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FOLATE (FOLIC ACID) MAY REDUCE BLOOD PRESSURE RISK

ABSTRACT Folate Intake and the Risk of Incident Hypertension Among US Women John P. Forman, MD; Eric B. Rimm, ScD; Meir J. Stampfer, MD, DrPH; Gary C. Curhan, MD, ScD Context Folate has important beneficial effects on endothelial function, but there is limited information about folate intake and risk of incident hypertension. Objective To determine whether higher folate intake is associated with a lower risk of incident hypertension. Design, Setting, and Participants Two prospective cohort studies of 93 803 younger women aged 27 to 44 years in the Nurses’ Health Study II (1991-1999) and 62 260 older women aged 43 to 70 years in the Nurses’ Health Study I (1990-1998), who did not have a history of hypertension. Baseline information on dietary folate and supplemental folic acid intake was derived from semiquantitative food frequency questionnaires and was updated every 4 years. Main Outcome Measure Relative risk of incident self-reported hypertension during 8 years of follow-up. Results We identified 7373 incident cases of hypertension in younger women and 12 347 cases in older women. After adjusting for multiple potential confounders, younger women who consumed at least 1000 µg/d of total folate (dietary plus supplemental) had a decreased risk of hypertension (relative risk [RR], 0.54; 95% confidence interval [CI], 0.45-0.66; P for trend <.001) compared with those who consumed less than 200 µg/d. Younger women’s absolute risk reduction (ARR) was approximately 8 cases per 1000 person-years (6.7 vs 14.8 cases). The multivariable RR for the same comparison in older women was 0.82 (95% CI, 0.69-0.97; P for trend = .05). Older women’s ARR was approximately 6 cases per 1000 person-years (34.7 vs 40.4 cases). When the analysis was restricted to women with low dietary folate intake (Conclusion Higher total folate intake was associated with a decreased risk of incident hypertension, particularly in younger women. JAMA. 2005;293:320-329. Author Affiliations: Renal Division (Drs Forman and Curhan), Channing Laboratory (Drs Forman, Rimm, Stampfer, and Curhan), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School and Departments of Epidemiology and Nutrition (Drs Forman, Rimm, Stampfer, and Curhan), Harvard School of Public Health, Boston, Mass.

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Hospitalization and Death Associated With Potentially Inappropriate Medication Prescriptions Among Elderly Nursing Home Residents

ABSTRACT Background This study examines the association of potentially inappropriate medication prescribing (PIRx) with hospitalization and death among elderly long-stay nursing home residents. Methods We defined PIRx using the combined version of the Beers criteria. Data were from the 1996 Medical Expenditure Panel Survey Nursing Home Component. The study sample included 3372 residents, 65 years and older, who had nursing home stays of 3 consecutive months or longer in 1996. We performed multivariate logistic regression analyses of longitudinal data using generalized estimating equations. Results Residents who received any PIRx had greater odds (odds ratio [OR], 1.27; P = .002) of being hospitalized in the following month than those receiving no PIRx. Residents with PIRx exposure for 2 consecutive months were at increased risk (OR, 1.27; P = .004) of hospitalization, as were those receiving PIRx in the second month only (OR, 1.80; P = .001), compared with those receiving no PIRx. Residents who received PIRx were at greater risk of death (OR, 1.28; P = .01) that month or the next. Residents with intermittent PIRx exposures were at greater odds of death (OR, 1.89; P<.001), compared with those with no PIRx exposure. Conclusions The association of PIRx with subsequent adverse outcomes (hospitalization and death) provides new evidence of the importance of improving prescribing practices in the nursing home setting. Arch Intern Med. 2005;165:68-74. January 10, 2005 Author Affiliations: Buehler Center on Aging, Feinberg School of Medicine, Northwestern University, Chicago, Ill (Dr Lau); Department of Health Policy and Management, Bloomberg School of Public Health (Dr Kasper), and Division of Geriatric Medicine and Gerontology, School of Medicine (Dr Bennett), The Johns Hopkins University, Baltimore, Md; Center for Financing, Access, and Cost Trends, Agency for Healthcare Research and Quality, Rockville, Md (Ms Potter); and School of Government and Public Administration, University of Baltimore (Dr Lyles).

