21 CFR 314.71 - Procedures for submission of a supplement to an approved application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Procedures for submission of a supplement to an approved application. 314.71 Section 314.71 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...

21 CFR 314.71 - Procedures for submission of a supplement to an approved application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Procedures for submission of a supplement to an approved application. 314.71 Section 314.71 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...

21 CFR 314.71 - Procedures for submission of a supplement to an approved application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Procedures for submission of a supplement to an approved application. 314.71 Section 314.71 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...

The efficacy of supplemental intraosseous anesthesia after insufficient mandibular block.

PubMed

Prohić, Samir; Sulejmanagić, Halid; Secić, Sadeta

2005-02-01

It is a well-known scientific fact that only a small percentage of infiltration of inferior alveolar nerve is clinically proven to be efficient. The objective of this study was to determine the anesthetic efficacy of supplemental intraosseous injection, used after the insufficient classical mandibular block that didn't provide deep pulp anesthesia of mandibular molar planed for extraction. The experimental teeth consisted of 98 mandibular molars with clinical indication for extraction. Based on the history of disease, we indicated the extraction of the tooth. After that each tooth was tested with a electric pulp tester P1. We tested the pulp vitality and precisely determined the level of vitality. After that, each patient received classical mandibular block, and the pulp vitality was tested again. If the pulp tester indicated negative vitality for the certain mandibular molar, and the patient didn't complain about pain or discomfort during the extraction, the molar was extracted and the result was added to anesthetic success rate for the classical mandibular block. If, five minutes after receiving the mandibular block, the pulp tester indicated positive vitality (parameters of vitality) or the patient complained about pain or discomfort (parameters of pain and discomfort), we used the Stabident intraosseous anesthesia system. Three minutes after the application of supplemental intraosseous injection the molar was tested with the pulp tester again. The anesthetic solution used in both anesthetic techniques is lidocaine with 1:100.000 epinephrine. The results of this study indicate that the anesthetic efficacy of the mandibular block is 74.5%, and that supplemental intraosseous anesthesia, applied after the insufficient mandibular block, provides pulpal anesthesia in 94.9% of mandibular molars. The difference between anesthetic efficacy of the classical mandibular block and anesthetic efficacy of the supplemental intraosseous anesthesia, applied after the

Efficacy of supplementation in filipino children.

PubMed

Tayao, Charisse Marie S

2015-01-01

At present, in the absence of an anemia prevention and screening program in Barangay Vasra, this will aid in the formation of programs that would teach about this health related issue, with an intervention that could be used efficiently by the health workers at the non-government organization run center. The aim of the following study is to establish the efficacy of iron supplementation alone versus iron and ascorbic acid supplementation in improving the hemoglobin (Hgb), hematocrit (Hct), reticulocyte count and red cell indices of anemic undernourished children 5-10 years of age at Lingap Center, Barangay Vasra, Quezon City. Anemic undernourished male and female children 5-10 years of age enrolled in the Supplementary Feeding Program of Lingap Center, Barangay Vasra, Quezon City. Prospective, experimental trial comparing two interventions-iron supplementation alone versus iron and ascorbic acid supplementation. A total of 25 children participated in this study, with a majority being female at 52% (13/25) of the total. Those who received iron supplementation alone for 6 months, while there were 50% (6/12) of either sex, whereas subjects who took iron and ascorbic acid supplementation for 6 months were predominantly female at 53.85% (7/13). Data obtained before and after iron supplementation alone revealed that there was an increase among the levels of Hgb, Hct, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and reticulocyte count, with the rise statistically significant. Hematological values gained before and after iron and ascorbic acid supplementation uncovered that there was an augmentation among the levels of Hct, MCV, MCH, MCHC and reticulocyte count, with the improvement statistically significant. Encompassing both interventions, the differences in findings were statistically significant in red blood cell (RBC) count, with the level progression statistically significant. Overall, the results

Efficacy of Supplementation in Filipino Children

PubMed Central

Tayao, Charisse Marie S.

2015-01-01

Introduction: At present, in the absence of an anemia prevention and screening program in Barangay Vasra, this will aid in the formation of programs that would teach about this health related issue, with an intervention that could be used efficiently by the health workers at the non-government organization run center. Objective: The aim of the following study is to establish the efficacy of iron supplementation alone versus iron and ascorbic acid supplementation in improving the hemoglobin (Hgb), hematocrit (Hct), reticulocyte count and red cell indices of anemic undernourished children 5-10 years of age at Lingap Center, Barangay Vasra, Quezon City. Methodology: Anemic undernourished male and female children 5-10 years of age enrolled in the Supplementary Feeding Program of Lingap Center, Barangay Vasra, Quezon City. Study Design: Prospective, experimental trial comparing two interventions-iron supplementation alone versus iron and ascorbic acid supplementation. Results: A total of 25 children participated in this study, with a majority being female at 52% (13/25) of the total. Those who received iron supplementation alone for 6 months, while there were 50% (6/12) of either sex, whereas subjects who took iron and ascorbic acid supplementation for 6 months were predominantly female at 53.85% (7/13). Data obtained before and after iron supplementation alone revealed that there was an increase among the levels of Hgb, Hct, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and reticulocyte count, with the rise statistically significant. Hematological values gained before and after iron and ascorbic acid supplementation uncovered that there was an augmentation among the levels of Hct, MCV, MCH, MCHC and reticulocyte count, with the improvement statistically significant. Encompassing both interventions, the differences in findings were statistically significant in red blood cell (RBC) count, with the level

75 FR 35044 - Notice of Approval of a Supplemental New Animal Drug Application; Penicillin G Procaine Suspension

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-21

...] Notice of Approval of a Supplemental New Animal Drug Application; Penicillin G Procaine Suspension AGENCY... Laboratories, Ltd. The supplemental NADA provides for a revised formulation of penicillin G procaine injectable... of NOROCILLIN (penicillin G procaine) Injectable Suspension by intramuscular injection in cattle...

Clinical Evidence Supporting US Food and Drug Administration Approval of Otolaryngologic Prescription Drug Indications, 2005-2014.

PubMed

Rathi, Vinay K; Wang, Bo; Ross, Joseph S; Downing, Nicholas S; Kesselheim, Aaron S; Gray, Stacey T

2017-04-01

Objective The US Food and Drug Administration (FDA) approves indications for prescription drugs based on premarket pivotal clinical studies designed to demonstrate safety and efficacy. We characterized the pivotal studies supporting FDA approval of otolaryngologic prescription drug indications. Study Design Retrospective cross-sectional analysis. Setting Publicly available FDA documents. Subjects Recently approved (2005-2014) prescription drug indications for conditions treated by otolaryngologists or their multidisciplinary teams. Drugs could be authorized for treatment of otolaryngologic disease upon initial approval (original indications) or thereafter via supplemental applications (supplemental indications). Methods Pivotal studies were categorized by enrollment, randomization, blinding, comparator type, and primary endpoint. Results Between 2005 and 2014, the FDA approved 48 otolaryngologic prescription drug indications based on 64 pivotal studies, including 21 original indications (19 drugs, 31 studies) and 27 supplemental indications (18 drugs, 33 studies). Median enrollment was 299 patients (interquartile range, 198-613) for original indications and 197 patients (interquartile range, 64-442) for supplemental indications. Most indications were supported by ≥1 randomized study (original: 20/21 [95%], supplemental: 21/27 [78%]) and ≥1 double-blinded study (original: 14/21 [67%], supplemental: 17/27 [63%]). About half of original indications (9/21 [43%]) and one-quarter of supplemental indications (7/27 [26%]) were supported by ≥1 active-controlled study. Nearly half (original: 8/21 [38%], supplemental: 14/27 [52%]) of all indications were approved based exclusively on studies using surrogate markers as primary endpoints. Conclusion The quality of clinical evidence supporting FDA approval of otolaryngologic prescription drug indications varied widely. Otolaryngologists should consider limitations in premarket evidence when helping patients make informed

21 CFR 314.70 - Supplements and other changes to an approved application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... application. (1)(i) Except as provided in paragraph (a)(1)(ii) of this section, the applicant must notify FDA... of change, the applicant must notify FDA about the change in a supplement under paragraph (b) or (c...

21 CFR 314.70 - Supplements and other changes to an approved application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... application. (1)(i) Except as provided in paragraph (a)(1)(ii) of this section, the applicant must notify FDA... of change, the applicant must notify FDA about the change in a supplement under paragraph (b) or (c...

77 FR 14480 - Defense Federal Acquisition Regulation Supplement: Commercial Determination Approval (DFARS Case...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

... acquisitions made pursuant to Federal Acquisition Regulation (FAR) 12.102(f)(1).'' This language clarifies that... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 212 RIN 0750-AH61 Defense Federal Acquisition Regulation Supplement: Commercial Determination Approval (DFARS Case 2011-D041) AGENCY...

Association between general self-efficacy level and use of dietary supplements in the group of American football players.

PubMed

Gacek, Maria

2016-01-01

Increased nutritional demands of athletes should be covered with a variable well-balanced diet, supported by dietary supplements stimulating synthesis of energy, development of muscle mass and strength, and improving physical capacity. The aim of this study was to analyze an association between the level of general self-efficacy and dietary supplement use among Polish athletes practicing American football on a competitive basis. The study included the group of 100 athletes (20-30 years of age, mean 24.27±2.76 years) who practiced American football on a competitive basis. The popularity of various dietary supplements was determined with an original survey, and the level of general self-efficacy with General Self-Efficacy Scale (GSES) by Schwarzer et al. Statistical analysis, conducted with Statistica 10.0 PL software, included intergroup comparisons with the Chi-square test. Isotonic drinks (74%), vitamin (65%) and mineral supplements (50%) and protein concentrates (53%) turned out to be the most popular ergogenic supplements among the American footballers. The group of less popular supplements included caffeine and/or guarana (44%), joint supporting supplements (40%), BCAA amino acids (39%), creatine (36%), carbohydrate concentrates (30%) and omega-3 fatty acids (30%). Analysis of a relationship between the popularity of ergogenic supplements and general self-efficacy showed that the athletes presenting with lower levels of this trait used multivitamin supplements significantly more often than did the persons characterized by lower self-efficacy levels (p<0.05). The popularity of some dietary supplements varied depending on the general self-efficacy level of the athletes; the popularity of vitamins was significantly higher among the sportsmen who presented with lower levels of this trait.

Patient use of dietary supplements: a clinician's perspective.

PubMed

Sadovsky, Richard; Collins, Nancy; Tighe, Ann P; Brunton, Stephen A; Safeer, Richard

2008-04-01

The estimated prevalence of dietary-supplement use among US adults was 73% in 2002. Appropriate use of dietary supplements within the paradigm of evidence-based medicine may be a challenge for medical doctors and non-physician clinicians. Randomized, controlled, clinical trial data, which are considered the gold standard for evidence-based decision making, are lacking. Standardized guidelines for the use of dietary supplements are lacking, and dietary supplements can bear unsupported claims. This article is intended to review clinically-relevant issues related to the widespread use of dietary supplements, with emphasis on regulatory oversight and safety. Review articles and clinical trial articles published up until December 2007 were selected based on a search of the MEDLINE electronic database using PubMed. The Food and Drug Administration (FDA) Website was also used as a resource. We used the search terms dietary supplement(s), vitamin supplements, mineral supplements, and Dietary Supplement and Health Education Act. Articles discussing dietary supplements and their regulation, prevalence of use, prescription and nonprescription formulations, and/or adverse events were selected for review. Articles discussing one or more of these topics in adults were selected for inclusion. New FDA regulations require dietary-supplement manufacturers to evaluate the identity, purity, strength, and composition of their products. However, these regulations are not designed to demonstrate product efficacy and safety, and dietary-supplement manufacturers are not required to submit efficacy and safety data to the FDA prior to marketing. Product contamination and/or mislabeling may undermine the integrity of dietary-supplement formulations. The use of dietary supplements may be associated with adverse events. Although there are new regulatory requirements for dietary supplements, these products will not require FDA approval or submission of efficacy and safety data prior to marketing

Efficacy of iron fortification compared to iron supplementation among Vietnamese schoolchildren

PubMed Central

Thi Le, Huong; Brouwer, Inge D; Burema, Jan; Nguyen, Khan Cong; Kok, Frans J

2006-01-01

The effect of iron fortification is generally assumed to be less than iron supplementation; however, the magnitude of difference in effects is not known. The present study aims to compare the efficacy of these two strategies on anaemia and iron status. After screening on low Hb, 425 anaemic children in six primary schools in Tam Nong district of Phu Tho province were included in a randomized, placebo-controlled trial comparing two groups receiving iron fortified instant noodles or iron supplementation for 6 months and a control group, with children in all groups having been dewormed. Blood samples were collected before and after intervention for haemoglobin, serum ferritin (SF), serum transferrin receptor (TfR), C-reactive protein (CRP), and haemoglobinopathies analysis. Regression analysis was used to assess the effect of iron fortification and iron supplementation on haemoglobin concentration, SF, TfR, body iron, and anaemic status as outcome variables. The improvement of haemoglobin, SF, and body iron level in the group receiving iron fortification was 42% (2.6 g/L versus 6.2 g/L), 20% (23.5 μg/L versus 117.3 μg/L), and 31.3% (1.4 mg/kg versus 4.4 mg/kg) of that in the iron supplementation group. The prevalence of anaemia dropped to 15.1% in the control group, with an additional reduction of anaemia of 8.5% in the iron supplementation group. The additional reduction due to iron fortification was 5.4%, which amounts to well over 50% of the impact of supplementation. In conclusion, the efficacy of iron fortification based on reduction of prevalence of anaemia, and on the change in haemoglobin level, is about half of the maximum impact of supplementation in case of optimal compliance. Thus, in a population of anaemic children with mild iron deficiency, iron fortification should be the preferred strategy to combat anaemia. PMID:17147795

Efficacy of iron fortification compared to iron supplementation among Vietnamese schoolchildren.

PubMed

Thi Le, Huong; Brouwer, Inge D; Burema, Jan; Nguyen, Khan Cong; Kok, Frans J

2006-12-05

The effect of iron fortification is generally assumed to be less than iron supplementation; however, the magnitude of difference in effects is not known. The present study aims to compare the efficacy of these two strategies on anaemia and iron status. After screening on low Hb, 425 anaemic children in six primary schools in Tam Nong district of Phu Tho province were included in a randomized, placebo-controlled trial comparing two groups receiving iron fortified instant noodles or iron supplementation for 6 months and a control group, with children in all groups having been dewormed. Blood samples were collected before and after intervention for haemoglobin, serum ferritin (SF), serum transferrin receptor (TfR), C-reactive protein (CRP), and haemoglobinopathies analysis. Regression analysis was used to assess the effect of iron fortification and iron supplementation on haemoglobin concentration, SF, TfR, body iron, and anaemic status as outcome variables. The improvement of haemoglobin, SF, and body iron level in the group receiving iron fortification was 42% (2.6 g/L versus 6.2 g/L), 20% (23.5 microg/L versus 117.3 microg/L), and 31.3% (1.4 mg/kg versus 4.4 mg/kg) of that in the iron supplementation group. The prevalence of anaemia dropped to 15.1% in the control group, with an additional reduction of anaemia of 8.5% in the iron supplementation group. The additional reduction due to iron fortification was 5.4%, which amounts to well over 50% of the impact of supplementation. In conclusion, the efficacy of iron fortification based on reduction of prevalence of anaemia, and on the change in haemoglobin level, is about half of the maximum impact of supplementation in case of optimal compliance. Thus, in a population of anaemic children with mild iron deficiency, iron fortification should be the preferred strategy to combat anaemia.

Simple educational intervention will improve the efficacy of routine antenatal iron supplementation.

PubMed

Senanayake, Hemantha M; Premaratne, Samanthi P; Palihawadana, Thilina; Wijeratne, Sumeda

2010-06-01

Sri Lanka has a policy of free provision of iron supplements to pregnant women. However, iron deficiency anemia remains common in pregnancy. We tested the hypothesis that educating women regarding improving bioavailability could improve the efficacy of iron supplementation. The education focused on how best supplements could be taken and on how they should be stored. We carried out a study using a quasi-experimental design on a group of women attending for antenatal care at a suburban University Obstetric Unit in Sri Lanka. The control group had care free of charge including iron supplementation and antihelminthic therapy. In addition, the study group received an education in small groups regarding maximizing bioavailability of iron. Hemoglobin and iron status of the women were compared between the groups at recruitment and at 34 weeks of gestation. The two groups were equally matched in demographic data, and hemoglobin and iron status. There were significant differences between the two groups at 34 weeks in the hemoglobin levels, serum ferritin levels, anemia rates and the number with low ferritin (P < 0.0001 for all parameters), with a favorable outcome in the study group. The study group had used the iron tablets in ways that improved their bioavailability. A simple health education improved the efficacy of iron supplementation in this population. Such interventions should be an integral part of iron supplementation programs, especially in populations whose habits tend to reduce the bioavailability of iron.

Efficacy of a food supplement in patients with hashimoto thyroiditis.

PubMed

Nordio, M; Basciani, S

2015-01-01

Thyroid inflammation has been commonly seen in recent decades, due to a series of factors and is considered as the most frequent thyroid illness. It is characterized by some distinctive traits, which include morphological and hormonal modifications, often in association with an elevated anti-thyroid autoantibody title. The aim of the therapy is to improve symptoms as fast as possible, treating inflammation and subsequent hypothyroidism, when present. Therefore, we evaluated the efficacy of a Food Supplement (FS) containing enzymes which is commonly used in various inflammatory processes and is able to modulate immune reactions during inflammation in a very rapid and efficacious way. An open, controlled study was then designed and 45 patients with Hashimoto thyroiditis were enrolled and divided into 3 groups (FS alone; thyroid hormones alone; FS plus thyroid hormones). Blood, morphological and subjective parameters were considered. The results obtained indicate that the FS used in our study is efficacious and safe when used alone and/or in combination with thyroid hormones in the treatment of autoimmune thyroiditis, as documented by the improvement of the majority of the parameters considered. The efficacy was considered faster than thyroid hormones alone as far as subjective symptomatology is considered. In conclusion, the use of the food supplement evaluated herein during inflammation may be considered an additional tool in clinicians’ hands, when facing patients with autoimmune thyroiditis, especially in presence of subjective symptomatology, in order to rapidly alleviate it.

Omega-3 Fatty Acid Formulations in Cardiovascular Disease: Dietary Supplements are Not Substitutes for Prescription Products.

PubMed

Fialkow, Jonathan

2016-08-01

Omega-3 fatty acid products are available as prescription formulations (icosapent ethyl, omega-3-acid ethyl esters, omega-3-acid ethyl esters A, omega-3-carboxylic acids) and dietary supplements (predominantly fish oils). Most dietary supplements and all but one prescription formulation contain mixtures of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Products containing both EPA and DHA may raise low-density lipoprotein cholesterol (LDL-C). In clinical trials, the EPA-only prescription product, icosapent ethyl, did not raise LDL-C compared with placebo. To correct a common misconception, it is important to note that omega-3 fatty acid dietary supplements are not US FDA-approved over-the-counter drugs and are not required to demonstrate safety and efficacy prior to marketing. Conversely, prescription products are supported by extensive clinical safety and efficacy investigations required for FDA approval and have active and ongoing safety monitoring programs. While omega-3 fatty acid dietary supplements may have a place in the supplementation of diet, they generally contain lower levels of EPA and DHA than prescription products and are not approved or intended to treat disease. Perhaps due to the lack of regulation of dietary supplements, EPA and DHA levels may vary widely within and between brands, and products may also contain unwanted cholesterol or fats or potentially harmful components, including toxins and oxidized fatty acids. Accordingly, omega-3 fatty acid dietary supplements should not be substituted for prescription products. Similarly, prescription products containing DHA and EPA should not be substituted for the EPA-only prescription product, as DHA may raise LDL-C and thereby complicate the management of patients with dyslipidemia.

Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis.

PubMed

Funk, Janet L; Frye, Jennifer B; Oyarzo, Janice N; Kuscuoglu, Nesrin; Wilson, Jonathan; McCaffrey, Gwen; Stafford, Gregory; Chen, Guanjie; Lantz, R Clark; Jolad, Shivanand D; Sólyom, Aniko M; Kiela, Pawel R; Timmermann, Barbara N

2006-11-01

Scientific evidence is lacking for the antiarthritic efficacy of turmeric dietary supplements that are being promoted for arthritis treatment. Therefore, we undertook studies to determine the antiarthritic efficacy and mechanism of action of a well-characterized turmeric extract using an animal model of rheumatoid arthritis (RA). The composition of commercial turmeric dietary supplements was determined by high-performance liquid chromatography. A curcuminoid-containing turmeric extract similar in composition to these supplements was isolated and administered intraperitoneally to female Lewis rats prior to or after the onset of streptococcal cell wall-induced arthritis. Efficacy in preventing joint swelling and destruction was determined clinically, histologically, and by measurement of bone mineral density. Mechanism of action was elucidated by analysis of turmeric's effect on articular transcription factor activation, microarray analysis of articular gene expression, and verification of the physiologic effects of alterations in gene expression. A turmeric fraction depleted of essential oils profoundly inhibited joint inflammation and periarticular joint destruction in a dose-dependent manner. In vivo treatment prevented local activation of NF-kappaB and the subsequent expression of NF-kappaB-regulated genes mediating joint inflammation and destruction, including chemokines, cyclooxygenase 2, and RANKL. Consistent with these findings, inflammatory cell influx, joint levels of prostaglandin E(2), and periarticular osteoclast formation were inhibited by turmeric extract treatment. These translational studies demonstrate in vivo efficacy and identify a mechanism of action for a well-characterized turmeric extract that supports further clinical evaluation of turmeric dietary supplements in the treatment of RA.

A Review of the Efficacy, Safety, and Clinical Implications of Naturally Derived Dietary Supplements for Dyslipidemia.

PubMed

Thaipitakwong, Thanchanit; Aramwit, Pornanong

2017-02-01

Dyslipidemia is recognized as a major cause of cardiovascular disease. A number of evidence-based guidelines recommend conventional synthetic drugs as standard therapy for dyslipidemia in clinical practice. However, antihyperlipidemic drugs have some serious side effects. Naturally derived dietary supplements are becoming attractive as an alternative strategy because of their high efficacy and safety, as supported by numerous data. Moreover, they could be considered an initial treatment for dyslipidemia. The aims of this literature review were to demonstrate the efficacy, safety, and clinical implications of dietary supplements for treating dyslipidemia. We reviewed the literature, including data from in vitro, in vivo, and human studies, and clinical guideline recommendations. We classified dietary supplements by their proposed mechanisms of action on lipid metabolism and also collected daily dosage recommendations, interactions with concurrent drugs and/or foods, dosage forms, and examples of commercially available products. Various types of naturally derived dietary supplements exhibit lipid-improving properties. Efficacy and safety are acceptable; however, their use in clinical practice will require further well-designed investigations and the support of scientific data.

TSO C-129 approvals and anticipated approvals

DOT National Transportation Integrated Search

2001-01-01

This document contains a table of the approvals and anticipated approvals of TSO-C129a equipment (the technical standard order (TSO) for Airborne Supplemental Navigation Equipment Using the Global Positioning System (GPS)). This TSO prescribes the mi...

Efficacy, Safety, and Regulatory Approval of Food and Drug Administration-Designated Breakthrough and Nonbreakthrough Cancer Medicines.

PubMed

Hwang, Thomas J; Franklin, Jessica M; Chen, Christopher T; Lauffenburger, Julie C; Gyawali, Bishal; Kesselheim, Aaron S; Darrow, Jonathan J

2018-04-24

Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non-breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non-breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression. Results Between 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non-breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non-breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy-designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non-breakthrough-designated drugs. Conclusion Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy

Unwarranted claims of drug efficacy in pharmaceutical sales visits: are drugs approved on the basis of surrogate outcomes promoted appropriately?

PubMed

Habibi, Roojin; Lexchin, Joel; Mintzes, Barbara; Holbrook, Anne

2017-11-01

This study compares physicians' recall of the claims of benefits on cardiovascular disease and diabetes made by pharmaceutical sales representatives for drugs approved on the basis of a surrogate outcome, i.e., an off-label claim, compared with those approved on the basis of a serious morbidity or mortality (clinical) outcome. Physicians in primary care practices in Montreal, Vancouver, Sacramento and Toulouse, who saw sales representatives as part of their usual practice and served a non-referral population, were contacted in blocks of 25 from a randomized list of all physicians practising in the relevant metropolitan area. We compared how frequently physicians reported that sales reps made claims of serious morbidity or mortality (clinically meaningful) benefits for drugs approved on the basis of surrogate outcomes vs. drugs approved on the basis of clinical outcomes. There were 448 promotions for 58 unique brand name cardiovascular and diabetes drugs. Claims of clinically meaningful benefit were reported in 156 (45%) of the 347 promotions for surrogate outcome drugs, constituting unwarranted efficacy claims, i.e., off-label promotion. Claims of clinical benefit were reported in 72 of the 101 promotions (71%) for drugs approved on the basis of clinical outcomes, adjusted OR = 0.3 (95% CI 0.2, 0.6), P < 0.001. Claims of efficacy made in sales visit promotions for drugs approved only on the basis of surrogate outcomes extended beyond the regulator-approved efficacy information for the product in almost half of promotions. Unapproved claims of drug efficacy constitute a form of off-label promotion and merit greater attention from regulators. © 2017 The British Pharmacological Society.

77 FR 59356 - Approval and Promulgation of Implementation Plans; North Carolina: Approval of Rocky Mount...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-27

... Promulgation of Implementation Plans; North Carolina: Approval of Rocky Mount Supplemental Motor Vehicle... is proposing to approve a revision to the North Carolina State Implementation Plan (SIP), submitted... supplements the original redesignation request and maintenance plan for Rocky Mount 1997 8-hour ozone area...

Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials

PubMed Central

Dong, Hongli; Pi, Fuhua; Ding, Zan; Chen, Wei; Pang, Shaojie; Dong, Wenya; Zhang, Qingying

2015-01-01

Background Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke. Methods A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions. Results B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12. Conclusions B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied. PMID:26355679

Examining the Mediating Effect of Self-Efficacy on Approval of Aggression and Proactive Aggression

ERIC Educational Resources Information Center

Hadley, Jade; Mowbray, Tony; Jacobs, Nicky

2017-01-01

Proactive aggression (PA) is goal-directed, hostile social behavior that has been linked to detrimental outcomes. It has been theorized that adolescents who believe aggression is a normal and acceptable social response (approval of aggression) are more likely to show PA. Confidence in one's ability to behave aggressively (self-efficacy about…

7 CFR 1717.901 - Early approval.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 11 2011-01-01 2011-01-01 false Early approval. 1717.901 Section 1717.901 Agriculture... for Supplemental Financing Required by 7 CFR 1710.110 § 1717.901 Early approval. (a) Conditions. If... supplemental financing early in the process, before funding is available for the concurrent RUS insured loan...

Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement.

PubMed

Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

2012-01-01

Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). In vivo toxicity studies were performed in male balb 'C' mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement.

Athletes and Supplements: Prevalence and Perspectives.

PubMed

Garthe, Ina; Maughan, Ronald J

2018-03-01

In elite sport, where opponents are evenly matched, small factors can determine the outcome of sporting contests. Not all athletes know the value of making wise nutrition choices, but anything that might give a competitive edge, including dietary supplements, can seem attractive. Between 40% and 100% of athletes typically use supplements, depending on the type of sport, level of competition, and the definition of supplements. However, unless the athlete has a nutrient deficiency, supplementation may not improve performance and may have a detrimental effect on both performance and health. Dietary supplements are classified as a subcategory of food, so manufacturers are not required to provide evidence of product safety and efficacy, nor obtain approval from regulatory bodies before marketing supplements. This creates the potential for health risks, and serious adverse effects have been reported from the use of some dietary supplements. Athletes who compete in sports under an anti-doping code must also realize that supplement use exposes them to a risk of ingesting banned substances or precursors of prohibited substances. Government systems of regulations do not include specific laboratory testing for banned substances according to the WADA list, so a separate regulatory framework to evaluate supplements for their risk of provoking a failed doping test is needed. In the high-performance culture typical of elite sport, athletes may use supplements regardless of possible risks. A discussion around medical, physiological, cultural, and ethical questions may be warranted to ensure that the athlete has the information needed to make an informed choice.

The Infatuation With Biotin Supplementation: Is There Truth Behind Its Rising Popularity? A Comparative Analysis of Clinical Efficacy versus Social Popularity.

PubMed

Soleymani, Teo; Lo Sicco, Kristen; Shapiro, Jerry

2017-05-01

Biotin, also known as Vitamin B7 or vitamin H, is a water-soluble B vitamin that acts as an essential cofactor for several carboxylases involved in the cellular metabolism of fatty acids, amino acids, and gluconeogenesis. Although there exists an incredible amount of social media hype and market advertising touting its efficacy for the improvement of hair quantity and quality, biotin's efficacy for hair remains largely unsubstantiated in scientific literature. We reviewed all pertinent scientific literature regarding the efficacy of biotin supplementation for hair growth and quality improvement, and we also investigated its popularity in society defined as a function of market analytics. To date, there have been no clinical trials conducted to investigate the efficacy of biotin supplementation for the treatment of alopecia of any kind, nor has there been any randomized controlled trial to study its effect on hair quality and quantity in human subjects. Because of the lack of clinical evidence, its use to improve hair quantity or quality is not routinely recommended. However, societal infatuation with biotin supplementation is not only propagated by its glamorization in popular media, its popularity is vastly disproportionate to the insufficient clinical evidence supporting it's efficacy in hair improvement. In other words, biotin supplements are quite "in vogue", without there being any real reason to be so.

J Drugs Dermatol. 2017;16(5):496-500.

Efficacy of dietary chromium (III) supplementation on tissue chromium deposition in finishing pigs.

PubMed

Wang, Min-Qi; Li, Hui; He, Yu-Dan; Wang, Chao; Tao, Wen-Jing; Du, Yong-Jie

2012-09-01

The study was conducted to evaluate the efficacy of different forms of trivalent chromium (Cr) supplementation on tissue chromium deposition in finishing pigs. A total of 96 pigs with an initial average body mass 65.57±1.05 kg were blocked by body mass and randomly assigned to four treatments with three replicates. Pigs were offered one of four diets including a control diet or the control diet supplemented with 200 μg/kg chromium from either chromium chloride (CrCl(3)), chromium picolinate (CrPic) or chromium nanocomposite (CrNano) for 40 days. During the trial, all pigs were given free access to feed and water. After feeding trial, eight pigs from each treatment were slaughtered for samples collection. The results showed that supplemental CrNano increased Cr content in blood, longissimus muscle, heart, liver, kidney, jejunum, and ileum (P<0.05). Supplemental Cr from three sources increased Cr excretion from all feces (P<0.05). Urinary Cr excretion was increased by CrNano or CrPic supplementation significantly. These results suggested that chromium nanocomposite exhibited more effective on tissue Cr deposition in pigs, which indicated higher absorption compared with CrCl(3) and CrPic.

Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement

PubMed Central

Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

2012-01-01

Objectives: Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). Materials and Methods: In vivo toxicity studies were performed in male balb ‘C’ mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. Results: No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. Conclusion: The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement. PMID:23087514

Consumers' perceptions of the dietary supplement health and education act: implications and recommendations.

PubMed

Dodge, Tonya

2016-01-01

In 1994, the United States Congress passed the Dietary Supplement Health and Education Act (DSHEA). The regulatory framework for dietary supplements created by DSHEA has led to significant misperceptions regarding consumers' understanding of the safety and efficacy of supplements. Research shows that consumers erroneously believe that: (1) supplements are approved by the government, (2) supplements have been tested for safety and effectiveness, (3) the content of supplements is analyzed, and (4) manufacturers are required to disclose known adverse effects to consumers. Furthermore, labelling requirements that are intended to provide transparency to consumers are relatively ineffective. The following four recommendations are offered for reforming DSHEA: (1) only allow structure-function claims that are supported by research evidence, (2) require manufacturers to list known adverse effects on the labels of dietary supplements, (3) require that the Food and Drug Administration analyzes the content of dietary supplements and (4) restrict the definition of dietary ingredients. These recommendations would bring DSHEA to more closely align with consumer expectations regarding the regulation of dietary supplements and would likely provide a safer landscape for the use of supplements. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Efficacy of multiple micronutrient supplementation for improving anemia, micronutrient status, growth, and morbidity of Peruvian infants.

PubMed

López de Romaña, Guillermo; Cusirramos, Sandra; López de Romaña, Daniel; Gross, Rainer

2005-03-01

Anemia, micronutrient deficiencies, and growth faltering are still common in Peru. The study objective was to determine the efficacy of different micronutrient supplements in preventing growth failure, anemia, and micronutrient deficiencies in Peruvian infants. Three hundred and thirteen infants aged 6 to 12 mo participated in a double-blind, masked, controlled trial in which they were randomly assigned to receive either a daily dose of iron (DI), a daily dose of multiple micronutrients (DMM), a weekly dose of multiple micronutrients, or a placebo (P) for 6 mo. None of the supplements tested prevented growth faltering or the morbidities common during infancy. Anemia and plasma homocysteine concentrations fell significantly in all groups during the study, but the mean change of plasma homocysteine during the trial period was significantly smaller in the DI group than in other groups, and the increase in hemoglobin concentrations was smaller in the P group than the micronutrient treatment groups. Plasma ferritin concentrations decreased least in the groups taking daily micronutrient supplements containing iron (DI and DMM). There were no significant differences among groups in mean final values or changes in plasma zinc, retinol, tocopherol, or riboflavin. Although the DMM intervention was the most efficacious for preventing anemia, iron, and zinc deficiencies, 15%, 20%, and 50% of this group still remained anemic, zinc deficient, and iron deficient, respectively, at the end of the study. Further research thus should investigate whether higher doses of iron and zinc, together with infection control measures, are more efficacious.

FDA-Approved Natural Polymers for Fast Dissolving Tablets

PubMed Central

Alam, Md Tausif; Parvez, Nayyar; Sharma, Pramod Kumar

2014-01-01

Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing), in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets. PMID:26556207

Anesthetic efficacy of the supplemental intraosseous injection for teeth with irreversible pulpitis.

PubMed

Parente, S A; Anderson, R W; Herman, W W; Kimbrough, W F; Weller, R N

1998-12-01

The purpose of this study was to determine the efficacy of a supplemental intraosseous injection (IOI) of 2% lidocaine with 1:100,000 epinephrine using the Stabident device, after conventional anesthetic methods had failed. Patients who experienced pain during endodontic access and required a supplemental IOI using 0.45 to 0.90 ml of the local anesthetic were identified. All 37 of the patients treated had teeth diagnosed with irreversible pulpitis. Thirty-four of the teeth were mandibular posterior teeth, 2 were maxillary posterior teeth, and 1 was a maxillary anterior tooth. Patients with maxillary teeth had received infiltration anesthesia, and those with mandibular teeth had received an inferior alveolar nerve block in conjunction with long buccal infiltration. A minimum of 3.6 ml of local anesthetic was used with the conventional techniques. Modified visual analogue scales, coupled with operator evaluations, were used to measure success. The Stabident IOI was an effective supplemental anesthetic technique in 89% (+/- 5.1) or 33/37 patients evaluated. The 95% confidence interval was 74 to 97%. The IOI was successful in 91% (+/- 4.9) of the mandibular posterior teeth (31/34), and 67% of the maxillary teeth (2/3).

Predicting the Efficacy of Protein-Energy Supplementation in Frail Older Adults Living in Community.

PubMed

Kim, C O

2014-01-01

Protein-energy malnutrition is a major cause of functional decline in the elderly and is clearly an important component of frailty. However, limited evidence is available about how to select frail individuals most benefiting from protein-energy supplementation. 1) To investigate factors associated with stronger benefits from protein-energy supplementation, and 2) to test the hypothesis that the severity of frailty is associated with the efficacy of protein-energy supplementation. Secondary analysis of data from a pre-post-intervention study and a clinical trial. National Home Healthcare Services in Gangbuk-gu, Seoul, South Korea. 123 community-dwelling frail older adults [usual gait speed (UGS) <0.6m/sec and Mini Nutritional Assessment (MNA) <24]. Each participant was received with two 200 mL per day of commercial liquid formula (providing additional 400 kcal of energy and 25 g of protein per day) for 12 weeks. Relative change in the Physical Functioning (PF) and Short Physical Performance Battery (SPPB) score between the baseline and 12-week follow-up assessments were measured. Multilevel mixed-effect linear regression analysis showed that a lower level of baseline UGS was associated with a greater improvement in PF and SPPB score after adjustment for age, gender, education, living status, beneficiary of public assistance, number of chronic diseases, compliance, and type of dataset (p<0.001). A lower level of baseline MNA score was associated with greater change in PF and SPPB score after adjustment for multiple covariates (p≤0.045). Participants with severe frailty (UGS <0.3 m/sec + MNA <17) showed 52.4% and 44.6% more relevant improvements in PF and SPPB score, respectively, than those with mild frailty (UGS 0.3-0.6 m/sec + MNA 17-24) (p<0.001). Slower UGS and lower MNA score are independently associated with the greater efficacy of protein-energy supplementation on functional status.

Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: Systematic review and meta-analysis.

PubMed

Makam, Raghavendra Charan P; Hoaglin, David C; McManus, David D; Wang, Victoria; Gore, Joel M; Spencer, Frederick A; Pradhan, Richeek; Tran, Hoang; Yu, Hong; Goldberg, Robert J

2018-01-01

Direct oral anticoagulants (DOACs) have emerged as promising alternatives to vitamin K antagonists (VKAs) for patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Few meta-analyses have included all DOACs that have received FDA approval for these cardiovascular indications, and their overall comparisons against VKAs have shortcomings in data and methods. We provide an updated overall assessment of the efficacy and safety of those DOACs at dosages currently approved for NVAF or VTE, in comparison with VKAs. We used data from Phase 3 randomized trials that compared an FDA-approved DOAC with VKA for primary prevention of stroke in patients with NVAF or for treatment of acute VTE. Among trial participants with NVAF, DOAC recipients had a lower risk of stroke or systemic embolism [Pooled Odds Ratio (OR) 0.76, 95% Confidence Interval (CI) (0.68-0.84)], any stroke (0.80, 0.73-0.88), systemic embolism (0.56, 0.34-0.93), and total mortality (0.89, 0.84-0.95). Safety outcomes also showed a lower risk of fatal, major, and intracranial bleeding but higher risk for gastrointestinal bleeding (GIB). Patients with acute VTE randomized to DOACs had comparable risk of recurrent VTE and death (OR 0.88, 95% CI 0.75-1.03), recurrent DVT (0.83, 0.66-1.05), recurrent non-fatal PE (0.97, 0.75-1.25), and total mortality (0.94, 0.79-1.12). Safety outcomes for DOACs showed a lower risk of major, fatal, and intracranial bleeding, but similar risk of GIB. Patients receiving DOACs for NVAF had predominantly superior efficacy and safety. Patients who were treated with DOACs for acute VTE had non-inferior efficacy, but an overall superior safety profile.

Efficacy of micellized vs. fat-soluble vitamin D3 supplementation in healthy school children from Northern India.

PubMed

Marwaha, Raman K; Yenamandra, Vamsi K; Ganie, Mohammed Asraf; Sethuraman, Gomathy; Sreenivas, Vishnubhatla; Ramakrishnan, Lakshmy; Mathur, Sathish K; Sharma, Vinod K; Mithal, Ambrish

2016-12-01

Vitamin D deficiency is a widely recognized public health problem. Efficacy of a recently developed micellized form of vitamin D3 has not been studied. Hence, we undertook this study to compare its efficacy with the conventionally used fat-soluble vitamin D3. In this open-labeled nonrandomized pilot study, we recruited 180 healthy children, aged 13-14 years in two groups and supplemented Group A (60 children) with 60,000 IU of fat-soluble vitamin D3/month with milk and Group B (120 children) with 60,000 IU/month of water miscible vitamin D3 under supervision for 6 months. Serum 25(OD)D, parathyroid hormone (PTH), calcium, phosphate, and alkaline phosphatase (ALP) levels were evaluated before and after supplementation in 156 children (54 in Group A and 102 in Group B) who completed the study. We observed a significantly greater increase in the serum 25(OH)D levels in group B as compared to group A (31.8±9.1 ng/mL vs. 23.7±10.4 ng/mL; p<0.001). All children in group B achieved adequate levels of serum 25(OH)D (>20 ng/mL) as against 83.3% children in group A. Serum PTH and ALP levels declined considerably in both the groups following supplementation. Vitamin D supplementation significantly increased the serum 25(OH)D levels in both groups. Miscible form of vitamin D3 appears to be better in achieving higher levels of serum 25(OH)D than that observed with a similar dose of fat-soluble vitamin D3. Further studies with different dose regimens are required to establish its efficacy over the conventionally used fat-soluble vitamin D3.

Efficacious Action and Social Approval as Interacting Dimensions of Self-Esteem: A Tentative Formulation Through Construct Validation

ERIC Educational Resources Information Center

Franks, David D.; Marolla, Joseph

1976-01-01

A theoretical and operational rationale is presented for the development of multidimensional measures of self-esteem. Self-esteem is conceptualized as a function of two processes reflected appraisals of significant others in one's social environment in the form of social approval, and the individual's feelings of efficacy and competence derived…

42 CFR 422.102 - Supplemental benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 3 2012-10-01 2012-10-01 false Supplemental benefits. 422.102 Section 422.102... (CONTINUED) MEDICARE PROGRAM (CONTINUED) MEDICARE ADVANTAGE PROGRAM Benefits and Beneficiary Protections § 422.102 Supplemental benefits. (a) Mandatory supplemental benefits. (1) Subject to CMS approval, an MA...

42 CFR 422.102 - Supplemental benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 3 2013-10-01 2013-10-01 false Supplemental benefits. 422.102 Section 422.102... (CONTINUED) MEDICARE PROGRAM (CONTINUED) MEDICARE ADVANTAGE PROGRAM Benefits and Beneficiary Protections § 422.102 Supplemental benefits. (a) Mandatory supplemental benefits. (1) Subject to CMS approval, an MA...

42 CFR 422.102 - Supplemental benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Supplemental benefits. 422.102 Section 422.102... (CONTINUED) MEDICARE PROGRAM (CONTINUED) MEDICARE ADVANTAGE PROGRAM Benefits and Beneficiary Protections § 422.102 Supplemental benefits. (a) Mandatory supplemental benefits. (1) Subject to CMS approval, an MA...

Efficacy of beta-hydroxy-beta-methylbutyrate supplementation in maintenance hemodialysis patients.

PubMed

Fitschen, Peter J; Biruete, Annabel; Jeong, Jinny; Wilund, Kenneth R

2017-01-01

Maintenance hemodialysis (MHD) patients suffer from a number of co-morbidities including declines in muscle mass and physical function. Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the amino acid leucine that has been shown to improve lean mass and physical function in elderly and clinical populations, but had not been studied in MHD patients. The purpose of this study was to investigate the efficacy of HMB in this population. We performed a double-blind, placebo-controlled, randomized trial to assess the effects of daily HMB supplementation on co-morbidities in MHD patients. MHD patients were recruited and assigned to either daily supplementation with HMB (n = 16) or placebo (n = 17) for 6 months. Measurements of body composition, bone density, strength, physical function, fall risk, quality of life, and blood parameters were measured at baseline and 6 months. Blood was drawn at baseline, 3, and 6 months to measure compliance. No significant effects of HMB on body composition, bone density, strength, physical function, fall risk, quality of life, or blood parameters were observed. On analysis of plasma HMB concentrations, 5 of 16 patients (31%) in the HMB group were found to be noncompliant at 3 or 6 months. Therefore, we performed a per-protocol analysis with compliant participants only and observed no significant differences in our outcomes of interest. These results do not support the efficacy of HMB to attenuate co-morbid conditions in MHD patients. Moreover, this highlights the need for future interventions targeted at reducing pill burden and improving pill compliance in this population. © 2016 International Society for Hemodialysis.

29 CFR 1952.385 - Changes to approved plans.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Puerto Rico § 1952.385 Changes to... approved Puerto Rico's plan supplement, which is generally identical to the Federal Voluntary Protection... Program. (b) Legislation. (1) On March 29, 1994, the Assistant Secretary approved Puerto Rico's revised...

29 CFR 1952.385 - Changes to approved plans.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Puerto Rico § 1952.385 Changes to... approved Puerto Rico's plan supplement, which is generally identical to the Federal Voluntary Protection... Program. (b) Legislation. (1) On March 29, 1994, the Assistant Secretary approved Puerto Rico's revised...

29 CFR 1952.385 - Changes to approved plans.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Puerto Rico § 1952.385 Changes to... approved Puerto Rico's plan supplement, which is generally identical to the Federal Voluntary Protection... Program. (b) Legislation. (1) On March 29, 1994, the Assistant Secretary approved Puerto Rico's revised...

Efficacy and safety of creatine supplementation in juvenile dermatomyositis: A randomized, double-blind, placebo-controlled crossover trial.

PubMed

Solis, Marina Yazigi; Hayashi, Ana Paula; Artioli, Guilherme Giannini; Roschel, Hamilton; Sapienza, Marcelo Tatit; Otaduy, Maria Concepción; De Sã Pinto, Ana Lucia; Silva, Clovis Artur; Sallum, Adriana Maluf Elias; Pereira, Rosa Maria R; Gualano, Bruno

2016-01-01

It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health-related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. Twelve weeks of creatine supplementation in JDM patients were well-tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter. © 2015 Wiley Periodicals, Inc.

12 CFR 1815.106 - Supplemental environmental review.

Code of Federal Regulations, 2010 CFR

2010-01-01

... requiring a supplemental environmental review that affect the physical environment until Fund approval for... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Supplemental environmental review. 1815.106... TREASURY ENVIRONMENTAL QUALITY § 1815.106 Supplemental environmental review. (a) The designated Fund...

29 CFR 1952.227 - Changes to approved plans.

Code of Federal Regulations, 2010 CFR

2010-07-01

... plans. (a) Legislation. (1) On March 29, 1994, the Assistant Secretary approved Tennessee's revised... October 24, 1996, the Assistant Secretary approved Tennessee's plan supplement, which is generally... 61 FR 55099, Oct. 24, 1996] ...

The Efficacy of a Pre-Workout Vegan Supplement on High-Intensity Cycling Performance in Healthy College-Aged Males.

PubMed

Gallien, Gabrielle; Bellar, David; Davis, Greggory R

2017-11-02

There is a limited supply of sport nutrition supplements currently available for vegan or vegetarian athletes. In addition, the efficacy of a vegan or vegetarian pre-workout supplement that does not contain any processed ingredients or stimulants is currently unknown. The purpose of the current study was to examine the effects of an unprocessed vegan pre-workout supplement on high-intensity cycling performance. Participants completed three separate cycling trials following the consumption of a vegan pre-workout supplement, an isocaloric processed supplement, or a zero-calorie placebo supplement. Each supplement was consumed 30 minutes prior to each trial, and each cycling trial was separated by a minimum of 72 hours. Supplements were administered using a randomized, double-blind cross-over design. Each cycling trial was performed at a workload equal to 80% VO 2peak until exhaustion. The average time in seconds (s) until exhaustion values for the vegan, isocaloric, and zero-calorie supplements were 482 ± 163, 480 ± 157, and 496 ± 238, respectively. Consumption of the vegan supplement did not significantly improve performance compared to an isocaloric and zero-calorie supplement (F = 0.12, p =.89). The results of this study indicate that individuals who choose a vegan pre-workout supplement (over an isocaloric or zero-calorie product) will not experience any acute decrements or ergogenic benefits in cycling performance. Although the present study does not support performance benefits of the tested vegan pre-workout supplement before cycling, additional research examining various exercise intensities and modalities is warranted.

Preapproval and postapproval availability of published comparative efficacy research on biological agents.

PubMed

Thomas, Rachel Hutchins; Freeman, Maisha Kelly; Hughes, Peter J

2013-07-15

Preapproval and postapproval availability of published comparative efficacy studies on biological agents approved between 2000 and 2010 was investigated. Approval packages published on the Food and Drug Administration (FDA) website were examined for all biological agents approved between 2000 and 2010 to determine if comparative efficacy studies were available at the time of FDA approval. The availability of comparative efficacy studies published subsequent to approval was determined by searching PubMed for randomized, active-controlled experimental or observational study designs that measured efficacy as the primary endpoint and were relevant to the original FDA-approved indication. From 2000 to 2010, 107 biological agents were approved by FDA. Of the biological agents with alternative treatments, 54.6% had comparative efficacy data available at the time of approval. Although standard-reviewed biological agents were more likely to have comparative efficacy trials included in the FDA approval packages than priority-reviewed biological agents, statistically significant differences are unlikely. Subsequent to approval, 58.1% of biological agents had at least one published comparative efficacy trial, representing a 3.5% absolute increase in the availability of comparative efficacy studies since the time of approval. Vaccines and biological agents in the hematologic diseases, oncology, and miscellaneous diseases classes had fewer published postapproval comparative efficacy studies per agent compared with the overall group of biological agents. Nearly half of all biological agents approved for marketing between 2000 and 2010 lacked publicly accessible, active-controlled efficacy studies at the time of drug approval; a slightly greater proportion of biological agents had comparative efficacy data published subsequent to their approval.

Influence of the dietary supplement health and education act on consumer beliefs about the safety and effectiveness of dietary supplements.

PubMed

Dodge, Tonya; Litt, Dana; Kaufman, Annette

2011-03-01

The authors conducted two studies to examine the influence of the U.S. Dietary Supplement Health and Education Act (DSHEA) on consumer beliefs about the safety and effectiveness of dietary supplements. Study 1 manipulated information about Food and Drug Administration (FDA) approval in the context of a dietary supplement designed to improve immune system functioning. Study 2 tested the effect of an educational intervention designed to improve knowledge about the DSHEA. Results of Study 1 highlighted deficits in consumer knowledge about FDA regulation of dietary supplements. Results also showed that information about FDA approval failed to have a statistically significant effect on beliefs about safety or effectiveness of the dietary supplement. Results of Study 2 showed that participants who were educated about the regulation of dietary supplements under the DSHEA rated dietary supplements as less safe and less effective than did participants in the control condition. The authors discuss the implications for consumers in the United States and for public policy.

