Friday, April 16, 2010

Urinary Dipstick Screening No Help When Patients Don't Have Pain

From Reuters Health Information

NEW YORK (Reuters Health) Apr 14 - Urinary dipstick and microscopy testing are not good at finding urinary tract infection when pain is not one of the symptoms, UK researchers report in the May issue of The Journal of Urology.

If international guidelines that recommend dipstick screening are followed, "many patients with urinary tract infection will go undiagnosed, which is no small matter given the prevalence of lower urinary tract symptoms," they said.

Last month, a separate team of researchers reported that urine dipsticks were ineffective in screening children for kidney disease. (See Reuters Health story of March 15, 2010.)

"I think that we must acknowledge serious deficiencies in our standard methods for screening out urinary infection," Dr. James Malone-Lee, senior author of the current study, told Reuters Health by e-mail.

Dr. Malone-Lee, of University College London, and colleagues obtained mid-stream urine samples from 508 patients and catheter urine samples from another 470 patients. These patients had symptoms such as frequency ("overactive bladder") or incontinence, but none of them had pain or urgency.

Using the patients' urine plus midstream samples from 42 healthy volunteers, the researchers compared leukocyte esterase, nitrite dipstick, and urine microscopy with routine urine culture (seeking 100,000 colony-forming units per mL).

Compared to standard culture of midstream urine, sensitivity and specificity, respectively, were 56% and 66% with leukocyte esterase, 10% and 99% with nitrite dipsticks, and 56% and 72% with microscopy.

In catheter specimens, sensitivity and specificity, respectively, were 59% and 84% with leukocyte esterase, 20% and 79% with dipsticks, and 66% and 73% with microscopy.

With standard culture, 15% of catheter specimens were positive. The proportion of positive cultures rose to 29% when the researchers used an enhanced culture method that could detect as few as 100 colony-forming units per mL.

The authors point out several "matters of considerable concern." For one thing, they say, the difference between the midstream and catheter urine data suggests the midstream samples were contaminated, which would mean the test results are unreliable.

Also, the fact that the rate of positive cultures nearly doubled with the more sensitive culture raises concerns over the accuracy of routine culture at 100,000 colony-forming units per mL.

Finally, they point out, nearly half of patients with overactive bladder had positive urine tests, which "indicates the need for closer scrutiny of the etiology" of this condition.

Based on these and other considerations, the investigators call for the establishment of "valid, evidence-based criteria for diagnosing urinary tract infections in patients with lower urinary tract symptoms."

Summing up, Dr. Malone-Lee added, "My practice has changed so that I pay greatest attention to the patients' symptoms, what they think is going on, and variations under treatment."

"I admit to a lifelong skepticism about the supremacy of technology over the ability of the human to reveal the nature of disease, if given the opportunity," he concluded.

J Urol 2010;183:1843-1847.

Despite Concerns, Soy Probably Safe for Thyroid

From Reuters Health Information

By Amy Norton

NEW YORK (Reuters Health) Apr 14 - Despite some concerns to the contrary, the soy-based dietary supplement genistein may not harm postmenopausal thyroid function, a new study finds.

Genistein is a type of soy isoflavone, a plant chemical that is structurally similar to estrogen. In a 2007 clinical trial, Italian researchers found that genistein supplements, along with calcium and vitamin D, appeared to help boost bone mass in postmenopausal women.

In this latest study, the researchers evaluated data from the same clinical trial -- this time looking at whether the genistein supplements had any effects on the women's thyroid function. The question stems from lab research showing that genistein and other isoflavones may decrease thyroid-hormone production.

The earlier research had suggested that isoflavones can interfere with iodine, explained Dr. Francesco Squadrito of the University of Messina, the senior researcher on the study.

However, he told Reuters Health by email, those studies used genistein doses that were 10 to 250 times higher than the doses used in his team's clinical trial -- 54 mg/day.

Dr. Squadrito and his colleagues found that among 77 study women followed for three years, those who used the genistein supplement showed no overall differences in thyroid function compared with women who were given a placebo.

