Calcium to Prevent Osteoporosis - Take More!

The totality of the evidence indicates that high calcium intake is important both for prevention and management of osteoporosis, and recent negative trials do not refute the much larger body of positive studies. The challenge is not to haggle over exactly how much is enough but, as the Surgeon General's report on osteoporosis put it, to recognize that current intake is far below optimal values. It is imperative to take action to augment calcium intake, both in the general population and particularly in persons being treated for osteoporosis. For many patients, calcium supplements are the most appropriate choice to ensure adequate intake. A number of different calcium compounds are used in supplements; the 2 main forms are calcium carbonate and calcium citrate. Although absorption of calcium citrate is similar to calcium carbonate, a calcium carbonate supplement contains 40% calcium vs the 21% found in calcium citrate.[52] Because formulations may contain different amounts of calcium, the number of tablets needed to obtain a recommended dose may vary. Figure 6 depicts the amount of calcium found in common compounds. Patients often erroneously believe that they are obtaining sufficient calcium through their diet. However, it is known that the median calcium intake in postmenopausal women in North America is substantially below existing recommendations.[11] Because milk and milk products provide the majority of dietary calcium in the United States, if a person is lactose-intolerant, a vegan (consuming no animal products), or avoids dairy products for other reasons, it may be especially challenging to obtain adequate amounts of calcium solely through diet.[50] In addition to being aware of the amount of dietary calcium they are ingesting, it is important that patients understand that absorption from foods can be affected by a number of factors, many of which have already been well described. These include age, vitamin D, pregnancy, and plant substances in the diet. Oxalates (found in chocolate and spinach) and phytate (found in whole grains) are among dietary substances that impair absorption. Therefore, 8 cups of spinach are needed to obtain the same amount of calcium obtained from an 8-ounce serving of milk or 1 cup of yogurt, which contain calcium in an easily absorbable form.[51] Vitamin D. Although vitamin D status has been discussed as a potential confounder of results in calcium studies, the importance of vitamin D in its own right must also be emphasized. It has long been recognized that vitamin D is important for calcium absorption, and recent studies have demonstrated that absorption efficiency increases with improving vitamin D status up to serum 25(OH)D levels of about 80 nmol/L (32 ng/mL).[43,44] Postmenopausal women, as reported in many studies, tend to have average serum 25(OH)D values ranging from 50 to 55 nmol/L (20 to 22 ng/mL)[43,45] and are therefore absorbing the calcium they ingest with reduced efficiency. Protein. As with vitamin D, protein plays an important role in its own right. Although North Americans are considered to consume generous amounts of protein it is also true that many fragile elderly individuals have low protein intake. If these same individuals are our osteoporosis patients, then they will probably not respond well to pharmacotherapy until their nutritional status is repaired. If deficient in calcium, vitamin D, and protein, many will be unresponsive to monotherapy, whether nutritional or pharmacologic. This is seen most obviously in patients with hip fracture, whose outcomes have been shown to improve dramatically with protein supplementation.[46] Exercise. Bones are designed to bear loads and to resist mechanical forces. Maintenance of adequate bone mass requires continued mechanical loading. Nutrition alone may slow the progress of disuse bone loss, but it will not block its full, ultimate expression. Optimal exercise regimens are uncertain, but impact loading appears to be more osteotrophic than, for example, weight lifting or swimming. In general, patients with osteoporosis need to maintain as vigorous an exercise program as is compatible with their bone fragility status. Good online sources of information for patients about calcium and or bone health include the National Institutes of Health, Office of Dietary Supplements;[51] American Osteoporosis Foundation;[54] and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.[53]

