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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
May 28, 2011

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NSAIDs and Diverticular Complications
SimplyThick - Not to Be Used in Some Infants
Colcrys and URL Pharma
Nuedexta Pricing Also Under Scrutiny
Food Allergy or Digestive Problem?
Managing Obesity in Primary Care: The Challenge Continues
Effect on Fracture Risk
Trial of Niacin to Increase HDL in High-Risk Patients Stopped Early After Showing No Benefit
Extended-Release Niacin Outperforms Ezetimibe in Lowering Cardiovascular Risk
Kids Who Sleep More Are Less Likely to Become Overweight
Fish Cut Female Heart Failure; Fried Fish Raised Risk
For Which Conditions Is Tai Chi Effective?
Revisiting Gestational Weight Gain in Obese Women
Eating Fish to Prevent Preterm Birth: No Need to Go Overboard
Bacterial Meningitis in the U.S.: An Update
Low Apgar Scores Linked with ADHD
Rethinking Zinc as First-Line Therapy for Wilson Disease

Gastroenterology 2011 May; 140:1427
NSAIDs and Diverticular Complications
Use of nonsteroidal anti-inflammatory drugs, including aspirin, was associated with higher risks for diverticular bleeding compared with nonuse of these drugs.
     Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with complications in the lower gastrointestinal tract, primarily diverticular bleeding and diverticulitis
(JW Gastroenterol Dec 12 2008).
     Now, investigators have conducted a prospective study of the effect of NSAIDs, including aspirin, on diverticular complications in 47,210 men enrolled in the Health Professionals Follow-Up Study. Approximately 29% of participants were regular aspirin users (≥2 times per week), and 5% used NSAIDs regularly. During follow-up of 22 years, 938 incident cases of diverticulitis and 256 cases of diverticular bleeding were documented. Results were as follows:

     Comment: These data suggest that patients with diverticulitis, particularly recurrent diverticulitis or complicated diverticulitis that has not been treated surgically, should be aware of the risks associated with NSAIDs, and alternatives should be considered when possible. The 81 mg dose of aspirin daily for cardiovascular prophylaxis might be reasonably safe for patients with diverticulitis. All dosages of aspirin and NSAIDs seem to increase the risk for diverticular bleeding.
Douglas K. Rex, MD Published in Journal Watch Gastroenterology May 27, 2011
     Citation(s):Strate LL et al. Use of aspirin or nonsteroidal anti-inflammatory drugs increases risk for diverticulitis and diverticular bleeding. Gastroenterology 2011 May; 140:1427. http://www.ncbi.nlm.nih.gov/pubmed/21320500?dopt=Abstract
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SimplyThick - Not to Be Used in Some Infants
     Parents and pediatricians are advised by the FDA not to use the thickening gel SimplyThick for infants born before 37 weeks. According to the FDA, 15 infants who had been given the product developed a life-threatening intestinal condition known as necrotizing enterocolitis; two of those infants died. The purpose of the thickener is to help those with swallowing problems keep their food down. For more information, please use the following links:
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Colcrys and URL Pharma
     Just a few weeks ago we had the uproar on the premature birth prevention drug Makena. Well, its déjà vu all over again, but we have all been aware of it. URL Pharma took a long-used gout drug, colchicine, and ran its version through clinical trials, placed a brand name of Colcrys on it, and obtained FDA approval and three years of exclusivity. It set a much, much higher price for the new drug (more than $5 per tablet) than what the former version carried; the product is the same but now the patient has to pay for the government approved version, despite the fact it has been used safely and effectively for ages.
     The pricing has been questioned from the beginning; now, however, four congressmen have written to URL's chief executive demanding some back-up for the company's higher price on a long-used drug. The documentation requested includes the cost of the trials necessary to win FDA approval, the marketing budget for the drug, its manufacturing costs, and projected sales and profits. The lawmakers are looking for a response by June 10.