The findings appeared online March 31 in the Journal of Clinical Endocrinology and Metabolism (http://jcem.endojournals.org/cgi/content/abstract/jc.2009-2779v1).

According to Dr. Squadrito, it is not surprising that studies would find thyroid effects of very high doses of genistein. However, he said, women are unlikely to consume such levels from soy-protein products or from soy foods.

As far as thyroid function is concerned, he said, "it is possible to conclude that genistein therapy is safe in postmenopausal women -- at least at the dose of 54 mg a day."

Soy contains several types of isoflavones, however, and more studies are needed to establish the safety of those compounds, according to Dr. Squadrito and his colleagues.

J Clin Endocrinol Metab 2010.

Thursday, April 8, 2010

Case Review in Adolescent Acne: Multifactorial Considerations to Optimizing Management

From Dermatology Nursing
Janet Selway

Posted: 03/30/2010; Dermatology Nursing. 2010;22(1) © 2010 Jannetti Publications, Inc.

Abstract
The management of pediatric and adolescent acne requires multifaceted considerations revolving around the patient, parents, and appropriate treatment. The following case report represents a typical scenario exemplifying the key role of the dermatology nurse practitioner in optimizing successful acne management outcomes.

Introduction
Acne vulgaris is common among adolescents; most, if not all, personally experience its impact or are directly involved with individuals who have the condition. Effects of acne may extend beyond the physical lesions; psychological and social implications associated with the condition can be equally severe. The management of acne is multifactorial and, fortunately, a number of therapeutic options are available. Nevertheless, careful consideration must be made, particularly among adolescents, to properly align appropriate treatment to optimize outcomes.

The role of nurse practitioners (NP) is particularly important, as the need for continual patient education, motivation, and followup can sometimes lapse in a typically busy clinical practice. Addressing patient concerns, evaluating treatment efficacy and tolerability, and monitoring adherence to treatment are critical components of acne management. The following case study represents a characteristic scenario where all of the aforementioned components play a considerable role in the NP's contributions to successful management.

Treatment Options
The key to successful acne treatment is matching an effective, manageable, and affordable plan with an individual. This is especially important for preteens and adolescents, who have the most difficulty complying with long-term plans (Eichenfield, Fried, Taylor, Paller, & Theos, 2005). Treatment possibilities for acne vulgaris include topical agents, systemic antibiotics, hormonal agents, and isotretinoin (Strauss et al., 2007).

Topical Treatment
Topical treatments target mild-to-moderate acne, which includes inflammatory and noninflammatory forms (Berson et al., 2003). According to American Academy of Dermatology guidelines, effective topical treatments include, among others, retinoids, BP alone, and combinations of BP with clindamycin or erythromycin (Strauss et al., 2007). Topical antibiotics alone are also effective treatments but, like systemic antibiotics, are associated with resistance. Less-effective options include salicylic acid, azelaic acid, sulfur, resorcinol, sodium sulfacetamide, aluminum chloride, and zinc. Simultaneous application of multiple topical agents can be effective, but agents should not be applied simultaneously unless compatible (Strauss et al., 2007). BP oxidizes and sunlight degrades topical retinoids; however, this is not true of adapalene (a second-generation topical retinoid) or microsphere formulations of tretinoin (Martin, Meunier, Montels, & Watts, 1998; Nyirady, Lucas, Yusuf, Mignone, & Wisniewski, 2002). Products with topical or oral clindamycin are contraindicated in patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis (sanofi-aventis U.S. LLC, 2007).

Topical retinoids (tretinoin, adapalene, and tazarotene) reverse abnormal desquamation and interfere with microcomedone formation (Berson et al., 2003). Topical retinoids alone are indicated for noninflammatory acne because of their anti-inflammatory properties (Strauss et al., 2007). Adapalene is a less-irritating alternative to topical tretinoin (Bershad, 2008). Tazarotene, a second-line retinoid, is a teratogen (Pregnancy Category X) and prohibited for use in women of child-bearing potential (Bershad, 2008).

