Multi-Criteria Decision Analysis Model for Assessing the Risk from Multi-Ingredient Dietary Supplements (MIDS).

Military personnel use dietary supplements (DS) for performance enhancement, bodybuilding, weight loss, and to maintain health. Adverse events, including cardiovascular (CV) effects, have been reported in military personnel taking supplements. Previous research determined that ingestion of multi-ingredient dietary supplements (MIDS), can lead to signals of safety concerns. Therefore, to assess the safety of MIDS, the Department of Defense via a contractor explored the development of a model-based risk assessment tool. We present a strategy and preliminary novel multi-criteria decision analysis (MCDA)-based tool for assessing the risk of adverse CV effects from MIDS. The tool integrates toxicology and other relevant data available on MIDS; likelihood of exposure, and biologic plausibility that could contribute to specific aspects of risk.Inputs for the model are values of four measures assigned based on the available evidence supplemented with the opinion of experts in toxicology, modeling, risk assessment etc. Measures were weighted based on the experts' assessment of measures' relative importance. Finally, all data for the four measures were integrated to provide a risk potential of 0 (low risk) to 100 (high risk) that defines the relative risk of a MIDS to cause adverse reactions.We conclude that the best available evidence must be supplemented with the opinion of experts in medicine, toxicology and pharmacology. Model-based approaches are useful to inform risk assessment in the absence of data. This MCDA model provides a foundation for refinement and validation of accuracy of the model predictions as new evidence becomes available.

Safety and performance benefits of arginine supplements for military personnel: a systematic review.

CONTEXT: Dietary supplements are widely used by military personnel and civilians for promotion of health. OBJECTIVE: The objective of this evidence-based review was to examine whether supplementation with l-arginine, in combination with caffeine and/or creatine, is safe and whether it enhances athletic performance or improves recovery from exhaustion for military personnel. DATA SOURCES: Information from clinical trials and adverse event reports were collected from 17 databases and 5 adverse event report portals. STUDY SELECTION: Studies and reports were included if they evaluated the safety and the putative outcomes of enhanced performance or improved recovery from exhaustion associated with the intake of arginine alone or in combination with caffeine and/or creatine in healthy adults aged 19 to 50 years. DATA EXTRACTION: Information related to population, intervention, comparator, and outcomes was abstracted. Of the 2687 articles screened, 62 articles meeting the inclusion criteria were analyzed. Strength of evidence was assessed in terms of risk of bias, consistency, directness, and precision. RESULTS: Most studies had few participants and suggested risk of bias that could negatively affect the results. l-Arginine supplementation provided little enhancement of athletic performance or improvements in recovery. Short-term supplementation with arginine may result in adverse gastrointestinal and cardiovascular effects. No information about the effects of arginine on the performance of military personnel was available. CONCLUSIONS: The available information does not support the use of l-arginine, either alone or in combination with caffeine, creatine, or both, to enhance athletic performance or improve recovery from exhaustion. Given the information gaps, an evidence-based review to assess the safety or effectiveness of multi-ingredient dietary supplements was not feasible, and therefore the development of a computational model-based approach to predict the safety of multi-ingredient dietary supplements is recommended.

Trends in Androgen Prescriptions From Military Treatment Facilities: 2007 to 2011.

INTRODUCTION: The role of testosterone in health and quality of life has become increasingly visible and overtly marketed to the public. Some evidence suggests that testosterone levels in men may be low because of a variety of reasons, including stress and environmental exposures. OBJECTIVE: This study examines trends in testosterone prescriptions dispensed by military treatment facilities (MTFs). METHODS: We examined data from the Department of Defense Pharmacy Data Transaction Service to determine the nature of androgen prescriptions dispensed through MTFs from 2007 through 2011. RESULTS: The number of androgen prescriptions increased more than two-fold across the military from 19,494 in 2007 to 45,270 in 2011. Most prescriptions (99%) were for men. Androgen prescription rates rose 23% per year from 2007 through 2011 (p < 0.001, CI 23-24%). The prescription rate for 35- to 44-year-olds increased more than any other age group, with annual increases averaging 33% (p < 0.001, CI 32-34%). CONCLUSION: The number of androgen prescriptions within MTFs rose significantly from 2007 through 2011. This is similar to rises in androgen prescriptions seen in civilian medical systems. Clinical indications for the sharp increase in testosterone prescriptions are unknown, and the indications for clinically appropriate testosterone replacement need further clarification.

Third-Party Evaluation: A Review of Dietary Supplements Dispensed by Military Treatment Facilities From 2007 to 2011.

