From Heartwire CME
News Author: Sue Hughes
CME Author: Hien T. Nghiem, MD
January 25, 2011 — A new Cochrane review has provoked controversy by concluding that there is not enough evidence to recommend the widespread use of statins in the primary prevention of heart disease.
The authors of the new Cochrane meta-analysis, led by Dr Fiona Taylor (London School of Hygiene and Tropical Medicine, UK), issued a press release questioning the benefit of statins in primary prevention and suggesting that the previous data showing benefit may have been biased by industry-funded studies.
This has led to headlines in many UK newspapers saying that the drugs are being overused and that millions of people are needlessly exposing themselves to potential side effects.
This has angered researchers who have conducted other large statin meta-analyses, who say the drugs are beneficial, even in the lowest-risk individuals, and their risk of side effects is negligible.
They maintain that the Cochrane reviewers have misrepresented the data, which they say could have serious negative consequences for many patients currently taking these agents.
The Cochrane authors reviewed data from 14 trials involving 34 272 patients. Outcomes in patients given statins were compared with outcomes in patients given placebos or usual care. Although results suggested that deaths were reduced on statins, the researchers say the effect is not large enough to justify the cost/effort and risk of adverse effects.
Senior author Dr Shah Ebrahim (South Asia Network for Chronic Disease, New Delhi, India) told heartwire that their review differed from others done in primary prevention in that it looked at just those at low risk, limiting the studies included to just those with populations where <10% had a previous history of cardiovascular disease (CVD).
It is probably a real effect but it means a lot of people have to be treated to gain this small benefit.
Ebrahim commented to heartwire : "If you look at the hard end points of all deaths and coronary deaths, the effects are consistent with both benefit and with the play of chance. But importantly, the absolute benefits are really rather small--1000 people have to be treated for one year to prevent one death. It is probably a real effect, but it means a lot of people have to be treated to gain this small benefit. As we don't know the harms, it seems wrong-minded to me to treat everyone with a statin. In these circumstances, lifestyle changes and stopping smoking would be far preferable."
I object to the conclusions they have drawn from their review.
But Dr Colin Baigent (Clinical Trials Service Unit, Oxford, UK) commented to heartwire : "I object to the conclusions they have drawn from their review. They say there is not good evidence of benefit, but their own data show significant reductions in deaths and cardiac events." And Baigent further objects to the Cochrane authors' suggestion that harms are not known with statins. "They didn't show any increase in adverse events in their review, but they then say the benefit is not worth the risk. That doesn't make sense."
Cochrane Results
The Cochrane review showed that in the eight trials that reported on total mortality, none of the individual trials showed strong evidence of a reduction in total mortality, but when the data were pooled, a relative risk reduction of 17% was observed with statin treatment. On combined fatal and nonfatal coronary heart disease (CHD) events, nine trials reported on this end point, with four trials showing evidence of a reduction in this combined outcome, which was maintained in the pooled analysis, with a 28% relative reduction. Seven trials reported on fatal and nonfatal stroke, and on pooled analysis, statin treatment was associated with a 22% relative reduction.
Cochrane Review: Risk Ratio of Major Events With Statins in Lower-Risk Primary-Prevention Patients
No excess in combined adverse events, cancers, or specific biochemical markers were found.
The authors conclude: "This current systematic review highlights the shortcomings in the published trials of statins for primary prevention. Selective reporting and inclusion of people with cardiovascular disease in many of the trials . . . in previous reviews of [statins'] role in primary prevention make the evidence impossible to disentangle without individual patient data."
They say that in people at high risk of cardiovascular events (>20% 10-year risk), "it is likely that the benefits of statins are greater than potential short-term harms, although long-term effects (over decades) remain unknown." They conclude: "Any decision to use statins for primary prevention should be made cautiously and in the light of an assessment of the patient's overall cardiovascular risk profile. Widespread use of statins in people at low risk of cardiovascular events--below a 1% annual all-cause mortality risk or an annual CVD event rate of below 2% observed in the control groups in the trials considered here--is not supported by the existing evidence."
Latest Oxford Meta-Analysis Not Included
The Cochrane review did not include the recent meta-analysis from the Oxford group, published late last year, which showed a clear reduction in events with statin therapy in primary-prevention patients.
Baigent noted that this meta-analysis was more reliable than the Cochrane review, as the Oxford researchers used individual patient data from all the trials. "Our 2010 meta-analysis in primary prevention is substantially more complete than the Cochrane review and provides direct and overwhelmingly statistically convincing evidence of a clear reduction in events in all patient groups, right down to those at the lowest risk."
On the possible hazards of taking these drugs, Baigent says: "Statin therapy is very safe. The most serious hazard, rhabdomyolysis, is very rare, and most often seen at high doses. There is a possibility that reducing low-density lipoprotein cholesterol might increase the risk of hemorrhagic stroke, but even in primary prevention these hazards would be much smaller than the benefits, and there is no reliable evidence for other hazards mentioned by the Cochrane authors, such as depression and cognitive impairment."
It All Comes Down to Economics
Baigent says the only argument against using statins in low-risk people is economic. "The absolute benefits of statin therapy become very small when used among people at low absolute risk, so it is important that the costs of such treatment are considered when weighing how widely statins should be used. That is a government decision."
In the UK, the National Institute for Clinical Excellence [NICE] currently recommends that statins not be used for people with a CHD risk below 20% over 10 years. Ebrahim says the Cochrane conclusions are in line with this.
But Baigent argues that the benefits of statins are clear at levels far below this threshold. "Whether or not it is economic to use them in the lowest-risk individuals is not for me to say, but generic statins are now very cheap, and there is clear evidence of benefit and safety based on substantial numbers of individuals studied in large-scale trials. So, when all the relevant randomized evidence is considered, there does not seem to me to be any justification at all for the Cochrane authors' claim that the evidence is unclear on this issue."
Educational Programs Also of Little Benefit
In a separate Cochrane review [2], the same group looked at the use of "healthy heart programs" that use counseling and educational methods to encourage people to reduce their risks for developing heart disease. These risk factors include high cholesterol, excessive salt intake, high blood pressure, excess weight, a high-fat diet, smoking, diabetes, and a sedentary lifestyle. They reviewed 55 trials that aimed to reduce more than one risk factor in people without evidence of cardiovascular disease. Results showed that after a median duration of 12 months of follow-up, multiple risk-factor intervention was associated with small reductions in risk factors, including blood pressure, cholesterol, and smoking, but had little or no impact on the risk of coronary heart disease mortality or morbidity. They conclude: "The methods of attempting behavior change in the general population are limited and do not appear to be effective. Different approaches to behavior change are needed and should be tested empirically before being widely promoted, particularly in developing countries where cardiovascular disease rates are rising."
In an accompanying editorial [3], Dr Carl Heneghan (University of Oxford, UK) suggests an alternative approach for policy is to focus on populationwide prevention. He reports that "legislating for smoke-free public spaces, redesigning public spaces to improve exercise, or reducing daily dietary salt intake prove generally effective and can be cost-saving interventions. Given the scale of the worldwide CVD problem, large-scale commissioned studies of multiple risk-factor interventions are urgently required."
References
1. Taylor F, Ward K, Moore THM, et al. Statins for the primary prevention of cardiovascular disease - Available here.Cochrane Database Syst Rev 2011; 1 (CD004816).
2. Ebrahim S, Taylor F, Ward K et al. Multiple risk factor interventions for primary prevention of coronary heart disease - Available here. Cochrane Database Syst Rev 2011; 1 (CD001561).
3. Heneghan C. Considerable uncertainty remains in the evidence for primary prevention of cardiovascular disease [editorial].Cochrane Libr2011 (January 19, 2011). Available here.
Clinical Context
CVD is mutifactorial in its causation, and lifestyle changes are the basis of any treatment strategy. Treatment usually includes eating a healthy diet, ceasing tobacco use, and increasing physical activity. Reducing high blood cholesterol, a risk factor for CVD events in people with and without a history of CHD, is an important goal of pharmacotherapy. Typically, statins are the first-line agents. Studies have demonstrated the effects of statins and its benefits in people with coronary artery disease; however, the case for primary prevention is less clear.
The aim of this study was to assess the effects, both harms and benefits, of statins in people with no history of CVD.
Study Highlights
* The investigators conducted a search within the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007), and EMBASE (2003 to March 2007) for trials comparing statins vs usual care or placebo. There were no language restrictions.
* Randomized controlled trials of statins with minimum duration of 1 year and follow-up of 6 months, trials of adults with no restrictions on their total low-density lipoprotein or high-density lipoprotein cholesterol levels, and trials in which 10% or less of participants had a history of CVD were included.
