Breast Cancer Treatment Guidelines

National Comprehensive Cancer Network (NCCN) Breast Cancer Guideline, Version 1.2007 Medscape Hematology-Oncology. 2006;9(2) ©2006 Medscape Posted 12/13/2006 Medscape Hematology-Oncology is pleased to present the latest update to the National Comprehensive Cancer Network (NCCN) Breast Cancer Guideline, Version 1.2007, released in December 2006. The updated Guideline, available for the first time on Medscape, was developed by a panel of 25 multidisciplinary breast cancer experts from NCCN member institutions. The panel met for 2 days in August 2006 to review evidence and formulate updated recommendations. All NCCN Guidelines are updated continuously, but at least once a year, with additional updates published when important new data that change practice standards are released. The update process includes extensive review of the current Guideline via institutional reviews at member institutions, review of recently published data, and formal input from the patient advocacy community. An agenda for the panel meeting is developed and panel members are assigned to present data regarding each agenda item. Relevant publications and results of the institutional review are distributed to panel members before the meeting. The published Guideline has 3 parts: an algorithm that follows the step-by-step clinical decision-making process; a manuscript that discusses the data the recommendations are based on and the issues that were considered by the panel; and a bibliography. Each recommendation is categorized according to both the level of evidence supporting the recommendation and the degree of consensus among the member institutions that the recommendation is appropriate. All panel members volunteer their time and expertise and accept no compensation for their efforts. They declare any potential conflicts of interest both in writing and verbally to each other. Panel members may be excluded from discussion of related topics if it is perceived that they have a significant conflict, at the discretion of the chair. Data may be submitted to the panel by the community, patient advocacy organizations, or industry representatives. Industry representatives are not allowed to participate in the panel discussions, nor are they allowed to make presentations to the panel. The panel has sole responsibility for evaluating data and determining the content of the Guideline. Guideline development is completely supported by member dues to NCCN. NCCN may accept industry funding only for dissemination of the Guidelines. The NCCN Breast Cancer Guideline is one of the NCCN Complete Library of Clinical Practice Guidelines in Oncology, which is available free of charge at http://www.nccn.org. The most recent version of each Guideline is always available on NCCN's Web site. NCCN also produces Guidelines for Patients for high-incidence cancers, including breast cancer and important supportive care issues, in cooperation with the American Cancer Society. These Guidelines for Patients are available at NCCN's Web site and in print format from the American Cancer Society. Click here to view: National Comprehensive Cancer Network Breast Cancer Guideline, Version 1.2007

