MTX Dose Can Be Kept Low When Combined With Enbrel in RA (CME/CE)

Action Points

• Note that this post-hoc analysis of two clinical trials found that etanercept is equally efficacious in the treatment of rheumatoid arthritis whether combined with low- or high-dose methotrexate.
• As patient response dictated methotrexate dose, these results may need to be validated in randomized dosing studies.

Clinical outcomes in patients with rheumatoid arthritis (RA) who are treated with etanercept (Enbrel) in combination with methotrexate (MTX) appear to be independent of MTX dosage, according to European investigators.

Consequently, they said, lower doses of MTX when used in combination with etanercept can be considered while maintaining efficacy and quality of life.

In a subanalysis of two large randomized trials of etanercept in RA, clinical responses measured in various ways "were similar for patients treated with etanercept plus MTX combination therapy, regardless of the MTX dose used," wrote Gaia Gallo, from Pfizer Europe, Rome, and colleagues online in RMD Open.

"Low-dose MTX (<10 mg/week) is sufficient to achieve efficacy outcomes similar to higher doses of MTX (10.0-17.5 mg/week, or >17.5 mg) when used in combination with etanercept," they concluded from their pooled analysis.

Following induction with MTX, "a maintenance dose of MTX <10 mg/week is sufficient to retain efficacy when used in combination with etanercept," they added.

The researchers pooled data from two clinical trials -- the Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis (COMET) study and the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) -- in which RA patients were randomized to receive MTX monotherapy or a combination of MTX and etanercept for 24 consecutive months.

Patients in the MTX arms in both trials received 7.5 mg/week, which could be increased to 15 mg/week and again to 20 mg/week if response was inadequate. Following dose titration, MTX dosage remained stable unless adverse events necessitated a reduction.

Patients within the MTX arm and within the etanercept-plus-MTX arm in the pooled TEMPO and COMET studies were divided into three groups according to their MTX dosage at 24 months: low dose (<10.0 mg/week); medium dose (10.0- 17.5 mg/week); or high dose (>17.5 mg /week).

There were 276 patients in the etanercept-plus-MTX arm and 218 in the methotrexate arm.

Outcomes at 24 months evaluated for each subgroup were Disease Activity Score in 28 joints (DAS28), attainment of low disease activity (LDA) and remission, and American College of Rheumatology 20%, 50%, and 70% (ACR20, 50, and 70) responses. Changes from baseline in the Health Assessment Questionnaire Disease Index (HAQ-DI) and EuroQol 5-Dimensions (EQ-5D) visual analogue scale (VAS) were also evaluated.

At 24 months, 55% of patients were receiving 10.0 to 17.5 mg/week of MTX, with a mean dosage of 11.0 mg/week and a median dosage of 10.0 mg/week.

"Clinical responses as measured by DAS28 LDA and remission rates, ACR 20/50/70 rates and change from baseline in DAS28 were similar for patients treated with etanercept-plus-MTX combination therapy, regardless of the MTX-e dose used," noted Gallo and colleagues.

At 24 months, more than 60% of patients randomized to etanercept plus MTX achieved DAS28 remission or LDA -- 68% in the low-dose MTX group, 69% in the medium-dose group, and 70% in the high-dose group.

More patients randomized to etanercept-plus-MTX combination therapy achieved DAS28 remission or LDA, or DAS28 remission only, compared with those randomly assigned to MTX monotherapy at all time points. Rates of DAS28 LDA did not appear to be related either to the MTX dose in either of the MTX arms of the study.

In the etanercept-plus-MTX arm, the rates of ACR20, ACR50, and ACR70 "were largely unaffected by the MTX dose at 6, 12, and 24 months," the authors wrote. ACR20 responses were achieved by 89% to 93% in each MTX dose group; ACR50 response in 73% to 79%, and ACR70 response in 56% to 59%.

"Rates of ACR 20, 50, or 70 were paradoxically inversely related to the dose in patients receiving MTX-e monotherapy," they added. Patients receiving any dose of MTX monotherapy were less likely to achieve ACR 20, 50, or 70 compared with those receiving etanercept plus MTX at 24 months.

Improvements from baseline in DAS28, HAQ-DI, and EQ-5D VAS were not dependent on MTX dosage in the etanercept-plus-MTX combination arm. Improvements from baseline to month 24 were of greater magnitude in those receiving etanercept plus MTX than in those receiving MTX monotherapy in all patient-reported outcome measures.

A lack of pharmacokinetic alternations to etanercept with concomitant MTX "could help to explain why increased efficacy of etanercept plus MTX over MTX monotherapy was not MTX dose-dependent in this study," the investigators postulated.

In addition, they noted that as a potential limitation, the study population may have been biased toward treatment responders, as evidenced by the stable dose of MTX over time in the two studies. In addition, pooling data from two studies with diverse patient populations (early disease in COMET, late disease in TEMPO) may have produced a result different from that of assessing the trials separately.

Two authors are full-time employees of Pfizer, and another is a full-time employee of Quanticate International, which was contracted by Pfizer to provide statistical input to the study and manuscript. One author was a former employee of Pfizer. Others report lecture fees/consultancy fees from Merck, UCB, Bristol-Myers Squibb, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boehringer Ingelheim, Takeda, Zydus, and Eli Lilly.

This post-hoc analysis was sponsored by Pfizer.

take posttest

Let's block ads! (Why?)

MTX Dose Can Be Kept Low When Combined With Enbrel in RA (CME/CE)

PodMed: A Medical News Roundup From Johns Hopkins (with audio)

PodMed is a weekly podcast from Johns Hopkins Medicine. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week's topics include asthma and under the tongue immunotherapy, reducing C. diff infections, safety of smoking cessation drugs, and antibiotic stewardship.

Program notes:

0:39 Safety of smoking cessation medicines

1:40 None increased risk of psychiatric problems

2:40 How about combinations?

3:07 Sublingual immunotherapy

4:08 In people with moderate to severe asthma

5:09 Limited FDA approval

5:44 Antibiotic stewardship

6:44 Identified top 20% of overprescribers

7:45 Nobody mandating change

8:00 Reducing C. diff infections in hospital

9:00 Estimated to save quite a lot

10:30 End

Let's block ads! (Why?)

PodMed: A Medical News Roundup From Johns Hopkins (with audio)

D.C. Week: Medicare Reforms Backed Up With New Rules

WASHINGTON -- Physicians waiting for recent Medicare payment reforms to be fleshed out were set at ease this week by two proposed rules that streamline reporting requirements while rewarding clinical practice improvements.

New Medicare Rules Would Increase Bonus Opportunities, Ease Reporting

The Obama Administration proposed two rules Wednesday that officials say will ease physicians' documentation requirements and give them new opportunities to earn bonuses for providing high-quality care.

One rule implements what is called the Quality Payment Program, which gives doctors two options for getting reimbursed under Medicare: they can participate either in the Merit-Based Incentive Payment System (MIPS) or Advanced Alternative Payment Models (APMs).

"There have been a myriad of programs [for physician payment] developed over the years," Andy Slavitt, acting administrator of the Centers for Medicare & Medicaid Services (CMS), told reporters on a conference call. He gave alternative programs such as accountable care organizations and shared savings programs as examples. The Quality Payment Program "replaces all these programs with a single platform. Physicians will have the opportunity to get paid more for investments that support patients, and do so with minimal burden."

The second proposed rule makes changes to the highly unpopular Meaningful Use program, which requires physicians to document making "meaningful use" of electronic health records (EHRs). "We are proposing to replace Meaningful Use with a new effort that moves the emphasis away from the use of information technology to one that supports patient care that is supported by better and more connected technology," Slavitt said.

FDA Advisory Panel Splits on Second DMD Drug

Weighing hard data against patient testimonials, an FDA advisory panel voted 7-6 that a new Duchenne muscular dystrophy (DMD) failed to meet the minimum standards for accelerated approval on Monday.

The Peripheral and Central Nervous System Drugs Advisory Committee's vote signaled a lack of "substantial evidence from adequate and well-controlled studies" to trigger dystrophin production at a level considered "reasonably likely to predict clinical benefit."

In other words, the chosen surrogate endpoint was inadequate to promote any claim that the drug would actually help DMD patients -- at least in the majority's view.

CMS Advisors Mull Concept of Tx-Resistant Depression

A CMS advisory panel, called to discuss definitions of treatment-resistant depression, met for a day and voted on several points, but ended the meeting without offering such a definition.

What the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) did do was express a high confidence level in certain criteria for treatment-resistant depression (TRD) that, members said, could be used as a research definition and translated to clinical use.

The panel also agreed that a definition for TRD does exist, but expressed doubts about primary care physicians' ability to apply this definition, and about how some treatment options fit into the overall TRD picture.

Opioid REMS Falls Short on Reaching Docs

The voluntary risk evaluation and mitigation strategy (REMS) for extended-release and long-acting (ER/LA) opioids fell short of its targeted prescriber goal, according to documents released ahead of a 2-day FDA advisory committee meeting next week.

In the first 2 years, 37,512 prescribers completed the training, accounting for just under half (47%) of the targeted 80,000 prescribers, FDA reviewers said. It's not clear if this is due to a lack of awareness or because of the availability of competing continuing education activities, they noted.

