• Comment to the FDA – Take Action re Bulk Chemical access for Veterinary Compounding
• PPIs Can Lower Magnesium
• FDA Cracks Down on Unapproved Cold and Allergy Drugs
• Are Diet and IQ Linked in Children?
• Dieting to End ADHD
• Bad News for Screen Junkies
• Timing and Type of Hormone Therapy Affect Breast Cancer Risk
• Estimating the Likelihood of Regaining Walking Ability After Spinal Cord Injury
• Infants, Solid Food, and Obesity
• Are In Vitro Fertilization Success Rates Lower in Overweight Men?
• Who Will Develop Complications of Preeclampsia?
Comment to the FDA – Take Action:
Re: Bulk Chemical access for Veterinary Compounding:
Comment Period Ends Tuesday, March 8th - Click on the Link to comment:
http://www.regulations.gov/#!documentDetail;D=FDA-2010-N-0528-0144
Please take a moment to register your comments to the FDA on this important issue. The FDA has proposed that compounding pharmacists should not have access to pure bulk chemicals needed to prepare medications. This would have the following effects:
1. Pre-manufactured products are permitted a +/- 10% variation in strength and potency per USP manufacturing guidelines. Pure Bulk ingredients from approved chemical sources are within 1-2% of stated composition. Compounding limited to pre-manufactured sources increases the inaccuracy of an end product by definition
2. Compounding limited to pre-manufactured products increases the cost to consumers as these starting sources are more expensive than bulk chemicals.
3. Using pure Bulk chemicals eliminates excipients and contaminants that are inherently found in pre-manufactured products that are NOT found in Puer, Bulk Chemicals.
Your comments are needed now.
Thank you
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PPIs Can Lower Magnesium
Nexium will soon carry a new warning that long-term use may cause low magnesium levels. Low magnesium can lead to complications, including muscle spasms, irregular heartbeat and seizures. If magnesium supplements do not help, patients may need to stop taking the drugs.
About 21 million U.S. patients filled prescriptions for the drugs in 2009; sales of Nexium, the market leader, topped $5 billion in 2010. The agency said there was little risk of low magnesium with lower-dose over-the-counter ulcer medicines if they are taken short term as directed.
http://www.reuters.com/article/2011/03/02/us-ulcer-drugs-idUSTRE7216AL20110302
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FDA Cracks Down on Unapproved Cold and Allergy Drugs
The FDA has announced a crackdown on the sale of prescription cold, cough and allergy products that were never approved by the FDA to be safe and effective. Approximately 500 products have not been formally evaluated by the FDA and will be removed from the market. This is the latest in a series of actions by the FDA to stop the sale of a variety of products that are being sold without FDA approval.
With some reports of complications from the products, such as irritability and over-sedation, the FDA is unaware of how widely the products might cause problems or even how commonly the products are used.
The FDA is removing roughly 500 prescription cough, cold, and allergy medications from the market because they have not gone through the proper approval process to evaluate safety, effectiveness, and quality.
Clinicians are prescribing these products without knowing their approval status, the agency says. The drugs were on the market before laws changed, requiring new drugs to undergo rigorous testing. Many of the drugs contain similar ingredients as children's over-the-counter cough and cold medicines that were relabeled in 2008 to limit their use to children older than 2 years of age because of potentially life-threatening side effects. The labels for unapproved drugs underwent no such revision.
With many alternative over-the-counter and prescription drugs already available and FDA-approved, the agency says that "an unapproved prescription product is an unnecessary risk."
Companies must stop manufacturing the indicated products within 90 days and stop shipping the products within 180 days. The FDA lists the products on its website, www.fda.gov. FDA officials stated that they were confident that consumers could get whatever relief they needed from cough, cold and allergy medications on the market by using the many over-the-counter and prescription products that had been approved by the FDA.
http://www.washingtonpost.com/wp-dyn/content/article/2011/03/02/AR2011030203206.html?moreheadlines
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J Epidemiol Community Health 2011 Feb 7;
Are Diet and IQ Linked in Children?
A healthy diet was positively associated with IQ at age 8 years.
