Online Marketing of Ephedra Weight Loss Supplements: Labeling and Marketing Compliance with the U.S. Food and Drug Administration Ban on Ephedra.

Objective: To characterize dietary supplements marketed online as "ephedra-containing or ephedra-like products" for weight management and to assess labeling/marketing compliance with the ban on the sale of ephedrine alkaloids. Materials and Methods: This cross-sectional study assessed websites selling ephedra-like supplements using the search term "buy ephedra." For each website, the first three featured products were characterized by evaluating the label for (1) Ephedra sp. or its alkaloid content, (2) serving size, (3) other ingredients, (4) directions, (5) side effects, (6) reported interactions, (7) recommendation to consult a health care provider, (8) recommendation to use with diet and exercise, and (9) Food and Drug Administration (FDA) disclaimer. Results: Thirty-six (71%) of the first 51 websites evaluated sold at least one weight loss product. A total of 105 products were assessed, 93 had labeling with 10 (11%) in possible violation of the ephedra ban. Five were labeled as containing ephedrine or ephedrine hydrochloride, two reported containing ephedrine alkaloids, and two reported containing unidentified Ephedra sp. not formulated as an extract; one reported containing Ma Huang. Sixty-seven (72%) products listed caffeine with a daily serving size averaging 400 mg. Other ingredients with stimulant properties include green tea, yohimbe, and phenylethylamine. Conclusions: Nearly 20% of websites sold weight loss products that potentially violated the 2004 ban of ephedra alkaloids. Ephedrine, unidentified Ephedra sp. not formulated as an extract, and Ma Huang were labeled as present in 11% of products evaluated. Incomplete reporting of adverse effects and drug interactions was common.

Violation of US regulations regarding online marketing and sale of e-cigarettes: FDA warnings and retailer responses.

BACKGROUND: The aim of this study was to characterise all 2018 Food and Drug Administration (FDA) warning letters specific to e-cigarette products and to evaluate whether online retailers complied with FDA requested actions. METHODS: All 2018 FDA e-cigarette warning letters issued by the Center for Tobacco Products to online retailers were reviewed and characterised. Date of issuance, name, type, and location of the retailer, and violation type were recorded. Retailer websites were rechecked a minimum of 30 days after the issuance of the warning letter to assess compliance with enforcement actions. RESULTS: One hundred and thirteen of 124 letters met the inclusion criteria; one duplicate letter and 10 letters unrelated to e-cigarettes were excluded. One manufacturer was cited for associating their e-liquid with prescription drugs, and when analysed, the e-liquid was found to contain phosphodiesterase inhibitors. A majority of violations, 98.2% (111/113), pertained to the sales of an e-cigarette product to a minor and/or use of marketing that appeals to children. The majority of websites (63.7%, 72/113) resolved all violations. However, 19.5% (22/113) inactivated their website, and 16.8% (19/113) did not fully correct all violations. CONCLUSIONS: Sales of e-cigarette products to minors and the purposeful marketing of e-liquids in a manner that appeals to children and adolescents continues to be problematic. While the warning letters were successful in getting a majority of online retailers to correct the stated violation, many sold other products that would be considered a violation of marketing to minors. The appearance of e-liquids that contain prescription medications is also alarming. Comprehensive and continued enforcement of online e-cigarette retailers is urgently needed.

Sources of drug information in neonatal guidelines of low- and middle-income countries.

OBJECTIVE: Identify drug information (DI) resources used in neonatal practice guidelines in low- and middle-income countries. METHODS: Individuals with knowledge of national neonatal guideline development completed a descriptive, cross-sectional survey. KEY FINDINGS: Eighty-five per cent (33/39) of respondents fully completed the survey. Physicians from university hospitals in Africa were primary respondents. Forty-five per cent (15/33) used a single national neonatal guideline. Primary neonatal resources for drug dosing and preparation were as follows: (1) World Health Organization Pocketbook of Hospital Care for Children, (2) Pediatric & Neonatal Dosage Handbook and (3) National Institute for Health and Care Excellence for Infants and Neonatal pathways. CONCLUSION: Low- and middle-income countries with single national neonatal guidelines cite a finite range of DI resources.

