Taking the Shots out of Orthopedic Surgery

As anyone who’s had knee or hip replacement surgery knows, post-op recovery can be long and painful. There’s the learning to walk again, the physical therapy and the dreaded daily injections in the belly.

While great strides have been made in surgery for degenerative joint disease, preventing post-op complications such as deep vein thrombosis (DVT) and pulmonary embolism (PE) remains problematic. Conventional antithrombotic agents (heparin and low-molecular-weight heparin) have to be given by injection into fatty subcutaneous tissue, usually into the leg or abdomen, for days or weeks after surgery and discharge from the hospital. Not surprisingly, acceptance of, and compliance with, thromboembolic prophylaxis is limited by the need for injections, the bruising and associated risks for bleeding.

Now it seems the days are numbered for injection therapy.  A recent meta-analysis of 22 randomized trials comparing oral factor Xa inhibitors with low-molecular-weight heparin injections in adults who underwent total hip or knee replacement has just been published in the Annals of Internal Medicine.

The results showed that new generation oral antithrombotic agents, including apixaban, edoxaban, and rivaroxaban, that do not require monitoring, actually led to fewer symptomatic deep venous thrombosis.

Furthermore, there was no difference between the groups in terms of mortality, non-fatal PE, major bleeding, or bleeding leading to reoperation. The study authors therefore predict that these oral agents will likely replace low-molecular-weight heparins.

As a likely candidate for future joint replacement, thanks to a family history of osteoarthritis, and joints wrecked by years of gymnastics and running, I for one am very grateful.

Rogue Reporting

According to an article just published in the Journal of General Internal Medicine, results of drug studies published in medical journals may be misleading.

The UCLA-Harvard study says that the drug trials published in the most influential medical journals including the New England Journal of Medicine, the Journal of the American Medical Association, The Lancet, the Annals of Internal Medicine, the British Medical Journal and the Archives of Internal Medicine are frequently designed in a way that yields misleading or confusing results.

Investigators analyzed all the randomized drug trials published in the above journals between June 1, 2008, and Sept. 30, 2010, to determine the prevalence of outcome measures that make data interpretation difficult.  In addition, they reviewed each study’s abstract to determine the percentage that reported results using relative rather than absolute numbers, which can also be misleading.

They specifically looked at three outcome measures that have received increasing criticism from scientific experts: surrogate outcomes, composite outcomes and disease-specific mortality and found that :

• 37% of the studies analyzed used surrogate outcomes – intermediate markers, such as a heart medication’s ability to lower blood pressure, but which may not be a good indicator of the medication’s impact on more important clinical outcomes, like heart attacks

• 34% used composite outcomes which consist of multiple individual outcomes of unequal importance lumped together, such as hospitalizations and mortality, making it difficult to understand the effects on each outcome individually

• 27% used disease-specific mortality, which measures deaths from a specific cause rather than from any cause. This may be a misleading measure because, even if a given treatment reduces one type of death, it could increase the risk of dying from another cause, to an equal or greater extent

“Patients and doctors care less about whether a medication lowers blood pressure than they do about whether it prevents heart attacks and strokes or decreases the risk of premature death,” said the study’s lead author, Dr. Michael Hochman, a fellow in the Robert Wood Johnson Foundation Clinical Scholars Program at the David Geffen School of Medicine at UCLA’s division of general internal medicine and health services research, and at the U.S. Department of Veterans Affairs’ Los Angeles Medical Center.

Dr. Danny McCormick, the study’s senior author and a physician at the Cambridge Health Alliance and Harvard Medical School, added: “Patients also want to know, in as much detail as possible, what the effects of a treatment are, and this can be difficult when multiple outcomes of unequal importance are lumped together.”

The authors also found that 45% of exclusively commercially funded trials used surrogate endpoints, whereas only 29% of trials receiving non-commercial funding did. Furthermore, while 39% of exclusively commercially funded trials used disease-specific mortality, only 16% of trials receiving non-commercial funding did.

The study also showed that 44% of abstracts reported results in relative rather than absolute numbers, which can be misleading.  “The way in which study results are presented is critical,” McCormick said. “It’s one thing to say a medication lowers your risk of heart attacks from two-in-a-million to one-in-a-million, and something completely different to say a medication lowers your risk of heart attacks by 50 percent. Both ways of presenting the data are technically correct, but the second way, using relative numbers, could be misleading.”

To remedy the problems identified by their analysis, Hochman and McCormick believe that studies should report results in absolute numbers, either instead of, or in addition to, relative numbers, and that committees overseeing research studies should closely scrutinize study outcomes to ensure that lower-quality outcomes, like surrogate makers, are only used in appropriate circumstances.

So who’s to blame?  The pharma companies for using outcomes that are most likely to indicate favorable results for their products, the study authors for writing them up that way or the journals for accepting the manuscripts?  Let us know what you think.

Clinical Research under scrutiny?

If you watched the news at all over the past week you probably saw CNN‘s Sanjay Gupta‘s confrontation with disgraced doctor Andrew Wakefield.  He, as you may recall was the author of the 1998 study that linked autism to some childhood vaccines and set off a worldwide scare for parents.