Tobacco Dependence

In America today, tobacco stands out as the agent most responsible for avoidable illness and death. Millions of Americans consume this toxin on a daily basis. Its use brings premature death to almost half a million Americans each year, and contributes to profound disability and pain in many ways. Approximately one-third of all tobacco users in this country will die prematurely because of their dependence on tobacco. In fact, tobacco use is the chief avoidable cause of illness and death in our society, causing cancer, heart disease, stroke, complications of pregnancy, and chronic obstructive pulmonary disease. Pharmacokinetics of Cigarette Smoke Within seconds of inhaling cigarette smoke, a bolus of nicotine travels from the carotid arteries to the brain where the molecules bind to nicotine receptors. Nicotine stimulates the norepinephrine and serotonin systems, enhancing concentration and memory and decreasing anxiety. This results in dopamine secretion that causes pleasurable sensations and relief of symptoms of nicotine deprivation. Nicotine also interacts with acetylcholine receptors, creating a variety of physiologic reactions. Some reactions are beneficial, such as suppressing appetite and pain, while others are not, such as elevated BP and nicotine addiction. Nicotine replacement therapy mimics but does not match these intense effects caused by the nicotine in cigarette smoke. (Fiore, M., & Westman, E. Using pharmacotherapy for cessation. Patient Care. 2001; 35(24):18-27.) Tobacco Dependence Shows Many Features of A Chronic Disease Tobacco dependence shows many features of a chronic disease. Although a minority of tobacco users achieves permanent abstinence in an initial quit attempt, the majority persist in tobacco use for many years and typically cycle through multiple periods of relapse and remission. By recognizing that tobacco dependence is a chronic condition, clinicians will better understand the relapsing nature of the ailment and the requirement for ongoing, rather than just acute care. This framework helps clinicians view relapse as a subsequent component of this chronic disease, rather than a lack of motivation or commitment on the patients' part or lack of ability on the clinicians' part. A failure to appreciate the chronic nature of tobacco dependence may undercut clinicians' motivation to treat tobacco use consistently. Helping Your Patient Develop A Quit Plan Set a quit date -- In preparation for quitting the patient should set a quit date, ideally within 2 weeks. The patient should tell their family, friends, and coworkers about the quit attempt and request understanding and support. Review past quit attempt experiences -- Urge the patient to consider reusing strategies that were helpful and to avoid situations that led to relapse. Anticipate challenges -- It is important for the patient to anticipate challenges to the planned quit attempt, particularly during the critical first few weeks (e.g., withdrawal symptoms such as negative mood, urges to smoke, and difficulty concentrating). Remove tobacco products -- Prior to quitting, patients should remove tobacco products from their environment and avoid smoking in places where he or she spends a lot of time (e.g., work, home, car). In addition, if a spouse or significant other is continuing to smoke, specific strategies to limit that risk should be established. Tobacco and alcohol -- About half of smokers who try to quit and relapse have their first drag of smoke with some alcohol in their bloodstream. Avoiding or limiting alcohol in the first few weeks after a quit attempt should be considered. Children and Adolescents The PHS Guideline recommends that clinicians screen pediatric and adolescent patients and their parents for tobacco use and provide a strong message about totally abstaining from tobacco use. A recent study has shown that adolescents' smoking status was identified in 72% of office visits, but smoking cessation counseling was provided at only 17% of clinic visits of adolescent smokers. Therefore, clinicians both need to assess adolescent tobacco use and offer cessation counseling and behavioral interventions shown to be effective with adults. It is also recommended that the content of these interventions be modified to be developmentally appropriate. Children and adolescents may benefit from community- and school-based intervention activities. The messages delivered by these programs should be reinforced by the clinician. The Guideline further recommends that clinicians in a pediatric setting offer stop-smoking advice to parents to limit children's exposure to second-hand smoke. The Youth Tobacco Cessation Collaborative (YTCC) was formed in 1998 to address the question of which strategies and treatments are most effective in assisting youth to quit smoking. The YTCC is composed of ten member organizations in the United States and Canada who are involved in funding research, program, and policy initiatives focused on youth tobacco use. In 2003, the YTCC published its National Youth Tobacco Cessation Blueprint establishing both short- and long-term goals "to insure that every young tobacco user (age 12 - 24) has access to effective cessation interventions by 2010" (Orleans, CT, et al. (2003). Youth Tobacco Cessation Collaborative and National Blueprint for Action. American Journal of Health Behavior, 27 (Suppl 2), S103-S119). On their website, the YTCC makes available current research on youth tobacco cessation. Clinicians working with adolescents who smoke may find this a valuable resource.