Benzoyl peroxide, a topical bactericidal agent available in a wide variety of formulations and concentrations, is a potent inhibitor of P. acnes and a weak keratolytic. Its oxidizing properties can bleach hair and colored fabrics (Berson et al., 2003).

Another topical antibacterial is dapsone (Aczone®). Topical antibiotics have the benefit of minimal side effects. However, because of potential resistance to P. acnes, they are more useful when used in combination with BP, since BP has been shown to minimize antibiotic resistance (Berson et al., 2003; Strauss et al., 2007).

Systemic Treatment
Systemic antibiotics are indicated for moderate-to-severe cases and treatment-resistant forms of inflammatory acne (Leyden, Del Rosso, & Webster, 2007). The most commonly prescribed antibiotics for acne are tetracycline, erythromycin, clindamycin, doxycycline, and minocycline (Tan & Tan, 2005). Systemic antibiotics are increasingly associated with bacterial resistance (Leyden et al., 2007; Strauss et al., 2007). Treatment guidelines indicate that minocycline is more effective than doxycycline (Strauss et al., 2007). Both are more efficacious than tetracycline. Oral erythromycin should be used only when tetracyclines cannot be used, such as in pregnancy or with allergies. When other antibiotics cannot be used, trimethoprim-sulfamethoxazole can be an effective alternative (Strauss et al., 2007).

Use of oral antibiotics (e.g., tetracycline, doxycycline, erythromycin, azithromycin) is typically associated with gastrointestinal irritation; long-term use of oral antibiotics may also induce vaginal candidiasis in women (Katsambas & Papakonstantinou, 2004). Doxycycline is more likely to induce photosensitivity reactions than the other commonly prescribed antibiotics (Strauss et al., 2007). Minocycline is more likely than doxycycline to induce hypersensitivity reactions, although these are rare. Long-term use of minocycline may cause cosmetically displeasing skin hyperpigmentation (Geria, Tajirian, Kihiczak, & Schwartz, 2009).

Hormonal agents are an alternative for females with acne and include estrogen-containing oral contraceptives and the oral anti-androgens spironolactone and cyproterone acetate. Hormonal therapy reduces sebum production caused by androgenic overstimulation and decreases androgen responsiveness of sebaceous glands (Berson et al., 2003).

Short-term, low-dose, oral corticosteroid therapy may provide temporary benefit for severe inflammatory acne and adrenal hyperandrogenism (Strauss et al., 2007).

Isotretinoin is indicated for severe recalcitrant nodular acne and in some patients with treatment-resistant acne resulting in physical scarring (Jones, 2007; Yan, 2006). Isotretinoin is the only systemic agent that has anti-inflammatory action, inhibits sebum production, and impacts follicular desquamation (Yan, 2006). Persons taking isotretinoin have been reported to experience mood disorders, depression, suicidal ideation, and suicide attempts, but no causal link has been established (Hull & D'Arcy, 2005; Strauss et al., 2007). Because isotretinoin is a teratogen, female patients of child-bearing potential may be treated with isotretinoin only if they are participating in the approved pregnancy prevention and management program known as iPLEDGETM (https://www.ipledgeprogram.com) (Jones, 2007; Strauss et al., 2007). Both male and female patients receiving isotretinoin must register with this program. The iPLEDGE program is a computer-based risk management program designed to eliminate fetal exposure to isotretinoin through a specially restricted distribution program approved by the U.S. Food and Drug Administration (FDA). The program's purpose is to ensure that no female patient starts isotretinoin therapy if pregnant or becomes pregnant while receiving isotretinoin therapy (Jones, 2007).

Other treatments include intralesional corticosteroid injections (Levine & Rasmussen, 1983). Data are limited regarding use of chemical peels, comedone removal, and herbal agents, and dietary restriction has no confirmed treatment benefit (Strauss et al., 2007).

http://www.medscape.com/viewarticle/718696

Wednesday, April 7, 2010

Chronic Stress and Memory Decline: A Classic Neuroendocrine Connection

Heads and Tales: The Neuroendocrine Blog of Alan R. Jacobs, MD
Alan Jacobs, MD, Neurology, 05:12PM Mar 23, 2010

A classic, not uncommon neuroendocrine syndrome is the relationship between chronic stress, the adrenal steroid hormone cortisol and both the size of the hippocampus and its memory functioning.