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Nuedexta Pricing Also Under Scrutiny
     Congress hasn't limited their latest pricing crusade to URL Pharma's Colcrys. The same group of congressional members who wrote URL to question the pricing on its gout drug has also jumped on Avanir, whose Nuedexta drug is a combination of two longtime generics (quinidine and dextromethorphan).
     Nuedexta won FDA approval last fall along with three years of exclusivity as a treatment for pseudobulbar effect, a condition in which patients lack the ability to control outbursts of intense crying or laughing (that may accompany neurological problems such as multiple sclerosis and brain trauma). The company has been asked to explain why these cheap generics, available for about $20 per month, cost $600 monthly when combined into Nuedexta.
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Food Allergy or Digestive Problem?
     Neither one is fun to experience, but there are some key differences between food allergies and digestive problems. One example: With a food allergy, you might get hives but you probably won't with a digestive condition. Find out how to determine which is behind your symptoms. By Krisha McCoy, MS Medically reviewed by Lindsey Marcellin, MD, MPH
When Loring Gotschall of Marblehead, Mass., eats avocados, bananas, raw chestnuts, or kiwi, she has an unusual reaction — severe abdominal pain for a couple of hours.  "I used to eat a banana every day for breakfast, and over time they started affecting me," she says. At first, she thought a digestive problem was causing the cramps, but she soon discovered that it might be a food allergy related to her known allergy to latex, found in some medical gloves and bandages. Certain foods, including avocado, banana, chestnut, kiwi, and pineapple, contain some of the same proteins as latex, which is made from natural rubber.
Is It a Food Allergy or a Digestive Problem?
     It turns out that Gotschall probably has a food allergy, but determining whether a reaction is a food allergy or digestive issue can be difficult. Food allergies and digestive problems, known as food intolerances, can have similar symptoms. With both conditions, eating certain foods can result in abdominal symptoms, including diarrhea, abdominal pain, and gas.
     But with most food allergies, certain symptoms can help distinguish them from a non-allergic digestive problem. "Food allergies, in most cases, are going to be associated with an acute onset of hives and/or lip or tongue swelling that is going to happen within 10 to 15 minutes of digesting the food, if not immediately," says Julie McNairn, MD, an allergist and immunologist in Cincinnati. This is not an uncommon problem: More than 3 percent of adults have one or more food allergies, according to a study in the Journal of Allergy and Clinical Immunology.
     If you often feel sick after consuming certain foods, it is possible that you could have a food allergy. Common symptoms include:

     But if you experience mainly abdominal symptoms after eating a certain food, such as milk, you may simply have a food intolerance, which means that your body cannot properly digest that particular food. That means your body cannot properly digest that food. "If you eat a food and it just causes your stomach to be upset, that is probably just an intolerance," says Dr. McNairn.
Diagnosing a Food Allergy
     If you notice a reaction when you eat certain types of foods, talk to your primary care physician. If he suspects a food allergy, you may be referred to an allergist who can determine whether you are allergic to certain food allergens or if you have an intolerance. Either way, your doctors can help come up with a plan to avoid the food and manage the symptoms when and if a reaction occurs.  You should do this sooner than later. Fear of having a reaction to foods can keep you from and get both your diet and your social life back into gear.
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Arch Pediatr Adolesc Med 2011 Apr 4
Managing Obesity in Primary Care: The Challenge Continues
A multicomponent primary care obesity intervention for young children did not have a significant effect on body-mass index.
     Few randomized trials indicate that primary care–based interventions for obesity in children lead to sustained reductions in body-mass index (BMI). The most convincing study involved 12 weeks of cognitive behavioral therapy. Even fewer data are available about management of obesity in preschool children. In a study of 475 children (age range, 2–6 years) with BMI >95th percentile (or >85th percentile if 1 parent was overweight), researchers compared 1-year outcomes between children at five practices randomized to provide a primary care–based intervention and those at five practices randomized to provide usual care. The intervention involved restructuring of practices based on a chronic care disease model and training nurses to use motivational interviewing and educational modules for families. Usual care involved well-child visits and follow-up appointments for checking weight.
