jeudi 11 août 2016
By the Numbers: Health Spending and Income
There was no dearth of studies, columns and thinkpieces exploring the slowdown in healthcare costs for the decade starting in 2004.
But the slowdown didn't affect everyone equally, according to a report in the July issue of Health Affairs , and the result is a growing disparity in health expenditures. Samuel L. Dickman and others looked at average annual healthcare costs for each of five income brackets. They found that the top quintile continued to see rapidly rising costs, the middle class held relatively steady and the lower class actually had costs decrease.
Doctors are likely performing more services or more expensive services for the wealthiest clients.
To the authors, the finding illustrates that more medical services are going to the group with the least need.
"The pattern of sharply rising spending for the wealthy and flat or slow growth for others mirrors the widening gap in the consumption of other goods and could represent a shift from need-based to income-based receipt of medical care. We fear that it might presage deepening disparities in health outcomes," they wrote.
Figures are inflation-adjusted in 2012 dollars. They are also adjusted for age and health.
By the Numbers: Health Spending and Incomemercredi 10 août 2016
Difficulties of Big Data: The Anesthesiology News Report
Several experts unravel the challenges of big data.
A recent meta-analysis found that neuraxial anesthesia reduces surgical site infections compared with general anesthesia in patients undergoing total joint arthroplasty.
The risk of being sued for malpractice is significantly greater for physicians who have already been sued, according to a study in The New England Journal of Medicine.
A recent study found that the number of OR personnel involved in the intraoperative period does not increase a patient's risk for surgical site infections.
Respiratory depression occurs more frequently and severely in patients receiving a GI-led colonoscopy than anesthesiology-assisted gastrointestinal endoscopy, according to new research.
The Anesthesiology News Report is brought to MedPage Today readers by our friends at Anesthesiology News, a McMahon Group title. Registration (free) may be required for some content.
Difficulties of Big Data: The Anesthesiology News ReportFeedback on TEE Ordering Cuts Inappropriate Use (CME/CE)
Personal feedback on one's rate of ordering inappropriate transthoracic echocardiography (TTE) -- along with a lecture on which scenarios are rarely appropriate -- improved utilization, a single-center trial suggested.
Rory B. Weiner, MD, of Boston's Massachusetts General Hospital, and colleagues subjected some of their staff cardiologists to an educational intervention: a lecture accompanied by an electronic information card, plus monthly feedback via email that revealed a count of "rarely appropriate" TTEs ordered and an explanation of why they were classified as such according to the 2011 American College of Cardiology appropriate use criteria.
This group showed a reduction in inappropriate outpatient TTEs ordered compared with attending cardiologists who received the lecture but not monthly feedback (10.5% versus 16.5%, OR 0.59, 95% CI 0.39 to 0.88) and a nonsignificant trend towards a higher rate of appropriate TTEs (77.6% versus 72.0%, OR 1.38, 95% CI 0.93 to 2.05), Weiner's group reported online in JAMA Cardiology.
The intervention and the control groups showed similar rates of ordering TTEs that "may be appropriate" as per the appropriate use criteria (11.9% versus 11.5%, OR 0.99, 95% CI 0.59 to 1.67).
"Results from our study indicate that attending academic cardiologists can amend their ordering of outpatient TTEs in response to education and feedback," they wrote.
Moreover, it appeared that experience did not affect the trend, as stratification by academic rank did not produce any outlying groups.
The most common reasons for inappropriate TTE were:
- Routine imaging within 3 years of prosthetic valve insertion (17.1% of cases)
- Routine screening for valvular stenosis less than a year apart between TTEs (15.0%)
- Routine surveillance of cardiomyopathy (10.5%) or ventricular function (8.4%)
Cases involving atrial fibrillation were the most common source of unclassifiable TTEs (3.3%), which appropriate use criteria guidelines did not designate as "appropriate," "may be appropriate," or "rarely appropriate." Other unclassifiable scenarios involved serial follow-up on cardiac resynchronization therapy without worsening heart failure or device dysfunction and left ventricular function assessment after revascularization.
"It is possible that the need for practice improvement in these domains is greater than believed, since the appropriate use criteria do not readily capture clinical practice in these particular settings," Weiner and colleagues suggested.
Their prospective, randomized trial included a staff of 66 attending cardiologists (one of whom retired during the course of the study and was excluded from the analysis) who saw patients from November 2013 to June 2014 .
"There are several limitations of this study," the investigators acknowledged.
"First, the trial was aimed at attending academic cardiologists, and the effect of performing this type of intervention on attending physicians from other disciplines (ie, general internists) is unknown. Noncardiologists (e.g., primary care, family practice, surgeons, neurologists) ordered up to half of the TTEs in a large Medicare database; therefore, any systemic efforts will need to include physicians other than cardiologists," they wrote, adding that future studies should include nurse practitioners who order TTEs.
"Second, this study was performed at an academic center, where several specialized referral cardiac programs (e.g., interventional valvular disease, thoracic aortic disease, and adult congenital heart disease) exist; therefore, our findings may not be generalizable to other practice environments."
They commented that it was impossible to blind their study participants and that "perhaps knowing that they were to receive individual feedback stimulated a change in ordering from the outset in the intervention group." Another caveat to their findings was the possibility that patterns in documentation changed in response to that monthly email, not actual practice.
Finally, "the sustainability of the impact of this type of intervention needs further study since there are discrepant data on the long-lasting effects of these types of interventions," the authors added.
To address some of the study's limitations, Weiner's group pointed to an ongoing, multi-center study on appropriate use criteria-based interventions in TTE ordering.
Weiner disclosed no relevant relationships with industry.
UNOS/OPTN Propose New Liver Allocation Plan
Liver transplantation might become more equitable under an allocation program being considered by the United Network for Organ Sharing (UNOS) and the Organ Procurement and Transplantation Network (OPTN).
The proposed plan, which will be released for public comment on Aug. 17, would change the geographic regions in which livers are allocated throughout the U.S. Under the current system, the country is divided into 11 different regions, and organs are allocated within each region based on how sick the patients on the transplant list are.
However, the regions vary greatly in terms of size and also vary a lot in terms of how many patients are waiting for transplants and how many potential donors there are, explained Ryutaro Hirose, MD, chair of the Liver and Intestinal Committee at OPTN, on a call with reporters.
In addition, the degree of illness that's required to get a transplant -- which is determined based on a 40-point scale known as a MELD score -- varies greatly from region to region. "In some areas of the country, you have to reach MELD score of 35 -- those are patients who are extremely ill and usually will die within a week," explained Hirose, who is also an organ transplant surgeon at the University of California San Francisco.
"Whereas in some areas, you have to have a score of 23, and those folks are sitting at home and we have to call them in for a transplant." As a result, there is as much as a 60% difference by geographic area in the rates of death within 3 months among patients who don't receive a transplant.
From 11 Regions to Eight
Under the proposed changes, the country would be divided up into eight regions. The sickest patients would continue to have the highest priority, Hirose said. "When we re-draw the lines, it actually matches better with organ supply and demand, and encourages better access." UNOS and OPTN employed a firm that used mathematical modeling "to select the best solutions that met the goals of decreasing this inequity within certain boundaries ... and to help with practical issues such as decreasing the amount of transport time to get a liver from one part of a district to another, and to make sure that any solution we came out with did not increase the number of waitlist deaths."
The map was also modified so that in places where a donor hospital is located, transplant candidates who are in a 150-mile "proximity circle" will get more priority on the list, "and that will keep organs from flying long distances for very small differences in the MELD score," Hirose explained.
If no patient in the geographic region needs or wants the liver, then UNOS and OPTN will prioritize the sicker patients nationwide by their MELD score, "from 40 all the way down to 29," to see if any of them could use it, Hirose said. "Then we would go back to more local distribution for less sick patients and then go back to a wider district and national distribution should no one want that liver or [if there were] nobody who could use that liver within the higher categories."
The model found that the variance in median MELD score required for a transplant would be cut in half by the new system, from 6.2 points to 2.9 points. It also found that pre-transplants deaths would not increase, and that 95% of transplants would take place within the assigned geographic area. Researchers did find that there would be an overall 2% decrease in the number of transplants performed, but "[they] have told us this was probably a very low reliability number," Hirose added.
Less Transplant Travel?
Hirose told MedPage Today that the new map could potentially reduce the issue of having some patients get an unfair advantage by moving from one area of the country -- where a higher MELD score is needed for a transplant -- to another area that has a lower required MELD score, something that the late Apple CEO Steve Jobs did.
"There are a fair number of patients who have the resources to move from one area of the country to another," he noted. "In some areas you only have to have a MELD score of 20 or 23, while within others, like where Steve Jobs came from, you have to have a score of 35. It's completely legal and within our policy to have folks multiple list ... [But] that really disadvantages folks without resources that can't travel."
In addition, there is also the insurance issue. "Folks with Medicaid are never going to be covered to have a transplant done somewhere else where the liver supply is much better, so you have an exacerbation of a very two-tiered system," said Hirose. "That's a different disparity -- not just where you live, but how much money you make and how well-insured you are."