Most studies of long-term effects of nutrition in early childhood focus on cardiovascular and metabolic outcomes. Less is known about the effect of children's diet on intelligence. In a prospective cohort study, researchers examined this association using data from parent-reported food-frequency questionnaires collected at ages 3, 4, 7, and 8.5 years for 13,988 children in England. At age 8.5 years, 7044 children (the study group) completed the Wechsler Intelligence Scale; these children were more likely to be girls, to have been breast-fed, and to have older mothers with higher levels of education than children without IQ data.
Three consistent dietary patterns were found at each time point: processed (convenience foods with high fat and sugar content), traditional (meat, poultry, potato, and vegetable), and health conscious (salad, fruit, vegetables, fish, pasta, and rice). A snacking dietary pattern (finger foods such as fruit, biscuits, bread, and cakes) was also found at age 3 years. In a fully adjusted analysis that controlled for many factors including mother's education and social class, the processed dietary pattern at age 3 years was negatively associated with IQ at age 8.5 years; each 1-standard deviation (SD) increase in processed-food score was associated with a 1.7- point decrease in IQ (P<0.0001). The health-conscious dietary pattern at age 8.5 years was positively associated with IQ; a 1-SD increase in health-conscious dietary pattern score was associated with a 1.2-point increase in IQ (P=0.001). The snacking pattern at age 3 years was associated with a significant 1-point increase in IQ at age 8.5 years (P<0.0001).
Comment: In this study, a diet high in fat, sugar, and processed food in early childhood was associated with a small reduction in IQ in school-age children, and a healthy diet of fruit, vegetables and fish in school-age children was associated with a small increase in IQ. Although the change in individual IQ scores was small, the effect on large populations of children could have greater significance (similar to the positive association between low lead levels and IQ). Do we need proof of a few additional IQ points to encourage healthy nutrition in children? Probably not, but the possibility might motivate some parents (and school cafeteria staff) to provide children with a healthy diet.
— Martin T. Stein, MD Published in Journal Watch Pediatrics and Adolescent Medicine March 2, 2011
Citation(s): Northstone K et al. Are dietary patterns in childhood associated with IQ at 8 years of age? A population-based cohort study. J Epidemiol Community Health 2011 Feb 7; [e-pub ahead of print]. (http://dx.doi.org/10.1136/jech.2010.111955)
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Lancet 2011 Feb 5; 377:494.
Dieting to End ADHD
A restricted diet led to equivocal results, and the diet might be difficult to institute.
Because studies have suggested possible roles for diet and immunoglobulin (Ig) in attention deficit hyperactivity disorder (ADHD), these researchers compared two diets in children with ADHD (age range, 4–8 years), who were recruited via advertisements.
In the multiphase study, 100 unmedicated children (mean age, 6.5) were randomized to an individually tailored, restricted diet or a normal diet for 5 weeks. Restricted-diet responders continued these diets and were rerandomized in a crossover design to challenge with foods that induced low or high IgG levels. Parents were not blinded to diets except for IgG-related foods; behavioral assessments were obtained by physicians, from their own observations and from parent reports, and occurred on different schedules for the two groups.
Of 41 patients who completed the restricted diet, 32 met improvement criteria for ADHD or oppositional defiant disorder. Of 30 children entering the second phase, 63% relapsed with a food challenge, but outcomes did not differ by the IgG level of the challenge.
Comment: Nonmedication therapies are especially important to study in developing children. This study, however, had several features that may have biased the findings. Physicians administered the assessments to parent informants who knew the diet contents, volunteered for a diet study, and provided a highly tailored diet to their children. Thus, parental objectivity might have been less than if teachers or other informants, who were blind to the diet but able to observe the children, had been used. Combining preschool and school-age children may be problematic, as they respond differently to methylphenidate (J Am Acad Child Adolesc Psychiatry 2006; 45:1284). Even if these findings are replicated, it is not known whether dietary restriction would normalize neurodevelopment, as seen with methylphenidate in imaging studies (e.g., Am J Psychiatry 2010; 167:977). Potential problems with dietary regimens include the psychological effects of nonparticipation in numerous age-appropriate activities (e.g., cake at birthday parties, peer outings to fast food places, same diet as siblings). Practitioners who offer dietary trials to families need to discuss the complicated logistics of tailored diets and lack of knowledge about neurodevelopmental and psychological effects of dietary therapy for ADHD.