* Drug treatments and other interventions were accepted, provided they were given to both groups of the intervention groups.
* 2 authors independently selected studies for inclusion and extracted data.
* Outcomes included all-cause mortality, fatal and nonfatal CHD, CVD, stroke events, combined endpoints (fatal and nonfatal CHD, CVD, and stroke events), change in blood total cholesterol concentration, revascularization, adverse events, quality of life, and costs.
* Relative risk was calculated for dichotomous data, and for continuous data, pooled weighted mean differences (with 95% confidence intervals) were calculated.
* 14 randomized control trials (16 trial groups; 34,272 participants) were included.
* 11 trials recruited patients with specific conditions (increased lipid levels, diabetes, hypertension, and microalbuminuria).
* All tested the effectiveness of a statin vs placebo, 9 studies tested pravastatin (10 - 40 mg/day) and atorvastatin (10 mg/day), 2 studies tested fluvastatin (40 - 80 mg/day) and lovastatin (20 - 40 mg/day), and the remaining studies tested simvastatin (40 mg/day).
* 2 trials — the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) 1998 and the Collaborative AtoRvastatin Diabetes Study (CARDS) 2004 — were stopped prematurely because of significant reductions in primary composite outcomes between the intervention and placebo groups.
* Results demonstrated that all-cause mortality risk was reduced by statins (relative risk, 0.83; 95% CI, 0.73 - 0.95), as were combined fatal and nonfatal CVD endpoints (relative risk, 0.70; 95% CI, 0.61 - 0.79).
* No significant risk reduction was observed in fatal CHD events and fatal and nonfatal stroke events.
* Benefits were also seen in the reduction of revascularization rates (relative risk, 0.66; 95% CI, 0.53 - 0.83).
* Total cholesterol and low-density lipoprotein cholesterol levels were reduced in all trials; however, there was evidence of heterogeneity of effects, possibly because of differences in the statin and dosage used as well as reporting biases.
* There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
* No statistical differences in outcomes were observed in age and sex.
* There was limited evidence to suggest that the use of statins for primary prevention may be cost effective and improve patient-perceived quality of life.
Clinical Implications
* According to the World Health Organization in 2008, the major causes of CVD are unhealthy diet, tobacco use, and physical inactivity.
* Although reductions in all-cause mortality risk, composite endpoints, and revascularizations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events, and inclusion of people with cardiovascular disease. Therefore, caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
Monday, February 7, 2011
Sunday, February 6, 2011
In Cancer Survival, 'Mind Matters,' Says Expert
From Medscape Medical News > Oncology
Nick Mulcahy
February 2, 2011 — Social support and psychologic/psychiatric interventions can improve survival in cancer but are "overlooked" in the treatment of the disease, argues a psychiatrist in an essay published in the February 2 issue of the Journal of the American Medical Association.
"A patient's personal mental management of the stresses associated with cancer" is a "natural ally" in the battle with this disease, writes David Spiegel, MD, from the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine in Palo Alto, California.
"It is plausible that interventions providing emotional and social support at the end of life have a positive influence on physiological stress-response systems that affect survival," he writes, suggesting a mechanism of action.
But another expert in the field of behavioral medicine noted that there is very little evidence of such survival benefit.
"Social support almost certainly makes people feel better, which is hugely important, and I wouldn't be surprised if it did improve survival," said Richard Sloan, PhD, from the Division of Behavioral Medicine at the Columbia University Medical Center in New York City. But, he added, there is no strong body of evidence that treatments and services addressing social or emotional issues improve survival in the field of cancer.
For instance, "I know of no study in cancer patients that shows that reducing depression improves survival," he said. "We should treat depression because it makes patients miserable, not because we think it may improve survival," he added.
Dr. Sloan's great concern about the discussion of the evidence regarding psychosocial support and cancer survival is how the information is received by the public, most importantly cancer patients.
"We have to be really careful not to oversell the interventions we have," he told Medscape Medical News. The reason? "People can feel at fault if they don't respond to a program," he said. In a recent editorial in the New York Times, Dr. Sloan discusses some of the history of "mind cure" movements in the United States. The editorial touches on the lack of scientific validity in the belief that personality or "a way of thinking" can influence disease outcomes. As he notes, a recent large study dismissed the idea that any personality type is associated with the risk of getting or surviving cancer.
Dr. Spiegel does not say that cancer can be cured by psychosocial interventions and makes no claims about the power of positive thinking. Instead, he argues that psychosocial support, which includes the discussion of death and learning how to manage pain and anxiety, might extend survival, particularly at the end of life. He summarizes: "It is not simply mind over matter — but mind matters."
Follows Palliative Care Study
Dr. Spiegel's essay comes about 6 months after a study on palliative care in cancer was published in the New England Journal of Medicine (2010;363:733-742). In that study, the introduction of palliative care — a program designed to minimize pain and improve quality of life — at diagnosis, in parallel with standard oncologic care, was associated with a significant improvement in survival in patients with metastatic nonsmall-cell lung cancer (NSCLS).
After discussing the palliative care study in his essay, Dr. Spiegel states that "there is increasing evidence that social support affects survival [in cancer]." He cites 2 studies in particular: a study in women with early-stage breast cancer, which was led by Barbara Andersen, PhD, from Ohio State University in Columbus (Cancer. 2008;113:3450-3458); and a study by Dr. Spiegel himself in women with metastatic breast cancer (Lancet. 1989;2:888-891).
To Medscape Medical News, he mentioned 3 other randomized trials and 1 matched-cohort trial that "have found that psychosocial treatment for patients with a variety of cancers produced both psychological and survival benefits." The cancers in these types of studies tend to be those with the poorest prognosis, including malignant melanoma, NSCLC, leukemia, and gastrointestinal tract cancers, Dr. Spiegel points out in his essay.
"For breast and other cancers, when aggressive antitumor treatments are less effective, supportive approaches appear to become more useful," observed Dr. Spiegel.
Dr. Andersen said that the quantity of cancer research that indicates a survival benefit of psychosocial interventions is not abundant. "There is not all that much data on social support in particular," she told Medscape Medical News.
Nonetheless, Dr. Andersen suggested that the palliative care study represents a pivotal moment in this area of research. The fact that the New England Journal of Medicine published it was "quite amazing," she said. The journal has a "history of considerable skepticism with regard to the importance of psychological and behavioral factors in cancer," she explained.
Dr. Andersen also pointed out that "there's a whole lot more going on in psychosocial interventions than just social support." For instance, in her breast cancer study, she and her colleagues note that the intervention was psychologist led, conducted in small groups, and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care.
Therein lies a problem, said Dr. Sloan. "It's hard to know which is the active agent" in such multifactorial studies. For instance, he wondered whether treatment adherence was the element of the Ohio State program that tipped the scale toward a survival benefit.
Dr. Andersen responded that adherence was not a factor in the differential survival.
Dr. Andersen would like the discussion about the benefits of psychosocial interventions and drug therapies and other treatments to not be a matter of "either/or." The various interventions should work together, she said.
The authors have disclosed no relevant financial relationships.
JAMA. 2011;305:502-503.
Nick Mulcahy
February 2, 2011 — Social support and psychologic/psychiatric interventions can improve survival in cancer but are "overlooked" in the treatment of the disease, argues a psychiatrist in an essay published in the February 2 issue of the Journal of the American Medical Association.
"A patient's personal mental management of the stresses associated with cancer" is a "natural ally" in the battle with this disease, writes David Spiegel, MD, from the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine in Palo Alto, California.
"It is plausible that interventions providing emotional and social support at the end of life have a positive influence on physiological stress-response systems that affect survival," he writes, suggesting a mechanism of action.
But another expert in the field of behavioral medicine noted that there is very little evidence of such survival benefit.
"Social support almost certainly makes people feel better, which is hugely important, and I wouldn't be surprised if it did improve survival," said Richard Sloan, PhD, from the Division of Behavioral Medicine at the Columbia University Medical Center in New York City. But, he added, there is no strong body of evidence that treatments and services addressing social or emotional issues improve survival in the field of cancer.
For instance, "I know of no study in cancer patients that shows that reducing depression improves survival," he said. "We should treat depression because it makes patients miserable, not because we think it may improve survival," he added.
Dr. Sloan's great concern about the discussion of the evidence regarding psychosocial support and cancer survival is how the information is received by the public, most importantly cancer patients.
"We have to be really careful not to oversell the interventions we have," he told Medscape Medical News. The reason? "People can feel at fault if they don't respond to a program," he said. In a recent editorial in the New York Times, Dr. Sloan discusses some of the history of "mind cure" movements in the United States. The editorial touches on the lack of scientific validity in the belief that personality or "a way of thinking" can influence disease outcomes. As he notes, a recent large study dismissed the idea that any personality type is associated with the risk of getting or surviving cancer.