The new map would mean that patients in some regions would need higher MELD scores than before in order to receive a transplant, so some people have raised the issue of whether more livers will be wasted on sicker patients who will end up dying even with a transplant. "Right now that hasn't happened in any of the allocation policies that could potentially do that; we haven't seen that yet," he said. Instead, "we've had better and better outcomes since the MELD score was put in place" to determine patient priority.
Other Issues Being Considered
The committee is also looking at several other issues; one involves the review boards in each region that decide whether to grant exceptions to the priority system to allow liver transplants for patients whose severity of illness might not be accurately reflected by their MELD score. The regional boards vary in the number of cases they get, how they review them, and how often they approve exceptions.
"So a related but separate proposal we are putting forth is the creation of a national review board to make more consistent, across the board and across the country, how these practices are done," said Hirose.
Another thing the committee is looking at is adjusting the number of MELD points patients with liver cancer get, he added. "Right now, patients with liver cancer are a little more advantaged than folks that don't have liver cancer, and we want to make sure we're giving everyone a fair opportunity to go ahead and get a liver transplant."
The comment period on the proposals will remain open until Oct. 14; final proposals will then be drafted and another comment period opened in January.
UNOS/OPTN Propose New Liver Allocation PlanIVF With Frozen Embryos May be Better in Women With PCOS (CME/CE)
Infertile women with polycystic ovary syndrome (PCOS) seemed to have a higher rate of live birth after undergoing in vitro fertilization (IVF) with frozen embryos compared with fresh embryos, a small study from China found.
Overall, nearly half (49.3%) the women with frozen embryo transfer had a live birth compared with 42% of women with fresh embryo transfer (relative risk 1.17, 95% CI 1.05 to 1.31, P=0.004). One potential explanation for this could be lower rates of pregnancy loss, as nearly a third of women in the fresh embryo group experienced a pregnancy loss compared to only 22.0% of the frozen-embryo group (RR 0.67, 95% CI 0.54 to 0.83, P<0.001), reported Zi-Jiang Chen, MD, of Shandong University in China, and colleagues.
Not only was the frequency of live birth after the first transfer higher, but frozen embryo transfer was associated with a significantly lower frequency of pregnancy loss and ovarian hyperstimulation syndrome, a potentially life-threatening medical condition affecting women taking fertility medication), they wrote in the New England Journal of Medicine.
However, compared with fresh embryo transfer, frozen embryo transfer was also linked with a higher rate of preeclampsia, they noted.
The frozen embryo versus fresh embryo debate has been long and ongoing among the IVF community, with certain recent evidence in favor of frozen embryo transfer. But this may be especially important for women with PCOS, the authors explained, because this population is particularly at risk for ovarian hyperstimulation syndrome (OHSS) and later pregnancy complications.
In an email to MedPage Today, Kaylen Silverberg, MD, of Ovation Fertility in Los Angeles, a national fertility service provider, said this confirms many of the findings about patients with PCOS that he has observed.
"Patients with PCOS are at high risk of ovarian hyperstimulation syndrome following IVF due, primarily, to their typically vigorous response to gonadotropin induced ovarian stimulation," said Silverberg, who was not involved with the research. "When embryos are frozen and the transfer is delayed until a subsequent cycle, the ovaries have a chance to recover. In addition, as no gonadotropin stimulation is required for frozen embryo transfers, embryos are transferred into a more physiologic uterine environment, there is essentially no risk of OHSS, and higher pregnancy rates result as well."
The researchers examined infertile women with PCOS undergoing their first IVF cycle. All the women were between ages of 20 and 34, and weighed at least 40 kg (about 88 lbs).
They randomized 762 patients to receive fresh embryo transfer and 726 patients to embryo cryopreservation, followed by frozen embryo transfer. Transfers occurred after 3 days of embryo development, and up to two embryos were transferred.
"This protocol potentially offers immediate benefits to women with PCOS, so practitioners should consider freezing all embryos for these patients," said co-author Richard Legro, MD, of Penn State College of Medicine in Hershey, in a statement.
The authors reported that the rates of OHSS were significantly higher among women with PCOS in the fresh group versus the frozen group (1.3% versus 7.1%, RR 0.19, P<0.001).
The preeclampsia rate among the frozen-embryo group was 4.4% compared with only 1.4% in the fresh-embryo group (RR 3.12, 95% CI 1.26 to 7.03, P=0.009). The authors said that this was consistent with prior observational studies, where frozen embryo transfers were associated with a higher risk of hypertensive disorders.
There were no significant differences in other pregnancy rates -- biochemical pregnancy, clinical pregnancy, ongoing pregnancy, ectopic pregnancy -- other pregnancy complications, neonatal complications, or congenital anomalies. The frozen embryo group had two stillbirths and five neonatal deaths, while the fresh embryo group had none.
But just because frozen embryo transfer was associated with positive outcomes when compared with fresh embryos, it does not mean there are no downsides to this procedure, pointed out Christos Coutifaris, MD, of University of Pennsylvania in Philadelphia, in an accompanying editorial. He argued that the many costs of frozen embryo transfer may be potential drawbacks.
"[There are] higher incremental financial costs (by a factor of 5 to 10) ... the emotional costs of deferring by 4 to 8 weeks the programmed frozen-embryo transfer, and the physical costs of additional treatments involving the administration of hormones, multiple injections and office visits," he wrote. "On the basis of current evidence, in women with a sufficient number of good quality embryos who are at low risk for implantation failure ... it may be reasonable to recommend fresh-embryo transfer as available."
Limitations to the study include that 10% of patients in each group may not have received the assigned treatment, which could have attenuated the between-group differences, as well as the fact that these results for women with PCOS may not be generalizable to other women undergoing IVF.
Also, the authors acknowledged that "the potential excess of neonatal death, owing primarily to prematurity, in the frozen-embryo group warrants attention."
They pointed out that the study was not designed to determine the mechanisms underlying their results, but "frozen-embryo transfer allows the ovary to recover from the ovarian stimulation and the exposed endometrial lining to shed, providing a fresh start for both."
The study was supported by the National Basic Research Program of China, the National Natural Science Foundation of China, and the Thousand Talents Program.
DAPT Score: Not the End-All in Decision-Making
The DAPT score does fine as a risk assessment for extended dual antiplatelet therapy (DAPT) -- but like similar tools, the real question is whether it is even used, clinicians said.
"From a methodologic standpoint, the construction of this score represents an elegant solution to a complicated problem: quantifying both benefits and harms from a therapeutic intervention into a singular metric from which clinical decisions can be based," Roxana Mehran, MD, and Usman Baber, MD, both of Mount Sinai Medical Center in New York City, wrote in a commentary online in JAMA Cardiology.
But the score failed to include certain "well-established correlates" like bleeding and body mass index, the duo noted. In addition, the DAPT trial that was the basis for the score did not enroll patients requiring triple therapy. Also, inherent in this tool is the assumption that thrombosis and bleeding are opposite and comparable risks, they added.
"These limitations notwithstanding, the DAPT score provides a timely and intuitive tool to inform a very important clinical decision. Certainly other scores will also be developed, and numerous studies will compare them in an effort to refine the decision-making process."
"However, as clinical investigators, it is critical that we do not lose sight of the forest from the trees and realize that, without implementation, the development of such scores alone will not improve the outcomes of our patients. To this end, it is sobering that only 30% to 40% of physicians use well-validated and long standing risk scores as part of routine clinical care," Mehran and Baber wrote.
"So for now, the clinician's evaluation of the patient remains paramount in the decision-making process, and although the risk scores are a great tool, their application will always be in the context of the clinician's perspective."
Mehran declared receiving research grant support from Eli Lilly/Daiichi Sankyo, Bristol-Myers Squibb, AstraZeneca, The Medicines Company, OrbusNeich, Bayer, and CSL Behring; and has worked as a consultant for Janssen Pharmaceuticals, Osprey Medical, Watermark Research Partners, and Medscape; is on the scientific advisory board of Abbott Laboratories and has given lectures sponsored by PlatformQ and Sanofi; and was also on the committee and data safety monitoring board of Covidien and Forest Laboratories and has stock or stock options in Claret Medical and the Elixir Medical Corporation.
ASCO, SGO Clarify Chemo Role in Ovarian Cancer (CME/CE)
All patients with stage IIIC or IV epithelial ovarian cancer associated with high clinical risk or a low likelihood of optimal surgical resection should receive neoadjuvant chemotherapy, according to a new clinical practice guideline.
The recommendation pertains to women who have high-risk features such as older age or a high comorbidity burden or who are unlikely to achieve optimal cytoreduction (<1 cm residual disease). Lower-risk patients with potentially resectable disease may receive neoadjuvant chemotherapy or undergo cytoreductive surgery.
Primary cytoreductive surgery is preferable for patients who have a high likelihood of achieving cytoreduction to <1 cm residual disease (ideally, no visible disease), concluded an expert panel representing the American Society of Clinical Oncology (ASCO) and the Society of Gynecologic Oncology (SGO). The recommendations were published online simultaneously in the Journal of Clinical Oncology and Gynecologic Oncology and posted on the ASCO and SGO websites.
