• N-Acetylcysteine for Treating Patients with COPD — A Randomized Trial
• Peripheral Artery Disease Increased Dramatically Over the Past Decade Worldwide
• Improve Your Marriage in 30 Minutes or Less!
• Having a Pet Dog Reduces Risk for Childhood Atopic Dermatitis
• Breast-Feeding Linked to Intelligence in Children
• U.S. Breast-Feeding Rates Up
• H. Pylori Eradication Might Reduce Recurrent Gastric Cancer After Surgery
• Outpatient Back-Pain Treatments Are Trending Against Guidelines
• Cancer Overdiagnosis, Overtreatment Targeted
• Tobacco Use Is Associated with Greater Disability in Multiple Sclerosis
• Hormone Use During Menopause and Cognitive Outcomes
• Supine Exercises for Orthostatic Hypotension in Older Adults
• Obesity Linked with Sensorineural Hearing Loss in Adolescents
• Is IVF Linked to Autism and Mental Retardation?
• The Taller the Woman, the Greater the Cancer Risk?
• Centrally Acting ACE Inhibitors Seem to Slow Cognitive Decline in Dementia
• Can Fluoroquinolones Cause Acute Kidney Injury
• Diabetes and Unhealthy Behaviors Seen Leading to Physical Disabilities
• GlaxoSmithKline's Activities in China Draw Concern
• Soy Supplementation Fails to Reduce Risk for Prostate Cancer Recurrence
MM: Oral NAC is an easy, inexpensive means of administration and apparently twice daily dosing is effective for COPD. We have used compounded nebulized NAC with great success over the years for COPD. If oral use is as effective, then it brings this alternative treatment within reach of many more patients with potentially few side effects.
Chest 2013 Jul; 144:106
N-Acetylcysteine for Treating Patients with COPD — A Randomized Trial
The drug improved airway mechanics and prevented recurrent exacerbations among patients with chronic obstructive pulmonary disease.
Because of its antioxidant effects, N-acetylcysteine (NAC) has been proposed as an adjunctive treatment for patients with chronic obstructive pulmonary disease (COPD). In this study, Hong Kong researchers randomized 120 patients with stable COPD who averaged two exacerbations and one COPD hospitalization during the previous year to receive either NAC (600-mg tablets, taken twice daily) or placebo.
At 1 year, measures of airway reactance and resistance improved significantly in the NAC group but not in the placebo group. COPD exacerbations occurred less often with NAC than with placebo (mean, 0.96 vs. 1.71; P=0.02). The proportions of patients with no exacerbation during the study year were 54% in the NAC group and 38% in the placebo group (P=0.09). No major adverse effects were reported.
Comment: When low-dose oral N-acetylcysteine (600 mg once daily) conferred no benefit in a previously published trial, that study's authors called for additional trials with higher doses (NEJM JW Gen Med Jun 10 2005). If the results of this new study of twice-daily dosing can be confirmed and extended, NAC indeed might have a role as adjunctive therapy in patients with COPD
Citation(s): Tse HN et al. High-dose N-acetylcysteine in stable COPD: The 1-year, double-blind, randomized, placebo-controlled HIACE study. Chest 2013 Jul; 144:106.
(http://dx.doi.org/10.1378/chest.12-2357)
http://www.ncbi.nlm.nih.gov/pubmed/23348146?access_num=23348146&link_
type=MED&dopt=Abstract
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MM: In real life situations PAD may be manifested by varicose veins and tired legs when doing normal tasks. People who are especially susceptible to these conditions are those who spend a lot of time on their feet such as nurses, teachers, doctors, pharmacists and sales clerks. At first the symptoms may be merely annoying or considered cosmetic but if not addressed, PAD can lead to possible embolism or stroke and progress from life tormenting to life threatening. Simple graduated compression hosiery may slow down progression of PAD and its ill effects or even prevent real problems from occurring if used prophylactically. Other products that have shown to be very helpful are products like Veno-Care containing herbs such as butcher's broom and horse chestnut.
Peripheral Artery Disease Increased Dramatically Over the Past Decade Worldwide
By Joe Elia
Lower-limb peripheral artery disease (PAD) has become a worldwide problem, and its prevalence over the past decade increased twice as fast in lower- and middle-income countries (by 29%) as it did in high-income countries (by 13%), according to Lancet estimates.