Chinese Herb Use by Patients at a San Francisco Chinatown Public Health Center.

OBJECTIVES: Chinese herbal medicine (CHM) use has not been well characterized in persons living in the United States who receive care by Western-trained healthcare providers. The primary objective of this study was to characterize use of CHM taken in the last 12 months by patients seen at a Chinatown public health center. DESIGN: Convenience sample survey. SETTING: Data collection occurred over 3 months at a San Francisco Chinatown public health center. PARTICIPANTS: Adult patients visiting their primary care provider. INTERVENTIONS: Completion of a voluntary 24-question survey on CHM use. OUTCOME MEASURES: Prevalence, type, and indications for use. RESULTS: Survey response rate was 29% (50/170). Seventy percent (35/50) of respondents had used CHM in the last 12 months and 94% (33/35) were also taking prescription medicines. The three most commonly used CHM were goji berry (37%), Dioscorea (31%), and ginseng (23%). The most common indications for herbs used in the last 12 months were general wellness (34%), cold/flu (25%), and headache (6%). Sixty-four percent of respondents had used Western medicine in combination with CHM within the last 12 months. Sixty-nine percent of respondents who used CHM did not tell their Western provider about this use. No patient had CHM use documented in the electronic medical record. CONCLUSIONS: Patients seen at a Chinatown public health center frequently used CHM products in conjunction with Western prescription medicines. Providers should routinely enquire about CHM use for health as a soup, tea, food, or pill and document this use in the medical record.

Omega-3 fatty acids and ginger in maternal health: pharmacology, efficacy, and safety.

Dietary supplements may be used by pregnant women if they perceive them to be natural and healthy products, if they are fearful of using prescription drugs, or if they are recommended by a health care provider. Usage surveys indicate that midwives feel comfortable in recommending some herbal products to their patients. There are sufficient data from randomized controlled trials on omega-3 fatty acids and ginger that their pharmacologic properties, efficacy, and safety data for specific indications in maternal health can be evaluated. Requests for information regarding these substances are likely to be encountered by health care providers who care for pregnant women. Omega-3 fatty acids benefit gestation, infant vision, and neurodevelopment, while effects on major depression in pregnancy and postpartum depression are less clear. Ginger is efficacious for nausea and vomiting in pregnancy but is limited in its safety data. Pharmacologic properties of each supplement and pathophysiology related to each indication are reviewed. It is recommended that pregnant and lactating women be advised to take an omega-3 fatty acid supplement daily, while the recommendation to use ginger is tentative and will likely be based on each practitioner's comfort level with the safety data that are presented.

Emergency department management of patients on warfarin therapy.

STUDY OBJECTIVE: To characterize warfarin management in the emergency department (ED). METHODS: This was a retrospective, cross-sectional, observational study of patients who were receiving warfarin and were discharged from a tertiary care, academic urban ED between June and August 2007. We abstracted patient demographics, presenting complaint, international normalized ratio (INR) if tested, indication for warfarin if documented, new medications administered or prescribed in the ED, and discharge instructions. Presenting complaints were categorized according to whether they were warfarin-related and concerning for thrombosis or bleeding. The primary outcome measure was the prevalence of warfarin therapy. The secondary outcome measures were frequency with which ED providers obtained an INR result, response to nontherapeutic results, administration or prescription of interacting medications, and percentage of patients receiving recommendations for anticoagulation follow-up. RESULTS: Two percent (111/7,195) of all patients presenting to and discharged from the ED during the study period were found to be receiving warfarin. Seventy-one percent (79/111) had an INR checked. Nontherapeutic INRs were recorded for 49% (39/79) of patients; ED providers intervened to address these results in 21% (8/39) of cases. Seventy-one percent (5/7) of patients with a supratherapeutic INR received an intervention compared with 9% (3/32) of patients with a subtherapeutic INR. Seventeen percent (19/111) and 13% (14/111) of patients received or were prescribed potentially interacting medications, respectively. Recommendations for specific anticoagulation follow-up were documented for 19% (21/111) of all patients. CONCLUSION: Patients receiving warfarin frequently present to the ED and often have nontherapeutic INRs. Potential areas for improvement in ED management include greater attention to subtherapeutic INRs, interacting medications, and discharge planning.