Nutrition in Cancer Survivors

More than 10 million persons in the United States are cancer survivors, and 65% of Americans diagnosed with cancer now live more than 5 years with a need for informed recommendations on nutrition and lifestyle, and yet the advice given by healthcare professionals is often conflicting. The current report by a panel of experts in nutrition, physical activity, and cancer convened by the ACS, based on current available evidence and updated from the 2003 report, has been prepared to guide healthcare professionals and patients about clinical practice recommendations for nutrition and lifestyle after a diagnosis of cancer. The sections address phases of survivorship, nutrition and physical activity, and selected cancer sites with specific recommendations. Even when evidence is incomplete, reasonable conclusions and recommendations are made based on noncancer studies to guide choices about body weight, foods, physical activity, and nutritional supplement use. Study Highlights At diagnosis and during cancer treatment, anorexia, early satiety, taste, smell, and gastrointestinal tract disturbances are most prevalent, with malnutrition and weight loss occurring in more than 50% of patients. The goal is to prevent deficiencies, preserve lean body mass, maximize quality of life, and consider effects of radiation, surgery, and chemotherapy. For cancer survivors, smaller, more frequent meals and intake of nutrient-dense foods can increase caloric intake. Short-term measures, such as pharmacotherapy, enteral, or intravenous parenteral feeding, can be considered. The American Society for Parenteral and Enteral Nutrition and the American Dietetic Association recommend using total parenteral nutrition selectively. Maintenance of a healthy weight is recommended as obesity has been linked to increased cancer risk. Exercise has been shown to be safe and can improve prognosis in breast and colorectal cancer. In the Nurses Health Study, as little as 1 to 3 hours per week of moderate intensity exercise was associated with a 26% to 40% reduction in risk for recurrent, breast-cancer–specific, and all-cause mortality. Patients who are immunocompromised should avoid public gyms until their white blood counts return to normal. Those undergoing irradiation should avoid chronic exposure to chlorine in swimming pools. Careful attention should be paid to balance to prevent falls. For patients who are obese or overweight, slow weight loss (no more than 2 lbs per week) using a well-balanced diet and increased physical activity to achieve 5% to 10% weight loss can confer survival benefits. A low-fat diet with avoidance of trans fatty acids (< 3% of total calories) and saturated fats (< 10% of daily calories) can improve survival for patients with breast and prostate cancer. At least 5 servings of colorful fruits and vegetables are recommended daily and considered protective for cancers, including lung, oral, esophageal, stomach, and colon cancer. Sugars do not contribute nutritional value and limiting sugar consumption is recommended. Patients who may be immunosuppressed should avoid foods with pathogenic organisms and practice food safety guidelines. The role of soy foods and supplements is uncertain, but soy is an excellent source of protein that can be recommended. High doses of soy isoflavones as supplements are not recommended for those with estrogen-receptor–positive breast cancer. There is no clear answer for whether antioxidants help or harm, and no more than 100% of the daily recommended dose should be taken. No direct evidence has determined whether consuming a vegetarian diet is healthful or harmful and individuals should be guided by the nutritional content. Alcohol intake advice should be tailored to individual survivors. Benefits relate to cardiovascular protection and are not specific for any cancers. Survivors with oral mucositis should avoid alcohol, which can irritate the mucosa. Cancer survivors should consume at least 8 cups of liquid daily. The role of calcium, folate, and selenium in preventing polyp recurrence in colorectal cancer is uncertain. Current evidence suggests that adherence to treatment and colonoscopic surveillance are the most important prognostic indicators. Low microbial diets are recommended for transplant recipients. High-dose beta-carotenes may increase risk for lung cancer. Malnutrition is the primary issue during cancer diagnosis and treatment, and exercise, healthy weight maintenance, and a balanced diet are key recommendations after treatment to prevent relapse and improve prognosis. Nutritional supplements, such as soy isoflavones, beta-carotene, and antioxidants, should be used with caution in cancer survivors, and low microbial diets are recommended for immunocompromised and transplant patients.

Folic Acid and Heart Disease and Stroke

Higher levels of homocysteine increase the risk for coronary heart disease and stroke. Although folic-acid therapy can reduce levels of serum homocysteine, results of studies examining the effects of folic-acid supplementation on the risk for cardiovascular disease have been mixed. The current meta-analysis finds that folic-acid supplementation does not improve the risk for cardiovascular disease outcomes or all-cause mortality among patients with a history of cardiovascular disease or end-stage renal disease.

Women with Breast Cancer Diagnosis and Pregnancy

Clinical Context Women of childbearing age diagnosed as having breast cancer may want to conceive a child after treatment, and currently, they are often advised to wait at least 2 years after treatment before conceiving. However, according to the current authors, there are no published data suggesting that postponing conception will alter either the outcome of the cancer or the pregnancy, and some reports suggest that pregnancy may favorably alter the prognosis, an effect called the "healthy mother" effect, which may occur because of self-selection among women with better prognosis. This is a population-based retrospective study covering 11 years, describing the prognosis of women who conceive after breast cancer diagnosis and treatment to examine impact on survival. Study Highlights The Western Australian data linkage system linking 15 million health records, which includes hospital morbidity, birth and death registries, mental health services, cancer registry and midwives' notifications. This was used to identify women who conceived after a diagnosis of breast cancer. Potential cases were first identified after hospital discharge with an International Classification of Diseases (ICD) code for breast cancer (invasive or in situ) for women aged 15 to 44 years. In the second stage, this cohort was used to identify ICD diagnostic or procedure codes for pregnancy and pregnancy outcome (such as abortion, miscarriage, ectopic pregnancy, stillbirth, or live birth). A single experienced researcher reviewed records for relevant data, including tumor characteristics and pregnancy management and outcomes. Cases of sterilization and breast cancer diagnosed outside Western Australia were excluded. 2539 women with pathologically confirmed breast caner were identified, of whom 123 (5%) had at least 1 pregnancy. Median age at cancer diagnosis was 31 years and at first subsequent pregnancy was 35 years. 77% of women had invasive ductal carcinoma with tumor size from 1 to 90 mm, and 47% of tumors were less than 20 mm. 64% of women had unaffected lymph nodes, and stage I (325) and II (53%), ie, good prognosis, were the most common. Most women had breast-conserving surgery and were likely to have radiotherapy. 41% of women had adjuvant chemotherapy, and 6% had hormone therapy. 56% had at least 1 pregnancy before the breast cancer diagnosis. 175 pregnancies were confirmed in the 123 women, and 37% had more than 1 pregnancy. 54% of women had a live birth. Median time from diagnosis of breast cancer to first subsequent pregnancy was 23 months. There were no stillbirths or ectopic pregnancies. 2 births occurred before 36 weeks. There was 1 set of twins and a singleton birth by Cesarean delivery. 50% of women conceived within 2 years of their diagnosis, and abortion was more common within 2 years of diagnosis (P = .012). Proportionally more abortions occurred in the first 6 months after breast cancer diagnosis and while the woman was undergoing active treatment (50% vs 45%). 85% of women who had a pregnancy after cancer were alive with a median follow-up of 128 months. All deaths were from breast-cancer–related causes. Recurrence occurred in 39% of women with a median time without recurrence of 42 months. The overall 5-year survival in women who conceived after breast cancer diagnosis was 92%, and 10-year survival was 86%. The authors noted that this was better than reported in other cohorts. 5- and 10-year survival rates from the first subsequent pregnancy were 87% and 85%. Subsequent pregnancy improved overall survival (HR, 0.59; P = .03). Subsequent pregnancy improved survival overall in women who waited 24 months to become pregnant (HR, 0.48; P = .009). Pregnancy had no significant effect for all women who waited at least 6 months to become pregnant. Pearls for Practice Conceiving at least 6 months after a diagnosis of breast cancer is associated with similar or improved survival compared with not conceiving after breast cancer diagnosis. Pregnancy is unlikely to compromise survival in women with breast cancer with good prognosis, and conception at less than 6 months after diagnosis is associated with a higher abortion rate.