Review: efficacy of alginate supplementation in relation to appetite regulation and metabolic risk factors: evidence from animal and human studies.

PubMed

Georg Jensen, M; Pedersen, C; Kristensen, M; Frost, G; Astrup, A

2013-02-01

This review provides a critical update on human and animal studies investigating the effect of alginate supplementation on appetite regulation, glycaemic and insulinemic responses, and lipid metabolism with discussion of the evidence on potential mechanisms, efficacy and tolerability. Dependent on vehicle applied for alginate supplementation, the majority of animal and human studies suggest that alginate consumption does suppress satiety and to some extent energy intake. Only one long-term intervention trial found effects on weight loss. In addition, alginates seem to exhibit beneficial influence on postprandial glucose absorption and insulin response in animals and humans. However, alginate supplementation was only found to have cholesterol-lowering properties in animals. Several mechanisms have been suggested for the positive effect observed, which involve delayed gastric emptying, increased viscosity of digesta and slowed nutrient absorption in the small intestine upon alginate gel formation. Despite reasonable efficacy and tolerability from the acute or short-term studies, we still realize there is a critical need for development of optimal alginate types and vehicles as well as studies on further long-term investigation on alginate supplementation in humans before inferring that it could be useful in the management of obesity and the metabolic syndrome. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

5 CFR 2634.103 - Executive agency supplemental regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... written approval of the Office of Government Ethics, issue supplemental regulations implementing this part.... 2634.103 Section 2634.103 Administrative Personnel OFFICE OF GOVERNMENT ETHICS GOVERNMENT ETHICS... of Government Ethics as supplemental confidential reporting. Note: Supplemental regulations will not...

7 CFR 1717.901 - Early approval.

Code of Federal Regulations, 2010 CFR

2010-01-01

... for Supplemental Financing Required by 7 CFR 1710.110 § 1717.901 Early approval. (a) Conditions. If... supplemental financing early in the process, before funding is available for the concurrent RUS insured loan... commitment from the private lender to provide a loan for the remaining amount of financing required, with...

21 CFR 814.47 - Temporary suspension of approval of a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.47 Temporary suspension of approval of a PMA. (a) Scope. (1) This section describes the procedures that FDA will follow in... the original PMA, as well as any PMA supplement(s), for a medical device. (2) FDA will issue an order...

21 CFR 814.47 - Temporary suspension of approval of a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.47 Temporary suspension of approval of a PMA. (a) Scope. (1) This section describes the procedures that FDA will follow in... the original PMA, as well as any PMA supplement(s), for a medical device. (2) FDA will issue an order...

21 CFR 814.47 - Temporary suspension of approval of a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.47 Temporary suspension of approval of a PMA. (a) Scope. (1) This section describes the procedures that FDA will follow in... the original PMA, as well as any PMA supplement(s), for a medical device. (2) FDA will issue an order...

Impact of folate supplementation on the efficacy of sulfadoxine/pyrimethamine in preventing malaria in pregnancy: the potential of 5-methyl-tetrahydrofolate.

PubMed

Nzila, Alexis; Okombo, John; Molloy, Anne M

2014-02-01

Malaria remains the leading cause of mortality and morbidity in children under the age of 5 years and pregnant women. To counterbalance the malaria burden in pregnancy, an intermittent preventive treatment strategy has been developed. This is based on the use of the antifolate sulfadoxine/pyrimethamine, taken at specified intervals during pregnancy, and reports show that this approach reduces the malaria burden in pregnancy. Pregnancy is also associated with the risk of neural tube defects (NTDs), especially in women with low folate status, and folic acid supplementation is recommended in pregnancy to lower the risk of NTDs. Thus, in malaria-endemic areas, pregnant women have to take both antifolate medication to prevent malaria and folic acid to lower the risk of NTDs. However, the concomitant use of folate and antifolate is associated with a decrease in antifolate efficacy, exposing pregnant women to malaria. Thus, there is genuine concern that this strategy may not be appropriate. We have reviewed work carried out on malaria folate metabolism and antifolate efficacy in the context of folate supplementation. This review shows that: (i) the folate supplementation effect on antifolate efficacy is dose-dependent, and folic acid doses required to protect pregnant women from NTDs will not decrease antifolate activity; and (ii) 5-methyl-tetrahydrofolate, the predominant form of folate in the blood circulation, could be administered (even at high dose) concomitantly with antifolate without affecting antifolate efficacy. Thus, strategies exist to protect pregnant women from malaria while maintaining adequate folate levels in the body to reduce the occurrence of NTDs.

Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.

PubMed

Barnes, Tristan A; Amir, Eitan; Templeton, Arnoud J; Gomez-Garcia, Susana; Navarro, Beatriz; Seruga, Bostjan; Ocana, Alberto

2017-05-01

New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. Drugs approved for solid tumor treatment between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the registration trials and pooled in a meta-analysis. Odds ratios for toxic death, treatment discontinuation and grade 3-4 toxicity were compared to control groups. The Micromedex Red Book was used to calculate the monthly price. Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a greater degree with groups 1 and 2 than with groups 3 and 4, (pooled HR: 0.54, 0.56, 0.63, and 0.76 for groups 1-4 respectively, p for difference <0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR: 0.77, 0.78, 0.68, and 0.83 for groups 1-4 respectively, p for difference=0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no significant difference between groups. There was no meaningful correlation between pricing and efficacy. Compared to control groups, immunotherapeutics and drugs targeting oncogenes or angiogenesis improve efficacy to a greater degree than chemotherapy. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy of probiotic supplement for gestational diabetes mellitus: a systematic review and meta-analysis.

PubMed

Pan, Jiajia; Pan, Qiangwei; Chen, Yumei; Zhang, Hongping; Zheng, Xiaodong

2017-09-19

Probiotic supplement might be beneficial for gestational diabetes mellitus. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the efficacy of probiotic supplement in gestational diabetes mellitus. PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of probiotic supplement in gestational diabetes mellitus were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcome were fasting serum insulin and fasting plasma glucose. Meta-analysis was performed using the fixed-effect or random-effect model. Six RCTs involving 830 patients were included in the meta-analysis. Overall, compared with control intervention in gestational diabetes mellitus, probiotic supplementation intervention was found to significantly reduce fasting serum insulin (Std. mean difference = -0.95; 95% CI = -1.73 to -0.17; p < .00001) and HOMA-IR (Std. mean difference = -1.12; 95% CI = -2.05 to -0.18; p = .02), but showed no substantial impact on fasting plasma glucose (Std. mean difference = -0.49; 95% CI = -1.05-0.08; p = .09), gestational age (Std. mean difference = 0.07; 95% CI = -0.20-0.34; p = .63), and gestational weight (Std. mean difference = -0.11; 95% CI = -0.38-0.16; p = .43). Compared with control intervention in gestational diabetes mellitus, probiotic supplementation was found to significantly reduce insulin resistance (HOMA-IR) and fasting serum insulin, but had no substantial influence on fasting plasma glucose, gestational age and gestational weight.

Perceived efficacy, indications, and information sources for medically indigent patients and their healthcare providers regarding dietary supplements.

PubMed

Clay, Patrick G; Glaros, Alan G; Clauson, Kevin A

2006-03-01

Evidence exists that medically indigent and minority patients use dietary supplements at rates as high or higher than that of the general population. Safety concerns regarding the use of dietary supplements are further exacerbated by a suboptimal level of patient disclosure and provider inquiry. To determine dietary supplement use, indications, perceived efficacy, and information sources of patients and providers using a pilot study in a clinic for the medically indigent. Five hundred self-administered patient surveys and 50 healthcare provider surveys were made available to any patient at a free health clinic in Kansas City, MO. Surveys were collected and descriptive analyses were performed. Three hundred eleven patient surveys were returned. Of the 37.3% (116/311) of respondents who had used dietary supplements, 13.8% (n = 16) had 10 comorbid conditions. Ninety-six dietary supplements were used for 8 medical condition categories. The 9 agents most frequently reported used were garlic (n = 32), aloe/green tea (n = 27 each), chamomile/echinacea (n = 24 each), St. John's wort (n = 22), ginseng (n = 18), and cranberry/Ginkgo biloba (n = 17 each). Patients reported a broad range of indications for taking dietary supplements. Patients reported (mean +/- SD) 2.37 +/- 4.23 agents as effective and 0.78 +/- 1.73 as ineffective or harmful. Provider surveys revealed that 60% (21/35) and 74% (26/35) were currently or had ever used dietary supplements, respectively. Fifty-seven percent (20/35) of providers reported attending educational programs on dietary supplements, and providers perceived patient supplement use to be most influenced by advertisements (40%) and friends (40%). The medically indigent population uses a wide variety of dietary supplements. There is little consistency in perceived indications, which may prevent clinicians from accurately predicting specific herbal use rationale given any individual's or population's set of comorbid conditions. Clinicians are

Efficacy and Safety of Leucine Supplementation in the Elderly.

PubMed

Borack, Michael S; Volpi, Elena

2016-12-01

Leucine supplementation has grown in popularity due to the discovery of its anabolic effects on cell signaling and protein synthesis in muscle. The current recommendation is a minimum intake of 55 mg ⋅ kg -1 . d -1 Leucine acutely stimulates skeletal muscle anabolism and can overcome the anabolic resistance of aging. The value of chronic leucine ingestion for muscle growth is still unclear. Most of the research into leucine consumption has focused on efficacy. To our knowledge, very few studies have sought to determine the maximum safe level of intake. Limited evidence suggests that intakes of ≤1250 mg ⋅ kg -1 . d -1 do not appear to have any health consequences other than short-term elevated plasma ammonia concentrations. Similarly, no adverse events have been reported for the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), although no studies have tested HMB toxicity in humans. Therefore, future research is needed to evaluate leucine and HMB toxicity in the elderly and in specific health conditions. © 2016 American Society for Nutrition.

42 CFR 422.102 - Supplemental benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Supplemental benefits. (a) Mandatory supplemental benefits. (1) Subject to CMS approval, an MA organization may require Medicare enrollees of an MA plan (other than an MSA plan) to accept or pay for services in addition to Medicare-covered services described in § 422.101. (2) If the MA organization imposes mandatory...

Efficacy and safety of protein supplements for U.S. Armed Forces personnel: consensus statement.

PubMed

Pasiakos, Stefan M; Austin, Krista G; Lieberman, Harris R; Askew, E Wayne

2013-11-01

To provide evidence-based guidance regarding the efficacy and safety of dietary protein supplement (PS) use by members of the U.S. Armed Forces, a panel of internationally recognized experts in the fields of protein metabolism and dietary supplement research was convened by the Department of Defense Center Alliance for Dietary Supplement Research and the U.S. Army Medical Research and Material Command. To develop a consensus statement, potential benefits, risks, and strategies to optimize military performance through PS use were considered in the context of specific warfighter populations and occupational demands. To maintain muscle mass, strength, and performance during periods of substantial metabolic demand and concomitant negative energy balance the panel recommended that warfighters consume 1.5-2.0 g · kg(-1) · d(-1) of protein. However, if metabolic demand is low, such as in garrison, protein intake should equal the current Military Dietary Reference Intake (0.8-1.5 g · kg(-1) · d(-1)). Although PS use generally appears to be safe for healthy adults, warfighters should be educated on PS quality, given quality-control and contamination concerns with commercial dietary supplements. To achieve recommended protein intakes, the panel strongly urges consumption of high-quality protein-containing whole foods. However, when impractical, the use of PSs (20-25 g per serving or 0.25-0.3 g · kg(-1) per meal), particularly after periods of strenuous physical activity (e.g., military training, combat patrols, and exercise), is acceptable. The committee acknowledges the need for further study of protein requirements for extreme, military-specific environmental conditions and whether unique metabolic stressors associated with military service alter protein requirements for aging warfighters.

Efficacy of a crosslinked hyaluronic acid-based hydrogel as a tear film supplement: a masked controlled study.

PubMed

Williams, David L; Mann, Brenda K

2014-01-01

Keratoconjunctivitis sicca (KCS), or dry eye, is a significant medical problem in both humans and dogs. Treating KCS often requires the daily application of more than one type of eye drop in order to both stimulate tear prodcution and provide a tear supplement to increase hydration and lubrication. A previous study demonstrated the potential for a crosslinked hyaluronic acid-based hydrogel (xCMHA-S) to reduce the clinical signs associated with KCS in dogs while using a reduced dosing regimen of only twice-daily administration. The present study extended those results by comparing the use of the xCMHA-S to a standard HA-containing tear supplement in a masked, randomized clinical study in dogs with a clinical diagnosis of KCS. The xCMHA-S was found to significantly improve ocular surface health (conjunctival hyperaemia, ocular irritation, and ocular discharge) to a greater degree than the alternative tear supplement (P = 0.0003). Further, owners reported the xCMHA-S treatment as being more highly effective than the alternative tear supplement (P = 0.0024). These results further demonstrate the efficacy of the xCMHA-S in reducing the clinical signs associated with KCS, thereby improving patient health and owner happiness.

Efficacy of Long-Term Oral Vitamin B12 Supplementation after Total Gastrectomy: Results from a Prospective Study

PubMed Central

Moleiro, Joana; Mão de Ferro, Susana; Ferreira, Sara; Serrano, Miguel; Silveira, Margarida; Dias Pereira, António

2018-01-01

Background/Objectives Vitamin B12 (VB12) deficiency is a common complication after total gastrectomy which may be associated with megaloblastic anemia and potentially irreversible neurologic symptoms. Intramuscular supplementation of VB12 has been considered the standard treatment, although it is associated with high costs and patient discomfort. Patients/Methods We performed a prospective uncontrolled study (ACTRN12614000107628) in order to evaluate the clinical and laboratory efficacy of long-term oral VB12 supplementation in patients submitted to total gastrectomy. All patients received daily oral VB12 (1 mg/day) and were evaluated every 3 months (clinical and laboratory evaluation: hemoglobin, VB12, total iron, ferritin, and folate). Results A total of 26 patients were included with a mean age of 64 years (29–79). Patients were included with a mean period of 65 months (3–309) after total gastrectomy. At inclusion time, 17/26 patients were under intramuscular VB12, and 9 had not started supplementation yet. There were normal serum VB12 levels in 25/26 patients (mean VB12 serum levels: 657 pg/mL). The mean follow-up period was 20 (8.5–28) months. During follow-up, all patients had normal VB12 levels and there was no need for intramuscular supplementation. The patient with low VB12 levels had an increase to adequate levels, which remained stable. There were no differences with statistical significance among VB12 levels at 6 (867 pg/mL), 12 (1,008 pg/mL), 18 (1,018 pg/mL), and 24 (1,061 pg/mL) months. Iron and folate supplementation was necessary in 21 and 7 patients, respectively. Conclusions Oral VB12 supplementation is effective and safe in patients who underwent total gastrectomy and should be considered the preferential form of supplementation. PMID:29761147

Dietary Supplements are Not all Safe and Not all Food: How the Low Cost of Dietary Supplements Preys on the Consumer.

PubMed

Sax, Joanna K

2015-01-01

Dietary supplements are regulated as food, even though the safety and efficacy of some supplements are unknown. These products are often promoted as 'natural.' This leads many consumers to fail to question the supplements' safety, and some consumers even equate 'natural' with safe. But, 'natural' does not mean safe. For example, many wild berries and mushrooms are dangerous although they are natural. Another example is tobacco--a key ingredient in cigarettes: it is natural, but overwhelming studies have established the harm of cigarette smoke. The Food and Drug Administration (FDA) requires safety and efficacy testing prior to market entry for drugs. In contrast, the FDA only has limited ability to regulate the entry of new dietary supplements into the marketplace because supplements are treated as food. Two main arguments support the current regulatory structure of dietary supplements: (1) cost and (2) access. But lower cost and increased access to dietary supplements do not necessary have any relationship to safety and efficacy. Manufacturers' marketing techniques tout the health benefits of their supplements. Meanwhile, consumers are ingesting supplements without scientific studies indicating whether or not they are harmful. The FDA Food Safety and Modernization Act, signed into law on January 4, 2011, did not address the safety concerns regarding dietary supplements. This article discusses the regulatory deficiencies concerning dietary supplements and proposes novel solutions to address this specific sector of the food supply. This article advocates for the use of scientific data to support a multi-tiered classification system to ensure that dietary supplements on the market are safe.

29 CFR 1953.6 - Review and approval of plan supplements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 1953.6 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION...) OSHA shall review a supplement to determine whether it is at least as effective as the Federal program.... If the review reveals any defect in the supplement, or if more information is needed, OSHA shall...

29 CFR 1953.6 - Review and approval of plan supplements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 1953.6 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION...) OSHA shall review a supplement to determine whether it is at least as effective as the Federal program.... If the review reveals any defect in the supplement, or if more information is needed, OSHA shall...

Efficacy of Probiotic Supplementation Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Deng, Jiaqi; Yan, Qiong; Yang, Chun; Xia, Guodong; Zhou, Xian

2016-01-01

Background Traditional Helicobacter pylori (H. pylori) eradication therapies have shown efficacies below 80% in several studies, and their use has been accompanied by antibiotic-related side effects. Some recent studies have reported that supplementing standard therapies with probiotics can improve the efficacy and tolerability of Helicobacter pylori eradication therapy. Objective To assess the effects of probiotic supplementation on the eradication rates and therapy-related adverse event rates of anti-Helicobacter pylori regimens. Methods We searched PubMed, Medline, the Cochrane Central Registry of Controlled Trials and the Chinese Biomedical Database for eligible randomized controlled trials published through July, 2015. Review Manager 5.3 was used for all statistical analyses. Results Thirteen randomized controlled trials involving a total of 2306 patients were included in our analysis. Intent-to-treat (ITT) analysis performed using a fixed-effects model (test for heterogeneity I2 = 45%) showed that the pooled relative risk (RR) of eradication was significantly higher in the probiotic supplementation group than in the control group [RR 1.15, 95% confidence interval (CI): 1.10–1.20, P<0.00001]. The incidence of total antibiotic-related side effects was lower in the probiotic supplementation group than in the control group, and the pooled RR (studies n = 9) was 0.71 (95% CI: 0.54–0.94, P = 0.02), as determined using a random-effects model (heterogeneity test I2 = 59%). Certain adverse events, such as nausea and vomiting (RR = 0.58, 95% CI 0.35–0.95, P = 0.03), diarrhea (RR = 0.51, 95% CI: 0.31–0.84, P = 0.008) and constipation (RR = 0.47, 95% CI: 0.28–0.80, P = 0.005), were reported at lower rates in the probiotic supplementation group than in the control group. Subgroup analysis showed that eradication rates were significantly improved in both adults (RR = 1.14, 95% CI: 1.09–1.19, P<0.00001) and children (RR = 1.24, 95% CI: 1.05–1.47, P = 0.01) in

Anesthetic efficacy of the supplemental intraosseous injection of 3% mepivacaine in irreversible pulpitis.

PubMed

Reisman, D; Reader, A; Nist, R; Beck, M; Weaver, J

1997-12-01

To determine the efficacy of a supplemental intraosseous injection of 3% mepivacaine in mandibular posterior teeth with irreversible pulpitis. Intraosseous injection pain, subjective heart rate increase, and pain ratings during endodontic treatment were also assessed. Forty-eight patients with irreversible pulpitis received conventional inferior alveolar nerve blocks. Electric pulp testing was used to determine pulpal anesthesia. Patients who were positive to the pulp testing, or negative to pulp testing but felt pain during endodontic treatment, received an intraosseous injection of 1.8 ml of 3% mepivacaine. A second intraosseous injection of 3% mepivacaine (1.8 ml) was given if the first injection was unsuccessful. Seventy-five percent of patients required an initial intraosseous injection because of failure to gain pulpal anesthesia. The inferior alveolar block was 25% successful; the first intraosseous injection increased success to 80%. A second intraosseous injection further increased success to 98%. These differences were significant (p < 0.05). Eight percent (4/48) of the initial intraosseous injections resulted in solution being expressed into the oral cavity: these were considered technique failures. For mandibular posterior teeth with irreversible pulpitis, a supplemental intraosseous injection of 3% mepivacaine increased anesthetic success. A second intraosseous injection, when necessary, further improved success.

78 FR 38256 - Approval and Promulgation of Air Quality Implementation Plans; Ohio; Redesignation of the Ohio...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-26

...EPA is issuing a supplement to its proposed approval of Ohio's request to redesignate the Ohio portion of the Parkersburg-Marietta, West Virginia-Ohio, area to attainment for the 1997 annual National Ambient Air Quality Standards (NAAQS or standard) for fine particulate matter (PM2.5). This supplemental proposal revises and expands the basis for proposing approval of the state's request, in light of developments since EPA issued its initial proposal on November 30, 2012. This supplemental proposal addresses the effects of a January 4, 2013, decision of the United States Court of Appeals for the District of Columbia (D.C. Circuit or Court) to remand to EPA two final rules implementing the 1997 PM2.5 standard. In this supplemental proposal, EPA is also proposing to approve a supplement to the emission inventories previously submitted by Ohio. EPA is proposing that the inventories for ammonia and volatile organic compounds (VOC), in conjunction with the inventories for nitrogen oxides (NOX), direct PM2.5, and sulfur dioxide (SO2) that EPA previously proposed to approve, meet the comprehensive emissions inventory requirements of the Clean Air Act (CAA or Act). EPA is seeking comment only on the issues raised in its supplemental proposal, and is not re-opening for comment other issues raised in its prior proposal.

30 CFR 250.285 - How do I submit revised and supplemental EPs, DPPs, and DOCDs?

Code of Federal Regulations, 2010 CFR

2010-07-01

... that the Regional Supervisor determines are likely to result in a significant change in the impacts... supplemental EPs, DPPs, and DOCDs? (a) Submittal. You must submit to the Regional Supervisor any revisions and supplements to approved EPs, DPPs, or DOCDs for approval, whether you initiate them or the Regional Supervisor...

Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Ju, Woong; Oh, Seung-Won; Park, Sang Min; Koo, Bon-Kwon; Park, Byung-Joo

2013-01-01

Objective To assess the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases. Design Meta-analysis of randomised controlled trials. Data sources and study selection PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov searched in June and November 2012. Two authors independently reviewed and selected eligible randomised controlled trials, based on predetermined selection criteria. Results Out of 2240 articles retrieved from databases and relevant bibliographies, 50 randomised controlled trials with 294 478 participants (156 663 in intervention groups and 137 815 in control groups) were included in the final analyses. In a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I2=42%). Overall, there was no beneficial effect of these supplements in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, provider of supplements, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation was associated with a marginally increased risk of angina pectoris, while low dose vitamin B6 supplementation was associated with a slightly decreased risk of major cardiovascular events. Those beneficial or harmful effects disappeared in subgroup meta-analysis of high quality randomised controlled trials within each category. Also, even though supplementation with vitamin B6 was associated with a decreased risk of cardiovascular death in high quality trials, and vitamin E supplementation with a decreased risk of myocardial infarction

Efficacy of Supplemental Phonics-Based Instruction for Low-Skilled Kindergarteners in the Context of Language Minority Status and Classroom Phonics Instruction

ERIC Educational Resources Information Center

Vadasy, Patricia F.; Sanders, Elizabeth A.

2010-01-01

This study tested the efficacy of supplemental phonics instruction for 84 low-skilled language minority (LM) kindergarteners and 64 non-LM kindergarteners at 10 urban public schools. Paraeducators were trained to provide the 18-week (January-May) intervention. Students performing in the bottom half of their classroom language group (LM and non-LM)…

21 CFR 514.106 - Approval of supplemental applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., storage, expiration dates, etc). (vi) A change in promotional material for a prescription new animal drug... application. Category II supplements include the following: (i) A change in the active ingredient... specifications of the active or inactive ingredients. (iii) A change in dose (amount of drug administered per...

21 CFR 514.106 - Approval of supplemental applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., storage, expiration dates, etc). (vi) A change in promotional material for a prescription new animal drug... application. Category II supplements include the following: (i) A change in the active ingredient... specifications of the active or inactive ingredients. (iii) A change in dose (amount of drug administered per...

Anesthetic efficacy of the supplemental intraosseous injection of 2% lidocaine with 1:100,000 epinephrine in irreversible pulpitis.

PubMed

Nusstein, J; Reader, A; Nist, R; Beck, M; Meyers, W J

1998-07-01

The purpose of this study was to determine the anesthetic efficacy of a supplemental intraosseous injection of 2% lidocaine with 1:100,000 epinephrine in teeth diagnosed with irreversible pulpitis. Fifty-one patients with symptomatic, vital maxillary, and mandibular posterior teeth diagnosed with irreversible pulpitis received conventional infiltrations or inferior alveolar nerve blocks. Pulp testing was used to determine pulpal anesthesia after "clinically successful" injections. Patients who were positive to the pulp tests, or were negative to the pulp tests but felt pain during endodontic access, received an intraosseous injection using 1.8 ml of 2% lidocaine with 1:100,000 epinephrine. The results demonstrated that 42% of the patients who tested negative to the pulp tests reported pain during treatment and required supplemental anesthesia. Eighty-one percent of the mandibular teeth and 12% of maxillary teeth required an intraosseous injection due to failure to gain pulpal anesthesia. Overall, the Stabident intraosseous injection was found to be 88% successful in gaining total pulpal anesthesia for endodontic therapy. We concluded that, for posterior teeth diagnosed with irreversible pulpitis, the supplemental intraosseous injection of 2% lidocaine (1:100,000 epinephrine) was successful when conventional techniques failed.

An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements.

PubMed

Cohen, Pieter A; Bloszies, Clayton; Yee, Caleb; Gerona, Roy

2016-01-01

The amphetamine isomer β-methylphenylethylamine (BMPEA) was first synthesized in the early 1930s, but its efficacy and safety in humans has not been studied. Recently, the United States Food and Drug Administration (FDA) detected BMPEA in dietary supplements labelled as containing Acacia rigidula. Over a year after the FDA reported its findings, we analyzed Acacia rigidula dietary supplements to determine if BMPEA had been removed. Supplements were analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry. Diluted methanolic extract from each supplement was run three times and each data set obtained was analyzed using Agilent MassHunter Qualitative Analysis. The presence of BMPEA was confirmed by accurate mass, retention time and mass spectra match against a reference standard. Quantification of BMPEA was determined using an eight-point calibration curve of spiked standard to a matrix blank. Twenty-one brands of Acacia rigidula supplements were analyzed. More than half (11/21; 52.4%) of the Acacia rigidula supplement brands contained BMPEA. The stimulant was present at quantities such that consumers following recommended maximum daily servings would consume a maximum of 93.7 mg of BMPEA per day. Consumers of Acacia rigidula supplements may be exposed to pharmacological dosages of an amphetamine isomer that lacks evidence of safety in humans. The FDA should immediately warn consumers about BMPEA and take aggressive enforcement action to eliminate BMPEA in dietary supplements. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

78 FR 11808 - Approval and Promulgation of Implementation Plans; Tennessee: Approve Knox County Supplemental...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-20

... INFORMATION: On December 18, 2012, EPA proposed to approve, through parallel processing, a draft revision to... County to account for changes in the emissions model and vehicle miles traveled projection model. EPA is... submit comments. FOR FURTHER INFORMATION CONTACT: Kelly Sheckler, Air Quality Modeling and Transportation...

21 CFR 515.11 - Supplemental medicated feed mill license applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Supplemental medicated feed mill license... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS MEDICATED FEED MILL LICENSE Applications § 515.11 Supplemental medicated feed mill license applications. (a) After approval of a medicated feed...

78 FR 20856 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Redesignation of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-08

...EPA is issuing a supplement to its proposed approval of the State of Indiana's request to redesignate the Indianapolis area to attainment for the 1997 annual National Ambient Air Quality Standards (NAAQS or standard) for fine particulate matter (PM2.5). This supplemental proposal revises and expands the basis for proposing approval of the state's request, in light of developments since EPA issued its initial proposal on September 27, 2011. This supplemental proposal addresses four issues, including the effects of two decisions of the United States Court of Appeals for the District of Columbia (D.C. Circuit or Court): the Court's August 21, 2012 decision to vacate and remand to EPA the Cross- State Air Pollution Control Rule (CSAPR) and the Court's January 4, 2013 decision to remand to EPA two final rules implementing the 1997 PM2.5 standard. In this supplemental proposal, EPA is also proposing to approve a supplement to the emission inventories previously submitted by the state. EPA is proposing that the inventories for ammonia and Volatile Organic Compounds (VOC), in conjunction with the inventories for nitrogen oxides (NOX), direct PM2.5, and sulfur dioxide (SO2) that EPA previously proposed to approve, meet the comprehensive emissions inventory requirement of the Clean Air Act (CAA). Finally, this supplemental proposal solicits comment on the state's January 17, 2013 submission of Motor Vehicle Emissions Budgets (MVEBs) developed using EPA's Motor Vehicle Emissions Simulator (MOVES) 2010a emissions model to replace the MOBILE6.2 based MVEBs previously submitted as part of the PM2.5 maintenance plan for the Indianapolis area. EPA is seeking comment only on the issues raised in its supplemental proposal, and is not re-opening for comment other issues raised in its prior proposal.

Adverse Effects of Nutraceuticals and Dietary Supplements.

PubMed

Ronis, Martin J J; Pedersen, Kim B; Watt, James

2018-01-06

Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions.

Dietary supplements for football.

PubMed

Hespel, P; Maughan, R J; Greenhaff, P L

2006-07-01

Physical training and competition in football markedly increase the need for macro- and micronutrient intake. This requirement can generally be met by dietary management without the need for dietary supplements. In fact, the efficacy of most supplements available on the market is unproven. In addition, players must be cautious of inadequate product labelling and supplement impurities that may cause a positive drug test. Nonetheless, a number of dietary supplements may beneficially affect football performance. A high endurance capacity is a prerequisite for optimal match performance, particularly if extra time is played. In this context, the potential of low-dose caffeine ingestion (2 - 5 mg . kg body mass(-1)) to enhance endurance performance is well established. However, in the case of football, care must be taken not to overdose because visual information processing might be impaired. Scoring and preventing goals as a rule requires production of high power output. Dietary creatine supplementation (loading dose: 15 - 20 g . day(-1), 4 - 5 days; maintenance dose: 2 - 5 g g . day(-1)) has been found to increase muscle power output, especially during intermittent sprint exercises. Furthermore, creatine intake can augment muscle adaptations to resistance training. Team success and performance also depend on player availability, and thus injury prevention and health maintenance. Glucosamine or chondroitin may be useful in the treatment of joint pain and osteoarthritis, but there is no evidence to support the view that the administration of these supplements will be preventative. Ephedra-containing weight-loss cocktails should certainly be avoided due to reported adverse health effects and positive doping outcomes. Finally, the efficacy of antioxidant or vitamin C intake in excess of the normal recommended dietary dose is equivocal. Responses to dietary supplements can vary substantially between individuals, and therefore the ingestion of any supplement must be assessed

Dietary Supplements: What You Need to Know

MedlinePlus

... must notify FDA about that ingredient prior to marketing. However, the notification will only be reviewed by FDA (not approved) and only for safety, not effectiveness. Manufacturers are required to produce dietary supplements in ...

76 FR 40624 - Approval and Promulgation of Implementation Plans; State of Kansas

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... in the proposal, as supplemented by this notice, as its rationale for the final rule. No public... approved emissions limits with limited public process or without requiring further approval by EPA, that... on proposals for three states in Region 5). EPA notes that these public comments on another proposal...

77 FR 59666 - Agency Information Collection Activities; Extension of a Currently Approved Collection; Comments...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

..., perceptions of school environment, and safety at school. (5) An estimate of the total number of respondents... Activities; Extension of a Currently Approved Collection; Comments Requested: School Crime Supplement (SCS...: Extension of a currently approved collection. [[Page 59667

First vaccine approval under the FDA Animal Rule

PubMed Central

Beasley, David W C; Brasel, Trevor L; Comer, Jason E

2016-01-01

The US Food and Drug Administration’s Animal Rule was established to facilitate licensure of new products for life-threatening conditions when traditional efficacy trials in humans are unethical or impractical. In November, 2015 BioThrax became the first vaccine to receive approval for a new indication via this pathway. The basis for this approval and use of Animal Rule or other non-traditional approval pathways for licensure of vaccines for serious conditions are discussed. PMID:29263855

76 FR 40619 - Approval and Promulgation of Implementation Plans; State of Missouri

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... in the proposal as supplemented by this rule, as its rationale for the final rule. No public comments... approved emissions limits with limited public process or without requiring further approval by EPA, that... for three states in Region 5). EPA notes that these public comments on another proposal are not...

Parenteral or Enteral Arginine Supplementation Safety and Efficacy.

PubMed

Rosenthal, Martin D; Carrott, Phillip W; Patel, Jayshil; Kiraly, Laszlo; Martindale, Robert G

2016-12-01

Arginine supplementation has the potential to improve the health of patients. Its use in hospitalized patients has been a controversial topic in the nutrition literature, especially concerning supplementation of septic patients. In this article, we review the relevant literature both for and against the use of arginine in critically ill, surgical, and hospitalized patients. The effect of critical illness on arginine metabolism is reviewed, as is its use in septic and critically ill patients. Although mounting evidence supports immunonutrition, there are only a few studies that suggest that this is safe in patients with severe sepsis. The use of arginine has been shown to benefit a variety of critically ill patients. It should be considered for inclusion in combinations of immunonutrients or commercial formulations for groups in whom its benefit has been reported consistently, such as those who have suffered trauma and those in acute surgical settings. The aims of this review are to discuss the role of arginine in health, the controversy surrounding arginine supplementation of septic patients, and the use of arginine in critically ill patients. © 2016 American Society for Nutrition.

29 CFR 1952.374 - Final approval determination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... plan does not cover private sector maritime employment; worksites located within Federal military... under the Federal program; to submit plan supplements in accordance with 29 CFR part 1953; to allocate..., DEPARTMENT OF LABOR (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Virginia § 1952.374...

29 CFR 1952.313 - Final approval determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 1902. Accordingly, the Hawaii plan was granted final approval and concurrent Federal enforcement... employment in Hawaii. The plan does not cover maritime employment in the private sector; Federal government... effective as operations under the Federal program; to submit plan supplements in accordance with 29 CFR part...

29 CFR 1952.374 - Final approval determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... plan does not cover private sector maritime employment; worksites located within Federal military... under the Federal program; to submit plan supplements in accordance with 29 CFR part 1953; to allocate..., DEPARTMENT OF LABOR (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Virginia § 1952.374...

29 CFR 1952.294 - Final approval determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... Accordingly, the Nevada plan was granted final approval and concurrent Federal enforcement authority was... Nevada. The plan does not cover Federal government employers and employees; any private sector maritime... under the Federal program; to submit plan supplements in accordance with 29 CFR Part 1953; to allocate...

29 CFR 1952.294 - Final approval determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Accordingly, the Nevada plan was granted final approval and concurrent Federal enforcement authority was... Nevada. The plan does not cover Federal government employers and employees; any private sector maritime... under the Federal program; to submit plan supplements in accordance with 29 CFR Part 1953; to allocate...

29 CFR 1952.374 - Final approval determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... plan does not cover private sector maritime employment; worksites located within Federal military... under the Federal program; to submit plan supplements in accordance with 29 CFR part 1953; to allocate..., DEPARTMENT OF LABOR (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Virginia § 1952.374...

Efficacy of an exercise and nutritional supplement program on physical performance and nutritional status in older adults with mobility limitations residing at senior living facilities

USDA-ARS?s Scientific Manuscript database

This cluster-randomized trial was designed to determine the efficacy of a 6-month exercise-nutritional supplement program (ENP) on physical function and nutritional status for older adults and the feasibility of implementing this program in a senior living setting. Twenty senior living facilities we...

Dietary Supplements and Sports Performance: Amino Acids

PubMed Central

Williams, Melvin

2005-01-01

This is the third in a series of six articles to discuss the major classes of dietary supplements (vitamins; minerals; amino acids; herbs or botanicals; metabolites, constituents/extracts, or combinations). The major focus is on efficacy of such dietary supplements to enhance exercise or sport performance. PMID:18500957

[Insufficient evidence supporting iron supplementation in anaemia during pregnancy].

PubMed

Wiegerinck, Melanie M; Mol, Ben Willem J

2012-01-01

The Royal Dutch Organization of Midwives (KNOV) recently presented their practice guideline 'Anaemia in midwifery practice'. The guideline identified available evidence on diagnosis, prognosis and treatment of anaemia in pregnancy. Anaemia based on iron deficiency and subsequent treatment with iron supplementation are probably the most frequent aspects of care for pregnant women. However, there is surprisingly enough no evidence of the efficacy of iron supplementation treatment on relevant clinical outcomes in pregnant women with anaemia. We plead to make the next guideline a multidisciplinary one. Such a guideline may lead to a large pragmatic trial evaluating the efficacy of iron supplementation treatment for patients with anaemia.

Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic.

PubMed

Citrome, L

2011-02-01

To describe the efficacy and safety of lurasidone for the treatment of schizophrenia. The pivotal registration trials were accessed by querying the literature databases PubMed, EMBASE, ISI Web of Knowledge, as well as http://www.fda.gov and http://www.clinicaltrials.gov for the search term 'lurasidone'. Product labelling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports, abstracts and posters. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Lurasidone is a second-generation antipsychotic approved for the treatment of schizophrenia at a recommended starting dose of 40 mg/day administered once daily with food (≥350 calories). The maximum recommended dose is 80 mg/day. Regulatory approval was based primarily on a clinical trial programme that included four 6-week randomised clinical trials demonstrating efficacy vs. placebo in acute patients with schizophrenia. One additional Phase II clinical trial was considered a failed study because neither lurasidone nor the active control, haloperidol, separated from placebo on the primary outcome measure. One additional Phase III study was completed after the new drug application was submitted to the US Food and Drug Administration. Efficacy outcomes appear consistently in favour of lurasidone 80 mg/day vs. placebo on multiple measures of psychopathology, however, at least two studies also demonstrated efficacy for the doses of 40 and 120 mg/day. NNT vs. placebo was 3-6 for response as defined by ≥20% reduction in psychopathological rating scale total scores from baseline, depending on the study and the dose. Response as defined by a ≥30% improvement yielded NNTs ranging from 7 to 13. The most common adverse events in the clinical trials were

The use of, and perceptions about, dietary supplements among patients with heart failure.

PubMed

Fan, Xiuzhen; Lee, Kyoung Suk; Frazier, Susan K; Lennie, Terry A; Moser, Debra K

2014-08-01

Dietary supplement use is widespread; patterns of use and perceptions about supplements in individuals with heart failure (HF) are not well understood. The purpose of this study was to describe the prevalence, patterns and reasons for use of dietary supplements, and to compare characteristics of, and perceptions about, safety and efficacy between dietary supplement user and non-user participants with HF. Patients with HF (n=99) completed a Dietary Supplement Questionnaire. Descriptive statistics were used to analyze the data. Independent sample t-tests, Fisher's exact test, and Chi square analyses compared dietary supplement users to non-users. More than half of the participants used at least one dietary supplement and almost all patients using dietary supplements reported they had informed their healthcare provider. Dietary supplements were taken to improve intake of dietary components and better individual health state. Participants thought that dietary supplements in general were safer and more effective than current evidence suggests. Users and non-users expressed similar perceptions. Patients who used dietary supplements were older (64±10 years vs 53±12 years) and had a lower body mass index (30.0±6.5 kg/m(2) vs 34.1±8.3 kg/m(2)) compared with patients who did not. Dietary supplement use was common in these participants with HF; global perceptions about safety and efficacy of dietary supplements were similar between users and non-users of dietary supplements. Systematic evaluation of dietary supplement use, with discussion about safety and efficacy may be constructive for patients with HF. © The European Society of Cardiology 2013.

Development of Safe and Effective Botanical Dietary Supplements

PubMed Central

2015-01-01

Regulated differently than drugs or foods, the market for botanical dietary supplements continues to grow worldwide. The recently implemented U.S. FDA regulation that all botanical dietary supplements must be produced using good manufacturing practice is an important step toward enhancing the safety of these products, but additional safeguards could be implemented, and unlike drugs, there are currently no efficacy requirements. To ensure a safe and effective product, botanical dietary supplements should be developed in a manner analogous to pharmaceuticals that involves identification of mechanisms of action and active constituents, chemical standardization based on the active compounds, biological standardization based on pharmacological activity, preclinical evaluation of toxicity and potential for drug–botanical interactions, metabolism of active compounds, and finally, clinical studies of safety and efficacy. Completing these steps will enable the translation of botanicals from the field to safe human use as dietary supplements. PMID:26125082

20 CFR 416.938 - What we mean by approved institutions or facilities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What we mean by approved institutions or facilities. 416.938 Section 416.938 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Drug Addiction and Alcoholism § 416.938 What we mean by approved...

Can claims, misleading information, and manufacturing issues regarding dietary supplements be improved in the United States?

PubMed

Gibson, James E; Taylor, David A

2005-09-01

The safety and effectiveness of over-the-counter (OTC) drugs are assessed through the Food and Drug Administration's (FDA's) OTC drug review. Prescription drugs are approved through the rigorous new drug application (NDA) process. In contrast, dietary supplements are regulated as foods, and the FDA must determine that a dietary supplement ingredient poses a "significant or unreasonable risk of illness or injury" instead of requiring the manufacturer to provide safety data. According to the FDA, there are more than 29,000 different dietary supplements available to consumers today. This momentum has its roots in consumer interest in health and self-care and suggests that Americans are searching for alternatives to conventional foods for physical and mental well being. The Committee on the Framework for Evaluating the Safety of Dietary Supplements was formed under the auspices of the Food and Nutrition Board that produced a report entitled Dietary Supplements: A Framework for Evaluating Safety. Categories of specific information identified for use are 1) human data, 2) animal studies, 3) in vitro experiments, and 4) information on related substances. Several factors were identified to guide the FDA in applying the framework. Two of these factors are expressed as follows: 1) "the appropriate scientific standard to be used to overturn this basic assumption of safety is to demonstrate significant or unreasonable risk, not prove that an ingredient is unsafe"; and 2) "approaches taken by diverse organizations and governmental bodies, both within and outside the United States, which evaluate the safety and at times efficacy of dietary supplement ingredients, vary in their relevance to the protection of the American public from risks associated with consumption of dietary supplement ingredients".

Regulatory and ethical issues with dietary supplements.

PubMed

Harris, I M

2000-11-01

Dietary supplements are commonly used, and many are effective or hold promise for treating various conditions. However, they do not require Food and Drug Administration (FDA) approval. Impurities and adulterants have been found in the products, mostly due to the lack of requirements for good manufacturing practices. In addition, as no standardization is required, the active ingredient may be absent or highly variable among manufacturers. The FDA published its 10-year plan for dietary supplements that addresses safety, labeling, boundaries, enforcement, research, and outreach. This endeavor, if put into place, will be instrumental in providing consumers with more confidence in the safety, composition, and labeling of dietary supplements.

What Is the Evidence for Use of a Supplemental Feeding Tube Device as an Alternative Supplemental Feeding Method for Breastfed Infants?

PubMed

Penny, Frances; Judge, Michelle; Brownell, Elizabeth; McGrath, Jacqueline M

2018-02-01

According to the Healthy People 2020 goals, the sustainability of breastfeeding duration rates within the United States has not been achieved. To increase these rates, it is important that women with breastfeeding difficulties receive the support needed to continue breastfeeding. When supplementation occurs, it is essential that the breastfeeding relationship be preserved. Various methods of supplementation are often recommended including use of the supplemental feeding tube device (SFTD). The question guiding this brief is "What evidence exists to support the use of an SFTD as a method of supplementation for breastfed infants?" The PubMed and CINAHL databases were queried for original research published in English from 1990 through July 2016. Search terms included "supplemental feeding tube," "breastfeeding," "term infants," "premature infants," "Supplemental Nursing System," "Lact-aid," and "supply line." Very limited research exists on the use of SFTDs as a method of supplementation for breastfed infants; however, existing research suggests that an SFTD may be useful as a supplementation method for breastfed infants. High-quality research is needed to evaluate the efficacy of using an SFTD for supporting exclusive and all breastfeeding rates. Nurses and providers need to be educated and trained in the use of SFTDs as well as all supplemental feeding methods. Information on efficacy and SFTD use should also be included in policies related to breastfeeding and human milk use. Further research should determine best methods of supplementation for breastfed infants and should examine differences in breastfeeding rates when using the SFTD for supplementation.

Twenty Years of the Dietary Supplement Health and Education Act--How Should Dietary Supplements Be Regulated?

PubMed

Wallace, Taylor C

2015-08-01

The Dietary Supplement Health and Education Act (DSHEA) of 1994 defines the FDA's statutory authority to regulate dietary supplement products in the United States. The dietary supplement industry has rapidly expanded since 1994, presenting an obvious need for "DSHEA 2.0." Current regulations surrounding dietary supplements have been increasingly and reasonably scrutinized, given their widespread use by over one-half of the US population as well as highly publicized safety concerns over the past 20 y. As the market continues to expand and evolve, so too must the laws that protect consumers from potential harm and misleading communication. This article is meant to begin a scientific dialogue on how regulations may be improved to provide both ease of access and safer products to the consumer by focusing on 4 topics: premarket approval, label claims, current Good Manufacturing Practices, and adverse event reporting. © 2015 American Society for Nutrition.

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

76 FR 28971 - Atlanta Gas Light Company; Notice of Petition for Rate Approval

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

...] Atlanta Gas Light Company; Notice of Petition for Rate Approval Take notice that on May 9, 2011, as supplemented on May 11, 2011, Atlanta Gas Light Company (Atlanta Gas Light) filed a petition pursuant to.... Atlanta Gas Light states the rate election consists of the maximum cost-based rates approved by the...

29 CFR 1952.224 - Final approval determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Federal program; to submit plan supplements in accordance with 29 CFR part 1953; to allocate sufficient..., DEPARTMENT OF LABOR (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Tennessee § 1952.224... benchmarks as revised in 1984 in response to a Court Order in AFL-CIO v. Marshall (CA 74-406), and was...

29 CFR 1952.224 - Final approval determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Federal program; to submit plan supplements in accordance with 29 CFR part 1953; to allocate sufficient..., DEPARTMENT OF LABOR (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Tennessee § 1952.224... benchmarks as revised in 1984 in response to a Court Order in AFL-CIO v. Marshall (CA 74-406), and was...

Confidence in the efficacy and safety of dietary supplements among United States active duty army personnel.

PubMed

Carvey, Christina E; Farina, Emily K; Lieberman, Harris R

2012-10-10

United States Army Soldiers regularly use dietary supplements (DS) to promote general health, enhance muscle strength, and increase energy, but limited scientific evidence supports the use of many DS for these benefits. This study investigated factors associated with Soldiers' confidence in the efficacy and safety of DS, and assessed Soldiers' knowledge of federal DS regulatory requirements. Between 2006 and 2007, 990 Soldiers were surveyed at 11 Army bases world-wide to assess their confidence in the effectiveness and safety of DS, knowledge of federal DS regulations, demographic characteristics, lifestyle-behaviors and DS use. A majority of Soldiers were at least somewhat confident that DS work as advertised (67%) and thought they are safe to consume (71%). Confidence in both attributes was higher among regular DS users than non-users. Among users, confidence in both attributes was positively associated with rank, self-rated diet quality and fitness level, education, and having never experienced an apparent DS-related adverse event. Fewer than half of Soldiers knew the government does not require manufacturers to demonstrate efficacy, and almost a third incorrectly believed there are effective pre-market federal safety requirements for DS. Despite limited scientific evidence supporting the purported benefits and safety of many popular DS, most Soldiers were confident that DS are effective and safe. The positive associations between confidence and DS use should be considered when developing DS-related interventions or policies. Additionally, education to clarify Soldiers' misperceptions about federal DS safety and efficacy regulations is warranted.

5 CFR 6401.103 - Prior approval for outside employment.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... 6401.103 Section 6401.103 Administrative Personnel ENVIRONMENTAL PROTECTION AGENCY SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE ENVIRONMENTAL PROTECTION AGENCY § 6401.103 Prior approval... an organization for which a different Deputy Ethics Official has responsibility, the employee must...

Bovine somatotropin supplementation of dairy cows. Is the milk safe?

PubMed

Daughaday, W H; Barbano, D M

Complex, biologically active proteins (eg, enzymes and hormones) can be manufactured safely and cost-effectively through applications of biotechnology. Some of these proteins (eg, human insulin, human somatotropin, rennet for cheese manufacture) are currently approved for medical or food processing applications. Bovine somatotropin (bST) for lactating dairy cattle is another product that can be produced via biotechnology and may allow dairy farmers to produce milk at a lower cost. In 1985, based on an evaluation of toxicological data, the Food and Drug Administration concluded that milk and meat from bST-supplemented cows was safe and wholesome. The Food and Drug Administration has authorized the use of milk and meat from bST-supplemented cows in the commercial food supply. Its evaluation of the impact of bST supplementation on the long-term health of dairy cattle is near completion, and bST may be approved for commercial use in early 1991.

National Athletic Trainers' Association Position Statement: Evaluation of Dietary Supplements for Performance Nutrition

PubMed Central

Buell, Jackie L; Franks, Rob; Ransone, Jack; Powers, Michael E; Laquale, Kathleen M; Carlson-Phillips, Amanda

2013-01-01

Objectives To help athletic trainers promote a “food-first” philosophy to support health and performance, understand federal and sport governing body rules and regulations regarding dietary supplements and banned substances, and become familiar with reliable resources for evaluating the safety, purity, and efficacy of dietary supplements. Background The dietary supplement industry is poorly regulated and takes in billions of dollars per year. Uneducated athletes need to gain a better understanding of the safety, eligibility, and efficacy concerns associated with choosing to take dietary supplements. The athletic trainer is a valuable athletic team member who can help in the educational process. In many cases, athletic trainers are asked to help evaluate the legality, safety, and efficacy of dietary supplements. For this position statement, our mission is to provide the athletic trainer with the necessary resources for these tasks. Recommendations Proper nutrition and changes in the athlete's habitual diet should be considered first when improved performance is the goal. Athletes need to understand the level of regulation (or lack thereof) governing the dietary supplement industry at the international, federal, state, and individual sport-participation levels. Athletes should not assume a product is safe simply because it is marketed over the counter. All products athletes are considering using should be evaluated for purity (ie, truth in labeling), safety, and efficacy. PMID:23672334

78 FR 18973 - Bridgeline Holdings, L.P.; Notice of Petition for Rate Approval

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... Holdings, L.P.; Notice of Petition for Rate Approval Take notice that on February 28, 2013, as supplemented on March 12, 2013, Bridgeline Holdings, L.P. filed for approval of rates for transportation services... TTY, call (202) 502-8659. Comment Date: 5:00 p.m. Eastern Time on Monday, April 1, 2013. Dated: March...