On May 3 and 4, two FDA advisory committees -- the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Managment Advisory Committee -- will meet to discuss how well the opioid REMS program is working. They'll be tasked with evaluating whether the program assures safe use of the drugs, isn't unnecessarily burdensome on patient access, and minimizes the burden on the healthcare delivery system.

Medicaid Plan Networks Must Meet Standards: CMS

States will need to establish network adequacy standards for Medicaid managed care providers under a final rule issued Monday by the Centers for Medicare and Medicaid Services (CMS).

"Today's final rule has four goals: supporting states' efforts to advance delivery system reform; strengthening the consumer experience of care; strengthening program integrity; and aligning rules across health insurance coverage programs to improve efficiency and help consumers," said Vikki Wachino, MPP, director for the Center for Medicaid and CHIP Services at CMS, on a conference call. As part of those goals, "Our final rule requires states to establish network adequacy standards, and to establish time and distance standards for primary care physicians, behavioral health providers, pharmacy providers, and pediatric dentists."

The rule also requires network adequacy standards for specialists, but leaves it up to states to decide which specialists and what the standards will be. "We agree with commenters that states should define this category and set network adequacy standards that are appropriate at the state level," the final rule stated.

Generic Rosuvastatin OK'd

Late Friday, the FDA announced that it had approved the first generic version of the widely prescribed statin drug rosuvastatin (Crestor).

Watson Pharmaceuticals was cleared to sell the generic product, in multiple dosages.

"The FDA is working hard to get first-time generic drugs approved as quickly as possible so patients can have increased access to needed treatments," said Kathleen Uhl, MD, director of the Office of Generic Drugs in the FDA's Center for Drug Evaluation and Research, in a statement.

Next Week

On Tuesday and Wednesday, the FDA's Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee will discuss findings of research on the extended-release and long-acting opioid analgesics REMS (risk evaluation and management strategy). And on Thursday, the same committees will discuss benzhydrocodone/acetaminophen oral tablets indicated for short-term management of acute pain.

Also on Wednesday, the Physician-Focused Payment Model Technical Advisory Committee (P-TAC) meets to discuss recommendations regarding payment reform under the Medicare Access and CHIP Reauthorization Act.

On Thursday through Saturday, the American College of Physicians will hold its annual Internal Medicine meeting.

Let's block ads! (Why?)

D.C. Week: Medicare Reforms Backed Up With New Rules

Neurological Symptoms Strike One in Five Primary Sjogren Patients (CME/CE)

Action Points

• Note that this large case series of individuals with Sjogren's syndrome suggests that neurologic symptoms are not uncommon in this population.
• Be aware that these symptoms were based on self-report, and may not reflect true neurologic disease.

Clinicians should watch for neurological involvement in patients with primary Sjogren's syndrome (pSS), especially in those with high disease activity or previous neurological involvement, researchers suggested.

In findings from the prospective French ASSESS (Assessment of Systemic Signs and Evolution in Sjogren's Syndrome) cohort), published in RMD Open, 18.9% of 392 patients had previous or current neurological manifestations at baseline.

The peripheral nervous system was involved in 16.1% of patients and the central nervous system in 3.6% -- results consistent with studies observing neurological symptoms in about 20% of pSS patients, reported Alain Saraux, MD, of the University of Western Brittany in Brest, France, and colleagues. While central nervous system manifestations are less common, they can cause severe morbidity.

"This is good news for patients," Saraux commented to MedPage Today. "The prevalence of central neurological manifestations is shown to be low, and new neurological manifestations are rare for patients with low disease activity and no prior neurological involvement." He added that higher-risk pSS patients at his institution will receive careful evaluation.

In the chart-review analysis, the mean age of participants (94% female) -- recruited during 2006-2009 at 15 French tertiary autoimmune disease centers -- was 58±12 years, mean age at diagnosis was 51±12, and mean follow-up was 33.9 months. The average EULAR Sjogren's syndrome disease activity index (ESSDAI) was 5.3±5.6. Evaluated by case report form, in terms of prevalence, 9.2% of symptoms were of pure sensory neuropathy, 5.3% of sensorimotor neuropathy, 1.3% of cerebral vasculitis, and 1.0% for myelitis.

Symptoms were associated with greater ESSADI-scored pSS activity: 9.4±6.8 versus 4.3±4.8 (P<0.001). The affected group also had more patients taking immunosuppressant or immunomodulatory drugs: 32.4% versus 13.8% (P=0003). By drug type the P values were: glucocorticoids (P<0.001), immunosuppressive or immunomodulatory drugs (P<0.001), and rituximab (P=0.004).

New neurological symptoms occurred at more than three times the rate in patients with previous symptoms: relative risk 3.918 (95% CI 1.91- 8.05, P<0.001).

The authors noted that follow-up in a Spanish study of systemic involvement in 921 pSS patients found peripheral and central nervous system manifestations in 10.4% and 2.7% of patients, respectively.

"The apparent discrepancy between these findings and ours may be ascribable to the use in the Spanish study of the ESSDAI to define neurological involvement, as opposed to a specific list of neurological manifestations in the [case report form] used in our study," Saraux and co-authors wrote. "Past or subtle neurological manifestations may therefore have been underestimated in the earlier study."

Saraux said he would like to see these results confirmed by magnetic resonance imaging studies comparing pSS patients and healthy people.

Commenting on the paper for MedPage Today, Daniel El-Bogdadi, MD, of Arthritis & Rheumatism Associates in Rockville, Md., said, "The large number of patients is a strong point for the study. However, the study is of course difficult to extrapolate to other populations regarding prevalence as all the study centers were in France. And I would have preferred to see a prospective evaluation rather than a chart review."

El-Bogdadi further noted that although symptomatic patients have greater disease activity, "this is limited by the fact that neurological manifestations contribute to the composite ESSDAI score, and elimination of the neurological manifestation results in no significant difference in ESSDAI scores between those with and without neurological manifestations. So it is not clear if neurologic manifestation is the result of higher disease activity."

In addition, the 14-symptom case report-based analysis may have underestimated the presence of subtle neurological manifestations and may have been inaccurate in diagnosis, El-Bogdadi said. The study had a higher prevalence of Sjogren's-related neurologic symptoms than studies using ESSDAI criteria but a lower prevalence than studies that used broader definitions of neurological manifestations such as psychiatric abnormalities and neurogenic bladder and fibromyalgia/fatigue.

He said that in terms of autoantibodies, 60% of patients were anti-SSA-positive and 30% were SSB-positive. "That is in line with previous studies noting that more than 50% of patients with neurological manifestations of Sjogren's may not have autoantibodies," he said. "This is significant in that the diagnosis of Sjogren's may not be clear initially."

He also observed that since SS is a long-term chronic disease, "we may not have a true accurate number for the actual prevalence of neurological manifestations over many years of the disease. The study assumes that neurologic manifestations may occur early in disease process."

El-Bogdadi pointed out that the causal link between SS and neurological manifestations remains unclear: "Occasionally in my clinic there are patients who present with both multiple sclerosis and the diagnosis of Sjogren syndrome, and delineating which is the primary process can be difficult. I think that close coordination with neurologists is important in this instance, and the determination of the actual primary process should not be solely the rheumatologist's opinion as in this study."

A positive finding of the study is that those developing neurologic manifestations usually have a history of neurologic symptoms or diagnosis before being diagnosed with SS, he added. But the treatment of the SS neurologic manifestations remains largely empirical and based on experience in treating neurologic involvement in systemic lupus erythematosus. "A more favorable therapeutic response maybe be seen in only a certain subtype of neurological involvement, and the same therapies cannot be applied to all the patients with peripheral neurologic manifestations or central nervous system manifestations."

El-Bogdadi called for proper categorization of which symptoms among patients respond favorably to treatment. "The specification of 7 peripheral and 7 central nervous system manifestations may be helpful to be able to better organize clinical trials," he said.

Addressing the study's limitations, he also pointed to the French-only study sites and the definition of manifestations via case report from criteria in the absence of a clear definition of pSS-related neurological manifestations, which may have missed a small proportion of manifestations. As for central nervous system or cranial nerve involvement, the number of affected patients was too small to draw firm conclusions, he said.

The study was supported by the French Ministry of Health.

The authors reported no financial disclosures.

take posttest

Let's block ads! (Why?)

Neurological Symptoms Strike One in Five Primary Sjogren Patients (CME/CE)

Marketing City Smells: That's Improbable!

Some people associate specific places with specific smells. A new study examines the potential to use these city smells as marketing tools.

Are chimps musical? Recent research reveals that chimps are able to produce drumming beats similar to those that characterize musical drumming.

Mouth size appears to correlate with perceived leadership ability and performance, according to two psychologists. Improbable Research discusses the intriguing new research in this week's podcast.

Fireflies are not as delightful as they may appear. The new book Silent Sparks explores the surprising world of these winged creatures.

Animals often court potential partners with ritualistic movements. In this video, humans mimic several different mating dances.

That's Improbable! is MedPage Today's weekly roundup of clinically, um, relevant finds at Improbable Research, which awards the Ig Nobel Prizes.

Let's block ads! (Why?)

Marketing City Smells: That's Improbable!