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Bone mineral density changes over two years in first-time users of Depo-Provera (depot medroxyprogesterone acetate)

ABSTRACT Objective: To compare longitudinal changes in bone mineral density (BMD) among first-time depot medroxyprogesterone acetate (DMPA) users to women using no hormonal contraception, and evaluate user characteristics associated with that BMD change. Design: Prospective longitudinal study. Setting: Healthy volunteers in an academic research environment. Patient(s) Women, aged 18 to 35, choosing DMPA for contraception (n = 178) and women using no hormonal contraception (n = 145). Main outcome measure(s) : Hip and spine BMD measured, at three-month intervals for 24 months, by dual energy x-ray absorptiometry. Result(s) : Mean hip BMD declined 2.8% (SE = 0.034) 12 months following DMPA initiation and 5.8% (SE = 0.096) after 24 months. Mean spine (L1–L3) BMD declined 3.5% (SE = 0.022) and 5.7% (SE = 0.034), respectively, after one and two years of DMPA use. Mean hip and spine BMD of control participants changed less than 0.9% over the same period. Among DMPA users, body mass index (BMI) change was inversely associated with BMD change at the hip, but not at the spine. Calcium intake, physical activity, and smoking did not influence BMD change in either group. Conclusion(s) : Hip and spine BMD declined after one DMPA injection and this decline continued with each subsequent injection for 24 months. With the exception of increasing BMI among DMPA users, no user characteristics offered protection against DMPA-related BMD loss. SOURCE: Fertility and Sterility, December 2004, Volume 82, Issue 6, Pages 1580-1586

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Incorporating nerve-gliding techniques in the conservative treatment of cubital tunnel syndrome

ABSTRACT Objective: To discuss the diagnosis and treatment of a patient with cubital tunnel syndrome and to illustrate novel treatment modalities for the ulnar nerve and its surrounding structures and target tissues. The rationale for the addition of nerve-gliding techniques will be highlighted. Clinical Features: Two months after onset, a 17-year-old female nursing student who had a traumatic onset of cubital tunnel syndrome still experienced pain around the elbow and paresthesia in the ulnar nerve distribution. Electrodiagnostic tests were negative. Segmental cervicothoracic motion dysfunctions were present which were regarded as contributing factors hindering natural recovery. Intervention and Outcomes: After 6 sessions consisting of nerve-gliding techniques and segmental joint manipulation and a home exercise program consisting of nerve gliding and light free-weight exercises, a substantial improvement was recorded on both the impairment and functional level (pain scales, clinical tests, and Northwick Park Questionnaire). Symptoms did not recur within a 10-month follow-up period, and pain and disability had completely resolved. Conclusions: Movement-based management may be beneficial in the conservative management of cubital tunnel syndrome. As this intervention is in contrast with the traditional recommendation of immobilization, comparing the effects of both interventions in a systematic way is an essential next step to determine the optimal treatment of patients with cubital tunnel syndrome. November/December 2004; Vol. 27, No. 9. Journal of Manipulative and Physiological Therapeutics

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Caffeine as a risk factor for chronic daily headache: A population-based study

ABSTRACT Objective: To investigate the possible association of dietary caffeine consumption and medicinal caffeine use with chronic daily headache (CDH). Methods: Population-based cases and controls were recruited from the Baltimore, MD, Philadelphia, PA, and Atlanta, GA, metropolitan areas. Controls (n = 507) reported 2 to104 headache days/year, and cases (n = 206) reported 180 headache days/year. Current and past dietary caffeine consumption and medication use for headache were based on detailed self-report. High caffeine exposure was defined as being in the upper quartile of dietary consumption or using a caffeine-containing over-the-counter analgesic as the preferred headache treatment. Results: In comparison with episodic headache controls, CDH cases were more likely overall to have been high caffeine consumers before onset of CDH (odds ratio [OR] = 1.50, p = 0.05). No association was found for current caffeine consumption (i.e., post CDH) (OR = 1.36, p = 0.12). In secondary analyses, associations were confined to younger (age <40) women (OR = 2.0, p = 0.02) and those with chronic episodic (as opposed to chronic continuous) headaches (OR = 1.69, p = 0.01), without physician consultation (OR = 1.67, p = 0.04) and of recent (Conclusion: Dietary and medicinal caffeine consumption appears to be a modest risk factor for chronic daily headache onset, regardless of headache type. Scher AI, et al. Neurology. December 14, 2004; Vol. 63, No. 11, pp. 2022-2027.