The use of herbs by california midwives.

OBJECTIVE: To characterize herbal product use (prevalence, types, indications) among Certified Nurse Midwives/Certified Midwives (CNMs/CMs) and Licensed Midwives (LMs) practicing in the state of California and to describe formal education related to herbal products received by midwives during midwifery education. DESIGN/SETTING/PARTICIPANTS: Cross-sectional survey/California/Practicing midwives. METHODS: A list of LMs and CNMs/CMs practicing in California was obtained through the California Medical Board (CMB) and the American College of Nurse Midwives (ACNM), respectively. The survey was mailed to 343 CNMs/CMs (one third of the ACNM mailing list) and 157 LMs (the complete CMB mailing list). RESULTS: Of the 500 surveys mailed, 40 were undeliverable, 146 were returned, and 7 were excluded (30% response rate). Of the 139 completed surveys, 58/102 (57%) of CNMs/CMs and 35/37 (95%) of LMs used herbs, and LMs were more comfortable than CNMs/CMs in recommending herbs to their patients. A majority of LMs had >20 hours of midwifery education on herbs whereas a majority of CNMs/CMs received 0 to 5 hours. Some CNMs/CMs indicated that their practice site limited their ability to use herbs. Common conditions in which LMs and CNMs/CMs used herbs were nausea/vomiting (86% vs. 83%), labor induction (89% vs. 58%), and lactation (86% vs. 65%). Specific herbs for all indications are described. CONCLUSION: Licensed midwives were more likely than CNMs/CMs to use herbs in clinical practice. This trend was likely a reflection of the amount of education devoted to herbs as well as herbal use limitations that may be encountered in institutional facilities.

A review of select vitamins and minerals used by postmenopausal women.

OBJECTIVES: The purpose of this review is to summarize the effectiveness of select vitamins, minerals and trace elements in postmenopausal women for their effects on bone health, cardiovascular health, breast cancer, cognition and vasomotor symptoms. METHODS: Review of the relevant literature and results from recent clinical studies, as well as critical analyses of published systematic reviews and meta-analyses were obtained from PubMed and Cochrane Library of Reviews. Vitamin A, the B vitamins, vitamin C, calcium, vitamin D, vitamin E, vitamin K, magnesium, selenium and zinc were selected for review. In circumstances where the vitamin, mineral or trace element has not been studied for a given condition, no information was provided. RESULTS AND DISCUSSION: All vitamins, minerals and trace elements play an important role in maintaining health and wellbeing among menopausal women. Adequate dietary intake is essential and supplementation should be considered in women with documented malabsorption syndromes or deficiencies. Based on a review of the literature, supplementation with vitamin C, D, K and calcium can also be recommended for proper maintenance of bone health. The only supplement studied for vasomotor symptoms was vitamin E and this vitamin lacked clinical support. Supplementation in healthy postmenopausal women with vitamins and minerals in diet or pill forms cannot be recommended currently for any other indications.

Emergency department management of pediatric asthma at a university teaching hospital.

BACKGROUND: Asthma is a major health problem and the most frequent cause of chronic illness and emergency department (ED) visits in children. Limited data examining the ED management of pediatric asthma within university teaching hospitals across the US exist. OBJECTIVE: To compare the ED management of children (aged 1-17 y) with asthma at a university teaching hospital using National Asthma Education and Prevention Program (NAEPP) guidelines. METHODS: All cases of pediatric asthma that presented to the University of California, San Francisco, Medical Center ED between October 1, 2003, and October 31, 2004, were included. Patients who required hospital admission were excluded. Data pertaining to patient demographics, primary diagnosis, pharmacologic management, diagnostic tests performed, and follow-up plans were abstracted and compared with NAEPP guidelines issued in 1997 and updated topics released in 2002. RESULTS: A total of 141 cases were identified. Mean patient age was 5.8 years. Most (61.7%) patients were male and of African American ethnicity (31.9%). Asthma severity was typically mild (66.7%) or moderate (29.1%). In persons at least 6 years of age (n = 58), peak expiratory flow rate (PEFR) was performed in 25.9% of cases. Pulse oximetry, however, was always performed. Based on NAEPP guidelines, beta-agonists and corticosteroids should have been used, but were not, in 2.8% and 31.9% of cases, respectively. At discharge, no corticosteroid prescription was given in 40.4% of the cases, no written action plan was prepared in 80.1% of the cases, no formal device training was administered in 67.3% of cases, and no peak flow meter was provided for persons at least 6 years of age in 50.0% of cases. CONCLUSIONS: NAEPP guidelines were met in all patients regarding pulse oximetry and in most patients with respect to the use of beta-agonists. Improvements could be made, however, in the use of corticosteroids in the ED; in performing PEFR measurements for persons at least 6 years of age upon arrival; and in providing formal device training, a written action plan, prescriptions for steroids, and peak flow meters at discharge.

