Clinical Health Updates

Sustained effects of false-positive mammogram results

Clinical Question:
What are the effects of false-positive mammogram results?

Bottom Line:
Some women with false-positive results on mammography may have differences in whether they return for mammography, occurrence of breast self-examinations, and levels of anxiety compared with women with normal results.

Reference:
Brewer NT, Salz T, Lillie SE. Systematic review: The long-term effects of false-positive mammograms. Ann Intern Med 2007;146:502-510.

Study Design:
Systematic review

Synopsis:
Although abnormal screening mammograms deleteriously affect the psychological well-being of women during the time immediately surrounding the tests, their long-term effects are poorly understood. The author characterized the long-term effects of false-positive screening mammograms on the behavior and well-being of women 40 years of age or older. English-language studies from the MEDLINE, Web of Science, EMBASE, CINAHL, PsycINFO, and ERIC databases through August 2006. Studies were identified that examined the effects of false-positive results of routine screening mammography on women’s behavior, well-being, or beliefs. Two investigators independently coded study characteristics, quality, and effect sizes. 23 eligible studies (n = 313,967) were identified. A random-effects meta-analysis showed that U.S. women who received false-positive results on screening mammography were more likely to return for routine screening than those who received normal results (risk ratio, 1.07 [95% CI, 1.02 to 1.12]). The effect was not statistically significant among European women (risk ratio, 0.97 [CI, 0.93 to 1.01]), and Canadian women were less likely to return for routine screening because of false-positive results (risk ratio, 0.63 [CI, 0.50 to 0.80]). Women who received false-positive results conducted more frequent breast self-examinations and had higher, but not apparently pathologically elevated, levels of distress and anxiety and thought more about breast cancer than did those with normal results.

LIMITATIONS:
Correlational study designs, a small number of studies, a lack of clinical validation for many measures, and possible heterogeneity.

Atkins equally or more effective for weight loss in premenopausal women

Clinical Question:
Which diet is most effective for maintaining weight loss in premenopausal women at 1 year?

Bottom Line:
In this study, premenopausal overweight and obese women on the Atkins diet lost comparable or more weight than similar women following other diet plans, including the Zone, Ornish, or LEARN (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition) diets. In addition, women on the Atkins diet showed equally or more improved overall metabolic effects. The difference in weight loss between the Atkins and Zone diet was statistically significant, but weight loss was not different among the other diets.

Reference:
Gardner CD, Kiazand A, Alhassan S, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and weight related risk factors among overweight premenopausal women. The A to Z weight loss study: A randomized controlled trial. JAMA 2007;297:969-977.

Study Design:
Randomized controlled trial (single-blinded)

Synopsis:
Popular diets, particularly those low in carbohydrates, have challenged current recommendations advising a low-fat, high-carbohydrate diet for weight loss. Potential benefits and risks have not been tested adequately. The authors compared 4 weight-loss diets representing a spectrum of low to high carbohydrate intake for effects on weight loss and related metabolic variables. Twelve-month randomized trial conducted in the United States from February 2003 to October 2005 among 311 free-living, overweight/obese (body mass index, 27-40) nondiabetic, premenopausal women. Participants were randomly assigned to follow the Atkins (n = 77), Zone (n = 79), LEARN (n = 79), or Ornish (n = 76) diets and received weekly instruction for 2 months, then an additional 10-month follow-up. Weight loss at 12 months was the primary outcome. Secondary outcomes included lipid profile (low-density lipoprotein, high-density lipoprotein, and non-high-density lipoprotein cholesterol, and triglyceride levels), percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure. Outcomes were assessed at months 0, 2, 6, and 12. The Tukey studentized range test was used to adjust for multiple testing. Weight loss was greater for women in the Atkins diet group compared with the other diet groups at 12 months, and mean 12-month weight loss was significantly different between the Atkins and Zone diets (P<.05). Mean 12-month weight loss was as follows: Atkins, -4.7 kg (95% confidence interval [CI], -6.3 to -3.1 kg), Zone, -1.6 kg (95% CI, -2.8 to -0.4 kg), LEARN, -2.6 kg (-3.8 to -1.3 kg), and Ornish, -2.2 kg (-3.6 to -0.8 kg). Weight loss was not statistically different among the Zone, LEARN, and Ornish groups. At 12 months, secondary outcomes for the Atkins group were comparable with or more favorable than the other diet groups.