Evaluation of the efficacy of separate oral supplements compared with the combined oral supplements of vitamins C and E on sperm motility in Wistar rats.

PubMed

Ogli, S A; Enyikwola, O; Odeh, S O

2009-12-01

Infertility is a major reproductive and social problem with a worldwide prevalence of 10-15%. While 11.8-39.0% of infertility cases are attributable to the female, 15.8-42.4% is attributed to the male and 8.0-11.1% to unknown factors. The study investigated the efficacy of the single versus combined regimes of antioxidant vitamins C and E oral supplements on sperm motility in the reproductively matured Wistar rats. Twenty [20] male Wistar rats aged 12 weeks and weighing between 182 g and 252 g were randomly grouped into 4 experimental blocks [A-D] of 5 rats each. Block A rats were served combined daily dose of 90 mg vitamin C and 15 mg vitamin E, block B rats had no treatment and served as control, block C rats were served daily dose of 15 mg vitamin E only while block D rats were served daily dose of 90 mg vitamin C only; all treatments were administered for 28 days. On the 29th day, the rats were humanely sacrificed and semen analyzed for sperm motility. The study showed that treatment with vitamins C and E as single regime significantly improved [P<0.01] the forward, progressive [category a] mean percentage sperm motility by 70 and 75 folds respectively while significantly decreasing [P<0.01] the non-progressive [category c] mean percent sperm motility by 8 and 5 folds respectively compared to the control mean percent sperm motility. We therefore conclude that sperm motility in the Wistar rats is significantly improved with the separate oral supplements of vitamins C and E as compared with the combined supplements.

29 CFR 1952.354 - Final approval determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... effective as operations under the Federal program; to submit plan supplements in accordance with 29 CFR part..., DEPARTMENT OF LABOR (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Arizona § 1952.354... benchmarks as revised in 1984 in response to a Court Order in AFL-CIO v. Marshall, (CA 74-406), and was...

29 CFR 1952.354 - Final approval determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... effective as operations under the Federal program; to submit plan supplements in accordance with 29 CFR part..., DEPARTMENT OF LABOR (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS Arizona § 1952.354... benchmarks as revised in 1984 in response to a Court Order in AFL-CIO v. Marshall, (CA 74-406), and was...

Review of nutritional supplements for the treatment of bipolar depression.

PubMed

Rakofsky, Jeffrey J; Dunlop, Boadie W

2014-05-01

Many patients view psychotropics with skepticism and fear and view nutritional supplements as more consistent with their values and beliefs. The purpose of this review was to critically evaluate the evidence base for nutritional supplements in the treatment of bipolar depression (BD). A literature search for all randomized, controlled clinical trials using nutritional supplements in the treatment of BD was conducted via PubMed and Ovid MEDLINE computerized database. The studies were organized into essential nutrients/minerals, nonessential nutrients, and combinations of nutritional products. Among essential nutrients/minerals, omega-3-fatty acids (O3FAs) have the strongest evidence of efficacy for bipolar depression, although some studies failed to find positive effects from O3FAs. Weak evidence supports efficacy of vitamin C whereas no data support the usefulness of folic acid and choline. Among nonessential nutrients, cytidine is the least supported treatment. Studies of N-acetylcysteine have not resolved its efficacy in treating acute depressive episodes relative to placebo. However, one study demonstrates its potential to improve depressive symptoms over time and the other, though nonsignificant, suggests it has a prophylactic effect. Studies of inositol have been mostly negative, except for 1 study. Those that were negative were underpowered but demonstrated numerically positive effects for inositol. There is no evidence that citicholine is efficacious for uncomplicated BD depression, though it may have value for comorbid substance abuse among BD patients. Finally, combination O3FA-cytidine lacks evidence of efficacy. The findings of this review do not support the routine use of nutritional supplements in the treatment or prophylaxis of BD depression. Studies with more rigorous designs are required before definitive conclusions can be made. Despite the inadequacy of the existing data, clinicians should remain open to the value of nutritional supplements: after

5 CFR 5001.104 - Prior approval for outside employment.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... 5001.104 Section 5001.104 Administrative Personnel INTERSTATE COMMERCE COMMISSION SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE INTERSTATE COMMERCE COMMISSION § 5001.104 Prior approval..., an employee of the Interstate Commerce Commission, other than a Commissioner, must obtain the written...

Oral potassium supplementation in surgical patients.

PubMed

Hainsworth, Alison J; Gatenby, Piers A

2008-08-01

Hospital inpatients are frequently hypokalaemic. Low plasma potassium levels may cause life threatening complications, such as cardiac arrhythmias. Potassium supplementation may be administered parenterally or enterally. Oral potassium supplements have been associated with oesophageal ulceration, strictures and gastritis. An alternative to potassium salt tablets or solution is dietary modification with potassium rich food stuffs, which has been proven to be a safe and effective method for potassium supplementation. The potassium content of one medium banana is equivalent to a 12 mmol potassium salt tablet. Potassium supplementation by dietary modification has been shown to be equally efficacious to oral potassium salt supplementation and is preferred by the majority of patients. Subsequently, it is our practice to replace potassium using dietary modification, particularly in surgical patients having undergone oesophagogastrectomy or in those with peptic ulcer disease.

Estimated cost efficacy of systemic treatments that are approved by the US Food and Drug Administration for the treatment of moderate to severe psoriasis.

PubMed

D'Souza, Logan S; Payette, Michael J

2015-04-01

Newer psoriasis treatments tout higher efficacy but are generally more expensive. We sought to estimate the cost efficacy of systemic psoriasis treatments that have been approved by the US Food and Drug Administration (FDA). A literature review of systemic psoriasis treatments that have been approved by the FDA was performed for the primary end point of a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75). Medication cost was referenced by wholesale acquisition cost (WAC), laboratory fees were obtained from the American Medical Association, and office visit fees are standard at our university. Total expenses were standardized by calculating cost per month of treatment considering the number needed to treat (NNT) to achieve PASI 75. Methotrexate ($794.05-1502.51) and cyclosporine ($1410.14-1843.55) had the lowest monthly costs per NNT to achieve PASI 75. The most costly therapies were infliximab ($8704.68-15,235.52) and ustekinumab 90 mg ($12,505.26-14,256.75). Monthly costs per NNT to achieve PASI 75 for other therapies were as follows: narrowband ultraviolet B light phototherapy ($2924.73), adalimumab ($3974.61-7678.78), acitretin ($4137.71-14,148.53), ustekinumab 45 mg ($7177.89-7263.99), psoralen plus ultraviolet A light phototherapy ($7499.46-8834.98), and etanercept ($8284.71-10,674.89). Drug rebates and incentives, potential adverse effects, comorbidity risk reduction, ambassador programs, and combination therapies were excluded. Our study provides meaningful cost efficacy data that may influence psoriasis treatment selection. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Herbal Supplements for Prostate Enlargement: Current State of the Evidence.

PubMed

Nabavizadeh, Reza; Zangi, Mahdi; Kim, Michelle M; Yavari Bejestani, Maryam; Tabatabaei, Shahin

2018-02-01

To provide a comprehensive review of the current state of herbal supplement market for lower urinary tract symptoms (LUTS) and correlate the ingredients of each product with available scientific evidence. Twenty-seven products from Amazon.com that were advertised as herbal supplements for LUTS and had listed their active ingredients were selected. Active ingredients were reviewed on Google Scholar. Product price, warranty, and consumer review information were also collected. A total of 58 unique active ingredients were identified. The mean number of ingredients was 8.26 (standard deviation 5.25). Whereas 17 (63%) products had an ingredient with a systematic review to support their use, 20 (74%) had an ingredient with conflicting evidence based on systematic reviews. Out of the supplements that contained ingredients supported by literature, all (100%) products simultaneously had other ingredients with no, conflicting, or refuting evidence. There was no (0%) product that contained only scientifically proven ingredients. There is no scientific study to evaluate these supplements as a whole. Despite the widespread use of herbal supplements for LUTS, there is scant scientific evidence to support their safety and efficacy. Lack of adequate regulation and government support for research and development are some of the factors that disincentivize researchers to study safety and efficacy of these products. We encourage physicians to warn their patients on the lack of adequate evidence to support the safety and efficacy of many of these supplements. Copyright © 2017 Elsevier Inc. All rights reserved.

7 CFR 1955.22 - State supplements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... regulation to provide guidance to FmHA or its successor agency under Public Law 103-354 officials. State supplements will be submitted to the National Office for post approval in accordance with FmHA or its successor agency under Public Law 103-354 Instruction 2006-B (available in any FmHA or its successor agency...

FY2007 Supplemental Appropriations for Defense, Foreign Affairs, and Other Purposes

DTIC Science & Technology

2007-07-02

the House approved two bills, H.R. 2206 and H.R. 2207 , that, together provided $123.3 billion in supplemental funding. H.R. 2206 divided funding for...and a second bill, H.R. 2207 ; and (3) the final, enacted FY2007 supplemental appropriations bill, H.R. 2206. Following Table 2, this report provides...Vetoed May 10, House-Passed, H.R. 2206/H.R. 2207 Final, Enacted Supplemental, H.R. 2206/P.L. 110-28 Iraq Troop Redeployment Sec. 1904: Requires a report

77 FR 3611 - Approval and Promulgation of Implementation Plans; North Carolina: Approval of Section 110(a)(1...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

... 27.73 4.94 35.88 56.14 Guilford 1.06 2.01 42.78 11.83 57.68 115.36 Total 6.07 3.83 90.62 21.11 121.63... of the 1997 8-hour ozone NAAQS through the year 2018 in the Triad Area. EPA is approving these SIP... 2018 for this attainment area. The May 18, 2011, supplemental information contained Appendix C SESARM...

Efficacy and safety of Chlorella supplementation in adults with chronic hepatitis C virus infection

PubMed Central

Azocar, Jose; Diaz, Arley

2013-01-01

AIM: To evaluate the safety and efficacy of Chlorella in 18 patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS: Eighteen adults with chronic infection by HCV genotype 1 received daily oral supplementation of Chlorella for 12 wk. Changes in the RNA levels of HCV, as well as those of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were evaluated following this treatment period. Paired t tests were conducted to compare the means of the different variables at the beginning and end of the study. Side effects and quality of life aspects were also compared between weeks 0 and 12 of the study period. RESULTS: A majority 84.61% of the patients had a significant decrease in their ALT levels from week 0 to week 12. Evaluation of side effects showed that Chlorella was well tolerated. Quality of life assessment showed that 76.9 of the participants reported an improvement in their energy levels and 46.1% reported an improvement in their perception of general health. Although 69.23% also showed a decrease in their AST levels, this was not statistically significant. Most patients that exhibited an improvement in their ALT and AST levels also showed a tendency toward a decreased HCV viral load. The HCV RNA levels showed a decrease in 69.23% of the patients, which along with changes in AST/ALT ratios from week 0 to week 12, these results were not statistically significant. CONCLUSION: Chlorella supplementation was well tolerated in patients with chronic HCV and associated with a significant decrease in ALT liver enzyme levels. PMID:23467073

Confidence in the efficacy and safety of dietary supplements among United States active duty army personnel

PubMed Central

2012-01-01

Background United States Army Soldiers regularly use dietary supplements (DS) to promote general health, enhance muscle strength, and increase energy, but limited scientific evidence supports the use of many DS for these benefits. This study investigated factors associated with Soldiers’ confidence in the efficacy and safety of DS, and assessed Soldiers’ knowledge of federal DS regulatory requirements. Methods Between 2006 and 2007, 990 Soldiers were surveyed at 11 Army bases world-wide to assess their confidence in the effectiveness and safety of DS, knowledge of federal DS regulations, demographic characteristics, lifestyle-behaviors and DS use. Results A majority of Soldiers were at least somewhat confident that DS work as advertised (67%) and thought they are safe to consume (71%). Confidence in both attributes was higher among regular DS users than non-users. Among users, confidence in both attributes was positively associated with rank, self-rated diet quality and fitness level, education, and having never experienced an apparent DS-related adverse event. Fewer than half of Soldiers knew the government does not require manufacturers to demonstrate efficacy, and almost a third incorrectly believed there are effective pre-market federal safety requirements for DS. Conclusions Despite limited scientific evidence supporting the purported benefits and safety of many popular DS, most Soldiers were confident that DS are effective and safe. The positive associations between confidence and DS use should be considered when developing DS-related interventions or policies. Additionally, education to clarify Soldiers’ misperceptions about federal DS safety and efficacy regulations is warranted. PMID:23051046

76 FR 30738 - Agency Information Collection Activities: Form G-845 and Form G-845 Supplement, Revision of a...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... Collection Activities: Form G-845 and Form G- 845 Supplement, Revision of a Currently Approved Information Collection; Comment Request ACTION: 30-Day Notice of Information Collection under Review: Form G- 845 and Form G-845 Supplement, Document Verification Request and Document Verification Request Supplement; OMB...

5 CFR 7701.102 - Prior approval for outside employment.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Prior approval for outside employment. 7701.102 Section 7701.102 Administrative Personnel INSTITUTE OF MUSEUM AND LIBRARY SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE INSTITUTE OF MUSEUM AND LIBRARY SERVICES § 7701...

5 CFR 7701.102 - Prior approval for outside employment.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Prior approval for outside employment. 7701.102 Section 7701.102 Administrative Personnel INSTITUTE OF MUSEUM AND LIBRARY SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE INSTITUTE OF MUSEUM AND LIBRARY SERVICES § 7701...

5 CFR 7701.102 - Prior approval for outside employment.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Prior approval for outside employment. 7701.102 Section 7701.102 Administrative Personnel INSTITUTE OF MUSEUM AND LIBRARY SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE INSTITUTE OF MUSEUM AND LIBRARY SERVICES § 7701...

Dietary supplements in the Department of Defense: possible solutions to optimizing force readiness.

PubMed

Gonsalves, Stephen; Stavinoha, Trisha; Hite, Linda; Costa, Janelle; Dilly, George; Deuster, Patricia A

2012-12-01

Dietary supplement use is common among military service members; approximately 17 to 20% report using high-risk weight-loss, performance-enhancing, and bodybuilding supplements. To date, no overarching policy or program has been approved or implemented to inform service members or educate health care providers on the potential adverse consequences of using multiple combinations of supplements or the pros and cons of supplements per se. A review of regulations, concerns, and possible solutions is provided. Importantly, the role of third-party certification and education is emphasized.

Miracle drug: Brazil approves never-tested cancer medicine.

PubMed

Kuchenbecker, Ricardo S; Mota, Daniel M

2017-07-01

Background Brazil recently approved synthetic phosphoetanolamine, a popularly dubbed 'cancer pill', a substance that has been shown to kill cancer cells in lab animal models but was not yet formally accessed in humans, and thus despite the existence of any evidence of its efficacy and safety. Methods The authors describe the recent decision of Brazil to aprove phosphoetanolamine in the context of growing 'judicialization' to promote access to medicines and thus reinforcing a growing sense of legal uncertainty. Results The approval of phosphoetanolamine despite the existence of any evidence of its efficacy and safety represents to the authors one of the saddest and surrealistic episodes in Brazil's recent public health history. Brazil's current economic crisis is fueling the 'judicialization' to promote access to medicines and thus reinforcing a growing sense of legal uncertainty in the context of rising economic constrains and a progressive failing state. The authors state that the Phosphoetanolamine's approval bill violates current legal prohibition of commercialisation of drugs without the Brazilian national drug regulatory agency's approval and thus may represent a potential menace to Brazil's pharmacogovernance and the country's governance to health technology assessment at the Brazilian national health systems. Conclusion Phosphoetanolamine's approval illustrates that the combination of flawed decision making, economic crisis and political interference may threaten weak governance mechanisms for drug regulation and health technology assessment and thus representing an extra burden in the sustainability of universal access-based national health systems.

Working with the U.S. Food and Drug Administration to obtain approval of products under the Animal Rule.

PubMed

Park, Glen D; Mitchel, Jules T

2016-06-01

While the development of medical products and approval by the U.S. Food and Drug Administration (FDA) is well known, the development of countermeasures against exposure to toxic levels of radiation, chemicals, and infectious agents requires special consideration, and there has been, to date, little experience in working with the FDA to obtain approval of these products. The FDA has published a regulation entitled "Approval of Biological Products when Human Efficacy Studies are not Ethical or Feasible." This regulation, known simply as the "Animal Rule," was designed to permit approval or licensing of drugs and biologics when efficacy studies in humans are not ethical or feasible. To date, 12 products have been approved under the Animal Rule. It is highly recommended that sponsors of products that are to be developed under the Animal Rule meet with the FDA and other government entities early in the development process to ensure that the efficacy and safety studies that are planned will meet the FDA's requirements for approval of the product. © 2016 New York Academy of Sciences.

5 CFR 550.1105 - Review and approval of agency regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... 550.1105 Section 550.1105 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE... agencies must submit regulations to the Office of Personnel Management (OPM) for review in accordance with....1104, the agency may issue any supplemental regulations or instructions, consistent with its approved...

Efficacy of micronutrient supplementation on skin aging and seasonal variation: a randomized, placebo-controlled, double-blind study.

PubMed

Fanian, Ferial; Mac-Mary, Sophie; Jeudy, Adeline; Lihoreau, Thomas; Messikh, Rafat; Ortonne, Jean-Paul; Sainthillier, Jean-Marie; Elkhyat, Ahmed; Guichard, Alexandre; Kenari, Kamran Hejazi; Humbert, Philippe

2013-01-01

Several studies have confirmed dramatic changes in skin surface parameters during the winter months. Although there are many studies supporting the positive effects of topical treatment, there are no published studies demonstrating the effects of oral supplementation in the prevention of negative skin changes during winter. The purpose of this study was to evaluate the efficacy of an oral micronutrient supplement in preventing the negative effects of winter weather on skin quality using noninvasive biometrologic instruments. This study included 80 healthy female volunteers aged 35-55 years with phototype II-IV skin. Randomization was balanced. Two tablets of a micronutrient supplement (Perfectil® Platinum) or placebo were administered once daily for 4 months. The volunteers were examined at baseline, after 4 months, and 6 weeks after termination of treatment (month 5.5). The evaluation included skin microrelief by Visioscan® as the main outcome, and the secondary outcomes were results on standard macrophotography, skin tension by Reviscometer®, skin high-frequency ultrasound, and self-assessment. For all pseudoroughness and microrelief indicators, there was a significant increase from baseline to month 4 in the placebo group (P<0.05) but no change in the active group. Descriptive statistics for the mean minimum, mean maximum, and minimum to maximum ratio on the nonexposed study zone showed a significant and dramatic difference between baseline and month 4 and between baseline and month 5.5 (P<0.05) in the active group, indicating decreasing anisotropy of the skin. High-frequency ultrasound on the exposed study zone revealed that skin thickness was significantly decreased in the placebo group during winter but was stable in the treated group (P<0.01). The photography scaling and self-assessment questionnaire revealed no significant changes in either group. These results indicate that the skin is prone to seasonal changes during winter, particularly in exposed

14 CFR 121.162 - ETOPS Type Design Approval Basis.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false ETOPS Type Design Approval Basis. 121.162 Section 121.162 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL...

5 CFR 8701.102 - Prior approval for outside employment.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... 8701.102 Section 8701.102 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE OFFICE OF MANAGEMENT AND BUDGET § 8701.102 Prior approval... employee of the Office of Management and Budget, other than a special Government employee, must obtain the...

21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.610 Approval... establish that the drug product is reasonably likely to produce clinical benefit in humans. In assessing the...

21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.610 Approval... establish that the drug product is reasonably likely to produce clinical benefit in humans. In assessing the...

21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.610 Approval... establish that the drug product is reasonably likely to produce clinical benefit in humans. In assessing the...

Efficacy of articaine versus lidocaine as a supplemental buccal infiltration in mandibular molars with irreversible pulpitis: a prospective, randomized, double-blind study.

PubMed

Rogers, Brandon S; Botero, Tatiana M; McDonald, Neville J; Gardner, Richard J; Peters, Mathilde C

2014-06-01

Profound pulpal anesthesia in mandibular molars with irreversible pulpitis (IP) is often difficult to obtain and often requires supplemental injections after an ineffective inferior alveolar nerve block (IANB). The purpose of this prospective, randomized, double-blind study was to compare the efficacy of 4% articaine with 2% lidocaine for supplemental buccal infiltrations (BIs) after an ineffective IANB in mandibular molars with IP. In addition, the use of articaine for IANB and intraosseous injections was investigated. One hundred emergency patients diagnosed with IP of a mandibular molar were selected and received an IANB with 4% articaine. All injections were 1.7 mL with 1:100,000 epinephrine. All patients reported profound lip numbness after IANB. Patients with ineffective IANB (positive pulpal response to cold or pain on access) randomly received 4% articaine or 2% lidocaine as a supplemental BI. Endodontic access was initiated 5 minutes after deposition of the infiltration solution. Success was defined as no pain or no more than mild pain during endodontic access and instrumentation as measured on a visual analogue scale. Seventy-four patients failed to achieve pulpal anesthesia after IANB with 4% articaine, resulting in IANB success rate of 26%. Success rates for supplemental BIs were 62% for articaine and 37% for lidocaine (P < .05). This effect was most pronounced in second molars (P < .05). Supplemental BI with articaine was significantly more effective than lidocaine. The IANB success rate of 4% articaine confirmed published data. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

75 FR 78779 - Order Approving Public Company Accounting Oversight Board Supplemental Budget Request To...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-16

...; Securities Exchange Act of 1934 Release No. 63526/December 10, 2010] Order Approving Public Company... Company Accounting Oversight Board (the ``PCAOB'') to oversee the audits of companies and related matters..., subject to approval by the Commission, auditing and related attestation, quality control, ethics, and...

An examination of structure-function claims in dietary supplement advertising in the U.S.: 2003-2009.

PubMed

Avery, Rosemary J; Eisenberg, Matthew D; Cantor, Jonathan H

2017-04-01

Dietary supplement advertising cannot claim a causal link between the product and the treatment, prevention, or cure of a disease unless manufacturers seek approval from the FDA for a health claim. Manufacturers can make structure-function (S-F) claims without FDA approval linking a supplement to a body function or system using words such as "may help" or "promotes." These S-F claims are examined in this study in order to determine whether they mimic health claims for which the FDA requires stricter scientific evidence. Data include S-F claims in supplement advertisements (N=6179) appearing in US nationally circulated magazines (N=137) from 2003 to 2009. All advertisements were comprehensively coded for S-F claims, seals of approval, and other claims of guarantee. S-F claims associate supplements with a wide variety of health conditions, many of which are serious diseases and/or ailments. A significant number of the specific verbs used in these S-F claims are indicative of disease treatment/cure effects, thereby possibly mimicking health claims to the average consumer. The strength of the clinical associations made are largely unsubstantiated in the medical literature. Claims that a product is "scientifically proven" or "guaranteed" were largely unsubstantiated by clinical literature. Ads carrying externally validating seals of approval were highly prevalent. S-F claims that strongly mimic FDA-prohibited health claims are likely to create confusion in interpretation and possible public health concerns are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

5 CFR 4501.103 - Prior approval for certain outside activities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... activities. 4501.103 Section 4501.103 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE OFFICE OF PERSONNEL MANAGEMENT § 4501.103 Prior approval... specialized skills or the same educational background as performance of the employee's official duties; (2...

Use of biomarkers for assessing radiation injury and efficacy of countermeasures

PubMed Central

Singh, Vijay K; Newman, Victoria L; Romaine, Patricia LP; Hauer-Jensen, Martin; Pollard, Harvey B

2016-01-01

Several candidate drugs for acute radiation syndrome (ARS) have been identified that have low toxicity and significant radioprotective and radiomitigative efficacy. Inasmuch as exposing healthy human volunteers to injurious levels of radiation is unethical, development and approval of new radiation countermeasures for ARS are therefore presently based on animal studies and Phase I safety study in healthy volunteers. The Animal Efficacy Rule, which underlies the Food and Drug Administration approval pathway, requires a sound understanding of the mechanisms of injury, drug efficacy, and efficacy biomarkers. In this context, it is important to identify biomarkers for radiation injury and drug efficacy that can extrapolate animal efficacy results, and can be used to convert drug doses deduced from animal studies to those that can be efficacious when used in humans. Here, we summarize the progress of studies to identify candidate biomarkers for the extent of radiation injury and for evaluation of countermeasure efficacy. PMID:26568096

5 CFR 6201.103 - Prior approval for outside employment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Prior approval for outside employment. 6201.103 Section 6201.103 Administrative Personnel EXPORT-IMPORT BANK OF THE UNITED STATES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE EXPORT-IMPORT BANK OF THE UNITED STATES § 6201.103 Prior...

Dietary supplement research portfolio at the NIH, 2009-2011.

PubMed

Garcia-Cazarin, Mary L; Wambogo, Edwina A; Regan, Karen S; Davis, Cindy D

2014-04-01

The U.S. dietary supplement market increased by 7.5% in 2012 compared with 2011, reaching $32.5 billion in sales. Therefore, federally supported research on dietary supplements is important to determine their health effects, safety, and efficacy. A portfolio analysis was performed across the NIH and the Office of Dietary Supplements (ODS) for fiscal years (FYs) 2009-2011 by using the databases Human Nutrition Research Information Management (HNRIM) and Computer Access to Research on Dietary Supplements (CARDS). The results indicated that total NIH dietary supplement-related funding for FYs 2009-2011 was $855 million ($295 million in 2009, $311 million in 2010, and $249 million in 2011). The institutes and centers with the highest investment in dietary supplement research were as follows: the National Heart, Lung, and Blood Institute ($135 million); the National Cancer Institute ($188 million); the National Center for Complementary and Alternative Medicine ($99 million); the National Institute of Diabetes and Digestive and Kidney Diseases ($68 million); the National Institute of Environmental Health Sciences ($58 million); and the ODS ($32 million). The dietary supplement ingredients receiving the most funding were botanicals (22%), vitamins (20%), lipids (14%), and minerals and trace elements (10%). The top 3 outcome research areas were cancer (61% of total dietary supplement investment), cardiovascular disease (47%), and women's reproductive health (38%). In FYs 2009, 2010, and 2011, the ODS provided 3.5%, 3.6%, and 4.1%, respectively, of the NIH investment in dietary supplement research. ODS funding focused on cellular, enzymatic, or molecular mechanisms (64% of total ODS funding). This portfolio analysis demonstrates that the NIH has committed substantial funding to dietary supplement research in an effort to expand the scientific knowledge base on the efficacy and safety of dietary supplements.

Dietary Supplements: Regulatory Challenges and Research Resources.

PubMed

Dwyer, Johanna T; Coates, Paul M; Smith, Michael J

2018-01-04

Many of the scientific and regulatory challenges that exist in research on the safety, quality and efficacy of dietary supplements are common to all countries as the marketplace for them becomes increasingly global. This article summarizes some of the challenges in supplement science and provides a case study of research at the Office of Dietary Supplements at the National Institutes of Health, USA, along with some resources it has developed that are available to all scientists. It includes examples of some of the regulatory challenges faced and some resources for those who wish to learn more about them.

Dietary Supplements: Regulatory Challenges and Research Resources

PubMed Central

Dwyer, Johanna T.; Coates, Paul M.; Smith, Michael J.

2018-01-01

Many of the scientific and regulatory challenges that exist in research on the safety, quality and efficacy of dietary supplements are common to all countries as the marketplace for them becomes increasingly global. This article summarizes some of the challenges in supplement science and provides a case study of research at the Office of Dietary Supplements at the National Institutes of Health, USA, along with some resources it has developed that are available to all scientists. It includes examples of some of the regulatory challenges faced and some resources for those who wish to learn more about them. PMID:29300341

77 FR 74820 - Approval and Promulgation of Implementation Plans; Tennessee: Knox County Supplemental Motor...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-18

... model and vehicle miles traveled (VMT) projection model. EPA is proposing approval of this draft SIP... Regional Office's normal hours of operation. The Regional Office's official hours of business are Monday... at that time, EPA approved mobile emissions and NONROAD models. New emissions data for both the new...

The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome.

PubMed

El-Hattab, Ayman W; Emrick, Lisa T; Williamson, Kaitlin C; Craigen, William J; Scaglia, Fernando

2013-12-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials.

The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome☆

PubMed Central

El-Hattab, Ayman W.; Emrick, Lisa T.; Williamson, Kaitlin C.; Craigen, William J.; Scaglia, Fernando

2013-01-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials. PMID:25411654

Safety and efficacy of tocotrienol supplementation for bone health in postmenopausal women: protocol for a dose-response double-blinded placebo-controlled randomised trial.

PubMed

Shen, Chwan-Li; Mo, Huanbiao; Yang, Shengping; Wang, Shu; Felton, Carol K; Tomison, Michael D; Soelaiman, Ima Nirwana

2016-12-23

Osteoporosis is a major health concern in postmenopausal women, and oxidative stress contributes to the development of bone loss. Cellular studies and ovariectomised rat model mimicking bone loss in postmenopausal women show the bone-protective effect of tocotrienols (TTs) with antioxidant capability. We aim to access the safety and efficacy of TT consumption for bone health in postmenopausal women. In this 12-week randomised double-blinded placebo-controlled trial for the effects of dietary TT supplementation in postmenopausal women, postmenopausal women aged 45 years and older with at least 1 year after menopause and bone mineral density T-score at the spine and/or hip 2.5 or more below the reference values will be randomly assigned to 3 daily supplements: (1) placebo group receiving 860 mg olive oil, (2) low TT group receiving 430 mg of 70% pure TTs (containing 300 mg TT) and (3) high TT group receiving 860 mg of 70% pure TTs (600 mg TT). The primary outcome measure will be urinary N-terminal telopeptide. The secondary outcome measures will be serum bone-specific alkaline phosphatase, receptor activator of nuclear factor-κB ligand, osteoprotegerin, urinary 8-hydroxy-2'-deoxyguanosine and quality of life. At 0, 6 and 12 weeks, the following will be assessed: (1) primary and secondary outcome measures; (2) serum TT and tocopherol concentrations; (3) physical activity and food frequency questionnaires. Liver function will be monitored every 6 weeks for safety. 'Intent-to-treat' principle will be employed for data analysis. A model of repeated measurements with random effect error terms will be applied. Analysis of covariance, χ 2 analysis and regression will be used for comparisons. This study was approved by the Bioethics Committee of the Texas Tech University Health Sciences Center. The findings of this trial will be submitted to a peer-reviewed journal in the areas of bone or nutrition and international conferences. NCT02058420; results

Marketing Approval of Ethical Kampo Medicines.

PubMed

Hakamatsuka, Takashi

2017-01-01

Kampo medicine is an original traditional medicine in Japan. Currently, 148 ethical Kampo formulations (Kampo prescription drugs) are registered in the National Health Insurance Price List. Kampo medicines can be prescribed under the national insurance system, which shows that they are part of conventional medicine in Japan. Japan has a unified drug approval system that does not distinguish between Western and Kampo medicines, and both are subject to the same regulations. The application for the market approval of ethical Kampo medicines is based on the general notification for drugs, i.e., "Handling of Ethical Combination Drugs" in "Precautions Necessary When Applying for Drug Marketing Approval" (Yakushokushinsa Notification No. 1121-12 of November 21, 2014). Furthermore, applications for the market approval of ethical Kampo medicines should follow the Kampo-specific notification of "Handling of Ethical Kampo Medicines" (Yakushin Notification No. 804 of June 25, 1980). Data from comparative studies with standard decoctions must be submitted with approval applications according to Yakushin 2 Notification No. 120 of May 31, 1985. The safety, efficacy, and quality of Kampo medicines are comprehensively assured by the Japanese Pharmacopoeia, Good Manufacturing Practice, Good Agricultural and Collection Practices, marketing approval certificate, approval standard, and pharmacovigilance. I believe that the basic framework for the market approval of ethical Kampo medicines has been established as described above. The key factors for the practical application of superior manufacturing technology and research achievements and the promotion of drug development are the specific guidelines for the approval of drugs of herbal origin.

Effect of low-dose, short-duration creatine supplementation on anaerobic exercise performance.

PubMed

Hoffman, Jay R; Stout, Jeffrey R; Falvo, Michael J; Kang, Jie; Ratamess, Nicholas A

2005-05-01

To examine the efficacy of a low-dose, short-duration creatine monohydrate supplement, 40 physically active men were randomly assigned to either a placebo or creatine supplementation group (6 g of creatine monohydrate per day). Testing occurred before and at the end of 6 days of supplementation. During each testing session, subjects performed three 15-second Wingate anaerobic power tests. No significant (p > 0.05) group or time differences were observed in body mass, peak power, mean power, or total work. In addition, no significant (p > 0.05) differences were observed in peak power, mean power, or total work. However, the change in the rate of fatigue of total work was significantly (p < 0.05) lower in the creatine supplementation group than in the placebo group, indicating a reduced fatigue rate in subjects supplementing with creatine compared with the placebo. Although the results of this study demonstrated reduced fatigue rates in patients during high-intensity sprint intervals, further research is necessary in examining the efficacy of low-dose, short-term creatine supplementation.

46 CFR 8.430 - U.S. Supplement to class rules.

Code of Federal Regulations, 2011 CFR

2011-10-01

... authorization to participate in the ACP, a recognized classification society must prepare, and receive Commandant (CG-521) approval of, a U.S. Supplement to the recognized classification society's class rules... of that classification society or applicable international regulations. ...

46 CFR 8.430 - U.S. Supplement to class rules.

Code of Federal Regulations, 2010 CFR

2010-10-01

... authorization to participate in the ACP, a recognized classification society must prepare, and receive Commandant (CG-521) approval of, a U.S. Supplement to the recognized classification society's class rules... of that classification society or applicable international regulations. ...

Herbal supplements: Research findings and safety.

PubMed

Pruitt, Rosanne; Lemanski, Ashley; Carroll, Adam

2018-05-17

Herbal supplements are used extensively worldwide without much awareness regarding their safety and efficacy. Extensive research to determine the safety, utility, and level of research support for commonly used herbs has culminated in an easily accessible summary chart for NP providers.

76 FR 9805 - Agency Information Collection Activities: Form G-845 and Supplement; Revision of a Currently...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... Collection Activities: Form G-845 and Supplement; Revision of a Currently Approved Information Collection; Comment Request ACTION: 60-Day Notice of Information Collection Under Review: Form G- 845 and Supplement... other forms of information technology, e.g., permitting electronic submission of responses. Overview of...

Efficacy of dietary supplementation with botanicals on carbohydrate metabolism in humans.

PubMed

Cefalu, William T; Ye, Jianping; Wang, Zhong Q

2008-06-01

Botanical products are widely used in nutritional supplementation for promotion of health or prevention of diseases. With the high prevalence of obesity and type 2 diabetes, abnormalities in carbohydrate metabolism are common in the general population and obtaining glycemic control is important in reducing the complications of diabetes. If shown to be effective, botanical products have a unique position in potentially aiding the general public in regard to obesity and diabetes. They can be obtained "over-the-counter" and may have less side effects compared to many synthetic drugs. Although most of the popular botanicals have a long history in folk medicine, there is paucity of data regarding their efficacy and safety, particularly as it relates to human studies. In this review, we discuss the data that was available in the literature for nine botanicals that are frequently promoted to help manage blood glucose. They are Bitter Melon (Momordica charantia), Fenugreek (trigonella foenum graecum), Gymnema Sylvestre, Ivy Gourd (Coccinia indica), Nopal or Prickly Pear Cactus (Opuntia streptacantha), Ginseng, Aloe Vera, Russian Tarragon (Artemisia dracunculus), and Garlic (Allium sativum). The discussion is emphasized on the clinical aspect of these botanicals. Due to the lack of sufficient evidence from clinical studies for any of the botanicals reviewed, it is premature to actively recommend use of any particular herb to treat either glucose or other risk factors. Thus, well defined randomized clinical trials are warranted in this area.

20 CFR 416.1525 - Request for approval of a fee.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Request for approval of a fee. 416.1525 Section 416.1525 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE... the representative performed; (ii) The complexity of the case; (iii) The level of skill and competence...

20 CFR 416.1525 - Request for approval of a fee.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Request for approval of a fee. 416.1525 Section 416.1525 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE... the representative performed; (ii) The complexity of the case; (iii) The level of skill and competence...

Efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids in dry eye syndrome: a systematic review of randomized clinical trials.

PubMed

Molina-Leyva, Ignacio; Molina-Leyva, Alejandro; Bueno-Cavanillas, Aurora

2017-12-01

To critically appraise scientific evidence regarding the efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids for the treatment of dry eye syndrome (DES). A systematic review of randomized clinical trials was performed. Two independent reviewers selected and analysed the scientific papers that met inclusion and exclusion criteria. Objective and subjective efficacy outcomes were assessed. The trials involved a total of 2591 patients in fifteen independent studies. All studies were published between 2005 and 2015. The supplements used were mostly omega-3 and omega-6 in different proportions. Subjective improvement was measured using mainly Ocular Surface Disease Index (OSDI) test and Dry Eye Severity Score (DESS) test: significant differences in favour of the experimental group were found in seven of the studies. The objective amelioration was assessed by lacrimal function parameters: Tear break-up time (TBUT) significantly increased in nine studies and Schirmer's test in four studies. We observed a discrete improvement in the parameters of tear function. Scientific evidence is not strong enough to systematically recommend the use of omega-3 and omega-6 fatty acids as a standalone treatment of DES independently from its aetiology. However, they could be considered as an effective alternative to topical treatment in patients with DES secondary to certain pathologies. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting: approval and efficacy

PubMed Central

Navari, Rudolph M

2009-01-01

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient characteristics (female gender, younger age, low alcohol consumption, history of motion sickness) are the major risk factors for CINV. This review provides a detailed description of palonosetron, a second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The chemistry and pharmacology of palonosetron are described, as well as the initial and recent clinical trials. Palonosetron has a longer half-life and a higher binding affinity than the first-generation 5-HT3 receptor antagonists. Palonosetron has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared to the first-generation 5-HT3 receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy. There were no clinically relevant adverse reactions reported in the palonosetron clinical trials which were different from the common reactions reported for the 5-HT3 receptor antagonist class. Due to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation. PMID:21188135

Efficacy of micronutrient supplementation on skin aging and seasonal variation: a randomized, placebo-controlled, double-blind study

PubMed Central

Fanian, Ferial; Mac-Mary, Sophie; Jeudy, Adeline; Lihoreau, Thomas; Messikh, Rafat; Ortonne, Jean-Paul; Sainthillier, Jean-Marie; Elkhyat, Ahmed; Guichard, Alexandre; Kenari, Kamran Hejazi; Humbert, Philippe

2013-01-01

Background Several studies have confirmed dramatic changes in skin surface parameters during the winter months. Although there are many studies supporting the positive effects of topical treatment, there are no published studies demonstrating the effects of oral supplementation in the prevention of negative skin changes during winter. The purpose of this study was to evaluate the efficacy of an oral micronutrient supplement in preventing the negative effects of winter weather on skin quality using noninvasive biometrologic instruments. Methods This study included 80 healthy female volunteers aged 35–55 years with phototype II–IV skin. Randomization was balanced. Two tablets of a micronutrient supplement (Perfectil® Platinum) or placebo were administered once daily for 4 months. The volunteers were examined at baseline, after 4 months, and 6 weeks after termination of treatment (month 5.5). The evaluation included skin microrelief by Visioscan® as the main outcome, and the secondary outcomes were results on standard macrophotography, skin tension by Reviscometer®, skin high-frequency ultrasound, and self-assessment. Results For all pseudoroughness and microrelief indicators, there was a significant increase from baseline to month 4 in the placebo group (P<0.05) but no change in the active group. Descriptive statistics for the mean minimum, mean maximum, and minimum to maximum ratio on the nonexposed study zone showed a significant and dramatic difference between baseline and month 4 and between baseline and month 5.5 (P<0.05) in the active group, indicating decreasing anisotropy of the skin. High-frequency ultrasound on the exposed study zone revealed that skin thickness was significantly decreased in the placebo group during winter but was stable in the treated group (P<0.01). The photography scaling and self-assessment questionnaire revealed no significant changes in either group. Conclusion These results indicate that the skin is prone to seasonal changes

78 FR 39704 - Agency Information Collection Activities: Revision of Approved Information Collection; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

... use of automated data processing (ADP) and information retrieval systems to administer SNAP. Section... DEPARTMENT OF AGRICULTURE Food and Nutrition Service Agency Information Collection Activities: Revision of Approved Information Collection; Comment Request--Supplemental Nutrition Assistance Program...

Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease.

PubMed

Dougherty, Kelly A; Bertolaso, Chiara; Schall, Joan I; Smith-Whitley, Kim; Stallings, Virginia A

2015-07-01

Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vit D supplemental dose to normalize vit D status is unknown. Five to 20-year-old African American children with (n=21) and without (n=23) SCD-SS were randomized to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for changes in vit D and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vit D status (mean±SD, 19.2±7.2 and 22.3±9.3 ng/mL, respectively). After 12 weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D≥32 ng/mL in >80% of subjects (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high-sensitivity C-reactive protein, and reduction in the percentage of subjects with a high platelet count.

21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS LICENSING Approval of Biological Products When Human Efficacy Studies Are Not Ethical or Feasible § 601.91 Approval based on evidence of effectiveness from... reasonably likely to produce clinical benefit in humans. In assessing the sufficiency of animal data, the...

21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS LICENSING Approval of Biological Products When Human Efficacy Studies Are Not Ethical or Feasible § 601.91 Approval based on evidence of effectiveness from... reasonably likely to produce clinical benefit in humans. In assessing the sufficiency of animal data, the...

21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS LICENSING Approval of Biological Products When Human Efficacy Studies Are Not Ethical or Feasible § 601.91 Approval based on evidence of effectiveness from... reasonably likely to produce clinical benefit in humans. In assessing the sufficiency of animal data, the...

Dietary Supplement Research Portfolio at the NIH, 2009–201112

PubMed Central

Garcia-Cazarin, Mary L.; Wambogo, Edwina A.; Regan, Karen S.; Davis, Cindy D.

2014-01-01

The U.S. dietary supplement market increased by 7.5% in 2012 compared with 2011, reaching $32.5 billion in sales. Therefore, federally supported research on dietary supplements is important to determine their health effects, safety, and efficacy. A portfolio analysis was performed across the NIH and the Office of Dietary Supplements (ODS) for fiscal years (FYs) 2009–2011 by using the databases Human Nutrition Research Information Management (HNRIM) and Computer Access to Research on Dietary Supplements (CARDS). The results indicated that total NIH dietary supplement–related funding for FYs 2009–2011 was $855 million ($295 million in 2009, $311 million in 2010, and $249 million in 2011). The institutes and centers with the highest investment in dietary supplement research were as follows: the National Heart, Lung, and Blood Institute ($135 million); the National Cancer Institute ($188 million); the National Center for Complementary and Alternative Medicine ($99 million); the National Institute of Diabetes and Digestive and Kidney Diseases ($68 million); the National Institute of Environmental Health Sciences ($58 million); and the ODS ($32 million). The dietary supplement ingredients receiving the most funding were botanicals (22%), vitamins (20%), lipids (14%), and minerals and trace elements (10%). The top 3 outcome research areas were cancer (61% of total dietary supplement investment), cardiovascular disease (47%), and women’s reproductive health (38%). In FYs 2009, 2010, and 2011, the ODS provided 3.5%, 3.6%, and 4.1%, respectively, of the NIH investment in dietary supplement research. ODS funding focused on cellular, enzymatic, or molecular mechanisms (64% of total ODS funding). This portfolio analysis demonstrates that the NIH has committed substantial funding to dietary supplement research in an effort to expand the scientific knowledge base on the efficacy and safety of dietary supplements. PMID:24523489

Challenges of conducting clinical trials of natural products to combat cancer.

PubMed

Paller, Channing J; Denmeade, Samuel R; Carducci, Michael A

2016-06-01

Numerous drugs that the US Food and Drug Administration (FDA) has approved for use in cancer therapy are derived from plants, including taxanes such as paclitaxel and vinca alkaloids such as vinblastine. Dietary supplements are another category of natural products that are widely used by patients with cancer, but without the FDA-reviewed evidence of safety and efficacy--be it related to survival, palliation, symptom mitigation, and/or immune system enhancement-that is required for therapy approval. Nearly half of patients in the United States with cancer report that they started taking new dietary supplements after being given a diagnosis of cancer. Oncologists are challenged in providing advice to patients about which supplements are safe and effective to use to treat cancer or the side effects of cancer therapy, and which supplements are antagonistic to standard treatment with chemotherapy, radiation, and/or immunotherapy. Despite the large number of trials that have been launched, the FDA has not approved any dietary supplement or food to prevent cancer, halt its growth, or prevent its recurrence. In this article, we review the primary challenges faced by researchers attempting to conduct rigorous trials of natural products, including shortages of funding due to lack of patentability, manufacturing difficulties, contamination, and lack of product consistency. We also highlight the methods used by dietary supplement marketers to persuade patients that a supplement is effective (or at least safe) even without FDA approval, as well as the efforts of the US government to protect the health and safety of its citizens by ensuring that the information used to market natural products is accurate. We close with a summary of the most widely used databases of information about the safety, efficacy, and interactions of dietary supplements.

The efficacy of protein supplementation during recovery from muscle-damaging concurrent exercise.

PubMed

Eddens, Lee; Browne, Sarah; Stevenson, Emma J; Sanderson, Brad; van Someren, Ken; Howatson, Glyn

2017-07-01

This study investigated the effect of protein supplementation on recovery following muscle-damaging exercise, which was induced with a concurrent exercise design. Twenty-four well-trained male cyclists were randomised to 3 independent groups receiving 20 g protein hydrolysate, iso-caloric carbohydrate, or low-calorific placebo supplementation, per serve. Supplement serves were provided twice daily, from the onset of the muscle-damaging exercise, for a total of 4 days and in addition to a controlled diet (6 g·kg -1 ·day -1 carbohydrate, 1.2 g·kg -1 ·day -1 protein, remainder from fat). Following the concurrent exercise session at time-point 0 h, comprising a simulated high-intensity road cycling trial and 100 drop-jumps, recovery of outcome measures was assessed at 24, 48, and 72 h. The concurrent exercise protocol was deemed to have caused exercise-induced muscle damage (EIMD), owing to time effects (p < 0.001), confirming decrements in maximal voluntary contraction (peaking at 15% ± 10%) and countermovement jump performance (peaking at 8% ± 7%), along with increased muscle soreness, creatine kinase, and C-reactive protein concentrations. No group or interaction effects (p > 0.05) were observed for any of the outcome measures. The present results indicate that protein supplementation does not attenuate any of the indirect indices of EIMD imposed by concurrent exercise, when employing great rigour around the provision of a quality habitual diet and the provision of appropriate supplemental controls.

Safety, Efficacy, and Legal Issues Related to Dietary Supplements

ERIC Educational Resources Information Center

Powers, Michael

2004-01-01

This article focuses on the effects of dietary supplements on collegiate and adult populations. Anabolic steroids, amphetamines, and other drugs have been used for decades to improve athletic performance. However, the legal issues and dangers associated with these drugs have resulted in reluctance by many athletes to use them. Because dietary…

Supplementing glycosylation: A review of applying nucleotide-sugar precursors to growth medium to affect therapeutic recombinant protein glycoform distributions.

PubMed

Blondeel, Eric J M; Aucoin, Marc G

2018-06-15

Glycosylation is a critical quality attribute (CQA) of many therapeutic proteins, particularly monoclonal antibodies (mAbs), and is a major consideration in the approval of biosimilar biologics due to its effects to therapeutic efficacy. Glycosylation generates a distribution of glycoforms, resulting in glycoproteins with inherent molecule-to-molecule heterogeneity, capable of activating (or failing to activate) different effector functions of the immune system. Glycoforms can be affected by the supplementation of nucleotide-sugar precursors, and related components, to culture growth medium, affecting the metabolism of glycosylation. These supplementations has been demonstrated to increase nucleotide-sugar intracellular pools, and impact glycoform distributions, but with varied results. These variations can be attributed to five key factors: Differences between cell platforms (enzyme/transporter expression levels); differences between recombinant proteins produced (glycan-site accessibility); the fermentation and sampling timeline (glucose availability and exoglycosidase accumulation); glutamine levels (affecting ammonia levels, which impact Golgi pH, as well as UDP-GlcNAc pools); and finally, a lack of standardized metrics for observing shifts in glycoform distributions (glycosylation indices) across different experiments. The purpose of this review is to provide detail and clarity on the state of the art of supplementation strategies for nucleotide-sugar precursors for affecting glycosylation in cell culture processes, and to apply glycosylation indices for standardized comparisons across the field. Copyright © 2018. Published by Elsevier Inc.

Systematic review of herbs and dietary supplements for glycemic control in diabetes.

PubMed

Yeh, Gloria Y; Eisenberg, David M; Kaptchuk, Ted J; Phillips, Russell S

2003-04-01

To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes. We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale. A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported. There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.

Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovita): a randomised, double-blind, placebo-controlled trial.