Researchers examined data from community-based studies in which PAD was defined by an ankle-brachial index of 0.90 or lower. The 34 studies encompassed over 100,000 participants. In high-income countries, PAD prevalence did not differ between men and women, but in other countries it was higher among women. Prevalence rose with age worldwide, reaching 10% by age 70 and 17% after age 80. The most important modifiable risk factor was smoking, followed by diabetes, hypertension, and hypercholesterolemia.
The authors call the dramatic increase in prevalence — to about 200 million cases — "a major public health challenge," given PAD's association with loss of mobility, functional decline, and cardiovascular risk.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61249-0/abstract
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MM: Even the best relationships go over bumps in the road on occasion and who couldn't benefit from "working on" their relationship? This article addresses an issue that challenges the American family and if a simple, relatively easy task of little to no cost can have a positive impact then I am all for it.
Psychol Sci 2013 Jun 26
Improve Your Marriage in 30 Minutes or Less!
In a randomized trial, a very brief program reduced marital dissatisfaction.
Normatively, marital happiness decreases over time. Because depression is linked to marital discord and divorce rates hover near 50%, interventions that reduce marital dissatisfaction have clinical and public health merit. For this Internet-based, controlled study, investigators recruited a community-based convenience sample of 120 heterosexual married couples (mean age, 40; mean marriage length, 11 years). Participants were assessed for relationship satisfaction, love, intimacy, trust, passion, and commitment every 4 months for 2 years (7 waves of assessments). For waves 2 through 7, each spouse also provided “fact-based,” behavior-focused summaries of their most significant disagreements and rated conflict-related distress.
At 12 months, the couples underwent randomization. The intervention was a 7-minute task in which the couples individually reappraised the conflicts they had just identified and wrote about them from the perspective of a neutral third party. They repeated the writing task during the next two assessments and were encouraged to apply these third-party perspectives during other disagreements. Midway between each subsequent wave, the intervention couples received e-mail reminders of the task, and control couples received friendly e-mail check-ins.
As predicted, marital quality deteriorated during the study. After year 1, however, the intervention group reported less conflict-related distress starting with the first reappraisal and no longer reported declining marital quality. Length of marriage did not moderate the findings.
Comment: A briefly sustained, prompted intervention may prevent progressive decline in marital quality. Additional fine-grained research is necessary to identify the characteristics of the couples most and least amenable to such interventions and to examine dosing, timing, duration, implementation, and mechanisms of action. Whether these interventions might actually preserve marriages and help clinical populations remains to be seen.
Citation(s): Finkel EJ et al. A brief intervention to promote conflict reappraisal preserves marital quality over time. Psychol Sci 2013 Jun 26; [e-pub ahead of print].
(http://dx.doi.org/10.1177/0956797612474938)
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MM: I have long been a proponent of having dogs for pets in households where family members have allergies. I feel that the hygiene hypothesis of early exposure to allergens and even to pathogenic microorganisms such as viruses, bacteria and fungus strengthens our immune systems through reasonable challenge.
J Allergy Clin Immunol 2013 May 28
Having a Pet Dog Reduces Risk for Childhood Atopic Dermatitis
This careful meta-analysis indicates that early exposure to dogs, but not cats, decreases risk for childhood atopic dermatitis by 25%.
The hygiene hypothesis was proposed in 1989 as a possible explanation for the rapidly increasing prevalence of atopic dermatitis (AD) and other allergic and autoimmune diseases in developed nations. This hypothesis posits that reduced exposure to infectious agents in early life alters immune system maturation. Findings on pet exposure and risk for (AD) in children are inconsistent. Therefore, researchers conducted a systematic review and meta-analysis of pooled data from 21 birth cohort studies (26 publications) that examined exposure to dogs, cats, or other pets during infancy or childhood and AD during infancy and childhood.
The pooled relative risk of AD was significantly reduced for exposure versus no exposure to dogs (0.72, 15 studies) and exposure to pets overall (0.75, 11 studies), but not for exposure to cats (0.94, 13 studies). Studies were moderately heterogeneous. Mitigating factors included geographic heterogeneity (Europe, 14 studies; U.S., 3 studies; Oceania, 3 studies; and Japan, 1 study), undefined pet-keeping practices (degree of exposure), inability to adjust for pet-avoidance behavior of parents (e.g., because of a family history of allergy), presence or absence of smoking, and education and income.