FDA OKs Pimavanserin for Hallucinations in Parkinson's

WASHINGTON -- The FDA has approved pimavanserin (Nuplazid) for the treatment of hallucinations and delusions associated with psychosis experienced by some people with Parkinson's disease, the agency announced Friday.

Hallucinations or delusions can occur in as many as 50% of patients with Parkinson's disease at some time during the course of their illness, the FDA said in a press release.

"Hallucinations and delusions can be profoundly disturbing and disabling," Mitchell Mathis, MD, director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research, said in the release. "Nuplazid represents an important treatment for people with Parkinson's disease who experience these symptoms." It is the first drug approved for this indication, the FDA noted.

In a 6-week clinical trial of 199 participants, Nuplazid was found to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening Parkinson's disease's primary motor symptoms.

The drug has a Boxed Warning advising of an increased mortality risk associated with the use of these drugs to treat older people with dementia-related psychosis, which would be an off-label use.

In clinical trials, the most common side effects reported by participants taking Nuplazid were swelling -- usually of the ankles, legs, and feet -- due to peripheral edema; nausea; and confused state.

In March, an FDA advisory committee voted 12-2 that the benefits of Nuplazid -- which had been granted both a breakthrough therapy designation and expedited review -- outweighed the risks in Parkinson's disease psychosis, although panel members still expressed reservations.

The Psychopharmacologic Drugs Advisory Committee (PDAC) did not make a direct vote on whether or not to recommend approval. However, it did decide that the drug appeared to be efficacious (12-to-2) and that the safety profile was adequately characterized (11-to-3).

Committee chairperson David Brent, MD, of the University of Pittsburgh, noted that panelists said that while the pros of the agent outweigh the cons, there are some caveats.

"There were concerns about safety, and an emphasis that the FDA should be as specific as possible in labeling the drug to restrict off-label use," Brent said. "But given the lack of alternatives and the poor quality of life in this condition, I think that explained the majority of endorsements for the favorable risk-benefit ratio."

In terms of alternatives, other antipsychotics such as olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) are used off-label to treat the condition, but these can block dopamine, which is the most commonly used medication to treat the motor symptoms of Parkinson's disease.

Instead, pimavanserin is a selective serotonin inverse agonist that targets serotonin 5HT2A receptors, so it can reduce the symptoms of hallucinations, delusions, and agitation without adversely impacting the motor symptoms of Parkinson's, the FDA said.

Let's block ads! (Why?)

FDA OKs Pimavanserin for Hallucinations in Parkinson's

How to Build Rapport With a Physician Recruiter

Welcome to this week's edition of Healthcare Career Insights. This weekly roundup highlights healthcare career-related articles culled from across the Web to help you learn what's next.

Melissa Byington is president of the locum tenens division of CompHealth, the nation's largest locum tenens physician staffing company and a leader in permanent and temporary allied healthcare staffing. Melissa's career in physician recruiting spans nearly two decades. She also serves as the president of the National Association of Locum Tenens Organizations (NALTO).

Let's block ads! (Why?)

How to Build Rapport With a Physician Recruiter

'Stop Hunting Zebras': What We Heard This Week

"It is now time to stop hunting zebras." -- Mindy Lefler, whose son has Duchenne muscular dystrophy, urging an FDA advisory panel to recommend approval of the investigational drug eteplirsen.

"These products can help [smokers] quit all tobacco use forever." -- John Britton, MD, head of a Royal College of Physicians (RCP) committee that endorsed e-cigarettes as stop-smoking aids.

"What this group is saying is not really relevant ... to the U.S. market." -- Erika Sward, American Lung Association spokesperson, on the RCP's statement.

"The question is how well, and how soon, and how precise can we be earlier on in, order to make a difference in peoples' lives." -- Madhukar Trivedi, MD, of the University of Texas Southwestern Medical Center in Dallas, during a CMS advisory committee meeting on treatment- resistant depression.

"I believe that for the first time, the FDA has given a drug accelerated status following a negative study." -- Paul Emery, MD, on a study of tocilizumab for systemic sclerosis.

"The mom changes the whole tone of family activities." -- Diana Ramos, MD, MPH, of the Los Angeles County health department, on a walking-based exercise program for new Hispanic mothers to help them lose weight gained during pregnancy.

"Physicians will have the opportunity to get paid more for investments that support patients, and do so with minimal burden." -- Andy Slavitt, acting administrator of the Centers for Medicare & Medicaid Services, discussing his agency's proposal to change the way physicians are reimbursed under Medicare.

"Do I want the FDA flying the plane, or a pilot who has 20 years experience?" -- Richard Fessler, MD, of Rush University Medical Center in Dallas, on the FDA's involvement in regulating how physicians prescribe opioids.

Let's block ads! (Why?)

'Stop Hunting Zebras': What We Heard This Week

Friday Feedback: The Continuing Problem of Opioids and Pain

An FDA advisory committee will meet next week to discuss the FDA's use of Risk Evaluation and Mitigation Strategies (REMS) to prevent diversion and abuse of opioid painkillers. The FDA, concerned about rising overdose deaths from prescription opioids, is considering more restrictive REMS features such as mandatory physician education and certification, and a wider range of opioid products to be covered.

We contacted pain management experts via email to ask:

Do you agree that opioids are overprescribed (i.e., given for excessive durations and/or for inappropriate indications)? Who is responsible for this overprescribing?

Is it currently too hard or too easy to prescribe opioids and for patients who need them to get them?

Many patients with chronic noncancer pain insist that opioids help them, even though systematic reviews have consistently found no solid evidence to support a benefit -- how can that be?

Are genuinely abuse-deterrent opioid products the solution?

The participants this week are:

Michael Weaver, MD, FASAM, professor and medical director, Center for Neurobehavioral Research on Addiction at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth)

Robert B. Goldberg, DO, executive dean, Touro College of Osteopathic Medicine in New York City

Richard Fessler, MD, PhD, professor, neurological surgery at Rush University Medical Center in Chicago

Melissa Weimer, DO, MCR, assistant professor, medicine, Division of Internal Medicine & Geriatrics at Oregon Health & Science University in Portland

Stacy Fischer, MD, associate professor at University of Colorado at Denver Anschutz Medical Campus in Aurora

Daniel Clauw, MD, professor, anesthesiology, medicine (Rheumatology) and psychiatry at University of Michigan in Ann Arbor

Dennis C. Ang, MD, MS, section chief, Rheumatology and Immunology, Wake Forest Baptist Medical Center in Winston-Salem, N.C.

Multi-Faceted Problem

Weaver: It is less an issue of "overprescribing" or "underprescribing" than it is of "appropriate prescribing" of opioids to patients, which includes monitoring for effectiveness of the treatment plan, as well as watching out for abuse and diversion to the black market. There are lots of factors involved in the origins of the problems related to opioids coming to attention in the U.S., including awareness of the need for treatment of pain by practitioners and other stakeholders, availability of newer formulations of opioids, incentives for prescribing opioids such as patient satisfaction scores, and lack of medical education about addiction.

Goldberg: The volume of prescribed opioid drugs shot up a few years ago. The increase was not explained by the number of cancer survivors, or by any increase in accidental injuries. Increased prescribing does track with a change in policy toward physician's consideration of pain. We can measure blood pressure, pulse, temperature and heart rate using sophisticated devices that demonstrate incredible interexaminer reliability. After that we present a card to the patient with pictures to record pain, a.k.a. the fifth vital sign. The efforts to add pain as the fifth vital sign was supported by the pharmaceutical industry. Add to that the move to rate the "medical visit experience," with surveys, there is no wonder that prescription volume climbed.

Fessler: It is likely that a few individuals do overprescribe opioids. The best approach to solving that problem is to identify and correct those individuals. The relatively heavy-handed approach of the FDA of imposing onerous restrictions on all physicians is not going to be helpful to patients who truly need the medications, or to doctors who prescribe them appropriately.

PCPs Share Blame

Weimer: Most studies show that overprescribing occurs in primary care and with pain specialists. That said, overprescribing can occur in other settings where it can be most detrimental such as in young people after surgical or dental procedures. Young people seem to be at most risk to develop problems such as addiction when prescribed opioids.

Fischer: The question of who is responsible is far more complex. It would be unfair to blame primary care providers. Many of these providers inherit patients who are already on high dose opioids. Providers have very few options to offer patients with poorly controlled pain. The problem is more of a systems issue with poor access to integrative therapies such as massage, acupuncture, and mental health support for chronic distress.

Clauw: Perhaps the worst offenders now are practitioners (surgeons, ER doctors, dentists) who prescribe overly large prescriptions for acute pain. When these drugs are prescribed for acute pain there are rarely REMS programs in place, nor are these patients warned about the potential hazards. Many of the "new starts" of opioids for chronic pain at present occur in this manner -- an individual gets their original opioid prescription for acute pain but either becomes addicted or misuses them for pain they were not prescribed for (i.e., their chronic pain). This often puts primary care physicians in a very awkward position where they are then asked to refill the prescription. Many of the opioids primary care doctors are continuing to prescribe were not purposefully started by them for chronic pain.