In the intervening years there have been countless lawsuits against vaccine manufacturers and millions of children who, perhaps needlessly, have gone unvaccinated.  Recently,  an investigative report published in the British Medical Journal called the original study an elaborate fraud.

So, is Dr Wakefield alone in manipulating clinical trial data?  Can we rely on other clinical studies to provide us with the truth?

No, not according to researchers at Johns Hopkins.  In a report published January 4th in the Annals of Internal Medicine the authors concluded that the vast majority of published clinical trials of a given drug, device or procedure are routinely ignored by scientists conducting new research on the same topic.

Trials being done may not be justified, because researchers are not looking at or at least not reporting what is already known.  In some cases, patients who volunteer for clinical trials may be getting a placebo for a medication that a previous researcher has already determined works or may be getting a treatment that another researcher has shown is of no value. In rare instances, patients have suffered severe side effects and even died in studies because researchers were not aware of previous studies documenting a treatment’s dangers.

Not surprising then that they go on to say, “the failure to consider existing evidence is both unscientific and unethical.”

The report argues that these omissions potentially skew scientific results, waste taxpayer money on redundant studies and involve patients in unnecessary research.

Conducting an analysis of published studies, the Johns Hopkins team concludes that researchers, on average, cited less than 21% of previously published, relevant studies in their papers. For papers with at least five prior publications available for citation, one-quarter cited only one previous trial, while another quarter cited no other previous trials on the topic. Those statistics stayed roughly the same even as the number of papers available for citation increased. Larger studies were no more likely to be cited than smaller ones.

“The extent of the discrepancy between the existing evidence and what was cited is pretty large and pretty striking,” said Karen Robinson, Ph.D., co-director of the Evidence Based Practice Center (EPIC) at the Johns Hopkins University School of Medicine and co-author of the research.  “It’s like listening to one witness as opposed to the other 12 witnesses in a criminal trial and making a decision without all the evidence. Clinical trials should not be started — and cannot be interpreted — without a full accounting of the existing evidence.”

The Hopkins researchers could not say why prior trials failed to be cited, but Robinson says one reason for the omissions could be the self-interest of researchers trying to get ahead.

Want to make sure that your clinical trials stay on track and that your publications are evidence-based?

Contact SRxA for more details.

Prescription Abandonment

You get sick, you go to the doctor, he or she writes you a prescription for some pills, you take it to the pharmacy and then…   Logic would suggest that the next steps would be that you pick up the prescription, take the medicine and get better.

Well, not always.  According to a new study published in the Annals of Internal Medicine almost 2% of these prescriptions are never picked up.

Using databases from a large retail pharmacy chain and a pharmacy benefits manager, researchers examined factors associated with prescription abandonment over a 3-month period.

Unsurprisingly, drugs with high copayments are the most likely to go unclaimed.  Prescriptions with copayments of $40 to $50 and prescriptions costing more than $50 were 3.40 times and 4.68 times more likely, respectively, to be abandoned than prescriptions with no copayment.

In addition, electronic prescriptions were 1.6 times more likely than non-electronic prescriptions to be left behind, and new prescriptions were almost three times more likely to be abandoned than previously filled prescriptions.

Interestingly, young adults were more likely than older patients to abandon their prescriptions, while opiates and anti-platelet agents were the least likely to be left behind.

Although the accompanying editorial called the low rate of abandonment “reassuring,” they suggest that physicians “remain mindful that costs are an important barrier to adherence and should aim to prescribe or recommend less expensive alternatives whenever feasible.”

SRxA’s Advisors can help pharmaceutical companies increase medication compliance and implement programs to lower the consumer cost of prescription drugs. Contact us today for more information.

Patients are from Mars, Physicians are from Venus!

Or so it would seem.  According to a study just published in the Annals of Internal Medicine there is a huge disparity between patients’ expectations of angioplasty versus those of their cardiologists.  While the majority of heart patients harbor the notion that angioplasty, a procedure performed to unblock clogged arteries, will cut their risk of heart attacks and death, cardiologists believe that its value is limited to reducing chest pain.

The research involved 27 cardiologists and 153 patients who consented to elective coronary catheterization and possible angioplasty, from Baystate Medical Center, Springfield, and Tufts University School of Medicine, Boston.

During angioplasty, a tube is inserted at the groin and snaked up to the affected artery, where a balloon opens the blockage. A stent is often left in place to help prop open the artery and maintain blood flow. Angioplasty involves some risk but the rate of death during the procedure is less than 1 percent, experts note.

Although 63% of cardiologists believed that the benefits of angioplasty were limited to angina symptom relief:

• 88% of patients believe that angioplasty would prevent heart attacks or fatal heart attacks

• 74% of patients thought that without the procedure  they would probably have a heart attack within 5 years

Furthermore, most patients stuck to their beliefs even after spending time with a cardiologist who explained the risks and benefits to them, and had them sign an informed consent form prior to the angioplasty.