Comment :The conflicting results regarding a link between pet exposure and childhood atopic diseases (allergic rhinitis, asthma, atopic dermatitis) probably stem from different methodologies in the individual studies and various meta-analyses. Furthermore, pet exposure appears to affect the risk for the three atopic diseases differently. This careful meta-analysis indicates that early exposure to dogs significantly reduces risk for childhood atopic dermatitis. Although the protective effect of dogs and pets overall is consistent with the hygiene hypothesis, the lack of a protective effect from cat exposure indicates that the association is complex
Citation(s): Pelucchi C et al. Pet exposure and risk of atopic dermatitis at the pediatric age: A meta-analysis of birth cohort studies. J Allergy Clin Immunol 2013 May 28; [e-pub ahead of print].
(http://dx.doi.org/10.1016/j.jaci.2013.04.009)
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MM: The moms and other members of La Leche should love this. Many of these moms have been criticized for nursing until their children are toddlers. Irrespective of the "sensitivities" of those who are embarrassed by seeing this, there may be a positive benefit beyond the immunological benefits and emotional attachment that is shared between mother and child.
Breast-Feeding Linked to Intelligence in Children
By Kelly Young
A longer duration of breast-feeding is associated with higher measures of childhood intelligence, according to a study in JAMA Pediatrics.
The breast-feeding status of roughly 1200 mothers was assessed when their infants were aged 6 and 12 months. Then at ages 3 and 7, the children took various intelligence tests. The mean duration of any breast-feeding was 6.4 months.
In models adjusted for the mother's IQ and other variables, children who had breast-fed at any point had higher test scores for receptive language at age 3 years and both verbal and nonverbal IQ at age 7. Longer duration of breast-feeding translated to higher scores.
The authors conclude: "These findings support national and international recommendations to promote exclusive breastfeeding through age 6 months and continuation of breastfeeding through at least age 1 year
http://archpedi.jamanetwork.com/article.aspx?articleid=1720224
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U.S. Breast-Feeding Rates Up
Breast-feeding rates in the United States have been slowly climbing in the last decade, according to data from the CDC's National Immunization Survey.
The proportion of infants who began breast-feeding rose from 71% in 2000 to 77% in 2010. The percentage still breast-feeding at age 6 months increased from 34% to 49% over the same time frame, while rates at 12 months increased from 16% to 27
http://www.cdc.gov/breastfeeding/data/NIS_data/index.htm
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Aliment Pharmacol Ther 2013 Jul 3
H. Pylori Eradication Might Reduce Recurrent Gastric Cancer After Surgery
Thirty-six months after subtotal gastrectomy for gastric cancer, patients who were H. pylori-free had less glandular atrophy and intestinal metaplasia than infected patients.
Intestinal metaplasia (IM) and glandular atrophy (GA) have been identified as preneoplastic conditions in patients infected with Helicobacter pylori. The role of H. pylori eradication in improving these conditions after subtotal gastrectomy for gastric cancer is unclear.
To investigate this issue, researchers in Korea randomized 190 patients with gastric cancer and H. pylori infection to receive 7 days of proton-pump inhibitor–based triple therapy or placebo prior to surgery. The greater and lesser gastric curvatures were biopsied prior to surgery and at 12 and 36 months after surgery and evaluated according to the updated Sydney criteria. H. pylori infection was determined by both a rapid urease test and histologic examination of endoscopic biopsies. Histological findings of GA and IM were scored to indicate presence and severity (absent, 0; mild, 1; moderate, 2; severe, 3).
At 36 months, 75% of patients in the treatment group were free of H. pylori compared with 41% of the placebo group. The mean GA and IM scores did not differ between the two groups. However, compared with H. pylori-infected patients, those without H. pylori had less atrophy (P=0.005) and IM (P=0.03).
Comment: The lack of difference in glandular atrophy or intestinal metaplasia between study groups at 36 months might be explained by a type II error. Histological scores for both were lower in the treatment group, but these differences did not reach statistical significance, possibly because of the low eradication rate in the treatment group, the high spontaneous remission rate in the placebo group, or the relatively large number of patients lost before the final analysis. As the authors concluded, the findings suggest that successful H. pylori eradication might reduce the preneoplastic changes in the gastric remnant after gastric surgery, but the clinical significance of the histologic changes remains to be determined.