"This guideline is a big step forward in one of the most contentious areas within gynecologic oncology," panel co-chair Alexi A. Wright, MD, of Dana-Farber Cancer Institute in Boston, said in a statement. "It provides clear recommendations to help patients and physicians make more evidence-based and informed decisions when women are first diagnosed with ovarian cancer."
In arriving at its recommendations, the panel relied primarily on the results of four published phase III clinical trials. The collective evidence from the trials showed neoadjuvant chemotherapy and interval cytoreduction to be noninferior to primary cytoreductive surgery followed by adjuvant chemotherapy. The two strategies led to similar progression-free and overall survival, but neoadjuvant chemotherapy and interval cytoreduction resulted in less perioperative morbidity and lower mortality.
"These evidence-based recommendations will improve the quality of care provided to women with ovarian cancer," said the panel's other co-chair, Mitchell I. Edelson, MD, of Abington Jefferson Health in Abington, Pa.
Three fourths of patients with ovarian cancer have advanced disease (stage IIIC/IV) at diagnosis. Until recently, primary cytoreductive surgery followed by adjuvant chemotherapy constituted standard of care for all patients with stage IIIC/IV epithelial ovarian cancer. However, many gynecologic oncologists have reconsidered the standard in light of clinical trial studies showing that neoadjuvant chemotherapy and interval cytoreduction resulted in similar outcomes with less morbidity.
To minimize uncertainty and provide guidance, ASCO and SGO convened a panel of ovarian cancer specialists representing the two organizations' membership. Specifically, the panel was asked "to provide guidance to clinicians and patients regarding the use of neoadjuvant chemotherapy (NACT) and interval cytoreduction among women with advanced epithelial ovarian cancer."
After reviewing the evidence, the panel recommended that all women with suspected stages IIIC or IV epithelial ovarian cancer undergo evaluation by a gynecologic oncologist before initiating treatment to determine the patients' suitability for primary cytoreductive surgery. The evaluation should include contrast-enhanced computed tomography imaging of the abdomen and pelvis to determine the extent of disease and feasibility of surgical resection.
With regard to the choice of primary surgery or neoadjuvant chemotherapy, the panel made the following five recommendations:
- Women should receive NACT if they have a high perioperative risk profile or a low likelihood of achieving cytoreduction to <1 cm residual disease (optimally, no visible residual disease);
- NACT or primary cytoreductive surgery is appropriate for physically fit patients who have "potentially resectable disease";
- Primary surgery is favored over NACT for women who have a high likelihood of achieving cytoreduction to <1 cm residual disease with acceptable morbidity;
- NACT is preferred for women who are physically fit but have a low likelihood of achieving cytoreduction to <1 cm residual disease; and
- The determination that a patient is not a candidate for NACT or primary surgery should be made after consultation with a gynecologic oncologist or medical oncologist.
Prior to administration of NACT, patients should have a biopsy to confirm the presence of invasive ovarian, fallopian tube, or primary peritoneal cancer. In exceptional cases when biopsy is not feasible, cytologic evaluation plus a serum CA-125:carcinoembryonic antigen ratio >25 is acceptable for confirmation of the diagnosis and exclusion of other potential diagnoses.
The panel recommended a platinum/taxane doublet as the preferred regimen for NACT but allowed for other choices as determined by individual patient factors. Interval cytoreduction should be performed after no more than four cycles of NACT in women who achieve stable disease or objective response.
"Patients with progressive disease on NACT have a poor prognosis," the panel noted. "Options include alternative chemotherapy regimens, clinical trials, and/or discontinuation of active cancer therapy and initiation of end-of-life care. In general, there is little role for surgery, and it is not typically advised, unless for palliation."
Wright disclosed no relevant relationships with industry. Edelson disclosed relationships with Merck. One or more co-authors disclosed relationships with Morphotek, Eisai, Vertex, Clovis Oncology, AstraZeneca, Exelixis, McKesson, Genentech/Roche, Boehringer Ingelheim, Abbvie, Sanofi, Novartis, Immunogen, Endocyte, Gradalis, Oxigene, Vertex, Pfizer, Tesaro, GamaMabs Pharma, Esperance Pharmaceuticals, MedImmune, OncoMed, Array BioPharma, Amgen, Johnson & Johnson, Merrimack, Millennium, Merck, Bayer, UpToDate, Aeterna Zentaris, TRM Oncology, Immunogen, Advaxis, Plasma Surgical, Exact Sciences, Putnam Global Health Care Fund, WEGO Health Solutions, Eye for Pharma, Biogen Idec, Bristol-Myers Squibb,GE Healthcare, GlaxoSmithKline, Hampton Medical Conferences, Intuitive Surgical, Janssen-Cilag, Menarini Ricerche Spa, Morphotek, Nektar, Novo Nordisk, Oasmia Pharmaceutical, PharmaMar, Phillips Gilmore Oncology, Quintiles Belgium, Schering-Plough, Sigma-Tau PHarmaceuticals, Telik, Kendle Inc., Chugai, Fresenius Biotech, Practa, Ipsen, Nerviano Medical Sciences, Sandoz, Vifor Harma, GCI Health, and Wyeth.
Mental health targets 'not being met'
CardioBrief: Experts Disagree on Lipid Screening in Kids
Once again, the U.S. Preventive Services Task Force (USPSTF) has performed an invaluable -- and almost certainly thankless -- service: In a series of papers published in the Journal of the American Medical Association and Annals of Internal Medicine, the USPSTF stated unequivocally that there is no good high-quality evidence to evaluate the risks and benefits of screening for lipid disorders in children, adolescents, and young adults.
With the exception of nutrition, it is hard to imagine an area in which high-quality evidence is so urgently needed, and so difficult to obtain.
Cardiovascular disease remains the single biggest killer in the world. But, of course, the vast majority of its victims are no longer young, and symptomatic disease is only the last stage of a decades-long asymptomatic process. The benefits of screening and treating symptomatic or high-risk adults are widely (but not universally) acknowledged. But what to do about younger people, who are at low-to-immediate risk but likely to be at high risk further down the road, remains highly controversial.
Now the USPSTF has performed an exhaustive search of the literature and determined that "the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders." Although screening can help identify children with familial hypercholesterolemia (FH) -- a group with a significantly elevated risk of cardiovascular disease, the USPSTF found "no evidence for the effect of screening for FH in childhood on lipid concentrations or cardiovascular outcomes in adulthood, or on the long-term benefits or harms of beginning lipid-lowering treatment in childhood."
The bottom line is that there are no good randomized clinical trials with hard outcomes in these populations. It is nearly impossible to perform a large enough trial for a long enough period to obtain reliable data about these populations. Even the highest-risk kids with FH will have a minuscule 10 year risk.
Screening Kids Defended
But the absence of evidence is not evidence of absence, as many have observed. In an editorial in JAMA Cardiology, Samuel Gidding, MD, of DuPont Hospital for Children, who served on the panel that developed the 2011 NHLBI and American Academy of Pediatrics guideline that gave a grade B recommendation to universal screening for cholesterol and treatment for severely elevated levels in children and adolescents.
Despite "exactly the evidence gaps identified by the USPSTF," he wrote, his group's recommendations "were driven by the consistency of the evidence relating severely elevated cholesterol levels to premature development of atherosclerosis as well as the impossibility and ethical limitations of conducting a 40-year randomized trial to prove that lowering LDL cholesterol in childhood prevents CVD events."
Gidding went on to explain why he supports a more aggressive approach despite the absence of evidence:
"A consequence of this approach is the lack of observed reductions in CVD rates during the past few years in those younger than 50 years. Event rates have decreased significantly in older individuals, for whom clinical trial data are abundant, but this benefit has not been shared by younger individuals. Many of these younger individuals are obese and have multiple risk factors, including dyslipidemia. Lipid assessment in obese individuals helps recognize this multiple-risk phenotype."
Less Is More
But a second editorial, in JAMA Internal Medicine, by Thomas Newman, MD, MPH, of the University of California San Francisco, and colleagues, offers an alternative perspective that starkly highlights the limitations of this position.
One key point is that Gidding ignored or downplayed any possible harms, such as diabetes from statin treatment. Albeit a low 0.3% over 2.7 years of treatment in clinical trial, Newman's group pointed out that there is simply no way to know "whether this risk increases with longer duration of treatment, which might be 50 years or longer for people treated beginning in childhood."
A more subtle point, and one almost impossible to measure, is whether people taking statins "may become less motivated to reduce their CVD risk in other ways." Nor did either the NHLBI or USPSTF guideline consider cost-effectiveness. Newman's group suggest that public health measures, rather than the individual medical assessment and treatment of children, will have a larger impact and be more cost effective.
Shared Decision-Making
Given the absence of solid evidence and the undeniable importance of the health issues at stake, James Stein, MD, of the University of Wisconsin in Madison, argued that "pediatric lipid screening is a perfect situation for shared decision-making between doctors, parents, and children."