Situations Vary

Fischer: Currently, I think it is neither too difficult or easy to prescribe opiates. However, with new FDA regulations, there is growing concern amongst palliative care and hospice providers that payment, compensation, and prescribing will become overly burdensome to physicians and patients who are facing life limited illness. This raises the concerns for barriers to adequate symptom relief for patients with opioid responsive pain or shortness of breath.

Ang: It is easy to prescribe opioids both in the primary care and emergency room settings. Due to patient's insistence physicians sometime are pushed to prescribe opiates.

Clauw: Opioids are still very commonly used in pain conditions where there is absolutely no evidence that they are effective and where there is even evidence that they may make the underlying pain condition worse (e.g., fibromyalgia, headache). The use of opioids for chronic pain is also a uniquely U.S. problem -- most countries are far more judicious with their use for chronic pain and reserve them for cancer pain and end-of-life care.

Weaver: The challenge for prescribers is to find the balance between compassionate prescribing of opioid analgesics for patients with chronic noncancer pain who may have risk factors for problems, and the duty to prevent abuse and diversion of opioids. The challenge for patients is to be aware that opioids may have some benefits, but also have serious risks, and to recognize that alternative pain management modalities can also be beneficial.

Goldberg: For patients with cancer pain, acute injury or who are status-post surgery, narcotics are properly available. The introduction of prescription monitoring programs have provided support and improved prescribing habits. Though not seamless to use, they give physician and patients pause and time to consider drug safety risks and benefits. Another shortfall to their use is that state boundaries prevent data sharing.

Systematic Reviews Imperfect

Fessler: The "results" of systematic reviews are fraught with huge methodological problems, among which are: 1) the question asked in the systematic review is often not the same as the questions asked in the papers being reviewed, 2) the detail available in systematic reviews is most often very superficial, 3) often the results depend upon the time period being assessed, and may not reflect the true effect of the treatment. In essence, "garbage in-garbage out"! Even in chronic noncancerous pain, appropriate management in pain clinics can certainly help patients.

Weaver: Studies of opioid effectiveness were done for acute pain in a short-term setting, and that data was extrapolated to long-term use of opioids for chronic pain, so not a lot of studies have been done on long-term use of opioids for chronic pain conditions across a range of patients, especially since these studies would take a long time to complete and would be very expensive if done thoroughly. Early guidelines and recommendations for treatment of chronic noncancer pain were modeled on the guidelines for cancer pain, including use of opioids. More recent studies of the effects of use of opioids in large populations of patients with chronic noncancer pain have shown that there are significant risks, so now that additional evidence is being used to guide clinical recommendations. This is how science advances and clinical care evolves with new information.

Different Patients, Different Responses

Ang: Even though the majority may not respond, 2.5% of patients with chronic noncancer pain may derive benefits from opiates by chance alone. One caveat, one has to be careful whether the benefits that patients report are truly from the analgesic effect of opiates, or more from the euphoric effect of opiates.

Goldberg: A single patient has no "control" to determine effectiveness. This makes me think about inappropriate antibiotic prescribing practices. Patients often present with a request or demand for an antibiotic. In spite of our training in infectious disease, many of us will prescribe an antibiotic rather than spend a half an hour explaining why it should not be used; knowing that if we do not, the patient will go to another provider and get it as if nothing was explained. Patient beliefs all too often outweigh our willingness to explain the risks involved.

Clauw: There are some patients with noncancer pain who truly benefit from opioids in that these drugs lead to improvements in pain and function. But there are far more who think the drugs are helping them but who clearly are functioning worse, and still in severe pain, despite taking opioids. Many chronic pain patients also like opioids because of their "anti-depressant" effects -- someone with depression who takes an opioids may not truly get high or euphoria but their life is slightly less unpleasant for the 30-60 minutes when the drug begins working and this reinforces the belief in their mind that these medications are helping their pain.

Fischer: We have endogenous opioid receptors throughout our bodies. Opioids can trigger reward centers in the brain so it is not surprising there is some subjective perception of benefit even though more objective pain scores or functional status do not show improvement of benefit from these drugs. If patients are using opioids, patients and providers should work together to titrate medication to functional goals for activity and exercise. Non-opioid adjuvants should be used whenever possible and screening and treatment of underlying mental health issues should be addressed.

Abuse-Deterrence a Chimera?

Weimer: No, I don't think that abuse deterrent opioids will solve the problem of the opioid epidemic. The solution will come with increased access to safe and effective pain care with non-opioids, patient and provider education, and access to addiction services in those cases where patients need it.

Clauw: It is like playing whack-a-mole. Once addicted someone will just move on to the next opioid that is not tamper-resistant. And now in the U.S., in most communities heroin is readily available and cheaper than any prescription opioid on the street, so even if all opioids were tamper-resistant I'm not sure it would help much given the current state of affairs.

Goldberg: The evidence is not strong enough to support their use. What we do know is that there are many modalities of physical agents, including the use of osteopathic manipulation, that have been shown to be effective in large numbers of clinical presentations.

Weaver: Abuse-deterrent formulations are one part of the solution, which also includes better education of prescribers about judicious opioid prescribing, screening patients for risks of opioid abuse or other addictions, monitoring of opioid effectiveness in patients, use of non-opioid pain management modalities, use of prescription drug monitoring programs, use of urine drug testing, and knowing how to stop opioids if the risks outweigh the benefits.

Fessler: Physicians now are more frequently judged on patient satisfaction, than on actual results. Making it more difficult to treat patients pain, is certainly going to impact patient satisfaction. This will impact a physicians decision on whether to accept a patient for care. Furthermore, the impact on suffering in pain after major surgery is almost unimaginable, and in my opinion unethical. The FDA needs to let physicians do their job. They do not have the training to prescribe medications, or the experience of caring for suffering patients on a daily basis. Take the analogy of flying a jet plane. Do I want the FDA flying the plane, or a pilot who has 20 years experience?

Let's block ads! (Why?)

Friday Feedback: The Continuing Problem of Opioids and Pain

QRISK2: A Reliable Cardiovascular Risk Calculator

Based on the 2013 lipid guidelines update, many of us stopped using the ATPIII/Framingham risk calculator and switched to the new pooled equations calculator. The AHA/ACC even released an excellent app -- encompassing both the pooled equations calculator and the lipid guideline -- called the ASCVD Risk Estimator. Previously on iMedicalApps we reviewed the ASCVD Risk Estimator and found it easy to use; it provides a wealth of information for both patients and providers.

Since 2009, the National Health Service (NHS) in the United Kingdom (U.K.) has been using QRISK. This risk calculator has both 10-year and lifetime risk calculations available, and has been updated annually. It has the advantage of a more diverse patient population than the old Framingham calculator and includes socioeconomic status -- calculated using postal codes for those living in the U.K. -- to help derive the risk calculation.

So how does the QRISK2-2014 app stand up to the venerable ASCVD Risk Estimator app?

Likes:

• Simple-to-use interface with easier data input (to a degree) compared to the ASCVD app
• Uses a more up-to-date and larger data set for risk calculations than Framingham or pooled equations apps
• One of the only medical apps to include socioeconomic status in the calculation (via postal codes for those in the U.K.)

Dislikes:

• Font along bottom of user interface difficult to read/use
• No lifetime risk calculation included
• Lacks additional lipid guideline information found in the ASCVD Risk Estimator app
• Not available for Android at this time

Bottom Line:

The evidence behind the QRISK2-2014 app is robust. This app has been utilized in the U.K. since 2009 and has been validated in cohorts of over 2 million people, including a more diverse racial population than Framingham. It has been shown in several research studies to outperform other risk calculators including Framingham. And the website for QRISK now has the option to use 2015 data.

Every provider in primary care and hospital medicine needs a good reliable CV risk calculator, and QRISK2-2014 fits the bill nicely. The medical app is a good alternative to the ASCVD Risk Estimator -- especially for those in the U.K. due to the ability to include postal codes. However, the QRISK2 app lacks some of the helpful information about the use of statins and lacks the lifetime risk calculation found in the ASCVD app.

Check out the full video review on iMedicalApps.

Note: The views expressed are those of the author and do not reflect the official policy of the Department of the Army, the Department of Defense, or the federal government.

Let's block ads! (Why?)

QRISK2: A Reliable Cardiovascular Risk Calculator

Septal Reduction Volumes; Primary Prevention Meds; 'Smoker's Paradox'

Septal reduction procedures are too often being done at low-volume centers, a study showed.

U.S. hospitals actually came in at a median of one septal myectomy case per year and 0.7 per year for alcohol septal ablation. Low septal myectomy volumes were associated with poorer outcomes, including in-hospital mortality and bleeding complications, researchers reported in JAMA Cardiology from analysis of the Nationwide Inpatient Sample from 2003 through 2011.

"Why would we subject our patients to this?" an accompanying editorial questioned. "The low-volume safety data are unacceptable. The middle volume data are not good enough. Even the highest volume tertile safety data are dramatically inferior to that achieved at hypertrophic cardiomyopathy Centers of Excellence."

Primary Prevention Meds

A meta-analysis of 35 systematic reviews to support the Million Hearts initiative showed "high-quality evidence" for efficacy in primary prevention of atherosclerotic cardiovascular disease (ASCVD) for aspirin and statins, while blood-pressure lowering therapy reduced coronary heart disease and stroke risk in primary prevention.