INTRODUCTION: Third-party certification/verification of dietary supplements (DS), although not mainstream, is one way to help ensure high-quality products. In the medical setting, physicians may prescribe DS to correct a deficiency or improve a health care outcome, and they want products of a certain standard of quality, free of adulteration/contamination. OBJECTIVE: We reviewed DS dispensed from all Department of Defense military treatment facilities over a 5-year period to determine which products had been third-party reviewed and certified/verified. METHODS: By using product name, manufacturer, and/or National Drug Codes, we examined product listings on the websites of three independent-evaluating organizations. RESULTS: Over 1.5 million dietary supplement prescriptions consisting of 753 different products were dispensed from 2007 through 2011. Less than 3.6% of the products examined were third-party certified/verified by any of the three most well-known evaluation organizations: 19 were verified by United States Pharmacopeial Convention; 9 products were reviewed and 8 certified by ConsumerLab; and none of the products were certified by NSF International. CONCLUSION: Most DS dispensed by military treatment facilities are not reviewed by a third party. This is not unexpected, as third party certification is not yet mainstream. However, one way to reduce potential hazards and exposure to unsafe products is to encourage use of supplements that have third-party certification/verification.

Trends in B-Vitamin Prescriptions From Military Treatment Facilities: 2007 to 2011.

INTRODUCTION: The use of B-vitamin supplements has increased over the last decade. Although use is widespread in both military and civilian populations, data on patterns of B-vitamin prescription rates are lacking. OBJECTIVE: This study examines trends in B-vitamin prescriptions dispensed by military treatment facilities. METHODS: We examined data from the Department of Defense Pharmacy Data Transaction Service to determine the nature of several B-vitamin prescriptions dispensed through military treatment facilities from 2007 through 2011. The eight B vitamins examined were B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (panthenol), B6 (pyridoxine), B7 (biotin), B9 (folic acid), and B12 (cobalamin). RESULTS: The number of B-vitamin prescriptions dispensed from military treatment facilities decreased 7% from 278,972 in 2007 to 260,472 in 2011. Individual vitamin prescription patterns varied widely. Vitamins B6, B9, and B12 were the most frequently prescribed in each year. Vitamin B2 prescriptions quadrupled between 2009 and 2011, and B12 prescriptions showed a steady increase over time. In contrast, vitamins B3, B6, and B9 prescriptions showed a steady decline, and vitamin B7 prescriptions decreased by 66% between 2008 and 2009. CONCLUSIONS: No single pattern in B-vitamin prescriptions was observed. The driving forces behind increases in prescribed and non-prescribed dietary supplement use remain speculative.

Trends in Mineral Supplement Prescriptions From Military Treatment Facilities: 2007 to 2011.

INTRODUCTION: Mineral supplements such as calcium and iron are readily available over the counter and are some of the most frequently consumed dietary supplements. Health care providers also prescribe mineral supplements for treatment of certain conditions and to maintain health. OBJECTIVE: This study examines trends in mineral-supplement prescriptions dispensed by military treatment facilities. METHODS: We examined data from the DoD Pharmacy Data Transaction Service to determine the nature of mineral-supplement prescriptions dispensed by MTFs from 2007 through 2011. RESULTS: Overall, 1,785,158 calcium, 844,655 iron, 166,207 magnesium, and 23,297 zinc prescriptions were dispensed over this 5-year period. Although the number of zinc prescriptions decreased considerably by an average of 30% across the 5-year period, calcium and magnesium prescriptions increased by 3% and 8%, respectively. The number of iron prescriptions dispensed was relatively stable across the 5 years. CONCLUSIONS: Patterns of mineral-supplement prescriptions in the military changed over the 5-year period examined. However, the patterns within the DoD medical system may or may not represent those of the civilian medical system. Because we could not determine the reasons why the mineral supplements were prescribed, we cannot report whether the supplements were effective for the intended uses.

Trends in Vitamin A, C, D, E, K Supplement Prescriptions From Military Treatment Facilities: 2007 to 2011.