All About Sleeping Better

Insomnia: Once you and your doctor have ruled out any medical problems that may be causing your insomnia, you might try self-care methods. "Good sleep hygiene" refers to practices you can follow to help ensure adequate, quality sleep. For good sleep hygiene, try to do the following: Stick to a regular bedtime schedule. Get out of bed at the same time each morning, even if it's a weekend or holiday. Avoid napping during the day. Avoid stressful activities and vigorous exercise for two hours before going to bed. Before going to bed, try relaxation techniques, such as deep breathing, yoga, or meditation. Make sure your bedroom is dark, quiet, and cool. Use earplugs or eye shades if needed. Leave the bedroom if you can't sleep. Go into another room and read or do something relaxing and quiet. Exercise regularly. Avoid substances that contain caffeine (such as coffee, tea, soft drinks, or diet pills). Avoid alcohol and nicotine before bed. Snoring: If your snoring is light, try these self-care techniques: Sleep on your side. Avoid alcohol, and don't smoke. Avoid sleeping pills and other sedatives. Also, seek treatment for any allergies or nasal obstructions you may have. Sleep apnea: Weight loss can improve but may not adequately treat sleep apnea. Avoiding alcohol and sleeping pills can also help. You may want to talk to your doctor about a technique called continuous positive airway pressure (CPAP). With CPAP, each night you wear a mask that increases the air pressure inside your throat. This prevents your airway from becoming too narrow and may allow you to sleep without interruption. Except in very carefully selected cases, surgery does not adequately treat anything more than the mildest degrees of sleep apnea (though it may be more effective for troublesome snoring). A dental brace that holds your lower jaw forward during sleep is an increasingly available option for snoring and mild to moderate sleep apnea. Pregnancy and sleep: Pregnant women who experience insomnia during pregnancy may find relief by taking afternoon naps, drinking warm milk, or taking a warm (not hot) bath before bedtime. Exercise during the day should help too. Expectant mothers may find it more comfortable to sleep on their side, with pillows supporting their head, abdomen, and topside knee. Women who are pregnant should not take sleeping pills or herbal sleeping remedies without talking with their doctor first. Narcolepsy: Often, naps help relieve narcolepsy but cannot be relied on exclusively. Your doctor may prescribe stimulants (such as Ritalin or dextroamphetamine) to make you more alert. Antidepressants may be used to treat cataplexy (drop attacks) or sleep paralysis, if present. Restless leg syndrome: Cutting your caffeine intake may help. Other self-help measures may include a warm bath or relaxation exercises before bed. Hot or cold packs on your legs may provide relief. Several effective medications are available. Restless leg syndrome is a very treatable condition. Nightmares/night terrors: If your child has a nightmare or night terror, the best medicine is comfort. If the dreams reoccur frequently, talk with your child's doctor about the problem. Age: The lighter sleep patterns of older adults can sometimes lead to sleep problems. However, studies show that older adults who exercise and keep active sleep better than those who don't. Elderly people who don't sleep well at night may find afternoon naps helpful. However, excessive naps will disrupt sleep at night. Getting adequate light during the day, particularly in the morning, is important. Lifestyle: You'll sleep better if you have good sleep hygiene and avoid caffeine, alcohol, nicotine, and heavy meals before bed. Regular exercise can improve sleep, as long as the exercise is performed at least two hours before bedtime. Medication: If you think prescription or over-the-counter medication may be causing your sleep problems, talk with your doctor. You may need to have your medication dose adjusted or may need to take a different kind of medication. Depression and anxiety: If depression or anxiety is keeping you up for more than a few nights, talk to your doctor about treatment. Heart failure and lung problems: If you experience breathlessness when you lie down to sleep or awaken in the night feeling breathless, you should see your doctor. You could have problems with your heart or lungs.

Hearing Loss and Aides

Technological advances in hearing aids and HATS have expanded the range of options available to improve the success of a device use. Today's hearing aids differ significantly from their analog predecessors because the application of digital signal processing has permitted many adaptive and/or automatic features. In the past decade, hearing instrument technology has developed to the point that digital hearing aids now constitute nearly 90% of all hearing aid sales in the U.S.[21] This growth has permitted decreases in the cost of digital technology so that digital hearing aids now span the range from entry-level prices to high-end pricing, thus allowing all users the option of digital technology. Included in the benefits of digital hearing aids are improved sound quality; multiple listening programs for different listening environments; advanced noise reduction strategies; acoustic feedback reduction; compatibility with remote control options; and flexibility in manipulation of the frequency, compression, and gain ( Table 1 ). These developments allow the audiologist considerable flexibility in choosing appropriate technology for the varied needs of older adults. Such features as automatic function of the telecoil (a hearing aid component for use with the telephone or for coupling to HATS) and multiple programs ensure that even those with limited manual dexterity or cognitive impairments can wear a device that optimizes performance across a broad range of listening environments. It is no longer necessary to find the switch or remember to return to a listening program when the conversation has ended for effective telephone use. Difficulty understanding speech amid noise is a common complaint for hearing aid users. Directional microphone technology has advanced to optimize the directional responsiveness of the hearing aid microphone in order to reduce the level of noise when the noise source is from an angle that is behind or beside the hearing aid user. Automatic directional systems are intended to accurately switch between directional and omnidirectional modes, and this option is available even in the lower-priced entry-level digital devices.