Citation(s): Cho S-J et al. Randomised clinical trial: The effects of Helicobacter pylori eradication on glandular atrophy and intestinal metaplasia after subtotal gastrectomy for gastric cancer. Aliment Pharmacol Ther 2013 Jul 3; [e-pub ahead of print].
(http://dx.doi.org/10.1111/apt.12402)
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Outpatient Back-Pain Treatments Are Trending Against Guidelines
By Joe Elia
Treatment of back and neck pain increasingly relies on strategies that run counter to published guidelines, a JAMA Internal Medicine study finds. A commentator argues that evidence-based guidelines are relatively new in this area — and need more work.
Researchers used data from federal surveys to examine outpatient treatment trends in 2-year increments between 1999 and 2010.
Between the 1999–2000 and the 2009–2010 periods, the following changes were noted:
- Guideline-concordant use of NSAIDs or acetaminophen dropped from 37% to 25%, while guideline-discordant use of narcotics increased from 19% to 29%.
- Referrals for physical therapy, at 20%, remained unchanged, while referrals to other physicians doubled, from 7% to 14%.
- Use of MRI or CT increased from 7% to 11%.
A commentator calls for better guidelines based on better evidence, while the study's authors remind us that the bill for spine-related pain totals $86 billion annually.
http://archinte.jamanetwork.com/article.aspx?articleid=1722522
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MM: Overdiagnosis of cancer or erring on the side of caution may not be the lesser of two evils in that a significant percentage of patients diagnosed with cancer may never be in a position that their conditions actually progress to a problematic level. None of us wants to be the exception that fails to act upon a diagnosis and then feels guilty that "we could have done more", yet if we take a closer look at Quality rather than simply quantity of life, it may be an easier decision to make.
Cancer Overdiagnosis, Overtreatment Targeted
By Joe Elia
A working group convened by the National Cancer Institute is proposing changes in the terminology used to describe cancer. The proposed changes, aimed at curbing overdiagnosis and the resulting overtreatment, are summarized in JAMA and received prominent play on the New York Times' electronic front page.
The authors urge that everyone — clinicians and patients — "must recognize that overdiagnosis is common and occurs more frequently with cancer screening." In addition, they point out that many screen-detected lesions, especially those of the breast and prostate, are indolent and "should not be labeled as cancers." They propose establishing registries of such lesions (which they call "indolent lesions of epithelial origin," or IDLEs) to observe how they progress.
Also proposed are reducing the use of low-yield diagnostic evaluation, raising the threshold for recall and biopsy, and focusing screening among those at high risk.
http://jama.jamanetwork.com/article.aspx?articleid=1722196
http://well.blogs.nytimes.com/2013/07/29/report-suggests-sweeping-changes-to-cancer-detection-and-treatment/?_r=0
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Brain 2013 Jul; 136:2298
Tobacco Use Is Associated with Greater Disability in Multiple Sclerosis
Compared with MS patients who never smoked, those who smoked when first diagnosed developed greater moderate-to-severe disability during a 15-year period.
Tobacco smoking is a permissive factor in the development of multiple sclerosis (MS), but the impact on the clinical course has not been established (NEJM JW Neurol Aug 3 2005). Investigators used data from a region-based U.K. MS clinic that included 895 complete cases with a median 15 years of follow-up. Study covariates included age at first clinical manifestation of disease, disease subtypes (e.g., relapsing or progressive), and treatment duration <1 year or ≥1 year. Smoking status was assessed during the clinic visit associated with the first clinical event and categorized as nonsmoker, ex-smoker, or current smoker.
Using the MS Severity Score, those who ever smoked were significantly more likely to be in the most severely disabled quartile of this scale (57% ever-smokers vs. 35% never-smokers). Compared with never-smokers, ever-smokers were 34% more likely to develop moderate disability in at least one system (Expanded Disability Status Scale score [EDSS] of 4.0) and 25% more likely to progress to require use of a cane to ambulate (EDSS = 6.0). Ex-smokers had a lower risk for disability than current smokers, a 35% reduction in risk for reaching EDSS 4.0, and a 31% reduction in risk for reaching EDSS 6.0.