Treatment of First Ankle Sprains

BACKGROUND: Acute ankle ligament sprains are treated with the use of controlled mobilization with protection provided by external support (eg, functional treatment); however, there is little information regarding the best type of external support to use. HYPOTHESIS: There is no difference between elastic wrapping, bracing, bracing combined with elastic wrapping, and casting for treatment of acute, first-time ankle ligament sprains in terms of the time a patient requires to return to normal function. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: Patients suffering their first ligament injury were stratified by the severity of the sprain (grades I, II, or III) and then randomized to undergo functional treatment with different types of external supports. The patients completed daily logs until they returned to normal function and were followed up at 6 months. RESULTS: Treatment of grade I sprains with the Air-Stirrup brace combined with an elastic wrap returned subjects to normal walking and stair climbing in half the time required for those treated with the Air-Stirrup brace alone and in half the time required for those treated with an elastic wrap alone. Treatment of grade II sprains with the Air-Stirrup brace combined with the elastic wrap allowed patients to return to normal walking and stair climbing in the shortest time interval. Treatment of grade III sprains with the Air-Stirrup brace or a walking cast for 10 days followed by bracing returned subjects to normal walking and stair climbing in the same time intervals. The 6-month follow-up of each sprain severity group revealed no difference between the treatments for frequency of reinjury, ankle motion, and function. CONCLUSION: Treatment of first-time grade I and II ankle ligament sprains with the Air-Stirrup brace combined with an elastic wrap provides earlier return to preinjury function compared to use of the Air-Stirrup brace alone, an elastic wrap alone, or a walking cast for 10 days.

Black Cohosh For Hot Flashes?

PURPOSE: Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment. Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal. METHODS: A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period. RESULTS: Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment. CONCLUSION: This trial failed to provide any evidence that black cohosh reduced hot flashes more than the pla