INTRODUCTION: Although prior studies have examined the prevalence of dietary supplement use among various populations, data on single vitamins prescribed by health care providers are limited. OBJECTIVE: This study examined trends in single-vitamin supplement (A, C, D, E, K) prescriptions by providers from military treatment facilities from 2007 to 2011. METHODS: We examined prescription data from the Department of Defense Pharmacy Data Transaction Service to determine trends in the aforementioned single-vitamin supplement prescriptions. Prescription rates per 1,000 active duty personnel were estimated using population data retrieved from the Defense Medical Epidemiology Database (i.e., [number of prescriptions/population size] × 1,000). RESULTS: Across the 5-year period, the number of vitamin D prescriptions per 1,000 active duty personnel increased 454%. In contrast, the number of vitamin A, vitamin E, and vitamin K prescriptions per 1,000 active duty personnel decreased by 32%, 53%, and 29% respectively. Vitamin C prescriptions remained relatively constant. Across all age groups, total single-vitamin supplement prescriptions increased by 180%. CONCLUSION: Together, prescriptions examined in this study increased steadily from 2007 to 2011, primarily because of the increase in vitamin D prescriptions. The exhibited trend reflects the current general-population pattern of dietary supplement use, with large increases in vitamin D and declines in vitamin E.

Energy drink and energy shot use in the military.

Use of energy drinks and energy shots among military personnel is controversial. High amounts of caffeine (the primary active ingredient in these products) may impact performance of military duties. The impact of caffeine overconsumption and potential subsequent side effects that might be experienced by service members with unique roles and responsibilities is a concern. Reported here are the prevalence of use, reasons for use, and side effects associated with consumption of energy drinks and energy shots among several populations of active duty personnel in the US military. A snowball survey was sent to over 10,000 active duty personnel. A total of 586 (∼6% response rate) individuals completed a 30-item electronic survey. Over half of respondents (53%) reported consuming an energy drink at least once in the past 30 days. One in five (19%) reported energy shot consumption in the prior 30 days. One in five (19%) also reported consuming an energy drink in combination with an alcoholic beverage. Age and gender were significantly associated with energy drink consumption. Young male respondents (18-29 years) reported the highest use of both energy drinks and energy shots. Among those reporting energy drink and energy shot use, the most common reasons for consumption were to improve mental alertness (61%) and to improve mental (29%) and physical (20%) endurance. Nearly two-thirds (65%) of users self-reported at least one side effect. The most commonly reported side effects included increased pulse rate/palpitations, restlessness, and difficulty sleeping. Use of energy products among military personnel is common and has the potential to impact warrior health and military readiness.

Evidence-based evaluation of potential benefits and safety of beta-alanine supplementation for military personnel.

This Department of Defense-sponsored evidence-based review evaluates the safety and putative outcomes of enhancement of athletic performance or improved recovery from exhaustion in studies involving beta-alanine alone or in combination with other ingredients. Beta-alanine intervention studies and review articles were collected from 13 databases, and safety information was collected from adverse event reporting portals. Due to the lack of systematic studies involving military populations, all the available literature was assessed with a subgroup analysis of studies on athletes to determine if beta-alanine would be suitable for the military. Available literature provided only limited evidence concerning the benefits of beta-alanine use, and a majority of the studies were not designed to address safety. Overall, the strength of evidence in terms of the potential for risk of bias in the quality of the available literature, consistency, directness, and precision did not support the use of beta-alanine by military personnel. The strength of evidence for a causal relation between beta-alanine and paresthesia was moderate.

Schizophrenia: multi-attribute utility theory approach to selection of atypical antipsychotics.

BACKGROUND: Current guidelines/algorithms recommend atypical antipsychotics as first-line agents for the treatment of schizophrenia. Because there are extensive healthcare costs associated with the treatment of schizophrenia, many institutions and health systems are faced with making restrictive formulary decisions regarding the use of atypical antipsychotics. Often, medication acquisition costs are the driving force behind formulary decisions, while other treatment factors are not considered. OBJECTIVE: To apply a multi-attribute utility theory (MAUT) analysis to aid in the selection of a preferred agent among the atypical antipsychotics for the treatment of schizophrenia. METHODS: Five atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole) were selected as the alternative agents to be included in the MAUT analysis. The attributes identified for inclusion in the analysis were efficacy, adverse effects, cost, and adherence, with relative weights of 35%, 35%, 20%, and 10%, respectively. For each agent, attribute scores were calculated, weighted, and then summed to generate a total utility score. The agent with the highest total utility score was considered the preferred agent. RESULTS: Aripiprazole, with a total utility score of 75.8, was the alternative agent with the highest total utility score in this model. This was followed by ziprasidone, risperidone, and quetiapine, with total utility scores of 71.8, 69.0, and 65.9, respectively. Olanzapine received the lowest total utility score. A sensitivity analysis was performed and failed to displace aripiprazole as the agent with the highest total utility score. CONCLUSIONS: This model suggests that aripiprazole should be considered a preferred agent for the treatment of schizophrenia unless found to be otherwise inappropriate.