     At baseline, mean BMI was 19.2 kg/m2 and 19.1 in the intervention and usual-care groups. At 1 year, BMI had increased by similar amounts in the two groups (mean increase, 0.31 and 0.49, respectively). In adjusted multivariate analysis, the intervention group had a smaller nonsignificant change in mean BMI compared with the usual-care group, a significantly greater relative reduction in television viewing, (–0.36 hours/day), and a nonsignificant reduction in intake of fast food and sugar-sweetened beverages. Post hoc analyses showed significant effects from the intervention on BMI among girls but not boys and among participants in households with annual incomes of ≤US$50,000.
     Comment: The late child psychiatrist Leon Eisenberg said that "Time with the patient will remain the currency of medical care." Taking adequate time to develop a therapeutic alliance with children and their parents can result in behavioral change, but the effect on childhood obesity is limited. The intervention in this study required a huge commitment for behavioral management, practice restructuring, and clinician training. Even so, BMI measurements at 1 year did not differ between patients who received the intervention and those who received usual care. Data for school-age children and adolescents are somewhat more encouraging but are limited to well-controlled environments with funding for personnel. Until we have interventions with long-term effects, we can do our best to encourage weight reduction through diet and physical activity, recognizing that our efforts may have limited benefits.
Martin T. Stein, MD Published in Journal Watch Pediatrics and Adolescent Medicine May 25, 2011
     Citation(s): Taveras EM et al. Randomized controlled trial to improve primary care to prevent and manage childhood obesity: The High Five for Kids study. Arch Pediatr Adolesc Med 2011 Apr 4; [e-pub ahead of print]. (http://dx.doi.org/10.1001/archpediatrics.2011.44)
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Effect on Fracture Risk
Dietary calcium intake above certain levels has little effect on women's risk for fracture or osteoporosis, according to a BMJ study.
     Researchers followed some 60,000 women, aged about 55 at study entry, for 20 years. Calcium intakes were estimated with food-frequency questionnaires, and a subcohort underwent measurements of bone mineral density.
     Subjects were separated into quintiles by cumulative calcium intake. Those in the lowest quintile were at greatest risk for having a first fracture of any type, hip fracture, or osteoporosis during follow-up, when compared with the middle quintile (reference group). After multivariable adjustment, those in the remaining higher-intake quintiles showed no greater advantage for avoiding fracture. In fact, hip fracture risk increased among those with the highest calcium intakes.
     The authors say their results suggest that in preventing osteoporotic fractures, "emphasis should be placed on individuals with a low intake of calcium rather than increasing the intake of those already consuming satisfactory amounts."
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J Clin Oncol 2011 Jan 1; 29:54
Trial of Niacin to Increase HDL in High-Risk Patients Stopped Early After
Showing No Benefit

     A major government study has been stopped early because it showed no benefit to raising HDL levels with niacin in patients at high risk for cardiovascular events, the National Heart, Lung, and Blood Institute announced Thursday.
In the AIM-HIGH trial, the rate of MI, stroke, hospitalization for acute coronary syndrome, or revascularization among some 3400 patients did not differ between a group taking statin plus high-dose niacin and one taking statin plus placebo during 32 months' follow-up. All patients had well-controlled LDL levels at entry, but had low HDL levels and high triglycerides.
     Asked to comment, Dr. Harlan Krumholz of Journal Watch Cardiology wrote: "This study reinforces that medications that change a risk factor do not necessarily change patient risk. Niacin, fibrates, and ezetimibe have so far failed to show that they improve patient outcomes in patients on statins. Be on guard for claims that are based only on how an intervention affects a risk factor — we need studies that show us the effect of these drugs on outcomes that patients experience."
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Extended-Release Niacin Outperforms Ezetimibe in Lowering
Cardiovascular Risk

     In patients with high cardiovascular risk, extended-release niacin is associated with better outcomes than ezetimibe, according to a New England Journal of Medicine study released online.
     Researchers randomized over 350 patients on long-term statins to added therapy with either niacin or ezetimibe. The primary endpoint was the difference in change of carotid artery intima–media thickness from baseline to 14 months between groups. After 208 patients had completed the trial, it was stopped when results significantly favored niacin.