PubMed

Mazumder, Sarmila; Taneja, Sunita; Bhatia, Kiran; Yoshida, Sachiyo; Kaur, Jasmine; Dube, Brinda; Toteja, G S; Bahl, Rajiv; Fontaine, Olivier; Martines, Jose; Bhandari, Nita

2015-04-04

Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality. The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established. We aimed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age. We undertook an individually randomised, double-blind, placebo-controlled trial in Haryana, India. We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana, India, aged 15-49 years, and screened every identified livebirth. Eligible participants were neonates whose parents consented to participate, were likely to stay in the study area until at least 6 months of age, and were able to feed orally at the time of enrolment. Participants were randomly assigned to receive oral capsules containing vitamin A (retinol palmitate 50,000 IU plus vitamin E 9·5-12·6 IU) or placebo (vitamin E 9·5-12·6 IU) within 72 h of birth. Randomisation was in blocks of 20 according to a randomisation list prepared by a statistician not otherwise involved with the trial. Investigators, participants' families, and the data analysis team were masked to treatment allocation. The primary outcome was mortality between supplementation and 6 months of age. Analysis included all participants assigned to study groups. This trial is registered with ClinicalTrials.gov, number NCT01138449, and the Indian Council of Medical Research Clinical Trial Registry, number CTRI/2010/091/000220. Between June 24, 2010, and July 1, 2012 we screened 47,777 neonates and randomly assigned 44,984 to receive vitamin A (22,493) or placebo (22,491). Between supplementation and 6 months of age, 656 infants died in the vitamin A group compared with 726 in the placebo group (29·2 per 1000 vs 32·3 per 1000; difference -3·1 per 1000, 95% CI -6·3 to 0·1; risk

Time to Optimize Supplementation: Modifying Factors Influencing the Individual Responses to Extracellular Buffering Agents

PubMed Central

Heibel, André B.; Perim, Pedro H. L.; Oliveira, Luana F.; McNaughton, Lars R.; Saunders, Bryan

2018-01-01

Blood alkalosis, as indicated by an increased blood bicarbonate concentration and pH, has been shown to be beneficial for exercise performance. Sodium bicarbonate, sodium citrate, and sodium or calcium lactate, can all result in increased circulating bicarbonate and have all independently been shown to improve exercise capacity and performance under various circumstances. Although there is considerable evidence demonstrating the efficacy of these supplements in several sports-specific situations, it is commonly acknowledged that their efficacy is equivocal, due to contrasting evidence. Herein, we discuss the physiological and environmental factors that may modify the effectiveness of these supplements including, (i) absolute changes in circulating bicarbonate; (ii) supplement timing, (iii) the exercise task performed, (iv) monocarboxylate transporter (MCT) activity; (v) training status, and (vi) associated side-effects. The aim of this narrative review is to highlight the factors which may modify the response to these supplements, so that individuals can use this information to attempt to optimize supplementation and allow the greatest possibility of an ergogenic effect.

48 CFR 731.205-71 - Salary supplements for Host Government employees.

Code of Federal Regulations, 2011 CFR

2011-10-01

... FOR INTERNATIONAL DEVELOPMENT GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 731.205-71 Salary supplements for Host Government employees. (a... Contracting Officer shall provide written approval to the contractor in order for such costs to be eligible...

The effectiveness of zinc supplementation in men with isolated hypogonadotropic hypogonadism.

PubMed

Liu, Yan-Ling; Zhang, Man-Na; Tong, Guo-Yu; Sun, Shou-Yue; Zhu, Yan-Hua; Cao, Ying; Zhang, Jie; Huang, Hong; Niu, Ben; Li, Hong; Guo, Qing-Hua; Gao, Yan; Zhu, Da-Long; Li, Xiao-Ying

2017-01-01

A multicenter, open-label, randomized, controlled superiority trial with 18 months of follow-up was conducted to investigate whether oral zinc supplementation could further promote spermatogenesis in males with isolated hypogonadotropic hypogonadism (IHH) receiving sequential purified urinary follicular-stimulating hormone/human chorionic gonadotropin (uFSH/hCG) replacement. Sixty-seven Chinese male IHH patients were recruited from the Departments of Endocrinology in eight tertiary hospitals and randomly allocated into the sequential uFSH/hCG group (Group A, n = 34) or the sequential uFSH plus zinc supplementation group (Group B, n = 33). In Group A, patients received sequential uFSH (75 U, three times a week every other 3 months) and hCG (2000 U, twice a week) treatments. In Group B, patients received oral zinc supplementation (40 mg day-1 ) in addition to the sequential uFSH/hCG treatment given to patients in Group A. The primary outcome was the proportion of patients with a sperm concentration ≥1.0 × 106 ml-1 during the 18 months. The comparison of efficacy between Groups A and B was analyzed. Nineteen of 34 (55.9%) patients receiving sequential uFSH/hCG and 20 of 33 (60.6%) patients receiving sequential uFSH/hCG plus zinc supplementation achieved sperm concentrations ≥1.0 × 106 ml-1 by intention to treat analyses. No differences between Group A and Group B were observed as far as the efficacy of inducing spermatogenesis (P = 0.69). We concluded that the sequential uFSH/hCG plus zinc supplementation regimen had a similar efficacy to the sequential uFSH/hCG treatment alone. The additional improvement of 40 mg day-1 oral zinc supplementation on spermatogenesis and masculinization in male IHH patients is very subtle.

Drug approval processes in Australian Paediatric Hospitals.

PubMed

Sinha, Y K; Craig, J C; Barclay, P; Taitz, J; South, M; Coulthard, K; Pearson, C; Erickson, S; Brien, J E

2010-09-01

To describe and evaluate the decision-making processes for drug approval in Australian paediatric hospitals. Multicentre descriptive study involving face-to-face interviews of drug and therapeutics committee chairs and secretaries, review of committee documents and drug submissions for all Australian paediatric hospital drug and therapeutics committees over a 1-year period. All eight paediatric hospitals in Australia. Eight committee chairs and seven secretaries or delegates. Total drug expenditure, number of formulary submissions, individual-patient use approvals and approval rates for each hospital from 1 July 2006 to 30 June 2007, stratified by therapeutic class. Qualitative description of the approval processes. Total drug expenditure varied from $A1.7 million (US$1.5 million) to $A11.1 million (US$9.8 million) per hospital. The number of formulary submissions also varied, from 7 to 21, but approval rate was high (76%-100%) and not significantly different among hospitals (p=0.17). Several committees approved identical submissions for five drugs. The number of individual-patient use applications varied considerably, ranging from 10 to 456 per hospital. Where estimable, individual-patient use approval was 76%-100% and variable (p=0.03). Quality of evidence relating to safety and efficacy of drugs being considered was regarded as the most important factors influencing decision making, with the cost less important. Most committees had poor infrastructural support for approval processes. No committee formally included a pharmaco-economic evaluation. Most drug submissions in tertiary paediatric hospitals are approved; however, workload, drug expenditure and individual-patient use schemes vary considerably. Duplication of effort occurs, and few committees are resourced sufficiently given their terms of reference.

Efficacy of iron-supplement bars to reduce anemia in urban Indian women: a cluster-randomized controlled trial.

PubMed

Mehta, Rajvi; Platt, Alyssa C; Sun, Xizi; Desai, Mukesh; Clements, Dennis; Turner, Elizabeth L

2017-03-01

Background: India's high prevalence of iron-deficiency anemia has largely been attributed to the local diet consisting of nonheme iron, which has lower absorption than that of heme iron. Objective: We assessed the efficacy of the consumption of iron-supplement bars in raising hemoglobin concentrations and hematocrit percentages in anemic (hemoglobin concentration <12 g/dL) Indian women of reproductive age. Design: The Let's be Well Red study was a 90-d, pair-matched, cluster-randomized controlled trial. A total of 361 nonpregnant women (age 18-35 y) were recruited from 10 sites within Mumbai and Navi Mumbai, India. All participants received anemia education and a complete blood count (CBC). Random assignment of anemic participants to intervention and control arms occurred within 5 matched site-pairs. Intervention participants received 1 iron-supplement bar (containing 14 mg Fe)/d for 90 d, whereas control subjects received nothing. CBC tests were given at days 15, 45, and 90. Primary outcomes were 90-d changes from baseline in hemoglobin concentrations and hematocrit percentages. Linear mixed models and generalized estimating equations were used to model continuous and binary outcomes, respectively. Results: Of 179 anemic participants, 136 (76.0%) completed all follow-up assessments (65 intervention and 71 control participants). Baseline characteristics were comparable by arm. Mean hemoglobin and hematocrit increases after 90 d were greater for intervention than for control participants [1.4 g/dL (95% CI: 1.3, 1.6 g/dL) and 2.7% (95% CI: 2.2%, 3.2%), respectively]. The anemia prevalence at 90 d was lower for intervention (29.2%) than for control participants (98.6%) (OR: 0.007; 95% CI: 0.001, 0.04). Conclusions: The daily consumption of an iron-supplement bar leads to increased hemoglobin concentrations and hematocrit percentages and to a lower anemia prevalence in the target population with no reported side effects. This intervention is an attractive option to

76 FR 35424 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

...; Defense Federal Acquisition Regulation Supplement; Acquisition of Information Technology AGENCY: Defense... techniques or other forms of information technology. The Office of Management and Budget (OMB) has approved... Information Technology, and the associated clauses at DFARS 252.239-7000 and 252.239-7006; OMB Control Number...

25 CFR 170.925 - Is ERFO funding supplemental to IRR Program funding?

Code of Federal Regulations, 2010 CFR

2010-04-01

... RESERVATION ROADS PROGRAM Miscellaneous Provisions Emergency Relief § 170.925 Is ERFO funding supplemental to... construction and maintenance funds for FHWA-approved repairs. If IRR construction or maintenance funds are used... used to reimburse the construction or maintenance funds expended. ...

21 CFR 514.8 - Supplements and other changes to an approved application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... method(s) or an addition, deletion, or substitution of steps in an aseptic processing operation; (D... solely affecting a natural product, a recombinant DNA-derived protein/polypeptide, or a complex or...) or references to previously approved documentation; (H) For a natural product, a recombinant DNA...

21 CFR 514.8 - Supplements and other changes to an approved application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... method(s) or an addition, deletion, or substitution of steps in an aseptic processing operation; (D... solely affecting a natural product, a recombinant DNA-derived protein/polypeptide, or a complex or...) or references to previously approved documentation; (H) For a natural product, a recombinant DNA...

21 CFR 514.8 - Supplements and other changes to an approved application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... method(s) or an addition, deletion, or substitution of steps in an aseptic processing operation; (D... solely affecting a natural product, a recombinant DNA-derived protein/polypeptide, or a complex or...) or references to previously approved documentation; (H) For a natural product, a recombinant DNA...

20 CFR 416.1225 - An approved plan to achieve self-support; general.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false An approved plan to achieve self-support; general. 416.1225 Section 416.1225 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... achieve self-support; general. If you are blind or disabled, we will pay you SSI benefits and will not...

20 CFR 416.1225 - An approved plan to achieve self-support; general.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false An approved plan to achieve self-support; general. 416.1225 Section 416.1225 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... achieve self-support; general. If you are blind or disabled, we will pay you SSI benefits and will not...

Dietary Supplements Commonly Used by Cancer Survivors: Are There Any Benefits?

PubMed

Marian, Mary J

2017-10-01

Following a cancer diagnosis, dietary supplements are reportedly used by 20%-80% of individuals. Supplements are most commonly used by breast cancer survivors, followed by patients with prostate, colorectal, and lung cancers, which is not surprising since these are the most common types of cancer diagnosed in adults. Reasons cited for such use include improving quality of life, reducing symptoms related to treatment and/or the disease process, and recommendation from medical practitioners; family and friends may also be an influence. However, controversy surrounds the use of dietary supplements, particularly during treatment-specifically, whether supplements affect treatment efficacy is unknown. This article discusses the evidence related to common dietary supplements used to prevent cancer or a recurrence.

Calcium supplementation in osteoporosis: useful or harmful?

PubMed

Chiodini, Iacopo; Bolland, Mark J

2018-04-01

Osteoporosis and fragility fractures are important social and economic problems worldwide and are due to both the loss of bone mineral density and sarcopenia. Indeed, fragility fractures are associated with increased disability, morbidity and mortality. It is known that a normal calcium balance together with a normal vitamin D status is important for maintaining well-balanced bone metabolism, and for many years, calcium and vitamin D have been considered crucial in the prevention and treatment of osteoporosis. However, recently, the usefulness of calcium supplementation (alone or with concomitant vitamin D) has been questioned, since some studies reported only weak efficacy of these supplementations in reducing fragility fracture risk. On the other hand, besides the gastrointestinal side effects of calcium supplements and the risk of kidney stones related to use of co-administered calcium and vitamin D supplements, other recent data suggested potential adverse cardiovascular effects from calcium supplementation. This debate article is focused on the evidence regarding both the possible usefulness for bone health and the potential harmful effects of calcium and/or calcium with vitamin D supplementation. © 2018 European Society of Endocrinology.

77 FR 3828 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

... Organizations; The Options Clearing Corporation; Order Granting Approval of Accelerated Delivery of Supplement to the Options Disclosure Document Reflecting Certain Changes to Disclosure Regarding Relative Performance Options January 19, 2012. On August 15, 2011, The Options Clearing Corporation (``OCC'') submitted...

78 FR 79567 - Supplemental Nutrition Assistance Program: Trafficking Controls and Fraud Investigations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

... DEPARTMENT OF AGRICULTURE Food and Nutrition Service 7 CFR Parts 271 and 274 RIN 0584-AE26 Supplemental Nutrition Assistance Program: Trafficking Controls and Fraud Investigations AGENCY: Food and Nutrition Service, USDA. ACTION: Final rule, Interim final rule; notice of approval of Information...

Hepatotoxicity of Herbal Supplements Mediated by Modulation of Cytochrome P450

PubMed Central

Chen, Taosheng

2017-01-01

Herbal supplements are a significant source of drug-drug interactions (DDIs), herb-drug interactions, and hepatotoxicity. Cytochrome P450 (CYP450) enzymes metabolize a large number of FDA-approved pharmaceuticals and herbal supplements. This metabolism of pharmaceuticals and supplements can be augmented by concomitant use of either pharmaceuticals or supplements. The xenobiotic receptors constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) can respond to xenobiotics by increasing the expression of a large number of genes that are involved in the metabolism of xenobiotics, including CYP450s. Conversely, but not exclusively, many xenobiotics can inhibit the activity of CYP450s. Induction of the expression or inhibition of the activity of CYP450s can result in DDIs and toxicity. Currently, the United States (US) Food and Drug Administration does not require the investigation of the interactions of herbal supplements and CYP450s. This review provides a summary of herbal supplements that inhibit CYP450s, induce the expression of CYP450s, and/or whose toxicity is mediated by CYP450s. PMID:29117101

75 FR 30451 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-01

... May 14, 2010. The ODD currently contains general disclosures on the characteristics and risks of...-linked securities. Accordingly, the ODD disclosure only covers the characteristics and risks of options...; Order Granting Approval of Accelerated Delivery of Supplement to the Options Disclosure Document...

Nutritional supplements and the EU: is anyone happy?

PubMed

Eberhardie, Christine

2007-11-01

In 2000 an estimated pound sterling 335 x 106 was spent on food supplements and herbal remedies in the UK. Until recently, The Trades Description Act 1968, the Food Safety Act 1990 and The Food Labelling Regulations 1996 (amended 2004) were the only form of regulation available to protect the public. The medical community has been concerned about the risk to patients of inaccurate dosages and poor-quality products as well as drug-nutrient and nutrient-nutrient interactions. Following growing concern about the type and quality of food supplements and herbal remedies available in the EU, the European Commission has published directives regulating food supplements (2002/46/EC) and herbal remedies (2004/24/EC and 2004/27/EC) available within the EU. The directives came into force in 2005 and limit the number and quality of permitted food supplements through the creation of a 'positive list' of approved supplements. In the present paper the new regulatory frameworks and the implications for the food supplement manufacturers, traditional and complementary therapists, the healthcare professions and patients will be examined. It would appear that there is considerable dissatisfaction with the regulations in their present form. Several questions remain: is regulation the answer; who decides which nutrients go on the positive list; what effect has the regulation had on patient safety and patient choice?

76 FR 64380 - Agency Information Collection Activities: Proposed Collection; Comments Requested; Supplemental...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... Information on Water Quality Consideration ACTION: 30-Day Notice of Information Collection. The Department of... currently approved collection. (2) Title of the Form/Collection: Supplemental Information on Water Quality..., including the validity of the methodology and assumptions used; --Enhance the quality, utility, and clarity...

76 FR 20435 - Notice of Approval of the Supplemental Finding of No Significant Impact and Record of Decision...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-12

.../Record of Decision (FONSI/ROD) for the Supplemental Environmental Assessment (EA) for changes proposed to... previously addressed in the December 2007 environmental assessment FONSI/ROD. The proposed changes include... Supplemental Finding of No Significant Impact and Record of Decision for the Supplemental Environmental...

Cinnamon supplementation in patients with type 2 diabetes mellitus.

PubMed

Pham, Antony Q; Kourlas, Helen; Pham, David Q

2007-04-01

Diabetes mellitus is the sixth leading cause of death in the United States, and most patients with the disease have type 2 diabetes. The effectiveness of cinnamon supplementation in patients with type 2 diabetes has received a great deal of media attention after a study was published in 2003. Although the efficacy of cinnamon in patients with diabetes has not been established, many patients seek other therapies and supplement their prescribed pharmacologic therapy with cinnamon. We conducted a literature search, limited to English-language human studies, using MEDLINE (1966-August 2006), EMBASE (1980-August 2006), International Pharmaceutical Abstracts (1970-August 2006), and Iowa Drug Information Service (1966-August 2006). References from articles and clinical trials were reviewed for additional sources; no abstracts were reviewed. We found two prospective, randomized, double-blind, placebo-controlled, peer-reviewed clinical trials and one prospective, placebo-controlled, peer-reviewed clinical trial that evaluated the efficacy of cinnamon supplementation in patients with type 2 diabetes; a total of 164 patients were involved in these trials. Two of the studies reported modest improvements in lowering blood glucose levels with cinnamon supplementation in small patient samples. One trial showed no significant difference between cinnamon and placebo in lowering blood glucose levels. Overall, cinnamon was well tolerated. These data suggest that cinnamon has a possible modest effect in lowering plasma glucose levels in patients with poorly controlled type 2 diabetes. However, clinicians are strongly urged to refrain from recommending cinnamon supplementation in place of the proven standard of care, which includes lifestyle modifications, oral antidiabetic agents, and insulin therapy.

PRN 96-4: Label Statements Involving Product Efficacy and Potential for Harm to Property

EPA Pesticide Factsheets

This notice explains EPA procedures in approving pesticide labels that include claims relating to the efficacy of agricultural pesticides and provides a warning to growers regarding reliance on label statements regarding pesticide efficacy.

Military-specific application of nutritional supplements: a brief overview.

PubMed

Hoedebecke, Kyle; Brink, Will

2015-01-01

The Soldiers of America's military endure numerous physical and mental challenges that demand strict physical fitness regimens, extreme mental agility, and a perpetual readiness to deploy at a moment's notice. The chronicity of these stressors has the potential to dramatically reduce performance - both directly and indirectly.  Because of this risk, many Soldiers turn to nutritional supplements with hopes of optimizing performance. Increasing amounts of research have demonstrated that various supplements may enhance overall physical prowess, health, and offer quicker recovery in the face of corporal or psychological extremes. Most individuals, including many medical and nutrition professionals, possess only an elementary comprehension of nutritional supplements and their effect on Soldiers in training or combat environments. Nevertheless, a grasp of these details is required for safety and optimal benefits. Various compounds have been evaluated - to include evidence within the military setting - and found to augment endurance, increase cognitive function, decrease knee pain, or offer hearing or lung protection in the face of high-energy impulses. These efficacious outcomes may serve to augment the health and longevity of these Soldiers; however, continued research is needed for efficacy and long-term safety within specific environments.

Provider and patient expectations for dietary supplement discussions.

PubMed

Tarn, Derjung M; Guzmán, Jennifer R; Good, Jeffrey S; Wenger, Neil S; Coulter, Ian D; Paterniti, Debora A

2014-09-01

Dietary supplement use in the United States is common. Patients can procure supplements without a prescription, and often do not disclose supplement use to their healthcare providers. Providers and patients may be uncertain about what would be appropriate or helpful in discussions of supplements during routine office visits. To explore provider and patient expectations for discussions of dietary supplements. Semi-structured interviews were conducted with a purposeful sample of healthcare providers from three specialties and their patients who reported taking supplements. Thirty-five outpatient providers (14 primary care, six integrative medicine, and 15 complementary and alternative medicine (CAM) providers) and 107 of their patients. Qualitative analysis of transcripts using grounded theory and iterative review. Both providers and patients raised twelve common topics about dietary supplements that they felt were important to discuss during office visits, such as: supplements taken; supplement risks (interactions, safety/harm, side effects/adverse events); treatment benefits; efficacy; alternative treatments; and patient expectations/preferences for treatment. Some topics were mentioned more frequently by providers than patients, such as how to take, reason for taking, and evidence for use. Providers raised several topics that were mentioned infrequently by patients. Supplement costs and regulations were not brought up by any patients, even though consideration of these topics could influence patient decisions to take supplements. Complementary healthcare providers brought up topics not mentioned by primary care providers, such as the importance of supplement brands and supplement mega-dosing. Patients and providers have concordant views about the need to discuss patient supplement use and ensure patient safety. Patients may undervalue, be unaware of, or discount information about cost or regulations that could affect their decision-making about supplement use

Do We Need Plant Food Supplements? A Critical Examination of Quality, Safety, Efficacy, and Necessity for a New Regulatory Framework.

PubMed

Abdel-Tawab, Mona

2018-04-01

Given the expanding market of plant food supplements (PFSs) not undergoing any pre-marketing authorization, the overall quality, safety and efficacy of PFSs were subjected to a critical examination. Although many high-quality PFSs exist on the legal market, quality concerns are in general justified. Besides economic adulteration, active ingredients dramatically differing from label claims and among products were reported in several studies. In addition, PFSs sold via the Internet may be intentionally adulterated with undeclared prescription drugs. Compared to PFSs with only one single herb, PFSs containing herbal mixtures were more involved in moderate and severe clinical courses. Although prohibited by regulation, misleading labels on PFSs are common. Above all, only vague evidence for the efficacy of PFSs exists. Notwithstanding the unproven efficacy and insufficient safety assessment, PFSs represent a relevant source for consumers to get access to herbal preparations in the United States and meanwhile also in Europe, as launching of licensed/registered European herbal medicinal products (HMPs) has steadily decreased. However, being non-vitamin, non-mineral products, PFSs are neither food nor drugs. In terms of protecting public health and providing the consumer with high-quality, effective, and safe PFSs, possibilities are shown how to deal with the many challenges of PFSs. Last but not least, suggestions are made for assigning PFSs a separate regulatory category being less regulated compared to HMPs but more strictly regulated compared to food laws including implementation of good manufacturing practices and a scientific pre-marketing review process by an expert commission. Georg Thieme Verlag KG Stuttgart · New York.

21 CFR 314.70 - Supplements and other changes to an approved application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of change, the applicant must notify FDA about the change in a supplement under paragraph (b) or (c... alternative under § 201.26 of this chapter satisfies the applicable requirements in paragraphs (a) through (c...) Notwithstanding the requirements of paragraphs (b) and (c) of this section, an applicant must make a change...

21 CFR 314.70 - Supplements and other changes to an approved application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of change, the applicant must notify FDA about the change in a supplement under paragraph (b) or (c... alternative under § 201.26 of this chapter satisfies the applicable requirements in paragraphs (a) through (c...) Notwithstanding the requirements of paragraphs (b) and (c) of this section, an applicant must make a change...

Chondroprotection using naturally occurring mineral supplementation formula in degenerative osteoarthritis of the knees.

PubMed

Bansal, Himanshu; Bansal, Anupama; Agrawal, Diwaker; Singh, Dhananjay; Deb, Kaushik

2014-01-01

To evaluate the therapeutic and safety efficacy of a naturally occurring mineral supplementation in the treatment of symptomatic knee osteoarthritis (OA). A prospective, single centre, study of 50 patients aged 50 years and above with painful and radiological Osteoarthritis of knees was carried out for one year. Patients received 40 drops of naturally occurring commercially available mineral supplement concentrate mineral drops purportedly derived from the Great Salt Lake in Utah. Efficacy was objectively confirmed by evaluating changes in the thickness of articular cartilage, joint space width, synovial fluid analysis and subjectively by changes in WOMAC scores and 6 Minute pain-free Walking Distance. The composite WOMAC scores were significantly improved by 17.2 points from a mean of 52 at baseline by year end. 18 (41%) patients showed improvement of more than 100 feet for the pain free distance covered during a 6 minute walk at one year follow-up. Ultrasonologicaly, at one year cartilage thickness improved by at least 0.01 mm in 9 (21%) patients. Though radiologicallynone of patient showed increase in joint space it was noticed that only 2(4.6%) patients had decline of joint space width of more than 0.5 mm. Average cell count reduced to 205/microlitre from a value of 520/microlitre at the start of study suggesting that the mineral supplement used had structural efficacy. Clinically relevant, statistically significant symptomatic and statistically insignificant structural improvement occurred over 1 year period in patients receiving the naturally occurring mineral supplement. The protection of the joint cartilages from progressive degeneration during osteoarthritis by these supplements indicates towards a chondrocyte regenerative potential of this supplement. Such regeneration may occur through activation of tissue specific adult chondrocyte precursors or stem cells.

Doctor-patient communication and cancer patients' choice of alternative therapies as supplement or alternative to conventional care.

PubMed

Salamonsen, Anita

2013-03-01

Cancer patients' use of complementary and alternative medicine (CAM) is widespread, despite the fact that clinical studies validating the efficacy of CAM remain sparse in the Nordic countries. The purpose of this study was to explore possible connections between cancer patients' communication experiences with doctors and the decision to use CAM as either supplement or alternative to conventional treatment (CT). The Regional Committee for Medical and Health Research Ethics and the Norwegian Data Inspectorate approved the study. From a group of 52 cancer patients with self-reported positive experiences from use of CAM, 13 were selected for qualitative interviews. Six used CAM as supplement, and seven as alternative to CT, periodically or permanently. Communication experiences with 46 doctors were described. The analysis revealed three connections between doctor-patient communication and patients' treatment decisions: (i) negative communication experiences because of the use of CAM; (ii) negative communication experiences resulted in the decision to use CAM, and in some cases to decline CT; and (iii) positive communication experiences led to the decision to use CAM as supplement, not alternative to CT. The patients, including the decliners of CT, wanted to discuss treatment decisions in well-functioning interpersonal processes with supportive doctors. In doctors' practices and education of doctors, a greater awareness of potential positive and negative outcomes of doctor-patient communication that concern CAM issues could be of importance. More research is needed to safeguard CAM users' treatment decisions and their relationship to conventional health care. © 2012 The Author. Scandinavian Journal of Caring Sciences © 2012 Nordic College of Caring Science.

A drug's life: the pathway to drug approval.

PubMed

Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

2013-10-01

In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

78 FR 33784 - Approval and Promulgation of Implementation Plans; Kentucky: Kentucky Portion of Cincinnati...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-05

... Promulgation of Implementation Plans; Kentucky: Kentucky Portion of Cincinnati-Hamilton, Supplement Motor.... SUMMARY: EPA is proposing to approve a revision to the Kentucky State Implementation Plan (SIP), submitted... maintenance plan for the Kentucky portion of the Cincinnati-Hamilton, OH-KY-IN, maintenance area for the 1997...

Effect of Medicinal Plant By-products Supplementation to Total Mixed Ration on Growth Performance, Carcass Characteristics and Economic Efficacy in the Late Fattening Period of Hanwoo Steers

PubMed Central

Lee, S. J.; Kim, D. H.; Guan, Le Luo; Ahn, S. K.; Cho, K. W.; Lee, Sung S.

2015-01-01

This study was conducted to evaluate the effect of medicinal plant by-products (MPB) supplementation to a total mixed ration (TMR) on growth, carcass characteristics and economic efficacy in the late fattening period of Hanwoo steers. Twenty seven steers (body weight [BW], 573±57 kg) were assigned to 3 treatment groups so that each treatment based on BW contained 9 animals. All groups received ad libitum TMR throughout the feeding trial until slaughter (from 24 to 30 months of age) and treatments were as follows: control, 1,000 g/kg TMR; treatment 1 (T1), 970 g/kg TMR and 30 g/kg MPB; treatment 2 (T2), 950 g/kg TMR and 50 g/kg MPB. Initial and final BW were not different among treatments. Resultant data were analyzed using general linear models of SAS. Average daily gain and feed efficiency were higher (p<0.05) for T1 than control, but there was no difference between control and T2. Plasma albumin showed low-, intermediate- and high-level (p<0.05) for control, T1 and T2, whereas non-esterified fatty acid was high-, intermediate- and high-level (p<0.05) for control, T1 and T2, respectively. Carcass weight, carcass rate, backfat thickness and rib eye muscle area were not affected by MPB supplementation, whereas quality and yield grades were highest (p<0.05) for T1 and T2, respectively. Daily feed costs were decreased by 0.5% and 0.8% and carcass prices were increased by 18.1% and 7.6% for T1 and T2 compared to control, resulting from substituting TMR with 30 and 50 g/kg MPB, respectively. In conclusion, the substituting TMR by 30 g/kg MPB may be a potential feed supplement approach to improve economic efficacy in the late fattening period of Hanwoo steers. PMID:26580440

Mechanistic Insights into the Efficacy of Sodium Bicarbonate Supplementation to Improve Athletic Performance.

PubMed

Siegler, Jason C; Marshall, Paul W M; Bishop, David; Shaw, Greg; Green, Simon

2016-12-01

A large proportion of empirical research and reviews investigating the ergogenic potential of sodium bicarbonate (NaHCO 3 ) supplementation have focused predominately on performance outcomes and only speculate about underlying mechanisms responsible for any benefit. The aim of this review was to critically evaluate the influence of NaHCO 3 supplementation on mechanisms associated with skeletal muscle fatigue as it translates directly to exercise performance. Mechanistic links between skeletal muscle fatigue, proton accumulation (or metabolic acidosis) and NaHCO 3 supplementation have been identified to provide a more targeted, evidence-based approach to direct future research, as well as provide practitioners with a contemporary perspective on the potential applications and limitations of this supplement. The mechanisms identified have been broadly categorised under the sections 'Whole-body Metabolism', 'Muscle Physiology' and 'Motor Pathways', and when possible, the performance outcomes of these studies contextualized within an integrative framework of whole-body exercise where other factors such as task demand (e.g. large vs. small muscle groups), cardio-pulmonary and neural control mechanisms may outweigh any localised influence of NaHCO 3 . Finally, the 'Performance Applications' section provides further interpretation for the practitioner founded on the mechanistic evidence provided in this review and other relevant, applied NaHCO 3 performance-related studies.

Anesthetic efficacy of the supplemental X-tip intraosseous injection in patients with irreversible pulpitis.

PubMed

Nusstein, John; Kennedy, Shawn; Reader, Al; Beck, Mike; Weaver, Joel

2003-11-01

The purpose of this study was to determine the anesthetic efficacy of the supplemental intraosseous injection, using the X-tip system in an apical location, in mandibular posterior teeth diagnosed with irreversible pulpitis when the conventional inferior alveolar nerve block failed. Thirty-three emergency patients, diagnosed with irreversible pulpitis of a mandibular posterior tooth, received an inferior alveolar nerve block and had moderate-to-severe pain on endodontic access. The X-tip system was used to administer 1.8 ml of 2% lidocaine with 1:100,000 epinephrine. The X-tip injection site was 3- to 7-mm apical to the mucogingival junction of the affected tooth. Success of the X-tip intraosseous injection was defined as none or mild pain on endodontic access or initial instrumentation. The results of this study demonstrated that 6 of 33 (18%) X-tip injections resulted in backflow of anesthetic solution into the oral cavity; none were successful in obtaining anesthesia. Twenty-seven of the remaining 33 X-tip injections (82%) were successful. We conclude that when the inferior alveolar nerve block fails to provide profound pulpal anesthesia, the X-tip system, when used in an apical location and when there was no backflow of the anesthetic solution into the oral cavity, was successful in achieving pulpal anesthesia in mandibular posterior teeth of patients presenting with irreversible pulpitis.

Too Little, Too Late: Ineffective Regulation of Dietary Supplements in the United States

PubMed Central

2015-01-01

Millions of people in the United States consume dietary supplements hoping to maintain or improve their health; however, extensive research has failed to demonstrate the efficacy of numerous supplements in disease prevention. In addition, concerns about the safety of routine and high-dose supplementation have been raised. The Food and Drug Administration regulates dietary supplement quality, safety, and labeling, and the Federal Trade Commission monitors advertisements and marketing; still, vast enforcement challenges remain, and optimal governmental oversight has not been achieved. If the composition and quality of ingredients cannot be reliably ensured, the validity of research on dietary supplements is questionable. Moreover, the health of the US public is put at risk. PMID:25602879

Exploring the Inhibitory Mechanism of Approved Selective Norepinephrine Reuptake Inhibitors and Reboxetine Enantiomers by Molecular Dynamics Study

NASA Astrophysics Data System (ADS)

Zheng, Guoxun; Xue, Weiwei; Wang, Panpan; Yang, Fengyuan; Li, Bo; Li, Xiaofeng; Li, Yinghong; Yao, Xiaojun; Zhu, Feng

2016-05-01

Selective norepinephrine reuptake inhibitors (sNRIs) provide an effective class of approved antipsychotics, whose inhibitory mechanism could facilitate the discovery of privileged scaffolds with enhanced drug efficacy. However, the crystal structure of human norepinephrine transporter (hNET) has not been determined yet and the inhibitory mechanism of sNRIs remains elusive. In this work, multiple computational methods were integrated to explore the inhibitory mechanism of approved sNRIs (atomoxetine, maprotiline, reboxetine and viloxazine), and 3 lines of evidences were provided to verify the calculation results. Consequently, a binding mode defined by interactions between three chemical moieties in sNRIs and eleven residues in hNET was identified as shared by approved sNRIs. In the meantime, binding modes of reboxetine’s enantiomers with hNET were compared. 6 key residues favoring the binding of (S, S)-reboxetine over that of (R, R)-reboxetine were discovered. This is the first study reporting that those 11 residues are the common determinants for the binding of approved sNRIs. The identified binding mode shed light on the inhibitory mechanism of approved sNRIs, which could help identify novel scaffolds with improved drug efficacy.

A critical appraisal of probiotics (as drugs or food supplements) in gastrointestinal diseases.

PubMed

Passariello, Annalisa; Agricole, Pascal; Malfertheiner, Peter

2014-06-01

Probiotics may be registered as food supplements or drugs. This article summarizes differences in European regulations of probiotics registered as food supplements and drugs, as well as issues related to the quality of probiotic products. For registration as a drug, the European Medicines Agency demands extensive and detailed quality, efficacy and safety evidence; whereas compulsory analyses requested for food supplements consist only in a nutritional analysis. As a result, the quality of those probiotics registered as drugs, compared to food supplements, is in general controlled with higher standards. Despite these differences and whatever the status of the probiotic product, its efficacy and safety has to be documented in well conducted randomized controlled trials (RCTs). Furthermore, this paper reviews recent evidence on the use of probiotics for gastrointestinal diseases, evaluating all the existing information up to January 2014. In all eligible published studies in which use of probiotics for gastrointestinal diseases were investigated and reported, no language limitations were applied. Special focus is placed on RCTs (or their meta-analyses) showing positive results, so that the findings may be applicable to everyday clinical practice. Currently, the best documented clinical areas appear to be probiotics efficacy for the treatment of acute gastroenteritis in children and for the prevention of antibiotic-associated diarrhea both in children and in adults. In other gastrointestinal conditions, some promising observations are emerging, but no definitive conclusions can be reached at present.

78 FR 53269 - Approval and Promulgation of Implementation Plans; Arkansas; Interstate Transport of Fine...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-29

...] Approval and Promulgation of Implementation Plans; Arkansas; Interstate Transport of Fine Particulate... technical supplement submitted on March 20, 2013, to address interstate transport for the 1997 and 2006 PM 2... SIP'' is amended by adding an entry at the end for ``Interstate transport for the 1997 and 2006 PM 2.5...

β-Alanine supplementation and military performance.

PubMed

Hoffman, Jay R; Stout, Jeffrey R; Harris, Roger C; Moran, Daniel S

2015-12-01

During sustained high-intensity military training or simulated combat exercises, significant decreases in physical performance measures are often seen. The use of dietary supplements is becoming increasingly popular among military personnel, with more than half of the US soldiers deployed or garrisoned reported to using dietary supplements. β-Alanine is a popular supplement used primarily by strength and power athletes to enhance performance, as well as training aimed at improving muscle growth, strength and power. However, there is limited research examining the efficacy of β-alanine in soldiers conducting operationally relevant tasks. The gains brought about by β-alanine use by selected competitive athletes appears to be relevant also for certain physiological demands common to military personnel during part of their training program. Medical and health personnel within the military are expected to extrapolate and implement relevant knowledge and doctrine from research performed on other population groups. The evidence supporting the use of β-alanine in competitive and recreational athletic populations suggests that similar benefits would also be observed among tactical athletes. However, recent studies in military personnel have provided direct evidence supporting the use of β-alanine supplementation for enhancing combat-specific performance. This appears to be most relevant for high-intensity activities lasting 60-300 s. Further, limited evidence has recently been presented suggesting that β-alanine supplementation may enhance cognitive function and promote resiliency during highly stressful situations.

Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity medications.

PubMed

Halpern, Bruno; Halpern, Alfredo

2015-02-01

Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.

Safety and Efficacy of Glucomannan for Weight Loss in Overweight and Moderately Obese Adults

PubMed Central

Keithley, Joyce K.; Swanson, Barbara; Mikolaitis, Susan L.; DeMeo, Mark; Zeller, Janice M.; Fogg, Lou; Adamji, Jehan

2013-01-01

Background. Few safe and effective dietary supplements are available to promote weight loss. We evaluated the safety and efficacy of glucomannan, a water-soluble fiber supplement, for achieving weight loss in overweight and moderately obese individuals consuming self-selected diets. Methods. Participants were randomly assigned to take 1.33 grams of glucomannan or identically looking placebo capsules with 236.6 mL (8 ounces) of water one hour before breakfast, lunch, and dinner for 8 weeks. The primary efficacy outcome was change in body weight after 8 weeks. Other efficacy outcomes were changes in body composition, hunger/fullness, and lipid and glucose concentrations. Safety outcomes included gastrointestinal symptoms/tolerance and serum liver enzymes and creatinine levels. Results. A total of 53 participants (18–65 years of age; BMI 25–35 kg/m2) were enrolled and randomized. The two groups did not differ with respect to baseline characteristics and compliance with the study supplement. At 8 weeks, there was no significant difference between the glucomannan and placebo groups in amount of weight loss (−.40 ± .06 and −.43 ± .07, resp.) or other efficacy outcomes or in any of the safety outcomes. Conclusions. Glucomannan supplements administered over 8 weeks were well tolerated but did not promote weight loss or significantly alter body composition, hunger/fullness, or lipid and glucose parameters. This trial is registered with NCT00613600. PMID:24490058

Implications of Recent Drug Approvals for Older Adults

PubMed Central

Eisenhower, Christine; Koronkowski, Michael; Marcum, Zachary

2016-01-01

More than 100 medications were approved by the US Food and Drug Administration as new drugs or for new indications in 2014 and 2015. Several of the new drugs may benefit older adults, but adverse events and pharmacokinetic changes due to aging must be considered. This article will focus on three recently approved drugs that are marketed for chronic conditions that can affect older adults: suvorexant, for treatment of insomnia; edoxaban, for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and for treatment of venous thromboembolism; and droxidopa, for treatment of symptomatic neurogenic orthostatic hypotension. Information about indications, mechanisms of action, dosing, efficacy, and safety are reviewed. The place of each agent in therapy for older adults is also discussed. PMID:27340374

Dietary supplements for athletes: emerging trends and recurring themes.

PubMed

Maughan, R J; Greenhaff, P L; Hespel, P

2011-01-01

Dietary supplements are widely used at all levels of sport. Changes in patterns of supplement use are taking place against a background of changes in the regulatory framework that governs the manufacture and distribution of supplements in the major markets. Market regulation is complicated by the increasing popularity of Internet sales. The need for quality control of products to ensure they contain the listed ingredients in the stated amount and to ensure the absence of potentially harmful substances is recognized. This latter category includes compounds prohibited under anti-doping regulations. Several certification programmes now provide testing facilities for manufacturers of both raw ingredients and end products to ensure the absence of prohibited substances. Athletes should carry out a cost-benefit analysis for any supplement they propose to use. For most supplements, the evidence is weak, or even completely absent. A few supplements, including caffeine, creatine, and bicarbonate, are supported by a strong research base. Difficulties arise when new evidence appears to support novel supplements: in recent years, β-alanine has become popular, and the use of nitrate and arginine is growing. Athletes seldom wait until there is convincing evidence of efficacy or of safety, but caution is necessary to minimize risk.

Supplemental care from a bioethical perspective.

PubMed

Carvalho, Regina Ribeiro Parizi; Fortes, Paulo Antônio de Carvalho; Garrafa, Volnei

2013-01-01

To describe and analyze, from the perspective of Intervention Bioethics, the legal, institutional and ethical contexts, the conflicts and regulations of supplemental health care in Brazil, since the approval of the regulatory law in 1998 until 2010. Qualitative research, using Intervention Bioethics as the theoretical reference. Bibliographical and documental study of the legislation, regulations and assistential framework, as well as interviews with members of the Supplemental Health Board. There was improvement in the records and rules of action in private health companies, as well as flow of information, contractual and financial guarantees provided to consumers. Conflicts persist regarding access to services and procedures, price increases, policies on autonomy and medical fees. There is a dispute with the public sector regarding the network of health services, with rising costs and no improvement in quality of care. Private participation in health demands comparative assessments and improvement of public-private care regulation, as well as promoting greater balance in the funding and reevaluation of the health care model. It is necessary to review the regulatory framework considering the supplementary, complementary or duplicate characteristic of assistance, the social actors involved, bioethical and political issues regarding associations between Supplemental Health Care and the National Health System (SUS). Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

21 CFR 99.305 - Exemption from the requirement to file a supplemental application.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., BIOLOGICS, AND DEVICES FDA Action on Submissions, Requests, and Applications § 99.305 Exemption from the... exemption from the requirement of a supplemental application, FDA shall approve or deny the application. (1) If FDA does not act on the application for an exemption within the 60-day period, the application for...

21 CFR 99.305 - Exemption from the requirement to file a supplemental application.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., BIOLOGICS, AND DEVICES FDA Action on Submissions, Requests, and Applications § 99.305 Exemption from the... exemption from the requirement of a supplemental application, FDA shall approve or deny the application. (1) If FDA does not act on the application for an exemption within the 60-day period, the application for...

21 CFR 99.305 - Exemption from the requirement to file a supplemental application.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., BIOLOGICS, AND DEVICES FDA Action on Submissions, Requests, and Applications § 99.305 Exemption from the... exemption from the requirement of a supplemental application, FDA shall approve or deny the application. (1) If FDA does not act on the application for an exemption within the 60-day period, the application for...

21 CFR 99.305 - Exemption from the requirement to file a supplemental application.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., BIOLOGICS, AND DEVICES FDA Action on Submissions, Requests, and Applications § 99.305 Exemption from the... exemption from the requirement of a supplemental application, FDA shall approve or deny the application. (1) If FDA does not act on the application for an exemption within the 60-day period, the application for...

Patient-Centered Drug Approval: The Role of Patient Advocacy in the Drug Approval Process.

PubMed

Mattingly, T Joseph; Simoni-Wastila, Linda

2017-10-01

Recent approval of eteplirsen for Duchenne muscular dystrophy (DMD), a rare disease with few treatment alternatives, has reignited the debate over the U.S. drug approval process. The evolution of legal and regulatory restrictions to the marketing and sale of pharmaceuticals has spanned more than a century, and throughout this history, patient advocacy has played a significant role. Scientific evidence from clinical trials serves as the foundation for drug approval, but the patient voice has become increasingly influential. Although the gold standard for establishing safety and efficacy through randomized controlled trials has been in place for more than 50 years, it poses several limitations for rare disorders where patient recruitment for traditional clinical trials is a major barrier. Organized efforts by patient advocacy groups to help patients with rare diseases access investigational therapy have had a legislative and regulatory effect. After approval by the FDA, patient access to therapy may still be limited by cost. A managed care organization (MCO) with the fiduciary responsibility of managing the health of a population must weigh coverage decisions for costly therapies with questionable effectiveness against alternatives within the constraint of a finite budget. Even when the FDA deems a drug safe and effective, an MCO may determine that the drug should only be made available at a tier level where out-of-pocket costs are still too high for many patients. This limitation of availability may be due to cost, other treatment alternatives, or outcomes from existing clinical evidence. However, if the MCO makes a costly new treatment for a rare disease readily available, it may temporarily satisfy a small contingency at the cost of all of its members. This article examines the risks and benefits of patient-centered drug approval and the potential economic effect of patient-centered drug approval on population health. There is no funding to disclose. Mattingly

Impact of Alternative Medical Device Approval Processes on Costs and Health

PubMed Central

George, Benjamin P.; Venkataraman, Vinayak; Dorsey, E. Ray

2014-01-01

Background Medical devices are often introduced prior to randomized‐trial evidence of efficacy and this slows completion of trials. Alternative regulatory approaches include restricting device use outside of trials prior to trial evidence of efficacy (like the drug approval process) or restricting out‐of‐trial use but permitting coverage within trials such as Medicare's Coverage with Study Participation (CSP). Methods We compared the financial impact to manufacturers and insurers of three regulatory alternatives: (1) limited regulation (current approach), (2) CSP, and (3) restrictive regulation (like the current drug approval process). Using data for patent foramen ovale closure devices, we modeled key parameters including recruitment time, probability of device efficacy, market adoption, and device cost/price to calculate profits to manufacturers, costs to insurers, and overall societal impact on health. Results For manufacturers, profits were greatest under CSP—driven by faster market adoption of effective devices—followed by restrictive regulation. Societal health benefit in total quality‐adjusted life years was greatest under CSP. Insurers’ expenditures for ineffective devices were greatest with limited regulation. Findings were robust over a reasonable range of probabilities of trial success. Conclusions Regulation restricting out‐of‐trial device use and extending limited insurance coverage to clinical trial participants may balance manufacturer and societal interests. PMID:25185975

Digital mammography. Why hasn't it been approved for U.S. hospitals?

PubMed

2000-01-01

Mammography is the only major imaging technique still unavailable in the United States in digital form. This is because the Food and Drug Administration (FDA) has been unable to devise an effective method for manufacturers to demonstrate the safety and efficacy of digital mammography systems. As a result, the agency has been unable to approve any of those systems for marketing in the United States. In this Regulatory Update, we describe FDA's recent efforts to help manufacturers obtain approval and the reasons those efforts have so far proved ineffective.

Weight Loss Nutritional Supplements

NASA Astrophysics Data System (ADS)

Eckerson, Joan M.

Obesity has reached what may be considered epidemic proportions in the United States, not only for adults but for children. Because of the medical implications and health care costs associated with obesity, as well as the negative social and psychological impacts, many individuals turn to nonprescription nutritional weight loss supplements hoping for a quick fix, and the weight loss industry has responded by offering a variety of products that generates billions of dollars each year in sales. Most nutritional weight loss supplements are purported to work by increasing energy expenditure, modulating carbohydrate or fat metabolism, increasing satiety, inducing diuresis, or blocking fat absorption. To review the literally hundreds of nutritional weight loss supplements available on the market today is well beyond the scope of this chapter. Therefore, several of the most commonly used supplements were selected for critical review, and practical recommendations are provided based on the findings of well controlled, randomized clinical trials that examined their efficacy. In most cases, the nutritional supplements reviewed either elicited no meaningful effect or resulted in changes in body weight and composition that are similar to what occurs through a restricted diet and exercise program. Although there is some evidence to suggest that herbal forms of ephedrine, such as ma huang, combined with caffeine or caffeine and aspirin (i.e., ECA stack) is effective for inducing moderate weight loss in overweight adults, because of the recent ban on ephedra manufacturers must now use ephedra-free ingredients, such as bitter orange, which do not appear to be as effective. The dietary fiber, glucomannan, also appears to hold some promise as a possible treatment for weight loss, but other related forms of dietary fiber, including guar gum and psyllium, are ineffective.

Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment

PubMed Central

Yasueda, Asuka; Urushima, Hayato; Ito, Toshinori

2015-01-01

Oxidative stress is a key component in carcinogenesis. Although radiation produces reactive oxygen species, some anticancer agents such as alkylating agents, platinum and antitumor antibiotics exert cytotoxicity by generating free radicals. Nonenzymatic exogenous antioxidants such as vitamins, minerals, and polyphenols can quench ROS activity. However, whether antioxidants alter antitumor effects during radiotherapy and some types of chemotherapy remains unclear. In the present study, we reviewed antioxidants as an adjuvant therapy for cancer patients during chemotherapy or radiotherapy. Electronic literature searches were performed to select all randomized controlled clinical trials (RCTs) in which antioxidants were administered to cancer patients along with chemotherapy or radiotherapy. Articles or abstracts written in English were included. In total, 399 reports received primary screening. Duplicated articles and those meeting the exclusion criteria (not RCT, not human, and no oral administration) were excluded. Finally, 49 reports matching the inclusion criteria were included. It was difficult to determine whether antioxidants affect treatment outcomes or whether antioxidants ameliorate adverse effects induced by chemotherapy and radiotherapy. It is desirable to use an evidence-based method to select supplements best suited to cancer patients. Although there are many opinions about risks or benefits of antioxidant supplementation, we could mostly conclude that the harm caused by antioxidant supplementation remains unclear for patients during cancer therapy, except for smokers undergoing radiotherapy. PMID:26503419

Fatty Acid and Phytosterol Content of Commercial Saw Palmetto Supplements

PubMed Central

Penugonda, Kavitha; Lindshield, Brian L.

2013-01-01

Saw palmetto supplements are one of the most commonly consumed supplements by men with prostate cancer and/or benign prostatic hyperplasia (BPH). Some studies have found significant improvements in BPH and lower urinary tract symptoms (LUTS) with saw palmetto supplementation, whereas others found no benefits. The variation in the efficacy in these trials may be a result of differences in the putative active components, fatty acids and phytosterols, of the saw palmetto supplements. To this end, we quantified the major fatty acids (laurate, myristate, palmitate, stearate, oleate, linoleate) and phytosterols (campesterol, stigmasterol, β-sitosterol) in 20 commercially available saw palmetto supplements using GC-FID and GC-MS, respectively. Samples were classified into liquids, powders, dried berries, and tinctures. Liquid saw palmetto supplements contained significantly higher (p < 0.05) concentrations of total fatty acids (908.5 mg/g), individual fatty acids, total phytosterols (2.04 mg/g), and individual phytosterols, than the other supplement categories. Powders contained significantly higher (p < 0.05) concentrations of total fatty acids than tinctures, which contain negligible amounts of fatty acids (46.3 mg/g) and phytosterols (0.10 mg/g). Our findings suggest that liquid saw palmetto supplements may be the best choice for individuals who want to take a saw palmetto supplement with the highest concentrations of both fatty acids and phytosterols. PMID:24067389

Fatty acid and phytosterol content of commercial saw palmetto supplements.