— Barbara Geller, MD Published in Journal Watch Psychiatry February 28, 2011
Citation(s): Pelsser LM et al. Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): A randomised controlled trial. Lancet 2011 Feb 5; 377:494. http://www.ncbi.nlm.nih.gov/pubmed/21296237?dopt=Abstract
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J Am Coll Cardiol 2011 Jan 18; 57:292
Bad News for Screen Junkies
Even after accounting for physical activity levels, spending a lot of discretionary time in front of a television or computer is an independent predictor of cardiovascular events.
In a recent study, the number of hours participants spent watching television was associated with cardiovascular mortality risk (JW Cardiol Feb 17 2010). However, little is known about the effects of screen time — not only television viewing but also other screen-based forms of entertainment — on different cardiovascular outcomes. These investigators used 2003 data from the Scottish Health Survey (SHS) to assess the effects of recreational screen time on all-cause mortality and fatal or nonfatal cardiovascular disease (CVD) events and to determine the extent to which such associations are mediated by metabolic (body mass index, HDL and total cholesterol levels) or inflammatory (C-reactive protein level) markers. More than 4500 SHS respondents (1945 men) were followed for approximately 4 years. The main variables of interest were interviewer-assessed non–employment-related screen time (<2 hours/day; 2 to <4 hours/day; and greater than or equal to 4 hours/day) and nonoccupational, moderate - to vigorous-intensity physical activity.
During nearly 20,000 person-years of follow-up, 215 CVD events and 325 all-cause deaths occurred. After multivariable adjustment, participants engaging in greater than or equal to 4 hours per day, as compared with <2 hours per day, of screen time had significantly increased risks for all-cause mortality and CVD events (hazard ratios, 1.52 and 2.30, respectively). The associations were slightly attenuated but remained significant after further adjustment for physical activity (HRs, 1.48 and 2.25, respectively). In subsequent analyses, metabolic and inflammatory cardiovascular risk factors collectively accounted for only about one quarter of the association between screen time and CVD events.
Comment: This large observational study suggests that recreational screen time is a powerful cardiovascular risk factor. The risk was only mildly attenuated by physical activity and was not explained by the presence of other CVD risk factors. Given that screen time is increasing, particularly in young people, population-based interventions to reduce screen time may have important implications for modifying cardiovascular outcomes.
— JoAnne M. Foody, MD Published in Journal Watch Cardiology March 2, 2011
Citation(s): Stamatakis E et al. Screen-based entertainment time, all-cause mortality, and cardiovascular events: Population-based study with ongoing mortality and hospital events follow-up. J Am Coll Cardiol 2011 Jan 18; 57:292. http://www.ncbi.nlm.nih.gov/pubmed/21232666?dopt=Abstract
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J Natl Cancer Inst 2011 Feb 16; 103:296
Timing and Type of Hormone Therapy Affect Breast Cancer Risk
British study suggests early initiation is riskier; findings on estrogen-only therapy contrast with WHI findings.
Hormone therapy (HT) initiated in recently menopausal women seems to lower risk for coronary artery disease and dementia (JW Womens Health Apr 8 2010 and JW Neurol Jan 4 2011). Now, U.K. investigators for the observational Million Women Study (MWS) have assessed whether timing of HT initiation affects breast cancer risk.
Compared with never use, initiation of estrogen-only HT within 5 years of menopause onset was associated with modestly elevated risk for breast cancer (relative risk, 1.43), whereas initiation 
5 years after onset of menopause was not associated with excess risk for breast cancer (RR, 1.05). Initiation of combination estrogen-progestin HT within 5 years of menopause also was associated with greater risk (RR, 2.04) than was later initiation (RR, 1.54).
