• Acetaminophen Receives a Labeling Change — Is Anything Safe?
• Increased Risk for Gastrointestinal Bleeding with New Oral Anticoagulants
• Advice for Community-Dwelling Elders: Eat Well, Exercise, and Stop Smoking
• Higher ω-3 Fatty Acid Levels Are Associated with Risk for Prostate Cancer
• Understanding Racial Differences in Survival Among Women with Breast Cancer
• Physical Punishment During Childhood Linked with Adult Disease
• What Do Physicians Think About Their Responsibility for Controlling Healthcare Costs?
• Osteonecrosis of the Jaw and Breast Cancer Treatment
MM: I get questions of what are my pain options on a daily basis. Acetaminophen has no effect on me. I have kidney or liver conditions or am taking blood thinners. What can I safely and effectively use? When I get these questions I frequently recommend All Flex Pro, the herbal and mineral combination that we have found clinically effective and useful for virtually all forms of painful inflammation.
Although the reactions described in this article are exceedingly rare, there is a subgroup of patients who tend to exhibit ready environmental sensitivities and this group should be cognizant of this danger. The general public is unlikely to experience a Stevens-Johnson reaction to acetaminophen.
Acetaminophen Receives a Labeling Change — Is Anything Safe?
This widely used drug is associated with severe skin reactions, but how often?
Acetaminophen is a commonly used, over-the-counter pain reliever and antipyretic agent. Billions of people worldwide take this medication annually. On August 1, 2013, the Food and Drug Administration elected to issue a warning to physicians and require a labeling change to warn consumers of the risk for serious skin reactions related to acetaminophen.
Comment: I was not able to find more than a handful of reports on PubMed of acetaminophen-related Stevens-Johnson Syndrome, toxic epidermal necrolysis, or acute generalized exanthematous pustulosis. Many of those I did find lacked evidence by my analysis of a strong cause-and-effect relationship between the drug and the skin reaction. Bottom line: Such a reaction is most likely extraordinarily rare, but clinicians caring for patients with severe adverse drug reactions should include acetaminophen in the list of drugs that might be responsible for such eruptions.
Citation(s): U.S. Food and Drug Administration. Acetaminophen: Drug safety communication — Association with risk of serious skin reactions. FDA 2013 Aug 1; [e-pub ahead of print].
(http://viajwat.ch/19gor3w)
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Gastroenterology 2013 Jul; 145:105
Increased Risk for Gastrointestinal Bleeding with New Oral Anticoagulants
Elevated risk was observed mostly in patients with acute coronary syndrome or venous thrombosis and in patients taking the drugs dabigatran or rivaroxaban.
Several new oral anticoagulants (nOACs) have been developed that inhibit thrombin or factor Xa, but study findings vary on their associated risk for bleeding complications, particularly gastrointestinal bleeding (GIB). Because there are no known reversal agents for these drugs, further research is essential.
In the current study, investigators conducted a systematic review and subsequent meta-analysis of 43 randomized trials comprising 151,578 patients. Trials compared nOACs with standard care (which could include other antiplatelet or anticoagulant therapy) for risk of bleeding. GIB was assessed in only 19 of these trials; no events occurred in 2 of those trials. The remaining 17 trials identified 1101 GIB events in 75,081 patients. The overall risk for GIB was increased with nOACs (odds ratio, 1.45; 95% confidence interval, 1.07–1.97), but the studies showed substantial heterogeneity. The increased risk was seen mainly in trials for acute coronary syndrome and venous thrombosis. Patients with atrial fibrillation or orthopedic procedures had no increased risk. Risk was increased with use of dabigatran or rivaroxaban but not with apixaban or edoxaban. The risk for any major bleeding was increased in patients taking nOACs (OR, 1.16; 95% CI, 1.00–1.34).
Comment: The authors conclude that patients taking new oral anticoagulants for acute coronary syndrome or venous thrombosis have an increased risk for gastrointestinal bleeding compared with patients receiving standard care. Despite the suggestion of increased risk, determination of the magnitude of risk or contributing risk factors is difficult because the studies were heterogeneous in both types of drug used and indications for use. Data on the use of other agents that either promote or prevent GIB were not available. As the authors urge, additional studies designed to identify the risk for GIB with each of these agents are needed to guide their use.
Citation(s): Holster IL et al. New oral anticoagulants increase risk for gastrointestinal bleeding: A systematic review and meta-analysis. Gastroenterology 2013 Jul; 145:105.