Dr. Spiegel does not say that cancer can be cured by psychosocial interventions and makes no claims about the power of positive thinking. Instead, he argues that psychosocial support, which includes the discussion of death and learning how to manage pain and anxiety, might extend survival, particularly at the end of life. He summarizes: "It is not simply mind over matter — but mind matters."
Follows Palliative Care Study
Dr. Spiegel's essay comes about 6 months after a study on palliative care in cancer was published in the New England Journal of Medicine (2010;363:733-742). In that study, the introduction of palliative care — a program designed to minimize pain and improve quality of life — at diagnosis, in parallel with standard oncologic care, was associated with a significant improvement in survival in patients with metastatic nonsmall-cell lung cancer (NSCLS).
After discussing the palliative care study in his essay, Dr. Spiegel states that "there is increasing evidence that social support affects survival [in cancer]." He cites 2 studies in particular: a study in women with early-stage breast cancer, which was led by Barbara Andersen, PhD, from Ohio State University in Columbus (Cancer. 2008;113:3450-3458); and a study by Dr. Spiegel himself in women with metastatic breast cancer (Lancet. 1989;2:888-891).
To Medscape Medical News, he mentioned 3 other randomized trials and 1 matched-cohort trial that "have found that psychosocial treatment for patients with a variety of cancers produced both psychological and survival benefits." The cancers in these types of studies tend to be those with the poorest prognosis, including malignant melanoma, NSCLC, leukemia, and gastrointestinal tract cancers, Dr. Spiegel points out in his essay.
"For breast and other cancers, when aggressive antitumor treatments are less effective, supportive approaches appear to become more useful," observed Dr. Spiegel.
Dr. Andersen said that the quantity of cancer research that indicates a survival benefit of psychosocial interventions is not abundant. "There is not all that much data on social support in particular," she told Medscape Medical News.
Nonetheless, Dr. Andersen suggested that the palliative care study represents a pivotal moment in this area of research. The fact that the New England Journal of Medicine published it was "quite amazing," she said. The journal has a "history of considerable skepticism with regard to the importance of psychological and behavioral factors in cancer," she explained.
Dr. Andersen also pointed out that "there's a whole lot more going on in psychosocial interventions than just social support." For instance, in her breast cancer study, she and her colleagues note that the intervention was psychologist led, conducted in small groups, and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care.
Therein lies a problem, said Dr. Sloan. "It's hard to know which is the active agent" in such multifactorial studies. For instance, he wondered whether treatment adherence was the element of the Ohio State program that tipped the scale toward a survival benefit.
Dr. Andersen responded that adherence was not a factor in the differential survival.
Dr. Andersen would like the discussion about the benefits of psychosocial interventions and drug therapies and other treatments to not be a matter of "either/or." The various interventions should work together, she said.
The authors have disclosed no relevant financial relationships.
JAMA. 2011;305:502-503.
Friday, February 4, 2011
Using ANA Patterns to Diagnose Autoimmune Disorders
From Medscape Rheumatology > Viewpoints
Kevin Deane, MD
Pattern on the Antinuclear Antibody-HEp-2 Test Is a Critical Parameter for Discriminating Antinuclear Antibody-Positive Healthy Individuals and Patients With Autoimmune Rheumatic Diseases
Mariz HA, Sato EI, Barbosa SH, Rodrigues SH, Dellavance A, Andrade LE
Arthritis Rheum. 2011;63:191-200.
Introduction
Testing for antinuclear antibodies (ANAs) is an important aspect of the clinical evaluation of patients with autoimmune rheumatic diseases (ARDs). Understanding how ANA patterns, titers, and extractable nuclear antigen (ENA) profiles are associated with disease or healthy states can help rheumatologists, as well as other healthcare providers, better utilize ANA testing to accurately identify disease. In this study, the authors evaluated the features of ANA testing that discriminated between healthy individuals and those with ARDs.
Study Summary
In Brazilian patients with a variety of known ARDs (N=138; 87 with systemic lupus erythematosus, 45 with systemic sclerosis, 11 with Sjögren syndrome, and 10 with inflammatory myopathy) and healthy controls (N=118), the authors evaluated ANA titers and patterns using indirect immunofluorescence (IIF) with HEp-2 cells as antigen. Additionally, in these groups, the authors tested for autoantibodies to the ENAs Sm, U1 RNP, SSA, and SSB using Ouchterlony methodology, and for antibodies to double-stranded DNA using the Crithidia luciliae assay.
The authors found that an ANA titer of 1:80 was 90.2% sensitive and 87.1% specific for an ARD; a titer of 1:1280 was 65.4% sensitive and 97.9% specific for an ARD. Also, the ANA patterns of nuclear homogeneous, coarse speckled, and centromeric were highly specific for patients with ARDs, while the nuclear dense fine speckled pattern only appeared in healthy individuals (this latter pattern was associated with a 75kd antigen on Western blot). Antibodies to ENAs were highly specific to patients with ARDs; anti-SSA positivity was present in only 1 healthy individual. Additionally, a subset (N=41) of the healthy individuals who were initially positive for ANA (> 1:80) with an IIF appearance of a dense fine speckled pattern were evaluated 4 years after initial testing, and none had developed an ARD.
The authors concluded that on ANA testing with IIF, the titer and pattern were helpful in discriminating between disease and healthy states.
Viewpoint
In the United States and elsewhere, there is increasing popularity of ANA testing by high-throughput methodologies such as ELISA or array-based assays that do not identify ANA patterns, even though there are concerns that these newer methodologies may lack the diagnostic accuracy for ARDs of IIF testing.[1] Although there are some flaws with this paper, the findings presented support that providing ANA testing by IIF may yield valuable clinical information, and, therefore, healthcare providers who evaluate patients with suspected ARDs may lose valuable clinical information if IIF testing is completely abandoned. As an editorial that accompanies this article points out,[2] the authors of this paper could have provided valuable data to inform the ongoing debate about which methodology for ANA testing is optimal for the identification of ARDs if comparison testing between ANA methodologies were performed. Going forward, such direct comparisons are crucial to allow providers to make the best decisions regarding which type of ANA testing methodology to use in clinical practice.
abstract
OBJECTIVE: To identify features of antinuclear antibody (ANA)-HEp-2 test results that discriminate ANA-positive healthy individuals and patients with autoimmune rheumatic diseases (ARDs).
METHODS: We sequentially retrieved data on 918 healthy individuals and 153 patients with ARDs after clinical assessment. ANA-positive healthy individuals for whom data were available were reevaluated after 3.6-5.0 years. An ANA-HEp-2 test result was considered positive when a clear ANA pattern was observed at 1:80 dilution in 2 distinct commercial HEp-2 slides by 2 blinded independent observers.
RESULTS: ANAs were present in 118 healthy individuals (12.9%) and 138 patients with ARDs (90.2%). The ANA titer was higher in patients with ARDs than in healthy individuals (P<0.001). The ANA pattern profile was distinct in the 2 groups. Nuclear homogeneous, nuclear coarse speckled, and nuclear centromeric patterns appeared exclusively in patients with ARDs. The nuclear dense fine speckled pattern occurred only in healthy individuals. The most frequent ANA pattern in both groups was the nuclear fine speckled pattern, which occurred at lower titer in healthy individuals than in patients with ARDs (P<0.001). Anti-extractable nuclear antigen was present in 1 healthy individual (anti-SSA/Ro) and in 52 patients with ARDs (37.7%). None of the 40 reevaluated healthy individuals developed ARDs, and 29 (72.5%) remained ANA positive. All healthy individuals who became ANA negative had an ANA titer of 1:80 at baseline.
CONCLUSION: Our findings suggest that the titer, and especially the pattern, on the ANA-HEp-2 test strongly enhances our ability to discriminate ANA-positive healthy individuals and patients with ARDs.
Kevin Deane, MD
Pattern on the Antinuclear Antibody-HEp-2 Test Is a Critical Parameter for Discriminating Antinuclear Antibody-Positive Healthy Individuals and Patients With Autoimmune Rheumatic Diseases
Mariz HA, Sato EI, Barbosa SH, Rodrigues SH, Dellavance A, Andrade LE
Arthritis Rheum. 2011;63:191-200.
Introduction
Testing for antinuclear antibodies (ANAs) is an important aspect of the clinical evaluation of patients with autoimmune rheumatic diseases (ARDs). Understanding how ANA patterns, titers, and extractable nuclear antigen (ENA) profiles are associated with disease or healthy states can help rheumatologists, as well as other healthcare providers, better utilize ANA testing to accurately identify disease. In this study, the authors evaluated the features of ANA testing that discriminated between healthy individuals and those with ARDs.