PubMed

Penugonda, Kavitha; Lindshield, Brian L

2013-09-13

Saw palmetto supplements are one of the most commonly consumed supplements by men with prostate cancer and/or benign prostatic hyperplasia (BPH). Some studies have found significant improvements in BPH and lower urinary tract symptoms (LUTS) with saw palmetto supplementation, whereas others found no benefits. The variation in the efficacy in these trials may be a result of differences in the putative active components, fatty acids and phytosterols, of the saw palmetto supplements. To this end, we quantified the major fatty acids (laurate, myristate, palmitate, stearate, oleate, linoleate) and phytosterols (campesterol, stigmasterol, β-sitosterol) in 20 commercially available saw palmetto supplements using GC-FID and GC-MS, respectively. Samples were classified into liquids, powders, dried berries, and tinctures. Liquid saw palmetto supplements contained significantly higher (p < 0.05) concentrations of total fatty acids (908.5 mg/g), individual fatty acids, total phytosterols (2.04 mg/g), and individual phytosterols, than the other supplement categories. Powders contained significantly higher (p < 0.05) concentrations of total fatty acids than tinctures, which contain negligible amounts of fatty acids (46.3 mg/g) and phytosterols (0.10 mg/g). Our findings suggest that liquid saw palmetto supplements may be the best choice for individuals who want to take a saw palmetto supplement with the highest concentrations of both fatty acids and phytosterols.

The use of mechanistic evidence in drug approval.

PubMed

Aronson, Jeffrey K; La Caze, Adam; Kelly, Michael P; Parkkinen, Veli-Pekka; Williamson, Jon

2018-06-11

The role of mechanistic evidence tends to be under-appreciated in current evidence-based medicine (EBM), which focusses on clinical studies, tending to restrict attention to randomized controlled studies (RCTs) when they are available. The EBM+ programme seeks to redress this imbalance, by suggesting methods for evaluating mechanistic studies alongside clinical studies. Drug approval is a problematic case for the view that mechanistic evidence should be taken into account, because RCTs are almost always available. Nevertheless, we argue that mechanistic evidence is central to all the key tasks in the drug approval process: in drug discovery and development; assessing pharmaceutical quality; devising dosage regimens; assessing efficacy, harms, external validity, and cost-effectiveness; evaluating adherence; and extending product licences. We recommend that, when preparing for meetings in which any aspect of drug approval is to be discussed, mechanistic evidence should be systematically analysed and presented to the committee members alongside analyses of clinical studies. © 2018 The Authors Journal of Evaluation in Clinical Practice Published by John Wiley & Sons Ltd.

Dietary supplements and human health: for better or for worse?

PubMed

Jerome-Morais, Anita; Diamond, Alan M; Wright, Margaret E

2011-01-01

Encouraged by the potential health benefits of higher dietary intake of substances with beneficial properties, the use of supplements containing these compounds has increased steadily over recent years. The effects of several of these, many of which are antioxidants, have been supported by data obtained in vitro, in animal models, and often by human studies as well. However, as carefully controlled human supplementation trials have been conducted, questions about the efficacy and safety of these supplements have emerged. In this Educational Paper, three different supplements were selected for consideration of the benefits and risks currently associated with their intake. The selected supplements include β-carotene, selenium, and genistein. The use of each is discussed in the context of preclinical and clinical data that provide evidence for both their use in reducing disease incidence and the possible liabilities that accompany their enhanced consumption. Variables that may influence their impact, such as lifestyle habits, baseline nutritional levels, and genetic makeup are considered and the application of these issues to broader classes of supplements is discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Is supplementation efficacious in maintaining adequate plasma levels of vitamin a and e for thalassemic patients undergoing hematopoietic stem cell transplantation? A cross-sectional study.

PubMed

Hajimahmoodi, Mannan; Hadjibabaie, Molouk; Hamidieh, Amir-Ali; Ahmadvand, Alireza; Kazempanah, Sahebeh; Sadeghi, Naficeh; Mansouri, Ava; Ghavamzadeh, Ardeshir

2014-02-01

Thalassemia along with hematopoietic stem cell transplantation (HSCT) can lead to major oxidative stress. Vitamins A and E are antioxidants which protect membrane from lipid peroxidation. We sought to determine for the first time, whether vitamins A and E supplementation is efficacious in maintaining or increasing plasma level of these vitamins in thalassemic children undergoing HSCT. A cross-sectional study was performed on 50 children with β-thalassemia major hospitalized for HSCT. Patients took a daily multivitamin. Plasma vitamins A and E levels were measured at four different times: on admission, HSCT day (day 0), day 7 and day 14 after HSCT. Findings : Plasma vitamin A and E were abnormal on admission in most patients (62.0% and 60.0% respectively). Ratio of patient with normal to abnormal plasma level of the vitamins improved from baseline to a peak on day 7 then deteriorated afterward until day 14. There was an increasingly positive correlation between daily oral intake and plasma vitamin A at different times, but plasma vitamin E showed inverse correlation at first which tended towards no correlation subsequently. In multivariate analysis, supplementation significantly changed plasma level of vitamin A at different measurement time (P=0.001) within study subjects. But, plasma level of vitamin E showed no significant difference (P=0.2). Our findings suggest that oral supplementation could have beneficial effects due to increasing plasma vitamin A level and preventing plasma vitamin E depletion.

Dosing and efficacy of glutamine supplementation in human exercise and sport training.

PubMed

Gleeson, Michael

2008-10-01

Some athletes can have high intakes of l-glutamine because of their high energy and protein intakes and also because they consume protein supplements, protein hydrolysates, and free amino acids. Prolonged exercise and periods of heavy training are associated with a decrease in the plasma glutamine concentration and this has been suggested to be a potential cause of the exercise-induced immune impairment and increased susceptibility to infection in athletes. However, several recent glutamine feeding intervention studies indicate that although the plasma glutamine concentration can be kept constant during and after prolonged strenuous exercise, the glutamine supplementation does not prevent the postexercise changes in several aspects of immune function. Although glutamine is essential for lymphocyte proliferation, the plasma glutamine concentration does not fall sufficiently low after exercise to compromise the rate of proliferation. Acute intakes of glutamine of approximately 20-30 g seem to be without ill effect in healthy adult humans and no harm was reported in 1 study in which athletes consumed 28 g glutamine every day for 14 d. Doses of up to 0.65 g/kg body mass of glutamine (in solution or as a suspension) have been reported to be tolerated by patients and did not result in abnormal plasma ammonia levels. However, the suggested reasons for taking glutamine supplements (support for immune system, increased glycogen synthesis, anticatabolic effect) have received little support from well-controlled scientific studies in healthy, well-nourished humans.

78 FR 11754 - Approval and Promulgation of Implementation Plans; Tennessee: Knox County Supplement Motor...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-20

... December 18, 2012, (77 FR 74820), EPA proposed to approve through parallel processing Tennessee's October... well as changes to future vehicle mix assumptions, that influence the emission estimations. TDEC has... 2014. \\2\\ A safety margin is the difference between the attainment level of emissions from all source...

78 FR 78796 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 314 and 601... Approved Drugs and Biological Products; Correction and Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Proposed rule; correction and extension of comment period. SUMMARY: The Food and...

78 FR 60704 - Approval and Promulgation of Air Quality Implementation Plan; Illinois; Redesignation of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... Oxides (NO X ), Sulfur Dioxide (SO 2 ), Volatile Organic Compound (VOC), ammonia, and primary PM 2.5... supplemental submission to the EPA on May 6, 2013, the IEPA submitted VOC and ammonia emission inventories to... Chicago area; approve 2002 primary PM 2.5 , NO X , SO 2 , VOC, and ammonia emission inventories for the...

Multivitamin supplementation in HIV infected adults initiating antiretroviral therapy in Uganda: the protocol for a randomized double blinded placebo controlled efficacy trial.

PubMed

Guwatudde, David; Ezeamama, Amara E; Bagenda, Danstan; Kyeyune, Rachel; Wabwire-Mangen, Fred; Wamani, Henry; Mugusi, Ferdinand; Spiegelman, Donna; Wang, Molin; Manabe, Yukari C; Fawzi, Wafaie W

2012-11-15

Use of multivitamin supplements during the pre-HAART era has been found to reduce viral load, enhance immune response, and generally improve clinical outcomes among HIV-infected adults. However, immune reconstitution is incomplete and significant mortality and opportunistic infections occur in spite of HAART. There is insufficient research information on whether multivitamin supplementation may be beneficial as adjunct therapy for HIV-infected individuals taking HAART. We propose to evaluate the efficacy of a single recommended daily allowance (RDA) of micronutrients (including vitamins B-complex, C, and E) in slowing disease progression among HIV-infected adults receiving HAART in Uganda. We are using a randomized, double-blind, placebo-controlled trial study design. Eligible patients are HIV-positive adults aged at least 18 years, and are randomized to receive either a placebo; or multivitamins that include a single RDA of the following vitamins: 1.4 mg B1, 1.4 mg B2, 1.9 mg B6, 2.6 mcg B12, 18 mg niacin, 70 mg C, 10 mg E, and 0.4 mg folic acid. Participants are followed for up to 18 months with evaluations at baseline, 6, 12 and 18 months. The study is primarily powered to examine the effects on immune reconstitution, weight gain, and quality of life. In addition, we will examine the effects on other secondary outcomes including the risks of development of new or recurrent disease progression event, including all-cause mortality; ARV regimen change from first- to second-line therapy; and other adverse events as indicated by incident peripheral neuropathy, severe anemia, or diarrhea. The conduct of this trial provides an opportunity to evaluate the potential benefits of this affordable adjunct therapy (multivitamin supplementation) among HIV-infected adults receiving HAART in a developing country setting. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01228578.

Efficacy of synbiotic supplementation in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of clinical trials: Synbiotic supplementation and NAFLD.

PubMed

Hadi, Amir; Mohammadi, Hamed; Miraghajani, Maryam; Ghaedi, Ehsan

2018-03-27

We systematically reviewed available randomized clinical trials (RCTs) to elucidate the overall effects of synbiotic supplementation in patients with nonalcoholic fatty liver disease (NAFLD). PubMed, Scopus, ISI Web of science and Google Scholar were searched up to December, 2017. All RCTs using synbiotic supplements to treat NAFLD included in this systematic review and meta-analysis. Mean Difference (MD) was pooled using a random-effects model. Eleven eligible databases from seven RCTs were identified for the present meta-analysis. Our results showed that synbiotic supplementation can decrease body weight, fasting blood sugar, insulin, low density lipoprotein cholesterol, total cholesterol, triglyceride, high-sensitivity C-reactive protein, tumor necrosis factor alpha, alanine transaminase and aspartate transaminase levels among patients with NAFLD. In contrast, synbiotic did not have favorable effects on body mass index (BMI), waist circumference, homeostasis model assessment for insulin resistance (HOMA-IR), and high density lipoprotein cholesterol (HDL) levels compared with the placebo group. The current study revealed that synbiotic supplementation has favorable effect on inflammatory factors, liver enzymes and some anthropometric indices, lipid profiles and glucose homeostasis parameters in patients with NAFLD.

Common use of dietary supplements for bipolar disorder: a naturalistic, self-reported study.

PubMed

Bauer, Michael; Glenn, Tasha; Conell, Jörn; Rasgon, Natalie; Marsh, Wendy; Sagduyu, Kemal; Munoz, Rodrigo; Lewitzka, Ute; Bauer, Rita; Pilhatsch, Maximilian; Monteith, Scott; Whybrow, Peter C

2015-12-01

Dietary supplements are taken by about half of Americans. Knowledge of dietary supplement use is important because they may interact with prescription drugs or other supplements, cause adverse reactions including psychiatric symptoms, or contain inherently toxic ingredients or contaminants. This study explores the use of dietary supplements by patients with bipolar disorder in the US. Data were obtained from an ongoing, naturalistic study of patients with bipolar disorder who received pharmacological treatment as usual. The patients self-reported their daily mood, sleep, and medications taken, including all drugs prescribed for bipolar disorder or that the patient felt impacted their mood. These included other prescribed drugs, over-the-counter drugs and dietary supplements. Drugs that received premarketing approval from the FDA were not included as dietary supplements. Patient demographics and daily medication use were characterized. Data were available from 348 patients in the US who returned a mean 249.5 days of data. In addition to prescribed psychiatric drugs, 101 of the 348 patients (29 %) used a dietary supplement for at least 7 days and 69 (20 %) used a supplement long term (for at least 50 % of days). Of the 101 supplement users, 72 (71.3 %) took one supplement daily. The 101 patients tried over 40 different supplements, and the long-term users took 19 different supplements. The most commonly taken supplements for both groups were fish oil, B vitamins, melatonin, and multivitamins. Patients using supplements were more likely to be white (p < 0.001), older (p = 0.009), and ill for more years (p = 0.025). Many patients with bipolar disorder use dietary supplements in addition to prescribed drugs. Physicians should obtain detailed information about all dietary supplements taken by patients with bipolar disorder.

Mediation of an efficacious HIV risk reduction intervention for South African men.

PubMed

O'Leary, Ann; Jemmott, John B; Jemmott, Loretta S; Bellamy, Scarlett; Icard, Larry D; Ngwane, Zolani

2015-10-01

"Men, Together Making a Difference!" is an HIV/STD risk-reduction intervention that significantly increased self-reported consistent condom use during vaginal intercourse compared with a health-promotion attention-control intervention among men (N = 1181) in Eastern Cape Province, South Africa. The present analyses were designed to identify mediators of the intervention's efficacy. The potential mediators were Social Cognitive Theory (SCT) constructs that the intervention targeted, including several aspects of condom-use self-efficacy, outcome expectancies, and knowledge. Mediation was assessed using a product-of-coefficients approach where an α path (the intervention's effect on the potential mediator) and a β path (the potential mediator's effect on the outcome of interest, adjusting for intervention) were estimated independently in a generalized estimating equations framework. Condom-use negotiation self-efficacy, technical-skill self-efficacy, and impulse-control self-efficacy were significant mediators. Although not mediators, descriptive norm and expected friends' approval of condom use predicted subsequent self-reported condom use, whereas the expected approval of sexual partner did not. The present results suggest that HIV/STD risk-reduction interventions that draw upon SCT and that address self-efficacy to negotiate condom use, to apply condoms correctly, and to exercise sufficient control when sexually aroused to use condoms may contribute to efforts to reduce sexual risk behavior among South African men. Future research must examine whether approaches that build normative support for condom use among men's friends are also efficacious.

Cognitex supplementation in elderly adults with memory complaints: an uncontrolled open label trial.

PubMed

Richter, Yael; Herzog, Yael; Eyal, Inbal; Cohen, Tzafra

2011-06-01

The components of the nutritional supplement Cognitex have been individually shown to have beneficial effects on cognitive function. We evaluated the efficacy of the nutritional supplement in improving cognitive function in elderly with memory complaints. Thirty participants received three capsules of the nutritional supplement per day for 12 weeks in an open label study. Efficacy and safety measures, assessed at baseline, 2 weeks, and 12 weeks of treatment, included cognitive evaluation using a computerized cognitive assessment tool, vital signs measurements, and physical examination. Twenty-six participants completed the 12-week study. A significant improvement in memory abilities (recall, recognition, and spatial short term) was observed following 2 weeks of Cognitex treatment (mean change from baseline: 11.15 ± 2.90, 8.68 ± 2.50, and 19.85 ± 6.19, respectively). Attention (sustained and focused), visual learning, and activities of daily living (executive functions and mental flexibility) were improved as well following this short supplementation period (mean change from baseline: 9.46 ± 3.80, 3.76 ± 1.50, 17.31 ± 5.33, 9.45 ± 3.73, and 9.92 ± 4.08, respectively). After 10 additional treatment weeks, activities of daily living demonstrated an additional statistically significant improvement while the beneficial effect observed for the rest of the tested parameters remained unchanged. The results indicate that the nutritional supplement may improve cognitive performance in elderly with memory complaints; however, further blinded and placebo-controlled studies are needed. Clinicaltrials.gov, Identifier: NCT00719953.

Impact of vitamin A supplementation on infant and childhood mortality

PubMed Central

2011-01-01

Introduction Vitamin A is important for the integrity and regeneration of respiratory and gastrointestinal epithelia and is involved in regulating human immune function. It has been shown previously that vitamin A has a preventive effect on all-cause and disease specific mortality in children under five. The purpose of this paper was to get a point estimate of efficacy of vitamin A supplementation in reducing cause specific mortality by using Child Health Epidemiology Reference Group (CHERG) guidelines. Methods A literature search was done on PubMed, Cochrane Library and WHO regional data bases using various free and Mesh terms for vitamin A and mortality. Data were abstracted into standardized forms and quality of studies was assessed according to standardized guidelines. Pooled estimates were generated for preventive effect of vitamin A supplementation on all-cause and disease specific mortality of diarrhea, measles, pneumonia, meningitis and sepsis. We did a subgroup analysis for vitamin A supplementation in neonates, infants 1-6 months and children aged 6-59 months. In this paper we have focused on estimation of efficacy of vitamin A supplementation in children 6-59 months of age. Results for neonatal vitamin A supplementation have been presented, however no recommendations are made as more evidence on it would be available soon. Results There were 21 studies evaluating preventive effect of vitamin A supplementation in community settings which reported all-cause mortality. Twelve of these also reported cause specific mortality for diarrhea and pneumonia and six reported measles specific mortality. Combined results from six studies showed that neonatal vitamin A supplementation reduced all-cause mortality by 12 % [Relative risk (RR) 0.88; 95 % confidence interval (CI) 0.79-0.98]. There was no effect of vitamin A supplementation in reducing all-cause mortality in infants 1-6 months of age [RR 1.05; 95 % CI 0.88-1.26]. Pooled results for preventive vitamin A

Caffeine and Creatine Content of Dietary Supplements Consumed by Brazilian Soccer Players.

PubMed

Inácio, Suelen Galante; de Oliveira, Gustavo Vieira; Alvares, Thiago Silveira

2016-08-01

Caffeine and creatine are ingredients in the most popular dietary supplements consumed by soccer players. However, some products may not contain the disclosed amounts of the ingredients listed on the label, compromising the safe usage and the effectiveness of these supplements. Therefore, the aim of this study was to evaluate the content of caffeine and creatine in dietary supplements consumed by Brazilian soccer players. The results obtained were compared with the caffeine content listed on the product label. Two batches of the supplement brands consumed by ≥ 50% of the players were considered for analysis. The quantification of caffeine and creatine in the supplements was determined by a high-performance liquid chromatography system with UV detector. Nine supplements of caffeine and 7 supplements of creatine met the inclusion criteria for analysis. Eight brands of caffeine and five brands of creatine showed significantly different values (p < .05) as compared with the values stated on the label. There were no significant differences between the two batches of supplements analyzed, except for one caffeine supplement. It can be concluded that caffeine and creatine dietary supplements consumed by Brazilian soccer players present inaccurate values listed on the label, although most presented no difference among batches. To ensure consumer safety and product efficacy, accurate information on caffeine and creatine content should be provided on all dietary supplement labels.

The use of dietary supplement among soldiers from the macedonian special operations regiment.

PubMed

Kjertakov, Metodija; Hristovski, Robert; Racaj, Muhamet

2013-01-01

To determine the prevalence and type of dietary supplement used, reasons for use, and sources of supplement information among Macedonian elite Soldiers. Anonymous self-reported questionnaires containing questions about demographic characteristics and dietary supplementation practices were distributed to 134 Soldiers, of whom 80 were recruited from the Ranger Battalion (R) and 54 from the Special Force Battalion (SF). The Soldiers completed and returned 132 questionnaires. Overall, 66.6% of the Soldiers, including 70.3% of SF and 64.1% of R, reported using supplements within the 3 months before the survey. On average, each of these Soldiers used 3.7 ? 2.9 supplements. The most commonly used supplements were multivitamins (50.0%) and vitamin C (47.7%). The most frequently cited reason for using supplements was to improve general health (51.6%). Primary sources of supplement information were friends (42.0%) and books/magazines (40.9%). Dietary supplement use was found to be common and widespread among this military subpopulation. Given this, and the fact that the majority of the Soldiers do not receive accurate information about supplements, educational intervention regarding the safety and efficacy of these products is needed if unnecessary or harmful supplementation practices are to be prevented. 2013.

A review of the efficacy and safety of oral antidiabetic drugs

PubMed Central

Stein, Stephanie Aleskow; Lamos, Elizabeth Mary; Davis, Stephen N

2014-01-01

Introduction Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes. Areas covered The efficacy and safety of metformin, SUs, TZDs, dipeptidyl peptidase-IV (DPP-4) inhibitors, meglitinide analogs, α-glucosidase inhibitors (AGIs), bile-acid sequestrants (BAS) and bromocriptine will be reviewed. Expert opinion Several new oral agents have been approved for type 2 diabetes management in recent years. It is important to understand the efficacy and safety of these medications in addition to the older agents to best maximize oral drug therapy for diabetes. Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin. They are a recommended alternative when metformin use is limited by gastrointestinal (GI) side effects or when SU treatment results in significant hypoglycemia or weight gain. Meglitinide analogs are limited by their frequent dosing, expense and hypoglycemia (repaglinide > nateglinide), while AGIs are also limited by their dosing schedule and GI side-effect profile. BAS and bromocriptine have the lowest efficacy with regard to HbA1c reduction, also are plagued by GI adverse reactions, but have a low risk of hypoglycemia. PMID:23241069

78 FR 53275 - Approval and Promulgation of Air Quality Implementation Plans; Ohio; Redesignation of the Ohio...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-29

... dioxide (SO 2 ), ammonia and volatile organic compounds (VOC) in the Parkersburg-Marietta area (Washington... provided ammonia and VOC emissions inventories to EPA to supplement the February 29, 2012, and April 16... addition, EPA is approving the 2005 NO X , SO 2 , and PM 2.5 emission inventories and 2007/2008 ammonia and...

The role of enzyme supplementation in digestive disorders.

PubMed

Roxas, Mario

2008-12-01

This article reviews various forms of enzyme supplementation used clinically in digestive and absorption disorders. Enzyme supplementation plays an integral role in the management of various digestive disorders, particularly with regard to exocrine pancreatic insufficiency. However, application of enzymes may also be beneficial for other conditions associated with poor digestion including lactose intolerance. Historically, porcine and bovine pancreatic enzymes have been the preferred form of supplementation for exocrine pancreatic insufficiency. Use of microbe-derived lipase has shown promise with studies indicating benefit similar to pancreatic enzymes, but at a lower dosage concentration and with a broader pH range. Safety and efficacy of enzymes derived from microbial species in the treatment of conditions such as malabsorption and lactose intolerance is promising. Plant-based enzymes, such as bromelain from pineapple, serve as effective digestive aids in the breakdown of proteins. Synergistic effects have been observed using a combination of animal-based enzymes and microbe-derived enzymes or bromelain.

Gaps, tensions, and conflicts in the FDA approval process: implications for clinical practice.

PubMed

Deyo, Richard A

2004-01-01

Despite many successes, drug approval at the Food and Drug Administration (FDA) is subject to gaps, internal tensions, and conflicts of interest. Recalls of drugs and devices and studies demonstrating advantages of older drugs over newer ones highlight the importance of these limitations. The FDA does not compare competing drugs and rarely requires tests of clinical efficacy for new devices. It does not review advertisements before use, assess cost-effectiveness, or regulate surgery (except for devices). Many believe postmarketing surveillance of drugs and devices is inadequate. A source of tension within the agency is pressure for speedy approvals. This may have resulted in "burn-out" among medical officers and has prompted criticism that safety is ignored. Others argue, however, that the agency is unnecessarily slow and bureaucratic. Recent reports identify conflicts of interest (stock ownership, consulting fees, research grants) among some members of the FDA's advisory committees. FDA review serves a critical function, but physicians should be aware that new drugs may not be as effective as old ones; that new drugs are likely to have undiscovered side effects at the time of marketing; that direct-to-consumer ads are sometimes misleading; that new devices generally have less rigorous evidence of efficacy than new drugs; and that value for money is not considered in approval.

75 FR 35957 - Supplemental Standards of Ethical Conduct for Employees of the Special Inspector General for Iraq...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-24

... Conduct for Employees of the Special Inspector General for Iraq Reconstruction AGENCY: Special Inspector... (OGE), is issuing an interim regulation for employees of the SIGIR that supplement the executive-branch... regulation requires SIGIR employees, except special Government employees, to obtain approval before engaging...

The challenge of establishing treatment efficacy for cutaneous vascular manifestations of systemic sclerosis.

PubMed

Pauling, John D

2018-05-01

The cutaneous vascular manifestations of systemic sclerosis (SSc) comprise Raynaud's phenomenon, cutaneous ulceration, telangiectasia formation and critical digital ischaemia; each of which are associated with significant disease-related morbidity. Despite the availability of multiple classes of vasodilator therapy, many of which have been the subject of RCTs, a limited number of pharmacological interventions are currently approved for the management of cutaneous vascular manifestations of SSc. Areas covered: A major challenge has been demonstrating treatment efficacy with examples of promising therapies yielding contrasting results in controlled trial settings. Differences between consensus best-practice guidelines, evidence-based recommendations and marketing approvals in different jurisdictions has resulted in geographic variation in clinical practice concerning the management of cutaneous vascular manifestations of SSc. Difficulty demonstrating treatment efficacy risks waning industry engagement for drug development programmes in this field. This article highlights the key challenges in establishing treatment efficacy and barriers that must be overcome to support successful clinical trial programmes across the spectrum of cutaneous vascular manifestations of SSc. Expert commentary: The paucity of approved treatments for cutaneous vascular manifestations of SSc relates as much to challenges in clinical trial design and the need for reliable clinical trial endpoints, as to lack of therapeutic options.

Phytotherapy and Nutritional Supplements on Breast Cancer

PubMed Central

Dourado, A.

2017-01-01

Breast cancer is the most frequent type of nonskin malignancy among women worldwide. In general, conventional cancer treatment options (i.e., surgery, radiotherapy, chemotherapy, biological therapy, and hormone therapy) are not completely effective. Recurrence and other pathologic situations are still an issue in breast cancer patients due to side effects, toxicity of drugs in normal cells, and aggressive behaviour of the tumours. From this point of view, breast cancer therapy and adjuvant methods represent a promising and challenging field for researchers. In the last few years, the use of some types of complementary medicines by women with a history of breast cancer has significantly increased such as phytotherapeutic products and nutritional supplements. Despite this, the use of such approaches in oncologic processes may be problematic and patient's health risks can arise such as interference with the efficacy of standard cancer treatment. The present review gives an overview of the most usual phytotherapeutic products and nutritional supplements with application in breast cancer patients as adjuvant approach. Regardless of the contradictory results of scientific evidence, we demonstrated the need to perform additional investigation, mainly well-designed clinical trials in order to establish correlations and allow for further validated outcomes concerning the efficacy, safety, and clinical evidence-based recommendation of these products. PMID:28845434

Plant based dietary supplement increases urinary pH

PubMed Central

Berardi, John M; Logan, Alan C; Rao, A Venket

2008-01-01

Background Research has demonstrated that the net acid load of the typical Western diet has the potential to influence many aspects of human health, including osteoporosis risk/progression; obesity; cardiovascular disease risk/progression; and overall well-being. As urinary pH provides a reliable surrogate measure for dietary acid load, this study examined whether a plant-based dietary supplement, one marketed to increase alkalinity, impacts urinary pH as advertised. Methods Using pH test strips, the urinary pH of 34 healthy men and women (33.9 +/- 1.57 y, 79.3 +/- 3.1 kg) was measured for seven days to establish a baseline urinary pH without supplementation. After this initial baseline period, urinary pH was measured for an additional 14 days while participants ingested the plant-based nutritional supplement. At the end of the investigation, pH values at baseline and during the treatment period were compared to determine the efficacy of the supplement. Results Mean urinary pH statistically increased (p = 0.03) with the plant-based dietary supplement. Mean urinary pH was 6.07 +/- 0.04 during the baseline period and increased to 6.21 +/- 0.03 during the first week of treatment and to 6.27 +/- 0.06 during the second week of treatment. Conclusion Supplementation with a plant-based dietary product for at least seven days increases urinary pH, potentially increasing the alkalinity of the body. PMID:18990209

Does Coenzyme Q10 Supplementation Mitigate Statin-Associated Muscle Symptoms? Pharmacological and Methodological Considerations.

PubMed

Taylor, Beth A

2018-04-01

Statin drugs markedly reduce low-density lipoprotein cholesterol and consequently the incidence of cardiac events. In approximately 5-10% of adults, these drugs are associated with a range of muscle side effects such as muscle pain, cramping and weakness. Reduction in mitochondrial coenzyme Q10 (CoQ10), or ubiquinone, has been proposed as a mechanism for these statin-associated muscle symptoms (SAMS), and thus various formulations of CoQ10 are marketed and consumed for the prevention and treatment of SAMS. However, data supporting the efficacy of CoQ10 are equivocal, with some studies showing that CoQ10 supplementation reduces the incidence and severity of SAMS and others finding no beneficial effects of supplementation. Methodological and pharmacological issues may confound interpretation of data on this topic. For example, many patients who report SAMS, such as those who have been enrolled in previous CoQ10 studies, may be experiencing non-specific (non-statin-associated) muscle pain. In addition, the effectiveness of oral CoQ10 supplementation to increase mitochondrial CoQ10 in human skeletal muscle is not well established. This manuscript will critically evaluate the published data on the efficacy of CoQ10 supplements in the prevention and treatment of SAMS.

78 FR 67985 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-13

... reference listed drug (RLD) upon submission to FDA of a ``changes being effected'' (CBE-0) supplement. The.... Effective Date VIII. Federalism IX. Request for Comments X. References Executive Summary Purpose of the.... Costs and Benefits The economic benefits to the public health from adoption of the proposed rule are not...

Study Protocol for a Randomized, Double-Blind, Community-Based Efficacy Trial of Various Doses of Zinc in Micronutrient Powders or Tablets in Young Bangladeshi Children

PubMed Central

Islam, M. Munirul; McDonald, Christine M.; Krebs, Nancy F.; Westcott, Jamie; Rahman, Ahmed Ehsanur; El Arifeen, Shams; Ahmed, Tahmeed; King, Janet C.; Black, Robert E.

2018-01-01

Zinc is essential to supporting growth in young children especially for tissues undergoing rapid cellular differentiation and turnover, such as those in the immune system and gastrointestinal tract. Therapeutic zinc supplementation has been initiated in low-income countries as part of diarrhea treatment programs to support these needs for young children, but the effects of preventive supplemental zinc as a tablet or as a multiple micronutrient powder (MNP) on child growth and diarrheal disease are mixed and pose programmatic uncertainties. Thus, a randomized, double-blind community-based efficacy trial of five different doses, forms, and frequencies of preventive zinc supplementation vs. a placebo was designed for a study in children aged 9–11 months in an urban community in Dhaka, Bangladesh. The primary outcomes of this 24-week study are incidence of diarrheal disease and linear growth. Study workers will conduct in-home morbidity checks twice weekly; anthropometry will be measured at baseline, 12 weeks and 24 weeks. Serum zinc and other related biomarkers will be measured in a subsample along with an estimate of the exchangeable zinc pool size using stable isotope techniques in a subgroup. Therapeutic zinc will be provided as part of diarrhea treatment, in accordance with Bangladesh’s national policy. Therefore, the proposed study will determine the additional benefit of a preventive zinc supplementation intervention. The protocol has been approved by the Institutional Review Boards (IRBs) of icddr,b and Children’s Hospital Oakland Research Institute (CHORI). The IRB review process is underway at the University of Colorado Denver as well.

Athlete Information Sources About Dietary Supplements: A Review of Extant Research.

PubMed

Denham, Bryan E

2017-08-01

In the United States, the Dietary Supplement Health and Education Act of 1994 (DSHEA) classified dietary supplements as a subcategory of food, exempting manufacturers from providing premarket evidence of product safety and efficacy. Under DSHEA, agencies such as the U.S. Food and Drug Administration (FDA) cannot inspect supplements until after the products have entered the marketplace. Recognizing that both limited resources and DSHEA prevent the FDA from conducting broad-based inspections on a regular basis, disreputable manufacturers have spiked products with drugs such as anabolic steroids and amphetamines. With contaminated supplements now causing athletes to fail drug tests and, in some instances, threatening public health, it becomes important to examine sources of supplement information. This article reviews 53 studies that have addressed athlete information sources about dietary supplements. It finds that athletes, in general, rely heavily on coaches and trainers as well as friends and family for information. Relative to U.S. athletes, those competing internationally appear more likely to seek information from a physician or nutritionist. The article offers recommendations for individuals and organizations based on the most frequent information sources identified by athletes.

Botanical and Dietary Supplements for Menopausal Symptoms: What Works, What Doesn’t

PubMed Central

Geller, Stacie E.; Studee, Laura

2006-01-01

All women reach menopause and approximately two-thirds of women develop menopausal symptoms, primarily hot flashes. Hormone therapy long was considered the first line of treatment for vasomotor symptoms. However, given the results of the Women’s Health Initiative, many women are reluctant use exogenous hormones for symptomatic treatment and are turning to botanicals and dietary supplement (BDS) products for relief. Despite the fact that there is limited scientific evidence describing efficacy and long term safety of such products, many women find these “natural treatments” appealing. Peri- and postmenopausal women are amongst the highest users of these products, but 70% of women do not tell their health care providers about their use. Compounding this issue is the fact that few clinicians ask their patients about use of BDS, largely because they have not been exposed to alternative medical practices in their training and are unfamiliar with these products. This paper reviews the botanicals and dietary supplements commonly used in menopause, (such as black cohosh, red clover, soy products, among others) as well as the available data on efficacy and safety. We searched the MEDLINE database from 1966 to December 2004 using terms related to botanical and dietary supplements and menopausal symptoms for peri- or postmenopausal women. Abstracts from relevant meetings as well as reference books and websites on herbal supplements were also searched. Randomized-controlled trials (RCTs) were used if available; open trials and comparison group studies were used when RCTs were not available. The evidence to date suggests that black cohosh is safe and effective for reducing menopausal symptoms, primarily hot flashes and possibly mood disorders. Phytoestrogen extracts, including soy foods and red clover appear to have at best only minimal effect on menopausal symptoms but have positive health effects on plasma lipid concentrations and may reduce heart disease. St. John�

Zinc supplementation in public health.

PubMed

Penny, Mary Edith

2013-01-01

Zinc is necessary for physiological processes including defense against infections. Zinc deficiency is responsible for 4% of global child morbidity and mortality. Zinc supplements given for 10-14 days together with low-osmolarity oral rehydration solution (Lo-ORS) are recommended for the treatment of childhood diarrhea. In children aged ≥ 6 months, daily zinc supplements reduce the duration of acute diarrhea episodes by 12 h and persistent diarrhea by 17 h. Zinc supplements could reduce diarrhea mortality in children aged 12-59 months by an estimated 23%; they are very safe but are associated with an increase in vomiting especially with the first dose. Heterogeneity between the results of trials is not understood but may be related to dose and the etiology of the diarrhea infection. Integration of zinc and Lo-ORS into national programs is underway but slowly, procurement problems are being overcome and the greatest challenge is changing health provider and caregiver attitudes to diarrhea management. Fewer trials have been conducted of zinc adjunct therapy in severe respiratory tract infections and there is as yet insufficient evidence to recommend addition of zinc to antibiotic therapy. Daily zinc supplements for all children >12 months of age in zinc deficient populations are estimated to reduce diarrhea incidence by 11-23%. The greatest impact is in reducing multiple episodes of diarrhea. The effect on duration of diarrheal episodes is less clear, but there may be up to 9% reduction. Zinc is also efficacious in reducing dysentery and persistent diarrhea. Zinc supplements may also prevent pneumonia by about 19%, but heterogeneity across studies has not yet been explained. When analyses are restricted to better quality studies using CHERG (Child Health Epidemiology Reference Group) methodology, zinc supplements are estimated to reduce diarrheal deaths by 13% and pneumonia deaths by 20%. National-level programs to combat childhood zinc deficiency should be

30 CFR 18.99 - Notice of approval or disapproval; letters of approval and approval plates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... approval or disapproval of the machine. (a) If the qualified electrical representative recommends field..., DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.99 Notice of approval or...

30 CFR 18.99 - Notice of approval or disapproval; letters of approval and approval plates.

Code of Federal Regulations, 2011 CFR

2011-07-01

... approval or disapproval of the machine. (a) If the qualified electrical representative recommends field..., DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.99 Notice of approval or...

49 CFR 451.16 - Action by approval authority-individual approval.

Code of Federal Regulations, 2013 CFR

2013-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.16 Action by approval authority-individual approval. (a) The...

49 CFR 451.16 - Action by approval authority-individual approval.

Code of Federal Regulations, 2011 CFR

2011-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.16 Action by approval authority-individual approval. (a) The...

49 CFR 451.16 - Action by approval authority-individual approval.

Code of Federal Regulations, 2012 CFR

2012-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.16 Action by approval authority-individual approval. (a) The...

49 CFR 451.16 - Action by approval authority-individual approval.

Code of Federal Regulations, 2010 CFR

2010-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.16 Action by approval authority-individual approval. (a) The...

49 CFR 451.16 - Action by approval authority-individual approval.

Code of Federal Regulations, 2014 CFR

2014-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.16 Action by approval authority-individual approval. (a) The...

Whole Food versus Supplement: Comparing the Clinical Evidence of Tomato Intake and Lycopene Supplementation on Cardiovascular Risk Factors12

PubMed Central

Burton-Freeman, Britt M.; Sesso, Howard D.

2014-01-01

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in the United States and worldwide. A link between diet and CVD is well established, with dietary modification a foundational component of CVD prevention and management. With the discovery of bioactive components beyond the essential nutrients of foods, a new era of nutritional, medical, botanical, physiologic, and analytical sciences has unfolded. The ability to identify, isolate, purify, and deliver single components has expanded the dietary supplement business and health opportunity for consumers. Lycopene is an example of a food component that has attracted attention from scientists as well as food, agriculture, and dietary supplement industries. A major question, however, is whether delivering lycopene through a supplement source is as effective as or more effective than consuming lycopene through whole food sources, specifically the tomato, which is the richest source of lycopene in the Western diet. In this review, we examined clinical trials comparing the efficacy of lycopene supplements with tomato products on intermediate CVD risk factors including oxidative stress, inflammation, endothelial function, blood pressure, and lipid metabolism. Overall, the present review highlights the need for more targeted research; however, at present, the available clinical research supports consuming tomato-based foods as a first-line approach to cardiovascular health. With the exception of blood pressure management where lycopene supplementation was favored, tomato intake provided more favorable results on cardiovascular risk endpoints than did lycopene supplementation. Indeed, future research that is well designed, clinically focused, mechanistically revealing, and relevant to human intake will undoubtedly add to the growing body of knowledge unveiling the promise of tomatoes and/or lycopene supplementation as an integral component of a heart-healthy diet. PMID:25469376

Iron deficiency anemia: pregnancy outcomes with or without iron supplementation.

PubMed

Bánhidy, Ferenc; Acs, Nándor; Puhó, Erzsébet H; Czeizel, Andrew E

2011-01-01

To estimate the efficacy of iron supplementation in anemic pregnant women on the basis of occurrence of pregnancy complications and birth outcomes. Comparison of the occurrence of medically recorded pregnancy complications and birth outcomes in pregnant women affected with medically recorded iron deficiency anemia and iron supplementation who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities. Of 22,843 cases with congenital abnormalities, 3242 (14.2%), while of 38,151 controls, 6358 (16.7%) had mothers with anemia. There was no higher rate of preterm births and low birth weight in the newborns of anemic pregnant women supplemented by iron. However, anemic pregnant women without iron treatment had a significantly shorter gestational age at delivery with a somewhat higher rate of preterm births but these adverse birth outcomes were prevented with iron supplementation. The rate of total and some congenital abnormalities was lower than expected and explained mainly by the healthier lifestyle and folic acid supplements. The secondary findings of the study showed a higher risk of constipation-related hemorrhoids and hypotension in anemic pregnant women with iron supplementation. A higher rate of preterm birth was found in anemic pregnant women without iron treatment but this adverse birth outcome was prevented with iron supplementation. There was no higher rate of congenital abnormalities in the offspring of anemic pregnant women supplemented with iron and/or folic acid supplements. Copyright © 2011 Elsevier Inc. All rights reserved.

Integrating dietary supplements into cancer care.

PubMed

Frenkel, Moshe; Abrams, Donald I; Ladas, Elena J; Deng, Gary; Hardy, Mary; Capodice, Jillian L; Winegardner, Mary F; Gubili, J K; Yeung, K Simon; Kussmann, Heidi; Block, Keith I

2013-09-01

Many studies confirm that a majority of patients undergoing cancer therapy use self-selected forms of complementary therapies, mainly dietary supplements. Unfortunately, patients often do not report their use of supplements to their providers. The failure of physicians to communicate effectively with patients on this use may result in a loss of trust within the therapeutic relationship and in the selection by patients of harmful, useless, or ineffective and costly nonconventional therapies when effective integrative interventions may exist. Poor communication may also lead to diminishment of patient autonomy and self-efficacy and thereby interfere with the healing response. To be open to the patient's perspective, and sensitive to his or her need for autonomy and empowerment, physicians may need a shift in their own perspectives. Perhaps the optimal approach is to discuss both the facts and the uncertainty with the patient, in order to reach a mutually informed decision. Today's informed patients truly value physicians who appreciate them as equal participants in making their own health care choices. To reach a mutually informed decision about the use of these supplements, the Clinical Practice Committee of The Society of Integrative Oncology undertook the challenge of providing basic information to physicians who wish to discuss these issues with their patients. A list of leading supplements that have the best suggestions of benefit was constructed by leading researchers and clinicians who have experience in using these supplements. This list includes curcumin, glutamine, vitamin D, Maitake mushrooms, fish oil, green tea, milk thistle, Astragalus, melatonin, and probiotics. The list includes basic information on each supplement, such as evidence on effectiveness and clinical trials, adverse effects, and interactions with medications. The information was constructed to provide an up-to-date base of knowledge, so that physicians and other health care providers would

Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial

PubMed Central

Badrasawi, M; Shahar, Suzana; Zahara, AM; Nor Fadilah, R; Singh, Devinder Kaur Ajit

2016-01-01

Background Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. Methodology This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. Results The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine (P<0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. Conclusion L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults. PMID:27895474

Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial.

PubMed

Badrasawi, M; Shahar, Suzana; Zahara, A M; Nor Fadilah, R; Singh, Devinder Kaur Ajit

2016-01-01

Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine ( P <0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults.

Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000-2012.

PubMed

Sacks, Leonard V; Shamsuddin, Hala H; Yasinskaya, Yuliya I; Bouri, Khaled; Lanthier, Michael L; Sherman, Rachel E

Some new drug applications fail because of inadequate drug performance and others are not approved because the information submitted to the US Food and Drug Administration (FDA) is unsatisfactory to make that determination. Resubmission of failed applications is costly, delaying marketing approval and the availability of new drugs to patients. To identify the reasons that FDA marketing approval for new drugs was delayed or denied. A retrospective review of FDA documents and extraction of data were performed. We examined all drug applications first submitted to the FDA between 2000 and 2012 for new molecular entities (NMEs), which are active ingredients never before marketed in the United States in any form. Using FDA correspondence and reviews, we investigated the reasons NMEs failed to obtain FDA approval. Reasons for delayed FDA approval or nonapproval of NME applications. Of the 302 identified NME applications, 151 (50%) were approved when first submitted and 222 (73.5%) were ultimately approved. Seventy-one applications required 1 or more resubmissions before approval, with a median delay to approval of 435 days following the first unsuccessful submission. Of the unsuccessful first-time applications, 24 (15.9%) included uncertainties related to dose selection, 20 (13.2%) choice of study end points that failed to adequately reflect a clinically meaningful effect, 20 (13.2%) inconsistent results when different end points were tested, 17 (11.3%) inconsistent results when different trials or study sites were compared, and 20 (13.2%) poor efficacy when compared with the standard of care. The frequency of safety deficiencies was similar among never-approved drugs compared with those with delayed approval (43 of 80 never approved [53.8%] vs 37 of 71 eventually approved [52.1%]; difference, 1.7% [95% CI, -14.86% to 18.05%]; P = .87). However, efficacy deficiencies were significantly more frequent among the never-approved drugs than among those with delayed approvals

[Usefulness of bifonazole for treatment of tinea pedis in the 20th year after approval].

PubMed

Mitsui, Hiroshi; Kanda, Naoko; Ohnishi, Takamitsu; Nakai, Kenji; Suzuki, Taku; Watanabe, Shinichi

2009-04-01

We studied the usefulness of Mycospor Cream 1% (hereinafter referred to as "bifonazole cream"), which was approved 20 years ago in Japan, with once-daily application in 16 patients with tinea pedis (plantar tinea pedis, n = 8; interdigital tinea pedis, n = 8). One of them discontinued after 2 weeks of study treatment due to aggravation of skin symptoms. This subject was excluded from assessment of mycological activity and skin-symptom improvement at 4 weeks after initiation of treatment, but included in overall clinical efficacy rating and usefulness rating as an "ineffective" and "useless" case. The mean (+/- SD) duration of study treatment among the 15 subjects (excluding the discontinued subject) was 26.5 +/- 2.3 days (range: 21 to 28 days). The mycological eradication rate at Week 4 was 100% (15/15 subjects). The scores on all skin symptoms (itching, redness, papules, blisters, pustules, maceration, and scaling) at Week 4 significantly improved from the respective baseline scores (p<0.05), and almost all skin symptoms disappeared. The skin-symptom improvement rate was 93% (14/15 subjects). The overall clinical efficacy rate, which was assessed based on mycological efficacy and skin-symptom improvement rating, was 81% (13/16 subjects). No adverse reaction was observed in any of the subjects. The usefulness rate, which was assessed based on overall clinical efficacy and safety rating, was 88% (14/16 subjects). In this study, we confirmed that the usefulness of bifonazole cream for the treatment of tinea pedis was consistent with the results of studies performed before approval and 10 years after approval. About 20 years have passed since its launch, but bifonazole cream still remains a useful antifungal drug for topical treatment of tinea pedis.

Ghanaian parents' perceptions of pre and postnatal nutrient supplements and their effects.

PubMed

Adams, Katherine P; Okronipa, Harriet; Adu-Afarwuah, Seth; Arimond, Mary; Kumordzie, Sika; Oaks, Brietta M; Ocansey, Maku E; Young, Rebecca R; Vosti, Stephen A; Dewey, Kathryn G

2018-04-15

Small-quantity lipid-based nutrient supplements (SQ-LNS) have been studied in efficacy and effectiveness trials, but little is known about how parents perceive the products and their effects. In a randomised trial in Ghana, efficacy of SQ-LNS provided to women during pregnancy and the first 6 months postpartum and to their children from 6 to 18 months of age was assessed by comparison with iron-folic acid (IFA) capsules and multiple micronutrient (MMN) capsules provided to women. In a follow-up study conducted when the index children from the original trial were between 4 and 6 years of age, we used survey-based methods to assess retrospective and current parental perceptions of nutrient supplements generally and of SQ-LNS and their effects compared with perceptions IFA and MMN capsules. Most parents perceived that the assigned supplements (SQ-LNS, IFA, or MMN) positively impacted the mother during pregnancy (approximately 89% of both mothers and fathers) and during lactation (84% of mothers and 86% of fathers). Almost all (≥90%) of mothers and fathers perceived that the assigned supplement positively impacted the index child and expected continued positive impacts on the child's health and human capital into the future. A smaller percentage of parents perceived negative impacts of the supplements (7%-17% of mothers and 4%-12% of fathers). Perceptions of positive impacts and of negative impacts did not differ by intervention group. The results suggest that similar populations would likely be receptive to programs to deliver SQ-LNS or micronutrient capsules. © 2018 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.

Airline policy for passengers requiring supplemental in-flight oxygen.

PubMed

Walker, Jacqueline; Kelly, Paul T; Beckert, Lutz

2009-05-01

The aim of this study was to investigate the current Australian/New Zealand airline policy on supplemental in-flight oxygen for passengers with lung disease. Fifty-four commercial airlines servicing international routes were surveyed. Information was gathered from airline call centres and web sites. The survey documented individual airline policy on in-flight oxygen delivery, approval schemes, equipment and cost. Of the 54 airlines contacted, 43 (81%) were able to support passengers requiring in-flight oxygen. The majority (88%) of airlines provided a cylinder for passengers to use. Airline policy for calculating the cost of in-flight oxygen differed considerably between carriers. Six (14%) airlines supplied oxygen to passengers free of charge; however, three of these airlines charged for an extra seat. Fifteen airlines (35%) charged on the basis of oxygen supplied, that is, per cylinder. Fourteen airlines (33%) had a flat rate charge per sector. This study confirmed that most airlines can accommodate passengers requiring supplemental oxygen. However, the findings highlight inconsistencies in airline policies and substantial cost differences for supplemental in-flight oxygen. We advocate an industry standardization of policy and cost of in-flight oxygen.

Evidence-Based Approach to Fiber Supplements and Clinically Meaningful Health Benefits, Part 1

PubMed Central

McRorie, Johnson W.