In an email, he commented:
"In the absence of strong data regarding benefits or harms, we need to be cautious and humble about making too strong a recommendation about what 'must' or 'must not' be done."
"In the end, the individuals best suited to decide are probably the child and their parents, when given the information in an unbiased fashion. Some are very concerned about heart disease and stroke, others more concerned about diabetes mellitus, anxiety, inconvenience, and financial costs. Fortunately, even a decade of delay in diagnosis and treatment likely makes a minimal difference for cardiovascular disease outcomes."
"It is a cop-out to say we can't do the research, though. There are many options ranging from randomized controlled trials to big data analyses to natural experiments that can inform this decision. If the question is so important, we should answer it."
"... A simple design would be a study of randomizing to screening or not and looking at long term outcomes in a real-world setting like a large simple trial. And if it 'costs too much,' then the question is either not important or the impact is too low. There also are many other sources of informative data you could get, too, like natural experiments and big data."
"When there is equipoise it's a place for docs and patients to talk – not for people who, though well intended – to make a rule by fiat. Look at what the nutrition recommendations did to obesity in the U.S. We can't just assume a benefit. It took 25 years to find that statins cause diabetes. It's a real risk that, although irrelevant in adults with CVD, is a huge issue at a population level and in people with no disease or who are at low risk. Same for muscle aches."
"If you don't have good data to support your recommendations, you can't force people to do it. Go get the data. In the mean time, bigger ticket items like obesity, air pollution, and poverty really need our attention."
Related Reading:
CardioBrief: Experts Disagree on Lipid Screening in KidsOpposing Trends Seen in Diabetic Kidney Disease (CME/CE)
From 1988 to 2014, no significant change occurred in the overall prevalence of diabetic kidney disease, but opposing trends were seen in its major subtypes, researchers said.
In an analysis of National Health and Nutrition Examination Survey (NHANES) data, impairments in estimated glomerular filtration rate (eGFR) became more common while albuminuria became less so, according to Maryam Afkarian, MD, PhD, of the University of Washington in Seattle, and colleagues writing in the Journal of the American Medical Association.
Rates of albuminuria during the four periods, with 6,251 participants overall, were as follows:
- 1988-1994: 20.8% (95% CI 16.3% to 25.3%)
- 1999-2004: 18.9% (95% CI 15.3% to 22.4%)
- 2005-2008: 17.9% (95% CI 14.0 to 21.9%)
- 2009-2014: 15.9% (95% CI 12.7% to 19.0%)
But over the same intervals, prevalence of reduced eGFR significantly increased:
- 1988-1994: 9.2% (95% CI 6.2% to 12.2%)
- 1999-2004: 11.6% (95% CI 8.5% to 14.6%)
- 2005-2008: 11.8% (95% CI 8.4% to 15.1%)
- 2009-2014: 14.1% (95% CI 11.3% to 17.0%)
These trends appeared to cancel each other out, as the prevalence of diabetic kidney disease overall -- defined as persistent albuminuria and/or persistent reduced eGFR -- did not change significantly over the four periods:
- 1988-1994: 28.4% (95% CI 23.8% to 32.9)
- 1999-2004: 27.3% (95% CI 23.1% to 31.4%)
- 2005-2008: 27.1% (95% CI 22.6% to 31.4%)
- 2009-2014: 26.2% (95% CI 22.6% to 29.9%)
Prevalence for severely reduced eGFR also rose during the 26-year study period (adjusted prevalence ratio 2.86 for the final period versus the first; 95% CI 1.38 to 5.91, P=0.004).
Furthermore, the authors noted a temporal trend in prevalence for albuminuria in terms of age and race/ethnicity, with the lowest rates seen in non-Hispanic whites younger than 65.
"Diabetes is the most common cause of end stage renal disease in the U.S., so understanding, preventing, and treating diabetic kidney disease is critical to reduce the numbers of people needing dialysis and kidney transplants," wrote Ian de Boer, MD, in an email to MedPage Today, "There have been major changes in the treatment of patients with diabetes over the last 30 years, so we were interested in evaluating how diabetic kidney disease was changing in this context."
NHANES participants included in the analysis were those 20 and older with type 1 or 2 diabetes, identified by use of a glucose-lowering medication (insulin or oral) when data were collected, and/or had a hemoglobin A1C of 6.5% or greater.
Albuminuria was identified by a urine albumin-to-creatinine ratio (ACR) of 30 mg/g or greater, which macroalbuminuria was classified as a urine ACR of 300 mg/g or greater. Cutoffs for reduced and severely reduced eGFR were set at 60 and 30 mL/min/1.73m2, respectively.
Because chronic kidney disease is most commonly caused by diabetes, the authors indicated their goal was "to identify priorities for DKD screening, target implementation of existing interventions, and design clinical trials for new treatments." Since the researchers found no significant change in the prevalence of diabetic kidney disease over the 26-year study period, they suggest new therapies are needed.
Limits to the study included lack of data identifying the causes of diabetic kidney disease. Additionally, the authors noted that the relatively small sample size of adult with type 1 diabetes was another limitation, such that the results mostly reflect trends in type 2 disease.
While the study was successful at including a large number of participants representative of the greater U.S. population, the authors note that future research is needed to show identify other potential factors contributing to chronic kidney disease other than diabetes.
"We need to understand the biology that's underlying the changes observed in this study. For example, what's going on in the kidneys of a patient with diabetes who has reduced GFR but no evidence of albuminuria?" de Boer told MedPage Today in an email.
"If we can understand the mechanisms of disease in today's patients, who are already often treated with good glucose and blood pressure control, then we can develop new, additional interventions to further reduce diabetic kidney disease. Advances in technology, including discovery technologies like proteomics, metabolomics, and genomics, have advanced rapidly and may help us gain this level of understanding."
The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Clinical and Translational Sciences, components of the National Institutes of Health, the American Diabetes Association, and Northwest Kidney Centers.
Tuttle disclosed relevant relationships with Eli Lilly, Amgen, Noxxon Pharma, and Boehringer-Ingelheim.
De Boer disclosed relevant relationships with Bayer, Boehringer-Ingelheim, Ironwood, Amgen, and Janssen.
Lymphoma Risk Stable With Anti-TNF in RA (CME/CE)
The risk of lymphoma among patients with rheumatoid arthritis (RA) was not increased if they were treated with tumor necrosis factor (TNF) inhibitors, analysis of data from the British biologics registry found.
Compared with RA patients treated with conventional disease-modifying anti-rheumatic drugs (DMARDs) and after propensity score adjustment, the hazard ratio for lymphoma with anti-TNF treatment was 1 (95% CI 0.56 to 1.80), according to Kimme L. Hyrich, MD, PhD, of the University of Manchester, and colleagues.
There also was no increased risk for the individual TNF inhibitors, with hazard ratios of 1 (95% CI 0.49 to 2.03) for adalimumab (Humira), 1.02 (95% CI 0.45 to 2.33) for etanercept (Enbrel), and 0.91 (95% CI 0.39 to 2.13) for infliximab (Remicade), the researchers reported online in Annals of the Rheumatic Diseases.
The risk of lymphoma is increased among patients with RA, particularly the diffuse large B-cell subtype, and concerns about a further increase with TNF inhibition have been present since these treatments were introduced. "The possible effects of TNF inhibition on lymphomagenesis are difficult to predict. TNF has pleiotropic effects in the promotion and progression of malignancy, with both tumor-promoting and tumor-inhibiting actions," they explained.
In a Swedish study from a decade ago, patients in the top decile of cumulative disease activity had a 60-fold increased risk of lymphoma compared with those with the lowest activity. In addition, an earlier study by the current researchers from the British Society for Rheumatology (BSR) registry found increased risks for both Hodgkin's lymphoma (standardized incidence ratio 12.82) and non-Hodgkin's lymphoma (SIR 3.12) among patients with RA not receiving biologics.
"Therefore, given the strong association between chronic inflammation and lymphoma development in RA, it is plausible that TNF inhibition could reduce the risk of lymphoma by reducing ongoing inflammation," Hyrich and colleagues wrote.
Yet the TNF inhibitors carry a black box warning citing risks of lymphoma.
Accordingly, to provide more comprehensive and detailed information and help clarify lymphoma risks, Hyrich and colleagues analyzed data from the BSR registry for 11,931 patients with exposure to TNF inhibitors and 3,367 with conventional DMARD treatment only.
Patients receiving TNF inhibitors were younger (56 versus 60, P<0.001), had longer disease duration (11 years versus 6 years, P<0.001), had higher Disease Activity Scores in 28 joints (6.6 versus 5.3, P<0.001), and higher mean Health Assessment Questionnaire scores (2 versus 1.5, P<0.001), indicating worse disability.
They also were more often steroid users (44% versus 23%, P<0.001) and had previous exposure to more conventional DMARDs (four versus two, P<0.001).
During a median follow-up of 6.5 years in the DMARD group and 8.6 years in the anti-TNF group, 114 lymphomas were diagnosed. Among the DMARD group, there were 30 cases in 19,473 patient-years, and in the anti-TNF group, there were 84 during 95,126 patient-years.