New Cardiopulmonary Resuscitation Guidlines (CPR)

CPR consisting of chest compression plus mouth-to-mouth ventilation is a major element in the chain of survival for people with cardiac arrest. However, although bystander CPR improves the likelihood of survival, it is attempted in less than one third of patients who collapse, partly due to the reluctance of bystanders to undertake mouth-to-mouth ventilation. In CPR guidelines, according to the current authors, cardiac-only resuscitation by bystanders is recommended in dispatch-assisted resuscitation or if a rescuer is unwilling or unable to do mouth-to-mouth ventilation, but this technique is not generally known or taught to the public. One study has shown that cardiac-only resuscitation results in better survival without neurologic impairment.

Saline Nasal Irrigations for Chronic "Sinus" Symptoms

Nasal irrigation previously has been demonstrated to be an effective, safe, and well-tolerated means to treat frequent or chronic rhinosinusitis. The current authors reported results from a randomized controlled trial of 6 months of therapy with 2% saline nasal irrigation vs usual care in the December 2002 issue of the Journal of Family Practice. The authors found that the use of saline was associated with fewer sinus symptoms, improved sinus-related quality of life, and reduced use of antibiotics and nasal sprays. A follow-up study to this trial demonstrated that participants in the original randomized trial continued to use nasal irrigation as a successful modality to treat rhinosinusitis. Given the apparent clinical success of nasal irrigation for frequent or chronic rhinosinusitis, the authors sought to examine qualitative data regarding the everyday benefits and drawbacks of irrigation from study participants. Their results are summarized in the "Study Highlights." Study Highlights Participants from the researchers' primary study were invited to participate in structured 30-minute interviews to explore their experience with nasal irrigation for rhinosinusitis. Patients included in the original study had either 2 episodes of acute sinusitis or 1 episode of chronic sinusitis in the past year. In addition, participants reported a moderate-to-severe overall daily quality-of-life burden associated with rhinosinusitis. Participants randomized to receive nasal irrigation had an educational session that included lessons on rhinosinusitis and individual coaching on the practice of nasal irrigation. 28 of the original 35 subjects who received nasal irrigation agreed to participate in the interviews for the current study. Their clinical data were similar to the original cohort as a whole. 4 main content themes emerged from these interviews: Patients felt empowered in being able to access, monitor, and adjust treatment with nasal irrigation on their own. They were pleased to be less reliant on clinician visits and antibiotics. Patients were enthusiastic regarding the efficacy of nasal irrigation in reducing sinus symptoms and improving their quality of life. Many subjects reported improvement within the first or second use of nasal irrigation. Patients cited fear of having water in the nasal cavity, initial unpleasant sensation of water in the nasal cavity, having to learn how to perform nasal irrigation effectively, the time to perform nasal irrigation, and occasional mild adverse effects as potential barriers to the use of nasal irrigation. Adverse effects included saline drainage and nasal burning, but these events were not strong enough to stop the practice of nasal irrigation. Patients noted that the initial education session, particularly individual coaching on the practice of nasal irrigation, was effective in overcoming many of the barriers to the use of nasal irrigation. In addition, their experience at home with adjusting the schedule, salinity, and temperature of nasal irrigation allowed for effective and well-tolerated treatment. Pearls for Practice Nasal irrigation with saline solution has been demonstrated to improve symptoms of rhinosinusitis, sinus-related quality of life, and the use of other medications for rhinosinusitis. This treatment appears effective over the long term. The current study demonstrates that patients with frequent or chronic rhinosinusitis may have some initial trepidation regarding the use of saline nasal irrigation, but some coaching on how to use irrigation along with self-adjustment of therapy allowed patients to overcome potential barriers to treatment. Patients find the use of nasal irrigation empowering and effective.

DHEA In Older Men

Because blood levels of dehydroepiandrosterone (DHEA) and testosterone decline with age, some people believe that DHEA and testosterone supplementation can reverse the effects of aging. This hypothesis was examined in a double-blind, placebo-controlled, randomized trial that included 87 men and 57 women aged 60 or older. Baseline levels of DHEA-S (the sulfated form of DHEA) in both sexes, and baseline levels of bioavailable testosterone in men, were required to be below the 15th percentile for normal young adults. Men received a DHEA tablet (75 mg) daily, a transdermal testosterone patch (5 mg daily), or double placebo; women received a DHEA tablet (50 mg) or placebo. After about 2 years of follow-up, no differences were noted between the active-drug and placebo groups in physical performance (i.e., aerobic capacity and muscle strength) or in quality of life as measured on a validated questionnaire. In the active-drug groups, small increases in bone density were noted only at the femoral neck in men and at the distal radius in women. These changes were much smaller than those typically seen with bisphosphonate drugs. No significant adverse events occurred. Comment In this well-done randomized trial, supplementation with DHEA or low-dose testosterone conferred no obvious benefits to older adults. Based on these and previous results, the authors and an editorialist conclude that DHEA and testosterone should not be used as anti-aging supplements. The editorialist also believes that DHEA should be treated as a regulated drug and not as a dietary supplement. — Allan S. Brett, MD