2015-01-01

Dietary fiber that is intrinsic and intact in fiber-rich foods (eg, fruits, vegetables, legumes, whole grains) is widely recognized to have beneficial effects on health when consumed at recommended levels (25 g/d for adult women, 38 g/d for adult men). Most (90%) of the US population does not consume this level of dietary fiber, averaging only 15 g/d. In an attempt to bridge this “fiber gap,” many consumers are turning to fiber supplements, which are typically isolated from a single source. Fiber supplements cannot be presumed to provide the health benefits that are associated with dietary fiber from whole foods. Of the fiber supplements on the market today, only a minority possess the physical characteristics that underlie the mechanisms driving clinically meaningful health benefits. The first part (current issue) of this 2-part series will focus on the 4 main characteristics of fiber supplements that drive clinical efficacy (solubility, degree/rate of fermentation, viscosity, and gel formation), the 4 clinically meaningful designations that identify which health benefits are associated with specific fibers, and the gel-dependent mechanisms in the small bowel that drive specific health benefits (eg, cholesterol lowering, improved glycemic control). The second part (next issue) of this 2-part series will focus on the effects of fiber supplements in the large bowel, including the 2 mechanisms by which fiber prevents/relieves constipation (insoluble mechanical irritant and soluble gel-dependent water-holding capacity), the gel-dependent mechanism for attenuating diarrhea and normalizing stool form in irritable bowel syndrome, and the combined large bowel/small bowel fiber effects for weight loss/maintenance. The second part will also discuss how processing for marketed products can attenuate efficacy, why fiber supplements can cause gastrointestinal symptoms, and how to avoid symptoms for better long-term compliance. PMID:25972618

Evidence-Based Approach to Fiber Supplements and Clinically Meaningful Health Benefits, Part 2

PubMed Central

McRorie, Johnson W.

2015-01-01

Dietary fiber that is intrinsic and intact in fiber-rich foods (eg, fruits, vegetables, legumes, whole grains) is widely recognized to have beneficial effects on health when consumed at recommended levels (25 g/d for adult women, 38 g/d for adult men). Most (90%) of the US population does not consume this level of dietary fiber, averaging only 15 g/d. In an attempt to bridge this “fiber gap,” many consumers are turning to fiber supplements, which are typically isolated from a single source. Fiber supplements cannot be presumed to provide the health benefits that are associated with dietary fiber from whole foods. Of the fiber supplements on the market today, only a minority possess the physical characteristics that underlie the mechanisms driving clinically meaningful health benefits. In this 2-part series, the first part (previous issue) described the 4 main characteristics of fiber supplements that drive clinical efficacy (solubility, degree/rate of fermentation, viscosity, and gel formation), the 4 clinically meaningful designations that identify which health benefits are associated with specific fibers, and the gel-dependent mechanisms in the small bowel that drive specific health benefits (eg, cholesterol lowering, improved glycemic control). The second part (current issue) of this 2-part series will focus on the effects of fiber supplements in the large bowel, including the 2 mechanisms by which fiber prevents/relieves constipation (insoluble mechanical irritant and soluble gel-dependent water-holding capacity), the gel-dependent mechanism for attenuating diarrhea and normalizing stool form in irritable bowel syndrome, and the combined large bowel/small bowel fiber effects for weight loss/maintenance. The second part will also discuss how processing for marketed products can attenuate efficacy, why fiber supplements can cause gastrointestinal symptoms, and how to avoid symptoms for better long-term compliance. PMID:25972619

Effects of herbal and dietary supplements on cognition in menopause: a systematic review.

PubMed

Clement, Yuri N; Onakpoya, Igho; Hung, Shao K; Ernst, Edzard

2011-03-01

Many postmenopausal women use herbal remedies and dietary supplements to counteract menopausal symptoms, including the decline in cognitive function. The aim of this systematic review is to evaluate the evidence regarding the efficacy of herbal and dietary supplements on cognition in menopause. Randomized clinical trials (RCTs) of herbal medicines and dietary supplements were identified using the Medline, EMBASE, AMED, PsycINFO, CINAHL and The Cochrane Library 2010 (Issue 2) electronic databases and by hand searches. Data were independently extracted and evaluated by two reviewers. Risk of bias was assessed by two independent reviewers using the Cochrane Collaboration tool. Twelve RCTs were included and five of these suggest that isoflavone, soy and Gingko biloba supplementation may improve cognition in postmenopausal women. However, most of the included studies had serious methodological flaws which demand a cautious interpretation of these findings. The evidence that herbal and dietary supplements might positively affect the cognitive decline during the menopause is not compelling. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Differences between dietary supplement and prescription drug omega-3 fatty acid formulations: a legislative and regulatory perspective.

PubMed

Collins, Nancy; Tighe, Ann P; Brunton, Stephen A; Kris-Etherton, Penny M

2008-12-01

The medical management of many diseases and conditions can include either restriction or provision of specific essential nutrients. When such nutrients are needed, there are often both prescription and nonprescription products available, as in the case of nicotinic acid or omega-3 fatty acids. Although they may seem to contain similar ingredients, there may be important differences between the prescription and dietary-supplement preparations. The manufacturing of prescription pharmaceutical products is regulated by the US Food and Drug Administration (FDA), which mandates standards for consistency and quality assurance. Dietary supplements are available to consumers under the provisions of the Dietary Supplement Health and Education Act of 1994, for which the FDA has the burden of proving a dietary supplement is harmful rather than requiring the manufacturer prove that the supplement is safe. Consumers and medical professionals should be aware of the important qualitative and quantitative differences between the FDA-approved prescription formulations and dietary supplements, particularly when an essential nutrient is part of the medical management of a disease or condition.

Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy

PubMed Central

Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; dela Peña, Ike

2016-01-01

Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a “safer” approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments. PMID:26966583

Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants

PubMed Central

Baack, Michelle L; Puumala, Susan E; Messier, Stephen E; Pritchett, Deborah K; Harris, William S

2016-01-01

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother’s milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective was to develop a DHA supplementation strategy to overcome these barriers. This double-blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50mg/d) in addition to standard nutrition for preterm infants (24–34 weeks GA) beginning in the first week of life. Blood FA levels were analyzed at baseline, full feedings and near discharge in DHA (n=31) or placebo supplemented (n=29) preterm infants. Term peers (n=30) were analyzed for comparison. Preterm infants had lower baseline DHA levels (p<0.0001). Those receiving DHA had a progressive increase in circulating DHA over time (from 3.33% to 4.09%, p<0.0001) while placebo-supplemented infants (receiving standard neonatal nutrition) had no increase over time (from 3.35% to 3.32%). Although levels increased with additional DHA supplementation, preterm infants still had lower blood DHA levels than term peers (4.97%) at discharge (p=0.0002). No differences in adverse events were observed between the groups. Overall, daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants. PMID:26846324

Flavonoids, the emerging dietary supplement against cisplatin-induced nephrotoxicity.

PubMed

Athira, K V; Madhana, Rajaram Mohanrao; Lahkar, Mangala

2016-03-25

The letter illustrates the emerging potential of flavonoids as dietary supplement to ameliorate cisplatin-induced nephrotoxicity and refers to the recent article on ''Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat'' by Chtourou et al. They demonstrated that supplementation of naringin, a flavanone glycoside, found in grape and citrus fruit species, can attenuate cisplatin-induced renal dysfunction via restoration of redox balance and suppression of inflammation, NF-κB activation and apoptosis. The chemotherapeutic efficacy of cisplatin has always compelled the researchers to find solution to ameliorate its side effects. In recent years, numerous candidates have been evaluated for their protective potential against cisplatin-induced nephrotoxicity and flavonoids have come up with promising results. The future prospects might be promising with a proper refinement and collective integration of the preclinical and clinical research in the field of flavonoid supplementation to cisplatin therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

New treatment options for chronic constipation: Mechanisms, efficacy and safety

PubMed Central

Camilleri, Michael

2011-01-01

The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes. PMID:22114755

A review of dietary supplement-induced renal dysfunction.

PubMed

Gabardi, Steven; Munz, Kristin; Ulbricht, Catherine

2007-07-01

Complementary and alternative medicine (CAM) is a multibillion-dollar industry. Almost half of the American population uses some form of CAM, with many using them in addition to prescription medications. Most patients fail to inform their health care providers of their CAM use, and physicians rarely inquire. Annually, thousands of dietary supplement-induced adverse events are reported to Poison Control Centers nationwide. CAM manufacturers are not responsible for proving safety and efficacy, because the Food and Drug Administration does not regulate them. However, concern exists surrounding the safety of CAM. A literature search using MEDLINE and EMBASE was undertaken to explore the impact of CAM on renal function. English-language studies and case reports were selected for inclusion but were limited to those that consisted of human subjects, both adult and pediatric. This review provides details on dietary supplements that have been associated with renal dysfunction and focuses on 17 dietary supplements that have been associated with direct renal injury, CAM-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, and hepatorenal syndrome. It is concluded that it is imperative that use of dietary supplements be monitored closely in all patients. Health care practitioners must take an active role in identifying patients who are using CAM and provide appropriate patient education.

Dietary supplements and team-sport performance.

PubMed

Bishop, David

2010-12-01

highlighted in this review needs to be conducted using team-sport athletes and using team-sport-relevant testing (e.g. single- and multiple-sprint performance). It should also be considered that there is no guarantee that dietary supplements that improve isolated performance (i.e. single-sprint or jump performance) will remain effective in the context of a team-sport match. Thus, more research is also required to investigate the effects of dietary supplements on simulated or actual team-sport performance. A second aim of this review was to investigate any health issues associated with the ingestion of the more commonly promoted dietary supplements. While most of the supplements described in the review appear safe when using the recommended dose, the effects of higher doses (as often taken by athletes) on indices of health remain unknown, and further research is warranted. Finally, anecdotal reports suggest that team-sport athletes often ingest more than one dietary supplement and very little is known about the potential adverse effects of ingesting multiple supplements. Supplements that have been demonstrated to be safe and efficacious when ingested on their own may have adverse effects when combined with other supplements. More research is required to investigate the effects of ingesting multiple supplements (both on performance and health).

Motivational Interviewing Skills are Positively Associated with Nutritionist Self-Efficacy

ERIC Educational Resources Information Center

Marley, Scott C.; Carbonneau, Kira; Lockner, Donna; Kibbe, Debra; Trowbridge, Frederick

2011-01-01

Objective: To examine the relationships between physical and social self-concepts, motivational interviewing (MI), and nutrition assessment skills with dimensions of counseling self-efficacy. Design: Cross-sectional survey. Setting: Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clinics. Participants: Sixty-five WIC…

Oral choline supplementation for postoperative pain

PubMed Central

Sidhu, N.; Davies, S.; Nadarajah, A.; Rivera, J.; Whittington, R.; Mercier, R. J.; Virag, L.; Wang, S.; Flood, P.

2013-01-01

Background Activation of nicotinic receptors with nicotine has been shown to reduce post-surgical pain in clinical and preclinical studies. Choline is a selective agonist at α7-type nicotinic receptors that does not have addictive or sympathetic activating properties. It is anti-nociceptive in animal studies. We conducted a double-blind randomized trial of oral choline supplementation with lecithin to aid in the treatment of pain after gynaecological surgery. Methods Sixty women having open gynaecological surgery were randomly assigned to receive 20 g of lecithin before surgery or placebo. Plasma choline concentration and tumour necrosis factor (TNF) were measured. Pain report was the primary outcome measure. Results We achieved a small but statistically significant increase in choline after surgery with oral supplementation. Plasma TNF was not decreased and pain report was not different between groups at rest or with movement. There were no adverse effects of treatment. Conclusions Oral supplementation with lecithin during the perioperative period resulted in very slow absorption and thus only a small increase in plasma choline was achieved. This concentration was inadequate to reduce TNF as has been shown in other studies. The absence of an anti-inflammatory effect was likely related to our failure to demonstrate efficacy in pain reduction. PMID:23568851

The clinical content of preconception care: nutrition and dietary supplements.

PubMed

Gardiner, Paula M; Nelson, Lauren; Shellhaas, Cynthia S; Dunlop, Anne L; Long, Richard; Andrist, Sara; Jack, Brian W

2008-12-01

Women of child-bearing age should achieve and maintain good nutritional status prior to conception to help minimize health risks to both mothers and infants. Many women may not be aware of the importance of preconception nutrition and supplementation or have access to nutrition information. Health care providers should be knowledgeable about preconception/pregnancy-related nutrition and take the initiative to discuss this information during preconception counseling. Women of reproductive age should be counseled to consume a well-balanced diet including fruits and vegetables, iron and calcium-rich foods, and protein-containing foods as well as 400 microg of folic acid daily. More research is critically needed on the efficacy and safety of dietary supplements and the role of obesity in birth outcomes. Preconception counseling is the perfect opportunity for the health care provider to discuss a healthy eating guideline, dietary supplement intake, and maintaining a healthy weight status.

Using cost-effectiveness analysis to evaluate targeting strategies: the case of vitamin A supplementation.

PubMed

Loevinsohn, B P; Sutter, R W; Costales, M O

1997-03-01

Given the demonstrated efficacy of vitamin A supplements in reducing childhood mortality, health officials now have to decide whether it would be efficient to target the supplements to high risk children. Decisions about targeting are complex because they depend on a number of factors; the degree of clustering of preventable deaths, the cost of the intervention, the side-effects of the intervention, the cost of identifying the high risk group, and the accuracy of the 'diagnosis' of risk. A cost-effectiveness analysis was used in the Philippines to examine whether vitamin A supplements should be given universally to all children 6-59 months, targeted broadly to children suffering from mild, moderate, or severe malnutrition, or targeted narrowly to pre-schoolers with moderate and severe malnutrition. The first year average cost of the universal approach was US$67.21 per death averted compared to $144.12 and $257.20 for the broad and narrow targeting approaches respectively. When subjected to sensitivity analysis the conclusion about the most cost-effective strategy was robust to changes in underlying assumptions such as the efficacy of supplements, clustering of deaths, and toxicity. Targeting vitamin A supplements to high risk children is not an efficient use of resources. Based on the results of this cost-effectiveness analysis and a consideration of alternate strategies, it is apparent that vitamin A, like immunization, should be provided to all pre-schoolers in the developing world. Issues about targeting public health interventions can usefully be addressed by cost-effectiveness analysis.

The role of calcium supplementation in healthy musculoskeletal ageing: an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases ...

USDA-ARS?s Scientific Manuscript database

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction ha...

Characteristics of Preapproval and Postapproval Studies for Drugs Granted Accelerated Approval by the US Food and Drug Administration

PubMed Central

Smalley, Katelyn R.; Kesselheim, Aaron S.

2017-01-01

Importance Drugs treating serious or life-threatening conditions can receive US Food and Drug Administration (FDA) accelerated approval based on showing an effect in surrogate measures that are only reasonably likely to predict clinical benefit. Confirmatory trials are then required to determine whether these effects translate to clinical improvements. Objective To characterize preapproval and confirmatory clinical trials of drugs granted accelerated approval. Design and Setting Publicly available FDA documents were reviewed to identify the preapproval trials leading to accelerated approval between 2009 and 2013. Information on the status and findings of required confirmatory studies was extracted from the FDA’s database of postmarketing requirements and commitments, ClinicalTrials.gov, and matched peer-reviewed publications. Follow-up ended on April 7, 2017. Exposures Granting of accelerated approval. Main Outcomes and Measures Characteristics of preapproval and confirmatory studies were compared in terms of study design features (randomization, blinding, comparator, primary end point). Subsequent regulatory decisions and estimated time between accelerated approval and fulfillment of regulatory requirements were summarized. Results The FDA granted accelerated approval to 22 drugs for 24 indications (19 for indications involving cancer treatment) between 2009 and 2013. A total of 30 preapproval studies supported the 24 indications. The median number of participants enrolled in the preapproval studies was 132 (interquartile range, 89-224). Eight studies (27%) included fewer than 100 participants and 20 (67%) included fewer than 200. At a minimum 3 years of follow-up, 19 of 38 (50%) required confirmatory studies were completed, including 18 published reports. Twenty-five of the 38 (66%) examined clinical efficacy, 7 (18%) evaluated longer follow-up, and 6 (16%) focused on safety The proportion of studies with randomized designs did not differ before and after

Comparison of dietary supplement product knowledge and confidence between pharmacists and health food store employees.

PubMed

Coon, Scott A; Stevens, Vanessa W; Brown, Jack E; Wolff, Stephen E; Wrobel, Mark J

2015-01-01

To determine pharmacists' and health food store employees' knowledge about the safety and efficacy of common, nonvitamin, nonmineral dietary supplements in a retail setting and confidence in discussing, recommending, and acquiring knowledge about complementary and alternative medicine (CAM). Cross-sectional survey. Central and western New York in May and June 2012. Knowledge and confidence survey scores based on true/false and Likert scale responses. Pharmacists' mean knowledge score was significantly higher than that of health food store employees (8.42 vs. 6.15 items of 15 total knowledge questions). Adjusting for differences in experience, education, occupation, and confidence, knowledge scores were significantly higher for pharmacists and those with a higher total confidence score. Pharmacists were significantly less confident about the safety and efficacy of CAM comparatively (13 vs. 16 items of 20 total questions). Pharmacists scored significantly higher than health food store employees on a survey assessing knowledge of dietary supplements' safety and efficacy. Despite the significant difference, scores were unacceptably low for pharmacists, highlighting a knowledge deficit in subject matter.

First identification and quantification of lorcaserin in an herbal slimming dietary supplement.

PubMed

Hachem, Rabab; Malet-Martino, Myriam; Gilard, Véronique

2014-09-01

The weight-loss drug lorcaserin, a FDA approved anorectic drug, was isolated from the dietary supplement "Lose quickly" claimed to be a pure natural fast slimming diet pill. After its purification by means of preparative liquid chromatography, its structure was characterized using LC-UV, NMR, MS, MS/MS, and IR spectroscopy. The amount of lorcaserin measured by qNMR was 6.6mg/capsule. Copyright © 2014 Elsevier B.V. All rights reserved.

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis.

PubMed

Chen, Zhe; Zhang, Lingli; Zeng, Linan; Yang, Xiaoyan; Jiang, Lucan; Gui, Ge; Zhang, Zuojie

2017-01-01

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4-15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice. Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect. Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: -18.05, 95% CI (-25.51, -10.58), P < 0.00001], 5day [MD: -23.49, 95% CI (-32.80, -14.18), P < 0.00001], 7day [MD: -33.01, 95% CI (-37.31, -28.70), P < 0.00001] treatment, but also decreased time of jaundice fading [MD: -1.91, 95% CI (-2.06, -1.75), P < 0.00001], as well as the duration of

Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.

PubMed

Saad, Khaled; Abdel-Rahman, Ahmed A; Elserogy, Yasser M; Al-Atram, Abdulrahman A; El-Houfey, Amira A; Othman, Hisham A-K; Bjørklund, Geir; Jia, Feiyong; Urbina, Mauricio A; Abo-Elela, Mohamed Gamil M; Ahmad, Faisal-Alkhateeb; Abd El-Baseer, Khaled A; Ahmed, Ahmed E; Abdel-Salam, Ahmad M

2018-01-01

Autism spectrum disorder (ASD) is a frequent developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. It has been previously reported that there is vitamin D deficiency in autistic children; however, there is a lack of randomized controlled trials of vitamin D supplementation in ASD children. This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3-10 years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. ASD patients were randomized to receive vitamin D3 or placebo for 4 months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at the beginning and at the end of the study. The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and the Autism Treatment Evaluation Checklist (ATEC). UMIN-CTR Study Design: trial number: UMIN000020281. Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD. This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD. At this stage, this study is a single RCT with a small number of patients, and a great deal of additional wide-scale studies are needed to

Polypharmacology of Approved Anticancer Drugs.

PubMed

Amelio, Ivano; Lisitsa, Andrey; Knight, Richard A; Melino, Gerry; Antonov, Alexey V

2017-01-01

The major drug discovery efforts in oncology have been concentrated on the development of selective molecules that are supposed to act specifically on one anticancer mechanism by modulating a single or several closely related drug targets. However, a bird's eye view on data from multiple available bioassays implies that most approved anticancer agents do, in fact, target many more proteins with different functions. Here we will review and systematize currently available information on the targets of several anticancer drugs along with revision of their potential mechanisms of action. Polypharmacology of the current antineoplastic agents suggests that drug clinical efficacy in oncology can be achieved only via modulation of multiple cellular mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Efficacy of a Fatty Acids Dietary Supplement in a Polyethylene Glycol-Induced Mouse Model of Retinal Degeneration

PubMed Central

Locri, Filippo; Lardner, Emma; Kvanta, Anders; Rusciano, Dario; Bagnoli, Paola

2017-01-01

Current knowledge of the benefits of nutrition supplements for eye pathologies is based largely on the use of appropriate animal models, together with defined dietary supplementation. Here, C57BL6 mice were subretinally injected with polyethylene glycol (PEG)-400, an established model of retinal degeneration with a dry age-related macular degeneration (AMD)-like phenotype, an eye pathology that lacks treatment. In response to PEG-400, markers of the complement system, angiogenesis, inflammation, gliosis, and macrophage infiltration were upregulated in both retinas and retinal pigment epithelium (RPE)/choroids, whereas dietary supplementation with a mixture based on fatty acids counteracted their upregulation. Major effects include a reduction of inflammation, in both retinas and RPE/choroids, and an inhibition of macrophage infiltration in the choroid, yet not in the retina, suggesting a targeted action through the choroidal vasculature. Histological analysis revealed a thinning of the outer nuclear layer (ONL), together with dysregulation of the epithelium layer in response to PEG-400. In addition, immunohistofluorescence demonstrated Müller cell gliosis and macrophage infiltration into subretinal tissues supporting the molecular findings. Reduced ONL thickness, gliosis, and macrophage infiltration were counteracted by the diet supplement. The present data suggest that fatty acids may represent a useful form of diet supplementation to prevent or limit the progression of dry AMD. PMID:28961167

Evaluation of efficacy of heartworm preventive products at the FDA.

PubMed

Hampshire, Victoria A

2005-10-24

The Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA/CVM) has authority under the United States Code 21 under Section 514.80 to monitor for adverse experiences of approved animal products. Although veterinarians voluntarily report suspect drug-related events to manufacturers, firms that market FDA-approved animal products must report serious events to the FDA within 15 working days of the veterinarian or pet-owner's call to them. Under the present regulations, canine heartworm preventatives are approved for 100% efficacy after testing in laboratory and field conditions. The report of lack of efficacy against heartworm larvae is a serious adverse drug event because the resulting condition or the treatment of the condition is life threatening. Information on lack of effect that are deemed possibly, probably, or definitely drug-related available for review under generic product on the FDA/CVM website Surveillance of these reports indicates there are some failures for virtually all heartworm prevention product categories. Most failures have been reported in heartworm-endemic states. At this time, it is unclear whether these are representative of the rare occurrences of failure that have been in existence for a long time, but not reported regularly or promptly, or whether there is a true increase in complaints of ineffectiveness and real variability between products. This paper discusses methods, personnel, and procedures in place in the Division of Surveillance that will aid the FDA to better assess heartworm preventive treatment failures. It discusses scoring paradigms presently utilized by FDA/CVM to assess severity of complaints of lack of efficacy against heartworms, and welcomes audience input as to how to improve existing processes. Results suggest that more comprehensive reporting will provide FDA/CVM more accurate surveillance information regarding efficacy problems. Such practices will permit FDA/CVM to better interpret both incidence and

Some Non-FDA Approved Uses for Neuromodulation: A Review of the Evidence.

PubMed

Lee, Samuel; Abd-Elsayed, Alaa

2016-09-01

Neuromodulation, including spinal cord stimulation and peripheral nerve field stimulation, has been used with success in treating several painful conditions. The FDA approved the use of neuromodulation for a few indications. We review evidence for neuromodulation in treating some important painful conditions that are not currently FDA approved. This review included an online web search for only clinical trials testing the efficacy of neuromodulation in treating coronary artery disease, peripheral vascular disease (PVD), headache, and peripheral field stimulation. Our systematic literature search found 10, 6, and 3 controlled studies relating to coronary artery disease, PVD, and headache, respectively. Our review also included 5 noncontrolled studies relating to peripheral field stimulation, as no controlled studies had been completed. This review article shows compelling evidence based on clinical trials that neuromodulation can be of benefit for patients with serious painful conditions that are not currently approved by the FDA. © 2015 World Institute of Pain.

The European Medicines Agency's approval of new medicines for type 2 diabetes.

PubMed

Blind, Eberhard; Janssen, Heidi; Dunder, Kristina; de Graeff, Pieter A

2018-05-08

Since 2005, more than 40 new medicines for the treatment of type 2 diabetes have been introduced on the market. These consist of 15 new active substances establishing three new classes of non-insulin products, and several new or modified insulin products and combinations. The approval of these products in Europe is regulated via the centralized procedure at the European Medicines Agency. Demonstration of benefit with regard to improved glucose control remains the principal outcome required from confirmatory studies to demonstrate efficacy. For the majority of these new medicines approved since 2005, cardiovascular outcome trials have now been completed, and have invariably supported the cardiovascular safety of these products. In some of these trials additional important benefits have been observed, for instance, a reduction in major adverse cardiovascular events and improvement of renal outcome. The existing regulatory framework and the continuous adaption of regulatory requirements to emerging developments will continue to guide the approval of new products in the future. © 2018 John Wiley & Sons Ltd.

Evaluation of the efficacy of Ajuga decumbens extract supplement in individuals with knee discomfort associated with physical activity: A randomized, double-blind, placebo-controlled study

PubMed Central

Sawada, Yoko; Sugimoto, Atsushi; Hananouchi, Takehito; Sato, Norimasa; Nagaoka, Isao

2017-01-01

The aim of the present study was to assess the efficacy and safety of the oral administration of Ajuga decumbens extract (ADE) supplement to individuals with knee discomfort associated with physical activity. A randomized, double-blind, placebo-controlled study was conducted using 48 subjects. The subjects were randomly allocated to an ADE diet group (oral administration of ADE-containing diet, n=24) or a placebo group (n=24), and the intervention was conducted for 12 weeks. A total of 22 subjects in the placebo group and 22 subjects in the ADE diet group were assessed to be eligible for assessment of the efficacy of supplement. Knee function was assessed by changes in the scores of the Japanese Knee Osteoarthritis Measure (JKOM) questionnaire and the scores of the Japan Orthopedic Association (JOA) criteria, as well as by analyzing the levels of type II collagen synthesis and degradation biomarkers (procollagen II C-terminal propeptide, cross-linked C-telopeptide of type II collagen, collagen type II cleavage and matrix metalloproteinase-13). Outcomes were measured at the baseline and at 4, 8 and 12 weeks from the start of administration. Subscale II (joint flexion/stiffness) of the JOA criteria was markedly improved in the ADE diet group compared with the placebo group at 8 and 12 weeks during the intervention. Furthermore, in the subgroup analyses using subjects with mild knee discomfort, subscale II (pain/stiffness) and IV (general activities) scores of JKOM were significantly improved (P<0.05) and total JKOM score was markedly improved in the ADE diet group compared with the placebo group at week 8 of the intervention. No adverse effects were identified for the administration of ADE. In conclusion, these observations suggest that the administration of an ADE-containing diet is safe and improves joint function (flexion and stiffness) and general activity in subjects with mild knee discomfort. Therefore, ADE could be a promising candidate as a functional food

Production test IP-376-D, Supplement B Irradiation of MGCR-HDR-3 Test Element

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baars, R.E.

The objective of this supplement to PT-IP-376-D, Irradiation of MGCR-HDR-3 Test Element is to authorize 1000 hours of operation at a maximum test specimen surface temperature of 1700 F. The original production test authorized a test duration of four months at a maximum specimen surface temperature of 1500 F; supplement A authorized extension of the test duration to ten months. The desired increase in surface temperature is requested to demonstrate the general feasibility of operation of the fuel element at 1700 F, and to obtain specific information on the performance of Hastelloy-X cladding and fuel bodies. The increased temperature hasmore » been approved by the Atomic Energy Commission.« less

Chromium Supplementation Improves Glucose Tolerance in Diabetic Goto-Kakizaki Rats

PubMed Central

Abdourahman, Aicha; Edwards, John G.

2016-01-01

Summary Chromium supplementation (Cr) may be useful in the management of diabetes and appears to improve some aspects of glucose handling. However, several studies have used either high doses of Cr supplementation or have placed control animals on a Cr-deficient diet. We therefore wanted to test whether Cr dosages in the ranges that more closely approximate recommended levels of supplementation in humans are efficacious in glycemic control under normal dietary conditions. Euglycemic Wistar or diabetic Goto-Kakizaki (GK) rats (a model of nonobese NIDDM) were assigned to water (control) or chromium picolinate (Cr-P) supplementation (1 or 10 mg/kg/day) groups for up to 32 weeks. Glucose tolerance was tested following an overnight fast by injecting sterile glucose (1.0 g/kg, i.p.) and then measuring blood glucose at select times to determine the sensitivity to glucose by calculation of the area under the curve. Cr-P did not significantly alter the growth of the animals. In the euglycemic Wistar rats, Cr-P supplementation did not alter the response to a glucose tolerance test. In the GK rats, Cr-P supplementation significantly improved glucose tolerance at both levels of Cr-P supplementation (1 mg/kg/day: H20; 100 ± 11%; Cr-P 70 6 8%; 10 mg/kg/day: H20; 100 ± 10%; Cr-P 66 ± 9 %). Cr-P supplementation produced a small improvement in some indices of glycemic control. There were no differences observed for the two levels of Cr-P supplementation suggested that we did not identify a threshold for Cr-P effects, and future studies may use lower doses to find a threshold effect for improving glucose tolerance in diabetics. PMID:18629917

The marketing of dietary supplements in North America: the emperor is (almost) naked.

PubMed

Temple, Norman J

2010-07-01

Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail ("junk mail"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.

Glycerophospholipid Supplementation as a Potential Intervention for Supporting Cerebral Structure in Older Adults

PubMed Central

Reddan, Jeffery M.; White, David J.; Macpherson, Helen; Scholey, Andrew; Pipingas, Andrew

2018-01-01

Modifying nutritional intake through supplementation may be efficacious for altering the trajectory of cerebral structural decline evident with increasing age. To date, there have been a number of clinical trials in older adults whereby chronic supplementation with B vitamins, omega-3 fatty acids, or resveratrol, has been observed to either slow the rate of decline or repair cerebral tissue. There is also some evidence from animal studies indicating that supplementation with glycerophospholipids (GPL) may benefit cerebral structure, though these effects have not yet been investigated in adult humans. Despite this paucity of research, there are a number of factors predicting poorer cerebral structure in older humans, which GPL supplementation appears to beneficially modify or protect against. These include elevated concentrations of homocysteine, unbalanced activity of reactive oxygen species both increasing the risk of oxidative stress, increased concentrations of pro-inflammatory messengers, as well as poorer cardio- and cerebrovascular function. As such, it is hypothesized that GPL supplementation will support cerebral structure in older adults. These cerebral effects may influence cognitive function. The current review aims to provide a theoretical basis for future clinical trials investigating the effects of GPL supplementation on cerebral structural integrity in older adults. PMID:29563868

42 CFR 84.30 - Certificates of approval; scope of approval.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Certificates of approval; scope of approval. 84.30 Section 84.30 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Approval and...

42 CFR 84.30 - Certificates of approval; scope of approval.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Certificates of approval; scope of approval. 84.30 Section 84.30 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Approval and...

42 CFR 84.30 - Certificates of approval; scope of approval.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Certificates of approval; scope of approval. 84.30 Section 84.30 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Approval and...

42 CFR 84.30 - Certificates of approval; scope of approval.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Certificates of approval; scope of approval. 84.30 Section 84.30 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Approval and...

42 CFR 84.30 - Certificates of approval; scope of approval.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Certificates of approval; scope of approval. 84.30 Section 84.30 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Approval and...

The impact of highly concentrated Mo and Cu dietary supplements, fed as a bolus, on the efficacy of chelated versus inorganic Cu in cattle on a low-Cu diet.

PubMed

Grace, N D; West, D M; Smith, S L; Knowles, S O

2013-11-01

To compare the efficacy of chelated versus inorganic forms of dietary Cu supplements, fed as a bolus, when challenged by a daily bolus of dietary Mo in cattle on a low-Cu diet. Forty non-lactating, Friesian dairy cows of adequate Cu status were assigned to four groups and fed a basal diet of baled silage containing 5.3 mg Cu and 0.4 mg Mo/kg DM. The experimental design was a factorial of two chemical forms of supplemental Cu and two levels of Mo intake, provided as pelleted grain supplements made from crushed barley/molasses plus Cu and Mo. The supplements contained 140 mg Cu/kg as Cu sulphate pentahydrate (CS), 140 mg Cu/kg as Cu glycinate (CG), CS plus 38 mg Mo/kg as sodium molybdate (CS+Mo), or CG plus 38 mg Mo/kg (CG+Mo). Commencing on Day 0, supplements were fed once daily (offered 1-1.2 kg/cow) and were completely consumed within 5-10 minutes, which constitutes a bolus type of administration. Liver samples were collected by biopsy at Days -24, 13, 41 or 47, and 69 for Cu determinations. The diets fed to the Cu+Mo groups were roughly equivalent to 25 mg Cu and 5.7 mg Mo/kg DM. Mean initial concentration of Cu in liver for all groups was 516 (SE 54) μmol Cu/kg fresh tissue. In cows supplemented with CS and CG, the final (Day 69) concentrations increased (p<0.01) to 939 (SE 166) and 853 (SE 163) μmol Cu/kg, respectively. These values were not different (p=0.72). For groups CS+Mo and CG+Mo, the final concentrations of 535 (SE 122) and 453 (SE 102) μmol Cu/kg were not different from initial values or from each other (p>0.25). The rate of accumulation of Cu in liver following bolus Cu and Mo intake was highly variable but was not affected by initial concentration of Cu in liver (p>0.9) or by the form of Cu (p>0.6). Mean rates of accumulation of Cu in liver were 4.0 (SD 3.8) and 0.65 (SD 2.0) μmol Cu/kg fresh tissue/day for the Cu-only treatments and the Cu+Mo treatments, respectively. When fed together as a bolus, high Mo intake negated the effect

49 CFR 451.13 - Action by approval authority-approval by design type.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) COAST GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.13 Action by approval authority-approval by design type. (a) The... of safety approval plates to the containers. Absence of individual inspections will not relieve the...

49 CFR 451.13 - Action by approval authority-approval by design type.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) COAST GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.13 Action by approval authority-approval by design type. (a) The... of safety approval plates to the containers. Absence of individual inspections will not relieve the...

49 CFR 451.13 - Action by approval authority-approval by design type.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) COAST GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.13 Action by approval authority-approval by design type. (a) The... of safety approval plates to the containers. Absence of individual inspections will not relieve the...

49 CFR 451.13 - Action by approval authority-approval by design type.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) COAST GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.13 Action by approval authority-approval by design type. (a) The... of safety approval plates to the containers. Absence of individual inspections will not relieve the...

49 CFR 451.13 - Action by approval authority-approval by design type.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) COAST GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS TESTING AND APPROVAL OF CONTAINERS Approval of New Containers § 451.13 Action by approval authority-approval by design type. (a) The... of safety approval plates to the containers. Absence of individual inspections will not relieve the...

New antirheumatic drugs: any real added value? A critical overview of regulatory criteria for their marketing approval.

PubMed

Bertele', Vittorio; Assisi, Alessandro; Di Muzio, Valeria; Renzo, Danila; Garattini, Silvio

2007-09-01

Rheumatoid arthritis (RA) is a systemic autoimmune disorder causing chronic polyarticular synovial inflammation and progressive joint damage. New anti-rheumatic drugs, such as leflunomide, infliximab, etanercept, adalimumab and anakinra, have recently become available. The aim of this paper is to summarize and critically evaluate the type of studies and clinical endpoints accepted by the European Medicines Agency (EMEA) to approve these new drugs. Information regarding the approval of antirheumatic drugs was obtained from European Public Assessment Reports (EPARs) and published pivotal studies. Leflunomide is the only non-biological disease-modifying anti-rheumatic drug (DMARD) to receive recent approval for RA treatment, but strong evidence of its superiority over conventional therapies is lacking. Anakinra in combination with methotrexate received approval as a DMARD for RA on the basis of two pivotal trials in which American College of Rheumatology response criteria (ACR 20 response) were used as the sole primary endpoint. For easier demonstration of efficacy, studies leading to first approval of etanercept, infliximab and adalimumab were carried out on non-responders to DMARDs. Once on the market, these drugs gained an extension of the indication to methotrexate-naïve patients. Studies that provided the basis for approval were not adequately designed, given the lack of an active control and the choice of ACR response as the only clinical endpoint. Consequently, only a weak proof of efficacy emerged for the treatment of signs and symptoms of RA, and these drugs failed to show real benefit in slowing radiographic progression. Serious infections, changes in blood cell counts, severe skin and hepatic infections were the main adverse events that emerged from the clinical studies. Therefore, the unconvincing benefit of the new antirheumatic drugs can scarcely outweigh the risk associated with their use. Moreover, the monthly costs in Italy of the new biological

U.S. Food and Drug Administration approval summary: Eltrombopag for the treatment of pediatric patients with chronic immune (idiopathic) thrombocytopenia.

PubMed

Ehrlich, Lori A; Kwitkowski, Virginia E; Reaman, Gregory; Ko, Chia-Wen; Nie, Lei; Pazdur, Richard; Farrell, Ann T

2017-12-01

The U.S. Food and Drug Administration (FDA) approved eltrombopag for pediatric patients with chronic immune (idiopathic) thrombocytopenia (ITP) ages ≥6 on June 11, 2015, and ages ≥1 on August 24, 2015. Approval was based on the FDA review of two randomized trials that included 159 pediatric patients with chronic ITP who had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. This manuscript describes the basis for approval of these applications. The FDA concluded that eltrombopag has shown efficacy and a favorable benefit to risk profile for pediatric patients with chronic ITP. © 2017 Wiley Periodicals, Inc.

International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine.

PubMed

Kreider, Richard B; Kalman, Douglas S; Antonio, Jose; Ziegenfuss, Tim N; Wildman, Robert; Collins, Rick; Candow, Darren G; Kleiner, Susan M; Almada, Anthony L; Lopez, Hector L

2017-01-01

Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson's, Huntington's disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy. These studies provide a large body of evidence that creatine can not only improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing rehabilitation from injuries, and helping athletes tolerate heavy training loads. Additionally, researchers have identified a number of potentially beneficial clinical uses of creatine supplementation. These studies show that short and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals and in a number of patient populations ranging from infants to the elderly. Moreover, significant health benefits may be provided by ensuring habitual low dietary creatine ingestion (e.g., 3 g/day) throughout the lifespan. The purpose of this review is to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition (ISSN).

Use of Vitamins and Dietary Supplements by Patients With Multiple Sclerosis: A Review.

PubMed

Evans, Emily; Piccio, Laura; Cross, Anne H

2018-04-23

Surveys of patients with multiple sclerosis report that most are interested in modifying their diet and using supplements to potentially reduce the severity and symptoms of the disease. This review provides an updated overview of the current state of evidence for the role that vitamins and dietary supplements play in multiple sclerosis and its animal models, with an emphasis on recent studies, and addresses biological plausibility and safety issues. Several vitamins and dietary supplements have been recently explored both in animal models and by patients with multiple sclerosis. Most human trials have been small or nonblinded, limiting their generalizability. Biotin and vitamin D are currently being tested in large randomized clinical trials. Smaller trials are ongoing or planned for other supplements such as lipoic acid and probiotics. The results of these studies may help guide clinical recommendations. At the present time, the only vitamin with sufficient evidence to support routine supplementation for patients with multiple sclerosis is vitamin D. Vitamin deficiencies should be avoided. It is important for clinicians to know which supplements their patients are taking and to educate patients on any known efficacy data, along with any potential medication interactions and adverse effects of individual supplements. Given that dietary supplements and vitamins are not subject to the same regulatory oversight as prescription pharmaceuticals in the United States, it is recommended that vitamins and supplements be purchased from reputable manufacturers with the United States Pharmacopeia designation.

[A new method for safety monitoring of natural dietary supplements--quality profile].

PubMed

Wang, Juan; Wang, Li-Ping; Yang, Da-Jin; Chen, Bo

2008-07-01

A new method for safety monitoring of natural dietary supplements--quality profile was proposed. It would convert passive monitoring of synthetic drug to active, and guarantee the security of natural dietary supplements. Preliminary research on quality profile was completed by high performance liquid chromatography (HPLC) and mass spectrometry (MS). HPLC was employed to analyze chemical constituent profiles of natural dietary supplements. The separation was completed on C18 column with acetonitrile and water (0.05% H3PO4) as mobile phase, the detection wavelength was 223 nm. Based on HPLC, stability of quality profile had been studied, and abnormal compounds in quality profile had been analyzed after addition of phenolphthalein, sibutramine, rosiglitazone, glibenclamide and gliclazide. And by MS, detector worked with ESI +, capillary voltage: 3.5 kV, cone voltage: 30 V, extractor voltage: 4 V, RF lens voltage: 0.5 V, source temperature: 105 degrees C, desolvation temperature: 300 degrees C, desolvation gas flow rate: 260 L/h, cone gas flow rate: 50 L/h, full scan mass spectra: m/z 100-600. Abnormal compound in quality profile had been analyzed after addition of N-mono-desmethyl sibutramine. Quality profile based on HPLC had good stability (Similarity > 0.877). Addition of phenolphthalein, sibutramine, rosiglitazone, glibenclamide and gliclazide in natural dietary supplements could be reflected by HPLC, and addition of N-mono-desmethyl sibutramine in natural dietary supplements could be reflected by MS. Quality profile might monitor adulteration of natural dietary supplements, and prevent addition of synthetic drug after "approval".

Valbenazine as the first and only approved treatment for adults with tardive dyskinesia.

PubMed

Sarva, Harini; Henchcliffe, Claire

2018-03-01

Valbenazine is a selective VMAT2 inhibitor that the FDA approved in April 2017 for the specific treatment of tardive dyskinesia (TD), a movement disorder commonly caused by dopamine blocking agents. Valbenazine acts to decrease dopamine release, reducing excessive movement found in TD. Areas covered: This drug profile reviews the development of valbenazine and the clinical trials that led to its approval as the first treatment specific to TD. The literature search was performed with the PubMed online database. Expert commentary: Two clinical trials assessing the efficacy of valbenazine have shown the reduction of antipsychotic-induced involuntary movement. No life threatening adverse effects were found. Data from a 42-week extension study demonstrated sustained response.

An evidence-based review of commonly used dietary supplements.

PubMed

Laird, John

2015-07-01

Use of complementary and alternative medicine (CAM) is increasing in the United States. Physician assistants need to know about the efficacy of CAM therapies if they practice integrative medicine (which combines CAM and traditional therapies), recommend a CAM therapy occasionally as part of their treatment plan, refer patients to CAM providers, or have patients who self-select CAM therapies. This article describes integrative medicine and reviews the most commonly used dietary supplements.

Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable.

PubMed

Fisher, Marc; Albers, Gregory W; Donnan, Geoffrey A; Furlan, Anthony J; Grotta, James C; Kidwell, Chelsea S; Sacco, Ralph L; Wechsler, Lawrence R

2005-08-01

Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval. The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed. The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.

TEDS-M 2008 User Guide for the International Database. Supplement 2: National Adaptations of the TEDS-M Questionnaires

ERIC Educational Resources Information Center

Brese, Falk, Ed.

2012-01-01

This supplement contains all adaptations made by countries to the international version of the TEDS-M questionnaires under careful supervision of and approval by the TEDS-M International Study Center at Michigan State University. This information provides users of the TEDS-M International Database with a guide to evaluate the availability of…

Vitamin B supplementation for diabetic peripheral neuropathy.

PubMed

Jayabalan, Bhavani; Low, Lian Leng

2016-02-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. Copyright © Singapore Medical Association.

Vitamin B supplementation for diabetic peripheral neuropathy

PubMed Central

Jayabalan, Bhavani; Low, Lian Leng

2016-01-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. PMID:26892473

Protein supplementation in U.S. military personnel.

PubMed

Pasiakos, Stefan M; Montain, Scott J; Young, Andrew J

2013-11-01

Protein supplements (PSs) are, after multivitamins, the most frequently consumed dietary supplement by U.S. military personnel. Warfighters believe that PSs will improve health, promote muscle strength, and enhance physical performance. The estimated prevalence of regular PS use by military personnel is nearly 20% or more in active-duty personnel, which is comparable to collegiate athletes and recreationally active adults, but higher than that for average U.S. civilians. Although the acute metabolic effects of PS ingestion are well described, little is known regarding the benefits of PS use by warfighters in response to the metabolic demands of military operations. When dietary protein intake approaches 1.5 g · kg(-1) · d(-1), and energy intake matches energy expenditure, the use of PSs by most physically active military personnel may not be necessary. However, dismounted infantry often perform operations consisting of long periods of strenuous physical activity coupled with inadequate dietary energy and protein intake. In these situations, the use of PSs may have efficacy for preserving fat-free mass. This article reviews the available literature regarding the prevalence of PS use among military personnel. Furthermore, it highlights the unique metabolic stressors affecting U.S. military personnel and discusses potential conditions during which protein supplementation might be beneficial.

Evaluating Supplemental Educational Service Providers: Suggested Strategies for States. A Guidebook Prepared for the Center on Innovation & Improvement. Second Edition

ERIC Educational Resources Information Center

Ross, Steven M.; Potter, Allison; Harmon, Jennifer

2006-01-01

This second edition of the Guidebook is designed to help state educational agencies (SEAs) create an effective system to evaluate state-approved supplemental educational service (SES) providers. The text includes tools and strategies that will help readers determine evaluation measures, identify possible evaluation methodologies, and address the…

[Isoflavone-containing dietary supplements].

PubMed

Lehmann, Leane; Soukup, Sebastian T; Gerhäuser, Clarissa; Vollmer, Günter; Kulling, Sabine E

2017-03-01

Isoflavones (IFs) from soy and other legumes have weak estrogenic properties. Isolated IFs are available as dietary supplements and advertised to alleviate symptoms of menopause. The present chapter provides an overview of the occurrence, the chemical structure of IFs and their metabolites, the market situation and reviews the current evidence on the efficacy and safety of IF-containing dietary supplements.The biological effectiveness of IFs is attributable to the activation of the estrogen receptor (ER). Studies on the influence of IFs on endogenous estrogen levels in women show inconsistent results. So far, the European Food Safety Authority (EFSA) has rejected all submitted health claims for IFs due to insufficient scientific evidence for any of the postulated health effects. Based on the results of their recent risk assessment, the EFSA concluded that the available human studies did not support the hypothesis of adverse effects of isolated IFs on the human mammary gland, uterus or thyroid in healthy postmenopausal women. However, the assessment does not allow a general statement on the safety of IF-containing dietary supplements. Studies in animal models are often not comparable with the complex interactions in humans due to differences in the metabolism of IFs, in the developmental stage at time of consumption and in the temporarily restricted uptake of IFs during certain stages of life. So far, for none of the advertised functions is unequivocal scientific evidence available. On the basis of available data, potential unwanted side effects cannot be fully excluded. This holds particularly true for women with undiagnosed diseases, especially for those with undetected precancerous lesions in the mammary gland.

Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels

PubMed Central

Binder, Elke; Bermúdez-Silva, Francisco J.; André, Caroline; Elie, Melissa; Romero-Zerbo, Silvana Y.; Leste-Lasserre, Thierry; Belluomo, llaria; Duchampt, Adeline; Clark, Samantha; Aubert, Agnes; Mezzullo, Marco; Fanelli, Flaminia; Pagotto, Uberto; Layé, Sophie; Mithieux, Gilles; Cota, Daniela

2013-01-01

Background Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed. Methodology/Principal Findings Male C57BL/6J mice were fed chow or a high-fat diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group) was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed. Conclusions/Significance These findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation is lacking in

Dronedarone for the treatment of atrial fibrillation and atrial flutter: approval and efficacy.

PubMed

Wolbrette, Deborah; Gonzalez, Mario; Samii, Soraya; Banchs, Javier; Penny-Peterson, Erica; Naccarelli, Gerald

2010-08-09

Dronedarone, a new Class III antiarrhythmic agent, has now been approved by the US Food and Drug Administration for use in patients with atrial fibrillation or atrial flutter. Approval came in March 2009 due to the positive results of the ATHENA trial showing significant reductions in all-cause mortality and cardiovascular hospitalization with dronedarone use. A post hoc analysis of the ATHENA data also suggested a decrease in stroke risk with this agent. However, due to safety concerns in the heart failure population in the earlier ANDROMEDA trial, dronedarone is not recommended for patients with an ejection fraction <35% and recent decompensated heart failure. Dronedarone is an amiodarone analog with multichannel blocking electrophysiologic properties similar to those of amiodarone, but several structural differences. Dronedarone's lack of the iodine moiety reduces its potential for thyroid and pulmonary toxicity. Preliminary data from the DIONYSOS trial, and an indirect meta-analysis comparing amiodarone with dronedarone, showed amiodarone to be more effective in maintaining sinus rhythm, while dronedarone was associated with fewer adverse effects resulting in early termination of the drug. Dronedarone is the first antiarrhythmic drug for the treatment of atrial fibrillation and atrial flutter shown to reduce cardiovascular hospitalizations. In patients with structural heart disease who have an ejection fraction >35% and no recent decompensated heart failure, dronedarone should be considered earlier than amiodarone in the treatment algorithm.

77 FR 21453 - Approval and Promulgation of Air Quality Implementation Plans; Colorado; Revisions to New Source...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

...EPA is approving those revisions adopted by the State of Colorado on April 16, 2004 to Regulation No. 3 (Stationary Source Permitting and Air Pollutant Emission Notice Requirements) that incorporate EPA's December 31, 2002 NSR Reforms. Colorado submitted the request for approval of these rule revisions into the State Implementation Plan (SIP) on July 11, 2005 and supplemented its request on October 25, 2005. EPA is approving only the portions of Colorado's revisions to Regulation Number 3 that relate to the prevention of significant deterioration (PSD) and non-attainment new source review (NSR) construction permit programs of the State of Colorado. Other revisions, renumberings, additions, or deletions to Regulation No. 3 made by Colorado as part of the April 16, 2004 final rulemaking are being acted on by EPA in a separate final action related to Colorado's Interstate Transport SIP (see proposed action at 76 FR 21835, April 19, 2011). Colorado has a federally approved NSR program for new and modified sources impacting attainment and non-attainment areas in the State. This action is being taken under section 110 of the Clean Air Act (CAA).

Zohydro approval by food and drug administration: controversial or frightening?