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The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%

 

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NIH Halts Use of COX-2 (Celebrex) Inhibitor in Large Cancer Prevention Trial

The National Institutes of Health (NIH) announced today that it has suspended the use of COX-2 inhibitor celecoxib (Celebrex™ Pfizer, Inc.) for all participants in a large colorectal cancer prevention clinical trial conducted by the National Cancer Institute (NCI). The study, called the Adenoma Prevention with Celecoxib (APC) trial, was stopped because analysis by an independent Data Safety and Monitoring Board (DSMB) showed a 2.5-fold increased risk of major fatal and non-fatal cardiovascular events for participants taking the drug compared to those on a placebo. Additional cardiovascular expertise was added to the safety monitoring committees at the request of the Steering Committees for this trial after a September 2004 report that the COX-2 inhibitor rofecoxib (Vioxx™) caused a two-fold increased risk of cardiovascular toxicities in a trial to prevent adenomas. The APC is a study of more than 2,000 people who have had a precancerous growth (adenomatous polyp) removed. They were randomized to take either 200 mg of celecoxib twice a day, 400 mg of celecoxib twice a day, or a placebo for three years. The trial began in early 2000 and is scheduled to have been completed by Spring 2005. Investigators at the 100 sites in the APC trial located primarily in the United States, with a few additional sites in the United Kingdom, Australia, and Canada, have been instructed to immediately suspend study drug use for all participants on the trial, although the participants will remain under observation for the planned remainder of the study. "Data from the report on rofecoxib (Vioxx) informed us of the need to focus on specific cardiovascular issues, and our Institutes brought in the experts to do so, said Elias A. Zerhouni, M.D., NIH Director. "Our overwhelming commitment is to advance the health and to protect the safety of participants in clinical trials. We are examining the use of these agents in all NIH-sponsored clinical studies. In addition, we are working closely with our colleagues at FDA to ensure that the public has the information they need to make informed decisions about the use of this class of drug." "The rigor of our clinical trials system has allowed us to find this problem," said NCI Director Andrew C. von Eschenbach, M.D. "We have a strong system that provides us with the opportunity to both find ways to effectively treat and prevent disease and to do so in a way that protects the lives and safety of the participants." NIH sponsors over 40 studies using celecoxib for the prevention and treatment of cancer, dementia and other diseases. In light of these new findings, NIH Director Zerhouni requested: • a full review of all NIH-supported studies involving this class of drug. • NIH Institutes to inform the principal investigators for all of these studies and will ask them to communicate directly with their study participants and explain the risks and benefits • NIH to ask each investigator to inform us of the their plan to analyze their data in light of the information • the Institutional Review Boards (IRBs) for all related trials to assess the new information and to conduct a safety review as well For Questions and Answers regarding this study, please go to:

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Discovery Shows New Vitamin C Health Benefits

CORVALLIS – Researchers in the Linus Pauling Institute at Oregon State University have made a major discovery about the way vitamin C functions in the human body – a breakthrough that may help explain its possible value in preventing cancer and heart disease. The study, which explores the role of vitamin C in dealing with the toxins that result from fat metabolism, was just published in a professional journal, Proceedings of the National Academy of Sciences. It contradicts the conclusions of some research that was widely publicized three years ago, which had suggested that this essential nutrient might actually have toxic effects. The new OSU study confirmed some of the results of that earlier laboratory study, which had found vitamin C to be involved in the formation of compounds potentially damaging to DNA. But that research, scientists say, only provided part of the story about what actually happens in the human body. The newest findings explain for the first time how vitamin C can react with and neutralize the toxic byproducts of human fat metabolism. “This is a previously unrecognized function for vitamin C in the human body,” said Fred Stevens, an assistant professor in the Linus Pauling Institute. “We knew that vitamin C is an antioxidant that can help neutralize free radicals. But the new discovery indicates it has a complex protective role against toxic compounds formed from oxidized lipids, preventing the genetic damage or inflammation they can cause.” Some earlier studies done in another laboratory had exposed oxidized lipids – which essentially are rancid fats – to vitamin C, and found some reaction products that can cause DNA damage. These test tube studies suggested that vitamin C could actually form “genotoxins” that damage genes and DNA, the types of biological mutations that can precede cancer. But that study, while valid, does not tell the whole story, the OSU researchers say. “It’s true that vitamin C does react with oxidized lipids to form potential genotoxins,” said Balz Frei, professor and director of the Linus Pauling Institute, and co-author on this study. “But the process does not stop there. We found in human studies that the remaining vitamin C in the body continues to react with these toxins to form conjugates - different types of molecules with a covalent bond - that appear to be harmless.” In human tests, the OSU scientists found in blood plasma extraordinarily high levels of these conjugates, which show this protective effect of vitamin C against toxic lipids. “Prior to this, we never knew what indicators to look for that would demonstrate the protective role of vitamin C against oxidized lipids,” Stevens said. “Now that we see them, it becomes very clear how vitamin C can provide a protective role against these oxidized lipids and the toxins derived from them. And this isn’t just test tube chemistry, this is the way our bodies work. “This discovery of a new class of lipid metabolites could be very important in our understanding of this vitamin and the metabolic role it plays,” Stevens said. “This appears to be a major pathway by which the body can get rid of the toxic byproducts of fat metabolism, and it clearly could relate to cancer prevention.” Oxidation of lipids has been the focus of considerable research in recent years, the scientists say, not just for the role it may play in cancer but also in other chronic diseases such as heart disease, Alzheimer’s disease, and autoimmune disorders. The toxic products produced by fat oxidation may not only be relevant to genetic damage and cancer, researchers believe, but are also very reactive compounds that damage proteins. For instance, there’s a protein in LDL, the “bad” cholesterol in your blood, which if damaged by toxic lipids can increase the chance of atherosclerotic lesions. In continuing research, the OSU team plans to study the role of this newly understood reaction between vitamin C and toxic lipids in atherosclerosis. In clinical studies they plan to examine the blood chemistry of patients who have been diagnosed with coronary artery disease, compared to a healthy control group. “In the early stages of atherosclerosis, it appears that some of these toxic lipids make white blood cells stick to the arterial wall, and start an inflammatory process that ultimately can lead to heart disease or stroke,” Frei said. “When we better understand that process and the role that micronutrients such as vitamin C play in it, there may be strategies we can suggest to prevent this from happening.” The new findings, the OSU scientists say, also point to new biomarkers that can be useful in identifying oxidative stress in the human body. They may provide an indicator of people who may be at special risk of chronic disease. By David Stauth, 541-737-0787 SOURCES: Fred Stevens, 541-737-9534 Balz Frei, 541-737-5078