Mifepristone effective tx for bleeding due to fibroids

Clinical Question:
Does treatment with mifepristone improve the quality of life for women with symptomatic fibroids?

Bottom Line:
Low-dose mifepristone improves leiomyoma-specific quality of life and reduces leiomyoma size among women with symptomatic leiomyomata. Treatment of uterine fibroids with mifepristone in premenopausal women reduces uterine volume, bleeding, and improves leiomyoma-related quality of life. Larger and longer studies are needed. Long-term effects on other patient-oriented outcomes of interest, such as fertility, should be assessed.

Reference:
Fiscella K, Eisinger SH, Meldrum S, Feng C, Fisher SG, Guzick DS. Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size. Obstet Gynecol 2006;108:1381-1387.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
The authors assessed the effect of low-dose mifepristone on quality of life, pain, bleeding, and uterine size among women with symptomatic leiomyomata. They studied 42 women with symptomatic uterine leiomyomata and uterine volume of 160 mL or more were randomized to mifepristone, 5 mg daily, or placebo for 26 weeks. Quality of life (Uterine Fibroid Symptoms Quality of Life Questionnaire and Medical Outcomes Study 36-Item Short Form survey) and uterine and leiomyoma size (ultrasonography) were assessed at baseline, and at 1 month, 3 months, and 6 months of treatment. Bleeding (daily logs and pictorial charts) and pain (McGill Pain Questionnaire) were assessed monthly. Endometrial pathology was assessed at baseline and 6 months. Forty-two women were randomized; 37 women completed all 6 months. Women randomized to mifepristone showed an improvement in leiomyoma-specific quality of life. Forty-one percent became amenorrheic, rates of anemia improved, and adjusted uterine size was reduced by 47%. Compared with the placebo group, improvements in these outcomes in the treatment group were significantly greater (P<.05 to .001). There were no significant differences in adverse effects between the groups. No endometrial hyperplasia was noted in any participant.

Black cohosh ineffective for vasomotor symptoms

Clinical Question:
Do soy, black cohosh, or a naturopathic multibotanical provide greater relief from vasomotor symptoms than placebo in menopausal or perimenopausal women?

Bottom Line:
Black cohosh used in isolation, or as part of a multibotanical regimen, shows little potential as an important therapy for relief of vasomotor symptoms. These results are similar to other research findings.

Reference:
Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo. Ann Intern Med 2006;145:869-879.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Herbal supplements are widely used for vasomotor symptoms. The authors test the efficacy of 3 herbal regimens and hormone therapy for relief of vasomotor symptoms compared with placebo. They did a 1-year randomized, double-blind, placebo-controlled trial conducted from May 2001 to September 2004 to Group Health, Washington State 351 women age 45 to 55 years with 2 or more vasomotor symptoms per day; 52% of the women were in menopausal transition and 48% were postmenopausal. They measure rate and intensity of vasomotor symptoms (1 = mild to 3 = severe), and Wiklund Vasomotor Symptom Subscale. The women were randomly assigned, using concealed allocation, to receive 1 of the following treatments daily for 1 year:1) Black cohosh, 160 mg daily; 2) multibotanical with black cohosh, 200 mg daily, and 9 other ingredients; 3) multibotanical plus dietary soy counseling; 4) conjugated equine estrogen, 0.625 mg daily, with or without medroxyprogesterone acetate, 2.5 mg daily; or 5) placebo. Vasomotor symptoms per day, symptom intensity, Wiklund Vasomotor Symptom Subscale score did not differ between the herbal interventions and placebo at 3, 6, or 12 months or for the average over all the follow-up time points (P > 0.05 for all comparisons) with 1 exception: At 12 months, symptom intensity was significantly worse with the multibotanical plus soy intervention than with placebo (P = 0.016). The difference in vasomotor symptoms per day between placebo and any of the herbal treatments at any time point was less than 1 symptom per day; for the average over all the follow-up time points, the difference was less than 0.55 symptom per day. The difference for hormone therapy versus placebo was -4.06 vasomotor symptoms per day for the average over all the follow-up time points (95% CI, -5.93 to -2.19 symptoms per day; P < 0.001).