The unadjusted hazard ratio for lymphoma in the anti-TNF group was 0.61 (95% CI 0.40 to 0.92). The final model with the propensity score included adjustments for age and sex, as well as multiple comorbidities including hypertension, ischemic heart disease, renal and liver disease, and diabetes, and disease characteristics such as severity, duration, and previous treatments.
In the conventional DMARD group, there were five Hodgkin's and 25 non-Hodgkin's lymphomas, while in the anti-TNF group, there were 12 Hodgkin's and 72 non-Hodgkin's cases. The most common subtype was diffuse large B-cell lymphoma.
Risks of lymphoma in the specific subtypes of lymphoma were not increased with anti-TNF treatment after propensity score adjustment:
- Hodgkin's lymphoma: HR 0.54 (95% CI 0.12 to 2.50)
- Non-Hodgkin's lymphoma: HR 1.10 (95% CI 0.58 to 2.08)
- Diffuse large B-cell lymphoma: HR 1.54 (95% CI 0.60 to 3.95)
Two patients in the DMARD group and three in the anti-TNF group had T-cell lymphomas, but none were the aggressive hepatosplenic subtype.
The authors noted, however, that the study was not powered to evaluate the relative risks of the specific subtypes of lymphoma. It also was not possible to adjust for cumulative disease activity.
"In conclusion, this study has ruled out an important risk of lymphoma in patients with RA exposed to TNF inhibitors over the background risk associated with RA .... This is consistent with other published data and the biological expectation that disease activity is the primary driver for lymphoma in RA," Hyrich and colleagues stated.
They called for additional follow-up to see if risks are altered by longer term and cumulative exposure to anti-TNF treatment.
BSR receives funding from AbbVie, Merck, Pfizer, Roche, Union Chimique Belge Pharma, and Swedish Orphan Biovitrum.
Hyrich disclosed relevant relationships with AbbVie and Pfizer.
Make the Diagnosis: More Than A Rash
Presentation
Case Findings: A 51-year-old woman visited her primary care doctor complaining of a rash, pruritus, myalgias, and muscle weakness that made normally easy tasks like standing from a seated position difficult. The rash was an erythematous blanching patch, spread across her back and shoulders like a shawl and across her chest in a V shape. She had also noticed that her fingernail folds were red and swollen.What is your diagnosis?
Learnings
Dermatomyositis is a multisystem autoimmune connective tissue disease that is most often characterized by a symmetric proximal extensor inflammatory myopathy, a characteristic violaceous cutaneous eruption, and pathogenic circulating autoantibodies. Dermatomyositis demonstrates a bimodal incidence, with the adult form most commonly seen in individuals aged 45-60, and the juvenile form found in children aged 10-15 years. A 2:1 female-to-male incidence ratio exists in adults.
While the etiology remains unclear, some evidence suggests that genetically susceptible individuals with certain HLA types mount aberrant cellular and humoral responses after exposure to malignancy, infection, or drug ingestion.
Clinical features of dermatomyositis can be categorized into cutaneous and systemic manifestations. Typical findings include a heliotrope rash, atrophic dermal papules of dermatomyositis (ADPDM; previously Gottron's papules), shawl sign, holster sign, photosensitivity, flagellate erythema, poikiloderma, calcinosis cutis and nail fold changes. Pruritus is also common.
Systemic manifestations of dermatomyositis include fatigue, malaise, myalgias, and the following:
- Musculoskeletal – Proximal extensor muscle group inflammation that leads to muscle pain and weakness. Patients may have difficulty getting up from a sitting position or combing their hair.
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- Gastrointestinal – Dysphagia can be seen due to esophageal muscle involvement.
Make the Diagnosis: More Than A Rash
Make the Diagnosis: Dizziness Dilemma
Presentation
Case Findings: A 42-year-old African American male presents with a report of dizziness and lightheadedness 3 days ago when he was standing up to go to the rest room. He denies any syncopal episodes. He has medically managed hypertension, hypercholesterolemia, and cardiomyopathy, and a last ejection fraction of 35% with defibrillator placement 4 months ago. His AICD did not fire during the dizziness episode. His last cardiac catheterization prior to AICD implantation revealed normal coronaries. The patient has been compliant with metoprolol 25 mg twice daily, lisinopril 10 mg daily, atorvastatin 40 mg daily. He denies any new medical regimen. His vital signs are BP 100/80 mm Hg and HR 66/min. His physical examination is normal without any clinical evidence of decompensation.What is best course of action based on what the ECG suggests?
Learnings
Correct Answer:
C. Continue current medical regimen. Obtain blood pressure and heart rate sitting and standing. This clinical presentation is consistent with orthostatic hypotension. The best course of action is to obtain orthostatics on the patient. Current physical examination and vital signs are stable. ECG shown reveals left ventricular hypertrophy with repolarization changes. There are no acute new changes to suggest any emergent intervention. Current evidence supports the use of ACE inhibitors and (to a lower level of evidence) beta-blocker therapy to impede maladaptive LV remodeling in patients with LV dysfunction to reduce mortality and morbidity. ARBs are reasonable alternatives to ACE inhibitors. In patients with previously established structural heart disease, the administration of agents known to have negative inotropic properties, such as nondihydropyridine calcium channel blockers and certain antiarrhythmics, should be avoided. Target levels of blood pressure lowering depend on major cardiovascular risk factors, (CAD, diabetes mellitus, or renal disease). Diuretic-based antihypertensive therapy has been shown to prevent heart failure in a wide range of target populations. In refractory hypertensive patients, spironolactone (25 mg) should be considered as an additional agent. Eplerenone, in synergy with enalapril, has also demonstrated reduction in LV mass. In this particular case, no additional diuretics or hypertensive agents are recommended.
Make the Diagnosis: Dizziness Dilemma
More Pasta, Smaller Waistline?
A study appearing in the journal Nutrition and Diabetes found a correlation between high pasta consumption and lower BMI. In this 150-second analysis, MedPage Today clinical reviewer F. Perry Wilson reviews whether the findings should be swallowed whole, and gives a lesson in the statistics behind "Simpson's Paradox."
F. Perry Wilson, MD, MSCE, is an assistant professor of medicine at the Yale School of Medicine. He earned his BA from Harvard University, graduating with honors with a degree in biochemistry. He then attended Columbia College of Physicians and Surgeons in New York City. From there he moved to Philadelphia to complete his internal medicine residency and nephrology fellowship at the Hospital of the University of Pennsylvania. During his post graduate years, he also obtained a Master of Science in Clinical Epidemiology from the University of Pennsylvania. He is an accomplished author of many scientific articles and holds several NIH grants. He is a MedPage Today reviewer, and in addition to his video analyses, he authors a blog, The Methods Man. You can follow @methodsmanmd on Twitter.
More Pasta, Smaller Waistline?ATS Report: Tighten Air Quality Standards to Save Lives
Modest reductions in allowable levels of ground-level ozone and fine particulate pollution would yield a host of health benefits, including nearly 10,000 deaths prevented each year, according to a report issued by the American Thoracic Society.
In a modeling study performed by researchers from the ATS and the Marron Institute of Urban Management at New York University, setting the 8-hour ozone standard at 0.060 parts per million and a limit of 11 mcg/m3 for 2.5-micron particulate matter (PM2.5) annual average levels would save 9,320 lives annually and prevent 21,400 "serious health events" including hospital admissions and emergency department visits.
Current standards set by the U.S. Environmental Protection Agency are 0.070 ppm for 8-hour ozone and 12 mcg/m3 for PM2.5.
The stricter standards evaluated in the new study would also prevent a total of 19.3 million "adverse impact days," when individuals are unable to go to work or school or must restrict their activities because of poor air quality, the researchers wrote in Annals of the American Thoracic Society.
The report identified areas that would benefit the most from stricter pollution limits. Topping the list was the Los Angeles metro region, followed by Riverside, Calif.; the New York City area; Phoenix; Pittsburgh; California's Central Valley; Houston; Cleveland; and Cincinnati.
Data for the study came from the EPA and previous studies linking health impacts from ground-level ozone and PM2.5, and the researchers -- led by Kevin Cromar, PhD, of the Marron Institute -- used the EPA's analytical models for determining pollution impacts.
"While there is information available about counties in the United States that exceed EPA air pollution standards, there has not been a similar source of information about how that air pollution actually affects the health of people living in those areas," said Cromar in an ATS press release.
The researchers promised to update the analysis regularly with fresh data on pollution and population.
The study was funded by the Marron Institute at NYU and the Turner Foundation.
Morning Break: High Times Sex; More on Zika; Opioid Marketing Code
Pfizer reached agreement with the city of Chicago on a painkiller marketing Code of Conduct. The pact "could potentially be used as a model for other drugmakers." (FiercePharma)
Hillary Clinton, at a Miami campaign stop, called on Congress to come back from summer recess to pass a Zika funding bill, echoing pleas from the state's Republican governor. (Reuters)
"Coercing athletes into using drugs": That's what legalizing sports doping would effectively do, writes Celine Gounder, MD, at Quartz.