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Vitamin E Supplements May Decrease the Risk of Lou Gehrig’s Disease (ALS)

Long-term use of vitamin E supplements may decrease the risk of amyotrophic lateral sclerosis (ALS), according to a study published online in the Annals of Neurology on November 4, 2004. ALS, also known as Lou Gehrig’s disease, is a neurodegenerative disease characterized by the death of motor neurons, which are nerves that control the movement of all voluntary muscles. This loss of motor neurons results in progressive muscle weakness, muscle atrophy, spastic paralysis and death within 1-5 years. More than 5,000 people in the U.S. are diagnosed with ALS each year, and currently there is no cure. Although the cause of motor neuron death in ALS is unknown, oxidative stress may play a role. Researchers from the Harvard School of Public Health and the American Cancer Society followed more than 900,000 men and women for sixteen years to determine whether antioxidant supplement use was associated with a decreased risk of developing ALS. They found that people who reported taking vitamin E supplements regularly for more than 10 years when the study began were 60% less likely to die from ALS than those who did not take vitamin E supplements. Participants in the study did not provide any information about the dose of the vitamin E supplements they took, but a typical vitamin E supplement contains 400 IU of synthetic d,l-alpha-tocopherol, which is equivalent to 200 IU of natural d-alpha-tocopherol. In contrast, vitamin C and multivitamin supplement use were not associated with ALS risk. Although these results need confirmation by future studies, they suggest that vitamin E may play a role in the prevention of ALS. Maret Traber, the Linus Pauling Institute’s vitamin E expert, notes that long-term use of vitamin E supplements can double vitamin E concentrations in the brain. Her work indicates that absorption of this fat-soluble antioxidant vitamin can be maximized by taking vitamin E supplements with dinner. More information on vitamin E can be found in the Linus Pauling Institute's Micronutrient Information Center. According to Joe Beckman, a scientist who studies ALS at the Linus Pauling Institute, taking vitamin E does not extend life once ALS is diagnosed, but the progression of the disease may be slowed, according to a recent clinical study. In such studies, patients are not instructed on how to best take vitamin E to maximize absorption. Dr. Beckman hopes that these new results will encourage further trials with more rapid and efficacious supplementation. He also notes that this study provides more convincing evidence for a pathogenic role of oxidative stress in ALS. Vitamin E may also protect against Alzheimer’s disease. A cross sectional study conducted in Cache County, Utah, and published in Annals of Neurology earlier this year showed that high intake of vitamin E and C together was associated with a substantially reduced incidence of Alzheimer’s disease. These two studies on ALS and Alzheimer’s provide accumulating evidence that antioxidant vitamins are important in the prevention of neurodegenerative diseases.