Quinine Drugs Removed from Market

FDA Removes Unapproved Quinine Drugs From Market Yael Waknine Medscape Medical News 2006. © 2006 Medscape December 13, 2006 — The US Food and Drug Administration (FDA) has ordered the removal of unapproved drug products containing quinine, citing serious safety concerns and deaths associated with their use. The action is part of a larger effort to remove all unsafe, unapproved drugs from the market.Since 1969, the FDA received 665 reports of serious adverse events (including 93 fatalities) associated with quinine use, according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program. Serious adverse events have included cardiac arrhythmias, thrombocytopenia, and severe hypersensitivity reactions; potentially serious interactions with other drugs can also occur.The FDA notes that only one quinine product (Qualaquin, made by Mutual Pharmaceutical Company, Inc) is currently approved by the FDA. Although indicated only for the treatment of uncomplicated Plasmodium falciparum malaria, the drug is often prescribed to treat leg cramps and similar conditions despite drug label warnings advising that the risks associated with its use in this setting outweigh potential benefits.Unapproved quinine drug products are marketed without these drug label warnings, which increases the risk for their misuse and potential consumption of doses that have not been reviewed or approved by the FDA. Because of its narrow therapeutic index, quinine must be used carefully; dose modifications and/or close monitoring may be required for patients with hepatic or renal impairment. Under the FDA order, all manufacturing of these products must cease within 60 days. However, some previously shipped merchandise may remain on pharmacy shelves for a short time. Consumers have been advised to contact their healthcare provider with any questions or concerns regarding their use of unapproved quinine products.Adverse events potentially related to quinine therapy should be reported to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