(http://dx.doi.org/10.1053/j.gastro.2013.02.041)
http://www.ncbi.nlm.nih.gov/pubmed/23470618?access_num=23470618&link_
type=MED&dopt=Abstract
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MM: Quality of Life (QOL) is affected as much by what we do and what we eat along with our social relationships as by anything else. If we can improve our overall health through healthy activities then we can improve our quality of life as well. After all, doesn't it matter just as much to live well and be able to enjoy and appreciate life as it does to live a long life? Eating a healthy diet, exercise and eliminating tobacco can achieve both of these goals.
BMJ 2013 Jul 23; 347:f4240
Advice for Community-Dwelling Elders: Eat Well, Exercise, and Stop Smoking
Low physical activity, smoking, and low intake of fruits and vegetables are associated with risk for disability.
Although certain behaviors have adverse effects on health, less is known about associations between unhealthful behaviors and disability in older adults. In this prospective study, investigators examined these relations.
Researchers periodically assessed 4000 French community dwellers (age, ≥65) who were disability-free at baseline. During a mean follow-up of 6.8 years, moderate-to-severe disability (e.g., impaired mobility, decline in activities of daily living) developed in 31% of participants. After adjustment for potentially confounding factors, low physical activity, smoking, and infrequent consumption of fruits and vegetables were associated with significant excess risk for disability (by 72%, 26%, and 24%, respectively); alcohol consumption was not associated with excess disability. Similar results were obtained after excluding patients who developed disability during the first 4 years of the study. Participants with three unhealthful behaviors had 2.5-fold increased risk for disability compared with participants with no unhealthful behaviors.
Comment: In this study, low-to-intermediate physical activity, smoking, and low intake of fruits and vegetables were associated with excess risk for disability among older community dwellers in France. The persistence of the findings after excluding patients who developed disability during the first 4 years of the study argues against reverse causation (e.g., disabled people are less likely to engage in healthful behaviors). Therefore, we have additional evidence that general recommendations for people to exercise more, quit smoking, and eat balanced diets are applicable to older adults.
Citation(s): Artaud F et al. Unhealthy behaviours and disability in older adults: Three-City Dijon cohort study. BMJ 2013 Jul 23; 347:f4240.
(http://dx.doi.org/10.1136/bmj.f4240)
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MM: Omega 3 fish oil is getting a bad rap in my opinion. The cardiac benefits that have been repeatedly demonstrated in multiple studies should not be over-shadowed by a possible negative impact on prostate cancer. After all, the general public is at a much greater risk of cardiac disease than prostate cancer. Cardiac disease (CD) moves rapidly to destroy a life whereas prostate cancer (PC) is typically a very slow and often hidden problem. CD is highly prevalent across the population and affects both genders as a primary cause of morbidity and mortality. PC, although highly prevalent in aging males is infrequently the primary cause of death or morbidity.
J Natl Cancer Inst 2013 Aug 7; 105:1132.
Higher ω-3 Fatty Acid Levels Are Associated with Risk for Prostate Cancer
This association now has been noted in two case-control studies.
In the randomized SELECT trial, vitamin E supplementation raised risk for prostate cancer compared with placebo (NEJM JW Gen Med Oct 25 2011). Now, researchers have used data from SELECT to confirm findings from a previous case-control study, published in 2011, that showed a positive association between ω-3 fatty acid levels and risk for high-grade prostate cancer (Am J Epidemiol 2011; 173:1429).The researchers performed a case-control study in which they compared 834 men with prostate cancer (diagnosed during SELECT) and 1393 age- and race-matched controls without prostate cancer. Plasma ω-3 fatty acid levels were measured in stored blood samples collected at the beginning of the trial. In analyses adjusted for potentially confounding variables, total ω-3 levels were associated positively with risk for prostate cancer (hazard ratio for highest vs. lowest quartile of ω-3 levels, 1.44 for low-grade cancer and 1.71 for high-grade cancer).
Comment: This report attracted considerable media attention, given the widespread use of ω-3 supplements. Importantly, this was an observational study of correlations between ω-3 blood levels and prostate cancer and not a randomized trial of ω-3 supplementation. However, the results are remarkably similar to those of the aforementioned 2011 case-control study. These findings — taken together with recent randomized trials in which ω-3 supplementation did not prevent coronary events (NEJM JW Gen Med May 8 2013 and JAMA 2012; 308:1024) — tip the balance further against use of ω-3 supplements.
Citation(s): Brasky TM et al. Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. J Natl Cancer Inst 2013 Aug 7; 105:1132.