Comment: Multiple sclerosis patients should be counseled about the plethora of health risks with regard to smoking, which now include an increased disability progression to use of a cane. Although ever-smokers (i.e., ex-smokers and current smokers) had a higher overall risk than those who never smoked, those who had quit fared better than those who were current smokers. This potential benefit gives patients with MS additional incentive to try to quit. Because smoking was assessed only at the start of the disease, future studies should evaluate the longitudinal effects of smoking status on disability over time. This could help differentiate whether smoking negatively affects the inflammatory stage, the neurodegenerative stage, or both.
Citation(s): Manouchehrinia A et al. Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study. Brain 2013 Jul; 136:2298.
(http://dx.doi.org/10.1093/brain/awt139)
http://brain.oxfordjournals.org/content/136/7/2298?ijkey=11588bf1b9a36fabefbad2
9a151ba105f77129bc&keytype2=tf_ipsecsha
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JAMA Intern Med 2013 Jun 24
Hormone Use During Menopause and Cognitive Outcomes
Seven years after women stopped randomized hormone therapy or placebo, cognition did not differ.
Identifying strategies to prevent age-related cognitive impairment remains an important but elusive goal. Until a decade ago, hormone therapy was considered tremendously promising for preventing dementia in older women. However, results from the Women's Health Initiative (WHI) trial, as well as from other trials, reported an unexpected finding: an increased risk for dementia and worse cognitive scores among older women (≥65 years) assigned to conjugated equine estrogen (CEE) compared with placebo. These results caused great concern and confusion among medical practitioners and patients and highlighted the differences between randomized trials and observational studies. However, some suggested that there is a “critical window” of exposure during the perimenopausal transition in which hormones must be administered to be protective.
Recent findings from the WHI group challenge this hypothesis. They conducted the Women's Health Initiative Memory Study in Younger Women (WHIMSY), in which 1168 participants from the WHI trial, aged 50 to 55 when assigned to hormone therapy or placebo, were administered cognitive testing by telephone approximately 7 years after the WHI trial ended (after an average of 7 years of treatment). At the time of the phone interview for WHIMSY, the mean age was 67. In these women, cognitive test scores across all domains were similar among those who had been assigned to hormone therapy compared with those assigned to placebo.
Comment: Hormone therapy remains the most efficacious treatment for hot flushes and other menopausal symptoms, so it is reassuring that there are no apparent deleterious cognitive outcomes for women exposed to hormones in their fifties. On the other hand, it is disappointing that early exposure was not beneficial. Of note, the women in WHIMSY started trial drug assignment an average of 4 to 8 years after menopause, so the study did not fundamentally address the issue of exposure during perimenopause or early menopause. Several other, ongoing or recently completed studies (including the KEEPS and ELITE trials) will address the “critical window” issue even more directly.
Citation(s): Espeland MA et al. Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years. JAMA Intern Med 2013 Jun 24; [e-pub ahead of print].
http://dx.doi.org/10.1001/jamainternmed.2013.7727
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J Am Geriatr Soc 2013 Jul; 61:1152
Supine Exercises for Orthostatic Hypotension in Older Adults
Leg exercises, done just before standing, attenuated the drop in systolic blood pressure.
For patients with symptomatic neurogenic orthostatic hypotension (e.g., related to neuropathy or to central disorders such as Parkinson disease), physical counter-maneuvers such as crossing the legs or flexing the leg muscles immediately on standing can be helpful. But some older patients with comorbidities such as osteoarthritis or problems with balance find these maneuvers difficult to perform while standing. In this study, researchers examined the effect of exercises done just before standing.
Forty-two Italian patients (mean age, 77) with osteoarthritis and orthostatic hypotension of various etiologies were divided into an exercise group and a control group. The exercise patients performed 10 repetitions of flexion and extension of the hips, knees, and ankles (with the help of a resistance band encircling the feet) during the half-minute just before standing, whereas controls simply went from a supine to a standing position. Mean systolic blood pressure (BP) taken immediately on standing fell by 27 mm Hg in the control group but only by 10 mm Hg in the exercise group — a significant difference. During the next 5 minutes, return to baseline BP occurred more slowly in the control group than in the exercise group.
