Growth and adiposity in newborns study (GAINS): The influence of prenatal DHA supplementation protocol.

BACKGROUND: Obesity and central fat mass (FM) accrual drive disease development and are related to greater morbidity and mortality. Excessive gestational weight gain (GWG) increases fetal fat accretion resulting in greater offspring FM across the lifespan. Studies associate greater maternal docosahexaenoic acid (DHA) levels with lower offspring FM and lower visceral adipose tissue during childhood, however, most U.S. pregnant women do not consume an adequate amount of DHA. We will determine if prenatal DHA supplementation is protective for body composition changes during infancy and toddlerhood in offspring exposed to excessive GWG. METHODS AND DESIGN: Infants born to women who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE; NCT02626299) will be invited to participate. Women were randomized to either a high 1000 mg or low 200 mg daily prenatal DHA supplement starting in the first trimester of pregnancy. Offspring body composition and adipose tissue distribution will be measured at 2 weeks, 6 months, 12 months, and 24 months using dual energy x-ray absorptiometry. Maternal GWG will be categorized as excessive or not excessive based on clinical guidelines. DISCUSSION: Effective strategies to prevent obesity development are lacking. Exposures during the prenatal period are important in the establishment of the offspring phenotype. However, it is largely unknown which exposures can be successfully targeted to have a meaningful impact. This study will determine if prenatal DHA supplementation modifies the relationship between maternal weight gain and offspring FM and FM distribution at 24 months of age. ETHICS AND DISSEMINATION: The University of Kansas Medical Center Institutional Review Board (IRB) approved the study protocol (STUDY00140895). The results of the trial will be disseminated at conferences and in peer reviewed publications. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03310983.

Impact of smoking on tooth loss in adults.

DesignCohort studyCohort selectionParticipants were recruited between 1994 and 1998 from the general population with the preferred ages of 35 to 65 years in women and 40 to 65 years in men.Exposure measurementSmoking was assessed using a questionnaire from which pack years of smoking were calculated. Educational attainment, body mass index, hypertension, diabetes, alcohol consumption and vitamin or mineral supplements were assessed from measurements and questionnaires. Tooth loss was also assessed by questionnaire returned between 2004 and 2006. With the exception of the tooth loss data analysis was based on data collected at baseline.Data analysisThe 24,373 participants who returned the tooth loss questionnaire were analysed. Two hundred and eighty-six (1.2%) were excluded, as they did not respond to either of the tooth loss questions, and an additional 106 (0.4%) were excluded because they gave inconsistent responses to the questions on tooth loss. Four hundred and thirteen (1.7%) participants with missing data on cigarette smoking and 192 (0.8%) participants with missing data in any of the covariates were also excluded. The association between smoking and number of teeth at baseline was assessed using negative binomial regression models to obtain relative risks and 95% confidence intervals (CIs).ResultsThe sample of 23,376 included 9,032 men and 14,344 women of which 4,394 (19%) were current cigarette smokers, and 7,268 (31%) were cigarette smokers. 1,566 (6.7%) were edentulous at baseline. Compared with never smokers, current smokers were more likely to be male, less educated, more likely to be hypertensive, and less likely to take vitamins/mineral supplements, and they had higher alcohol consumption. Cigarette smoking was associated with higher prevalence of tooth loss at baseline as well as higher incidence of tooth loss during follow-up. The association between cigarette smoking and incident tooth loss during follow-up for the fully adjusted model (adjusted for age, sex, education, diabetes, body mass index, waist-to-hip ratio, hormone replacement therapy, contraception, intake of vitamin and mineral supplements, physical activity, alcohol intake, hypertension, and cardiovascular disease) is shown in the table.ConclusionsThere is a strong dose-dependent association between cigarette smoking and the risk of tooth loss. The risk declines after cessation of cigarette smoking; however, the risk may remain elevated for up to 20 years compared with never smokers. Efforts to improve the oral health of the population should include the prevention of smoking as well the promotion of smoking cessation.

Management of iron overload in hemoglobinopathies: what is the appropriate target iron level?

Patients with thalassemia become iron overloaded from increased absorption of iron, ineffective erythropoiesis, and chronic transfusion. Before effective iron chelation became available, thalassemia major patients died of iron-related cardiac failure in the second decade of life. Initial treatment goals for chelation therapy were aimed at levels of ferritin and liver iron concentrations associated with prevention of adverse cardiac outcomes and avoidance of chelator toxicity. Cardiac deaths were greatly reduced and survival was much longer. Epidemiological data from the general population draw clear associations between increased transferrin saturation (and, by inference, labile iron) and early death, diabetes, and malignant transformation. The rate of cancers now seems to be significantly higher in thalassemia than in the general population. Reduction in iron can reverse many of these complications and reduce the risk of malignancy. As toxicity can result from prolonged exposure to even low levels of excess iron, and survival in thalassemia patients is now many decades, it would seem prudent to refocus attention on prevention of long-term complications of iron overload and to maintain labile iron and total body iron levels within a normal range, if expertise and resources are available to avoid complications of overtreatment.