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Asthma exacerbations in children immediately following stressful life events: a Cox’s hierarchical regression

ABSTRACT Background: A recent prospective study of children with asthma employing a within subject, over time analysis using dynamic logistic regression showed that severely negative life events significantly increased the risk of an acute exacerbation during the subsequent 6 week period. The timing of the maximum risk depended on the degree of chronic psychosocial stress also present. A hierarchical Cox regression analysis was undertaken to examine whether there were any immediate effects of negative life events in children without a background of high chronic stress. Methods: Sixty children with verified chronic asthma were followed prospectively for 18 months with continuous monitoring of asthma by daily symptom diaries and peak flow measurements, accompanied by repeated interview assessments of life events. The key outcome measures were asthma exacerbations and severely negative life events. Results: An immediate effect evident within the first 2 days following a severely negative life event increased the risk of a new asthma attack by a factor of 4.69 (p = 0.00). In the period 3–10 days after a severe event there was no increased risk of an asthma attack (p = 0.5). In addition to the immediate effect, an increased risk of 1.81 was found 5–7 weeks after a severe event (p = 0.002). This is consistent with earlier findings. There was a statistically significant variation due to unobserved factors in the incidence of asthma attacks between the children. Conclusion: The use of statistical methods capable of investigating short time lags showed that stressful life events significantly increase the risk of a new asthma attack immediately after the event; a more delayed increase in risk was also evident 5–7 weeks later. Thorax 2004;59:1046-1051 © 2004 BMJ Publishing Group Ltd & British Thoracic Society

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Chinese herb Berberine lowers cholesterol in new way

Berberine, a Chinese herb lowers LDL ("bad") cholesterol in anew way from drugs like Lipitor or Zocor, a new study shows. The herb has a history of medicinal use in both Ayurvedic and Chinese medicine. Click on the link below for more:

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Footwear Style and Risk of Falls in Older Adults

ABSTRACT Objectives: To determine how the risk of a fall in an older adult varies in relation to style of footwear worn. Design: Nested case-control study. Setting: Group Health Cooperative, a large health maintenance organization in Washington state. Participants: A total of 1,371 adults aged 65 and older were monitored for falls over a 2-year period; 327 qualifying fall cases were compared with 327 controls matched on age and sex. Measurements: Standardized in-person examinations before fall occurrence, interviews about fall risk factors after the fall occurred, and direct examination of footwear were conducted. Questions for controls referred to the last time they engaged in an activity broadly similar to what the case was doing at the time of the fall. Results: Athletic and canvas shoes (sneakers) were the styles of footwear associated with lowest risk of a fall. Going barefoot or in stocking feet was associated with sharply increased risk, even after controlling for measures of health status (adjusted odds ratio=11.2, 95% confidence interval (CI)=2.4-51.8). Relative to athletic/canvas shoes, other footwear was associated with a 1.3-fold increase in the risk of a fall (95% CI=0.9-1.9), varying somewhat by style. Conclusion: Contrary to findings from gait-laboratory studies, athletic shoes were associated with relatively low risk of a fall in older adults during everyday activities. Fall risk was markedly increased when participants were not wearing shoes. Journal of the American Geriatrics Society Volume 52 Issue 9 Page 1495 - September 2004

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Dairy intakes affect bone density in the elderly

ABSTRACT Background: Race and sex differences in the effect of diet on bone mineral density (BMD) at the hip in the elderly are unknown. Objectives: This study related cross-sectional nutrient and dairy product consumption to hip BMD in white and black men and women aged >60 y and evaluated the influence of nutrient and dairy product consumption on changes in BMD in a white cohort participating in a calcium, vitamin D, or placebo trial. Design: The Health Habits and History Questionnaire was used in 289 white women and 116 white men who participated in the trial and in 265 black women and 75 black men to predict total hip and femoral neck BMD or changes in BMD. Results: Blacks had higher calcium intakes than did whites (700 and 654 mg/d, respectively; P = 0.0094), and men had higher calcium intakes than did women (735 and 655 mg/d, respectively; P = 0.0007). For men, the correlation between total hip BMD and dairy calcium intake after adjustment for age, race, and weight was 0.23 (P < 0.005); this relation was not significant in women (r = 0.02, P = 0.12). Similar results were found for femoral neck BMD. In the longitudinal study, calcium supplementation reduced bone loss from the total hip and femoral neck in those who consumed Conclusions: Cross-sectional results indicated that higher dairy product consumption is associated with greater hip BMD in men, but not in women. Calcium supplementation protected both men and women from bone loss in the longitudinal study of whites. American Journal of Clinical Nutrition, Vol. 80, No. 4, 1066-1074, October 2004