Four more local Zika cases were reported in the Wynwood area (Miami Herald) which is "Ground Zero" for the Zika virus. The New York Times takes a closer look.
A microcephalic Houston-area baby's death was tied to its mother's Zika infection, which was contracted during travel to Latin America. (Texas Dept. of State Health Services)
A hospital in Maryland is investigating the recent deaths of two newborns possibly linked to Pseudomonas. (NBC/Video)
Could a new class of drugs prevent 50,000 deaths a year worldwide from three seemingly unrelated parasitic diseases? (CNN)
George Daley, a prominent stem cell scientist, was named the new dean of the Harvard Medical School. (STAT)
Prescription drug price reductions and "single payer" healthcare will face statewide votes this fall. (AP)
A demonstration project aimed at helping chronically ill seniors stay in their homes has saved more than $10 million. (CMS)
Food giant Cargill said it would stop using gentamicin in turkeys.
If an Italian legislator has her way, vegan parents could be jailed. (Reuters)
Duke researchers developed the first device to image children's retinas. (Medgadget)
Are 450,000 condoms enough to protect athletes and their sex partners at the Rio Olympics? Yahoo Sports asks around at the games.
Lilly's phase III trial of breast cancer drug abemaciclib should continue despite missing its primary efficacy endpoint in an interim analysis, says the study's data safety and monitoring board.
Fire broke out in a Baghdad hospital, killing 12 premature infants. (Reuters)
Small study compares sex with alcohol to sex with pot. (Pittsburgh Post-Gazette)
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.
Morning Break: High Times Sex; More on Zika; Opioid Marketing CodeA Patient's Journey: Sometimes It's Not All About Prostate Cancer
Howard Wolinsky a journalist based in the Chicago area, was diagnosed with early prostate cancer in 2010. In an ongoing series of articles for MedPage Today, he describes his journey from diagnosis to the decision to chose active surveillance. In this latest installment, he explains how a change in protocol turned up an unexpected finding.
A funny thing happened on the way to my latest prostate biopsy.
For the first time, I underwent a rectal swab in an exam room at NorthShore University HealthSystem in Glenview, about 50 miles from my home in Chicago's southern suburbs. The test had to be at least 2 weeks before I was scheduled to have the biopsy in July.
It seemed strange. It got stranger.
The results from the rectal culture revealed fluoroquinolone-resistant E. coli in my digestive tract. Only weeks earlier, I had had a bout of diverticulitis. My internist prescribed ciprofloxacin (Cipro), which must have altered the bugs in my gut and given a boost to antibiotic-resistant bugs.
I've had five previous biopsies. Each time, I was prescribed antibiotics. I took them for a few days. I never had an infection. But no one ever looked to see if I was carrying antibiotic resistant bugs.
We've heard a lot in recent years about antibiotic resistance.
At least 2 million Americans per year become infected with antibiotic-resistant bacteria, and at least 23,000 people die as a result of these infections, according to the Centers for Disease Control and Prevention.
Now I found myself right in the middle of the issue.
I was advised to come to the oncology department at NorthShore to receive an intravenous infusion of two grams of ceftriaxone an hour before the biopsy.
I wondered why NorthShore was taking these precautions and how successful they had been.
I asked Becky Smith, MD, an infectious diseases attending and the chief hospital epidemiologist at NorthShore about my concerns.
There's Something Happening Here
She said national infection rates with transrectal ultrasound prostate biopsies range from 2% to 6%.
The worst type of post-prostate biopsy infectious complication is bacteremia, which affects 0.1% to 2.2% of cases.
Smith said that around 2005, ID experts began to observe that some patients who had undergone prostate biopsies were developing E. coli infections resistant to fluoroquinolone, just the sort of situation in which I found myself.
Ciprofloxacin or levofloxacin were the most commonly prescribed because they reach high levels in the prostate.
Smith stressed that NorthShore never had "a problem" with these infections – meaning that their rate of infections was within the expected rate in the literature. But to stay ahead of the problem with increasing rates of fluorquinolone resistance in 2006, infectious disease specialists at NorthShore recommended a different approach.
"Instead of just giving levofloxacin, which was traditionally prescribed, patients received two antibiotics to cover (with the second antibiotic) for the 20% chance that the patient was carrying fluoroquinolone-resistant bacteria," she said.
Smith said the bacteria kept fighting back, introducing plasmids to bacterial DNA that made the "little bad guys" even more resistant to cephalosporins and penicillins. She said about 8% of the population has extended spectrum beta-lactamase producing (ESBL) bacteria, adding that most oral antibiotics do not cover ESBLs.
In 2012, Smith said she looked at the data from NorthShore. "Our infection rate was less than 1%. But that's still one out of 100 people who might have to come back to the hospital after a prostate biopsy. That's bad for them, and if there was a way to reduce that number, we needed to do it," she said.
Fighting Back
As a result, NorthShore in 2012 launched a quality-improvement project to introduce rectal swabbing for patients who are undergoing prostate biopsies. "This way we could not only detect whether a patient was carrying fluoroquinolone-resistant E. coli, but also avoid giving two antibiotics to patients who did not need them and therefore improve antimicrobial stewardship," Smith said.
Since the implementation of the screening protocol, NorthShore has noted ongoing improvement in their already low rates of post-prostate biopsy infectious complications, virtually eliminating complications that would result in ER visits or re-hospitalization.
Smith said this review is retrospective and that a randomized controlled study is needs to be done to determine if screening and modification of periprocedure, antibiotic prophylaxis results in fewer post-biopsy infectious complications. "We've seen an already good infection rate go to almost nothing," she said. "But, not everyone will buy into this until prospective research is done."
Outside the procedure suite, is this information useful to someone like me with fluoroquinolone-resistant E. coli?
Smith said that over time, my status could change. If I have another biopsy at NorthShore, I would be screened again. She advised me to inform my internist, which I did via his group's portal. "It's good knowledge to have, and you're not branded for life," she said.
Smith added: "If you had a serious infection and did not have culture results to guide antibiotic therapy (that is, you did not know if the bacteria were susceptible) doctors would likely avoid giving you empiric antibiotic therapy with a fluoroquinolone antibiotic in case of resistance."
A Patient's Journey: Sometimes It's Not All About Prostate CancerWhat About that Annual Physical?
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What About that Annual Physical?mardi 9 août 2016
PAs That Fight Childhood Obesity: Physicians Practice
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.
PAs That Fight Childhood Obesity: Physicians PracticePostprostatectomy PSA May Predict Salvage RT Benefit (CME/CE)
The benefits of salvage radiotherapy after radical prostatectomy varied significantly by the duration of delay to salvage therapy, PSA dynamics, and other prostatectomy-related factors, a large retrospective review showed.
Initiating salvage radiotherapy at a postprostatectomy PSA level ≤0.5 ng/mL was associated with significantly lower rates of biochemical relapse, distant metastasis, and cause-specific mortality at 5 and 10 years, as compared with receipt of salvage therapy at higher PSA levels.
Receipt of salvage therapy at postprostatectomy PSA levels ≤0.5 ng/mL led to about a 10-point absolute improvement in overall survival (OS) at 10 years, although the difference did not achieve statistical significance, reported Thomas Pisansky, MD, of the Mayo Clinic in Rochester, Minn., and colleagues online in the Journal of Clinical Oncology.
"These observations reaffirm findings of previous studies but also demonstrate, for the first time to our knowledge, the benefit of early salvage radiotherapy related to survival outcomes," the authors concluded.
"Taken together, these findings argue against prolonged monitoring of detectable post-radical prostatectomy PSA levels that delays initiation of salvage radiotherapy and serve as an important component of shared decision making between patient and physician," they added.
As the authors acknowledged, the study reinforces findings from previous investigations into the relationships among PSA level, salvage radiotherapy, and outcomes in prostate cancer, said David Beyer, MD, of Cancer Centers of Northern Arizona in Sedona.
"This study is very good to see, and it does break a little new ground," Beyer, president of the American Society for Radiation Oncology (ASTRO), told MedPage Today. "What they've done that's different from previous studies is that they've gone on to show why it's better to give the salvage therapy early."
Randomized trials showed that salvage radiotherapy reduced the rate of biochemical relapse and improved metastasis-free survival in men with postprostatectomy detectable PSA levels. Results of single-institution studies suggested reductions in cause-specific and all-cause mortality with salvage radiotherapy versus observation after radical prostatectomy. The evidence led to endorsement of salvage radiotherapy in joint consensus guidelines adopted by the ASTRO and the American Urological Association.
Studies established PSA level at the time of salvage radiotherapy as prognostic for subsequent risk of biochemical relapse. However, the association between PSA at salvage therapy and distant metastasis or cause-specific mortality remained unclear. Pisansky and colleagues addressed the unresolved issue in a retrospective review of 1,067 who received postprostatectomy salvage radiotherapy from January 1987 to July 2013.