Study Summary
In Brazilian patients with a variety of known ARDs (N=138; 87 with systemic lupus erythematosus, 45 with systemic sclerosis, 11 with Sjögren syndrome, and 10 with inflammatory myopathy) and healthy controls (N=118), the authors evaluated ANA titers and patterns using indirect immunofluorescence (IIF) with HEp-2 cells as antigen. Additionally, in these groups, the authors tested for autoantibodies to the ENAs Sm, U1 RNP, SSA, and SSB using Ouchterlony methodology, and for antibodies to double-stranded DNA using the Crithidia luciliae assay.
The authors found that an ANA titer of 1:80 was 90.2% sensitive and 87.1% specific for an ARD; a titer of 1:1280 was 65.4% sensitive and 97.9% specific for an ARD. Also, the ANA patterns of nuclear homogeneous, coarse speckled, and centromeric were highly specific for patients with ARDs, while the nuclear dense fine speckled pattern only appeared in healthy individuals (this latter pattern was associated with a 75kd antigen on Western blot). Antibodies to ENAs were highly specific to patients with ARDs; anti-SSA positivity was present in only 1 healthy individual. Additionally, a subset (N=41) of the healthy individuals who were initially positive for ANA (> 1:80) with an IIF appearance of a dense fine speckled pattern were evaluated 4 years after initial testing, and none had developed an ARD.
The authors concluded that on ANA testing with IIF, the titer and pattern were helpful in discriminating between disease and healthy states.
Viewpoint
In the United States and elsewhere, there is increasing popularity of ANA testing by high-throughput methodologies such as ELISA or array-based assays that do not identify ANA patterns, even though there are concerns that these newer methodologies may lack the diagnostic accuracy for ARDs of IIF testing.[1] Although there are some flaws with this paper, the findings presented support that providing ANA testing by IIF may yield valuable clinical information, and, therefore, healthcare providers who evaluate patients with suspected ARDs may lose valuable clinical information if IIF testing is completely abandoned. As an editorial that accompanies this article points out,[2] the authors of this paper could have provided valuable data to inform the ongoing debate about which methodology for ANA testing is optimal for the identification of ARDs if comparison testing between ANA methodologies were performed. Going forward, such direct comparisons are crucial to allow providers to make the best decisions regarding which type of ANA testing methodology to use in clinical practice.
abstract
OBJECTIVE: To identify features of antinuclear antibody (ANA)-HEp-2 test results that discriminate ANA-positive healthy individuals and patients with autoimmune rheumatic diseases (ARDs).
METHODS: We sequentially retrieved data on 918 healthy individuals and 153 patients with ARDs after clinical assessment. ANA-positive healthy individuals for whom data were available were reevaluated after 3.6-5.0 years. An ANA-HEp-2 test result was considered positive when a clear ANA pattern was observed at 1:80 dilution in 2 distinct commercial HEp-2 slides by 2 blinded independent observers.
RESULTS: ANAs were present in 118 healthy individuals (12.9%) and 138 patients with ARDs (90.2%). The ANA titer was higher in patients with ARDs than in healthy individuals (P<0.001). The ANA pattern profile was distinct in the 2 groups. Nuclear homogeneous, nuclear coarse speckled, and nuclear centromeric patterns appeared exclusively in patients with ARDs. The nuclear dense fine speckled pattern occurred only in healthy individuals. The most frequent ANA pattern in both groups was the nuclear fine speckled pattern, which occurred at lower titer in healthy individuals than in patients with ARDs (P<0.001). Anti-extractable nuclear antigen was present in 1 healthy individual (anti-SSA/Ro) and in 52 patients with ARDs (37.7%). None of the 40 reevaluated healthy individuals developed ARDs, and 29 (72.5%) remained ANA positive. All healthy individuals who became ANA negative had an ANA titer of 1:80 at baseline.
CONCLUSION: Our findings suggest that the titer, and especially the pattern, on the ANA-HEp-2 test strongly enhances our ability to discriminate ANA-positive healthy individuals and patients with ARDs.
Analysis Suggests Back Disease May Run in Families
From Medscape Medical News
Norra MacReady
February 4, 2011 — In an analysis of a database of more than 2 million people, first-degree and third-degree relatives of people with lumbar disc disease had a significantly increased relative risk of developing the back condition themselves compared with expected rates for the general population. "The results of this study support a heritable predisposition to lumbar disc disease," lead author Alpesh A. Patel, MD, and colleagues from the departments of Orthopaedics and Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, report in the February 2 issue of the Journal of Bone and Joint Surgery.
Low back pain is common and costly — its estimated lifetime risk in the United States is 84%, with an annual cost that exceeds $100 billion — yet its etiology remains incompletely understood, the authors write. Several earlier studies have hinted at a familial predisposition, but "we are aware of no study that has evaluated the familial clustering of lumbar disc disease on a population-based, multigenerational level."
To test the hypothesis that lumbar disc disease may be inherited, the authors analyzed data from both the Utah Population Database, which permits the tracking of medical information on the founding pioneers of Utah and their descendents, and the University of Utah Health Sciences Center data warehouse, which has diagnosis and procedure data on all patients treated at the University Hospital. Together, the databases contain information on more than 2.4 million patients. Only patients and control participants with at least 3 generations of genealogical data were included in the study.
Of those individuals, 1254 people had at least 1 diagnosis of lumbar disc disease or lumbar disc herniation, along with the requisite genealogical data. The authors tested for heritability in 2 ways: by estimating the relative risk for lumbar disease in relatives and by determining a genealogical index of familiality (GIF). They compared their findings in affected families with the expected results for the general population of Utah.
First-degree relatives of people with lumbar disc disease had a relative risk of 4.15 of having the disease themselves (95% confidence interval [CI], 2.82 - 6.10; P < .001). In third-degree relatives, the relative risk was 1.46 (95% CI, 1.06 - 2.01; P = .027). Relative risk was slightly elevated in second-degree relatives, at 1.15, but this was not significant (95% CI, .71 - 1.87; P = .60), perhaps because of limitations in the data.
The GIF tests the hypothesis that there is no excess familial clustering, or relatedness, of the phenotype of interest by measuring excess relationships between pairs of patients compared with pairs of control participants. "It is not the absolute value of the GIF statistic that reveals excess relatedness of disease, but the relative value of the case-GIF to the control-GIF," the authors explain. In this analysis, the case overall GIF was 3.05 compared with a mean control GIF of 2.51 (P < .001 for overall GIF), suggesting "a significant excess of relationships among patients compared with controls."
The investigators relied on International Classification of Diseases, Ninth Revision, codes to identify patients, so diagnostic accuracy may have varied, depending on physician specialty and experience, they noted. Also, they were unable to determine disease severity and response to treatment. Genetically, the population of Utah is similar to the US population and to the northern European population from which the founders of Utah came, so the findings may be generalized to those groups.
Now that a genetic predisposition to lumbar disc disease has been identified, the authors conclude, "identification of the specific genetic products responsible for lumbar disc disease may help in the development of potential biologic interventions to prevent and/or treat lumbar disc disease in the population at large."
In an accompanying editorial published online, David A. Wong, MD, from the Denver Spine Center, Greenwood Village, Colorado, commends Dr. Patel and colleagues for their study design and conclusion. Dr. Wong remarks on the future possibilities that may lead researchers to identify specific genes responsible for spine and other musculoskeletal disorders, akin to what is currently known about breast cancer. He states: "We can look forward to more genetic research in the area of the spine. Inevitably better treatments are likely to be found. Perhaps the treatment for so-called black disc disease is lurking on the horizon."
J Bone Joint Surg Am. 2011;93:225-229. Abstract
Norra MacReady
February 4, 2011 — In an analysis of a database of more than 2 million people, first-degree and third-degree relatives of people with lumbar disc disease had a significantly increased relative risk of developing the back condition themselves compared with expected rates for the general population. "The results of this study support a heritable predisposition to lumbar disc disease," lead author Alpesh A. Patel, MD, and colleagues from the departments of Orthopaedics and Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, report in the February 2 issue of the Journal of Bone and Joint Surgery.
Low back pain is common and costly — its estimated lifetime risk in the United States is 84%, with an annual cost that exceeds $100 billion — yet its etiology remains incompletely understood, the authors write. Several earlier studies have hinted at a familial predisposition, but "we are aware of no study that has evaluated the familial clustering of lumbar disc disease on a population-based, multigenerational level."
To test the hypothesis that lumbar disc disease may be inherited, the authors analyzed data from both the Utah Population Database, which permits the tracking of medical information on the founding pioneers of Utah and their descendents, and the University of Utah Health Sciences Center data warehouse, which has diagnosis and procedure data on all patients treated at the University Hospital. Together, the databases contain information on more than 2.4 million patients. Only patients and control participants with at least 3 generations of genealogical data were included in the study.