Analysis of ephedra-free labeled dietary supplements sold in the San Francisco Bay area in 2003.

OBJECTIVE: To sample dietary supplements (DS) labeled as ephedra-free to evaluate whether products met their labeling claim. METHODS: One control DS product containing ephedra alkaloids and 29 DS labeled as ephedra-free were purchased from various retail locations in San Francisco. All products were sent to the California Department of Health Services (CDHS), Food and Drug Laboratory for content and quantity analysis. All laboratory personnel were blinded to product names and labeled contents. All DS products were screened for the presence of undeclared drugs, ephedra alkaloids, and heavy metals including lead, arsenic, cadmium and mercury. All products were also evaluated for compliance with the labeling requirements of the Dietary Supplement Health and Education Act (DSHEA) of 1994. RESULTS: None of the DS labeled as ephedra-free tested positive for the presence of ephedra alkaloids; as expected, the control product did test positive. Heavy metals were detected in three ephedra-free labeled DS products. All 24 products that tested positive for caffeine listed caffeine or a botanical source of caffeine on the DS label. All but two products were in compliance with DS labeling as required by DSHEA. CONCLUSIONS: This study demonstrates that manufacturers met their labeling claims for ephedra-free products. Special attention should be given to the presence of heavy metals and other drugs like caffeine, synephrine, and botanical sources of caffeine as these ingredients have replaced ephedra.

The use of herbs and dietary supplements in gynecology: an evidence-based review.

Consumers frequently use herbs and dietary supplements to treat chronic conditions that are poorly responsive to prescription drugs or when prescription drugs carry a high side effect burden. Women may use herbs and supplements for chronic gynecologic conditions, such as menopause, premenstrual syndrome, dysmenorrhea, cyclic mastalgia, and infertility. This review is an evidence-based evaluation of herbs and supplements for these conditions. Therapies that carry a higher level of support from randomized controlled trial evidence include black cohosh for menopause; vitamins B(1) and E for dysmenorrhea; calcium, vitamin B(6), and chasteberry for premenstrual syndrome; and chasteberry for cyclic mastalgia. There were too few trials involving herbs and supplements in infertility to warrant a solid recommendation, but chasteberry, antioxidants, and Fertility Blend have some preliminary support. Midwives may want to consider these alternatives in addition to more traditional treatment options when meeting with patients.

Evaluation of herbal dietary supplements marketed on the internet for recreational use.

BACKGROUND: The Internet is a popular tool for marketing and purchasing herbal dietary supplements (DS). Various Web sites sell these products purely for recreational use. OBJECTIVE: To describe the content of Web sites that advertise and market herbal DS for recreational use (ie, for the purpose of altering mood/behavior/or perception, "getting high," or as a substitute for a drug of abuse). METHODS: Four major search engines and the search terms "buy herbal high" and "buy legal high" were used to identify Web sites selling herbal DS for recreational use. Web sites were evaluated for their country of origin and for compliance with the Dietary Supplement Health and Education Act (DSHEA). Products were evaluated for their ingredient lists, effect claims, comparisons with illicit drugs, adverse effects, drug interactions, and contraindications. RESULTS: Twenty-eight unique Web sites with 119 products were evaluated. Most sites were in the US (54%) and were in compliance with DSHEA. Forty-seven percent of the products were likened to illicit drugs, typically marijuana (48%) or 3-,4-methylene dioxyamphetamine (Ecstasy; 23%). The most common product ingredients were ephedra alkaloids (27%), Salvia divinorum (17%), kava (10%), guarana (10%), Acorus calamus (10%), and damiana (10%). Effect claims frequently involved the products' use as a hallucinogen (51%) or stimulant (39%). Sixty-four percent of the sites mentioned adverse effects, and 54% mentioned drug interactions. CONCLUSIONS: This study demonstrates that herbal DS are being marketed for use as legal alternatives to illicit drugs of abuse. Healthcare professionals need to be aware of this trend and the products that are involved.