Comment: Women initiate HT primarily for relief of menopausal symptoms, which are most severe soon after menopause; thus, HT typically is initiated within 5 years of menopause onset, which makes the results of this study clinically relevant. Editorialists note that these findings agree with those of the Women's Health Initiative (WHI) clinical trial in showing that breast cancer risk is incrementally greater with earlier than with later initiation of HT. However, the findings diverge with respect to the effects of estrogen-only HT on breast cancer risk. WHI investigators found no suggestion that estrogen-only HT raised risk in any subgroup and also observed protection against breast cancer among women in the estrogen-only group who were highly adherent to study medication. The editorialists suggest that mammogram frequency might account for the discrepancy: WHI participants all had normal results on baseline mammograms and could only continue study medication if they underwent annual mammograms. In the MWS, breast cancers identified at initial mammograms were included in the analyses, and participants were offered subsequent mammography screening every 3 years (to which adherence varied).
I plan to continue counseling those of my patients with intact uteri that long-term use of combination HT is associated with modest excess risk for breast cancer. For those patients who have undergone hysterectomies, I will continue to discuss the current understanding that estrogen-only therapy does not affect breast cancer risk.
— Andrew M. Kaunitz, MD Published in Journal Watch Women's Health March 3, 2011
Citation(s): Beral V et al. Breast cancer risk in relation to the interval between menopause and starting hormone therapy. J Natl Cancer Inst 2011 Feb 16; 103:296. (http://dx.doi.org/10.1093/jnci/djq527) http://www.ncbi.nlm.nih.gov/pubmed/21278356?dopt=Abstract
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http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62276-3/fulltext
Estimating the Likelihood of Regaining Walking Ability After Spinal Cord Injury
A prediction rule based on age and four simple clinical exams can predict the likelihood that a patient who has suffered traumatic spinal cord injury will be able to walk in a year.
The work is reported in the Lancet.
Researchers first established the rule by examination of data collected prospectively over 7 years from some 500 patients with spinal cord injury. The data were then used to formulate the prediction rule, whose outcome measure is the ability to walk indoors independently 1 year after injury. In addition to age (younger or older than 65), the clinical measures — assessed within 15 days after injury — were motor scores of the quadriceps femoris (nerve supply, L3) and the gastrocsoleus (nerve supply, S1) muscles and scores for light-touch sensation on dermatomes L3 and S1.
The rule, tested prospectively on an additional group of patients, showed "excellent" ability to discriminate between those who would and would not be able to walk independently by 1 year.
The Lancet, Early Online Publication, 4 March 2011; doi:10.1016/S0140-6736(10)62276-3
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Pediatrics 2011 Mar; 127:e544
Infants, Solid Food, and Obesity
Timing of solid food introduction was significantly associated with risk for obesity in formula-fed infants but not in breast-fed infants.
The best time to introduce solid food to infants is controversial. Boston investigators examined the association between timing of solid food introduction and obesity in a prospective birth cohort. Parents were questioned about mode of feeding and introduction of solid food at 6 months and 3 years after birth.
Of the 847 infants, 67% were breast-fed (defined as partially breast-fed for greater than or equal to 4 months) and 33% were formula-fed (never breast-fed or breast-fed for <4 months). At age 3 years, 9% of children were obese (body-mass index greater than or equal to 95th percentile) — 7% of breast-fed children and 13% of formula-fed children. Timing of introduction of solid food was not associated with obesity in breast-fed infants, but introduction of solid food before age 4 months was associated with significantly increased risk for obesity in formula-fed infants (odds ratio, 6.3).
Comment: Unfortunately, this study suffers from some limitations of previous studies mentioned by the authors, including small sample size (especially the number of breast-fed infants who received solids before age 4 months), recall bias, and arbitrary classification of feeding status. However, the results support a recent controversial review reinforcing numerous international recommendations that solid food should not be introduced before age 4 months, but questioning the wisdom of delaying introduction of solids beyond age 4 months in both formula-fed and breast-fed infants in developed countries (JW Pediatr Adolesc Med Mar 2 2011). So what do we tell parents? I believe that exclusive breast-feeding up to age 4 months still is optimal. With respect to introduction of solids in developed countries after 4 months, data are uncertain and all bets are off.