The authors of the study noted that the benefits obtained by angioplasty can often be achieved with medication alone, and only patients who are actually having a heart attack or coronary event can expect a reduced risk of future heart attacks and death from angioplasty.

The number of angioplasties done for stable heart patients has decreased lately.  According to the American Heart Association, about 1.3 million such procedures are done in the United States each year.

Once again, this study highlights the “disconnect” between what doctors know and what patients understand. In order to have real informed consent, patients have to understand not just the risks, but also the benefits of whatever treatment is proposed.

One reason for patients’ misunderstanding is the common belief, that if a treatment is offered, it must have curative benefits.

However, the problem of patient understanding isn’t limited to angioplasty but is common in many areas of medicine. According to a previous study from the Mayo Clinic, doctors don’t always do a good job of knowledge transfer in a way that patients and family members can understand. Graphs and charts are not going to work for many patients.

SRxA and our team of problem based learning expert Advisors can help physicians, institutions and device manufacturers produce patient-centric materials to assist with informed consent. Contact us today to find out more.

Animal, Vegetable, or …Clinical Trial?

Several clinical trials in the past 10 years have demonstrated that a low-carbohydrate, high-fat, high-protein diet is at least as effective as a calorie-restricted, high-carbohydrate, low-fat diet for weight loss and improvement of risk factors such as blood pressure, blood sugar and lipid levels.

While older observational studies linked dietary fat with poor health outcomes, newer systematic reviews, have absolved fat, with the exception of trans-fat. Many such studies have implicated refined sugars and starches instead.

Yet, in contrast to the robust understanding we have about diet and risk factors, our knowledge about the effect of diet on mortality is much more sparse, A new study, just published in the Annals of Internal Medicine study attempts to address this gap.

Researchers found that an animal-based low-carbohydrate dietary pattern increased the risk for death, whereas a plant-based low-carbohydrate diet lowered the risk.

Having analyzed food frequency questionnaires from 85,000 women from the Nurses’ Health Study and 45,000 men from the Health Professionals’ Follow-Up Study over  20 years’ they found:

• People who had the highest scores for an animal-based low-carbohydrate diet were at increased risk for all-cause and cardiovascular mortality.
• Those with the highest plant-based low-carbohydrate diet scores had a reduced risk for all-cause and cardiovascular mortality.
• Men who more closely followed any low-carbohydrate diet had a higher cancer mortality risk.

The question is how to understand this new information in the context of the existing knowledge on diet and health and research design.

Observational studies have great strengths but also significant limitations.  For now, it seems that no one can legitimately claim that a low-carbohydrate diet is either harmful or safe with any degree of certainty.

Word on Health would love for you to weigh in on this.

The Risks And Rewards Of Inviting Patients To Review Their Medical Records

Technology has placed vast amounts of medical information literally a mouse click away. Indeed, 57% of Americans say they get their primary medical information from the internet.  Maybe that’s because, an individual’s main potential source of information, the doctor’s notes, taken after a visit are not traditionally part of the discussion. Such records have long been out of bounds.

After patient encounters, doctors have long written notes ranging, from cryptic abbreviations on an index card to lyrical essays. Yet despite a patient’s legal right to read their doctor’s note, few do. Although literature suggests that promoting active patient involvement in care may improve doctor-patient communication and clinical outcomes, both patients and doctors express everything from enthusiasm to dismay when it comes to sharing the visit note.

In Open Notes: Doctors and Patients Signing On,  researchers speculate about the risks and rewards of making clinicians’ notes transparent to patients.  “Opening documents that are often both highly personal and highly technical is anything but simple,” say the investigators from Beth Israel Deaconess Medical Center.

Their OpenNotes study will include more than 100 primary care doctors and 25,000 patients who will be invited to read their notes.  Some primary care doctors interviewed as part of a pre-study assessment “…anticipated both clinical benefits and efficiencies from incorporating laboratory findings and recommendations into the note, thereby obviating the need for a follow-up letter.” They hoped for improved patient education and more active involvement by patients in their care.

On the other hand, some doctors “worry first and foremost about the effect on their time, including calls, letters and e-mails as patients seek clarifications, disagree with statements, or correct what the doctors consider trivial errors of fact.”

Others were concerned they would have to leave out important information, omit frightening diagnostic or therapeutic considerations, or that patients would not understand that ‘SOB’ stood for ‘shortness of breath.’   And some were simply embarrassed about how they write!

From the patient perspective, views are also somewhat mixed.  For some of the patients, the dialogue inherent in the process was appealing.  On the other hand, some clearly do not want to read what their doctors write because they are worried about discovering something they would rather not know, finding potential diagnoses that might make them anxious, or reading what their doctors really thought of them.

The study will use secure Internet portals and only include notes written during the trial period. While they are gathering considerable data from the patient and doctors’ experiences during the study period, investigators say their ultimate question is whether the participants will want to leave the OpenNotes switch on after 12 months.

What do you think about sharing notes with your doctor or patients?  Word on Health is waiting to hear from you.