Of those individuals, 1254 people had at least 1 diagnosis of lumbar disc disease or lumbar disc herniation, along with the requisite genealogical data. The authors tested for heritability in 2 ways: by estimating the relative risk for lumbar disease in relatives and by determining a genealogical index of familiality (GIF). They compared their findings in affected families with the expected results for the general population of Utah.
First-degree relatives of people with lumbar disc disease had a relative risk of 4.15 of having the disease themselves (95% confidence interval [CI], 2.82 - 6.10; P < .001). In third-degree relatives, the relative risk was 1.46 (95% CI, 1.06 - 2.01; P = .027). Relative risk was slightly elevated in second-degree relatives, at 1.15, but this was not significant (95% CI, .71 - 1.87; P = .60), perhaps because of limitations in the data.
The GIF tests the hypothesis that there is no excess familial clustering, or relatedness, of the phenotype of interest by measuring excess relationships between pairs of patients compared with pairs of control participants. "It is not the absolute value of the GIF statistic that reveals excess relatedness of disease, but the relative value of the case-GIF to the control-GIF," the authors explain. In this analysis, the case overall GIF was 3.05 compared with a mean control GIF of 2.51 (P < .001 for overall GIF), suggesting "a significant excess of relationships among patients compared with controls."
The investigators relied on International Classification of Diseases, Ninth Revision, codes to identify patients, so diagnostic accuracy may have varied, depending on physician specialty and experience, they noted. Also, they were unable to determine disease severity and response to treatment. Genetically, the population of Utah is similar to the US population and to the northern European population from which the founders of Utah came, so the findings may be generalized to those groups.
Now that a genetic predisposition to lumbar disc disease has been identified, the authors conclude, "identification of the specific genetic products responsible for lumbar disc disease may help in the development of potential biologic interventions to prevent and/or treat lumbar disc disease in the population at large."
In an accompanying editorial published online, David A. Wong, MD, from the Denver Spine Center, Greenwood Village, Colorado, commends Dr. Patel and colleagues for their study design and conclusion. Dr. Wong remarks on the future possibilities that may lead researchers to identify specific genes responsible for spine and other musculoskeletal disorders, akin to what is currently known about breast cancer. He states: "We can look forward to more genetic research in the area of the spine. Inevitably better treatments are likely to be found. Perhaps the treatment for so-called black disc disease is lurking on the horizon."
J Bone Joint Surg Am. 2011;93:225-229. Abstract
Tuesday, February 1, 2011
USA Adult Immunization Schedule for 2011 Released
From Medscape Medical News
Laurie Barclay, MD
January 31, 2011 — In October 2010, the Advisory Committee on Immunization Practices (ACIP) approved the Adult Immunization Schedule for 2011, which includes several changes.
An adult woman receives a vaccine at her primary care provider's office.
The 2011 schedule, which reflects current recommendations for the licensed vaccines, is published in the February 1 issue of the Annals of Internal Medicine. The 2011 schedule was also approved by the American Academy of Family Physicians, American College of Obstetricians and Gynecologists, and the American College of Physicians.
"The notation for seasonal influenza vaccine in the figure and footnotes was changed to reflect the expanded recommendation for annual influenza vaccination for everyone 6 months of age or older, which was approved by ACIP in February 2010," write Abigail Shefer, MD, Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, and colleagues.
"In October 2010, ACIP issued a permissive recommendation for use of the tetanus, diphtheria, pertussis (Tdap) vaccine in adults aged 65 years or older; approved the recommendation that Tdap can be administered regardless of how much time has elapsed since the last tetanus and diphtheria (Td)–containing vaccine;
and approved a recommendation for a 2-dose series of meningococcal vaccine in adults with certain high-risk medical conditions. The vaccines listed in the Figure have been reordered to keep all universally recommended vaccines together (for example, influenza, Td/Tdap, varicella, human papillomavirus [HPV], and zoster)."
Other changes include clarifications to the footnotes for the measles, mumps, rubella; HPV; and Haemophilus influenza type B (Hib) vaccines and for revaccination with pneumococcal polysaccharide (PPSV). A vaccine series does not need to be restarted, regardless of the time elapsed between doses.
Specific Updated Changes
Specific changes in the schedule for 2011 include the following:
* All persons at least 6 months old, including all adults, should be vaccinated against seasonal influenza. Adults at least 65 years old may receive the high-dose influenza vaccine (Fluzone; sanofi-pasteur, Swiftwater, Pennsylvania), licensed in 2010 for use in this age group, as an option.
* Persons at least 65 years old in close contact with an infant younger than 12 months should receive Tdap vaccine, and all persons at least 65 years old may receive Tdap vaccine. Tdap should be administered regardless of time elapsed since receiving the last Td-containing vaccine.
* Either quadrivalent human papillomavirus (HPV4) vaccine or bivalent (HPV2) vaccine is recommended for girls and women.
* For revaccination with PPSV, 1-time revaccination after 5 years applies only to persons 19 through 64 years old with indicated chronic conditions, namely chronic renal failure or the nephrotic syndrome, functional or anatomic asplenia, or immunocompromising conditions.
* For adults with anatomic or functional asplenia or persistent complement component deficiencies and adults with HIV infection who are vaccinated with meningococcal conjugate vaccine (MCV4), a 2-dose series of meningococcal vaccine is recommended, with the 2 doses given 2 months apart.
For those with other indications, a single dose of meningococcal vaccine is still recommended.
Information in the new schedule clarifies that MCV4 is a quadrivalent vaccine.
* Information regarding the Hib vaccine clarifies which high-risk persons may receive 1 dose of Hib vaccine, namely persons who have sickle cell disease, leukemia, or HIV infection, or those who have had a splenectomy, if they have not previously received Hib vaccine.
Additional Schedule Highlights
Additional highlights of the Adult Immunization Schedule include the following:
* Adults younger than 65 years whose previous Td status is unknown should receive 1 dose of Tdap. Tdap should be administered immediately to postpartum women, close contacts of infants younger than 12 months, and healthcare workers.
* Girls 11 to 12 years old should receive HPV4 or HPV2. Catch-up vaccination in girls may be given until age 26 years. Boys and men 9 to 26 years old may be given HPV4 to lower their risk of acquiring genital warts.
* All persons at least 60 years old should receive a single dose of vaccine against herpes zoster, regardless of whether personal history is positive for herpes zoster.
* Recommendations for varicella vaccination are unchanged. Two vaccine doses at least 4 weeks apart should be given to all adults born during or after 1980 who have no evidence of immunity to varicella.
Healthcare workers should not be considered to have immunity against varicella simply because of their age.
Pregnant women should be evaluated for evidence of varicella immunity, and those lacking such evidence should receive the first dose of varicella vaccine on completion or termination of pregnancy and before discharge from the healthcare facility.
The second dose should be given 4 to 8 weeks after the first dose.
* Hepatitis A vaccination should be given to anyone seeking protection from hepatitis A virus (HAV) infection, men who have sex with men, users of injection drugs, persons working with HAV-infected primates or with HAV in a research laboratory setting, persons with chronic liver disease and persons who receive clotting factor concentrates, and persons traveling to or working in countries with high or intermediate endemicity of hepatitis A.
* Hepatitis B vaccination should be given to anyone seeking protection from hepatitis B virus (HBV) infection, persons with more than 1 sex partner during the previous 6 months, persons seeking evaluation or treatment of a sexually transmitted disease, current or recent injection-drug users, men who have sex with men, healthcare personnel and public safety workers exposed to blood or other potentially infectious body fluids, persons with end-stage renal disease, persons with HIV infection, persons with chronic liver disease, household contacts and sex partners of persons with chronic HBV infection, clients and staff members of institutions for persons with developmental disabilities, and international travelers to countries with a high or intermediate prevalence of chronic HBV infection.
Ann Intern Med. 2011:154:168-173. Full text
Laurie Barclay, MD
January 31, 2011 — In October 2010, the Advisory Committee on Immunization Practices (ACIP) approved the Adult Immunization Schedule for 2011, which includes several changes.
An adult woman receives a vaccine at her primary care provider's office.
The 2011 schedule, which reflects current recommendations for the licensed vaccines, is published in the February 1 issue of the Annals of Internal Medicine. The 2011 schedule was also approved by the American Academy of Family Physicians, American College of Obstetricians and Gynecologists, and the American College of Physicians.
"The notation for seasonal influenza vaccine in the figure and footnotes was changed to reflect the expanded recommendation for annual influenza vaccination for everyone 6 months of age or older, which was approved by ACIP in February 2010," write Abigail Shefer, MD, Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, and colleagues.