Smoking cessation drugs helped 6-month quit rates, but "the direct effects on ASCVD were poorly reported," researchers reported in JAMA Cardiology.

The study didn't look at lifestyle intervention, such as diet, exercise, and the like, because "essentially all included trials of ASCVD prevention included background recommendations of therapeutic lifestyle change in combination with study drugs."

The researchers suggested their "systematic process, with study quality assessment using standardized tools, could be used as a potential model for more rapid development of trustworthy guidelines."

'Smoker's Paradox'

Smokers are more likely to survive their hospitalization for revascularization in ST-segment elevation myocardial infarction (STEMI), an analysis of the National Inpatient Sample databases found.

While some of the association dissipated with risk adjustment, the in-hospital mortality odds remained 40% lower compared with nonsmokers, according to the study in the Journal of the American Heart Association. Length of stay, post-procedure bleeding, and in-hospital cardiac arrest were also less likely for smokers.

Why might smokers do better? First author of the study Tanush Gupta, MD, of New York Medical College in Valhalla, suggested some mechanisms in an email interview with MedPage Today:

"The first likely mechanism is unmeasured confounding. Smokers with STEMI in our study were on average 8 years younger than nonsmokers and had lower prevalence of most cardiovascular comorbid conditions. Although we adjusted for both age and comorbid conditions in our statistical regression models, there is a possibility that there is continued unmeasured confounding at play.

"The likely biological mechanism for the smoker's paradox in STEMI patients is the enhanced activity of antiplatelet drugs such as clopidogrel and prasugrel in smokers. There is ample evidence that these drugs, especially clopidogrel, are much more potent in smokers than in nonsmokers. Even bivalirudin has been shown to be more efficacious in smokers. Since both anti-platelets and anti-thrombotics are used universally in STEMI patients, greater potency of these drugs in STEMI patients could explain these findings."

Childhood Obesity in China

As the world's most populous country increasingly adopts the Western lifestyle, childhood obesity rates have shot up from less than 1% in 1985 to more than 17% in boys and 9% in girls in 2014.

These findings from national surveys of schoolchildren in China over the 29-year period appeared in the European Journal of Preventive Cardiology.

"It is the worst explosion of childhood and adolescent obesity that I have ever seen," journal editor Joep Perk, MD, of Sweden's Linnaeus University, said in a press release. "The study is large and well run, and cannot be ignored. China is set for an escalation of cardiovascular disease and diabetes, and the popularity of the western lifestyle will cost lives."

In Other News

And finally, it's more trouble for the company founded on the original balloon-expandable stent. Palmaz Scientific has not only declared bankruptcy but is now being investigated for misconduct. See the full story in MedPage Today here.

Let's block ads! (Why?)

Septal Reduction Volumes; Primary Prevention Meds; 'Smoker's Paradox'

Drug-Coated Balloons: Where Is the Benefit? (CME/CE)

Action Points

• Note that this meta-analysis of randomized trials suggest that the use of drug-coated balloons are superior to noncoated balloons and drug-eluting stents for infra-popliteal stenosis in terms of vessel patency, but not in terms of clinical efficacy.
• Major adverse events were also similar between the groups.

For the percutaneous revascularization of infrapopliteal arteries, drug-coated balloons improve angiographic outcomes but not clinical endpoints, according to a meta-analysis published in JACC: Cardiovascular Interventions.

Lesions treated with drug-coated balloons showed lower late lumen loss (LLL) than those getting uncoated balloons or drug-eluting stents (DES, P=0.04).

Yet for a variety of patient-centered measures over a median of 12 months' follow-up, patients treated with drug-coated balloons fared no better (or worse) than their control counterparts:

• Target lesion revascularization (18.3% versus 29.1%, P=0.12)
• Amputation (13.3% versus 14.9%, P=0.86)
• Death (11.4% versus 10.6%, P=0.59)
• Major adverse events (29.9% versus 38.5%, P=0.70)
• Rutherford Class 5-6 (66.0% versus 55.6%, P=0.65)

"In comparison to uncoated balloon or DES, the treatment of infrapopliteal arteries with drug-coated balloon is associated with similar clinical outcomes and favorable angiographic efficacy at 1-year follow-up," Salvatore Cassese, MD, PhD, of German Heart Centre, and colleagues reported in the online publication.

"The favorable angiographic outcome associated with drug-coated balloons seems due to inhibition of neointimal proliferation and positive vessel remodeling," they added. "However, in patients suffering from advanced stages atherosclerotic disease of infrapopliteal vessels a positive angiographic result does not improve per se clinical outcomes (e.g., lower amputations, complete ulcer healing, etc.) unless aggressive wound care management is adopted."

Meanwhile, writers of an accompanying editorial -- Thomas Zeller, MD, of Germany's Universitaets-Herzzentrum, and Michael R. Jaff, DO, of Massachusetts General Hospital in Boston -- questioned the validity of the LLL findings.

They asked: "First of all, are the angiographic findings correct? Are drug-coated balloons really superior in terms of LLL over uncoated percutaneous transluminal angioplasty and DES?

"Interestingly, only the three uncontrolled studies using the IN.PACT Amphirion drug-coated balloons resulted in superior LLL outcomes," they continued, "whereas both independently core laboratory adjudicated and fully industry funded studies found identical LLL outcomes for the drug-coated balloon and percutaneous transluminal angioplasty cohorts.

"The potentially incorrect interpretation of a favorable angiographic outcome without a clinical benefit in this meta-analysis might result in problematic conclusions such as the one suggesting that patency does not matter in infrapopliteal interventions in general," Zeller and Jaff wrote.

"The Yukon BTK study comparing DES with bare metal stents resulted not only in a significantly reduced restenosis rate favoring the DES at 2 years of follow-up," they added, "but as a result of the improved patency also resulted in a reduced target vessel revascularization and amputation rate underlining the relevance of a patent vessel in the long run."

To date, the ability to maintain lasting effects from the endovascular treatment of longer infrapopliteal lesions "remains one of the last significant challenges," according to the editorialists.

The meta-analysis included five randomized trials and a total of 641 patients.

Cassese's group acknowledged that it had been limited by the flaws of the original trials. In addition, "the limited numbers of patients, and the lack of a standardized wound care management in the majority of trials included preclude definitive assumption regarding the comparative clinical efficacy of these revascularization strategies," the authors admitted.

Owing to the scant data in favor of treating infrapopliteal lesions with drug-coated balloons, Zeller and Jaff noted, "this technology is not reimbursed even in countries where dedicated reimbursement is established for drug-coated balloon treatment of femoro-popliteal lesions, such as Germany."

"The conclusion drawn by the authors of this meta-analysis that drug-coated balloons result in favorable angiographic outcome compared to percutaneous transluminal angioplasty or DES must be interpreted with caution," the editorialists declared.

And, they added, "the results of this meta-analysis cannot be generalized to other commercially available drug-coated balloons without published clinical study data or to those drug-coated balloons still under clinical evaluation."

Cassese declared no relevant conflicts of interest.

Zeller reported consulting for Boston Scientific, Cook, Medtronic, W. L. Gore, Veryan, Spectranetics, Trireme, and Terumo.

take posttest

Let's block ads! (Why?)

Drug-Coated Balloons: Where Is the Benefit? (CME/CE)

Age, Disease Duration Predict Anti-TNF Use in AS

GLASGOW -- Among patients with ankylosing spondylitis, factors that were independent predictors of being treated with a tumor necrosis factor (TNF) inhibitor included age and patient global score and functional index, analysis of data from the British Society for Rheumatology (BSR) biologics register showed.

For each 5-year increase in age and disease duration, there was a 15% to 20% decrease in the likelihood of a patient receiving treatment with a TNF inhibitor, reported Gareth T. Jones, PhD, of the University of Aberdeen in Scotland.

On the Bath Ankylosing Spondylitis Global Index (BASG), for each 1-point difference there was a 21% increase in likelihood of receiving a TNF inhibitor, while on the BAS functional index (BASFI), each 1-point difference was associated with a 27% increased likelihood, both of which were statistically significant.

However, on the BAS Disease Activity Index (BASDAI), which is a central requirement in the U.K. for access to biologic therapy in ankylosing spondylitis, the odds ratio for anti-TNF treatment was not statistically significant, at 1.18, Jones said at the annual meeting of the British Society for Rheumatology (BSR) here.

"This suggests that we're treating the patient and not just the disease activity, and parallels data we have in the Scotland ankylosing spondylitis register, which suggests that in terms of quality of life, the BASFI and BASG are better predictors," he said.

"The TNF inhibitors have been around for well over a decade now, and are recommended for the treatment of ankylosing spondylitis in patients who have responded inadequately or who can't tolerate nonsteroidals. But a number of questions remain about the safety and benefits of these drugs over the long term, and also because a lot of the data are from highly selected clinical trial populations."

The aim of the current study was to characterize patients who were biologics-naïve and to examine the differences between patients starting anti-TNF therapy and those who were continuing on conventional treatment, he said.

The study population was drawn from the BSR biologics register and included 1,012 patients with ankylosing spondylitis whose median age was 50 and whose median disease duration was 8 years. Three-quarters were men.