     Two accompanying editorials bemoan the trial's early end, arguing that all patients studied up to the point of stoppage should have been analyzed, not just those who completed 14 months' therapy. Nonetheless, both support the use of niacin over ezetimibe in high-risk patients, and both point to trials, now under way, that may provide more definitive results. In Journal Watch Cardiology, Dr. Harlan Krumholz says that these results "will not be available for many years. In the meantime, ezetimibe should be a drug of last resort, if it is used at all."
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Kids Who Sleep More Are Less Likely to Become Overweight
     The more sleep that young children get, the less likely they are to become overweight, according to a longitudinal study in BMJ.
     Researchers in New Zealand followed some 240 children from ages 3 to 7. Sleep was measured with accelerometers at ages 3, 4, and 5, while body mass index and body composition were measured yearly.
     After multivariable adjustment, each additional hour of sleep from ages 3 to 5 was associated with a reduction in BMI of 0.49 at age 7 — corresponding to a reduction in body weight of 0.7 kg in a child of median height. Differences in fat mass index, rather than fat-free mass index, accounted for the reduced BMI. In addition, each extra hour of sleep was associated with a 61% reduction in the risk for being overweight at age 7.
     The authors speculate that both behavioral and hormonal factors may play a role in the sleep-weight connection.
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Article from Vital Choices Newsletter
(http://newsletter.vitalchoice.com/e_article002115919.cfm?x=bjv2vVK ,b1h1R7NC)
May 26, 2011
Fish Cut Female Heart Failure; Fried Fish Raised Risk
Huge women's health study links fatty fish to reduced heart failure risk; fried fish of any kind raised the risk
by Craig Weatherby
     By now it's quite clear that fish and fish oil curb the risk of stroke and cardiovascular disease and their undesirable outcomes ... but deep-fried fish appears to raise heart and stroke risks.
     More recently, evidence that fish and fish oil also curb the risk of heart failure has been growing  ... see “Fish Oil Trial Finds More Heart-Failure Benefits”. Heart failure is a burgeoning affliction that affects about five million Americans, as detailed in the sidebar, “Heart failure: A growing plague”, below. There’s even evidence that fish curbs heart failure risk in men and women alike … findings from, among other sources, the large Swedish studies we reported in “Female Heart Failure Cut by Fish” and “Fatty Fish May Cut Men's Heart-Failure Risk”.
 Preliminary evidence from two clinical trials supports the presumption that the omega-3s in fish explain its heart-failure benefits: see “Fish Oil May Help Congestive Heart Failure” and “Heart Failure Findings Favor Omega-3s over Statin Drug”. Now, we have supporting evidence that fish deters heart failure from the even larger Women's Health Initiative … one of the most far-reaching investigations of women’s health in America (Belin RJ et al. 2011).
     Cardiovascular disease (CVD) is a key underlying cause of heart attacks and heart failure. And most studies link fishy diets and omega-3 fish oil supplements alike to reduced risk of CVD … probably because omega-3s lower triglycerides and raise HDL (good) cholesterol while moderating inflammation, oxidative stress, and blood pressure.  
Huge study finds fatty fish lowers heart risks; fried fish raises them
     The Women's Health Initiative (WHI) focuses on heart disease, cancer, and fractures in postmenopausal women … a 15-year project that includes epidemiological studies and controlled clinical trials. The epidemiological or “observational” part of WHI – called the Women's Health Initiative Observational Study (WHI-OS) – compares participants’ diets and lifestyles to their health outcomes over a 10-year period. The latest WHI-OS data analysis covered 84,493 postmenopausal women aged 50 to 79; average age 63 (Belin RJ et al. 2011). Its findings echo those of prior population studies, which consistently linked fatty, non-fried fish to reduced heart disease risk, but tied fried fish of any kind to higher heart risk (see our sidebar, "Fried fish clearly raise heart risks"). Compared with women who rarely ate fish, women who reported eating five or more servings of baked or broiled fatty fish per week were 30 percent less likely to develop heart failure within the decade. In contrast, eating fried fish just once a week appeared to raise the risk of developing heart failure by 50 percent. Most of the reduction in heart-failure risk with frequent consumption of broiled or baked fish was due to eating fatty fish such as salmon, sardines, mackerel, and other species high in fat … therefore also high in omega-3 fatty acids.Smaller risk reduction was associated with eating non-fried tuna or white fish (e.g., pollock, sole, snapper, or cod). However, as with most diet surveys, the one used in this study probably did not ask women to differentiate between relatively lean “light” canned tuna (i.e., skipjack, tongol) and relatively fatty “white” canned tuna (albacore).