Some studies have looked at this, for example, by taking large groups of people and asking them to record how much stress they have experienced over time. These stressors could involve financial, occupational, marital and health related matters.
Subject also have their cortisol blood levels measured, their memory tested and the volume of their hippocampi measured by brain MRI. The hippocampus is part of the temporal lobes of the brain and is considered the "organ of short-term memory".

Studies like this find a range in the amount of stress each member of the group reports, with some experiencing low levels for a short time, others experiencing high levels over a long time, and the rest falling somewhere in between these extremes. And, members in the part of the group with the highest amounts of stress also have the highest amounts of cortisol in their bloodstreams, while members in the part of the group with the lowest amounts of stress have the lowest amounts of cortisol. If members of these two groups are compared on hippocampal size and memory scores, the high-stress/high cortisol group has smaller hippocampi and poorer memory scores and the low stress/ low cortisol group has larger hippocampi and better memory scores. Importantly, in studies such as -
Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing''s disease
Biological Psychiatry, Volume 46, Issue 12, Pages 1595-1602, M.Starkman et al - where the chronic stress goes away over time, then cortisol levels decline, the size of the hippocampus increases and memory scores improve back to normal.

Cortisol is a hormone that helps us deal with stress.
Over the short term it can actually sharpen memory functioning, presumably to allow us to better deal with the cause of the stress.
However, longer-term exposure to high levels of cortisol can hurt brain cells, especially those cells in the hippocampus.
This is thought to be caused by an overuse condition.
To protect themselves from burnout, the hippocampal cells seem to reduce their connections to each other so they are stimulated less.
When done by millions of cells the whole hippocampus shrinks a little and functions a bit less. The MRI and the memory tests can see this.

The good news is this syndrome is reversible if the chronic stress can be reduced.

Vibration Improves Balance in Fibromyalgia

From Reuters Health Information

Apr 02 - Tilt platform vibration helps women with fibromyalgia develop better balance, Spanish researchers have found.

Nearly half of fibromyalgia patients have poor balance, the authors note. While whole body vibration has been shown to improve balance, bone mass, and motor capacity in older people, until now there have been no controlled studies of intensive vibration therapy using a tilt platform in people with fibromyalgia.

A research team led by Dr. Narcis Gusi, from the University of Extremadura in Caceres recruited 41 women with fibromyalgia, ages 41 to 65, and randomized 21 to vibration therapy. The 20 women in the control group received usual care with no physical therapy.

The intervention involved 3 sessions per week for 12 weeks, with a tilt platform providing low-frequency (12.5 Hertz) anteroposterior vibration. Each session included a 10-minute warm-up of slow walking followed by six repetitions of vibration for up to 60 seconds each.

In the intervention group, two subjects quit because of scheduling conflicts and one because of acute pain in the legs, while two in the control group dropped out due to lack of interest.

In intent-to-treat analysis, the dynamic balance index improved by 36% in the vibration group but remained unchanged in the control group. Women with the worst balance and heaviest weight at baseline had the greatest improvements (p < 0.001).

In their March 16th online report in Arthritis Care & Research, the researchers say the tilt vibration therapy has the potential "to help reduce bone mass loss and improve strength and speed, which are critical for reacting and preventing stumbles and falls."

However, longer term studies are needed to see if the results translate into clinical benefits, such as a reduction in falls or changes in pain thresholds.

Arthritis Care Res 2010.

Soy Won't Reduce Cholesterol After Menopause

From Reuters Health Information

Apr 02 - Eating extra soy for one year doesn't help postmenopausal women cut their cholesterol levels, new research shows.

The findings support the Food and Drug Administration's 2007 move to reevaluate its decade-old decision allowing soy product makers to claim heart benefits, Dr. Sara Chelland Campbell of Florida State University in Tallahassee and her colleagues say.