Data in the registry include various clinical measures, patient-reported outcomes, and history of extra-articular disease features, as well as objective measures of inflammation such as C-reactive protein (CRP).

A total of 25% of patients at baseline were starting anti-TNF therapy.

A variety of factors appeared to differentiate patients starting a TNF inhibitor in a univariate analysis, including younger age (OR for each additional year 0.98, 95% CI 0.97-0.99), high levels of fatigue (OR 2.86, 95% CI 2.05-3.97), a history of uveitis (OR 1.48, 95% CI 1.06-2.06), and low mood (OR 2.76, 95% CI 2-3.79).

In addition, compared with never smokers or former smokers, current smokers were 2.5 times more likely to receive anti-TNF treatment.

Moreover, for each 1-unit increase on the BASDAI, there was a 70% increase in the likelihood of TNF inhibitor treatment in the univariate analysis. This was no longer significant on the multivariate analysis, however.

Elevated CRP also was an independent predictor (OR 1.78, 95% CI 1.12-2.83).

"We have shown in a real-world population various factors that independently predicted TNF inhibitor prescription among patients with ankylosing spondylitis, which did not include the BASDAI, which is the central tenet of the National Institute for Health and Care Excellence criteria for access to these therapies," Jones concluded.

Jones reported financial support from AbbVie, Pfizer, and UCB.

Let's block ads! (Why?)

Age, Disease Duration Predict Anti-TNF Use in AS

Room for Improvement in Emergency Surgery Quality

In this video, Martin Paul, MD, of Johns Hopkins Medicine in Baltimore, discusses a new study in JAMA Surgery that found just seven procedures account for 80% of the admissions, deaths, and complications associated with emergency surgeries. Researchers at Brigham and Women's Hospital in Boston examined more than 400,000 emergency surgical procedures over a 4-year period.

Paul wrote in an accompanying editorial that the human costs of these emergency surgical procedures are "staggering," and that the study findings could be used to promote quality improvement in these surgeries.

Let's block ads! (Why?)

Room for Improvement in Emergency Surgery Quality

EndoBreak: Apple's Diabetes App; Pop-Star Soda Controversy

Apple has a suite of new healthcare apps, one of which is designed to help people manage their diabetes. (CNET)

"Zinc fluxes accompany human egg activation," write scientists in Scientific Reports. The "zinc spark" is a marker of early human development.

Some in Mexico have said that the tax on sugary drinks did not reduce consumption of soda there, but the Secretariat of Health argues that this is impossible to determine with raw sales data. They crunch the numbers and show why it's necessary to correct for several variables.

Other researchers crunched different numbers on how Philadelphia's proposed sugar tax would affect people there. They found that within a few years of implementation, about 2,300 cases of diabetes would be avoided per year. (Philly.com)

The Center for Science in the Public Interest urged pop star Selena Gomez to not help Coke market their products to children.

Skipping breakfast likely isn't a reliable way to lose weight, writes STAT.

"Researchers detected transient increases in enzymes indicative of kidney health that correlated with specific phases of the female reproductive hormone cycle," according to the American Society of Nephrology.

A new study in Nature Genetics suggests that type 1 and type 2 diabetes could share a common genetic link, despite the clinical differences. (diaTribe)

EndoBreak is a collection of interesting news from the endocrinology world. It runs weekly. Contact the author at p.brown@medpagetoday.com for suggestions.

Let's block ads! (Why?)

EndoBreak: Apple's Diabetes App; Pop-Star Soda Controversy

Gout and Osteoarthritis: Is There a Link? (CME/CE)

Action Points

• Note that this observational study found no association between a history of gout and the presence of osteoarthritis.
• Be aware that the sample size, just 53 patients with gout, limits the precision of this (null) finding.

No statistically significant association could be found between gout and osteoarthritis (OA) of the hand, knee, or foot in a small study, researchers said.

However, the analysis, published in BMC Musculoskeletal Disorders, provided hints that people with gout may be more likely than those without gout to have OA affecting the small joints of the hands and feet, and less likely to have large joint OA at the knee. With just 53 gout patients included in the study, it may have been underpowered to find clear associations.

In the study, believed to be the first to examine the relationship between gout and radiographic OA across multiple joint sites, Megan Bevis, of Keele University in Staffordshire, England, and colleagues used baseline data from three prospective population-based cohorts of patients age 50 and older with pain in the hand, knee, and foot.

The analysis included 53 people with gout who were identified though primary care medical records. Each of these was matched based on age, gender, and study cohort to four participants without gout (the total in the nongout group was 211 since one patient with gout could only be matched to three controls.)

All study participants had analysis of the 16 joints in each hand while 27 gout and 108 nongout subjects had knee analysis and 25 with gout and 99 without gout had foot analysis. The researchers used relevant atlases to assess and score radiographic OA.

Hand OA was defined as Kellgren and Lawrence (K&L) grade ≥ 2 affecting interphalangeal joints (IPJs) on at least two rays on each hand. Moderate to severe hand OA was K&L grade ≥ 3 on at least two rays on each hand.

Patellofemoral (PF) joint OA was defined as K&L grade ≥ 2 on the skyline view and/or the presence of a definitive superior or inferior patellar osteophyte (Burnett grade ≥ 1) on the lateral view in either knee. Tibiofemoral (TF) joint OA was defined as K&L grade ≥ 2 on the posterior-anterior (PA) view and/or the presence of definitive osteophyte (Burnett grade ≥ 1) on the posterior tibial surface on the lateral view in either knee.

OA at each of the five foot joints first metatarsophalangeal joint [1stMTPJ], first and second cuneometatarsal joints [CMJ], navicular first cuneiform joint [N1stCJ], and talonavicular joint) was defined as a Menz grade ≥ 2 for osteophytes or joint space narrowing (JSN) on either the dorso-plantar or lateral view in either foot.

The researchers adjusted the analyses for body mass index (BMI) and diuretic use in all three analyses, and further adjusted for hand pain in the hand analysis and knee pain in the knee analysis. They did not adjust for foot pain in the foot analysis as all subjects had foot pain.

In the hand analysis, there was no statistically significant association found between gout and radiographic hand OA on univariable analysis or after adjustments. Although nonsignificant, those with gout showed trends toward having nodal hand OA (adjusted odds ratio [aOR] 1.46; 95% confidence interval [CI] 0.61-350), and having eight or more hand joints affected with moderate to severe radiographic hand OA (aOR 3.57; 95% CI 0.62-20.45).

The knee analysis, which excluded a patient with gout who had missing x-ray data and the matched controls, found no statistically significant associations between gout and knee OA in either unadjusted or adjusted analyses. However, the results suggested that subjects with gout might be less likely to have TF (aOR 0.44; 95% CI 0.15-1.29) and PF (aOR 0.70; 95% CI 0.22-2.22) OA than those without gout, the researchers said.

In the foot analysis, again there was no statistically significant associations between gout and OA. Patients with gout, however, had four times the odds of having three or more foot joints affected with radiographic OA (aOR 4.00; 95% CI 0.99-16.10).

And although a nonsignificant finding, those with gout were more likely to have foot OA affecting at least one joint or a specific joint (the 1stMTPJ, the N1stCJ, and the TNJ) compared with those without gout.

"1stMTPJ involvement is not surprising as it is a common site for both OA and gout, and an association with OA has been suggested as a possible explanation for the striking predilection of gout for this joint," the team wrote.

They explained that the frequency of OA at individual foot joints may reflect the association of gout with generalized OA, or that the pain associated with gout could alter biomechanics of the foot, potentially predisposing to subsequent OA.

"Further research is needed to understand the relationship between gout and OA, using robust case definitions based on crystal identification and imaging," the authors concluded.

A possible limitation of the study was its inadequate statistical power. Other weaknesses were that the study involved secondary analyses of data from existing cohorts and relied on primary care records for a diagnosis of gout.

Reached for a comment, Jasvinder Singh, MD, MPH, of the University of Alabama at Birmingham, said the study is important since the relationship between gout, the most common inflammatory arthritis, and OA, thought to be the most common non-inflammatory arthritis, is "a very understudied subject."

Although the study's lack of statistical significance could be because there is no true relationship, Singh said he believes it is because the study had too few patients with gout, and so lacked the power to adequately test the hypothesis that there is an association with OA.

The lack of statistical power, however, does not mean that the results are not clinically meaningful, he said: "I think the study brings to light potential meaningful clinical associations that need to be investigated" in studies with a larger sample size of gout patients.

Such studies, he added, may conclude that the associations in the current study that did not quite meet statistical significance, "actually are going to turn out to be significant."

The authors reported no financial disclosures.

take posttest

Let's block ads! (Why?)

Gout and Osteoarthritis: Is There a Link? (CME/CE)

New York Slashes Opioid Use in Childbearing-Age Women

A dramatically lower proportion of child-bearing-age women in New York state's Medicaid program received a prescription for an opioid than the national average, researchers found.

From 2008 to 2013, 20% of women ages 15 to 44 received a prescription for an opioid drug -- far fewer than a national estimate of 39.4% seen in an earlier study of Medicaid enrollees from a selection of U.S. states, according to data published in the April 29 issue of Morbidity & Mortality Weekly Report.