Study called scientifically solid and supportive of fatty, non-fried fish
     Women with a history of heart attack were excluded from the study, and the researchers adjusted the results to account for the influence of known heart failure risk factors. The women were surveyed for diet information, including their fish consumption and usual preparation form (baked, broiled, or fried). Based on their replies to the diet survey, women were divided into five categories of broiled or baked fish consumption – from less than once a month (the so-called “reference” group) to five or more times a week – and three categories of fried fish consumption: from less than once a month to one or more times a week. According to Dr. Rachel Johnson at the University of Vermont – a member of the AHA’s nutrition committee – the study had a “strong design”, since it was a large, lengthy, and relied on a “rich database.” (Busko M 2011). But it’s important to note that, as with most population studies, the researchers had to try to account for the influences of other risk factors – so-called “confounders” – which can skew the results. For example, the women who ate the fattiest, broiled or baked fish tended to be younger and more physically fit and to follow a healthier diet. And the women who ate the most fried fish of any kind were more likely to smoke and to have a higher body-mass index (BMI), higher systolic BP, diabetes, atrial fibrillation, and coronary heart disease (clogged, inflamed major heart vessels).
     Still, as Dr. Johnson said, “The take-home message is that if you are not already regularly eating fish, try to add it to your diet, and have it in a preparation method retaining the beneficial aspects of fish.” (Busko M 2011) She also noted that the AHA recommends at least two servings of fish a week, and added, “There is certainly no harm in eating more than two servings a week, particularly if you have risk factors.” (Busko M 2011). The authors noted that they found no significant associations between heart-failure risk and estimated intakes of omega-3 EPA+DHA (from fish), omega-3 ALA (from plant foods), or trans fats. Therefore, they cautioned – apparently ignorant of the clinical evidence contradicting this concern – that omega-3 fish oil might not deliver heart-failure benefits to the same degree whole fatty does. We’d agree, however, that other constituents in fatty fish – such as vitamin D – may reduce heart failure risk, and that people eating a diet high in fish likely eat less meat and poultry, which are generally less heart-healthful.
     Sources: Belin RJ, Greenland P, Martin L, et al. Fish intake and the risk of incident heart failure: The Women's Health Initiative. Circ Heart Fail. 2011; DOI:10.1161/CIRCHEARTFAILURE.110.960450. Busko M. Baked/broiled fish reduces HF, fried fish ups risk. May 25, 2011. Accessed at http://www.theheart.org/article/1231133.do Marchioli R, Levantesi G, Silletta MG, Barlera S, Bernardinangeli M, Carbonieri E, Cosmi F, Franzosi MG, Latini R, Lucci D, Maggioni AP, Moretti L, Nicolosi GL, Porcu M, Rossi MG, Tognoni G, Tavazzi L; GISSI-HF Investigators. Effect of n-3 polyunsaturated fatty acids and rosuvastatin in patients with heart failure: results of the GISSI-HF trial. Expert Rev Cardiovasc Ther. 2009 Jul;7(7):735-48.Gissi-HF Investigators, Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Oct 4;372(9645):1223-30. Epub 2008 Aug 29.
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Br J Sports Med 2011 May 16
For Which Conditions Is Tai Chi Effective?
Systematic review finds benefit only for falls prevention and psychological health.