In an online paper in Menopause March 3rd, the researchers noted that recent studies investigating soy and cholesterol levels in postmenopausal women have been short, or have only looked at individual soy components. They conducted the current study to investigate the long-term effects of soy protein in food, specifically 25 g of soy protein and 60 mg of isoflavones every day for a year, in women after menopause.

They enrolled 87 overweight postmenopausal women who were younger than 65, 62 of whom completed the study. Study participants had moderately high total cholesterol levels (236 mg/dL in the control group, 231 mg/dL in the soy group) and were randomly assigned to eat soy products, or comparable products containing casein, for a year. The products included a snack bar, drink mix, and cereal.

Total cholesterol and HDL levels increased slightly in the women given soy products, the researchers found, but soy had no effect on LDL cholesterol or triglyceride levels.

Average total cholesterol rose by 18 points (to 254 mg/dL) in the control group and by 12 points (to about 243 mg/dL) in the soy group. HDL levels increased from 58 to 63 mg/dL in the control group, and from 57 to 60 mg/dL in the soy group.

Since 1999, Dr. Campbell and her colleagues note, the FDA has allowed soy product labeling to claim that diets low in saturated fat and cholesterol, along with 25 g of soy protein daily, "may reduce the risk of heart disease."

Other recent studies have called this benefit into question, the researchers add, and the AHA in 2000 changed its position to say that the benefit of soy protein or isoflavones is "minimal at best."

The researchers conclude: "Our results support the large body of literature showing no favorable alterations in the lipid profile as a result of the incorporation of 25 g/day of soy protein in the diet."

Menopause 2010.

Friday, April 2, 2010

Time Magazine Questions Statin Risks and Benefits in Women, But Experts Say Drugs Safe and Effective

From Heartwire
Michael O'Riordan

March 30, 2010 (New York, New York) — Do statins work equally for men and women? That's the question put forth by Time magazine last week in an article examining the relative risks and benefits between the sexes. While some question whether the evidence is strong enough to support their use, most experts believe that the lipid-lowering medications have undeniable value in women and worry the Time article may cause undue fear or drug cessations.

"I think a take-home point is that, on average, women have lower risks of coronary heart disease than men, at any age and over a lifetime," Dr James Stein (University of Wisconsin, Madison) told heartwire . "So it is more difficult for a woman to reach risk thresholds that indicate need for treatment. But heart disease is the leading killer of women. If you are at increased risk, it does not matter if you are male or female--you need intervention, and statins are effective and safe in both men and women."

The article, by Catherine Elton, documents the case of one woman, "healthy by nearly every measure--except her cholesterol level," treated with a statin that led to severe muscle pain. Eventually, the myopathy is so severe, she stops the statin. Another woman, with high cholesterol and diabetes, begins treatment with a statin and soon forgets how to do basic math and gets lost driving to familiar places.

"Researchers also don't know why women are more likely than men to suffer side effects from statins and many other drugs but posit that lower body weight and hormonal fluctuations play a role," writes Elton. "Biological explanations aside, the larger point is the same: with any treatment, the benefits should outweigh the risks."

Dr Richard Karas (Tufts University Medical Center, Boston, MA) told heartwire the article is "having a large impact in the community" and that he disagrees with the fear and uncertainty it may have caused. Patients are upset, he added, and are calling clinicians asking if they should stop their medication.

Lower Absolute Risk in Women

Speaking with heartwire, Dr James de Lemos (University of Texas Southwestern, Dallas) said that he "finds it hard to believe there are any biological differences in the effects of statins between the sexes." The relevant issue, he said, is that women have a lower absolute risk of ischemic events than men, and this alters the risk/benefit profile, as well as the relative costs. He added that "myopathy is a bit more common in women, but usually in older women, usually treated with higher doses of statins." He said statin therapy typically doesn't pose a problem in younger women treated with the drugs.