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Risk of Community-Acquired Pneumonia and Use of Gastric Acid–Suppressive Drugs

ABSTRACT Context Reduction of gastric acid secretion by acid-suppressive therapy allows pathogen colonization from the upper gastrointestinal tract. The bacteria and viruses in the contaminated stomach have been identified as species from the oral cavity. Objective To examine the association between the use of acid-suppressive drugs and occurrence of community-acquired pneumonia. Design, Setting, and Participants Incident acid-suppressive drug users with at least 1 year of valid database history were identified from the Integrated Primary Care Information database between January 1, 1995, and December 31, 2002. Incidence rates for pneumonia were calculated for unexposed and exposed individuals. To reduce confounding by indication, a case-control analysis was conducted nested in a cohort of incident users of acid-suppressive drugs. Cases were all individuals with incident pneumonia during or after stopping use of acid-suppressive drugs. Up to 10 controls were matched to each case for practice, year of birth, sex, and index date. Conditional logistic regression was used to compare the risk of community-acquired pneumonia between use of proton pump inhibitors (PPIs) and H2-receptor antagonists. Main Outcome Measure Community-acquired pneumonia defined as certain (proven by radiography or sputum culture) or probable (clinical symptoms consistent with pneumonia). Results The study population comprised 364 683 individuals who developed 5551 first occurrences of pneumonia during follow-up. The incidence rates of pneumonia in non–acid-suppressive drug users and acid-suppressive drug users were 0.6 and 2.45 per 100 person-years, respectively. The adjusted relative risk for pneumonia among persons currently using PPIs compared with those who stopped using PPIs was 1.89 (95% confidence interval, 1.36-2.62). Current users of H2-receptor antagonists had a 1.63-fold increased risk of pneumonia (95% confidence interval, 1.07-2.48) compared with those who stopped use. For current PPI users, a significant positive dose-response relationship was observed. For H2-receptor antagonist users, the variation in dose was restricted. Conclusion Current use of gastric acid–suppressive therapy was associated with an increased risk of community-acquired pneumonia. Author Affiliations: Department of Gastroenterology, University Medical Center St. Radboud, Nijmegen, the Netherlands (Drs Laheij and Jansen); and Department of Medical Informatics (Drs Laheij, Sturkenboom, Dieleman, and Stricker and Mr Hassing), Pharmacoepidemiology Unit, Department of Epidemiology and Biostatistics (Drs Sturkenboom and Stricker), and Internal Medicine (Dr Dieleman), Erasmus MC University, Medical Center Rotterdam, Rotterdam, the Netherlands. JAMA. 2004;292:2012-2013.

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A Randomized Trial of Medical Care With and Without Physical Therapy and Chiropractic Care With and Without Physical Modalities for Patients With Low Back Pain: 6-Month Follow-Up Outcomes From the UCLA Low Back Pain Study

 

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Folic acid supplementation enhances repair of the adult central nervous system

ABSTRACT Folic acid supplementation has proved to be extremely effective in reducing the occurrence of neural tube defects (NTDs) and other congenital abnormalities in humans, suggesting that folic acid can modulate key mechanisms for growth and differentiation in the central nervous system (CNS). To prevent NTDs, however, supplemental folate must be provided early in gestation. This suggests that the ability of folic acid to activate growth and differentiation mechanisms may be confined to the early embryonic period. Here, we show that folic acid can enhance growth and repair mechanisms even in the adult CNS. Using lesion models of CNS injury, we found that intraperitoneal treatment of adult rats with folic acid significantly improves the regrowth of sensory spinal axons into a grafted segment of peripheral nerve in vivo. Regrowth of retinal ganglion cell (RGC) axons into a similar graft also was enhanced, although to a smaller extent than spinal axons. Furthermore, folic acid supplementation enhances neurological recovery from a spinal cord contusion injury, showing its potential clinical impact. The results show that the effects of folic acid supplementation on CNS growth processes are not restricted to the embryonic period, but can also be effective for enhancing growth, repair, and recovery in the injured adult CNS. Ann Neurol 2004;56:221-227

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The Relation of Breastfeeding and Body Mass Index to Asthma and Atopy in Children: A Prospective Cohort Study to Age 6 Years