     Tai chi, a gentle exercise program that emphasizes controlled breathing and relaxation, has been evaluated as a potential therapy for many diseases and chronic conditions, but results are inconsistent (JW Gen Med May 3 2011 and JW Gen Med Aug 19 2010). Several recent systematic reviews have been conducted to resolve these inconsistencies, and this study is a "review of the reviews." After a search of the English, Chinese, and Korean medical literature, researchers identified 35 systematic reviews of tai chi; at least 11 reviews were conducted by one of the authors of this meta-review.
     The 35 reviews addressed the value of tai chi in more than 15 diseases and chronic conditions, including cancer, Parkinson disease, rheumatoid arthritis, and cardiovascular disease. Of the four reviews that addressed falls prevention, three showed positive benefit, and one was equivocal. Of the five reviews that addressed psychological health, four were positive, and one was equivocal. The remaining reviews showed no consistent benefit for any other condition.
     Comment: Given the nature of tai chi — which is gentle, rhythmic, and nonspecific — its lack of specific benefit for metabolic and cardiovascular conditions is not surprising. However, its benefits in preventing falls and improving psychological health are clear, and it can be recommended for these specific purposes, especially in older people.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine May 26, 2011
     Citation(s): Lee MS and Ernst E. Systematic reviews of t'ai chi: An overview. Br J Sports Med 2011 May 16; [e-pub ahead of print]. (http://dx.doi.org/10.1136/bjsm.2010.080622)
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Obstet Gynecol 2011 May; 117:1065
Revisiting Gestational Weight Gain in Obese Women
Low weight gain — and even weight loss — was not associated with excess risk for adverse pregnancy outcomes.
     Institute of Medicine (IOM) guidelines on gestational weight gain (JW Womens Health Jul 2 2009) have been questioned because they classify obesity into a single category (body-mass index [BMI], ≥30.0 kg/m2) with one range for recommended gestational weight gain (5.0–9.0 kg). In a population-based cohort study of Swedish Medical Birth Registry data from >46,000 obese women categorized as WHO class I (BMI range, 30.0–34.9), II (35.0–39.9), or III (≥40.0), researchers evaluated adverse pregnancy outcomes associated with four IOM categories of gestational weight change (<0.0 kg [loss]; 0.0–4.9 kg [low gain]; 5.0–9.0 kg [recommended gain]; and >9 kg [excessive gain]). Outcomes were preeclampsia, cesarean or operative vaginal delivery, blood loss, small- or large-for-gestational-age infant, fetal distress, and low Apgar score.
     Overall, only 27% of women gained weight within the recommended IOM range. Compared with women who gained 5.0–9.0 kg, those who lost weight during pregnancy (particularly those in classes II and III) had lower risk for cesarean delivery and large-for-gestational-age neonates and similar risk for preeclampsia, excessive blood loss at delivery, operative birth, low Apgar scores, and fetal distress. Risk for small-for-gestational-age infants was twofold higher among class III women who lost weight compared with those who gained 5.0–9.0 kg; however, at 3.7%, this risk was still low.
     Comment: Even when obese women lost weight during pregnancy, maternal and neonatal risks for adverse outcomes generally did not rise (and risk for cesarean delivery fell). The excess risk for small-for-gestational-age infants in class III obese women who lost weight was only slightly above the overall rate of 3.6% in the Swedish general population. These findings suggest that, especially for women of class II and III obesity, weight loss during pregnancy generally is safe; however, careful management and attention to nutritional quality are essential.
Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health May 26, 2011
     Citation(s): Blomberg M. Maternal and neonatal outcomes among obese women with weight gain below the new Institute of Medicine recommendations. Obstet Gynecol 2011 May; 117:1065.
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Obstet Gynecol 2011 May; 117:1071.
Eating Fish to Prevent Preterm Birth: No Need to Go Overboard
Moderate dietary fish consumption was associated with lower risk for recurrent PTB; greater intake did not provide further protection.