New Research on Care/Prevention of Chronic Diseases

Introduction Chronic disease prevention and management were hot topics receiving daily attention at the 2006 American Academy of Family Physicians (AAFP) Scientific Assembly. A comprehensive evidence-based lifestyle management plan for cardiovascular disease prevention was offered by Steven Masley, MD, FAAFP.[1] Alvin Lin, MD, FAAFP, and Kay M. Nelsen, MD, discussed how "good is not good enough" in our current approach to chronic disease care and offered new, more rigorous targets for physicians and patients alike.[2] Evidence-Based Lifestyle Changes for Cardiovascular Disease Guidelines for patients and physicians from the American Heart Association (AHA), the American Diabetic Association (ADA) and other organizations advocate lifestyle change including diet, exercise, smoking cessation, and other behaviors to improve cardiovascular (CV) risk. The number of research studies which pinpoint and specify the rationale for making changes, and the risk reduction associated with each lifestyle change, has grown significantly. This body of literature empowers physicians to better counsel patients on prevention of adverse CV events, particularly stroke and myocardial infarction. Dr. Masley reviewed the mechanism for plaque formation and rupture as the basis for a paradigm switch from coronary procedures such as angioplasty to diet change. Despite data supporting prevention, the United States spent $200 billion on CV therapies in 1998 with only 6% expended on preventive strategies for patients.[3] Yet interventional cardiology was associated with a failure rate of 40%, preventing only 1 of 30-40 deaths, and improving only 1 of 30-40 CV events.[3] The procedures also carried the risks for loss of cognitive function, death, and stroke.[4] Indications for revascularization procedures should only be angina and restoration exercise capacity. Among risk factors identified for CV disease, the top 5 are: Cholesterol; Diabetes mellitus (DM); Smoking; Hypertension; and Obesity. Ethnic differences exist for each risk factor[5]; for example, obesity and hypercholesterolemia have a higher prevalence among blacks and Hispanics compared with Asians. Dr. Masley suggested that exercise treadmill testing is useful for predicting CV risk because exercise capacity is a powerful predictor of mortality.[6,7] Class I evidence for stress testing indicated for evaluation of includes: Known CV disease; Suspected angina; Diabetics embarking on an exercise program; and An occupation that affects public health. Measures of cardiac fitness include the 1-minute heart rate recovery and the blood pressure (BP) response. Plaque assessment using carotid intimal media thickness is another tool that can help track responses to lifestyle change or medication.[8] The following 10 lifestyle steps were described by Dr. Masley to reduce adverse CV events: Step 1: Reduce low-density lipoprotein (LDL) cholesterol using a combination of dietary measures such as adding soy and garlic,[9] switching from saturated and hydrogenated fats to unsaturated fats, increasing plant sources of omega-3 fats,[10] and increasing monounsaturated nut intake of walnuts, almonds, and pecans[11,12] before medications are considered. Step 2: Improve total cholesterol/high-density lipoprotein cholesterol (TC/HDL) and triglyceride/HDL cholesterol (TG/HDL) ratios to reverse the metabolic syndrome epidemic. Increasing HDL levels may be achieved with prolonged regular aerobic exercise of no less than 30-45 minutes daily[13] and moderate alcohol intake of 1-2 drinks daily.[14,15] A modest increase may be seen with garlic,[16] onion (3% to 5% improvement), and soy (up to 5% improvement)[17] intake. The type of carbohydrate eaten affects insulin levels and TC/HDL ratios, and glycemic load is more important than glycemic index.[18] Hence, a high-fiber intake of grains, beans, vegetables, and fruits has a beneficial effect, while consumption of fluffy whole wheat breads and potatoes can raise postprandial blood sugar levels. Step 3: Increase intake of beneficial foods. Follow diets, such as the Mediterranean or Japanese diet, high in vegetables and fruits, fiber, olive oil, and soy[19,20]; the emphasis should be on adding healthy -- rather than eliminating unhealthy -- foods. More specifically, soy isoflavones (from, for example, edamame beans) are associated with possible reduction of clot formation[21,22] and improved endothelial function.[23,24] Dark cocoa reduces clotting and is a potent antioxidant, thereby suppressing LDL oxidation and, possibly, lowering plaque formation.[25] Step 4: Change type of fat intake to nuts and olive and canola oils, but remain mindful of calories associated with high nut consumption. One handful of walnuts has 280 calories, but if eaten before a meal can help to induce satiety and reduce overall caloric intake.[26] Saturated fats should be avoided because of: Increased clot formation; Weight gain; and Increased LDL cholesterol. Trans fats in margarines and processed foods should be avoided and lean proteins (chicken and turkey) should be selected over red meats. Step 5: Reduce LDL oxidation by: Eating at least 5 servings of fruits and vegetables daily, especially the most colorful produce (like blueberries, pomegranates, and red and black beans)[27]; and Adding garlic[28] and spices,[29] particularly capsaicin and curcumin from chili and turmeric, respectively. Step 6: Decrease clotting and CV events using: Omega-3 fats; Garlic; Moderate alcohol; and A baby aspirin for primary and/or secondary prevention of CV and cerebrovascular events, if there are no contraindications. Fish and seafood (which should be eaten 2-3 times weekly) are excellent sources of omega-3 fats; Dr. Masley's first-choice recommendations are: Salmon; Trout; Sardines; Mussels; and Oysters, followed by: Shellfish; Mahi mahi; and Halibut. His choices reflect lower mercury levels of less than 2 ppm; intake of big-mouthed fish, such as yellow-tail tuna, increases exposure to higher mercury content. Flax, soy products, nuts, green leafy vegetables, canola oil, and fish oil supplements also contain omega-3 fats. The dosing of omega-3 depends on its indication: 300 mg daily for health maintenance; 3-4 g daily for hypertriglyceridemia; 2-4 g for anti-inflammatory purposes or for disc herniation; and 1-2 g for arrhythmias. Fish oil supplements should be selected on the basis of independent testing for heavy metals, low levels of lipid peroxides (they should not taste fishy or rancid), and dosed to minimize risk for bleeding and drug interactions. Step 7: Enhanced arterial function and BP is best achieved by 30-60 minutes of moderate activity for 6 days a week burning at least 2000 kcal weekly, and strength training 2-3 times weekly working at least 8-12 body parts and targeting blood pressure (BP) at 110/70 mm Hg (below pre-hypertensive levels).