How Low Should We Go With the LDL

Introduction These days, even most laypersons know that low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol and that the class of drugs known as statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) is a proven treatment for patients with elevated levels of serum LDL cholesterol. For the physician, this guideline-mandated, evidence-based treatment strategy is supported by the results of numerous large, randomized, placebo-controlled clinical trials,[1-6] which have demonstrated highly significant reductions in the risk of death or cardiovascular events in populations with (secondary prevention) or without (primary prevention) a history of coronary artery disease (CAD). The 2003 National Cholesterol Education Program guidelines recommended that patients with established CAD or diabetes (sometimes called a "CAD equivalent") should be treated to reach a target LDL cholesterol level < 100 mg/dL.[7,8] In demonstrating their protection against future events, these first placebo-controlled statin trials employed standard doses to reduce LDL cholesterol levels by 25% to 35%. In other words, large reductions in LDL cholesterol can be achieved, and the guidelines set a target level -- do we have a final answer on how to treat our CAD (and diabetic) patients? While statins have been proven over the last decade to be among the safest and most efficacious drugs in the physician's armamentarium, these historic results have still left some remaining questions: What LDL level should be the threshold for initiating statin treatment? What kind of reductions, with what kind of benefit, have subsequent trials with more potent ("second generation") statins and/or higher doses of the first-generation statins demonstrated? How low can/should LDL cholesterol be lowered? Is there a "J" curve, below which the risk outweighs the benefits with the more intensive statin dosing? How High to Start Treatment? The question of the threshold for initiation of statin treatment was investigated in the Heart Protection Study (HPS), the largest study at that time to investigate the benefits of cholesterol lowering, and the results were presented at the American Heart Association meeting in 2001. While reinforcing the results of the earlier trials, HPS also reported that, regardless of the baseline LDL cholesterol level (above or even starting below 100 mg/dL), patients received the benefit of protection against cardiovascular events with the standard dose of simvastatin used in the study.[4] One simple way to interpret this result was to say that since all patients seemed to benefit from the statin therapy, it might not be necessary to measure for baseline cholesterol levels in patients - instead, simply treat all high-risk patients with statin therapy. (People often joke that we should just "put statins in the drinking water.") Further support for this concept can be found in the data from the Cholesterol Treatment Trialists (CTT) meta-analysis, which inspected the results in over 90,000 patients enrolled in the large placebo-controlled trials of standard-dose statin therapy. This analysis found that risk of CAD death or myocardial infarction (MI) was reduced by 23% (P < .0001), and the risk of any major vascular event by 21% (P < .0001), with consistency of benefit in every subgroup examined.[9] Thus, the conclusion appears as simple as the results of HPS suggest: For all patients at risk (another subject, but primarily meaning blood pressure, overweight, smoking, diabetes, family history), whatever their baseline LDL level, statin therapy will lower their risk. However, this begs the question of whether the benefit observed is based on just receiving statin therapy, or whether the degree of lipid lowering mattered. In other words, is it a qualitative factor (the drug, ie, statins) or a quantitative factor (the LDL level achieved) that matters? How Low Have We Achieved So Far? Once HPS and the initial placebo-controlled trials had established the undoubted efficacy of statin therapy, it became unethical to assess cholesterol lowering against a placebo. Recently, however, 4 large outcomes trials involving almost 28,000 patients have assessed more intensive statin therapy vs "standard" statin doses as used in the earlier trials, to reach target LDL cholesterol levels of < 130 mg/dL in stable CAD patients and <100 mg/dL in patients with additional risk (eg, diabetes). PROVE IT-TIMI 22 The Pravastatin or Atorvastatin Evaluation and Infection Treatment - Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) trial compared standard therapy with a proven agent (pravastatin 40 mg, which achieved a median LDL level of 95 mg/dL, thus meeting the current National Cholesterol Education Program [NCEP] III Guideline target of LDL < 100 mg/dL[7]) vs intensive therapy with a new agent (atorvastatin 80 mg, which achieved a median LDL level of 62 mg/dL) in patients hospitalized for an acute coronary syndrome (ACS) event.[10] This 33-mg/dL difference resulted in a very clear and highly significant (P = .005) benefit of the more intensive statin treatment, with a 16% reduction in the risk of death and major cardiovascular events that emerged rapidly, and was seen over the subsequent 2 years following an acute coronary syndrome.[10] The interesting and very important point was that this large and highly significant benefit was achieved on top of active therapy with a proven standard-dose statin (since a placebo control would have been unethical). Moreover, this benefit emerged as early as 15 days after randomization and achieved statistical significance by 30 days for the composite endpoint of death, MI, or recurrent ACS.[11] A second trial in ACS patients, A to Z, showed similar trend toward benefit, but had limited power due to a smaller-than-anticipated number of events.