      Supplementation with {omega}-3 fatty acids beginning at 16 to 21 weeks' gestation does not prevent recurrent preterm birth (PTB) in high-risk women, but is prior dietary fish intake beneficial? In a substudy of their trial of {omega}-3 supplementation to avert PTB in women who had experienced one or more preterm deliveries, U.S. investigators from the Maternal Fetal Medicine Units Network evaluated fish consumption before study enrollment. A total of 852 participants completed food frequency questionnaires to assess fish intake during the time from last menstrual period to randomization.
     PTB occurred in 49% of the 253 women who ate fish once monthly or not at all compared with 36% of the 599 women who ate fish more often (P<0.001). In analysis adjusted for many variables (e.g., age, education, smoking status, body-mass index, race or ethnicity, number of previous PTBs), risk for PTB fell with increasing fish consumption, reaching a nadir at an intake of three times weekly (adjusted odds ratio, 0.60).
     Comment: In this cohort of women with histories of preterm birth, those with lowest fish consumption during early pregnancy were at excess risk for recurrent PTB compared with those who ate fish more frequently; consumption beyond three times weekly, however, did not confer additional protection. The authors acknowledge that few measures of socioeconomic status were available for analysis of potential confounders; also, participants received weekly injections of 17 α-hydroxyprogesterone caproate, so the results might not apply to other pregnant populations. Moreover, although seafood is a good source of nutrients, the FDA notes that certain types of fish should be avoided because they might contain environmental contaminants.
Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health May 26, 2011
     Citation(s): Klebanoff MA et al. Fish consumption, erythrocyte fatty acids, and preterm birth. Obstet Gynecol 2011 May; 117:1071.
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N Engl J Med 2011 May 26; 364:2016
Bacterial Meningitis in the U.S.: An Update
Although immunization programs have reduced the incidence of this disease, the case fatality rate has not declined.
     Pediatric immunization programs that include the Haemophilus influenzae type B and heptavalent protein-polysaccharide pneumococcal conjugate vaccines have substantially reduced the incidence of bacterial meningitis. Now, using data from two surveillance systems of the Emerging Infections Programs Network (Active Bacterial Core surveillance and Foodborne Diseases Active Surveillance Network), researchers have studied trends in bacterial meningitis incidence and epidemiology in the U.S. from 1998 through 2007.
     Data from eight surveillance areas (~17.4 million people) were analyzed. Bacterial meningitis was defined as the presence of H. influenzae, Streptococcus pneumoniae, group B Streptococcus, Listeria monocytogenes, or Neisseria meningitidis in cerebrospinal fluid or another normally sterile site in conjunction with a clinical diagnosis of meningitis. These five pathogens were selected because they collectively account for most bacterial meningitis cases in the U.S.
     Over the entire study period, 3188 meningitis cases were identified, of which 14.8% were fatal. From 2003 through 2007, 1670 cases were identified, with a 13.0% fatality rate. On the basis of these data, the researchers estimated that 4100 cases and 500 deaths occurred annually in the U.S. during these latter years.
     Between 1998 and 2007, the incidence of bacterial meningitis caused by these five pathogens decreased by 31% (95% confidence interval, –33 to –29). The median age of patients increased from 30.3 to 41.9 (P<0.001). The case fatality rate did not change during the surveillance period (15.7% in 1998–1999 and 14.3% in 2006–2007; P=0.51). S. pneumoniae was the predominant pathogen identified (56.9% of cases overall).
     Comment: The success of vaccination programs in children is laudable and provides impetus for additional vaccine development, as well as for initiation of such programs in developing countries, where they are often lacking. In addition, novel interventions for the management of bacterial meningitis are desperately needed: The case fatality rate has not improved in years. Until that happens, however, empirical antibiotic therapy that includes coverage for resistant strains of S. pneumoniae should be initiated as early as possible in an effort to reduce morbidity and mortality.
Larry M. Baddour, MD Published in Journal Watch Infectious Diseases May 25, 2011
     Citation(s): Thigpen MC et al. Bacterial meningitis in the United States, 1998–2007. N Engl J Med 2011 May 26; 364:2016
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J Pediatr 2011 May; 158:775.