ABSTRACT Objectives We investigated the relationship between breastfeeding, asthma and atopy, and child body mass index (BMI). Methods From a prospective birth cohort (n = 2860) in Perth, Western Australia, 2195 children were followed up to age 6 years. Asthma was defined as doctor-diagnosed asthma and wheeze in the last year, and atopy was determined by skin prick test of 1596 children. Breastfeeding, BMI, asthma, and atopy were regressed allowing for confounders and the propensity score for overweight. Results Using fractional polynomials, we found no association between breastfeeding and overweight. Less exclusive breastfeeding was associated with increased asthma and atopy, and BMI increased with asthma. Conclusions Less exclusive breastfeeding leads to increases in child asthma and atopy and a higher BMI is a risk factor for asthma. Wendy H. Oddy and Jill L. Sherriff are with the Department of Nutrition, Dietetics and Food Science, Curtin University of Technology, Perth, Australia. Wendy H. Oddy, Nicholas H. de Klerk, Garth E. Kendall, Peter D. Sly, and Fiona J. Stanley are with the Centre for Child Health Research, University of Western Australia, Telethon Institute for Child Health Research, West Perth, Australia. Lawrence J. Beilin, Kevin B. Blake, and Louis I. Landau are with the Faculty of Medicine and Dentistry, University of Western Australia, West Perth. Correspondence: Requests for reprints should be sent to Wendy H. Oddy, PhD, MPH, Telethon Institute for Child Health Research, PO Box 855, West Perth, Western Australia 6872, Australia (e-mail: [email protected]).

A Potential Natural Treatment for Attention-Deficit/Hyperactivity Disorder: Evidence From a National Study

ABSTRACT Objective We examined the impact of relatively "green" or natural settings on attention-deficit/hyperactivity disorder (ADHD) symptoms across diverse subpopulations of children. Methods Parents nationwide rated the aftereffects of 49 common after-school and weekend activities on children’s symptoms. Aftereffects were compared for activities conducted in green outdoor settings versus those conducted in both built outdoor and indoor settings. Results In this national, nonprobability sample, green outdoor activities reduced symptoms significantly more than did activities conducted in other settings, even when activities were matched across settings. Findings were consistent across age, gender, and income groups; community types; geographic regions; and diagnoses. Conclusions Green outdoor settings appear to reduce ADHD symptoms in children across a wide range of individual, residential, and case character Frances E. Kuo is with the Department of Natural Resources and Environmental Sciences and the Department of Psychology, University of Illinois at Urbana-Champaign. Andrea Faber Taylor is with the Department of Natural Resources and Environmental Sciences, University of Illinois at Urbana-Champaign. Correspondence: Requests for reprints should be sent to Frances E. Kuo, PhD, Human Environment Research Laboratory, University of Illinois at Urbana-Champaign, 1103 S Dorner Dr, Urbana, IL 61801 (e-mail: [email protected]).

Oral Erythromycin and the Risk of Sudden Death from Cardiac Causes

Wayne A. Ray, Ph.D., Katherine T. Murray, M.D., Sarah Meredith, M.B., B.S., Sukumar Suguna Narasimhulu, M.B., B.S., M.P.H., Kathi Hall, M.S., and C. Michael Stein, M.B., Ch.B. ABSTRACT Background Oral erythromycin prolongs cardiac repolarization and is associated with case reports of torsades de pointes. Because erythromycin is extensively metabolized by cytochrome P-450 3A (CYP3A) isozymes, commonly used medications that inhibit the effects of CYP3A may increase plasma erythromycin concentrations, thereby increasing the risk of ventricular arrhythmias and sudden death. We studied the association between the use of erythromycin and the risk of sudden death from cardiac causes and whether this risk was increased with the concurrent use of strong inhibitors of CYP3A. Methods We studied a previously identified Tennessee Medicaid cohort that included 1,249,943 person-years of follow-up and 1476 cases of confirmed sudden death from cardiac causes. The CYP3A inhibitors used in the study were nitroimidazole antifungal agents, diltiazem, verapamil, and troleandomycin; each doubles, at least, the area under the time–concentration curve for a CYP3A substrate. Amoxicillin, an antimicrobial agent with similar indications but which does not prolong cardiac repolarization, and former use of erythromycin also were studied, to assess possible confounding by indication Results The multivariate adjusted rate of sudden death from cardiac causes among patients currently using erythromycin was twice as high (incidence-rate ratio, 2.01; 95 percent confidence interval, 1.08 to 3.75; P=0.03) as that among those who had not used any of the study antibiotic medications. There was no significant increase in the risk of sudden death among former users of erythromycin (incidence-rate ratio, 0.89; 95 percent confidence interval, 0.72 to 1.09; P=0.26) or among those who were currently using amoxicillin (incidence-rate ratio, 1.18; 95 percent confidence interval, 0.59 to 2.36; P=0.65). The adjusted rate of sudden death from cardiac causes was five times as high (incidence-rate ratio, 5.35; 95 percent confidence interval, 1.72 to 16.64; P=0.004) among those who concurrently used CYP3A inhibitors and erythromycin as that among those who had used neither CYP3A inhibitors nor any of the study antibiotic medications. In contrast, there was no increase in the risk of sudden death among those who concurrently used amoxicillin and CYP3A inhibitors or those currently using any of the study antibiotic medications who had formerly used CYP3A inhibitors. Conclusions The concurrent use of erythromycin and strong inhibitors of CYP3A should be avoided. Source Information: From the Division of Pharmacoepidemiology, Department of Preventive Medicine (W.A.R., S.M., K.H.), and the Departments of Medicine and Pharmacology, Divisions of Cardiology (K.T.M.), Clinical Pharmacology (K.T.M., S.S.N., C.M.S.), and Rheumatology (C.M.S.), Vanderbilt University School of Medicine; and the Geriatric Research, Education, and Clinical Center, Nashville Veterans Affairs Medical Center (W.A.R.) — both in Nashville. Address reprint requests to Dr. Ray at [email protected].