Comment: When they are effective, nonpharmacologic maneuvers are preferable to drug therapies for orthostatic hypotension in older patients. This study suggests that recommending supine leg exercises, done just before standing, is a promising approach. However, these findings should be confirmed in patients with more-severe orthostasis, and long-term improvement in symptoms should be demonstrated.
Citation(s): Galizia G et al. Counteracting effect of supine leg resistance exercise on systolic orthostatic hypotension in older adults. J Am Geriatr Soc 2013 Jul; 61:1152.
(http://dx.doi.org/10.1111/jgs.12313)
http://www.ncbi.nlm.nih.gov/pubmed/23750850?access_num=
23750850&link_type=MED&dopt=Abstract
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Laryngoscope 2013 Jun 11
Obesity Linked with Sensorineural Hearing Loss in Adolescents
Obesity nearly doubled the risk for unilateral low-frequency hearing loss.
Hearing loss is not a well-known adverse health consequence of obesity in adults. Researchers examined this association in 1488 adolescents aged 12 to 19 years using cross-sectional data from the 2005–2006 National Health and Nutrition Examination Survey.
Body-mass indexes from the 5th to 85th percentile were considered normal weight, from 86th to 94th percentile were overweight, and ≥95th percentile were obese. Compared with normal-weight teens, obese teens had a greater prevalence of low-frequency unilateral sensorineural hearing loss (SNHL; >15 dB, 15% vs. 8%) as well as bilateral low- and unilateral and bilateral high-frequency SNHL, but these trends were not statistically significant. In multivariate analysis that controlled for numerous risk factors (e.g., smoke exposure, poverty, various noise exposures), obesity was independently and significantly associated with a 1.85 increased risk for unilateral low-frequency SNHL.
Comment: Hearing loss has not previously been on my radar as a comorbidity of obesity. Although these data do not address whether or how obesity leads to hearing loss, the prevalence of hearing loss in adolescents is rising, most likely due to noise exposure (NEJM JW Pediatr Adolesc Med Sep 8, 2010), so it seems prudent to counsel teens about risk factors for hearing loss, including obesity.
Citation(s): Lalwani AK et al. Obesity is associated with sensorineural hearing loss in adolescents. Laryngoscope 2013 Jun 11; [e-pub ahead of print].
(http://dx.doi.org/10.1002/lary.24244)
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JAMA 2013 Jul 3; 310:75
Is IVF Linked to Autism and Mental Retardation?
Compared with spontaneous conception, in vitro fertilization was associated with slightly higher risk for mental retardation.
Although more than 5 million infants have been born worldwide as a result of in vitro fertilization (IVF), information about their neural development is limited. Swedish investigators used national health registers to evaluate risks for autistic disorder and mental retardation after spontaneous conception or IVF in a population-based, prospective cohort study of the >2.5 million offspring born in Sweden from 1982 through 2007. All offspring were followed through 2009; about 1.2% (almost 31,000) were conceived with IVF.
Of 6959 children with autistic disorder, 103 (1.5%) were born following IVF. Of 15,830 with mental retardation, 180 (1.1%) were born after IVF. Risk for autistic disorder was not significantly increased after IVF (relative risk, 1.14; 95% confidence interval, 0.94–1.39), but risk for mental retardation was significantly increased (RR, 1.18; 95% CI, 1.01–1.36). In analysis limited to singletons, this excess risk was not statistically significant, suggesting an association with multiple births and preterm births. IVF with intracytoplasmic sperm injection (ICSI) was associated with higher risk for autistic disorder and mental retardation compared with IVF without ICSI; use of surgically extracted sperm for ICSI was also associated with excess risk for both disorders, although among singletons, this risk was no longer statistically significant.
Comment: Couples undergoing in vitro fertilization should be reassured that absolute risks for autism spectrum disorders and mental retardation in their offspring are small indeed. The increased risk associated with intracytoplasmic sperm injection is of concern because it makes biological sense that sperm abnormalities might preclude spontaneous conception in couples with male-factor infertility; however, the low incidence of these neurologic disorders necessitates confirmation of the present findings. In addition, the extent to which the excess risk might arise from IVF, or from infertility itself, is not yet clear. An editorialist notes the importance of continually monitoring IVF infants and children for neurodevelopmental impairment to help understand and eliminate even modest risks.