"In October 2010, ACIP issued a permissive recommendation for use of the tetanus, diphtheria, pertussis (Tdap) vaccine in adults aged 65 years or older; approved the recommendation that Tdap can be administered regardless of how much time has elapsed since the last tetanus and diphtheria (Td)–containing vaccine;
and approved a recommendation for a 2-dose series of meningococcal vaccine in adults with certain high-risk medical conditions. The vaccines listed in the Figure have been reordered to keep all universally recommended vaccines together (for example, influenza, Td/Tdap, varicella, human papillomavirus [HPV], and zoster)."
Other changes include clarifications to the footnotes for the measles, mumps, rubella; HPV; and Haemophilus influenza type B (Hib) vaccines and for revaccination with pneumococcal polysaccharide (PPSV). A vaccine series does not need to be restarted, regardless of the time elapsed between doses.
Specific Updated Changes
Specific changes in the schedule for 2011 include the following:
* All persons at least 6 months old, including all adults, should be vaccinated against seasonal influenza. Adults at least 65 years old may receive the high-dose influenza vaccine (Fluzone; sanofi-pasteur, Swiftwater, Pennsylvania), licensed in 2010 for use in this age group, as an option.
* Persons at least 65 years old in close contact with an infant younger than 12 months should receive Tdap vaccine, and all persons at least 65 years old may receive Tdap vaccine. Tdap should be administered regardless of time elapsed since receiving the last Td-containing vaccine.
* Either quadrivalent human papillomavirus (HPV4) vaccine or bivalent (HPV2) vaccine is recommended for girls and women.
* For revaccination with PPSV, 1-time revaccination after 5 years applies only to persons 19 through 64 years old with indicated chronic conditions, namely chronic renal failure or the nephrotic syndrome, functional or anatomic asplenia, or immunocompromising conditions.
* For adults with anatomic or functional asplenia or persistent complement component deficiencies and adults with HIV infection who are vaccinated with meningococcal conjugate vaccine (MCV4), a 2-dose series of meningococcal vaccine is recommended, with the 2 doses given 2 months apart.
For those with other indications, a single dose of meningococcal vaccine is still recommended.
Information in the new schedule clarifies that MCV4 is a quadrivalent vaccine.
* Information regarding the Hib vaccine clarifies which high-risk persons may receive 1 dose of Hib vaccine, namely persons who have sickle cell disease, leukemia, or HIV infection, or those who have had a splenectomy, if they have not previously received Hib vaccine.
Additional Schedule Highlights
Additional highlights of the Adult Immunization Schedule include the following:
* Adults younger than 65 years whose previous Td status is unknown should receive 1 dose of Tdap. Tdap should be administered immediately to postpartum women, close contacts of infants younger than 12 months, and healthcare workers.
* Girls 11 to 12 years old should receive HPV4 or HPV2. Catch-up vaccination in girls may be given until age 26 years. Boys and men 9 to 26 years old may be given HPV4 to lower their risk of acquiring genital warts.
* All persons at least 60 years old should receive a single dose of vaccine against herpes zoster, regardless of whether personal history is positive for herpes zoster.
* Recommendations for varicella vaccination are unchanged. Two vaccine doses at least 4 weeks apart should be given to all adults born during or after 1980 who have no evidence of immunity to varicella.
Healthcare workers should not be considered to have immunity against varicella simply because of their age.
Pregnant women should be evaluated for evidence of varicella immunity, and those lacking such evidence should receive the first dose of varicella vaccine on completion or termination of pregnancy and before discharge from the healthcare facility.
The second dose should be given 4 to 8 weeks after the first dose.
* Hepatitis A vaccination should be given to anyone seeking protection from hepatitis A virus (HAV) infection, men who have sex with men, users of injection drugs, persons working with HAV-infected primates or with HAV in a research laboratory setting, persons with chronic liver disease and persons who receive clotting factor concentrates, and persons traveling to or working in countries with high or intermediate endemicity of hepatitis A.
* Hepatitis B vaccination should be given to anyone seeking protection from hepatitis B virus (HBV) infection, persons with more than 1 sex partner during the previous 6 months, persons seeking evaluation or treatment of a sexually transmitted disease, current or recent injection-drug users, men who have sex with men, healthcare personnel and public safety workers exposed to blood or other potentially infectious body fluids, persons with end-stage renal disease, persons with HIV infection, persons with chronic liver disease, household contacts and sex partners of persons with chronic HBV infection, clients and staff members of institutions for persons with developmental disabilities, and international travelers to countries with a high or intermediate prevalence of chronic HBV infection.
Ann Intern Med. 2011:154:168-173. Full text
ACP Issues Guidelines for Diagnostic Imaging for Low Back Pain
From Medscape Medical News
Laurie Barclay, MD
January 31, 2011 — Routine imaging for low back pain with radiography or advanced imaging methods, such as computed tomography (CT) scanning or magnetic resonance imaging (MRI), does not improve patient health, according to recommendations issued by the Clinical Guidelines Committee of the American College of Physicians (ACP) regarding high-value healthcare for diagnostic imaging for low back pain.
Imaging scan of lower back
The new guidelines, which are first in a series to help physicians and patients identify misused medical treatments and to practice high-value healthcare, are published in the February 1 issue of Annals of Internal Medicine. The recommendations target internists, family physicians, and other clinicians treating adults with low back pain.
"Low back pain is one of the most common reasons for a patient to see a physician and many patients with low back pain receive routine imaging that is not beneficial and may even be harmful," said second author Amir Qaseem, MD, PhD, MHA, director of clinical policy for ACP, in a news release. "Unnecessary imaging can lead to a series of unnecessary additional tests, interventions, follow ups, and referrals that do not improve patient outcomes."
The new recommendations are based on a systematic review and meta-analysis conducted for the diagnosis and treatment of low back pain joint clinical practice guideline from ACP and the American Pain Society. Available imaging modalities for the low back include radiography, CT, and MRI.
Specific recommendations include the following:
* Diagnostic imaging is indicated for patients with low back pain only if they have severe progressive neurologic impairments or signs or symptoms indicating a serious or specific underlying condition, or if they are candidates for invasive interventions. Routine imaging is not associated with clinically meaningful benefits in other patients and can lead to harms.
* Immediate imaging is recommended for patients with acute low back pain who have major risk factors for cancer, risk factors for spinal infection, risk factors for or signs of the cauda equina syndrome, or severe or progressive neurologic deficits.
* Imaging after a trial of treatment is recommended for patients who have minor risk factors for cancer, risk factors for inflammatory back disease, risk factors for vertebral compression fracture, signs or symptoms of radiculopathy, or risk factors for or symptoms of symptomatic spinal stenosis.
* Decisions for subsequent imaging should be guided by development of new symptoms or changes in current symptoms, with repeated imaging recommended only in patients with new or changed low back symptoms.
* Efforts to reduce routine imaging will be most effective if these efforts consider clinician behaviors, patient expectations, and financial incentives.
* Patient education is needed to inform patients of current and effective standards of care and to educate them regarding the benefits and potential harms of diagnostic imaging.
Evidence that expanding imaging to patients without indications for advanced or repeated imaging does not improve outcomes includes randomized trials of routine imaging vs usual care without routine imaging in patients without indications for diagnostic imaging. Findings from these trials suggested no clinically meaningful benefits from expanded imaging on outcomes regarding pain, function, quality of life, or mental health. In addition, there is a weak correlation between most imaging findings and symptoms, acute low back pain has a favorable prognosis with or without imaging, the prevalence of serious or specific underlying conditions is low, and the impact of imaging on treatment decisions is unclear.
Potential harms of unnecessary imaging include the radiation exposure involved in lumbar radiography and CT; hypersensitivity reactions and contrast nephropathy for use of iodinated contrast with CT; and the possibility that subsequent unnecessary, invasive, and expensive procedures could be performed. In addition, knowledge of clinically irrelevant imaging findings might hinder recovery by causing patients to worry more, focus excessively on minor back symptoms, or avoid exercise or other recommended activities for fear of causing more structural damage.
Talking Points Advised
To overcome barriers to evidence-based practice regarding use of imaging for low back pain, the ACP recommends using talking points based on evidence-based guidelines to facilitate patient education. Evidence-based online or print education material to supplement face-to-face education may help overcome time constraints. Clinicians who are uncertain about the need for imaging can be reassured once they recognize the low likelihood of serious conditions in the absence of clinical risk factors and review the evidence showing no benefit associated with routine imaging. The ACP also recommends that clinician incentives be based on providing appropriate care, in addition to patient satisfaction.