[12] Treat to New Targets (TNT) The Treat to New Targets (TNT) trial was similar to PROVE IT except that it enrolled patients with stable CAD and tested treatment with high-dose vs standard-dose atorvastatin. Again, in this trial there was a highly significant reduction (22%) in major cardiac events,[13] and the benefit was seen with reductions in cardiovascular death, MI, the need for revascularization, and stroke. IDEAL The Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) trial compared atorvastatin 80 mg with simvastatin 20-40 mg in patients with a prior MI and who qualified for statin therapy according to NCEP guidelines. The intensive statin treatment lowered LDL cholesterol by 23 mg/dL, and this resulted in an 11% reduction in the primary endpoint of CAD death, MI, or resuscitated cardiac arrest that just missed being statistically significant (P = .07).[14] However, when the results were reassessed post hoc, using the TNT endpoint (which also included stroke), there was a significant 13% reduction in the primary endpoint (P = .02), and when using the primary endpoint from the PROVE IT-TIMI 22 trial (any cardiovascular event including revascularization), there was a highly significant 16% reduction (P < .001).[14] REVERSAL Additional supportive data for the benefit of intensive statin therapy came from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial.[15] In this study, 654 patients who were referred for coronary angiography were randomized to 18 months with intensive (atorvastatin 80 mg) vs moderate (pravastatin 40 mg) statin therapy. The primary endpoint was change in the actual volume of atheroma in designated segments of the coronary arteries, as measured using an intravascular ultrasound (IVUS) technique. In this study, the LDL levels achieved by the 2 treatments were quite different, 110 mg/dL and 79 mg/dL, for the standard and intensive groups, respectively. A significantly lower rate of progression of coronary artery disease was seen in atheroma volume in the intensive therapy arm (-0.4% vs +2.7%, P = .02). These anatomic data support the clinical events data from the 4 clinical outcomes trials in showing that lowering LDL into the range of 70 mg/dL appears better than just lowering LDL below 100 mg/dL. Side Effects With regard to safety, 2 issues have been raised. The first is the issue of (transient) elevations of liver and muscle enzymes. Increases in liver function tests and creatine kinase levels of 1% to 3% are seen in patients on standard- or high-dose statin therapy, compared with elevations of 1% to 2% in the patients treated with placebo.[10,13,16] Once patients began being treated with the more recent high-dose statin regimens, these liver enzyme function elevations were slightly more common. In the PROVE IT-TIMI 22 trial, there were more patients in the intensive group who had transient increases in their liver function tests (alanine aminotransferase > 3 times the upper limit of normal), appearing in approximately 3% of patients receiving atorvastatin 80 mg vs 1% of patients on pravastatin 40 mg (P < .001). However, CK elevations, myalgias, and cessation of the study medication due to report of muscle aches or CK elevations were similar in the 2 groups (approximately 3%). There were no cases of rhabdomyolysis in either group of the trial. Overall, rhabdomyolysis is very rare; in the recent CTT meta-analysis, there were just 9 cases (0.023%) in 39,884 patients treated with statins, vs 6 cases (0.015%) found in 39,817 treated with placebo, which equates to a nonsignificant excess of just 3 patients (0.01%).[9] Looked at another way, this safety profile of statins is quite impressive, in that 90%-95% of patients can tolerate the statins, even at maximal doses, as tested in the recent trials. Nevertheless, although this class of drugs is quite safe, it does require both physicians and patients to monitor for these side effects and adjust the doses accordingly. How Low Is Still Safe? Is there a bottom? Is there an LDL level below which the decrease in risk of events starts to be outweighed by an increase in risk of deleterious effects? This can be separated into 2 questions: How low is still safe? How low is the most efficacious? Safety What about the safety of achieving ultra-low LDL levels? An analysis by Wiviott and colleagues[17] looked carefully at the results of liver function enzyme tests, creatinine kinase elevations, and other side effects among patients who achieved very low LDL levels (ie, < 40 mg/dL or in the range 40 to 60 mg/dL) and found no differences in any of these adverse safety events.[17] Intriguingly, as the achieved LDL reached this new ultra-low range, the rate of death or cardiovascular events continued to drop lower and lower, suggesting that a target LDL of < 70 mg/dL might not be the lowest target to achieve in order to get maximum benefit. However, the important take-home message from this safety analysis is that if a patient is on a high-dose statin, and his or her LDL comes back at 42 mg/dL, there is no need to reduce the dose. How Low Is Low Enough? So -- how low should we go? The current evidence supports, and the NCEP Guideline Committee suggests, that the "therapeutic option" should be to get LDL levels to < 70 mg/dL for high-risk patients (ie, those with a recent ACS or with established CAD or CAD equivalent). However, I aim for this level in practice with all of my patients, as I believe many cardiologists do also. But -- is this the "optimal" level? We don't know if we have reached the bottom yet. We are currently conducting the IMPROVE IT trial, which will compare 2 of the optimal current regimens, simvastatin vs Vytorin (simvastatin plus ezetimibe). The target will be to reach median achieved LDL levels of approximately 65 mg/dL vs 50 mg/dL, respectively. When we see the results of IMPROVE IT, we should see whether we need to set our LDL cholesterol targets even lower. For the moment, however, I try to get all of my patients with CAD (and/or peripheral arterial disease or prior stroke) to < 70 mg/dL. This seems to be the best evidence-based medicine at the moment. References