Citation(s): Sandin S et al. Autism and mental retardation among offspring born after in vitro fertilization. JAMA 2013 Jul 3; 310:75.
(http://dx.doi.org/10.1001/jama.2013.7222)
Cedars MI. In vitro fertilization and risk of autistic disorder and mental retardation. JAMA 2013 Jul 3; 310:42.
(http://dx.doi.org/10.1001/jama.2013.7223)
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The Taller the Woman, the Greater the Cancer Risk?
By Amy Orciari Herman
Taller postmenopausal women face higher risks for 10 types of cancer, according to a study in Cancer Epidemiology, Biomarkers and Prevention.
Researchers examined the association between height and cancer risk among some 145,000 Women's Health Initiative participants. During roughly 12 years of follow-up, 14% received diagnoses of invasive cancer.
After multivariable adjustment, the risk for all cancers increased significantly, by 13%, with each 10-cm (4-inch) increase in height. In particular, risks for the following types of cancer were increased: breast, colon, colorectal, endometrial, melanoma, multiple melanoma, ovarian, rectal, renal, and thyroid. Additional adjustment for cancer screening did not alter the results.
The researchers say height should be considered "a marker for one or more exposures that influence cancer risk rather than a risk factor itself."
http://cebp.aacrjournals.org/content/early/2013/07/25/1055-9965.EPI-13-0305.abstract
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Centrally Acting ACE Inhibitors Seem to Slow Cognitive Decline in Dementia
By Joe Elia
Patients with dementia taking centrally acting angiotensin-converting enzyme (ACE) inhibitors show slower cognitive decline than those not taking the drugs, a BMJ Open study finds. The difference was small, however, and of "uncertain clinical significance," the authors write.
Some 360 patients with Alzheimer's, vascular, or mixed dementia underwent cognitive testing at baseline and again at 6 months.
Those taking centrally acting ACE inhibitors (perindopril, captopril, lisinopril, ramipril, trandolapril, fosinopril, prinivil, or monopril) at baseline showed a slower 6-month rate of decline in scores on the Standardized Mini-Mental State Examination than those not taking the drugs, but the difference was not significant. Patients just starting on the drugs showed a significant improvement in cognitive scores over the first 6 months, an effect that may be related to better compliance, according to the authors
http://bmjopen.bmj.com/content/3/7/e002881.full
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CMAJ 2013 Jul 9; 185:E475
Can Fluoroquinolones Cause Acute Kidney Injury
A case-control study suggests a modest, but significant, association.
Case reports have suggested that fluoroquinolone antibiotics occasionally cause acute kidney injury. In this case-control study, researchers used a claims database of 767,000 men (age range, 40–85) to compare fluoroquinolone exposure in 1300 men hospitalized for acute kidney injury (cases) and 13,000 similarly aged men hospitalized for other reasons (controls).
Cases were twice as likely as controls to have received oral fluoroquinolones during the week before hospital admission (8.4% vs. 3.9%); in analyses adjusted for comorbidities, other medications, and indication for fluoroquinolone use, the association between acute kidney injury and current fluoroquinolone use was significant (rate ratio, 2.18). The RR was similar when patients with urinary infections were excluded. In contrast, less-recent fluoroquinolone use and current use of amoxicillin or azithromycin were not associated with acute kidney injury. One additional case of acute kidney injury occurred per 1529 fluoroquinolone users. Excess risk was noted for all three commonly prescribed fluoroquinolones: ciprofloxacin, levofloxacin, and moxifloxacin (Avelox). Combined use of quinolones and renin–angiotensin-system blockers elevated risk further (RR for acute kidney injury, 4.46).
Comment: Even if this association between fluoroquinolones and acute kidney injury represents cause and effect, the very small absolute risk should not preclude appropriate prescribing of quinolones. But we should keep the association in mind, particularly when a fluoroquinolone-treated patient unexpectedly is feeling poorly.
Citation(s): Bird ST et al. Risk of acute kidney injury associated with the use of fluoroquinolones. CMAJ 2013 Jul 9; 185:E475.