"Addressing inefficiencies in diagnostic testing could minimize potential harms to patients and have a large effect on use of resources by reducing both direct and downstream costs," the guidelines authors write. "In this area, more testing does not equate to better care. Implementing a selective approach to low back imaging, as suggested by the ...ACP and American Pain Society guideline on low back pain, would provide better care to patients, improve outcomes, and reduce costs."
Financial support for the development of this guideline came exclusively from the ACP operating budget. Some of the guidelines authors have disclosed various financial relationships with Wellpoint, Palladian Health, Consumers Union, Blue Cross Blue Shield Association, American Pain Society, ACP, and Anthem/Wellpoint. Disclosures can also be viewed at the Annals of Internal Medicine Web site .
Ann Intern Med. 2011;154:181-189. Full text
Laurie Barclay, MD
January 31, 2011 — Routine imaging for low back pain with radiography or advanced imaging methods, such as computed tomography (CT) scanning or magnetic resonance imaging (MRI), does not improve patient health, according to recommendations issued by the Clinical Guidelines Committee of the American College of Physicians (ACP) regarding high-value healthcare for diagnostic imaging for low back pain.
Imaging scan of lower back
The new guidelines, which are first in a series to help physicians and patients identify misused medical treatments and to practice high-value healthcare, are published in the February 1 issue of Annals of Internal Medicine. The recommendations target internists, family physicians, and other clinicians treating adults with low back pain.
"Low back pain is one of the most common reasons for a patient to see a physician and many patients with low back pain receive routine imaging that is not beneficial and may even be harmful," said second author Amir Qaseem, MD, PhD, MHA, director of clinical policy for ACP, in a news release. "Unnecessary imaging can lead to a series of unnecessary additional tests, interventions, follow ups, and referrals that do not improve patient outcomes."
The new recommendations are based on a systematic review and meta-analysis conducted for the diagnosis and treatment of low back pain joint clinical practice guideline from ACP and the American Pain Society. Available imaging modalities for the low back include radiography, CT, and MRI.
Specific recommendations include the following:
* Diagnostic imaging is indicated for patients with low back pain only if they have severe progressive neurologic impairments or signs or symptoms indicating a serious or specific underlying condition, or if they are candidates for invasive interventions. Routine imaging is not associated with clinically meaningful benefits in other patients and can lead to harms.
* Immediate imaging is recommended for patients with acute low back pain who have major risk factors for cancer, risk factors for spinal infection, risk factors for or signs of the cauda equina syndrome, or severe or progressive neurologic deficits.
* Imaging after a trial of treatment is recommended for patients who have minor risk factors for cancer, risk factors for inflammatory back disease, risk factors for vertebral compression fracture, signs or symptoms of radiculopathy, or risk factors for or symptoms of symptomatic spinal stenosis.
* Decisions for subsequent imaging should be guided by development of new symptoms or changes in current symptoms, with repeated imaging recommended only in patients with new or changed low back symptoms.
* Efforts to reduce routine imaging will be most effective if these efforts consider clinician behaviors, patient expectations, and financial incentives.
* Patient education is needed to inform patients of current and effective standards of care and to educate them regarding the benefits and potential harms of diagnostic imaging.
Evidence that expanding imaging to patients without indications for advanced or repeated imaging does not improve outcomes includes randomized trials of routine imaging vs usual care without routine imaging in patients without indications for diagnostic imaging. Findings from these trials suggested no clinically meaningful benefits from expanded imaging on outcomes regarding pain, function, quality of life, or mental health. In addition, there is a weak correlation between most imaging findings and symptoms, acute low back pain has a favorable prognosis with or without imaging, the prevalence of serious or specific underlying conditions is low, and the impact of imaging on treatment decisions is unclear.
Potential harms of unnecessary imaging include the radiation exposure involved in lumbar radiography and CT; hypersensitivity reactions and contrast nephropathy for use of iodinated contrast with CT; and the possibility that subsequent unnecessary, invasive, and expensive procedures could be performed. In addition, knowledge of clinically irrelevant imaging findings might hinder recovery by causing patients to worry more, focus excessively on minor back symptoms, or avoid exercise or other recommended activities for fear of causing more structural damage.
Talking Points Advised
To overcome barriers to evidence-based practice regarding use of imaging for low back pain, the ACP recommends using talking points based on evidence-based guidelines to facilitate patient education. Evidence-based online or print education material to supplement face-to-face education may help overcome time constraints. Clinicians who are uncertain about the need for imaging can be reassured once they recognize the low likelihood of serious conditions in the absence of clinical risk factors and review the evidence showing no benefit associated with routine imaging. The ACP also recommends that clinician incentives be based on providing appropriate care, in addition to patient satisfaction.
"Addressing inefficiencies in diagnostic testing could minimize potential harms to patients and have a large effect on use of resources by reducing both direct and downstream costs," the guidelines authors write. "In this area, more testing does not equate to better care. Implementing a selective approach to low back imaging, as suggested by the ...ACP and American Pain Society guideline on low back pain, would provide better care to patients, improve outcomes, and reduce costs."
Financial support for the development of this guideline came exclusively from the ACP operating budget. Some of the guidelines authors have disclosed various financial relationships with Wellpoint, Palladian Health, Consumers Union, Blue Cross Blue Shield Association, American Pain Society, ACP, and Anthem/Wellpoint. Disclosures can also be viewed at the Annals of Internal Medicine Web site .
Ann Intern Med. 2011;154:181-189. Full text
Thursday, January 27, 2011
For the First Time, Sunscreen Shown to Reduce Melanoma
From Medscape Medical News > Oncology
RCT with nearly 15-year data
Nick Mulcahy
January 25, 2011 — Melanoma in adults might be preventable with the regular use of sunscreen — that is, with the daily application to the head, neck, arms, and hands, according to Australian researchers who conducted a rare randomized controlled trial of sunscreen use.
The study randomized 1621 adults to regular sunscreen use or to discretionary use, which included no use at all.
The regular application of sunscreen with a sun protection factor of 15 or more during a 5-year treatment period reduced the incidence of new primary melanomas during a subsequent 10-year follow-up period, report the study authors, led by Adele Green, MB BS, PhD, from the University of Queensland in Brisbane.
"Our findings provide reassurance . . . about sunscreen's ability to prevent melanoma," write Dr. Green and her colleagues in the January 20 issue of the Journal of Clinical Oncology.
Two editorialists, who wrote an essay that accompanies the study, mostly endorse the findings.
"The question of its efficacy with respect to melanoma prevention should no longer deter scientists or clinicians from recommending sunscreen use," write Phyllis Gimotty, PhD, and Karen Glanz, PhD, MPH, from the University of Pennsylvania School of Medicine in Philadelphia.
However, Dr. Gimotty and Dr. Glanz, who are cancer epidemiologists, quibble about the study statistics, saying that the study's P values "could be considered of borderline significance."
But these experts in statistical methods ultimately yield to the study authors' conclusions. "The trial's findings are the first to provide strong evidence for a reduction in the incidence of invasive melanoma after regular application of broad-spectrum sunscreen in adults," the pair write.
Highest Rate of Skin Cancer in the World
The new findings come from the Nambour Skin Cancer Prevention Trial, which was conducted in Queensland — a region with "the highest rate of skin cancer in the world," the editorialists point out.
Dr. Green and her colleagues previously reported that regular sunscreen use during the initial 5-year study period prevented squamous cell carcinomas of the skin (Cancer Epidemiol Biomarkers Prev. 2006;15:2546-2548).
In their current paper, the authors report results at 10 years after that 5-year trial ended. In the 10 years after trial cessation, 11 new primary melanomas were identified in the daily sunscreen group, compared with 22 in the discretionary group. This represents a "reduction of the observed rate in those randomly assigned to daily sunscreen use" (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.24 to 1.02; P = .051).
Furthermore, an exploratory analysis indicated that there was a "substantial" reduction in invasive melanomas (3 cases in the regular use group and 11 in the control group; HR, 0.27; 95% CI, 0.08 to 0.97; P =.045), compared with that for preinvasive in situ melanomas (8 vs 11 cases; HR, 0.73; 95% CI, 0.29 to 1.81; P = .49).
The study findings are not limited to Australians, say the authors.
"They also have implications for white people living in temperate climates in North America and Europe," they write, adding that such people might have an increased risk for melanoma because of "their predilection for holidays in sunny places."
How to Apply and Reapply Daily Sunscreen
The editorialists make a set of recommendations to clinicians on the basis of the trial's landmark findings. But before doing so, they say that this study is something special.
"The trial was an ambitious and unique study," they write. "It is unlikely that another trial of comparable scope and rigor will be conducted in the foreseeable future."