Effective iron chelation practice for patients with ß-thalassemia major.

Chronic blood transfusion is the only treatment for severe anemia in patients with ß-thalassemia major. However, red blood cell transfusions lead to iron overload and subsequent organ damage because of the toxic effects of iron. The heart is particularly vulnerable to iron toxicity, and heart failure is the leading cause of death among these patients. Iron chelation therapy prevents or reverses iron loading, thereby reducing the risk of complications from excess iron. Serum ferritin and liver iron concentration often are used to gauge the risk of organ iron overload, but these measurements may not correlate well with cardiac iron load. Magnetic resonance imaging (MRI) is a noninvasive diagnostic tool that can provide a more direct measure of iron concentration in both the heart and liver. Cardiac iron determined by MRI is expressed as a function of T2*, in which higher values represent lower concentrations. Changes in T2* are used to assess the effectiveness of iron chelation and to adjust therapy. Early treatment and compliance are keys to successful therapy. Nursing strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. The efficacy and safety of iron chelators, as well as nursing best practices, are reviewed.

Treating thalassemia major-related iron overload: the role of deferiprone.

Over the last 20 years, management for thalassemia major has improved to the point where we predict that patients' life expectancy will approach that of the normal population. These outcomes result from safer blood transfusions, the availability of three iron chelators, new imaging techniques that allow specific organ assessment of the degree of iron overload, and improvement in the treatment of hepatitis. In October 2011, the Food and Drug Administration licensed deferiprone, further increasing the available choices for iron chelation in the US. The ability to prescribe any of the three chelators as well as their combinations has led to more effective reduction of total body iron. The ability to determine the amount of iron in the liver and heart by magnetic resonance imaging allows the prescription of the most appropriate chelation regime for patients and to reconsider what our aims with respect to total body iron should be. Recent evidence from Europe has shown that by normalizing iron stores not only are new morbidities prevented but also reversal of many complications such as cardiac failure, hypothyroidism, hypogonadism, impaired glucose tolerance, and type 2 diabetes can occur, improving survival and patients' quality of life. The most effective way to achieve normal iron stores seems to be with the combination of deferoxamine and deferiprone. Furthermore, outcomes should continue to improve in the future. Starting relative intensive chelation in younger children may prevent short stature and abnormal pubertal maturation as well as other iron-related morbidities. Also, further information should become available on the use of other combinations in chelation treatment, some of which have been used only in a very limited fashion to date. All these advances in management require absolute cooperation and understanding of parents, children, and, subsequently, the patients themselves. Only with such cooperation can normal long-term survival be achieved, as adherence to treatment is now likely the primary barrier to longevity.

Systematic review of hyperbaric oxygen therapy for cerebral palsy: the state of the evidence.

A systematic review of the evidence was conducted on the benefits and adverse effects of hyperbaric oxygen treatment (HBOT) for cerebral palsy (CP). Studies of any HBOT regimen in patients with CP were included except for case reports and case series. Electronic databases (e.g. MEDLINE, EMBASE), professional society databases, and reference lists were searched to identify studies. Study quality was assessed using predefined criteria relevant to the study design. Two randomized controlled trials and four observational studies were identified. Best evidence came from a randomized controlled trial which found that HBOT at 1.75 atmospheres (atm) and 1.3 atm of room air resulted in similar improvements in motor function (5-6%). Other outcomes also indicated no difference between the HBOT and room air. Observational studies reported improvements in motor function to a similar degree. Other evidence was insufficient to clarify the benefits and/or adverse effects of HBOT for CP. Both HBOT and pressurized room air resulted in improvements in motor function compared with baseline. Similar improvements were seen in the observational studies. Children undergoing HBOT were reported to experience adverse events, including seizures and the need for ear pressure equalization tube placement, but the incidence was unclear. Future research is needed to determine the efficacy of pressurized room air or non-pressurized oxygen in equivalent amounts by mask, compared with standard treatments.

Hyperbaric oxygen therapy for stroke: a systematic review of the evidence.