PubMed

Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

2014-01-01

consequences, despite numerous regulations enforced by multiple organizations. The approval of Zohydro and its defense from the FDA were based on a misunderstanding of the prevalence of chronic severe disabling pain. Based on inaccurate data from the Institute of Medicine, in part caused by conflicts of interest, 100 million persons have been described to suffer from severe pain - the correct number is 22.6 million. This manuscript analyzes 3 important principles of drug approval and utilization based on safety, efficacy, and medical necessity. Based on the limited literature that the authors were able to review including that which was submitted to the FDA by the manufacturers, it appears the safety, efficacy, and medical necessity were not demonstrated. In fact, the study submitted to the FDA showed a 50% pain improvement in only 48% of the patients in the treatment group and 21% of the patients in the placebo group at 85 day follow-up. This is a statistically significant result but its clinical relevance is unknown. The FDA approval decision occurring against the backdrop of the advisory panel recommendation is concerning and may result in serious consequences in the future.

Effect of soy isoflavone supplementation on nitric oxide metabolism and blood pressure in menopausal women

USDA-ARS?s Scientific Manuscript database

Isoflavones, having chemical structures similar to estrogens, are believed to stimulate nitric oxide production and thus lower blood pressure. The efficacy of soy isoflavone supplementation to stimulate nitric oxide production and lower blood pressure in menopausal women with high normal blood press...

Vitamin C supplementation in pregnancy.

PubMed

Rumbold, Alice; Ota, Erika; Nagata, Chie; Shahrook, Sadequa; Crowther, Caroline A

2015-09-29

Vitamin C supplementation may help reduce the risk of pregnancy complications such as pre-eclampsia, intrauterine growth restriction and maternal anaemia. There is a need to evaluate the efficacy and safety of vitamin C supplementation in pregnancy. To evaluate the effects of vitamin C supplementation, alone or in combination with other separate supplements on pregnancy outcomes, adverse events, side effects and use of health resources. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies. All randomised or quasi-randomised controlled trials evaluating vitamin C supplementation in pregnant women. Interventions using a multivitamin supplement containing vitamin C or where the primary supplement was iron were excluded. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Twenty-nine trials involving 24,300 women are included in this review. Overall, 11 trials were judged to be of low risk of bias, eight were high risk of bias and for 10 trials it was unclear. No clear differences were seen between women supplemented with vitamin C alone or in combination with other supplements compared with placebo or no control for the risk of stillbirth (risk ratio (RR) 1.15, 95% confidence intervals (CI) 0.89 to 1.49; 20,038 participants; 11 studies; I² = 0%; moderate quality evidence), neonatal death (RR 0.79, 95% CI 0.58 to 1.08; 19,575 participants; 11 studies; I² = 0%), perinatal death (average RR 1.07, 95% CI 0.77 to 1.49; 17,105 participants; seven studies; I² = 35%), birthweight (mean difference (MD) 26.88 g, 95% CI -18.81 to 72.58; 17,326 participants; 13 studies; I² = 69%), intrauterine growth restriction (RR 0.98, 95% CI 0.91 to 1.06; 20,361 participants; 12 studies; I² = 15%; high quality evidence), preterm birth (average RR 0.99, 95% CI 0.90 to 1.10; 22,250 participants; 16 studies; I² = 49%; high quality evidence

Androgen Supplementation During Aging: Development of a Physiologically Appropriate Protocol

PubMed Central

Sorwell, Krystina G.; Garyfallou, Vasilios T.; Garten, Jamie; Weiss, Alison; Renner, Laurie; Neuringer, Martha; Kohama, Steven G.

2014-01-01

Abstract Men show an age-related decline in the circulating levels of testosterone (T) and dehydroepiandrosterone sulfate (DHEAS). Consequently, there is interest in developing androgen supplementation paradigms for old men that replicate the hormone profiles of young adults. In the present study, we used old (21–26 years old) male rhesus monkeys as a model to examine the efficacy of an androgen supplementation paradigm that comprised oral T administration (12 mg/kg body weight, dissolved in sesame oil/chocolate) in the evening, and two oral DHEA administrations, 3 hr apart (0.04 mg/kg body weight, dissolved in sesame oil/chocolate) in the morning. After 5 days of repeated hormone supplementation, serial blood samples were remotely collected from each animal hourly across the 24-hr day, and assayed for cortisol, DHEAS, T, 5α-dihydrotestosterone (DHT), estrone (E1), and 17β-estradiol (E2). Following androgen supplementation, T levels were significantly elevated and this was associated with a more sustained nocturnal elevation of T's primary bioactive metabolites, DHT and E1 and E2. Plasma DHEAS levels were also significantly elevated after androgen supplementation; DHEAS levels rose in the early morning and gradually declined during the course of the day, closely mimicking the profiles observed in young adults (7–12 years old); in contrast, cortisol levels were unaltered by the supplementation. Together the data demonstrate a non-invasive androgen supplementation paradigm that restores youthful circulating androgen levels in old male primates. Because this paradigm preserves the natural circulating circadian hormone patterns, we predict that it will produce fewer adverse side effects, such as perturbed sleep or cognitive impairment. PMID:24134213

Predicting intentions to consume functional foods and supplements to offset memory loss using an adaptation of protection motivation theory.

PubMed

Cox, D N; Koster, A; Russell, C G

2004-08-01

The widespread use of dietary supplements and so-called 'functional foods' is thought to be partially motivated by self-control of health. However, whilst consumers want foods associated with well-being or disease prevention, they are unlikely to be willing to compromise on taste or technology. This presents a dilemma for promoters of functional foods. Middle-aged consumers' intentions to consume functional foods or supplements that may improve memory were tested within an adaptation of Protection Motivation theory (PMT). Participants evaluated text descriptions of four products described as: having an unpleasant bitter taste (Natural-FF); having 'additives' to reduce bitterness (Sweetened-FF); being genetically modified to enhance function (GM-FF) and Supplements. Participants were recruited as being of high and low perceived vulnerability to memory failure. In total, 290 middle-aged consumers (aged 40-60 years) participated in the study. Motivations to consume the GM-FF were the lowest. There were gender differences between intention to consume the supplements, Natural-FF and Sweetened-FF and product differences within genders. Women were less favourable than men in their attitudes towards genetic modification in general. Regression analyses indicated that PM predictors of intention to consume functional foods or supplements explained 59-63% of the variance (R2). Overall, perceived 'efficacy' (of the behaviour) and self-efficacy were the most important predictors of intentions to consume.

Efficacy of zinc sulfate supplement on febrile seizure recurrence prevention in children with normal serum zinc level: A randomised clinical trial.

PubMed

Fallah, Razieh; Sabbaghzadegan, Saeideh; Karbasi, Sedighah Akhavan; Binesh, Fariba

2015-01-01

Serum zinc level might be related to pathogenesis of febrile seizure (FS). The purpose of this study was to evaluate efficacy and safety of oral zinc supplementation on FS recurrence prevention in non-zinc-deficient children. In a randomized clinical study, one hundred 18 to 60 mo old children with normal zinc level with first simple FS were referred to Shahid Sadoughi Hospital, Yazd, Iran from May 2012 to June 2013, were randomly assigned to two groups to receive 2 mg/kg/d zinc sulfate for six consecutive months or placebo as control group and were followed up for 1 y for FS recurrence. 41 girls and 59 boys with mean age of 2.47 ± 1.01 y were evaluated. Race, mean weight, height and body fat were similar in both groups. FS recurrence occurred in 19 children (38%) in the control group [95% confidence interval (CI): 19.45%-53.95%] and in 11 children (22%) in the zinc sulfate (95% CI: 57.47%-89.13%) groups, respectively; and the zinc group had lower FS recurrence (P = 0.03). The mean serum zinc level before intervention was lower in children with FS recurrence (72.43 ± 14.58 μg/dL versus 96.33 ± 12.69 μg/dL, P = 0.04). Gastrointestinal side effects (vomiting in five children, heartburn in two children and abdominal pain in one child) were seen in 16% of the zinc group and vomiting occurred in two children (4%) in control group and frequency of adverse events was similar in the two groups (P = 0.1). Zinc supplementation should be considered as effective and safe in prevention of FS recurrence. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of host nutrition on virulence and fitness of entomopathogenic nematodes: Lipid- and protein-based supplements in Tenebrio molitor diets

PubMed Central

Shapiro-Ilan, David; Rojas, M. Guadalupe; Morales-Ramos, Juan A.; Lewis, Edwin E.; Tedders, W. Louis

2008-01-01

Entomopathogenic nematodes, Heterorhabditis indica and Steinernema riobrave, were tested for virulence and reproductive yield in Tenebrio molitor that were fed wheat bran diets with varying lipid- and protein-based supplements. Lipid supplements were based on 20% canola oil, peanut, pork or salmon, or a low lipid control (5% canola). Protein treatments consisted of basic supplement ingredients plus 0, 10, or 20% egg white; a bran-only control was also included. Some diet supplements had positive effects on nematode quality, whereas others had negative or neutral effects. All supplements with 20% lipids except canola oil caused increased T. molitor susceptibility to H. indica, whereas susceptibility to S. riobrave was not affected. Protein supplements did not affect host susceptibility, and neither lipid nor protein diet supplements affected reproductive capacity of either nematode species. Subsequently, we determined the pest control efficacy of progeny of nematodes that had been reared through T. molitor from different diets against Diaprepes abbreviatus and Otiorhynchus sulcatus. All nematode treatments reduced insect survival relative to the control (water only). Nematodes originating from T. molitor diets with the 0% or 20% protein exhibited lower efficacy versus D. abbreviatus than the intermediate level of protein (10%) or bran-only treatments. Nematodes originating from T. molitor lipid or control diets did not differ in virulence. Our research indicates that nutritional content of an insect host diet can affect host susceptibility to entomopathogenic nematodes and nematode fitness; therefore, host media could conceivably be optimized to increase in vivo nematode production efficiency. PMID:19259513

Dietary supplement adverse events: report of a one-year poison center surveillance project.

PubMed

Haller, Christine; Kearney, Tom; Bent, Stephen; Ko, Richard; Benowitz, Neal; Olson, Kent

2008-06-01

The safety and efficacy of dietary supplements is of growing concern to regulators, health-care providers and consumers. Few scientific data exist on clinical effects and potential toxicities of marketed products. Harmful supplements may not be identified for months or years with existing adverse event monitoring mechanisms. Retrospective review of poison center statistics to capture supplement-associated toxicity also has limitations. We collaborated with the FDA Center for Food Safety and Nutrition (CFSAN) to conduct a 1-year prospective surveillance study of dietary supplement-related poison control center calls in 2006. Prompt follow-up of symptomatic cases, laboratory analysis of implicated dietary supplements, and causality assessment by a case review expert panel were performed. Of 275 dietary supplements calls, 41% involved symptomatic exposures; and two-thirds were rated as probably or possibly related to supplement use. Eight adverse events required hospital admission. Sympathomimetic toxicity was most common, with caffeine products accounting for 47%, and yohimbe products accounting for 18% of supplement-related symptomatic cases. Suspected drug-herb interactions occurred in 6 cases, including yohimbe co-ingested with buproprion (1) and methamphetamine (3), and additive anticoagulant/antiplatelet effects of NSAIDs taken with fish oils (1) and ginkgo (1). Laboratory analysis identified a pharmacologically active substance in 4 cases; supplement toxicity was ruled unlikely when analytical testing was negative in 5 cases. Most supplement-related adverse events were minor. Clinically significant toxic effects were most frequently reported with caffeine and yohimbe-containing products. Active surveillance of poison control center reports of dietary supplement adverse events enables rapid detection of potentially harmful products, which may facilitate regulatory oversight.

30 CFR 250.283 - When must I revise or supplement the approved EP, DPP, or DOCD?

Code of Federal Regulations, 2011 CFR

2011-07-01

...); (2) Change the surface location of a well or production platform by a distance more than that specified by the Regional Supervisor; (3) Change the type of production or significantly increase the volume... revise your approved EP, DPP, or DOCD when you propose to: (1) Change the type of drilling rig (e.g...

Motivational interviewing skills are positively associated with nutritionist self-efficacy.

PubMed

Marley, Scott C; Carbonneau, Kira; Lockner, Donna; Kibbe, Debra; Trowbridge, Frederick

2011-01-01

To examine the relationships between physical and social self-concepts, motivational interviewing (MI), and nutrition assessment skills with dimensions of counseling self-efficacy. Cross-sectional survey. Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clinics. Sixty-five WIC nutritionists. Counseling self-efficacy on topics related to physical activity and nutritional behaviors and in the presence of language and cultural differences. Multiple linear regression. Nutritionists' perception of their own MI skills was positively associated with their self-efficacy for counseling clients of a culture different than their own, when counseling about physical activity, and when counseling about nutrition behavior. Hispanic ethnicity and social self-concept were positively associated with counseling self-efficacy when culture differences were present. Physical self-concept was positively associated with self-efficacy related to physical activity topics. Nutrition assessment skill was negatively associated with self-efficacy for working with non-English-speaking clients. Development of MI skills and strategies to improve social and physical self-concept may increase WIC nutritionists' counseling self-efficacy, particularly when counseling clients from diverse backgrounds. Copyright © 2011 Society for Nutrition Education. Published by Elsevier Inc. All rights reserved.

Efficacy of β-mannanase supplementation to corn-soya bean meal-based diets on growth performance, nutrient digestibility, blood urea nitrogen, faecal coliform and lactic acid bacteria and faecal noxious gas emission in growing pigs.

PubMed

Upadhaya, Santi Devi; Park, Jae Won; Lee, Jae Hwan; Kim, In Ho

2016-01-01

A study was conducted to determine the efficacy of β-mannanase supplementation to a diet based on corn and soya bean meal (SBM) on growth performance, nutrient digestibility, blood urea nitrogen (BUN), faecal coliforms and lactic acid bacteria, and noxious gas emission in growing pigs. A total of 140 pigs [(Landrace × Yorkshire) × Duroc; average body weight 25 ± 3 kg] were randomly allotted to a 2 × 2 factorial arrangement with dietary treatments consisting of hulled or dehulled SBM without or with supplementation of 400 U β-mannanase/kg. During the 6 weeks of experimental feeding, β-mannanase supplementation had no effect on body weight gain, feed intake and gain:feed (G:F) ratio. Compared with dehulled SBM, feeding hulled SBM caused an increased feed intake of pigs in the entire trial (p = 0.05). The G:F ratio was improved in pigs receiving dehulled SBM (p < 0.05). Dietary treatments did not influence the total tract digestibility of dry matter, nitrogen and gross energy. Enzyme supplementation reduced (p < 0.05) the population of faecal coliforms and tended to reduce the NH3 concentration after 24 h of fermentation in a closed box containing faecal slurry. Feeding hulled SBM tended to reduce NH3 emission on days 3 and 5 of fermentation. In conclusion, mannanase supplementation had no influence on growth performance and nutrient digestibility but showed a positive effect on reducing coliform population and tended to reduce NH3 emission. Dehulled SBM increased G:F ratio and hulled SBM tended to reduce NH3 emission.

Psychology of Supplementation in Sport and Exercise: Motivational Antecedents and Biobehavioral Outcomes

NASA Astrophysics Data System (ADS)

Lutz, Rafer; Arent, Shawn

Research concerning the physiological and biobehavioral effects of supplements commonly used in sport or exercise settings has multiplied rapidly over the last decade. However, less attention has been directed to understanding the motivational pathways leading to sport and exercise supplement use. This chapter summarizes known usage rates for sport/fitness supplements and describes motivational theories and constructs that may be of use for understanding individuals' use of these substances. In this respect, we contend that researchers should consider behavioral approaches, the theory of planned behavior, balance theory, achievement goal theory, social physique anxiety, and muscle dysmorphia as useful for developing an understanding of the psychological influences on supplement use. For some of the latter theories/constructs, research has already shown support for their explanatory abilities, whereas research is scant and the utility for understanding sport/exercise supplement use is yet to be determined for many of the theories. In addition to describing the motivation behind supplement use, this chapter summarizes the biobehavioral effects of a select group of supplements commonly used to improve performance, fitness, or health. Specifically, we consider psychobiological effects of caffeine, creatine, Ginkgo biloba, and St. John's wort related to enhanced arousal, improved memory and cognition, enhanced brain function and protection, and reduced depression. There is promising initial evidence for the efficacy of these compounds in producing favorable psychological outcomes, although certain shortcomings of many studies on these compounds must be taken into account before reaching definitive conclusions.

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis

PubMed Central

Chen, Zhe; Zhang, Lingli; Zeng, Linan; Yang, Xiaoyan; Jiang, Lucan; Gui, Ge; Zhang, Zuojie

2017-01-01

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4–15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice. Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect. Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: −18.05, 95% CI (−25.51, −10.58), P < 0.00001], 5day [MD: -23.49, 95% CI (−32.80, −14.18), P < 0.00001], 7day [MD: −33.01, 95% CI (−37.31, −28.70), P < 0.00001] treatment, but also decreased time of jaundice fading [MD: −1.91, 95% CI (−2.06, −1.75), P < 0.00001], as well as

The Effects of Magnesium Supplementation on Subjective Anxiety and Stress—A Systematic Review

PubMed Central

Boyle, Neil Bernard; Lawton, Clare; Dye, Louise

2017-01-01

Background: Anxiety related conditions are the most common affective disorders present in the general population with a lifetime prevalence of over 15%. Magnesium (Mg) status is associated with subjective anxiety, leading to the proposition that Mg supplementation may attenuate anxiety symptoms. This systematic review examines the available evidence for the efficacy of Mg supplementation in the alleviation of subjective measures of anxiety and stress. Methods: A systematic search of interventions with Mg alone or in combination (up to 5 additional ingredients) was performed in May 2016. Ovid Medline, PsychInfo, Embase, CINAHL and Cochrane databases were searched using equivalent search terms. A grey literature review of relevant sources was also undertaken. Results: 18 studies were included in the review. All reviewed studies recruited samples based upon an existing vulnerability to anxiety: mildly anxious, premenstrual syndrome (PMS), postpartum status, and hypertension. Four/eight studies in anxious samples, four/seven studies in PMS samples, and one/two studies in hypertensive samples reported positive effects of Mg on subjective anxiety outcomes. Mg had no effect on postpartum anxiety. No study administered a validated measure of subjective stress as an outcome. Conclusions: Existing evidence is suggestive of a beneficial effect of Mg on subjective anxiety in anxiety vulnerable samples. However, the quality of the existing evidence is poor. Well-designed randomised controlled trials are required to further confirm the efficacy of Mg supplementation. PMID:28445426

The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review.

PubMed

Boyle, Neil Bernard; Lawton, Clare; Dye, Louise

2017-04-26

Anxiety related conditions are the most common affective disorders present in the general population with a lifetime prevalence of over 15%. Magnesium (Mg) status is associated with subjective anxiety, leading to the proposition that Mg supplementation may attenuate anxiety symptoms. This systematic review examines the available evidence for the efficacy of Mg supplementation in the alleviation of subjective measures of anxiety and stress. A systematic search of interventions with Mg alone or in combination (up to 5 additional ingredients) was performed in May 2016. Ovid Medline, PsychInfo, Embase, CINAHL and Cochrane databases were searched using equivalent search terms. A grey literature review of relevant sources was also undertaken. 18 studies were included in the review. All reviewed studies recruited samples based upon an existing vulnerability to anxiety: mildly anxious, premenstrual syndrome (PMS), postpartum status, and hypertension. Four/eight studies in anxious samples, four/seven studies in PMS samples, and one/two studies in hypertensive samples reported positive effects of Mg on subjective anxiety outcomes. Mg had no effect on postpartum anxiety. No study administered a validated measure of subjective stress as an outcome. Existing evidence is suggestive of a beneficial effect of Mg on subjective anxiety in anxiety vulnerable samples. However, the quality of the existing evidence is poor. Well-designed randomised controlled trials are required to further confirm the efficacy of Mg supplementation.

Identification and quantification of vinpocetine and picamilon in dietary supplements sold in the United States.

PubMed

Avula, Bharathi; Chittiboyina, Amar G; Sagi, Satyanarayanaraju; Wang, Yan-Hong; Wang, Mei; Khan, Ikhlas A; Cohen, Pieter A

2016-01-01

Vinpocetine and picamilon are drugs prescribed in many countries to treat a variety of cerebrovascular disorders. In the United States, vinpocetine and picamilon have never been approved by the US Food and Drug Administration, but they are both available for sale directly to consumers as dietary supplements. We designed our study to determine the accuracy of supplement labels with regard to the presence and quantity of vinpocetine and picamilon. A validated ultra-high performance liquid chromatography-photodiode-array method was developed for the quantification of vinpocetine and picamilon. The separation was achieved using a reversed phase (C-18) column, photodiode array detection, and water/acetonitrile as the mobile phase. Vinpocetine and picamilon were detected at concentrations as low as 10 and 50 ng/mL, respectively. The presence of vinpocetine and picamilon was confirmed using reference standards. Twenty-three supplements labelled as containing vinpocetine were available for sale at two large supplement retail chains; 17 contained vinpocetine with quantities ranging from 0.3 to 32 mg per recommended daily serving. No vinpocetine was detected in six of the sampled supplements. The supplement label implied that vinpocetine was a constituent of lesser periwinkle in three of the supplements. Of the 31 picamilon supplements available for sale from a variety of retailers: 30 contained picamilon in quantities ranging from 2.7 to 721.5 mg per recommended daily serving. We found that consumers cannot obtain accurate information from supplement labels regarding the presence or quantity of vinpocetine and picamilon. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

The art and science of choosing efficacy endpoints for rare disease clinical trials.

PubMed

Cox, Gerald F

2018-04-01

An important challenge in rare disease clinical trials is to demonstrate a clinically meaningful and statistically significant response to treatment. Selecting the most appropriate and sensitive efficacy endpoints for a treatment trial is part art and part science. The types of endpoints should align with the stage of development (e.g., proof of concept vs. confirmation of clinical efficacy). The patient characteristics and disease stage should reflect the treatment goal of improving disease manifestations or preventing disease progression. For rare diseases, regulatory approval requires demonstration of clinical benefit, defined as how a patient, feels, functions, or survives, in at least one adequate and well-controlled pivotal study conducted according to Good Clinical Practice. In some cases, full regulatory approval can occur using a validated surrogate biomarker, while accelerated, or provisional, approval can occur using a biomarker that is likely to predict clinical benefit. Rare disease studies are small by necessity and require the use of endpoints with large effect sizes to demonstrate statistical significance. Understanding the quantitative factors that determine effect size and its impact on powering the study with an adequate sample size is key to the successful choice of endpoints. Interpreting the clinical meaningfulness of an observed change in an efficacy endpoint can be justified by statistical methods, regulatory precedence, and clinical context. Heterogeneous diseases that affect multiple organ systems may be better accommodated by endpoints that assess mean change across multiple endpoints within the same patient rather than mean change in an individual endpoint across all patients. © 2018 Wiley Periodicals, Inc.

Nutritional supplements for diabetes sold on the internet: business or health promotion?

PubMed

Covolo, Loredana; Capelli, Michela; Ceretti, Elisabetta; Feretti, Donatella; Caimi, Luigi; Gelatti, Umberto

2013-08-26

Diabetes is one of the most widespread chronic disease. Although many medications are available for the treatment and prevention of diabetes, many people turn to nutritional supplements (NSs). In these years, the online sales have contributed to the growth of use of nutritional supplement. The aim of the research was to investigate the type of information provided by sales websites on NSs, and analyse the existence of scientific evidence about some of the most common ingredients found in available NSs for diabetes. A web search was conducted in April 2012 to identify web sites selling NSs in the treatment of diabetes using Google, Yahoo and Bing! and the key word used was "diabetes nutritional supplements". Website content was evaluated for the quality of information available to consumers and for the presence of a complete list of ingredients in the first NS suggested by the site. Subsequently, in order to analyze the scientific evidence on the efficacy of these supplements a PubMed search was carried out on the ingredients that were shared in at least 3 nutritional supplements. A total of 10 websites selling NSs were selected. Only half of the websites had a Food and Drug Administration disclaimer and 40% declared clearly that the NS offered was not a substitute for proper medication. A total of 10 NS ingredients were searched for on PubMed. Systematic reviews, meta-analyses or randomized control trials were present for all the ingredients except one. Most of the studies, however, were of poor quality and/or the results were conflicting. Easy internet access to NSs lacking in adequate medical information and strong scientific evidence is a matter of public health concern, mainly considering that a misleading information could lead to an improper prevention both in healthy people and people suffering from diabetes. There is a clear need for more trials to assess the efficacy and safety of these NSs, better quality control of websites, more informed physicians and

Clinical studies on chromium picolinate supplementation in diabetes mellitus--a review.

PubMed

Broadhurst, C Leigh; Domenico, Philip

2006-12-01

Chromium (Cr) picolinate (CrPic) is a widely used nutritional supplement for optimal insulin function. A relationship among Cr status, diabetes, and associated pathologies has been established. Virtually all trials using CrPic supplementation for subjects with diabetes have demonstrated beneficial effects. Thirteen of 15 clinical studies (including 11 randomized, controlled studies) involving a total of 1,690 subjects (1,505 in CrPic group) reported significant improvement in at least one outcome of glycemic control. All 15 studies showed salutary effects in at least one parameter of diabetes management, including dyslipidemia. Positive outcomes from CrPic supplementation included reduced blood glucose, insulin, cholesterol, and triglyceride levels and reduced requirements for hypoglycemic medication. The greater bioavailability of CrPic compared with other forms of Cr (e.g., niacin-bound Cr or CrCl(3)) may explain its comparatively superior efficacy in glycemic and lipidemic control. The pooled data from studies using CrPic supplementation for type 2 diabetes mellitus subjects show substantial reductions in hyperglycemia and hyperinsulinemia, which equate to a reduced risk for disease complications. Collectively, the data support the safety and therapeutic value of CrPic for the management of cholesterolemia and hyperglycemia in subjects with diabetes.

Caffeine Toxicity Due to Supplement Use in Caffeine--Naïve Individual: A Cautionary Tale.

PubMed

Lystrup, Robert M; Leggit, Jeffery C

2015-08-01

Thousands of military members self-medicate with dietary supplements containing unknown quantities of pharmacologically active compounds. These poorly regulated substances can cause real harm to the military population, especially when they contain stimulants such as caffeine. When taken regularly, caffeine has several performance-enhancing benefits. However, when used excessively or in vulnerable populations, caffeine can cause several unwanted side effects such as nervousness, sensory disturbances, insomnia, arrhythmia, excitability, inattentiveness, restlessness, mood changes, gastrointestinal disturbances, and even psychosis. Vulnerable patients include the caffeine-naïve, physiologically stressed, young, and mentally ill patients. One such case describes a caffeine-naïve service member who suffered an adverse reaction after taking an allegedly moderate dose of caffeine from a pill he obtained from a teammate. This case highlights the importance of supplement awareness among service members, increased provider vigilance, third party verification, and enhanced regulation on the approval and marketing of dietary supplements. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Beneficial Effects of Oral Supplementation With Ovoderm on Human Skin Physiology: Two Pilot Studies.

PubMed

Aguirre, Andrés; Gil-Quintana, Erena; Fenaux, Marisa; Erdozain, Sandra; Sarria, Itziar

2017-11-02

Collagens and hyaluronic acid have long been used in pharmaceuticals and food supplements for the improvement of skin elasticity and hydration. These compounds provide the building blocks of the skin. Ovoderm is an oral supplement obtained from eggshells that contains naturally occurring collagen and glycosaminoglycans, such as hyaluronic acid. We evaluated the efficacy of Ovoderm on skin biophysical parameters related to cutaneous aging such as elasticity, hydration, and pigmentation. Two pilot studies were run to assess the effect of daily oral supplementation with 300 mg Ovoderm on skin parameters. The first consisted of a self-assessment questionnaire intended to perform an assessment on skin, hair, and nail health after 50 days of treatment. The second measured the effect of 5-week treatment on hydration by corneometry, on elasticity with the cutometer, and on pigmentation with the mexameter. In the pilot study 1, participants were predominantly satisfied with the effects obtained on general face (100% volunteers satisfied) and body (94% volunteers satisfied) skin condition and skin properties (100% volunteers satisfied with facial skin softness, 94% with facial skin hydration, and 89% with body skin hydration) and partly with effects on hair (67% volunteers satisfied) and nail (50% volunteers satisfied) condition. The study 2 revealed a statistically significant improvement in skin elasticity (12% increase, p =.0136), a tendency to reduce skin pigmentation (5% decrease), and no significant change in skin hydration. Our study reflects that oral supplementation with Ovoderm is efficacious to reduce the gradual loss of skin elasticity characteristic of aged skin, which helps to improve the appearance of the skin.

A Low Dose Caffeine and Carbohydrate Supplement does not Improve Athletic Performance during Volleyball Competition

PubMed Central

PFEIFER, DAVID R.; ARVIN, KELSEY M.; HERSCHBERGER, COURTNEY N.; HAYNES, NICHOLAS J.; RENFROW, MATTHEW S.

2017-01-01

Dietary supplements are widely used to enhance sport performance and the combination of carbohydrate and caffeine (CHO+CAF) has yielded particularly high performance gains. Though the effects of a CHO+CAF supplement have been studied in a laboratory environment, little research exists on the effects of supplementation during competition. Therefore, the purpose of this study was to determine the effects of a CHO+CAF supplement on athletic performance in competition. Eight female collegiate volleyball players completed three testing sessions under three different conditions separated by approximately one week each: CHO+CAF supplement, placebo (PBO), and control (CTL) using a randomized, cross-over design. Blood glucose (BG) was assessed prior to supplementation and immediately after set three. The supplement and PBO were administered prior to play and between sets two and three. Following three sets of play, three performance tests were completed: vertical jump (VJ), agility (AGL), and repeated 30-m sprint ability (RSA). While CHO+CAF supplementation significantly increased BG, the performance tests were not different (p>.05) among the testing conditions. These findings suggest that the amount of the supplement used in this study is not beneficial to VJ, AGL, and RSA in female volleyball players. As these performance tests were largely anaerobic and non-glycolytic in nature, the ergogenicity of the supplement may have been underutilized. Additionally, coaches and athletes should not only be aware of what ingredients are in the supplements they choose, but the amount of those ingredients as they may modify the efficacy of the supplement to impact performance. PMID:28515832

Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors

PubMed Central

Diop-Frimpong, Benjamin; Chauhan, Vikash P.; Krane, Stephen; Boucher, Yves; Jain, Rakesh K.

2011-01-01

The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan—a clinically approved angiotensin II receptor antagonist with noted antifibrotic activity—can enhance the penetration and efficacy of nanomedicine. We found that losartan inhibited collagen I production by carcinoma-associated fibroblasts isolated from breast cancer biopsies. Additionally, it led to a dose-dependent reduction in stromal collagen in desmoplastic models of human breast, pancreatic, and skin tumors in mice. Furthermore, losartan improved the distribution and therapeutic efficacy of intratumorally injected oncolytic herpes simplex viruses. Finally, it also enhanced the efficacy of i.v. injected pegylated liposomal doxorubicin (Doxil). Thus, losartan has the potential to enhance the efficacy of nanotherapeutics in patients with desmoplastic tumors. PMID:21282607

[Development of guidance for the approval process of brand-new medical products and regenerative medicine products].

PubMed

Niimi, Shingo

2015-01-01

Ministry of Health, Labour and Weltare has been conducting development of guidance for the approval process of brand-new medical products/development of guidance for medical devices in collaboration with Ministry of Economy, Trade and Industry as part of measures to promote practical use of brand-new medical products since 2005. The objective of this project is to expedite the processes from developmental process of medical devices to approval review and to introduce the medical devices to medical front quickly.. Ministry of Health, Labour and Welfare side has been making guidance for the guide in approval process of brand-new medical products and regeneration medicine products to aim at acceleration and facilitation of development and approval process of innovative medical products. Twenty-two of the guidance have been issued as director of the evaluation and licensing division. The evaluation index about safety and efficacy required for medical devices and regenerative medicine products in progress were put together in these guidance and useful for medical devices developer to understand the point at the approved review. Therefore, I think that the evaluation index could also contribute to the efficient product development. The guidance about implantable artificial heart is issued as the representative example which was useful in the approved review.

An Evaluation of the Supplemental Instruction Programme in a First Year Calculus Course

ERIC Educational Resources Information Center

Fayowski, V.; MacMillan, P. D.

2008-01-01

Supplemental Instruction (SI) incorporates collaborative learning in small, peer-led, group settings in order to integrate instruction in learning and reasoning skills with course content. Several meta-analyses speak to the efficacy of SI but fail to address selection bias due to ability/motivation and gender. In this study, SI was paired with a…

Effect of Preventive Supplementation with Zinc and Other Micronutrients on Non-Malarial Morbidity in Tanzanian Pre-School Children: A Randomized Trial

PubMed Central

Veenemans, Jacobien; Schouten, Laura R. A.; Ottenhof, Maarten J.; Mank, Theo G.; Uges, Donald R. A.; Mbugi, Erasto V.; Demir, Ayşe Y.; Kraaijenhagen, Rob J.; Savelkoul, Huub F. J.; Verhoef, Hans

2012-01-01

Background The efficacy of preventive zinc supplementation against diarrhea and respiratory illness may depend on simultaneous supplementation with other micronutrients. We aimed to assess the effect of supplementation with zinc and multiple micronutrients on diarrhea and other causes of non-malarial morbidity. Methods and Findings Rural Tanzanian children (n = 612) aged 6–60 months and with height-for-age z-score < –1.5 SD were randomized to daily supplementation with zinc (10 mg) alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Children were followed for an average of 45 weeks. During follow-up, we recorded morbidity episodes. We found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on rates of diarrhea, respiratory illness, fever without localizing signs, or other illness (guardian-reported illness with symptoms involving skin, ears, eyes and abscesses, but excluding trauma or burns). Zinc supplementation reduced the hazard rate of diarrhea by 24% (4%–40%). By contrast, multi-nutrients seemed to increase this rate (HR; 95% CI: 1.19; 0.94–1.50), particularly in children with asymptomatic Giardia infection at baseline (2.03; 1.24–3.32). Zinc also protected against episodes of fever without localizing signs (0.75; 0.57–0.96), but we found no evidence that it reduced the overall number of clinic visits. Conclusions We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by concurrent supplementation with other micronutrients. By reducing rates of fever without localizing signs, supplementation with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics. Trial Registration ClinicalTrials.gov NCT00623857 PMID:22870238

The approval process for biosimilar erythropoiesis-stimulating agents.

PubMed

Wish, Jay B

2014-09-05

A biosimilar drug or follow-on biologic drug is defined by the Public Health Service Act as a product that is "highly similar to the reference product notwithstanding minor differences in clinically active components and there are no clinically meaningful differences between the biologic product and the reference product in terms of the safety, purity and potency of the product." The advantage of biosimilar drugs is that they are significantly less expensive than the reference products, allowing for increased accessibility and cost savings. Recognizing these advantages, the US Congress passed the Biologics Price Competition and Innovation Act in 2009 as part of health care reform. The Biologics Price Competition and Innovation Act allows sponsors of biosimilar agents to seek approval by showing structural and functional similarity to the reference agent, with the extent of required clinical studies to be determined on the basis of the degree of biosimilarity with the reference product. The goal is to bring biosimilar agents to the market more efficiently while still protecting the safety of the public. The European Union has had such a process in place for a number of years. Two biosimilar epoetin agents have been approved in the European Union since 2007, and their companies are conducting trials to seek approval in the United States, because Amgen's patent protection for epoetin alfa expires in 2014. Trials completed for European Union approval of both agents showed similar efficacy and safety to the reference epoetin alfa. As with all biologics, immunogenicity concerns may persist because of the fragility of the manufacturing process and the worldwide experience with pure red cell aplasia as a result of epoetin therapy. The uptake of biosimilar epoetins after approval in the United States will depend on the balance of cost advantage against safety concerns. Competition in the marketplace will likely decrease the cost of the reference agent as well. Copyright �

CLSI performance standards for antimicrobial susceptibility testing of bacteria isoloated from aquatic animals; second information supplement. CLSI document VET03/VET04-S2

USDA-ARS?s Scientific Manuscript database

The supplemental information presented in this document is intended for use with the antimicrobial susceptibility testing procedures published in the following Clinical and Laboratory Standards Institute (CLSI) approved documents VET03-A Methods for Antimicrobial Disk Susceptibility Testing of Bacte...

Participation of the elderly, women, and minorities in pivotal trials supporting 2011-2013 U.S. Food and Drug Administration approvals.

PubMed

Downing, Nicholas S; Shah, Nilay D; Neiman, Joseph H; Aminawung, Jenerius A; Krumholz, Harlan M; Ross, Joseph S

2016-04-14

Pivotal trials, the clinical studies that inform U.S. Food and Drug Administration (FDA) approval decisions, provide the foundational evidence supporting the safety and efficacy of novel therapeutics. We determined the representation of the elderly, women, and patients from racial and ethnic minorities in pivotal trials and whether the FDA is making subgroup efficacy analyses among these subpopulations available to the public. We conducted a cross-sectional study of novel therapeutics approved by the FDA between 2011 and 2013. Using publicly available FDA documents, we collected information on the demographic characteristics of pivotal trial participants (age ≥65 years, sex [male, female], race [white, black, Asian, other], and ethnicity [Hispanic, non-Hispanic]) and determined the availability of subgroup analyses by age, sex, race, and ethnicity. We identified 86 novel therapeutic that were approved by the FDA between 2011 and 2013 for 92 indications on the basis of 206 pivotal trials. The median age of pivotal trial patients was 53.1 years (interquartile range 40.6-60.6), and the mean proportion of patients ≥65 years of age was 28.9 % (95 % CI 23.5-34.4 %). Similar proportions of pivotal trial participants were male (mean 50.3 %, 95 % CI 45.3-55.2 %) and female (mean 49.7 %, 95 % CI 44.7-54.7 %). Most participants were white (mean 79.2 %, 95 % CI 75.9-82.6 %), while the mean proportion of black patients was 7.4 % (95 % CI 5.5-9.3 %), that of Asian patients was 7.4 % (95 % CI 5.2-9.7 %), and that of patients of other races was 5.9 % (95 % CI 4.4-7.5 %). Information about ethnicity was available for only 59.8 % of indications, and where such data were available, the mean proportion of Hispanic participants was 13.3 % (95 % CI 10.3-16.3 %). FDA reviewers performed and made available subgroup efficacy analyses by age, sex, and race for at least one of the pivotal trials used as the basis of approval for over 80 % of indications. Although women are equally

Effect of taking dietary supplement on hematological and biochemical parameters in male bodybuilders an equation model

PubMed Central

Meamar, Rokhsareh; Maracy, Mohammad; Nematollahi, Shahrzad; Yeroshalmi, Shemouil; Zamani-Moghaddam, Ali; Ghazvini, Mohammad Reza Aghaye

2015-01-01

Background: The improved physical action following administration of supplements to bodybuilders was supported by changes in laboratory parameters. Despite the fact that these supplements are sometimes associated both advantage and side effects, this study were conducted for the purpose of evaluating the possible effects of some commonly used supplements in bodybuilders on the hematological and biochemical parameters. Materials and Methods: In this study, we included 40 male bodybuilders as cases and 40 controls in the age group of 20-40 years. They used different kinds of supplements for 1 year. In general, all the supplements used were classified into two groups: hormonal and non-hormonal. Laboratory tests were requested for evaluation of hematological and biochemical parameters. Results: In an equation model, we found that weight (P = 0.024), duration of bodybuilding (P < 0.001), and duration of hormone supplement consumption (P < 0.001) were loaded significantly on the latent variables, demographic and dietary supplement, respectively. The relationship between dietary supplement and biochemical and hematological parameters was significant (P = 0.01) and some of these parameters including creatinine (P = 0.023), blood aspartate aminotransferase (AST) (P < 0.001), alanine aminotransferase (ALT) (P < 0.001), and red blood cell distribution (RDW) (P = 0.046) had a significant role than others. In a multivariate regression model, we found that WBC (P < 0.001), platelets (P < 0.001), blood urea nitrogen (BUN; P < 0.001), creatinine (P < 0.001), AST (P = 0.005), and ALT (P = 0.001) were higher in athletes than in controls. Conclusions: It is strongly advised that there should be some concerns about possible supplement-induced changes in the laboratory exams for bodybuilders. The available supplements are unchecked and not approved by the US Food and Drug Administration (FDA). More studies should be designed for a better and precise administration of each supplement in

Efficacy of azilsartan medoxomil with chlorthalidone in hypertension.

PubMed

Baker, William L; Nigro, Stefanie C; White, William B

2014-07-01

Azilsartan medoxomil (AZL) is the most recently approved angiotensin receptor blocker (ARB) for treating patients with hypertension. A fixed-dose combination product with AZL and the thiazide-like diuretic chlorthalidone (CLD) is now available to treat individuals who require additional blood pressure lowering. For this review, a literature search was conducted using MEDLINE and the keywords and MeSH terms azilsartan, azilsartan medoxomil, chlorthalidone, thiazide, blood pressure and hypertension. References for retrieved articles were also scanned for relevant citations. No language restrictions were used. AZL is structurally related to candesartan and has been shown to provide more potent angiotensin receptor antagonism versus other ARBs. CLD is a thiazide-like diuretic with a longer half-life and greater blood pressure lowering efficacy than hydrochlorothiazide. The combination of AZL plus CLD has superior efficacy to other ARBs alone or in combination with hydrochlorothiazide based on extensive evaluation in clinical trials. This superior efficacy is not offset by a large imbalance in clinically important adverse events.

Dietary supplementation with a superoxide dismutase-melon concentrate reduces stress, physical and mental fatigue in healthy people: a randomised, double-blind, placebo-controlled trial.

PubMed

Carillon, Julie; Notin, Claire; Schmitt, Karine; Simoneau, Guy; Lacan, Dominique

2014-06-19

We aimed to investigate effects of superoxide dismutase (SOD)-melon concentrate supplementation on psychological stress, physical and mental fatigue in healthy people. A randomized, double-blind, placebo-controlled trial was performed on 61 people divided in two groups: active supplement (n = 32) and placebo (n = 29) for 12 weeks. Volunteers were given one small hard capsule per day. One capsule contained 10 mg of SOD-melon concentrate (140 U of SOD) and starch for the active supplement and starch only for the placebo. Stress and fatigue were evaluated using four psychometric scales: PSS-14; SF-36; Stroop tests and Prevost scale. The supplementation with SOD-melon concentrate significantly decreased perceived stress, compared to placebo. Moreover, quality of life was improved and physical and mental fatigue were reduced with SOD-melon concentrate supplementation. SOD-melon concentrate supplementation appears to be an effective and natural way to reduce stress and fatigue. trial approved by the ethical committee of Poitiers (France), and the ClinicalTrials.gov Identifier is NCT01767922.

30 CFR 28.20 - Certificates of approval; scope of approval.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Certificates of approval; scope of approval. 28.20 Section 28.20 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS FUSES FOR USE WITH DIRECT CURRENT IN PROVIDING SHORT-CIRCUIT...

Three newly approved drugs for chronic lymphocytic leukemia (CLL): Incorporating ibrutinib, idelalisib and obinutuzumab into clinical practice

PubMed Central

Sanford, David; Wierda, William G.; Burger, Jan A.; Keating, Michael J.; O’Brien, Susan M.

2016-01-01

Three agents have received FDA approval for treatment of chronic lymphocytic leukemia (CLL) within the last year. Ibrutinib and idelalisib block B-cell receptor signaling through inhibition of BTK and PI3Kδ molecules respectively, interfering with several pathways required for leukemia cell survival. Idelalisib has shown efficacy in in the relapsed setting and is currently approved for use in combination with rituximab. Ibrutinib has been studied in patients with relapsed CLL and as frontline therapy. In the relapsed setting, these agents produce durable remissions, and may be preferable to retreatment with chemoimmunotherapy for many patients. Ibrutinib is also effective treatment for patients with deletion 17p and is approved as frontline therapy in this patient group, although it does not appear to completely abrogate this adverse prognostic factor. These agents have a unique side effect profile and longer follow-up is required to further understand tolerability and rare adverse effects. Obinutuzumab is a type-2 monoclonal anti-CD20 antibody which results in direct and antibody-dependent cell-mediated cytotoxicity of leukemia cells. It is approved in combination with chlorambucil, and has shown efficacy in the frontline setting in patients unfit for more intensive chemoimmunotherapy. It produces increased response rates and minimal residual disease (MRD) negativity in comparison with chlorambucil/rituximab and is associated with an advantage in progression free survival but not yet overall survival. These agents underscore our advancement in the understanding of the biology of CLL and will improve outcomes for many patients with CLL. PMID:25817936

[Ten years experience with the first approved biosimilar recombinant human growth hormone drug in normal clinical practice].

PubMed

López-Siguero, Juan Pedro; Palla García, Margarida; Martínez Busto, Elena; Rebollo, Francisco José; Pombo, Manuel

2018-04-01

Recombinant human growth hormone (rhGH) is the first biosimilar drug approved by the European Medicines Agency in 2006, using the biosimilar registration process. It was authorised for the treatment of growth hormone deficiency, and growth disorders associated with Turner's syndrome, chronic renal failure, Prader-Willi syndrome, and growth disorders in children/adolescents born small for gestational age, and replacement therapy in adults with pronounced growth hormone deficiency. This review is focused on the scientific evidence published about this drug in the last ten years, including the clinical trials on which the approval of the regulatory authority is based, and the most relevant studies evaluating the clinical impact of the drug in clinical practice. The equivalence between biosimilar and original product has been confirmed in the clinical trials published by Romer et al. and López-Siguero et al. Furthermore, studies carried out in real-life conditions confirm its long-term efficacy and safety, as well as the absence of clinical impact by switching treatment from the original to the biosimilar product. The number of patients receiving this medication has continuously increased since its approval. Its equivalence with the original product has been verified. Preliminary data from the post-authorisation PATRO study confirm the efficacy and safety of the biosimilar product in comparison with data from clinical trials. However, final results must be evaluated at the end of the study, which will provide additional information about the long-term efficacy and safety of the biosimilar drug. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Protein Supplementation Does Not Affect Myogenic Adaptations to Resistance Training.

PubMed

Reidy, Paul T; Fry, Christopher S; Igbinigie, Sherry; Deer, Rachel R; Jennings, Kristofer; Cope, Mark B; Mukherjea, Ratna; Volpi, Elena; Rasmussen, Blake B

2017-06-01

It has been proposed that protein supplementation during resistance exercise training enhances muscle hypertrophy. The degree of hypertrophy during training is controlled in part through the activation of satellite cells and myonuclear accretion. This study aimed to determine the efficacy of protein supplementation (and the type of protein) during traditional resistance training on myofiber cross-sectional area, satellite cell content, and myonuclear addition. Healthy young men participated in supervised whole-body progressive resistance training 3 d·wk for 12 wk. Participants were randomized to one of three groups ingesting a daily 22-g macronutrient dose of soy-dairy protein blend (PB, n = 22), whey protein isolate (WP, n = 15), or an isocaloric maltodextrin placebo (MDP, n = 17). Lean mass, vastus lateralis myofiber-type-specific cross-sectional area, satellite cell content, and myonuclear addition were assessed before and after resistance training. PB and the pooled protein treatments (PB + WP = PRO) exhibited a greater whole-body lean mass %change compared with MDP (P = 0.057 for PB) and (P = 0.050 for PRO), respectively. All treatments demonstrated similar leg muscle hypertrophy and vastus lateralis myofiber-type-specific cross-sectional area (P < 0.05). Increases in myosin heavy chain I and II myofiber satellite cell content and myonuclei content were also detected after exercise training (P < 0.05). Protein supplementation during resistance training has a modest effect on whole-body lean mass as compared with exercise training without protein supplementation, and there was no effect on any outcome between protein supplement types (blend vs whey). However, protein supplementation did not enhance resistance exercise-induced increases in myofiber hypertrophy, satellite cell content, or myonuclear addition in young healthy men. We propose that as long as protein intake is adequate during muscle overload, the adaptations in muscle growth and function will not

30 CFR 746.14 - Approval, disapproval or conditional approval, of mining plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., of mining plan. 746.14 Section 746.14 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR FEDERAL LANDS PROGRAM REVIEW AND APPROVAL OF MINING PLANS § 746.14 Approval, disapproval or conditional approval, of mining plan. The Secretary shall approve, disapprove or...

A Descriptive Study of Enrollment in Supplemental Educational Services in the Four RRE Appalachia Region States. REL 2012-No.109

ERIC Educational Resources Information Center

Ford, James; Harrison, Lynn; Mokher, Christine; Franceschini, Louis; Zoblotsky, Todd

2012-01-01

The supplemental educational services program is a core provision of the No Child Left Behind (NCLB) Act of 2001. The program offers free tutoring in reading/language arts and math from state-approved providers outside of regular school hours. This report explores differences across states and school urban and rural locales in providing…

Improving the Efficiency and Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury

DTIC Science & Technology

2014-12-01

functional recovery improved in spinal injured rats using glibenclamide (Glib), an FDA approved anti-diabetic drug that targets SUR1 receptors on... protocols in rat model of SCI. • Established that glibenclamide is neuroprotective across different types of SCI but that efficacy is related to the location...the relative efficacy of glibenclamide with other neuroprotective drugs (Riluzole, systemic hypothermia). Data show that glibenclamide has superior

Combined Supplementation of Choline and Docosahexaenoic Acid during Pregnancy Enhances Neurodevelopment of Fetal Hippocampus.

PubMed

Thomas Rajarethnem, Huban; Megur Ramakrishna Bhat, Kumar; Jc, Malsawmzuali; Kumar Gopalkrishnan, Siva; Mugundhu Gopalram, Ramesh Babu; Rai, Kiranmai Sesappa

2017-01-01

Choline is an essential nutrient for humans which plays an important role in structural integrity and signaling functions. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, highly enriched in cell membranes of the brain. Dietary intake of choline or DHA alone by pregnant mothers directly affects fetal brain development and function. But no studies show the efficacy of combined supplementation of choline and DHA on fetal neurodevelopment. The aim of the present study was to analyze fetal neurodevelopment on combined supplementation of pregnant dams with choline and DHA. Pregnant dams were divided into five groups: normal control [NC], saline control [SC], choline [C], DHA, and C + DHA. Saline, choline, and DHA were given as supplements to appropriate groups of dams. NC dams were undisturbed during entire gestation. On postnatal day (PND) 40, brains were processed for Cresyl staining. Pups from choline or DHA supplemented group showed significant ( p < 0.05) increase in number of neurons in hippocampus when compared to the same in NC and SC groups. Moreover, pups from C + DHA supplemented group showed significantly higher number of neurons ( p < 0.001) in hippocampus when compared to the same in NC and SC groups. Thus combined supplementation of choline and DHA during normal pregnancy enhances fetal hippocampal neurodevelopment better than supplementation of choline or DHA alone.