Analysis of baseline characteristics showed that a majority of the patients had pathologic stage T2 (56.2%) or T3a (27.4%) prostate cancer, and 98.3% did not have nodal involvement. About 30% of the men had Gleason grade ≤6 disease and 49.7% had Gleason 7. A similar proportion of patients (49%) had positive and negative surgical margins, and pre-salvage radiotherapy PSA level was ≤0.5 ng/mL in 45.3% of cases. Almost 85% of the men received no androgen deprivation therapy (ADT).
Total radiation dose was:
- <66 Gy in 30.7%
- 66 to 67.99 Gy in 17.8%
- 68 to 71.99 Gy in 34.7%
- ≥72 Gy in 16.8%
During a median follow-up of 8.9 years, biochemical relapse occurred in 54% of the patients, resulting in a 5-year biochemical relapse rate of 49.9%, increasing to 64.3% at 10 years. Multivariate analysis showed that increasing tumor stage, Gleason score, and PSA at salvage therapy increased the likelihood of biochemical relapse, whereas a cumulative radiotherapy dose ≥68 Gy and receipt of ADT reduced the likelihood.
The authors reported that 208 patients developed distant metastasis, resulting in 5- and 10-year incidences of 10.9% and 19.9%, respectively. By multivariate analysis, pathologic T3b and Gleason ≥7 increased the risk of distant metastasis.
The data showed that 280 patients died during follow-up, including 110 deaths attributed to prostate cancer. OS was 92.9% at 5 years and 77.3% at 10 years. Cause-specific mortality was 3.0% and 10.4% at 5 and 10 years, respectively.
Each doubling of the PSA level at the time of salvage radiotherapy increased the risk of biochemical relapse by 30% (P<0.001), distant metastasis by 32% (P<0.001), cause-specific mortality by 40% (P<0.001), and overall mortality by 12% (P=0.02).
A comparison of a pre-salvage therapy PSA of ≤0.5 versus >0.5 ng/mL resulted in 5-year biochemical relapse rates of 42% versus 56% (P<0.001), 10-year relapse rates of 60% versus 68% (P<0.001), distant metastasis rate of 7% versus 14% at 5 years and 13% versus 25% at 10 years (P<0.001), cause-specific mortality of 1% versus 4% and 6% versus 13% at 5 and 10 years, respectively (P<0.001), and overall survival of 94% versus 92% and 83% versus 73% (NS).
Study limitations included its observational nature and the potential for lead-time bias with an early detection method such as PSA monitoring, the authors stated.
Pisansky disclosed no relevant relationships with industry. One co-author disclosed a relevant relationship with Pfizer.
Scrubs Outside the Hospital: Good or Bad?
Every few months when things are slow, someone publishes an article about the imaginary dangers associated with doctors wearing scrubs in public. A recent version is from The Atlantic. An associate editor saw some people in scrubs having lunch in a restaurant and was, of course, horrified. She questioned the magazine's medical editor, Dr. James Hamblin, whose response was remarkably reasoned (until the end).
He pointed out that it might not have been doctors because everyone, including secretaries (and even custodial people in my hospital), now wears scrubs to work. Dr. Hamblin rightly added that there is a lot of debate about the issue. He speculated that some guys wear scrubs in public as a signal to women that they are doctors.
But at the end of the piece, he said it was OK if his colleague were to "tell off" the people she saw eating lunch in scrubs.
Since I've been married for 38 years, I don't need to wear scrubs in public to attract women. Anyway, they tend to flock to me even when I'm dressed in civilian clothing.
Being "old school," I don't like to see people wearing scrubs outside the hospital. I just think it sends the wrong message; and what's worse, it continues to provoke folks into writing letters, blogs, and newspaper and magazine columns full of indignation.
However, I can't get worked up about this, and here's why: Yes, bacteria can be found on scrubs. But one has to wear something to work, and whatever one wears can occasionally become contaminated. After all, it is a hospital. There is no evidence that bacteria on scrubs spread disease. Nor is there evidence that bacteria on other objects such as ties, white coats, cell phones, stethoscopes, computer keyboards, or numerous other articles shown to be contaminated has made people sick.
In addition to the large number of ancillary hospital personnel who wear scrubs, here are some others: my dentist and his staff, including his secretary and his hygienists, and my dog's veterinarian, his secretaries, and the guy who holds my terrified dog.
I don't see a simple solution to this problem. Scrubs are sold in stores. Anyone can buy them. They come in all colors. A nurse at my hospital wears a set of desert camouflage scrubs with a matching backpack. I don't know how to tell him that the desert camo doesn't work. It's easy to spot him as he stands out rather clearly amid the solid colors of the unit's walls and the white sheets on the beds. He would blend in better if he could find a set of "hospital beige"-colored scrubs.
I would also suggest that telling people off is 1) rude; and, 2) possibly hazardous to your health. You never know what that person you're telling off might do when confronted.
What do you think about wearing scrubs outside the hospital?
"Skeptical Scalpel" is a surgeon who blogs at his self-titled site, Skeptical Scalpel. This article originally appeared in Physician's Weekly, and also appeared on KevinMD.com.
Scrubs Outside the Hospital: Good or Bad?Pelzman's Picks: Sen. Warren on Data Sharing
- U.S. Sen. Elizabeth Warren, JD (D-Mass.), explores the importance of data sharing in the New England Journal of Medicine ~ Strengthening Research through Data Sharing
- Should doctors be held criminally liable if their patient dies from an opioid overdose? Y. Tony Yang, ScD, LLM, MPH, and Rebecca L. Haffajee, JD, MPH, ask in Mayo Clinic Proceedings ~ Murder Liability for Prescribing Opioids: A Way Forward?
- Are medical homes effective? Kip Sullivan asks in The Health Care Blog ~ Are CMS's "Medical Homes" Underfunded or Unfocused?
- "Before a drug can be marketed, it has to go through rigorous testing to show it is safe and effective. Surgery, though, is different," Gina Kolata writes in The New York Times ~ Why "Useless" Surgery Is Still Popular
- Controversy stirs over warning notices on sugary drink adverts, Dean Schillinger, MD, and Michael F. Jacobson, PhD, write in JAMA ~ Science and Public Health on Trial
- "The federal government's readmission penalties on hospitals will reach a new high as Medicare withholds more than half a billion dollars in payments over the next year," Jordan Rau writes in Kaiser Health News ~ Medicare's Readmission Penalties Hit New High
- NIH may end its ban on funding for a controversial type of research, Lenny Bernstein writes in The Washington Post ~ NIH may allow funding for human-animal stem cell research
Fred N. Pelzman, MD, of Weill Cornell Internal Medicine Associates and weekly blogger for MedPage Today, follows what's going on in the world of primary care medicine. Pelzman's Picks is a compilation of links to blogs, articles, tweets, journal studies, opinion pieces, and news briefs related to primary care that caught his eye.
Pelzman's Picks: Sen. Warren on Data SharingXeljanz Offers Better Outcomes in Early RA (CME/CE)
The use of tofacitinib (Xeljanz) monotherapy was more effective in reducing the signs and symptoms of early rheumatoid arthritis (RA) versus those of established RA, researchers reported.
Of the 956 patients in the study, 54% had early RA -- defined as less than 1 year duration -- while the rest had established RA. Patients were randomized into three treatment arms of 5 mg tofacitinib two times a day (373), 10 mg two times a day (397), or methotrexate weekly (186). For signs and symptoms of disease, treatment response was statistically significantly greater at 24 months in those patients with early RA who received tofacitinib 5 mg two times a day, according to Roy Fleischmann, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues.
Also, when compared to methotrexate (MTX), monotherapy with the oral Janus kinase inhibitor significantly improved the signs of symptoms of RA, and effectively inhibited joint damage in methotrexate-naïve patients, regardless of the duration of RA, they wrote in RMD Open.
Treatment of RA is designed to achieve disease remission or, if that's not possible, to improve the signs or symptoms of the disease and inhibit or reverse functional disability. Fleischmann's group pointed out that recent studies have demonstrated that disease duration could determine the effectiveness of treatment, suggesting that early treatment offers a way of preserving physical function and preventing disability.
"It has been postulated that the early stages of RA may, therefore, offer a therapeutic window of opportunity in which to prevent joint damage from occurring," they wrote, noting that window could extend anywhere from 3 months to 2 years following the appearance of symptoms.
They carried out a post hoc analysis of the ORAL Start study, a 24-month, phase III trial that compared tofacitinib monotherapy with methotrexate monotherapy in methotrexate-naïve patients with RA.
They evaluated the efficacy of treatment with tofacitinib by using ACR response rates (ACR 20, ACR50, and ACR70) and disease activity scores in 28 joints (DAS28-4) erythrocyte sedimentation rate (DA28-4 ESR). They also assessed physical function using the Health Assessment Questionnaire-Disability Index and used van der Heijde modified total Sharp scores to to evaluate the radiographic progression of joint structural damage.
The authors reported no significant difference between early and established RA in the tofacitinib 10 mg two times a day or methotrexate groups, suggesting that their analysis "did not provide any definitive support for the concept of a window of opportunity."
They also determined that patients with either early or established RA showed a significant reduction in signs and symptoms of disease, as well as improvements in physical functioning and inhibition of radiographic progress when treated with either tofacitinib 5 or 10 mg compared with methotrexate monotherapy.