All About Lice

Myth Fact All children with lice scratch or itch. Initial infestation may produce no signs or symptoms for 4 - 6 weeks. Lice jump or fly from head to head. Lice can be dislodged from hair by air movements giving the appearance of flying. Lice live in carpets, beds, clothes, and sofas Lice can only live for 24-48 hours away from a human host. Lice die immediately after treatment. Lice may take several hours to die following treatment. One treatment is enough. Due to loss of residual activity of pediculicides, two treatments are recommended to kill newly hatched nymphs. Permethrin based products are 100% ovicidal. Permethrin kills 70% of eggs with one treatment. Everyone in the family should be treated. Only those with a proven infestation should be treated, although everyone should be checked daily to weekly. Head lice prefer long or dirty hair. The likelihood of infestation is not affected by hair length or cleanliness. Table 2. Treatment Categories for Lice Therapies Standard pediculicides • Historically considered standard treatment; however instance of resistance have made it necessary to explore new alternatives• Not recommended for children <2 yrs• Apply to entire scalp Permethrin Nix® Permethrin-based RID®, R&C ®, Pronto®, A-200®, Kwellada-P®, Clear Lice System® Malathion Ovide® Lindane Kildane®, Kwell®, Scabene® Oral agents •Off-label use Ivermectin Stromectol® Trimethoprim/ Sulfamethoxazole Bactrim®, Septra® Non-neurotoxic pediculicides • Exoskeleton integrity dehydration pediculicide• Recently approved by Health Canada Isopropyl myristate 50% and ST-cyclomethicone 50% and ST-cyclomethicone 50% Resultz™ • Dry-on suffocation-based pediculicide Active agent unclear Nuvo® Method = Cetaphil® Cleanser Mechanical removal • Only treatment recommended for children <2 years n/a n/a Environmental intervention • Important to prevent recurrence n/a n/a Alternative treatments • Published data is sparse • Caution should be advised until more data is available. n/a n/a

Calcium and Vitamin D Preventing Osteoporosis

FDA Updates Health Claim for Calcium and Osteoporosis Proposal Would Give Consumers More Information to Make Healthy Food Choices The Food and Drug Administration (FDA) is proposing to allow new claims on foods and dietary supplements containing calcium and Vitamin D to show their potential to reduce the risk of osteoporosis. The proposed rule would allow manufacturers to include new information on their food and supplement labeling and to eliminate certain other information, described below. "This is important information for all citizens," said Robert E. Brackett, Ph.D., director of FDA's Center for Food Safety and Nutrition. "All persons lose bone with age, and the loss can influence an individual's risk of developing osteoporosis. Maintenance of an adequate intake of calcium and vitamin D in all stages of life can help lower one's risk." Today's action is part of FDA's continued commitment to helping consumers make informed and healthy food choices, and responds to a health claim petition submitted by the Beverage Institute for Health and Wellness, The Coca-Cola Company. The proposed rule would amend one of the first health claims authorized in 1993 through the Nutrition Labeling and Education Act of 1990 for the relationship between calcium intake and osteoporosis. The proposal would amend this existing health claim by allowing for claims of a reduced risk of osteoporosis with the consumption of both calcium and vitamin D. The proposed rule also would eliminate certain requirements that were a part of the required claim language in the existing calcium and osteoporosis health claim. However, FDA is not changing its conclusion that there is still significant scientific agreement to support claims for calcium intake and reduced risk of osteoporosis. "Osteoporosis is a significant public health problem, especially for women," said Kathleen Uhl, MD, assistant commissioner of FDA's Office of Women's Health. "This new labeling should assist consumers to select foods - and women especially since women do the majority of food shopping in the US - that provide adequate calcium and Vitamin D intake and hopefully prevent the occurrence of osteoporosis in themselves and their family members." FDA's decision to amend the existing health claim is based on the agency's review of the publicly available scientific evidence, which included the 2004 Surgeon General's report on Bone Health and Osteoporosis and the 2000 NIH Consensus Statement on Osteoporosis, Prevention, Diagnosis and Therapy. Specifically, FDA is proposing to change the calcium and osteoporosis health claim to: Add a claim for calcium and vitamin D together and a reduced risk of osteoporosis. Shorten the claim language by: Dropping the reference to sex, race, and age since the benefits apply to both sexes at all ages and race categories. Dropping the need to identify the mechanism by which calcium reduces the risk of osteoporosis. Dropping the requirement that the claim state that there are limits to benefit of calcium intakes above 200% of the Daily Value.