Efficacy of a 2-month dietary supplementation with polyunsaturated fatty acids in dry eye induced by scopolamine in a rat model.

PubMed

Viau, Sabrina; Maire, Marie-Annick; Pasquis, Bruno; Grégoire, Stéphane; Acar, Niyazi; Bron, Alain M; Bretillon, Lionel; Creuzot-Garcher, Catherine P; Joffre, Corinne

2009-08-01

This study was conducted to evaluate the efficacy of dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) in dry eye in a rat model. Female Lewis rats were fed with diets containing (1) gamma-linolenic acid (GLA), (2) eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), or (3) GLA + EPA + DHA, for 2 months before the induction of dry eye using a continuous delivery of scopolamine and during scopolamine treatment. Two, 10 and 28 days after dry-eye induction, clinical signs of corneal dryness were evaluated in vivo using fluorescein staining. MHC II expression and mucin rMuc5AC production in the conjunctival epithelium were evaluated by immunostaining. Lipids and prostaglandins (PGs) E(1) and E(2) were analysed from the exorbital lacrimal gland (LG). Dietary PUFAs minimised the occurrence of corneal keratitis 28 days after induction of dry eye. The decrease in mucin production observed on the conjunctival epithelium was partially prevented by EPA + DHA supplementation after 2 days of scopolamine treatment, as well as by GLA and GLA + EPA + DHA diets after 10 days of treatment. The overexpression of MHC II in the conjunctival epithelium caused by dry eye induction was significantly reduced only with the GLA + EPA + DHA diet after 28 days of treatment. Dietary PUFAs were incorporated into phospholipids of the exorbital LG. Induction of dry eye was associated with a significant increase in PGE(1) and PGE(2) levels in the exorbital LG, which was inhibited by dietary EPA + DHA at 10 days (for PGE(2)) and 28 days (for PGE(1)). Dietary GLA, EPA and DHA significantly interfered with lipid homeostasis in the exorbital LG and partially prevented the course of dry eye. In particular, our results demonstrate the efficacy of the combination of n-6 and n-3 PUFAs.

Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA.

PubMed

Cohen, Pieter A; Avula, Bharathi; Venhuis, Bastiaan; Travis, John C; Wang, Yan-Hong; Khan, Ikhlas A

2017-01-01

Oxilofrine (4-[1-hydroxy-2-(methylamino)propyl]phenol) is a pharmaceutical stimulant prescribed in dosages of 16 to 40 mg to stimulate the heart and increase blood pressure. It has never been approved for use in the USA as a prescription drug or as a dietary supplement. Several athletes, however, have been banned from sport for testing positive for oxilofrine and have claimed that they inadvertently consumed oxilofrine in sports supplements. Consumption of supplements containing oxilofrine may also pose serious health risks. For example, one brand of supplements containing oxilofrine has been linked to serious adverse events including vomiting, agitation, and cardiac arrest. We designed our study to determine the presence and quantity of oxilofrine in dietary supplements sold in the USA. A validated ultra-high performance liquid chromatography-quadrupole time of flight-mass spectrometry method was developed for the identification and quantification of oxilofrine. The separation was achieved using a reversed phase column, mass spectrometry detection, and a water/acetonitrile gradient as the mobile phase. The presence of oxilofrine was confirmed using a reference standard. We analyzed 27 brands of supplements labelled as containing a synonym of oxilofrine ('methylsynephrine') and found that oxilofrine was present in 14 different brands (52%) at dosages ranging from 0.0003 to 75 mg per individual serving. Of the supplements containing oxilofrine, 43% (6/14) contained pharmaceutical or greater dosages of oxilofrine. Following instructions on the label, consumers could ingest as much as 250 mg of oxilofrine per day. The drug oxilofrine was found in pharmacological and greater dosages in supplements labelled as containing methylsynephrine. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Calcium and Vitamin D Supplementation and Loss of Bone Mineral Density in Women Undergoing Breast Cancer Therapy

PubMed Central

Datta, Mridul; Schwartz, Gary G.

2013-01-01

An unintended consequence of breast cancer therapies is an increased risk of osteoporosis due to accelerated bone loss. We conducted a systematic review of calcium and/or vitamin D (Ca±D) supplementation trials for maintaining bone mineral density (BMD) in women with breast cancer using the “before-after” data from the Ca±D supplemented comparison group of trials evaluating the effect of drugs such as bisphosphonates on BMD. Whether Ca±D supplements increase BMD in women undergoing breast cancer therapy has never been tested against an unsupplemented control group. However, results from 16 trials indicate that the Ca±D doses tested (500-1500 mg calcium; 200-1000 IU vitamin D) were inadequate to prevent BMD loss in these women. Cardiovascular disease is the main cause of mortality in women with breast cancer. Because calcium supplements may increase cardiovascular disease risk, future trials should evaluate the safety and efficacy of Ca±D supplementation in women undergoing breast cancer therapy. PMID:23932583

Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial

USDA-ARS?s Scientific Manuscript database

Isoflavones are naturally occurring plant estrogens that are abundant in soy. Although purported to protect against bone loss, the efficacy of soy isoflavone supplementation in the prevention of osteoporosis in postmenopausal women remains controversial. Our aim was to test the effect of soy isoflav...

Oral nutritional supplementation in patients undergoing peritoneal dialysis: a randomised, crossover pilot study.

PubMed

Salamon, Karen M; Lambert, Kelly

2018-06-01

Malnutrition is a significant problem in those undergoing peritoneal dialysis (PD). Factors such as gastrointestinal (GI) symptoms and the need for a fluid reduced diet can limit tolerance and thereby the efficacy of oral nutritional supplements to treat malnutrition. To evaluate the acceptability and impact of two different forms of oral nutrition supplementation for 16 weeks on nutritional markers and quality of life of malnourished patients undergoing PD. A randomised, within-subject cross-over study. Patients assessed as malnourished or with serum albumin <35 g/l were recruited. Participants were randomised to receive either 200 ml of a 1.25 kcal/ml nutrition supplement or a high protein nutrition supplement bar, for eight weeks. Each group then crossed over to receive the alternative supplement for eight weeks. Total intervention time was 16 weeks. Serum albumin, serum transthyretin and food intake were evaluated at baseline, at 8 and 16 weeks. Subjective Global Assessment, the presence of GI symptoms and quality of life were evaluated at baseline and 16 weeks. Sixteen weeks of nutritional support was associated with statistically significant improvements in weight and a reduction in the proportion of patients who were malnourished. There was no difference in the impact of bars compared with liquid oral nutrition supplementation. Patients preferred the fluid supplement to the bars. Sixteen weeks of nutritional support improved nutritional status in malnourished patients on PD. © 2017 European Dialysis and Transplant Nurses Association/European Renal Care Association.

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status.

PubMed

Singh, Vijay K; Garcia, Melissa; Seed, Thomas M

2017-09-01

The threat of a radiological/nuclear event is a critical concern for all government agencies involved in national security and public health preparedness. Countermeasures that are safe, easily administered, and effective at diminishing or eliminating adverse health effects to individuals and the overall public health impact of radiation exposure are urgently needed. Radiation countermeasures included in this three-part series have been classified under various subheadings based specifically on their developmental stages for United States Food and Drug Administration (FDA) approval. We have included FDA-approved agents for acute radiation syndrome (ARS) in part I. This is part II in which we have reviewed FDA-approved agents for limited indications, internalized radionuclides, emesis, late effects, radiomitigators available in the strategic national stockpile (SNS), agents with FDA investigational new drug (IND) status, and those with NHP efficacy data without FDA IND. Agents discussed in part III are those agents that have been peer reviewed, published, and have demonstrated significant survival benefits in animal models of ARS. Agents investigated in in vitro models only or studied in animal models without peer-reviewed publications have not been included. The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. A number of promising radiation countermeasures are currently moving forward with continued support and effort by both governmental agencies and by publicly and privately held pharmaceutical companies. There is a limited number of countermeasures which are progressing well following the Animal Rule and may get approved in the near future, thus serving to close the gap of this critically important, unmet radiobiomedical need.

Pharmacotherapy of focal epilepsy in children: a systematic review of approved agents.

PubMed

Arya, Ravindra; Glauser, Tracy A

2013-04-01

Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug, patient and socioeconomic situation. This paper systematically reviews the available efficacy/effectiveness evidence for various anti-epileptic drugs (AED) as monotherapy and adjunctive therapy for partial-onset seizures in children. Relevant randomized clinical trials (RCTs) were identified by a structured PubMed search, supplemented by an additional hand search of reference lists and authors' files. Eligible studies were reviewed and data extracted into tables. Included RCTs were classified based on accepted published criteria. Only efficacy and effectiveness outcome measures were evaluated since there is little scientifically rigorous comprehensive AED adverse effects data. Oxcarbazepine is the only AED with Class I evidence for efficacy/effectiveness as initial monotherapy for partial-onset seizures in children. Carbamazepine, clobazam, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, vigabatrin and zonisamide have, at best, Class III efficacy/effectiveness evidence for monotherapy of partial-onset seizures in children. For adjunctive therapy, gabapentin, lamotrigine, levetiracetam, oxcarbazepine and topiramate have Class I efficacy/effectiveness evidence for treatment of pediatric partial-onset seizures. This efficacy/effectiveness analysis must not be used in isolation when selecting therapy. AED selection for a specific child needs to integrate a drug's efficacy/effectiveness data with its safety and tolerability profile, pharmacokinetic properties, available formulations, and patient specific characteristics. It is critical that physicians and patients incorporate all these relevant variables when choosing AED therapy.

The Evidence for Efficacy of HPV Vaccines: Investigations in Categorical Data Analysis

ERIC Educational Resources Information Center

Gibbs, Alison L.; Goossens, Emery T.

2013-01-01

Recent approval of HPV vaccines and their widespread provision to young women provide an interesting context to gain experience with the application of statistical methods in current research. We demonstrate how we have used data extracted from a meta-analysis examining the efficacy of HPV vaccines in clinical trials with students in applied…

Maternity hospital practices and breast feeding self-efficacy in Finnish primiparous and multiparous women during the immediate postpartum period.

PubMed

Koskinen, Katja S; Aho, Anna L; Hannula, Leena; Kaunonen, Marja

2014-04-01

to explore the relationship between maternity hospital practices and breast feeding self-efficacy. the data were collected using a cross-sectional survey. The study is a part of a larger longitudinal research and development project called 'Urban parenthood'. three urban maternity hospitals in Southern Finland. altogether 1400 questionnaires were given out and 573 primiparous and multiparous women completed the questionnaire within a week after childbirth. The response rate was 41%. early and successful initiation of breast feeding, rooming-in and exclusive breast feeding during the hospital stay were associated with higher maternal breast feeding self-efficacy in both primiparous and multiparous women. The reason (medical or non-medical), frequency or method (bottle or cup) for supplementation was not associated with breast feeding self-efficacy. breast feeding experiences during the immediate postpartum period have an association with breast feeding self-efficacy. Mothers who are not able to initiate breast feeding within an hour after birth or whose infants are supplemented during the hospital stay may benefit from additional support and breast feeding counselling. Copyright © 2013 Elsevier Ltd. All rights reserved.

Determinants of dietary supplement use--healthy individuals use dietary supplements.

PubMed

Kofoed, Christina L F; Christensen, Jane; Dragsted, Lars O; Tjønneland, Anne; Roswall, Nina

2015-06-28

The prevalence of dietary supplement use varies largely among populations, and previous studies have indicated that it is high in the Danish population compared with other European countries. The diversity in supplement use across countries indicates that cultural and environmental factors could influence the use of dietary supplements. Only few studies investigating the use of dietary supplements have been conducted in the Danish population. The present cross-sectional study is based on 54,948 Danes, aged 50-64 years, who completed self-administrated questionnaires on diet, dietary supplements and lifestyle between 1993 and 1997. A health index including smoking, physical activity, alcohol and diet, and a metabolic risk index including waist circumference, urinary glucose and measured hypertension were constructed. Logistic regression was used to investigate these determinants in relation to the intake of dietary supplements. We found that 71 % of the participants were dietary supplement users; female sex, older age groups and higher educated participants were more likely to be users of any dietary supplements. One additional point in the health index was associated with 19, 16 and 9 % higher likelihood of being user of any, more common and less common supplements, respectively. In the metabolic risk index, one additional point was associated with 17 and 16 % lower likelihood of being user of any supplement and more common supplements, respectively. No significant association was found for less common supplement use. In conclusion, those with the healthiest lifestyle were more likely to use dietary supplements. Thus, lifestyle and dietary composition should be considered as confounders on supplement use and health outcomes.

Herbal medications and other dietary supplements. A clinical review for physicians caring for older people.

PubMed

Pitkälä, Kaisu H; Suominen, Merja H; Bell, J Simon; Strandberg, Timo E

2016-12-01

Evidence for the safety and effectiveness of dietary supplements is mixed. The extent to which older people use dietary supplements concomitantly with conventional medications is often under-appreciated by physicians. We conducted a literature review on clinical considerations associated with dietary supplement use, focusing on benefits and harms, motivations for use and contribution to polypharmacy among older people. Vitamin D ≥ 800 IU has demonstrated benefits in fracture prevention. Vitamins A, E, and β-carotene have been associated with an increase in total mortality in several meta-analyses. A range of non-vitamin dietary supplements have been studied in randomized controlled trials but their efficacy remains largely unclear. Supplement use has been associated with a range of adverse events and drug interactions yet physicians rarely initiate discussions about their use with older patients. Older people may take dietary supplements to exercise control over their health. Given the contribution of supplements to polypharmacy, supplements may be targeted for "deprescribing" if the risk of harm is judged to outweigh benefits. This is best done as part of a comprehensive, patient-centered approach. A respectful and non-judgmental discussion may result in a shared decision to reduce polypharmacy through cessation of dietary supplements. KEY MESSAGES Herbal medications and other dietary supplements are highly prevalent among older people. Physicians are often unaware that their patients use herbal medications and other dietary supplements concomitantly with conventional medications. Herbal medications and other dietary supplements contribute to high rates of polypharmacy, particularly among older people with multimorbidity. Herbal medications and other dietary supplements can interact with conventional medications and be associated with a range of adverse events. Physicians need to be patient-centered and non-judgmental when initiating discussions about

A rational regulatory approach for positron emission tomography imaging probes: from "first in man" to NDA approval and reimbursement.

PubMed

Barrio, Jorge R; Marcus, Carol S; Hung, Joseph C; Keppler, Jennifer S

2004-01-01

We propose a new regulatory approach for positron emission tomography (PET) molecular imaging probes, essential tools in today's medicine. Even though the focus of this paper is on positron-emitting labeled probes, it is also justified to extend this proposed regulatory approach to other diagnostic nuclear medicine radiopharmaceuticals. Key aspects of this proposal include: (1) PET molecular imaging probes would be placed in a "no significant risk" category, similar to that category for devices in current Food and Drug Administration (FDA) regulations, based on overwhelming scientific evidence that demonstrates their faultless safety profile; (2) the FDA-sanctioned Radioactive Drug Research Committee (RDRC) will oversee all diagnostic research with these probes. The newly defined RDRC should approve "first in man" use; supervise a broader spectrum of diagnostic research protocols, including those looking to demonstrate initial efficacy, as well as multicenter clinical trials and the use of molecular imaging probes as a screening tool in drug discovery. The current investigational new drug (IND) mechanism is thus eliminated for these diagnostic probes; (3) when a molecular imaging probe has demonstrated diagnostic efficacy, FDA approval (i.e., NDA) will be sought. The review will be done by a newly constituted Radioactive Drug Advisory Committee (RDAC) composed of experts chosen by the professional societies, who would provide a binding assessment of the adequacy of the safety and efficacy data. When the RDAC recommends its diagnostic use on scientific and medical grounds, the molecular imaging probe becomes FDA approved. After a molecular imaging probe is approved for a diagnostic indication, the existing mechanism to seek reimbursement will be utilized; and (4) the FDA would retain its direct oversight function for traditional manufacturers engaged in commercial distribution of the approved diagnostic molecular imaging probes (i.e., under NDA) to monitor

Therapy of Hypoparathyroidism With PTH(1–84): A Prospective Six Year Investigation of Efficacy and Safety

PubMed Central

Cusano, Natalie E.; Fan, Wen-Wei; Delgado, Yasmine; Zhang, Chengchen; Costa, Aline G.; Cremers, Serge; Dworakowski, Elzbieta; Bilezikian, John P.

2016-01-01

Context: Human recombinant (rh)PTH(1–84) was recently approved for the treatment of refractory hypoparathyroidism, based upon a short-term phase 3 clinical trial. Long-term data are needed, because no time limit was placed on the treatment period. Objective: We studied the effect of long-term rhPTH(1–84) treatment in hypoparathyroidism for up to 6 years. Design: Prospective open-label study. Setting: Referral center. Patients: A total of 33 subjects with hypoparathyroidism. Interventions: rhPTH(1–84) treatment was initiated at a starting dose of 100 μg every other day for 6 years. Due to the availability of new dosages during the 6-year time period of the study, the dose could be and was adjusted for most patients to a daily dosing regimen. Main Outcome Measures: Supplemental calcium and vitamin D requirements, serum and urinary calcium (monthly for 6 mo and then biannually), serum phosphorus, bone turnover markers, and bone mineral density (BMD) biannually. Results: Treatment with rhPTH(1–84) progressively reduced supplemental calcium requirements over 6 years by 53% (P < .0001) and 1,25-dihydroxyvitamin D requirements by 67% (P < .0001). Sixteen subjects (48%) were able to eliminate 1,25-dihydroxyvitamin D supplementation completely. Serum calcium concentration remained stable, and urinary calcium excretion fell. Lumbar spine BMD increased (3.8 ± 1%, P = .004) as did total hip BMD (2.4 ± 1%, P = .02), whereas femoral neck BMD remained stable and the distal one third radius decreased (−4.4 ±1%, P < .0001). Bone turnover markers increased significantly, reaching a 3-fold peak above baseline values at 1 year and subsequently declining but remaining higher than pretreatment values. Hypercalcemia was uncommon (12 episodes over 6 y; 2.5% of all values). Conclusions: Long-term, continuous therapy of hypoparathyroidism for 6 years with rhPTH(1–84) is associated with reductions in supplemental calcium and calcitriol requirements, stable serum calcium

Review of the safety and efficacy of vitamin A supplementation in the treatment of children with severe acute malnutrition.

PubMed

Iannotti, Lora L; Trehan, Indi; Manary, Mark J

2013-09-12

World Health Organization (WHO) guidelines recommend for children with severe acute malnutrition (SAM), high-dose vitamin A (VA) supplements be given on day 1 of admission, and on days 2 and 14 in the case of clinical signs of vitamin A deficiency (VAD). Daily low-dose VA follows, delivered in a premix added to F-75 and F-100. This study aimed to systematically review the evidence for safety and effectiveness of high-dose VA supplementation (VAS) in treatment of children with SAM. A comprehensive literature review was undertaken for all relevant randomized controlled trials (RCT) and observational studies from 1950 to 2012. Studies identified for full review were evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology using a set of pre-defined criteria: indirectness; inconsistency; imprecision; and study limitations. A quality rating of high, moderate, or low was then assigned to each study, and only those attaining moderate to high were considered in making recommendations. Of the 2072 abstracts screened, 38 met criteria for full review, and 20 were rated moderate to high quality. Only one study replicated the WHO VA protocol in children with SAM. Indirectness was a critical limitation, as studies were not exclusive to children with SAM. There was inconsistency across trials for definitions of malnutrition, morbidities, and ages studied; and imprecision arising from sub-group analyses and small sample sizes. Evidence showed improved outcomes associated with low-dose compared to high-dose VAS, except in cases presenting with signs of VAD, measles, and severe diarrhea or shigellosis. Adverse outcomes related to respiratory infection, diarrhea, and growth were associated with high-dose VAS in children who were predominantly adequately nourished. No adverse effects of the high dose were found in children with SAM in the trial that replicated the WHO VA guideline. This is the first systematic review of the safety and

Anesthetic efficacy and heart rate effects of the supplemental intraosseous injection of 2% mepivacaine with 1:20,000 levonordefrin.

PubMed

Guglielmo, A; Reader, A; Nist, R; Beck, M; Weaver, J

1999-03-01

The purpose of this study was to determine the anesthetic efficacy and heart rate effects of a supplemental intraosseous injection of 2% mepivacaine with 1:20,000 levonordefrin. Through use of a repeated-measures design, 40 subjects randomly received 3 combinations of injections at 3 separate appointments. The combinations were as follows: inferior alveolar nerve (IAN) block (with 3% mepivacaine) + intraosseous injection of 1.8 mL of 2% mepivacaine with 1:20,000 levonordefrin; IAN block + intraosseous injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine (positive control); IAN block + mock intraosseous injection (negative control). Each first molar, second molar, and second premolar was blindly tested with a pulp tester at 2-minute cycles for 60 minutes after injection. Anesthesia was considered successful when 2 consecutive readings of 80 were obtained. Heart rate (pulse rate) was measured with a pulse oximeter. One hundred percent of the subjects had lip numbness with the IAN block + intraosseous mock technique and IAN block + intraosseous techniques. The anesthetic success rates for IAN block + mock intraosseous injection, IAN block + intraosseous lidocaine, and IAN block + intraosseous mepivacaine, respectively, were as follows: 80%, 100%, and 100% for the first molar; 90%, 100%, and 100% for the second molar; 77%, 97%, and 97% for the second premolar. For the first molar and second premolar, the differences were significant (P< .05) when the intraosseous mepivacaine and lidocaine techniques were compared with the IAN block + mock intraosseous injection. There were no significant differences between the intraosseous mepivacaine and lidocaine techniques. Eighty percent of the subjects had a mean increase in heart rate of 23-24 beats per minute with the intraosseous injection of the mepivacaine and lidocaine solutions; there were no significant differences between results with the 2 solutions. We concluded that intraosseous injection of 1.8 mL of 2

Supplemented vaccination with tandem repeat M2e virus-like particles enhances protection against homologous and heterologous HPAI H5 viruses in chickens.

PubMed

Song, Byung-Min; Kang, Hyun-Mi; Lee, Eun-Kyoung; Jung, Suk Chan; Kim, Min-Chul; Lee, Yu-Na; Kang, Sang-Moo; Lee, Youn-Jeong

2016-01-27

Highly pathogenic avian influenza (HPAI) H5 viruses derived from A/Goose/Guangdong/1/96 have been continuously circulating globally, severely affecting the public health and poultry industries. The matrix 2 protein ectodomain (M2e) is considered a promising candidate for a universal cross-protective influenza vaccine that provides more effective control over HPAI H5 viruses harboring variant hemagglutinin (HA)-antigens. Here, we evaluated the protective efficacy of a tandem repeat construct of heterologous M2e presented on virus-like particles (M2e5x VLPs) either alone or as a supplement against HPAI H5 viruses in a chicken model. Chickens immunized with M2e5x VLPs alone induced M2e-specific antibodies but were not protected against HPAI H5. The homo- and cross-protective efficacy of M2e5x VLP-supplemented vaccination of chickens was also examined. Importantly, supplementation with M2e5x VLPs induced significantly higher levels of antibodies specific for M2e and different viruses as well as provided improved protection against homologous and heterologous HPAI H5 viruses. Considering the limited efficacy of inactivated vaccines, supplement vaccination with M2e5x VLPs may be an effective measure for preventing outbreaks of HPAI viruses that have the ability to constantly change their antigenic properties in poultry. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of protein supplementation on muscular performance and resting hormonal changes in college football players.

PubMed

Hoffman, Jay R; Ratamess, Nicholas A; Kang, Jie; Falvo, Michael J; Faigenbaum, Avery D

2007-01-01

The effect of protein supplementation on athletic performance and hormonal changes was examined in 21 experienced collegiate strength/power athletes participating in a 12-week resistance training program. Subjects were randomly assigned to either a protein supplement (PR; n = 11) or a placebo (PL; n = 10) group. During each testing session subjects were assessed for strength (one repetition maximum [1-RM] bench press and squat), power (Wingate anaerobic power test) and body composition. Resting blood samples were analyzed at weeks 0 (PRE), 6 (MID) and 12 (POST) for total testosterone, cortisol, growth hormone, and IGF-1. No difference was seen in energy intake between PR and PL (3034 ± 209 kcal and 3130 ± 266 kcal, respectively), but a significant difference in daily protein intake was seen between PR (2.00 g·kg body mass[BM](-1)·d(-1)) and PL (1.24 g·kgBM(-1)·d(-1)). A greater change (p < 0.05) in the ∆ 1-RM squat was seen in PR (23.5 ± 13.6 kg) compared to PL (9.1 ± 11.9 kg). No other significant strength or power differences were seen between the groups. Cortisol concentrations were significantly lower at MID for PL and this difference was significantly different than PR. No significant changes were noted in resting growth hormone or IGF-1 concentrations in either group. Although protein supplementation appeared to augment lower body strength development, similar upper body strength, anaerobic power and lean tissue changes do not provide clear evidence supporting the efficacy of a 12-week protein supplementation period in experienced resistance trained athletes. Key pointsCollegiate strength/power athletes may not meet daily recommended energy or protein needs.When athletes are provided a protein supplement they appear to meet the recommended daily protein intake for strength/power athletes.Protein supplementation did augment lower body strength development in experienced strength/power athletes.Results of upper body strength, anaerobic power and lean

Efficacy of rivastigmine tartrate, transdermal system, in Alzheimer's disease.

PubMed

Nieto, Rachel A; Deardorff, William James; Grossberg, George T

2016-01-01

As the most common major neurocognitive disorder, Alzheimer's disease (AD) will play an increasingly important role both socially and financially as the population ages. Approved treatments for AD are symptomatic in nature and show modest improvements in cognition and global functioning among patients with AD. This article focuses on the pharmacokinetics, pharmacodynamics, efficacy, and safety of the transdermal patch form of the cholinesterase inhibitor rivastigmine. The rivastigmine transdermal system is approved for the treatment of patients with mild, moderate, and severe AD. Three randomized trials have shown the rivastigmine patch to be efficacious and tolerable across all stages of AD. The rivastigmine patch offers several advantages over the capsule form, including decreased peak to trough plasma fluctuations, reduced rates of nausea and vomiting, better treatment adherence, higher probability of reaching the target dose, ease of administration, and greater satisfaction among caregivers. These factors may be especially important in patients with severe AD, in which patients are more vulnerable to adverse side effects from higher doses. While the patch is more expensive than generic therapies, patient populations that may benefit from the patch include those that are particularly sensitive to GI side effects, have chronic gastrointestinal problems, have difficulty swallowing medications, or have failed to respond with high doses of other generic options.

Absorption and bioeffects of an isoflavone-based supplementation in postmenopausal women

PubMed Central

Pampaloni, Barbara; Bartolini, Silvia; Bartolini, Elisa; Ottanelli, Silva; Masi, Laura; Romani, Annalisa; Tanini, Annalisa; Vignolini, Pamela; Brandi, Maria Luisa

2009-01-01

Epidemiological studies suggest that consumption of isoflavones rich diets can improve several postmenopausal complications. The aim of this study was to investigate the absorption and the efficacy of isoflavonic supplementation in the treatment of menopausal symptoms. 36 postmenopausal women received 75 mg/day of isoflavones in the form of tablets, for six months. 21 subjects concluded the treatment. Plasmatic and urinary samples were collected before and after the treatment, along with a dietary interview. Isoflavones were determined in biological samples and in commercial administered supplements by a HPLC/DAD system. Results showed the presence of genistein (from 0.043 to 1.820 micromol/L) in plasma samples, and of genistein (from 2.486 to 20.363 micromol/24h) and daidzein (from 11.106 to 98.091 micromol/24h) in the urines of the treated women. In the 21 completers the Greene Climateric scale value for hot flushes changed from 3 to 1 or 0. No changes of the endometrial thickness and of the breast tissue were detected. The analysis of the supplement content in the tablets was in agreement with what declared by the producer. Administration of isoflavone supplements produced a decrease of symptoms in this cohort of postmenopausal women monitored for isoflavone absorption. PMID:22461255

Effect of Folic Acid and Vitamin B12 on Pemetrexed Antifolate Chemotherapy in Nutrient Lung Cancer Cells

PubMed Central

Yang, Tsung-Ying; Chang, Gee-Chen; Hsu, Shih-Lan; Huang, Yi-Rou; Chiu, Ling-Yen

2013-01-01

Pemetrexed (MTA) is a multitargeted antifolate drug approved for lung cancer therapy. Clinically, supplementation with high doses of folic acid (FA) and vitamin B12 (VB12) lowers MTA cytotoxicities. An antagonistic effect of FA/VB12 on MTA efficacy has been proposed. However, patients who receive FA/VB12 show better tolerance to MTA with improved survival. The aims of this study are to investigate the modulation of FA and VB12 on MTA drug efficacy in human nonsmall cell lung cancer (NSCLC) cell lines. The sensitivities of cells, apoptosis, and MTA-regulated proteins were characterized to determine the possible effects of high doses of FA and VB12 on MTA efficacy. MTA has the lowest efficacy under 10% serum conditions. However, supplementation with FA and VB12 individually and additively reversed the insensitivity of NSCLC cells to MTA treatment with 10% serum. The enhanced sensitivities of cells following FA/VB12 treatment were correlated with increasing apoptosis and were specific to MTA but not to 5-fluorouracil (5-FU). Enhanced sensitivity was also associated with p21WAF1/Cip1 expression level. Our results revealed no antagonistic effect of high doses of FA/VB12 on MTA efficacy in cancer cells grown in nutrient medium. Furthermore, these data may partially explain why supplementation of FA and VB12 resulted in better survival in MTA-treated patients. PMID:23984356

Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals, supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems.

PubMed

Aboalnaja, Khaled Omer; Yaghmoor, Soonham; Kumosani, Taha Abdullah; McClements, David Julian

2016-09-01

The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability. The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given. Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.

Injunctive peer misperceptions and the mediation of self-approval on risk for driving after drinking among college students.

PubMed

Kenney, Shannon R; LaBrie, Joseph W; Lac, Andrew

2013-01-01

Of the alcohol-related risks faced by college students, it is arguable that none presents a greater public health hazard than driving after drinking (DAD). The present study examined the extent to which students' injunctive misperceptions toward DAD predicted the likelihood to engage in DAD and how this relation was mediated by self-approval of DAD. Participants were 2,848 college students (59.1% female, 64.6% Caucasian) from two U.S. West Coast universities who completed confidential web-based surveys assessing DAD beliefs and behaviors. Results revealed that respondents tended to overestimate their peers' approval toward DAD. Moreover, the subgroups likely to engage in DAD--men, 21 + years of age, Greek affiliated students, Caucasians, students with a family history of alcohol abuse--were also more likely to misperceive (i.e., overestimate) their peers' level of approval toward DAD. Using binary logistic regression analyses, self-approval of DAD emerged as an important statistical mediator in the relation between misperception of typical student approval toward DAD and engagement in DAD. Results point to the considerable role injunctive peer misperceptions may play in the pathways leading to drinking-driving risk. These findings provide preliminary support for DAD-specific social normative interventions, either complementing or supplementing existing alcohol interventions. By targeting high-risk student subgroups and communicating accurate drinking-driving norms, these proposed interventions have the potential to reduce self-approval and incidence of DAD.

Acute L-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men.

PubMed

Wax, Benjamin; Kavazis, Andreas N; Webb, Heather E; Brown, Stanley P

2012-04-17

Dietary supplements containing L-arginine are marketed to improve exercise performance, but the efficacy of such supplements is not clear. Therefore, this study examined the efficacy of acute ingestion of L-arginine alpha-ketoglutarate (AAKG) muscular strength and endurance in resistance trained and untrained men. Eight resistance trained and eight untrained healthy males ingested either 3000mg of AAKG or a placebo 45 minutes prior to a resistance exercise protocol in a randomized, double-blind crossover design. One-repetition maximum (1RM) on the standard barbell bench press and leg press were obtained. Upon determination of 1RM, subjects completed repetitions to failure at 60% 1RM on both the standard barbell bench press and leg press. Heart rate was measured pre and post exercise. One week later, subjects ingested the other supplement and performed the identical resistance exercise protocol. Our data showed statistical significant differences (p<0.05) between resistance trained and untrained males for both 1RM and total load volume (TLV; multiply 60% of 1RM times the number of repetitions to failure) for the upper body. However, 1RM and TLV were not statistically different (p>0.05) between supplementation conditions for either resistance trained or untrained men in the bench press or leg press exercises. Heart rate was similar at the end of the upper and lower body bouts of resistance exercise with AAKG vs. placebo. The results from our study indicate that acute AAKG supplementation provides no ergogenic benefit on 1RM or TLV as measured by the standard barbell bench press and leg press, regardless of the subjects training status.

38 CFR 17.65 - Approvals and provisional approvals of community residential care facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... approvals of community residential care facilities. 17.65 Section 17.65 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Community Residential Care § 17.65 Approvals and provisional approvals of community residential care facilities. (a) An approval of a facility meeting all of...

Prevalence and predictors of children's dietary supplement use: the 2007 National Health Interview Survey1234

PubMed Central

Dwyer, Johanna; Nahin, Richard L; Rogers, Gail T; Barnes, Patricia M; Jacques, Paul M; Sempos, Christopher T; Bailey, Regan

2013-01-01

Background: Little is known about the characteristics of US children who are dietary supplement users. Objective: We described the prevalence and predictors of and reasons for giving children dietary supplements. Design: The study included children <18 y of age who participated in the Complementary and Alternative Medicine supplement of the National Health Interview Survey of 2007 whose proxies provided complete information on child dietary supplement use. Results: A total of 37% of subjects used dietary supplements, 31% of subjects used multivitamin mineral (MVM) products exclusively, 4% of subjects used single vitamins or minerals solely or in combination with MVMs, and 2% of subjects used nonvitamin, nonmineral products either solely or in combination with other supplements. Users were more likely than nonusers to be Asian, white, or non-Hispanic; belong to families with higher parental education and income levels; reside in areas other than the South; be in good, very good, or excellent health; have private health insurance; and have a usual place at which they received conventional medical care. Children (3%) with the most disease burden and health care were more likely to use supplements than were healthier children. Supplements were given for the prevention or treatment of many illnesses and conditions. Neither the caregiver's reasons nor specific supplements used were consistently associated with particular conditions. Conclusions: The 37% of US children who used any type of dietary supplements differed from nonusers in family socioeconomic status and many other health-related characteristics. Users were given supplements to prevent or treat many illnesses and conditions for which there is only limited evidence of their efficacy. PMID:23576049

Belief in the efficacy of alternative medicine among general practitioners in The Netherlands.

PubMed

Knipschild, P; Kleijnen, J; ter Riet, G

1990-01-01

A survey among 293 GPs in the Netherlands showed that many believe in the efficacy of common alternative procedures. High scores were especially found for manual therapy, yoga, acupuncture, hot bath therapy and homoeopathy. Other procedures, such as iridology, faith healing and many food supplements, were considered less useful.

To supplement or not to supplement: a metabolic network framework for human nutritional supplements.

PubMed

Nogiec, Christopher D; Kasif, Simon

2013-01-01

Flux balance analysis and constraint based modeling have been successfully used in the past to elucidate the metabolism of single cellular organisms. However, limited work has been done with multicellular organisms and even less with humans. The focus of this paper is to present a novel use of this technique by investigating human nutrition, a challenging field of study. Specifically, we present a steady state constraint based model of skeletal muscle tissue to investigate amino acid supplementation's effect on protein synthesis. We implement several in silico supplementation strategies to study whether amino acid supplementation might be beneficial for increasing muscle contractile protein synthesis. Concurrent with published data on amino acid supplementation's effect on protein synthesis in a post resistance exercise state, our results suggest that increasing bioavailability of methionine, arginine, and the branched-chain amino acids can increase the flux of contractile protein synthesis. The study also suggests that a common commercial supplement, glutamine, is not an effective supplement in the context of increasing protein synthesis and thus, muscle mass. Similar to any study in a model organism, the computational modeling of this research has some limitations. Thus, this paper introduces the prospect of using systems biology as a framework to formally investigate how supplementation and nutrition can affect human metabolism and physiology.

Dietary Supplements

MedlinePlus

... For Consumers Consumer Information by Audience For Women Dietary Supplements: Tips for Women Share Tweet Linkedin Pin it ... or 10877-382-4357. To Learn More about Dietary Supplements Information for Consumers on Using Dietary Supplements NIH ...

Efficacy of an Exercise and Nutritional Supplement Program on Physical Performance and Nutritional Status in Older Adults With Mobility Limitations Residing at Senior Living Facilities.

PubMed

Corcoran, Michael P; Nelson, Miriam E; Sacheck, Jennifer M; Reid, Kieran F; Kirn, Dylan; Fielding, Roger A; Chui, Kenneth K H; Folta, Sara C

2017-07-01

This cluster-randomized trial was designed to determine the efficacy of a 6-month exercise-nutritional supplement program (ENP) on physical function and nutritional status for older adults and the feasibility of implementing this program in a senior living setting. Twenty senior-living facilities were randomized to either a 3 day per week group-based ENP led by a trained facility staff member or a health education program (SAP). Participants (N = 121) completed a short physical performance battery, 400-m walk, handgrip strength test, and mini-nutrition assessment. 25-hydroxyvitamin D [25(OH)D], insulin-like growth-factor 1 (IGF-1), and activity level were also measured. The ENP did not significantly improve physical function or nutritional status compared with the SAP. Compared with baseline, participants in the ENP engaged in 39 min less physical activity per week at 6 months. Several facility characteristics hindered implementation of the ENP. This study highlights the complexity of implementing an evidence-based program in a field setting.

CYD-TDV dengue vaccine: systematic review and meta-analysis of efficacy, immunogenicity and safety.

PubMed

Godói, Isabella Piassi; Lemos, Livia Lovato Pires; de Araújo, Vânia Eloisa; Bonoto, Braúlio Cesar; Godman, Brian; Guerra Júnior, Augusto Afonso

2017-03-01

Dengue virus (DENV) is a serious global health problem. CYD-TDC (Dengvaxia ® ) was the first vaccine to gain regulatory approval to try and address this problem. Summarize all available evidence on the immunogenicity, efficacy and safety of the CYD-TDV dengue vaccine. Meta-analysis and systematic review. The best and worst immunogenicity results were for DENV4 and DENV1, respectively. Vaccine efficacy of 60% was derived from studies with participants aged 2-16 years old, with DENV4 and DENV2 presenting the best and worst results, respectively. Erythema and swelling were more frequent with CYD-TDV. No differences were detected for systemic adverse events. CYD-TDV showed moderate efficacy in children and adolescents. From the immunogenicity results in adults, we can expect satisfactory efficacy from vaccination in this population.

42 CFR 488.61 - Special procedures for approval and re-approval of organ transplant centers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Approval. Centers that have lost their Medicare approval may seek re-entry into the Medicare program at any... 42 Public Health 5 2012-10-01 2012-10-01 false Special procedures for approval and re-approval of... ENFORCEMENT PROCEDURES Special Requirements § 488.61 Special procedures for approval and re-approval of organ...

42 CFR 488.61 - Special procedures for approval and re-approval of organ transplant centers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Approval. Centers that have lost their Medicare approval may seek re-entry into the Medicare program at any... 42 Public Health 5 2011-10-01 2011-10-01 false Special procedures for approval and re-approval of... ENFORCEMENT PROCEDURES Special Requirements § 488.61 Special procedures for approval and re-approval of organ...

42 CFR 488.61 - Special procedures for approval and re-approval of organ transplant centers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Approval. Centers that have lost their Medicare approval may seek re-entry into the Medicare program at any... 42 Public Health 5 2013-10-01 2013-10-01 false Special procedures for approval and re-approval of... ENFORCEMENT PROCEDURES Special Requirements § 488.61 Special procedures for approval and re-approval of organ...

42 CFR 488.61 - Special procedures for approval and re-approval of organ transplant centers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Approval. Centers that have lost their Medicare approval may seek re-entry into the Medicare program at any... 42 Public Health 5 2010-10-01 2010-10-01 false Special procedures for approval and re-approval of... ENFORCEMENT PROCEDURES Special Requirements § 488.61 Special procedures for approval and re-approval of organ...

Monitoring the efficacy of omega-3 supplementation on liver steatosis and carotid intima-media thickness: a pilot study.

PubMed

Lacasse, M-C; Tang, A; Dubois, J; Alvarez, F; Spahis, S; Chagnon, M; Deschênes, S; Levy, E

2017-06-01

To determine the effects of omega-3 supplementation on liver fat and carotid intima-media thickness (IMT) and to assess accuracy of ultrasound (US) for grading liver steatosis. In this one-way crossover pilot study, we assigned children with obesity and liver steatosis to receive 1.2 g daily of omega-3 supplementation vs. inactive sunflower oil for 24 or 12 weeks. Liver fat content was assessed by magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) and US, and common carotid IMT by US. Statistical analysis included Chi-square, Student's t -tests, ANOVA tests and receiver operating characteristic (ROC) curves. Omega-3 supplementation was associated with a trend towards decrease in MRS-determined liver fat fraction (0.7% and 2.1% decrease in the 24-week and 12-week omega-3 group, respectively) compared with the sunflower oil group (1.0% increase). These changes were not significant, whether assessed by MRS ( P  = 0.508), MRI ( P  = 0.508) or US ( P  = 0.678). Using US, the area under the ROC curves were 0.964, 0.817 and 0.783 for distinguishing inferred steatosis grades 0 vs. 1-2-3, 0-1 vs. 2-3 and 0-1-2 vs. 3, respectively, indicating good accuracy of US-based fat grading. Omega-3 supplementation was associated with a decrease in US-determined IMT (0.05-mm decrease in the 24-week omega-3 group. A 0.015-mm increase was found in the 12-week omega-3 group, and a 0.007-mm decrease in the sunflower oil group ( P  = 0.003). Omega-3 supplementation had no significant effect on liver fat fraction, but led to carotid IMT decrease in children with obesity and liver steatosis.

Interactions of commonly used dietary supplements with cardiovascular drugs: a systematic review.

PubMed

Kanji, Salmaan; Seely, Dugald; Yazdi, Fatemeh; Tetzlaff, Jennifer; Singh, Kavita; Tsertsvadze, Alexander; Tricco, Andrea C; Sears, Margaret E; Ooi, Teik C; Turek, Michele A; Skidmore, Becky; Ansari, Mohammed T

2012-05-31

The objective of this systematic review was to examine the benefits, harms and pharmacokinetic interactions arising from the co-administration of commonly used dietary supplements with cardiovascular drugs. Many patients on cardiovascular drugs take dietary supplements for presumed benefits and may be at risk for adverse supplement-drug interactions. The Allied and Complementary Medicine Database, the Cochrane Library, EMBASE, International Bibliographic Information on Dietary Supplements and MEDLINE were searched from the inception of the review to October 2011. Grey literature was also reviewed.Two reviewers independently screened records to identify studies comparing a supplement plus cardiovascular drug(s) with the drug(s) alone. Reviewers extracted data using standardized forms, assessed the study risk of bias, graded the strength of evidence and reported applicability. Evidence was obtained from 65 randomized clinical trials, 2 controlled clinical trials and 1 observational study. With only a few small studies available per supplement, evidence was insufficient for all predefined gradable clinical efficacy and harms outcomes, such as mortality and serious adverse events. One long-term pragmatic trial showed no benefit from co-administering vitamin E with aspirin on a composite cardiovascular outcome. Evidence for most intermediate outcomes was insufficient or of low strength, suggesting no effect. Incremental benefits were noted for triglyceridemia with omega-3 fatty acid added to statins; and there was an improvement in levels of high-density lipoprotein cholesterol with garlic supplementation when people also consumed nitrates Evidence of low-strength indicates benefits of omega-3 fatty acids (plus statin, or calcium channel blockers and antiplatelets) and garlic (plus nitrates or warfarin) on triglycerides and HDL-C, respectively. Safety concerns, however, persist.

The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis.

PubMed

Zhu, Mingming; Xu, Xitao; Nie, Fang; Tong, Jinlu; Xiao, Shudong; Ran, Zhihua

2011-08-01

The use of selective leukocytapheresis for the treatment of ulcerative colitis (UC) has been evaluated in several open and controlled trials, with varying outcomes. A meta-analysis was performed to better assess the efficacy and safety of selective leukocytapheresis as supplemental therapy compared with conventional pharmacotherapy in patients with UC. All randomized trials comparing selective leukocytapheresis supplementation with conventional pharmacotherapy were included from electronic databases and reference lists. A meta-analysis that pooled the outcome effects of leukocytapheresis and pharmacotherapy was performed. A fixed effect model or random effect model was selected depending on the heterogeneity test of the trials. Nine randomized controlled trials met the inclusion criteria contributing a total of 686 participants. Compared with conventional pharmacotherapy, leukocytapheresis supplementation presented a significant benefit in promoting a response rate (OR, 2.88, 95% CI: 1.60-5.18) and remission rate (OR, 2.04; 95% CI, 1.36-3.07) together with significant higher steroid-sparing effects (OR, 10.49; 95% CI, 3.44-31.93) in patients with active moderate-to-severe UC by intention-to-treat analysis. Leukocytapheresis was more effective in maintaining clinical remission for asymptomatic UC patients than conventional therapy (OR, 8.14; 95% CI, 2.22-29.90). The incidence of mild-moderate adverse effects was much less frequent in the leukocytapheresis groups than conventional pharmacotherapy groups (OR, 0.16; 95% CI, 0.04-0.60). Few severe adverse events were observed. Current data indicate that leukocytapheresis supplementation may be more efficacious on improving response and remission rates and tapering corticosteroid dosage with excellent tolerability and safety than conventional pharmacotherapy in patients with UC. In addition, more high-quality randomized controlled trials are required to confirm the higher efficacy of leukocytapheresis in patients with UC.

Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis.

PubMed

Ganesan, Murali; Feng, Dan; Barton, Ryan W; Thomes, Paul G; McVicker, Benita L; Tuma, Dean J; Osna, Natalia A; Kharbanda, Kusum K

2016-11-01

Alcohol-induced reduction in the hepatocellular S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio impairs the activities of many SAM-dependent methyltransferases. These impairments ultimately lead to the generation of several hallmark features of alcoholic liver injury including steatosis. Guanidinoacetate methyltransferase (GAMT) is an important enzyme that catalyzes the final reaction in the creatine biosynthetic process. The liver is a major site for creatine synthesis which places a substantial methylation burden on this organ as GAMT-mediated reactions consume as much as 40% of all the SAM-derived methyl groups. We hypothesized that dietary creatine supplementation could potentially spare SAM, preserve the hepatocellular SAM:SAH ratio, and thereby prevent the development of alcoholic steatosis and other consequences of impaired methylation reactions. For these studies, male Wistar rats were pair-fed the Lieber-DeCarli control or ethanol (EtOH) diet with or without 1% creatine supplementation. At the end of 4 to 5 weeks of feeding, relevant biochemical and histological analyses were performed. We observed that creatine supplementation neither prevented alcoholic steatosis nor attenuated the alcohol-induced impairments in proteasome activity. The lower hepatocellular SAM:SAH ratio seen in the EtOH-fed rats was also not normalized or SAM levels spared when these rats were fed the creatine-supplemented EtOH diet. However, a >10-fold increased level of creatine was observed in the liver, serum, and hearts of rats fed the creatine-supplemented diets. Overall, dietary creatine supplementation did not prevent alcoholic liver injury despite its known efficacy in preventing high-fat-diet-induced steatosis. Betaine, a promethylating agent that maintains the hepatocellular SAM:SAH, still remains our best option for treating alcoholic steatosis. Copyright © 2016 by the Research Society on Alcoholism.

Oral Omega-3 Supplementation Lowers Intraocular Pressure in Normotensive Adults.

PubMed

Downie, Laura Elizabeth; Vingrys, Algis Jonas

2018-05-01

Elevated intraocular pressure (IOP) is the major modifiable risk factor for the sight-threatening eye disease, glaucoma. We investigated whether oral omega-3 supplements affect IOP in normotensive adults. We undertook a pooled analysis of data from two double-masked, placebo-controlled randomized trials (Australian New Zealand Clinical Trials Registry, ACTRN12614001019695, ACTRN12615000173594) that investigated the efficacy and safety of oral omega-3 supplementation for treating ocular surface inflammation. Recruitment involved adults ( n = 105) with IOP <21 mm Hg, and without a current or prior glaucoma diagnosis. Participants were randomly allocated to either an oral omega-3 (∼1000 mg/day eicosapentaenoic acid + ∼500 mg/day docosahexaenoic acid ± 900 mg/day α-linolenic acid) or placebo (olive oil, 1500 mg/day) supplement. IOP was quantified at baseline and after 3 months of supplementation (day 90). Change in IOP, relative to baseline, was compared between groups. At baseline, participants were of similar age (omega-3/placebo groups: mean ± SEM, 33.7 ± 1.7, n = 72/35.6 ± 3.0 years, n = 33), sex (65%/79% female), and had similar IOP (14.3 ± 0.3/13.8 ± 0.5 mm Hg). At day 90, IOP was reduced to 13.6 ± 0.3 mm Hg in the omega-3 group; controls had a slight IOP increase to 14.2 ± 0.4 mm Hg ( P < 0.05). Oral omega-3 supplementation for 3 months significantly reduced IOP in normotensive adults. To our knowledge, this is the first study to report that omega-3 fatty acids lower IOP in humans. These findings justify further investigation into the therapeutic potential of omega-3 supplementation for reducing IOP, to prevent and/or treat conditions with IOP elevation, including ocular hypertension and glaucoma.

Efficacy of a First-Grade Responsiveness-to-Intervention Prevention Model for Struggling Readers

ERIC Educational Resources Information Center

Gilbert, Jennifer K.; Compton, Donald L.; Fuchs, Douglas; Fuchs, Lynn S.; Bouton, Bobette; Barquero, Laura A.; Cho, Eunsoo

2013-01-01

This randomized control trial examined the efficacy of a multitiered supplemental tutoring program within a first-grade responsiveness-to-intervention prevention model. Struggling first-grade readers (n = 649) were screened and progress monitored at the start of the school year. Those identified as unresponsive to general education Tier 1 (n =…