Regarding the side effects, Karas noted that women are smaller and tend to be older when they are prescribed statins, and this might contribute to the different side-effect profile between the sexes. Still, these differences are not reasons enough to think the drugs would benefit women to a lesser extent than men, especially since LDL cholesterol predicts coronary heart disease risk in women.

Dr Scott Grundy (University of Texas Southwestern, Dallas) told Time that the "underrepresentation of women in drug trials does not discount statins' benefit; it results only in a failure to show a statistically significant effect," something most experts polled by heartwire also believe.

Grundy highlighted a recent analysis of Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER), a study he believes provides evidence supporting the use of the cholesterol-lowering medication in women. In that analysis, looking just at women enrolled in JUPITER, led by Dr Samia Mora (Brigham and Women's Hospital, Boston, MA), rosuvastatin 20 mg significantly reduced the relative risk of the primary end point--a composite of MI, stroke, revascularization, hospitalization for unstable angina, and death from cardiovascular causes--by 46% [2]. The reduction in risk was supported by evidence in a meta-analysis of 13 154 women included in primary-prevention statin trials.

In addition to these findings, Stein pointed to the Cholesterol Treatment Trialists' collaboration, a prospective meta-analysis of data from 90 056 subjects in 14 randomized statin trials from 1994 to 2000, a study that found no difference in statin effectiveness by sex.

In Time, Elton writes that the women were more likely to develop diabetes than men in JUPITER and that the number needed to treat to prevent one event was also higher. Moreover, the article suggested that the reduction in clinical events was the result of larger reductions in softer end points, such as hospitalization for unstable angina and revascularization.

Dr Rita Redberg (University of California San Francisco), who is quoted in the Time article, told heartwire the key issue is that "millions of healthy American women are taking statins, which have never been shown to reduce MI or lengthen life and have an untold number of side effects, worse in women than men."

To heartwire , de Lemos said these findings are likely the result of a lack of statistical power. With fewer women and their lower baseline risk, it is harder to demonstrate a benefit, he said. Dr Pamela Douglas (Duke University, Durham, NC) agreed, adding that this "also may mean that the threshold for use should be different in men and women, but it doesn't mean statins don't have value in women. de Lemos added that clinicians are now beginning to address the importance of lifetime risk, and from this perspective, even in women with lower baseline risk, statin therapy reduces clinical events.

In response to the Time article, as well as a recent Food and Drug Administration advisory released last week about simvastatin (Zocor, Merck/Schering-Plough), the American Heart Association (AHA) issued a commentary reminding "patients that controlling cholesterol is critical for preventing coronary heart disease and reducing heart attack." It says that myopathy is uncommon and reversible, but it can be a reason to discontinue or reduce the dose of treatment.

"Because of the well-documented benefit of cholesterol lowering with statins, the association advises that patients respect the benefit of statin therapy and consider discontinuation only after a discussion with the appropriate healthcare provider," according to the AHA. "For the person who experiences myopathy with a statin, other alternatives should be discussed with their physician. Patients who are taking statins and not experiencing any side effects should continue to take their medication unless advised for other reasons to stop by their healthcare provider."

Karas reports receiving research grants from AstraZeneca and Kos Pharmaceuticals; serving on the speakers' bureaus of and/or receiving honoraria from Kos, AstraZeneca, Merck, and Pfizer; and serving as a consultant to Kos Pharmaceuticals. de Lemos reports consulting fees/honoraria from Tethys and Johnson & Johnson; speaker's bureau fees from the Bristol-Myers Squibb/Sanofi-Aventis partnership; research grants from Roche; serving on the data safety and monitoring board of Bristol-Myers Squibb; and financial benefits from AstraZeneca and Daiichi-Sankyo. Stein reports research grants from Siemens and serving on the data safety and monitoring board of Abbott, Lilly, and Takeda. Grundy reports grant and research support from Bristol-Myers Squibb, Merck, and Pfizer and serving as a consultant or on the advisory board of Merck, Merck/Schering-Plough, AstraZeneca, Pfizer, and GlaxoSmithKline. Redberg reports no conflicts of interest.

References