Dietary supplement-related adverse events reported to the California Poison Control System.

PURPOSE: Dietary supplement (DS)-related adverse events (AEs) reported to the California Poison Control System (CPCS) were studied. METHODS: The CPCS database was used to search for all telephone calls from consumers concerning DS-related AEs received during the six-month period between April and September 2002. The calls were characterized according to the substance involved, the caller's age (adult or pediatric), and the type of ingestion (accidental or intentional). Each exposure in which symptoms were reported was categorized as involving an AE. Each AE was assessed for severity and causality. RESULTS: Data on a total of 1183 telephone calls were retrieved, of which 828 calls (70%) met the study's inclusion criteria. DS exposure occurred in 389 adults (47%) and 438 children (53%). DS ingestion was accidental in 360 patients (43%) and intentional in 467 patients (56%). Exposure resulted in an AE in 480 patients (58%). AEs were reported in 353 patients (74%) who ingested products containing ephedra; other exposures frequently involved zinc, kava, creatine, and valerian. AEs were classified as moderate in 198 patients (41%) who ingested a DS and as severe in 40 patients (8%). One patient had a fatal reaction. Among the 480 AEs in DS-exposed consumers, the DS was classified as the definite cause of 1 AE (<1%) and a probable cause of 237 (49.4%). The most frequently reported AE symptoms were increased heart rate (45%), agitation (30%), vomiting (30%), and nausea (15%). CONCLUSION: A majority of DS-related AEs reported by consumers to CPCS involved ephedra-containing products.

Botanicals and dietary supplements in diabetic peripheral neuropathy.

BACKGROUND: Many persons use botanicals and dietary supplements for chronic conditions that do not respond to traditional Western medications. Tricyclic antidepressants, a common treatment option for diabetic neuropathy, can have many side effects and are a poor choice in certain populations (eg, the elderly). As such, patients might turn to botanicals and dietary supplements, not realizing that these products are not well regulated. METHODS: This article reviews botanicals and dietary supplements that have been involved in randomized controlled trials (RCTs) for diabetic neuropathy. We searched MEDLINE for English-language literature dating from 1966 to April 2001 using the following subject headings: (1) diabetes and botanical, herb, and supplement, (2) neuropathy and botanical, herb, and supplement, and (3) diabetic neuropathy and botanical, herb, and supplement. RESULTS: Our search found agents that might improve symptoms of neuropathy (eg, evening primrose oil, alpha-lipoic acid, capsaicin) without affecting glucose control. Botanicals and dietary supplements involved in only one RCT or associated with little clinical benefit were reviewed in brief. CONCLUSIONS: Evening primrose oil, alpha-lipoic acid, and capsaicin have received the greatest attention for their use in diabetic neuropathy, but further studies are needed to confirm their efficacy. Patients using these products need to be informed of potential drug interactions and side effects.

Milk thistle for the treatment of liver disease: a systematic review and meta-analysis.