The difference could be due to the state's strong efforts to curb opioid overprescribing, but that proportion could be downsized yet further, said Brian Gallagher, MS, of the New York State Department of Health, and colleagues in MMWR.

"Opportunities exist for physicians and other healthcare providers treating women of reproductive age who are pregnant or might become pregnant to use other effective non-opioid pharmacologic or non-pharmacolgic treatments to reduce the risk for adverse pregnancy outcomes," they wrote.

Opioid exposure during pregnancy can cause neonatal abstinence syndrome (NAS) and has been linked to birth defects, Gallagher and colleagues explained. NAS is thought to be of particular concern as the nation continues to struggle with an epidemic of addiction to prescription and, now, illicit opioids such as heroin.

New York has attempted to be proactive in curbing opioid overprescribing, most recently with the I-STOP program, which forces clinicians to check the state's prescription drug monitoring program (PDMP) before writing an opioid script.

To assess the state's success in minimizing opioid prescribing for childbearing-age women, the researchers looked at data on about 800,000 women ages 15 to 44 who were continuously enrolled in the state's Medicaid program from 2008 to 2013.

In addition to examining opioid prescribing for this group overall, Gallagher and colleagues also investigated prescribing in subgroups stratified by risk of becoming pregnant.

The highest frequency of opioid prescribing (27.3%) was among those with an indication for contraceptive use or infertility.

The next highest (17.3%) was among those who had no indication for contraceptive use, and the lowest proportion was among those who'd had a live birth (9.5%).

"Although New York's proportion of opioid prescriptions among female Medicaid recipients who had a live birth is lower than a recent U.S. estimate, these results suggest nearly one in 10 women in this group may have been exposed to opioids in the prenatal period," they wrote.

The state's opioid policies "might contribute to the lower proportion of opioid prescribing in New York compared with opioid prescribing in most other states and the U.S. overall," the group asserted.

The study was limited by the fact that it looked only at dispensed scripts and could not validate whether the women actually took these prescriptions. Also, women might be using nonprescribed contraceptive methods such as condoms, or they might not be sexually active. And finally, the study might not be generalizable outside of women who are continuously enrolled in Medicaid.

Gallagher and colleagues called for more research into why these women are even prescribed opioids at all, instead of other pain medications, and that physicians should ascertain pregnancy status, sexual activity, and contraceptive use before prescribing opioid pain medications.

The authors disclosed no financial relationships with industry.

Let's block ads! (Why?)

New York Slashes Opioid Use in Childbearing-Age Women

Actemra's Benefits Hold Up for 5 Years in JIA (CME/CE)

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Note that this 5-year follow-up of patients doing well on tocilizumab for juvenile idiopathic arthritis showed that the anti Il-6 agent retained its already high efficacy levels.

GLASGOW -- The efficacy of tocilizumab (Actemra) for systemic juvenile idiopathic arthritis (JIA) has been maintained for 5 years, a three-part phase III study has shown.

Among a cohort of 92 children with systemic JIA who completed the first 2 years of a trial known as TENDER, the American College of Rheumatology (ACR) 30% improvement response was met by all patients at that time point, while ACR 50, 70, and 90 responses were seen in 100%, 94.4%, and 76.4%, respectively, according to Eileen Baildam, MD, of Alder Hey Children's Hospital in Liverpool.

"The 2-year results demonstrated that the IL-6 receptor inhibitor tocilizumab was effective -- extremely effective, actually -- in the treatment of severe systemic JIA, which really is one of the worst diseases we treat in pediatric rheumatology.

"It's easy to forget how severe it was before we had treatments like this that have altered the disease course," she added.

At 5 years, among the 29 patients who continued on the standard regimen of tocilizumab, ACR 70 and 90 responses were still high, at 83% and 60%, respectively, she reported at the annual meeting of the British Society for Rheumatology here.

TENDER was a three-part study that initially enrolled 112 patients with severe, persistent systemic JIA. In part 1, they were randomized to receive placebo or tocilizumab, 8 mg/kg every 2 weeks for those weighing 30 kg or more, and 12 mg/kg every 2 weeks for those weighing less than 30 kg. At the end of that 12-week phase, in part 2, all patients received open-label tocilizumab with weight-based dosing through week 104.

In part 3, which continued through week 260, those patients who achieved clinically inactive disease had the option of an alternative dosing schedule, receiving the medication but at 3- to 4-week intervals and then possibly tapering all their medications.

Among the 89 patients who entered part 3 of the trial, 50 continued on the 2-week interval dosing, while 39 had been in full clinical remission for at least 12 weeks and opted for the alternative schedule.

Of the 39 who went on the alternative prolonged dosing schedule, 32 completed the study. But those patients were not included in this part 3 analysis, so the efficacy reports for the last part of the study "most certainly represent an underestimation of the efficacy of the treatment," Baildam said.

Among the children who entered part 3, the mean age was 9.5 and disease duration was 5 years. The patients had severe disease, with 19 to 20 active joints and erythrocyte sedimentation rates averaging 57 mm/h, and 40% reported fevers during the previous week.

Among patients who continued on the 2-week dosing, 32 completed the study. Of that group, 27% had clinically inactive disease at 5 years.

Among the 66 patients who completed the study, 31 had been taking oral steroids and 34 had been on methotrexate. A total of 17 of the patients were able to stop the steroids and six stopped methotrexate. In addition to the patients who no longer were taking steroids, another 40% had decreased the dose, and the average methotrexate dose had decreased from 10.1 to 5.1/m²/week.

The most common severe adverse events were gastroenteritis and varicella.

Serious adverse events occurred at rates of 23.3/100 patient-years at year 2 and at rates of 21.9/100 patient years at year 5, while serious infections were seen at rates of 10.9/100 and 10.1/100 patient years, respectively.

By year 5, there had been four deaths -- one from sepsis, which was considered possibly treatment-related.

There also had been three cases of macrophage activation syndrome, "as one would expect, in this severe group of patients," she said.

Neutropenia and liver function abnormalities occurred, with one-quarter of patients having grade 3 neutrophil reductions, and 10% to 11% of patients had small increases in their alanine aminotransferase levels.

"This was a landmark study of systemic JIA and biologics -- the first one to be licensed for use in systemic JIA. It's a really important study," she concluded.

Baildam reported financial relationships with Roche and Chugai.

take posttest

Let's block ads! (Why?)

Actemra's Benefits Hold Up for 5 Years in JIA (CME/CE)

Morning Break: DNA in the WC; Neighborhoods and Foods; Big Business Deals

The pathway to regenerative medicine might run through your own bathroom, according to Chinese researchers. (CNN)

Tell your patients with unneeded prescription opioids: Saturday is National Prescription Drug Take-Back Day, brought to you by the good folks at the Drug Enforcement Administration.

Looking for a way to boost the health of your microbiome? Look no further than these three items, which many of us already consume regularly. (Los Angeles Times)

Many in Congress want to scrap an Obama Administration proposal to cut drug costs in Medicare Part B. (The Hill)

The neighborhood you live in may limit your access to healthier eating choices. (Ohio State University; The Professional Geographer)

Andrew Bindman, MD, is the new director of the Agency for Healthcare Research and Quality; he replaces Richard Kronick, PhD, who stepped down in March. (AcademyHealth)

MedPage Today partner VICE News reports that, although speculation about the cause music icon Prince's death has focused on prescription drugs, flu might have been a factor.

More alarms about the potential health hazards -- specifically, cancer risk -- associated with air pollution. (Cancer Epidemiology, Biomarkers, Prevention)

When you're 6'7" and 310 pounds, it's hard to hide behind a gas mask while taking bong hits, as a top NFL draft prospect learned the hard way. (USA Today)

The film hasn't been made yet, but the prospect of Will Ferrell playing a cognitively impaired President Reagan -- billed as a "hilarious political satire" -- is already controversial. (The Mercury-News)

When in need of surgery, shopping around for the best price might not be the highest priority, but maybe it should be a higher priority. (NPR)

Abbott will pay $25 billion to acquire device maker St. Jude Medical. (Bloomberg)

And Sanofi has bid $9.3 billion for a Medivation buyout, though the latter's management are resisting. (Reuters)

Teva said its ProAir RespiClick albuterol inhaler has been approved for asthmatic children age 4-11; it's been on the market since last for older asthma patients.

Morning Break is a daily guide to what's new and interesting on the Web for healthcare professionals, powered by the MedPage Today community. Got a tip? Send it to us: MPT_editorial@everydayhealthinc.com.

Let's block ads! (Why?)

Morning Break: DNA in the WC; Neighborhoods and Foods; Big Business Deals

Mindfulness May Cut Relapse Risk in Recurrent Depression (CME/CE)

Action Points

• Mindfulness-based cognitive therapy (MBCT) is effective at reducing risk of relapse in patients with recurrent depression, especially in those with the most severe symptoms before treatment, according to a meta-analysis.
• Note that MBCT is also effective compared with other active treatments and its effects are not restricted to particular groups defined by age, educational level, marital status, or sex.

Mindfulness-based cognitive therapy (MBCT) was effective at reducing risk of relapse in patients with recurrent depression, especially in those with the most severe residual symptoms, a meta-analysis showed.