(http://dx.doi.org/10.1093/jnci/djt174)
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MM: It appears the key take away from this article is that early detection and treatment seems to play a major role in improved outcomes and black women are typically diagnosed at a much later time in their cancers than white women are. If this is the case then we need to concentrate more efforts on educating women of color about breast health and detection. On the other hand, we need to be careful about not over-diagnosing and obtaining false positives in an effort to save lives and improve outcomes. As always, its a thin line to walk in order to get the best of both worlds.
JAMA 2013 Jul 24; 310:38
Understanding Racial Differences in Survival Among Women with Breast Cancer
Survival disparities between black and white women are largely explained by differing presentation characteristics at diagnosis.
To better understand why black women have poorer breast cancer outcomes than white women, investigators analyzed Surveillance, Epidemiology and End Results (SEER)–Medicare data from 7400 black women and 100,000 white women with breast cancer diagnoses between 1991 and 2005. Women were matched in three sets based on demographics (age, year of diagnosis, and SEER site), presentation (comorbidities and tumor biology), and treatment.
The demographics match showed that 5-year survival was 12.9% lower among black women than white women. This difference was 4.4% when presentation characteristics were added to the match and 3.6% when treatment was added. Treatment differences accounted for only 0.8% of the 12.9% survival disparity; however, the interval between diagnosis and treatment was longer in black women. Racial disparities in overall survival did not change appreciably throughout the study period.
Comment: This carefully performed population-based analysis shows that differences at presentation account for most of the survival disparities between black and white women with breast cancer: Black women presented with more-advanced disease and more comorbid conditions and had poorer access to preventive and primary care. The authors note that treatment is more effective earlier in the course of the disease; thus, if black women present for diagnosis sooner, optimizing treatment could play a more important role in reducing racial disparities in survival.
Citation(s): Silber JH et al. Characteristics associated with differences in survival among black and white women with breast cancer
JAMA 2013 Jul 24; 310:389.
(http://dx.doi.org/10.1001/jama.2013.8272)
See more at:
http://www.jwatch.org/na31900/2013/08/08/understanding-racial-differences-survival-among-women-with?query=etoc_jwwomen#sthash.OXIAvpA9.dpuf
http://www.ncbi.nlm.nih.gov/pubmed/23917289?access_num=23917289&link_
type=MED&dopt=Abstract
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Pediatrics 2013 Aug; 132:e333
Physical Punishment During Childhood Linked with Adult Disease
Reports of childhood physical punishment (not maltreatment) increased risk for adult cardiovascular disease, arthritis, and obesity.
In a recent study, harsh punishment in children was significantly associated with adult mood and anxiety disorders, alcohol and drug abuse or dependence, and personality disorders (NEJM JW Pediatr Adolesc Med Aug 15 2012). Now, the same research group has reported on the relation between harsh physical punishment in childhood and adult physical health.
In a nationally representative survey of 34,000 U.S. adults (response rate, 87%), participants were asked during face-to-face interviews about harsh physical punishment (e.g., pushing, grabbing, shoving, and hitting) during childhood and physical health conditions. Harsh physical punishment did not include more severe child maltreatment (i.e., physical abuse causing residual marks, bruises, or injury; sexual or emotional abuse; physical or emotional neglect; and exposure to intimate partner violence). Diagnosis of physical health conditions were made by a health professional (except for obesity, which was calculated based on self-reported weight and height).
In analysis adjusted for sociodemographic variables, family dysfunction and mental disorders, reports of harsh physical punishment in childhood were associated with increased risk for cardiovascular disease, arthritis, and obesity (adjusted odds ratios, 1.38, 1.35, and 1.24, respectively).
Comment: Chronic toxic stress, as a mediator of neuroendocrine and immune functions that impact early brain development, has been hypothesized as an explanation for the association between harsh physical punishment during early childhood and adult disease (NEJM JW Pediatr Adolesc Med Feb 27 2013).The association reported in this study must be cautiously interpreted because the data relied on recall memory of the participants. In an accompanying editorial, the authors note that only 3.6% of respondents reported that they experienced harsh physical punishment. The low prevalence is surprising given the definition used for harsh physical punishment and the exclusion of maltreatment. This study extends the results of a landmark retrospective report on the relation between adverse childhood events and adult physical health (Am J Prev Med 1998; 14:245) by adding cardiovascular disease, obesity, and arthritis to the list of adverse physical outcomes that includes obstructive pulmonary disease, diabetes, alcohol use, and liver disease.
Citation(s): Afifi TO et al. Harsh physical punishment in childhood and adult physical health. Pediatrics 2013 Aug; 132:e333. (http://dx.doi.org/10.1542/peds.2012-4021) Abstract/FREE Full Text Berger RP and Zolotor AJ. Is there an association between physical punishment in childhood and physical health in adulthood? Pediatrics 2013 Aug; 132:e500.