Lighten the Load: Backpack Strategies for Parents From the American Chiropractic Association

ARLINGTON, Va. -- As students savor the last precious days of summer vacation, parents are out making the final run for school supplies. So, parents, take note -- when back to school shopping this year there is one essential item that requires very special attention: your child's backpack. Backpack weight is becoming an increasing problem, and studies show that heavy backpacks can lead to both back pain and poor posture, noted the American Chiropractic Association (ACA). In fact, in 2001 backpacks were the cause of 7,000 emergency room visits and countless complaints of muscle spasms, neck and shoulder pain. "In my own practice, I have noticed a marked increase in the number of young children who are complaining about back, neck and shoulder pain," said Dr. Scott Bautch, a chiropractor from Wausau, Wis., and noted ergonomics expert. "The first question I ask these patients is, 'Do you carry a backpack to school?' Almost always, the answer is 'yes.'" This painful trend among youngsters isn't surprising when you consider the disproportionate amounts of weight they carry in their backpacks -- often slung over just one shoulder. According to Dr. Bautch, "Many of these kids are carrying a quarter of their body weight over their shoulders for a large portion of the day. That's equivalent to a 180-pound man carrying around a 45- pound load." Thankfully, backpacks have undergone a radical evolution in recent years and now many are designed to be ergonomic while remaining fashionable. Not to mention, the backpack of today has adapted to keep up with our changing lives. Children not only pack heavy schoolbooks, band instruments and running shoes into their backpacks, many of them also tuck away popular electronics -- such as laptops, cellular phones, MP3 players, CD players and personal digital assistants (PDA) -- into specially designed compartments inside their backpacks. Bulging backpacks offer a significant risk to children, but parents can help limit the strain on young necks, backs and shoulders. The ACA offers the following tips to help prevent the pain caused by backpack misuse. --- Make sure your child's backpack weighs no more than 10 percent of his or her body weight. A heavier backpack will cause your child to stoop forward in an attempt to support the additional weight. --- The backpack should never hang more than 4 inches below the waistline. A backpack that hangs too low increases the weight on the shoulders, causing your child to lean forward when walking. --- A backpack with individualized compartments helps position the contents most effectively. Make sure that pointy or bulky objects are packed away from the area that will rest on your child's back, and try to place the heaviest items closet to the body. --- Bigger is not necessarily better. The more room there is in a backpack, the more your child will carry and the heavier the backpack will be. --- Urge your child to wear both shoulder straps. Lugging the backpack around by one strap can cause a disproportionate shift of weight to one side, leading to neck and muscle spasms, as well as low-back pain. --- Wide, padded straps are very important. Non-padded straps are uncomfortable, and can dig into your child's shoulders. --- The shoulder straps should be adjustable so the backpack can be fitted to your child's body. Straps that are too loose can cause the backpack to dangle uncomfortably and cause spinal misalignment and pain. --- If the backpack is still too heavy, talk to your child's teacher. Ask if your child could leave the heaviest books at school, and bring home only lighter handout materials or workbooks. Ask the teacher for a set oftext books to keep at home. Chiropractic has been practiced in the United States for more than 100 years, and each year, millions of Americans trust their health to one of the nation's 60,000 doctors of chiropractic. To read research studies about the effectiveness of chiropractic care, visit ACA's website at:

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