Patients receiving MBCT had a significantly reduced risk of depressive relapse within a 60-week follow-up period compared with those who received usual care (HR 0.69, 95% CI 0.58-0.82), Willem Kuyken, PhD, of the Warneford Hospital at Oxford University, and colleagues reported online in JAMA Psychiatry.

Patients receiving MBCT had comparable outcomes to those who received other active treatments (HR 0.79, 95% CI 0.64-0.97), they reported.

"While previous research has shown the superiority of MBCT compared with usual care, this study provides important new evidence that MBCT is also effective compared with other active treatments and that its effects are not restricted to particular groups defined by age, educational level, marital status, or sex," the researchers wrote.

"The finding that MBCT may be most helpful for patients with higher levels of depressive symptoms adds to an emerging consensus that the greater the risk for depressive relapse/recurrence, the more benefit MBCT offers."

These results both replicate and extend previous work, Kuyken and colleagues said: "We found that MBCT reduces the risk of depressive relapse/recurrence compared with the current mainstay approach, maintenance antidepressants."

Although MBCT teaches patients at high risk of relapse how to keep depressive symptoms at bay, its protective effect appears to fade over time. In addition, patients whose symptoms were not as severe "appeared to receive less benefit," they said.

In the study -- an update to a previous meta-analysis -- individual patient data was compiled from 9 published randomized trials of MBCT in Europe and North America. The data were identified using EMBASE, PubMed/Medline, PsycINFO, Web of Science, Scopus, and the Cochrane Controlled Trials Register, and had been conducted from November 2010 to November 2014.

A total of 1,258 patients were included. Three-quarters were female and the mean age was 47.1 years. Among 1,234 participants, the mean age at onset of depression was 26 years and in 1,200 participants, 694 (57.8%) had 5 or more past depressive episodes.

The analysis demonstrated that there was no statistically significant interaction with MBCT treatment between sociodemographic factors such as age, sex, education, and relationship status or psychiatric variables including age at onset and the number of previous episodes of depression.

The researchers pointed out that a recent meta-analysis comparing the effectiveness of all psychological interventions to prevent recurrence with usual care and antidepressants has suggested that protective effects of MBCT are comparable to cognitive therapy versus usual care and interpersonal therapy versus usual care.

"The meta-analysis by Kuyken et al provides strong evidence that MBCT is effective in reducing risk of depressive relapse and is particularly effective for patients with higher levels of depressive severity before treatment," Richard Davidson, PhD, founder of the Center for Healthy Minds at the University of Wisconsin-Madison, commented in an accompanying editorial.

Previous studies have indicated that one of the key variables behind the effectiveness of MBCT is how often individuals put it into practice, Davidson noted. "While this type of association is not always present, it is a potentially very important variable and may account for considerable variability across patients and across studies."

Daily practice logs "can provide useful information with which to correlate changes in clinical and other outcomes," he added.

Looking ahead, there is an opportunity to take a closer look at which patients benefit most from MBCT, the mechanisms behind its beneficial effect, and how to more effectively measure the mediators of therapeutic change, Davidson said.

"Combining insights and methods from basic cognitive and affective neuroscientific research on mindfulness with future clinical trials provides a framework for addressing these additional questions," he wrote.

An examination of the synergistic effect of MBCT and "neuroplasticity enhancers" such as physical exercise might also be of interest, he said.

The researchers made a number of recommendations for future trials that relate directly to the limitations of their analysis and which could help "address remaining uncertainties and improve the rigor of the field."

An active control group should be considered, as well as the use of comparable primary and secondary outcomes such as the Structured Clinical Interview for DSM for depressive relapse, they said. In addition, they recommended that key variables such as race/ethnicity and employment be considered, that follow-up time be lengthened, that steps be taken to ensure generalizability of results, and that data sharing systems be created to systematically record and report adverse events.

The study was supported by the Wellcome Trust, the National Institute for Health Research Healthy Technology Assessment program, the National Institute for Health Research Collaboration for Leadership in Applied Health Research, Care South West Peninsula at the Royal Devon, Exeter National Health Service Foundation Trust, and the Medical Research Council.

Kuyken is director of the Oxford Mindfulness Centre, which was founded by study co-author, Mark Williams, PhD, its director until 2013. Anne Speckens, MD, is founder and clinical director of the Radboud UMC Centre for Mindfulness; and Helen Ma, PhD, is director of the Centre for Mindfulness, Hong Kong. Zindel Segal, PhD, disclosed a relationship with NogginLabs.

Davidson disclosed that his editorial research was funded by the National Center for Complementary and Integrative Health of the National Institutes of Health as well as several gifts to the Center for Healthy Minds, a nonprofit corporation associated with the Center for Healthy Minds at the University of Wisconsin-Madison. Davidson also disclosed that he is founder and president of Healthy Minds Innovations.

take posttest

Let's block ads! (Why?)

Mindfulness May Cut Relapse Risk in Recurrent Depression (CME/CE)

Have the Big Journals Lost Credibility?

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.

© 2016 MedPage Today, LLC. All rights reserved. Use of this site constitutes acceptance of the MedPageToday.com terms of use and privacy policy. The material on this site is for informational purposes only, and is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

Let's block ads! (Why?)

Have the Big Journals Lost Credibility?

Walking Program Helps New Moms Shed Pounds (CME/CE)

Walking Program Helps New Moms Shed Pounds (CME/CE)

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• A low-cost intervention promoting the benefits of walking helped Hispanic mothers return to their pre-pregnancy weight within 6 months of delivery, with many showing a net weight loss.
• Note that the study is part of a larger effort by the health department -- known as Choose Health LA Moms -- to get more new mothers to do three things to promote health and weight loss: walk, breastfeed, and drink water.

WASHINGTON -- A low-cost intervention promoting the benefits of walking helped Hispanic mothers return to their prepregnancy weight within 6 months of delivery, with many showing a net weight loss, researchers said here.

"The study showed that the moms not only walked more, but they walked more with the children, their baby, and their partner," Diana Ramos, MD, MPH, director of reproductive health at the Los Angeles County Department of Health and a co-author of the study, told MedPage Today in an interview at the National Hispanic Medical Association annual conference. "So the mom changes the whole tone of family activities."

The study, presented as a poster at the meeting, was led by the health department's Lonnie Resser, MPH.

In the U.S., 23% of total births are to Hispanic women and 51% of Hispanic women are overweight or obese before pregnancy, the authors noted in their poster. And in Los Angeles County, 58% of the approximately 133,000 births are to Hispanic women; overweight and obesity affects both the women and their children.

To see whether encouraging walking postpartum would help combat the problem, the investigators enrolled 39 women at 2 weeks postpartum. Participants received one weekly text message, as well as an online lesson promoting the benefits of walking, for 6 months. The lessons also included goals in terms of minutes to walk per day, while the text messages included both reminders and motivation. Participant progress was addressed with monthly questionnaires.

Prior to becoming pregnant, 56% of participants were obese or overweight; none were underweight.

The researchers accommodated both English- and Spanish-speakers in their study, with 56% of the texts and lessons in English, and 44% in Spanish.

At the end of 6 months, study participants had lost an average of 107.5% of the weight they had gained during their pregnancy, the researchers found (P<0.05). In addition, the percentage of participants walking an average of 30 minutes a day, 5 days a week rose from 41% at baseline to 65%, and 97% of participants said they planned to continue with the walks after the study concluded.

Initially, the program gave pedometers to the new mothers and tracked their steps, "but what ended up happening is that they lost the pedometer ... so it was just easier to track time," said Ramos. "So we did the average estimate of the number of steps a person takes in 15 minutes and just guesstimated [from there]."

The researchers also had to remind moms that walking inside the house also counted as walking, not just walking outside, she added.

The study is part of a larger effort by the health department -- known as Choose Health LA Moms -- to get more new mothers to do three things to promote health and weight loss: walk, breastfeed, and drink water, Ramos explained. That program includes text messages and education in all three areas.

"Normally if they're going to get back to their pre-pregnancy weight, it takes 2 years; our moms participating in the program got back to their pre-pregnancy weight in 12 weeks," she said.

The mothers who are immediately postpartum receive motivation and education on breastfeeding. "We encourage them, 'Yes, you have enough breast milk,' because many times moms think 'I don't have enough breast milk; the baby is crying' when it may not be that they're hungry, it may be gas or other issues," said Ramos.

The nice thing about the program -- which is free to participants -- is that all of the interventions are free or low-cost, she said. "If you think about it, the Affordable Care Act already pays for breastfeeding support; it pays for breast pumps and all the equipment needed, so it's something that is already available to them. Water is low-cost, and walking is low-cost too."

Women who do all three interventions are the most successful at losing weight, she said. The program did get some pushback from critics who pointed out that it requires a cellphone, "but if you look at all of the data, 95% of women who are less than 29 years old send about 108 text messages a day. This is how they communicate," she said. "And then they get all their information online."

The department would welcome anyone who wants to replicate the program elsewhere, she said. "We've had several states call us and say, 'How can we replicate your program? Because the outcomes are amazing.'"

The authors disclosed no relevant relationships with industry.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco

take posttest

Let's block ads! (Why?)

Walking Program Helps New Moms Shed Pounds (CME/CE)