Additionally, there were no "meaningful differences in safety parameters seen between patients with early and established RA," the authors noted. For instance, 82.1% of those with early RA and in the 5-mg twice daily group experienced treatment-emergent adverse events versus 76.7% with established disease who received 5 mg twice daily.
Fleischmann's group concluded that "in line with the principle of treating to target, the best results with tofacitinib or MTX are obtained in patients with early RA. Therefore, the diagnosis of RA should be made, and treatment started, as early as possible after the development of symptoms."
However, if 3 months of aggressive methotrexate therapy results in a less than significant response, the researchers suggested it would "be reasonable" to add tofacitinib to methotrexate. If methotrexate therapy results in an inadequate response, or if methotrexate is not tolerated, patients could be switched to tofacitinib monotherapy.
The study had limitations including the fact that disease duration was defined by the reporting of the amount of time since diagnosis, rather than by any objective criteria.
"Diagnosis of RA will vary from clinic to clinic, depending on local practice; the fact that the mean duration of disease for patients in the established RA group was around 6 years, but that these patients were still MTX-naive, highlights the potential uncertainty around disease duration for some patients," they stated.
The study was supported by Pfizer. Some co-authors are company employees.
Fleischmann disclosed relevant relationships with Pfizer. Co-authors disclosed relevant relationships with Dutch Arthritis Foundation, the Dutch NIH, the EU, Merck, UCB, Bristol-Myers Squibb, Biotest AG, Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boehringer, Takeda, Eli Lilly, AbbVie, BiogenIDEC, Biotest, Celgene, GlaxoSmithKline, Jansen, MSD, and Vertex.
USPSTF Punts on Universal Screening for Lipid Disorders in Kids (CME/CE)
Insufficient evidence exists to recommend universal screening for heterozygous familial hypercholesterolemia and multifactorial dyslipidemia in children and adolescents, the U.S. Preventive Services Task Force declared.
This final recommendation ("I" statement) updated a 2007 statement that examined screening for dyslipidemia among children and adolescents, but did not specifically address heterozygous familial hypercholesterolemia (FH). The grade, however, remained unchanged.
While there was adequate "short-term" evidence that pharmacotherapy, such as statins, reduced lipid levels among children with FH, there was inadequate evidence on the benefits of either medication or lifestyle interventions on children with multifactorial dyslipidemia. The panel also found inadequate evidence on the potential harms of screening for lipid disorders in children.
"The USPSTF concludes that the current evidence is insufficient and that the balance of benefits and harms of screening for lipid disorders in asymptomatic children and adolescents 20 years or younger cannot be determined," according to Kristen Bibbins-Domingo, PhD, of the USPSTF, and colleagues, writing in the Journal of the American Medical Association.
David Grossman, MD, also of the USPSTF, told MedPage Today that he believed that with additional studies, the answers to these questions can be properly established, citing a recent USPSTF recommendation for the use of aspirin in the prevention of cardiovascular disease.
"Every time we have an I statement, we really do look ourselves in the eye and ask ourselves could we ever move off an I to a letter grade, and we do believe there has been some development of evidence in this area," he said. "With properly designed studies and longitudinal follow-up, we can establish answers to these questions. Part of the problem is pediatric studies haven't been as well-funded as adult studies, but we believe these kinds of studies are doable."
Contrary to Other Guidelines
But the Task Force view differed from guidelines established in 2011 by the National Heart, Lung and Blood Institute and the American Academy of Pediatrics, which recommended universal screening for cholesterol levels among children and teens.
"What I heard from the primary care community is they just weren't sure which way to go, but in ensuing years, I've seen more and more of them following the guidelines to do universal screening," said Laurie Armsby, MD, of Oregon Health & Science University in Portland, who was not involved with the USPSTF review. "The referring physicians who have sent patients to me following universal screening have found the education and the intensive discussions very beneficial, so I think that over the past 5 years, the field has demonstrated a benefit in the pediatric population."
Editorials in several JAMA journals seemed to agree with Armsby's view. Samuel Gidding, MD, of A.I. Dupont Hospital for Children in Wilmington, Del., argued that the 2011 panel was more focused on whether screening could help prevent atherosclerosis in adolescents as opposed to reducing overt cardiovascular disease (CVD) events in adulthood.
"Recommendations of the 2011 panel were driven by the consistency of the evidence relating severely elevated cholesterol levels to premature development of atherosclerosis as well as the impossibility and ethical limitations of conducting a 40-year randomized trial to prove that lowering [LDL] cholesterol in childhood prevents CVD events," he wrote in JAMA Cardiology. "The 2011 ... panel was specifically concerned about individuals who were likely to have early CVD, but were not included in clinical and epidemiologic studies begun at age 40 years and later."
Another editorialist, writing in JAMA Pediatrics, drew a parallel between screening for lipid levels in adolescents and another form of screening that the USPSTF recommended: screening for obesity in children and adolescents.
"The questions related to obesity are more focused on short-term childhood outcomes and whether BMI can be improved in childhood by intervention," wrote Stephen R. Daniels, MD, of University of Colorado at Denver, adding that obesity screening does not focus on prevention of long-term conditions, such as nonalcoholic fatty liver disease or type 2 diabetes.
"Why should we screen for obesity, but have insufficient information to reach a conclusion for screening for heterozygous FH when there seem to be important parallels in these clinical entities?" he argued.
"Low-Value Care"
Some clinicians, though, backed the USPSTF's reluctance to support screening in light of the economic and emotional costs that come with diagnoses, as well as the risks that go with treatment.
"I am a Pink Floyd fan: 'Teacher, leave those kids alone,'" said Paul Thompson, MD, of Hartford Hospital, who had no role in the USPSTF review.
"I wish we would begin to get that straight as a medical nation because so much of screening [in general] only results in anxiety, unnecessary testing, and inappropriate treatment. With kids in this instance, I think we run the risk of making them medically anxious and treating them early with drugs for a long period of time," he told MedPage Today.
An editorial in JAMA Internal Medicine agreed with this view, noting that uncovering the hundreds of thousands of children with potential high cholesterol who then might be treated with statins could increase their risk of developing diabetes.
"In intermediate- and high-risk adults, increased risks of diabetes and weight gain may be outweighed by the projected benefit of CVD reduction, but in children there is near-zero benefit and much harm from the decades of increased diabetes and obesity risk one might expect from starting statin therapy in childhood," wrote Thomas B. Newman, MD, and two colleagues at the University of California San Francisco.
They noted that under the NHLBI guidelines, an estimated 200,000 children would qualify for statin therapy.
Instead, Newman and colleagues argued for more "high-value solutions," such as lifestyle interventions related to diet, exercise, and smoking as opposed to focusing on screening.
Grossman said that the Task Force recognized the importance of diet and exercise as key to the prevention of especially multifactorial disease, which is associated with obesity. He commented that clinicians need to make decisions about patients on an individual basis.
"We need to recognize certain risks and be clear about what those risks are," he said. "It is reasonable to test certain patients for lipids, and clinicians should use this information in order to better inform their clinical judgment."
Future of Research
A JAMA editorial by Elaine M. Urbina, MD, of Cincinnati Children's Hospital Medical Center, and Sarah D. de Ferranti, MD, of Boston Children's Hospital, argued that "novel methods" are needed to provide evidence for pediatric lipid screening and treatment. They saw a potential light at the end of the tunnel with ongoing cohort studies.
"The completion of the 40-year follow-up of seven international cohorts that have been evaluating cardiovascular risk factors since the 1970s and 1980s will help inform the discussion about screening for lipid disorders in children and adolescents," they wrote. "Once these data are available, analyses could be performed to estimate cost-benefit of screening for dyslipidemia in youth."
But Armsby argued that waiting for specific data linking screening to long-term changes in morbidity and mortality was not necessary for another concerted public health campaign that was embraced by doctors, schools, and families alike.
"We didn't educate kids about smoking because we had data that showed if we got kids to stop smoking as kids, those same kids wouldn't develop lung cancer as adults – we extrapolated that if smoking caused lung cancer and we stopped kids from smoking, we would have fewer kids developing lung cancer when they were older," she said. "We didn't wait for the longitudinal study."
Bibbens-Domingo reported having consulted for the Institute for Clinical and Economic Review on the cost-effectiveness of a new class of lipid-lowering drugs.
Urbina reports grants from the NIH and AHA and travel support from AtCor Medical.
de Ferranti reports grants from the NIH and the New England Congenital Cardiology Research Fund and royalties from UpToDate.
Newman and colleagues disclose no relevant financial relationships.
Gidding reported relationships with the FH Foundation; research funding from the NHLBI and the National Institute of Diabetes and Digestive and Kidney Diseases as coinvestigator of the CARDIA and TODAY studies; honoraria from the International Atherosclerosis Society; and membership on the 2011 NHLBI and AAP panel that established guidelines for universal screening.
Daniels is a member of both a data monitoring committee for Novo Nordisk and an advisory committee for Sanofi.
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