One of the study's lessons is that "clear instructions" to the public are needed about "use and reapplication." In the study, the 812 men and women randomized to sunscreen intervention were given a free unlimited supply of broad-spectrum sunscreen (8% [by weight] 2-ethylhexyl p-methoxycinnamate and 2% [by weight] 4-tert-butyl-4′-methoxy-4-dibenzoylmethane) with a sun protection factor of 16.
"They were asked to apply it to head, neck, arms, and hands every morning (and reapplication was advised after heavy sweating, bathing, or long sun exposure)," write the authors.
This part of the study is important because, as the editorialists point out, surveys indicate that pediatricians regularly advise parents to have children wear sunscreen when playing outdoors, but "usually do not give advice about optimal use and reapplication."
The editorialists also advise, as many experts do, "patients at high risk for skin cancer because of phenotypic characteristics (fair skin, freckling, tendency to sunburn, and so on), who live in or visit sunny climates, and/or who have a family history of melanoma to routinely and thoroughly apply sunscreen before going outside."
The regular use of sunscreen should become a "habit" for high-risk and highly exposed adults and children, say Dr. Gimotty and Dr. Glanz.
However, they also point out that "sunscreen use alone will not likely reduce the incidence of skin cancer."
These latest findings should not be an excuse to drop other sun protections, the editorialists write. "Excess exposure to ultraviolet rays should be avoided, clothing should be used to shield skin from the sun, and sun-safe environments should be used for outdoor recreation," they write.
Latent Effect
Compliance was fairly high in the study among the regular sunscreen users, say the authors. Compliance was assessed using the average self-reported frequencies of application, participant diaries, and the weight of returned sunscreen bottles.
Approximately 75% of the regular users complied and used sunscreen daily; 25% of this group also applied sunscreen to nonintervention sites (trunk and/or lower limbs).
Because it would have been unethical to have had a placebo sunscreen as part of the study, the investigators had the control group consist of men and women who used sunscreen at their own discretion. The majority of participants in the control group either did not apply sunscreen (38%) or applied it once or twice a week at most (35%); 8% applied it to nonintervention sites, report the authors.
Sun exposure was similar between the regular- and discretionary-use groups during the trial, the authors report. Use of sun protection measures other than sunscreen was also similar during the trial — approximately 60% of both groups usually sought shade and around 75% usually wore a hat.
The prevention of melanoma indicated by the study might point to a latent of effect of sunscreen, suggest the authors, because most of the regular sunscreen users stopped the daily application of sunscreen at 5 years.
"On the basis of reports of active participants, 25% of those randomly assigned to daily sunscreen continued to use sunscreen on a regular basis after the trial, compared with 18% of the nonintervention group," write the authors.
Dr. Green reports receiving research funding from L'Oréal Recherche.
J Clin Oncol. 2011.29;249-250, 257-263. Abstract, Abstract
RCT with nearly 15-year data
Nick Mulcahy
January 25, 2011 — Melanoma in adults might be preventable with the regular use of sunscreen — that is, with the daily application to the head, neck, arms, and hands, according to Australian researchers who conducted a rare randomized controlled trial of sunscreen use.
The study randomized 1621 adults to regular sunscreen use or to discretionary use, which included no use at all.
The regular application of sunscreen with a sun protection factor of 15 or more during a 5-year treatment period reduced the incidence of new primary melanomas during a subsequent 10-year follow-up period, report the study authors, led by Adele Green, MB BS, PhD, from the University of Queensland in Brisbane.
"Our findings provide reassurance . . . about sunscreen's ability to prevent melanoma," write Dr. Green and her colleagues in the January 20 issue of the Journal of Clinical Oncology.
Two editorialists, who wrote an essay that accompanies the study, mostly endorse the findings.
"The question of its efficacy with respect to melanoma prevention should no longer deter scientists or clinicians from recommending sunscreen use," write Phyllis Gimotty, PhD, and Karen Glanz, PhD, MPH, from the University of Pennsylvania School of Medicine in Philadelphia.
However, Dr. Gimotty and Dr. Glanz, who are cancer epidemiologists, quibble about the study statistics, saying that the study's P values "could be considered of borderline significance."
But these experts in statistical methods ultimately yield to the study authors' conclusions. "The trial's findings are the first to provide strong evidence for a reduction in the incidence of invasive melanoma after regular application of broad-spectrum sunscreen in adults," the pair write.
Highest Rate of Skin Cancer in the World
The new findings come from the Nambour Skin Cancer Prevention Trial, which was conducted in Queensland — a region with "the highest rate of skin cancer in the world," the editorialists point out.
Dr. Green and her colleagues previously reported that regular sunscreen use during the initial 5-year study period prevented squamous cell carcinomas of the skin (Cancer Epidemiol Biomarkers Prev. 2006;15:2546-2548).
In their current paper, the authors report results at 10 years after that 5-year trial ended. In the 10 years after trial cessation, 11 new primary melanomas were identified in the daily sunscreen group, compared with 22 in the discretionary group. This represents a "reduction of the observed rate in those randomly assigned to daily sunscreen use" (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.24 to 1.02; P = .051).
Furthermore, an exploratory analysis indicated that there was a "substantial" reduction in invasive melanomas (3 cases in the regular use group and 11 in the control group; HR, 0.27; 95% CI, 0.08 to 0.97; P =.045), compared with that for preinvasive in situ melanomas (8 vs 11 cases; HR, 0.73; 95% CI, 0.29 to 1.81; P = .49).
The study findings are not limited to Australians, say the authors.
"They also have implications for white people living in temperate climates in North America and Europe," they write, adding that such people might have an increased risk for melanoma because of "their predilection for holidays in sunny places."
How to Apply and Reapply Daily Sunscreen
The editorialists make a set of recommendations to clinicians on the basis of the trial's landmark findings. But before doing so, they say that this study is something special.
"The trial was an ambitious and unique study," they write. "It is unlikely that another trial of comparable scope and rigor will be conducted in the foreseeable future."
One of the study's lessons is that "clear instructions" to the public are needed about "use and reapplication." In the study, the 812 men and women randomized to sunscreen intervention were given a free unlimited supply of broad-spectrum sunscreen (8% [by weight] 2-ethylhexyl p-methoxycinnamate and 2% [by weight] 4-tert-butyl-4′-methoxy-4-dibenzoylmethane) with a sun protection factor of 16.
"They were asked to apply it to head, neck, arms, and hands every morning (and reapplication was advised after heavy sweating, bathing, or long sun exposure)," write the authors.
This part of the study is important because, as the editorialists point out, surveys indicate that pediatricians regularly advise parents to have children wear sunscreen when playing outdoors, but "usually do not give advice about optimal use and reapplication."
The editorialists also advise, as many experts do, "patients at high risk for skin cancer because of phenotypic characteristics (fair skin, freckling, tendency to sunburn, and so on), who live in or visit sunny climates, and/or who have a family history of melanoma to routinely and thoroughly apply sunscreen before going outside."
The regular use of sunscreen should become a "habit" for high-risk and highly exposed adults and children, say Dr. Gimotty and Dr. Glanz.
However, they also point out that "sunscreen use alone will not likely reduce the incidence of skin cancer."
These latest findings should not be an excuse to drop other sun protections, the editorialists write. "Excess exposure to ultraviolet rays should be avoided, clothing should be used to shield skin from the sun, and sun-safe environments should be used for outdoor recreation," they write.
Latent Effect
Compliance was fairly high in the study among the regular sunscreen users, say the authors. Compliance was assessed using the average self-reported frequencies of application, participant diaries, and the weight of returned sunscreen bottles.
Approximately 75% of the regular users complied and used sunscreen daily; 25% of this group also applied sunscreen to nonintervention sites (trunk and/or lower limbs).
Because it would have been unethical to have had a placebo sunscreen as part of the study, the investigators had the control group consist of men and women who used sunscreen at their own discretion. The majority of participants in the control group either did not apply sunscreen (38%) or applied it once or twice a week at most (35%); 8% applied it to nonintervention sites, report the authors.
Sun exposure was similar between the regular- and discretionary-use groups during the trial, the authors report. Use of sun protection measures other than sunscreen was also similar during the trial — approximately 60% of both groups usually sought shade and around 75% usually wore a hat.
The prevention of melanoma indicated by the study might point to a latent of effect of sunscreen, suggest the authors, because most of the regular sunscreen users stopped the daily application of sunscreen at 5 years.
"On the basis of reports of active participants, 25% of those randomly assigned to daily sunscreen continued to use sunscreen on a regular basis after the trial, compared with 18% of the nonintervention group," write the authors.
Dr. Green reports receiving research funding from L'Oréal Recherche.
J Clin Oncol. 2011.29;249-250, 257-263. Abstract, Abstract
Subscribe to:
Posts (Atom)