[30] Salt intake should be limited to less than 2400 mg daily, while calcium and magnesium should be maintained at 100 mg and 500 mg daily respectively. Step 8: Judicious use of supplements is advised because of variability in evidence for efficacy and the lack of standardized manufacturing guidelines. Dr. Masley recommended adequate intake of: Folic acid 400 mcg daily (diet plus supplement); Vitamin B6 -- 10-25 mg daily; Vitamin B12 -- 10-1000 mcg; and Phytosterols from plant foods. Evidence for using coenzyme Q10, hawthorne, and acetyl-L-carnitine is inconclusive and these are not currently recommended for cardiac health. Step 9: Stress management should directly address adequate sleep (at least 7 hours daily) and restful and relaxing activities such as meditation, yoga, and deep prayer. Step 10: Success at making lifestyle changes is linked to: Physician attention to patient beliefs; Limitations and goals; and Venues for offering intensive and effective lifestyle change in practice, including the group medical visit model specifically focused on CV targets, regular chart review, and documentation of patient progress. Management of Chronic Disease: When Is Good Not Good Enough? Drs. Lin and Nelsen discussed how chronic diseases are a major cause of disability in the United States, reviewing the major causes of death and morbidity[2]: Childhood obesity; Arthritis; Adult DM; Hypertension; and Hypercholesterolemia. They presented data that provide physicians with specific and more rigorous goals and endpoints for the control of DM, cholesterol, and BP. As Dr. Nelsen explained, global focus of organizations such as the World Health Organization, United Nations, and the World Bank continues to be on infectious rather than chronic diseases. Despite the change in chronic disease management from acute hospital admission to ambulatory care delivery, the use of information systems and team-based healthcare, the goals of continuity of care, service integration, and patient education provided through patient-centered care are far from being reached worldwide. The burden of chronic diseases continues to rise with 29 million deaths worldwide in 2002 from[31]: CV disease; Cancer; Chronic respiratory disease; and DM. According to an important trial, "a combination of personal and non-personal health interventions could lower the global incidence of CV events by as much as 50%.[32]" Government action to reduce salt content of processed foods is an example of a non-personal health intervention. Case in Point: Diabetes Mellitus Twenty-one million Americans were diagnosed with DM in 2005 and 10 million over 60 years have DM currently. Only 1 out of 5 Healthy People 2000 goals were met for the US population namely, a small 3% reduction in amputations from DM.[33,34] The goals related to DM that have not been met are reduction of: Disease incidence; Renal disease; and Blindness. Only one half of diabetics are taking proper medications.[35] Health disparities in DM management persist, and although 90% of patients with DM see physicians, they are not well monitored for: Hemoglobin A1c (HbA1c) levels; Self glucose testing; Annual urinary albumin screening; and Foot care. Health education occurs for less than 50%.[36] Data from a meta-analysis propose HbA1c goals as low as possible, suggesting that there is no threshold that is too low.[37] In one study, for every 1% drop in HbA1c there was a 21% decrease in all-cause mortality and adverse endpoints. Another study demonstrated a 28% increased risk for death for every 1% increase in HbA1c value, regardless of BP, cholesterol level, body mass index, and smoking status.[38] The Lower the Better Even in those without DM, lower HbA1c is associated with reduced CV and all-cause mortality. LDL cholesterol goals for DM have been well articulated by the AHA and the American College of Cardiologists with atheromatous regression and reduced CV mortality demonstrated at lower levels when LDL is lowered to 60 mg/dL.[39] Like HbA1c and LDL cholesterol in DM, BP control is now guided by the "lower is better" principle. Regardless of comorbidities including DM, lower levels of BP are associated with better outcomes of mortality and CV events. The risk for CV morbidity and mortality begins at a BP of 115/75 mm Hg, and for every increase in blood pressure of 20 mm Hg systolic or 10 mm Hg diastolic, the risk for CV events increases 2-fold.[40] Conversely, every 2-mm Hg drop in systolic BP translates into a 10% drop in stroke incidence and a 7% drop in CV events. Some data are slightly more hopeful, including a study showing that diabetes processes of care (such as eye and foot exams, measurement of microalbuminuria, diabetic education, and vaccinations) and intermediate outcomes (for example, HbA1c and LDL cholesterol) have improved nationally in the United States in the past decade.[41] This same trial, however, showed that: 2 in 5 persons with diabetes still have poor LDL cholesterol control; 1 in 3 persons still has poor BP control; and 1 in 5 persons still has poor glycemic control. Summary Drs. Lin and Nelsen concluded that physicians need to be more aggressive with all lifestyle strategies that lead to reduced HbA1c, LDL cholesterol, and BP in both diabetic and nondiabetic patients. For diabetic patients, target HbA1c should be as low as possible. For LDL cholesterol, diabetics should aim for levels below 70 mg/dL. Patients with hypertension should be controlled to levels at or below 115/75 mm Hg.

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