PURPOSE: Milk thistle, an herbal compound, is the dietary supplement taken most frequently by patients with chronic liver disease. We performed a systematic review of the literature to determine the efficacy and safety of this herb for the treatment of liver disease. METHODS: We searched English and non-English reports through July 1999 using thirteen databases and reference lists, and contacting manufacturers and technical experts. Reviewers independently screened all reports to identify randomized placebo-controlled trials that evaluated milk thistle for the treatment of liver disease. Outcomes of primary interest included mortality, histological findings on liver biopsy specimens, serum aminotransferase and albumin levels, and prothrombin times. RESULTS: Fourteen trials met inclusion criteria. Four trials reported outcomes for mortality among 433 participants. The overall summary odds ratio for mortality in the milk thistle group compared with placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.5; P = 0.6). Three trials assessed histology on liver biopsy; study quality was inversely associated with the likelihood of histological benefit for milk thistle compared with placebo. There were no differences in serum alanine aminotransferase, aspartate aminotransferase, or albumin levels, or prothrombin times, among participants assigned to milk thistle compared with those assigned to placebo. The only statistically significant difference was a greater reduction in alanine aminotransferase levels among patients with chronic liver disease assigned to milk thistle (-9 IU/L, 95% CI: -18 to -1 IU/L; P = 0.05), but this reduction was of negligible clinical importance and no longer statistically significant after limiting analyses to studies of longer duration or of higher quality. The frequency of adverse effects was low and, in clinical trials, indistinguishable from placebo. CONCLUSION: Treatment with milk thistle appears to be safe and well tolerated. We found no reduction in mortality, in improvements in histology at liver biopsy, or in biochemical markers of liver function among patients with chronic liver disease. Data are too limited to exclude a substantial benefit or harm of milk thistle on mortality, and also to support recommending this herbal compound for the treatment of liver disease.

Dietary supplement use among menopausal women attending a San Francisco health conference.

OBJECTIVE: This study examined the usage patterns of dietary supplements during menopause, providing information about type, prevalence, and rationale for use. METHODS: A survey instrument was distributed to self-identified peri- or postmenopausal women at a San Francisco women's health conference in March 2000. RESULTS: Of the 100 eligible women, 29% used hormone replacement therapy (HRT) alone, 16% used HRT with dietary supplements (Combo group), 32% used dietary supplements alone, and 13% used no product or used supplements excluded in this survey. The most common dietary supplements were soy (29%), ginkgo biloba (16%), and black cohosh (10%). Only 54% of women using dietary supplements reported such usage to their primary care providers. Women using HRT alone reported relief of hot flashes significantly more often than those using dietary supplements alone (63% vs. 30%; p = 0.016). Women using combination therapy reported enhanced improvement in vaginal dryness, libido, and mood compared with those using HRT alone. Perceived quality of life and overall control of menopausal symptoms were highest among women using dietary supplements alone and women using combination therapy, respectively. Satisfaction with menopausal counseling from a primary care provider was significantly greater in women receiving HRT alone ( p = 0.02) and combination therapy ( p = 0.006) compared with women receiving dietary supplements alone. CONCLUSIONS: Dietary supplements were frequently used during menopause. Combined use of dietary supplements and HRT seemed to be associated with enhanced relief of certain menopausal symptoms. Women using dietary supplements alone seemed particularly dissatisfied with the menopausal counseling provided by a primary care provider.

Characterizing adverse events reported to the California Poison Control System on herbal remedies and dietary supplements: a pilot study.

OBJECTIVE: The purpose of this study was to (1) characterize the population who uses and reports adverse events to the California Poison Control System (CPCS) related to herbal remedies (HR) and dietary supplements (DS), (2) to assess whether adverse drug reactions (ADRs) occur within the usual recommended dosing, and (3) to describe the nature of adverse events. METHODS: A retrospective search of HR and DS related calls was conducted between January 1997 and June 1998. Data collection included the demographics of callers, types of exposures, substances involved, amounts ingested and severity. RESULTS: Of the 918 HR and DS calls received, 259 (28.2%) were drug information queries, 599 (65.3%) were exposures, and 60 (6.5%) were excluded. Exposures occurred most often in pediatric patients 324 (54.1%), but exposures resulting in ADRs occurred most often in adults at recommended doses. There were 233 ADRs, of which 67 (28.8%) occurred in children. The most common products involved in ADRs were zinc (38.2%), echinacea (7.7%), chromium picolinate (6.4%) and witch hazel (6%). Severity of ADRs required no treatment or was minor in a majority of cases, but may have contributed to hospitalization in three. CONCLUSION: Children were involved in a majority of exposure calls to the CPCS involving HR and DS. Adults, however, were more likely to develop an ADR from these products due to intentional exposure. Overall, the ADRs caused by HR and DS were mild, could be managed at home and rarely resulted in a severe outcome or other sequelae. Products involved in ADRs were consistent with the most common HR and DS products used by adult U.S. consumers.