— Howard Bauchner, MD Published in Journal Watch Pediatrics and Adolescent Medicine March 2, 2011
Citation(s): Huh SY et al. Timing of solid food introduction and risk of obesity in preschool-aged children. Pediatrics 2011 Mar; 127:e544. (http://dx.doi.org/10.1542/peds.2010-0740) http://www.ncbi.nlm.nih.gov/pubmed/21300681?dopt=Abstract
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J Assist Reprod Genet 2010 Sep; 27:539
Are In Vitro Fertilization Success Rates Lower in Overweight Men?
Retrospective analysis says yes, except when intracytoplasmic sperm injection is used.
Prevalence of obesity is rising worldwide, and the detrimental effects of this condition on female fertility have become apparent. Moreover, obese women with overweight or obese partners have as much as twofold lower fertility than do obese women with normal-weight partners. In a retrospective study at a single center, investigators tested the hypothesis that in vitro fertilization (IVF) success rates would be negatively affected in men with body-mass index (BMI) greater than or equal to 25 kg/m2.
Of 290 analyzed cycles, 115 (40%) resulted in clinical pregnancies. This rate was 34% when male BMI was greater than or equal to 25 and 53% when male BMI was <25. The effect of high male BMI was independent of female BMI or number of embryos transferred. When intracytoplasmic sperm injection (ICSI) was used, overweight male status was not associated with lower pregnancy rates.
Comment: These data suggest that sperm from overweight men are impaired, and that this abnormality (which remains uncharacterized) can be overcome by use of intracytoplasmic sperm injection. Still, the study is retrospective, so the results should not lead IVF centers to use ICSI routinely for men who are overweight. Prospective studies clearly are warranted; nonetheless, these results point to yet another unfortunate consequence of obesity.
— Robert W. Rebar, MD Published in Journal Watch Women's Health February 3, 2011
Citation(s): Keltz J et al. Overweight men: Clinical pregnancy after ART is decreased in IVF but not in ICSI cycles. J Assist Reprod Genet 2010 Sep; 27:539 http://www.ncbi.nlm.nih.gov/pubmed/20635132?dopt=Abstract
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Lancet 2011 Jan 15; 377:219
Who Will Develop Complications of Preeclampsia?
Predictive model identified women at excess risk for poor outcomes.
Foretelling which women with preeclampsia will develop fatal or life-threatening complications has proven difficult. To develop a predictive model, investigators followed 2023 women in Canada, Australia, New Zealand, and the U.K. who were admitted to tertiary care hospitals with preeclampsia or who developed preeclampsia after admission. Potential predictors of poor outcomes included variables encompassing demographics, medical and obstetric histories, and clinical and laboratory findings.
A total of 261 women experienced adverse outcomes, for which six variables (gestational age, chest pain or dyspnea, serum creatinine level, platelet count, aspartate aminotransaminase level, and oxygen saturation) were predictive. The model predicted adverse outcomes within 48 hours of admission with 76% sensitivity and 87% specificity; area under the curve of the receiver operating characteristic was 88%, and remained >70% even after 7 days.
Comment: This ambitious study has provided insight into the natural history of preeclampsia, as well as a strategy for directing interventions toward women who are at highest risk for serious complications of preeclampsia. A risk calculator is available; however, the model's clinical use might be limited given that many of its individual components (e.g., gestational age, maternal liver function) are already used in isolation to guide obstetric care — and other components themselves (e.g., dyspnea, chest pain) can be considered adverse outcomes of preeclampsia rather than predictors of adverse outcomes. Thus, whether application of this model will result in better outcomes remains unclear; and, as editorialists note, further adaptation and testing of the algorithm must take place in settings other than tertiary care centers in high-income countries. The investigators plan to validate the model in middle- and low-resource countries.
— Anna Wald, MD, MPH Published in Journal Watch Women's Health January 27, 2011
Citation(s): von Dadelszen P et al. Prediction of adverse maternal outcomes in pre-eclampsia: Development and validation of the fullPIERS model. Lancet 2011 Jan 15; 377:219. http://www.ncbi.nlm.nih.gov/pubmed/21185591?dopt=Abstract
