’t involved with the research, he wrote an editorial that was published with the Leuppi study. He noted that the 5-day treatment group had a 65% reduction in cumulative steroid exposure compared to the longer-treatment group (200 mg median prednisone exposure versus 560 mg).5

Dr. Sin said that while many clinicians had adopted the shorter course of steroid treatment for COPD exacerbations before the REDUCE trial, others—especially those trained decades ago when 6 to 8 weeks of treatment was the norm—still treat patients for 2 weeks or longer.

He added that although clinicians are doing a better job of treating COPD in general, this isn’t necessarily the case for COPD exacerbations.

“The sad reality is that the treatments we use for acute exacerbations today are no different from the ones we were using 20 years ago,” he said. “We used antibiotics then and we still do. We used oxygen and steroids then and we still do. The fundamental tenets of treatment haven’t changed over the past 20 or 30 years. We need better therapies.”

Published: 02/18/2014


Monday, March 17, 2014

Study: Colon cancer incidence, death rates down among Americans 50 and older.

The Wall Street Journal (3/17, Beck, Subscription Publication) reports that research suggests that colon cancer incidence among individuals in the US aged 50 and older has declined 30% of the past decade, with the decline being driven by an increase in colonoscopies.

        USA Today (3/17, Szabo) reports that additionally, “death rates from colon cancer...have fallen, declining at a rate of about 3% a year over the past decade, the report found.” The largest “declines in colon cancer incidence were in people over age 65, who qualify for Medicare, which makes colon cancer screenings available for free.” The study also indicated that “declines in colon cancer rates became more dramatic in more recent years, falling at an annual rate of 7.2% a year from 2008 to 2010.”

        The National Journal (3/17, Subscription Publication) reports that the findings were published in...CA: A Cancer Journal for Clinicians. Investigators “evaluated data from the CDC and the National Cancer Institute in preparing the report.” The Journal points out that “the data comes as the Health and Human Services Department and National Colorectal Cancer Roundtable – an organization founded by the Centers for Disease Control and Prevention and the American Cancer Society – make a new nationwide push to increase screening rates to 80 percent by 2018.”

        Modern Healthcare (3/17, Rice, Subscription Publication) reports, however, that “screening rates remain low among the poor and uninsured, the report said, and there were substantial racial and ethnic differences in both incidence and death rates.” The CNN (3/17) “The Chart” blog and MedPage Today (3/17, Bankhead) also cover the story.

Sunday, March 16, 2014

FDA finds no link between incretin-based drugs, pancreatic complications

Data do not support a causal association between incretin-based drugs and pancreatitis or pancreatic cancer, concluded a review by U.S. and European regulatory agencies.
Researchers from the FDA and the European Medicines Agency (EMA) outlined how they conducted comprehensive evaluations in response to postmarketing reports of pancreatitis and pancreatic cancer in patients using incretin-based drugs. Their conclusions appeared in a Feb. 27 Perspective in the New England Journal of Medicine.
The FDA reevaluated more than 250 toxicology studies completed as part of all marketing applications for incretin-based drugs. The studies, conducted in nearly 18,000 healthy animals, found no overt pancreatic toxic effects or pancreatitis. The EMA conducted a similar review and found no drug-induced pancreatic tumors in rats and mice that had been treated for up to 2 years with incretin-based drugs, even at doses that greatly exceed the level of human clinical exposure.
To gather data that might more closely match the drugs' uses in humans, the FDA required drugmakers to conduct 3-month pancreatic toxicity studies in a rodent model of diabetes. Three studies submitted to the FDA found no treatment-related adverse effects on the pancreas.
Clinical safety databases reviewed by the FDA included data from more than 200 trials, involving about 41,000 participants, more than 28,000 of whom were exposed to an incretin-based drug. In these trials, 15,000 patients received a drug for 24 weeks or more, and 8,500 received a drug for 52 weeks or more. EMA conducted a similar review. Small imbalances in the incidence of pancreatitis were reported in premarketing trials, but a pooled analysis of data from 14,611 patients with type 2 diabetes in 25 clinical trials of sitagliptin showed no compelling evidence of an increased risk of pancreatitis or pancreatic cancer.
The agencies also looked at 2 cardiovascular outcome trials: the Saxagliptin Assessment of Vascular Outcomes Recorded (SAVOR) trial and the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial. There were similar rates of acute pancreatitis in the treatment and placebo groups in both trials. There were also similar rates of pancreatic cancer in the drug and placebo groups in the SAVOR trial, with no incidence of pancreatic cancer in either group in the EXAMINE trial.
The FDA and the EMA agreed that the data do not currently support a causal association between incretin-based drugs and pancreatitis or pancreatic cancer. "Although the totality of the data that have been reviewed provides reassurance, pancreatitis will continue to be considered a risk associated with these drugs until more data are available; both agencies continue to investigate this safety signal," the Perspective concluded.