(http://dx.doi.org/10.1542/peds.2013-1631)
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JAMA 2013 Jul 24/31; 310:380
What Do Physicians Think About Their Responsibility for Controlling Healthcare Costs?
Most accept some responsibility for reducing costs but are not very enthusiastic about reforms that limit reimbursement.
Physicians' views about controlling healthcare costs might be helpful in developing effective policies. To assess physicians' attitudes toward and perceived responsibility for controlling healthcare costs, researchers surveyed a random sample of 2556 U.S. physicians (mean age, 51; 70% men), most of whom were in group or salaried practices (only 15% were in government or academic settings).
Roughly 60% of respondents said trial lawyers, health insurance companies, hospitals and health systems, and pharmaceutical and device manufacturers have the major responsibility for lowering healthcare costs, as opposed to physicians themselves (36%) and professional societies (27%); 52% of physicians assigned major responsibility to patients. About 90% of respondents expressed some or strong support for “limiting access to expensive treatments with little net benefit” and using cost-effectiveness data to guide treatment. They were less supportive of “penalizing providers for avoidable readmissions” and bundling payments, and they strongly opposed “eliminating fee-for-service payment models.” A significant proportion (76%) said they were aware of the costs of tests and treatments they recommend. About half the respondents were somewhat or very enthusiastic about “reducing compensation for the highest-paid specialties,” but the authors don't tell us whether primary care physicians answered this item differently from highly paid specialists.
Comment: Not surprisingly, most physicians believe someone else bears the responsibility for controlling healthcare costs and are unenthusiastic about interventions that limit their practice autonomy or income. I am skeptical of the respondents' confidence that they know the costs of tests and treatments, perhaps because of my own limitations here. Major changes in the way healthcare is delivered and funded inevitably will conflict with the views of many (perhaps most) physicians.
Citation(s): Tilburt JC et al. Views of US physicians about controlling health care costs.
JAMA 2013 Jul 24/31; 310:380.
(http://dx.doi.org/10.1001/jama.2013.8278)
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J Clin Oncol 2013 Jun 24
Osteonecrosis of the Jaw and Breast Cancer Treatment
Adjuvant zoledronic acid was associated with low incidence of ONJ and did not affect oral quality of life.
The prior, industry-supported AZURE trial (N Engl J Med 2011 Oct 13; 365:1396) demonstrated that the bisphosphonate zoledronic acid (ZA), in combination with standard adjuvant systemic therapy, had no effect on disease-free survival in the overall study population of patients with stage II or III breast cancer, although it significantly reduced the risk for recurrence and death in the subset of postmenopausal patients. Bisphosphonate therapy has also been associated with osteonecrosis of the jaw (ONJ), characterized by exposed bone, most commonly in the mandible, as well as by loose teeth, draining fistulas, secondary infections, and localized pain.
Now, investigators have evaluated the incidence and impact of ONJ in 3360 women in the AZURE trial. Patients were randomized to receive standard adjuvant systemic therapy alone (controls) or with ZA (4 mg for 19 doses over 5 years). All potential occurrences of ONJ were reported as serious adverse events and centrally reviewed. In addition, 362 study participants completed the Oral Health Impact Profile–14 to assess oral quality of life (QoL) around the time they completed 5 years of the study.
During a median follow-up of 73.9 months, 33 possible cases of ONJ were reported, all in ZA-treated patients; 26 were confirmed as consistent with a diagnosis of ONJ, representing a cumulative incidence of 2.1%. Neither the prevalence nor severity of oral QoL differed significantly between ZA-treated patients and controls.
Comment: The incidence of osteonecrosis of the jaw was low in the AZURE study and other trials (e.g., Ann Oncol 2012; 23:1341), but ONJ can be debilitating. Medical treatments and surgical debridement are used with variable success. The quality-of-life analysis in a subset of AZURE study patients indicates no compromise in outcome, but, importantly, this small analysis does not compare the QoL in patients with ONJ versus those without the diagnosis of ONJ. The possibility of ONJ should be discussed with all patients receiving either zoledronic acid or denosumab as a component of breast cancer treatment.
Citation(s): Rathbone EJ et al. Osteonecrosis of the jaw and oral health–related quality of life after adjuvant zoledronic acid: An adjuvant zoledronic acid to reduce recurrence trial subprotocol (BIG01/04).
J Clin Oncol 2013 Jun 24; [e-pub ahead of print].
(http://dx.doi.org/10.1200/JCO.2012.46.4792)
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