Annual mammography starting at 40 doesn’t lower breast CA mortality

Clinical Question:
Does starting annual mammography at age 40 decrease breast cancer mortality?

Bottom Line:
The reduction in breast-cancer mortality observed in this trial is not significant, it is consistent with results of other trials of mammography alone in this age-group. Future decisions on screening policy should be informed by further follow-up from this trial and should take account of possible costs and harms as well as benefits.

Reference:
Moss SM, Cuckle H, Evans A, et al, for the Trial Management Group. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’ follow-up: a randomised controlled trial. Lancet 2006;368:2053-2060.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
The efficacy of screening by mammography has been shown in randomised controlled trials in women aged 50 years and older, but is less clear in younger women. A meta-analysis of all previous trials showed a 15% mortality reduction in invited women aged 40-49 years at study entry, but this finding could be due in part to screening of women after age 50 years. The Age trial was designed to study the effect on mortality of inviting women for annual mammography from age 40 years. 160,921 women aged 39-41 years were randomly assigned in the ratio 1:2 to an intervention group of annual mammography to age 48 years or to a control group of usual medical care. The trial was undertaken in 23 NHS breast-screening units in England, Wales, and Scotland. The primary analysis was based on the intention-to-treat principle and compared mortality rates in the two groups at 10 years’ follow-up. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN24647151. At a mean follow-up of 10.7 years there was a reduction in breast-cancer mortality in the intervention group, in relative and absolute terms, which did not reach statistical significance (relative risk 0.83 [95% CI 0.66-1.04], p=0.11; absolute risk reduction 0.40 per 1000 women invited to screening [95% CI -0.07 to 0.87]). Mortality reduction adjusted for non-compliance in women actually screened was estimated as 24% (RR 0.76, 95% CI 0.51-1.01).

Radiotherapy increases survival in Stage I/II breast CA

Clinical Question:
Does radiotherapy provide incremental benefit to chemotherapy following modified radical mastectomy in Stage I and II
breast cancer?

Bottom Line:
Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer. Another paper in the same issue of the journal confirms these results in high−risk women (Overgaard, N Engl J Med 1997; 337:949−55).

Reference:
Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node−positive premenopausal women
with breast cancer. N Engl J Med 1997; 337: 956−62.

Study Design:
Randomized controlled trial

Synopsis:
Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began to decline in the 1980s because it failed to improve overall survival. We prospectively tested the efficacy of combining radiotherapy with chemotherapy. From 1978 through 1986, 318 premenopausal women with node-positive breast cancer were randomly assigned, after modified radical mastectomy, to receive chemotherapy plus radiotherapy or chemotherapy alone. Radiotherapy was given to the chest wall and locoregional lymph nodes between the fourth and fifth cycles of cyclophosphamide, methotrexate, and fluorouracil. After 15 years of follow-up, the women assigned to chemotherapy plus radiotherapy had a 33 percent reduction in the rate of recurrence (relative risk, 0.67; 95 percent confidence interval, 0.50 to 0.90) and a 29 percent reduction in mortality from breast cancer (relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.99), as compared with the women treated with chemotherapy alone.

Soy, black cohosh may have some benefit for menopause sx

Clinical Question:
Which complementary and alternative medicine approaches are effective in decreasing symptoms of menopause?

Bottom Line:
There is no evidence of benefit of acupuncture, magnet therapy, stress reduction, exercise, progressive muscle relaxation, or traditional Chinese herbal therapy on menopausal symptoms. Black cohosh, which has been associated with liver toxicity, and soy supplements may decrease hot flashes in some patients, and osteopathic manipulation was effective in one study.