OBJECTIVE: To identify the benefits and harms of using hyperbaric oxygen therapy to treat acute or subacute stroke or the chronic effects of a stroke. We aimed to identify any gaps in the evidence to provide guidance for future research. DESIGN: A systematic review of the evidence. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Library, HealthSTAR, CINAHL, MANTIS, bibliographic databases from professional societies and hyperbaric oxygen therapy practitioners, and reference lists. Databases were searched from inception to December 2003. STUDIES: Controlled clinical trials and observational studies published in English. PARTICIPANTS: Patients with ischaemic stroke in any inpatient or outpatient setting. OUTCOMES: Mortality, functional health outcomes and adverse events. DATA COLLECTION AND ANALYSIS: Using predetermined criteria, two reviewers assessed each study for inclusion, and abstracted data about study design, population, interventions, and outcomes. We assigned an overall quality rating (good, fair, or poor) based on internal validity. RESULTS: We identified only four randomized controlled trials and one controlled clinical trial. The best evidence shows no benefit to hyperbaric oxygen therapy in patients with stroke, but because the stage of patients enrolled (acute, subacute, or chronic), the documentation of type and severity of stroke, and the dosage of hyperbaric oxygen therapy given varied considerably, the generalizability of these results is limited. We identified 17 observational studies; all were poor quality. CONCLUSIONS: The overall evidence is insufficient to determine the effectiveness of hyperbaric oxygen therapy in any subgroup of stroke patients. To determine if hyperbaric oxygen therapy for stroke provides any benefit and that these outweigh potential harms, good quality studies are needed.

Hyperbaric oxygen therapy for traumatic brain injury: a systematic review of the evidence.

OBJECTIVE: To identify the benefits and harms of hyperbaric oxygen therapy (HBOT) to treat traumatic brain injury (TBI). DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, HealthSTAR, CINAHL, MANTIS, professional society databases, and reference lists. Databases were searched from inception through December 2003. STUDY SELECTION: We included English-language studies of patients with TBI given HBOT and evaluating functional health outcomes. DATA EXTRACTION: Data were abstracted by 1 reviewer and checked by a second. Study quality was rated as good, fair, or poor. DATA SYNTHESIS: Two fair-quality randomized controlled trials of patients with severe brain injury reported conflicting results. One found no difference in mortality (48% HBOT vs 55% control) or morbidity at 1 year. In young patients with brainstem contusion, significantly more regained consciousness at 1 month with HBOT (67%) than control (11%) (P<.03). The other found a significant decrease in mortality in the HBOT group at 1 year (17%) compared with controls (31%) (P=.037). This decrease in mortality was accompanied by an increase in proportion of patients with severe disability. Patients with intracranial pressure (ICP) greater than 20 mmHg or a Glasgow Coma Scale score of 4 to 6 had significantly lower mortality at 1 year than controls. Five observational studies did not provide better evidence of effectiveness or adverse events. Two indicated a potential for initially reducing elevated ICP in some patients. However, rebound elevations higher than pretreatment levels occurred in some patients. Adverse events, including seizures, pulmonary symptoms, and neurologic deterioration, were reported; however, no study systematically assessed adverse events, and none reported adverse events in control groups. CONCLUSIONS: The evidence for HBOT for TBI is insufficient to prove effectiveness or ineffectiveness, and more high-quality studies are needed. The evidence indicates that there is a small chance of a mortality benefit, which may depend on subgroup selection. The effect on functional status and the incidence and clinical significance of adverse effects are unclear.

Routine vitamin supplementation to prevent cardiovascular disease: a summary of the evidence for the U.S. Preventive Services Task Force.

BACKGROUND: Antioxidant vitamins are thought to play a role in atherosclerosis. Supplementation of these nutrients has been explored as a means of reducing cardiovascular morbidity and mortality. PURPOSE: To assess the evidence of the effectiveness of vitamin supplementation, specifically vitamins A, C, and E; beta-carotene; folic acid; antioxidant combinations; and multivitamin supplements, in preventing cardiovascular disease. DATA SOURCES: Cochrane Controlled Trials Registry and MEDLINE (1966 to September 2001), reference lists, and experts. STUDY SELECTION: The researchers selected English-language reports of randomized trials and cohort studies that assessed vitamin supplementation in western populations and reported incidence of or death from cardiovascular events. They also included reports of good- or fair-quality clinical trials of primary and secondary prevention and good- or fair-quality prospective cohort studies. Studies that examined only dietary nutrients or did not provide separate estimates for supplements were not included. DATA EXTRACTION: Two reviewers abstracted descriptive information and data on cardiovascular outcomes and mortality from included studies. The researchers assessed study quality using predetermined criteria. DATA SYNTHESIS: Evidence tables were constructed to summarize data from included studies. The researchers summarized the strength, level, and quality of the overall evidence for the effectiveness of each of the vitamin supplements in preventing or treating cardiovascular disease. CONCLUSIONS: Some good-quality cohort studies have reported an association between the use of vitamin supplements and lower risk for cardiovascular disease. Randomized, controlled trials of specific supplements, however, have failed to demonstrate a consistent or significant effect of any single vitamin or combination of vitamins on incidence of or death from cardiovascular disease. Understanding the sources of these differences will permit researchers to better analyze the cohort study data and to better design long-term clinical trials.