New OTC Pain Medicine Rules from the FDA

FDA Proposes Labeling Changes to Over-the-Counter Pain Relievers The Food and Drug Administration (FDA) today proposed to amend the labeling regulations on over-the-counter (OTC) Internal Analgesic, Antipyretic, and Antirheumatic (IAAA) drug products to include important safety information regarding the potential for stomach bleeding and liver damage and when to consult a doctor. OTC IAAA drug products, commonly known as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, naproxen and ketoprofen, are used to treat pain, fever, headaches, and muscle aches. To help ensure safe use of OTC products, and to provide consumers with the labeling necessary for them to make more informed medical decisions, FDA is proposing the following label changes: For Products Containing Acetaminophen To require new warnings which would highlight the potential for liver toxicity, particularly when using acetaminophen in high doses, when taking more than one product with acetaminophen, and when taken with moderate amounts of alcohol; To require that the ingredient acetaminophen be prominently identified on the product's principal display panel (PDP) of the immediate container, and the outer carton (if applicable). For Products Containing NSAIDs To require new warnings for products that contain an NSAID which would highlight the potential for stomach bleeding in persons over age 60, in persons who have had prior ulcers or bleeding, in persons who take a blood thinner, when taking more than one product containing an NSAID, when taken with moderate amounts of alcohol, and when taking for longer time than directed; and To require that the name of the NSAID ingredient and the term "NSAID" be prominently identified on the product's PDP of the immediate container and the outer carton (if applicable). The new labeling would be required for all OTC drug products that contain only an IAAA ingredient, as well as for products that contain an IAAA ingredient with other ingredients, such as cold symptom relievers. Consumers may also be taking IAAA ingredients in their prescription medications, which makes it important to alert them of the contents of their OTC medications, so they do not take too much of an IAAA ingredient. FDA based its proposal for labeling changes on previous Advisory Committee discussions, recommendations, and public comments (see http://www.fda.gov/ohrms/dockets/ac/cder02.htm#NonprescriptionDrugs) and a review of the scientific literature. A number of manufacturers of OTC internal analgesic drug products already have voluntarily implemented labeling changes to identify these potential safety concerns. Comments on the current proposal, to be published in the December 26, 2006 Federal Register may be sent to Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to: (http://www.fda.gov/ohrms/dockets/default.htm ).

Recommended prevention of Avian Flu - WHO

In a nonpandemic situation, recommendations for treatment of patients with confirmed or strongly suspected infection with avian influenza A (H5N1) are as follows: Patients should receive oseltamivir treatment as soon as possible (strong recommendation). Clinicians might administer zanamivir (weak recommendation). If neuraminidase inhibitors are available, clinicians should not administer amantadine alone as a first-line treatment (strong recommendation). If neuraminidase inhibitors are not available and especially if the virus is known or likely to be susceptible, clinicians might administer amantadine as a first-line treatment (weak recommendation). If neuraminidase inhibitors are available, clinicians should not administer rimantadine alone as a first-line treatment (strong recommendation). If neuraminidase inhibitors are not available and especially if the virus is known or likely to be susceptible, clinicians might administer rimantadine as a first-line treatment (weak recommendation). If neuraminidase inhibitors are available and especially if the virus is known or likely to be susceptible, clinicians might administer a combination of neuraminidase inhibitor and M2 inhibitor (weak recommendation). This should only be done in the context of prospective data collection. High-risk exposure groups should receive oseltamivir as chemoprophylaxis continuing for 7 to 10 days after the last known exposure (strong recommendation). In moderate-risk exposure groups, oseltamivir may be administered as chemoprophylaxis, continuing for 7 to 10 days after the last known exposure (weak recommendation). Low-risk exposure groups should probably not receive oseltamivir for chemoprophylaxis (weak recommendation). Additional recommendations address prophylaxis and treatment with other agents and in specific groups including pregnant women. "The greatest barrier to implementation results from the limited availability of the neuraminidase inhibitors and the lack of resistance data," the panel concludes. "Emergence of novel human influenza A viral subtypes or a change in the pathogenicity or transmissibility of H5N1 virus strains, availability of new pharmacological agents, or important clinical research data on H5N1 will necessitate an update of these guidelines. In view of the potential for rapid change in the situation in relation to avian influenza, WHO will continue to monitor these factors carefully before deciding when to revise or update the recommendations. Lancet Infect Dis. 2007;7:21-31.