Low Apgar Scores Linked with ADHD
In a population-based study, Apgar scores were inversely associated with risk for attention-deficit/hyperactivity disorder.
     Low Apgar scores have been linked with some neurological diseases, but whether low scores are associated with attention-deficit/hyperactivity disorder (ADHD) is unknown. Investigators examined this association in a population-based cohort study of all 980,902 singleton births in Denmark during 1988 through 2001. Children were monitored from age 3 years until a diagnosis of hyperkinetic disorder (an International Classification of Diseases diagnosis that includes core behavioral criteria consistent with ADHD), a first medication for ADHD, migration, death, or the year 2006. A total of 8234 children with ADHD were identified.
     Five-minute Apgar scores were inversely associated with risk for ADHD in analysis adjusted for potential confounders including low birth weight, prematurity, family history of mental health, maternal socioeconomic status, and maternal history of smoking. Compared with children with Apgar scores of 9 or 10, children with scores of 1 to 4 had a 75% higher risk and children with scores of 5 to 6 had a 63% higher risk for ADHD.
     Comment: This is the largest study to examine an association between Apgar scores and ADHD. Although the results are based on retrospective data obtained from national registries rather than on clinical assessment, they are strengthened by inclusion of all births in a country with a universal healthcare system and linked registries. In view of the increasingly strong evidence that ADHD is a biological condition (JW Pediatr Adolesc Med Jan 9 2008 and JW Pediatr Adolesc Med Oct 27 2010), these results suggest that a low Apgar score at 5 minutes interacts with genetic factors in the development of ADHD.
Martin T. Stein, MD Published in Journal Watch Pediatrics and Adolescent Medicine May 25, 2011
     Citation(s): Li J et al. Low Apgar scores and risk of childhood attention deficit hyperactivity disorder. J Pediatr 2011 May; 158:775.
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Gastroenterology 2011 Apr; 140:1189.e1
Rethinking Zinc as First-Line Therapy for Wilson Disease
Chelation therapy with D-penicillamine or trientene had lower failure rates than zinc monotherapy.
     Wilson disease (WD), although rare, is associated with significant morbidity and mortality if untreated. The mainstay of initial therapy is copper chelation with agents such as D-penicillamine and trientene. A previous study suggested that zinc monotherapy was effective in patients with mainly neurological symptoms or asymptomatic hepatic disease (JW Gastroenterol Jan 8 2010). However, that study was a small case series without a comparison group.
     Now, in a larger study, European researchers have compared the long-term effectiveness of zinc monotherapy with that of chelating agents by retrospectively assessing initial symptoms, treatment regimens, and outcomes in 288 patients during a median follow-up of 17.1 years. Median age at onset of disease was 17.5. Outcomes included treatment failure, adverse events, and survival. Treatment failure was defined as liver enzyme elevation ≥2 times the upper limit of normal or baseline level at discontinuation, with an increase in urinary copper level despite treatment.
     At diagnosis, 68.1% of patients had hepatic symptoms, 34.4% had neurological symptoms, and 11.1% were asymptomatic. The zinc-only group had a higher rate of treatment failure than the chelator-only group (16.0% vs. 1.3%; P<0.001) and lower survival (P<0.001). Furthermore, patients who did not respond to zinc therapy responded when switched to a chelating agent. Frequency of adverse events was similar between groups.
     Comment: This study suggests that although zinc therapy was effective in the majority of WD patients, it was less effective and had a lower survival rate than chelating agents. Importantly, when zinc therapy was ineffective in preventing hepatic deterioration, reintroduction of a chelating agent was beneficial. Therefore, zinc monotherapy should not be considered first-line therapy for long-term treatment of WD, but if used, must be closely monitored for treatment failure.
Atif Zaman, MD, MPH Published in Journal Watch Gastroenterology May 27, 2011
     Citation(s): Weiss KH et al. Zinc monotherapy is not as effective as chelating agents in treatment of Wilson disease. Gastroenterology 2011 Apr; 140:1189.e1.

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