(http://dx.doi.org/10.1503/cmaj.121730)
http://www.cmaj.ca/content/185/10/E475?ijkey=
e79e73b9c61d1fa92ba93e8561dc9d0c8bf37b71&keytype2=tf_ipsecsha
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Diabetes and Unhealthy Behaviors Seen Leading to Physical Disabilities
By Joe Elia
Two studies, one based on a meta-analysis and another on a French cohort, track the likely path to physical disabilities as patients with diabetes or unhealthy lifestyles age.
A Lancet Diabetes & Endocrinology meta-analysis of 26 studies of people aged 55 and older found that diabetes of any type was associated with increased risk for disability, including impaired mobility (odds ratio, 1.7), limitations to activities of daily living (OR, 1.8), and limitations on instrumental activities, such as shopping or using the telephone (OR, 1.7).
A BMJ study of some 4000 community-dwelling people aged 65 and older followed for 12 years found associations between disability and unhealthy behaviors: a 72% increased disability risk associated with low or intermediate physical activity; a 24% increased risk from a diet low in fruits and vegetables; and a 26% increased risk from current smoking and former smoking (quit within the past 15 years). People with three unhealthy behaviors had a 2.5-fold risk for disability, relative to those with none.
http://www.thelancet.com/journals/landia/article/PIIS2213-8587(13)70046-9/abstract
http://www.bmj.com/content/347/bmj.f4240
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GlaxoSmithKline's Activities in China Draw Concern
By Joe Elia
Two articles in the New York Times point to bribery and tainted research involving GlaxoSmithKline employees in China. Other companies' activities are also being investigated by Chinese authorities.
One report points to the activities of a small Shanghai travel agency used by several drug makers. Investigators, according to the report, say the agency "worked with Glaxo to bribe doctors, hospitals and government officials." A Glaxo official acknowledged that some of its senior executives in China "appear to have acted outside of our processes and controls, which breaches Chinese law." The company says it is working with Chinese security officials.
Another report, based on an internal Glaxo investigation obtained by the Times, faults the research practices at the company's Shanghai research center, which develops neurology drugs. According to the Times account, research on using ozanezumab in humans was undertaken before safety studies in animals had been completed. The company says the problems have been addressed.
http://www.nytimes.com/2013/07/23/business/global/glaxo-says-executives-may-have-broken-chinese-law.html?_r=0
http://www.nytimes.com/2013/07/23/business/global/drug-research-in-china-falls-under-a-cloud.html
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JAMA 2013 Jul 10; 310:170
Soy Supplementation Fails to Reduce Risk for Prostate Cancer Recurrence
In patients with locally advanced disease after radical prostatectomy, biochemical recurrence was similar with a daily soy-protein supplement or a placebo.
Given the geographic disparity of prostate-cancer incidence, a number of factors may affect risk for the disease, including diet. For example, in much of Asia, incidence of prostate cancer is relatively low compared with the U.S., but consumption of soy-based foods is relatively high. To determine whether soy protects against prostate cancer, U.S. investigators assessed disease recurrence in patients who consumed a daily soy supplement after radical prostatectomy. Prostate-specific antigen (PSA) recurrence was used as a surrogate for clinical benefit.
A total of 177 patients with locally advanced disease (defined using standard criteria) were randomized in double-blind fashion to receive a daily beverage containing 20 grams of protein from a soy isolate or a placebo (calcium caseinate) within 4 months of surgery for up to 2 years. The primary endpoints were the 2-year rate of PSA recurrence (defined as development of a PSA level ≥0.07 ng/mL) and the time to biochemical recurrence.
The dietary intervention was well tolerated without toxicity, and the adherence rate was >90%. However, a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group led to early closure of the study for lack of benefit. The rate of biochemical recurrence was 28.3% overall, and was similar in the intervention and placebo groups (27.2% and 29.5%; P=0.89). The median time to recurrence, among those who developed recurrence, was nonsignificantly longer in the placebo group (44.0 and 31.5 weeks; P=0.62).
Comment: Prevention studies are difficult to perform. They require large numbers of patients and long and expensive follow-up. Furthermore, it is not at all clear that using high-risk patients with established disease provides a useful surrogate model for dietary intervention.
Citation(s): Bosland MC et al. Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy: A randomized trial. JAMA 2013 Jul 10; 310:170.
(http://dx.doi.org/10.1001/jama.2013.7842)
http://www.ncbi.nlm.nih.gov/pubmed/23839751?access_num=23839751&link_
type=MED&dopt=Abstract
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