Reference:
Nedrow A, Miller J, Walker M, Nygren P, Huffman LH, Nelson HD. Complementary and alternative therapies for the management of menopause-related symptoms. Arch Intern Med 2006;166:1453-1465.

Study Design:
Systematic review

Synopsis:
The goal of this systematic review was to assemble all available clinical research evaluating any of the 5 categories of complementary and alternative medicine: biologically based (dietary supplements and vitamins), mind-body, energy, manipulative and body-based, and whole medical systems (eg, ayurveda). The review used the evidence report/technology assessment methodology of the Agency for Healthcare Policy and Research. The authors searched multiple databases and reference lists of identified articles, contacted experts, and searched Web sites for randomized placebo-controlled trials and meta-analyses published in English. Much of the literature on herbal therapies is published in German, though it doesn’t appear that they excluded any applicable German-language studies. Two investigators independently evaluated the quality of the research using the criteria from the United States Preventive Services Task Force.

Although studies graded as poor quality found a benefit with soy supplements (dietary, supplements, or red clover), the effect on symptoms in fair or good studies were mixed, with some studies showing improvement in hot flashes. The largest study of black cohosh demonstrated a benefit in a variety of menopausal symptoms. However, black cohosh has been linked in the United Kingdom to abnormal liver function. Stress reduction, aerobic exercise, progressive muscle relaxation were not effective in fair- or poor-quality studies. One study of 10 treatments with low-force osteopathic manipulation showed a decrease in symptoms. Neither reflexology nor magnet treatment were effective. Traditional Chinese medical herbs were also ineffective, as was acupuncture; ginseng produced improvement in mood and health scores but did not affect hot flashes.

Distraction decreases child’s anxiety during procedures

Clinical Question:
Does distracting children undergoing laceration repair decrease their anxiety and pain?

Bottom Line:
The use of distraction techniques is effective in reducing situational anxiety in older children and lowering parental perception of pain distress in younger children. This technique may have a role in improving the quality of management of procedural pain in a pediatric emergency department (ED) setting.

Reference:
Sinha M, Christopher NC, Fenn R, Reeves L. Evaluation of nonpharmacologic methods of pain and anxiety management for laceration repair in the pediatric emergency department. Pediatrics 2006;117:1162-1168.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
We know distraction can diminish anxiety and pain during procedures: Think of the Lamaze method used in childbirth. The researchers conducting this study evaluated the effect of age-appropriate distractions on 240 children between the ages of 6 years and 18 years presenting to an emergency department for simple laceration repair. After receiving a topical anesthetic, the children were randomly assigned, using concealed allocation, to either their choice of distraction or waiting without distraction with study personnel. The children in the distraction group were offered a CD player with headphones, video games, or a cartoon video. They could also choose to have a book read to them. Children allocated to the distraction group who weren’t interested in any of the distractions were given help blowing bubbles. Suturing was performed in a standardized manner. Using a 7-point facial pain scale, pain did not differ between the 2 groups. Parental assessment of pain distress, as measured using a 100-mm visual analog scale, was significantly less in distracted children younger than 10 years (P <.01), though preprocedure scores in both groups were very low (2.91 – 3.31 of a possible 10). Children older than 10 years were evaluated using the State Trait Anxiety Inventory for Children, and anxiety scores on this scale were lower in the children receiving distraction, with a change from the start to the end of the procedure of 12.3 (95% CI, 10.5 – 14.2) in the distracted group and 6.1 (4.6 – 7.5) in the control group (P <.001).

Gabapentin somewhat helpful for hot flashes after breast cancer

Clinical Question:

Does gabapentin (Neurontin) effectively reduce hot flashes in women with a history of breast cancer?

Bottom Line:

Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer.

Reference:

Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: A randomised double-blind placebo-controlled trial. Lancet 2005;366:818-24.

Study Design:

Randomized controlled trial (double-blinded)

Funding:

Unknown/not stated

Setting:

Outpatient (specialty)

Allocation:

Concealed

Synopsis:

Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer. 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat. Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity.