Pieter A. Cohen

Educational Outcomes of the Harvard Medical School-Cambridge Integrated Clerkship: A Way Forward for Medical Education

Purpose The authors report data from the Harvard Medical School–Cambridge Integrated Clerkship (CIC), a model of medical education in which students’ entire third year consists of a longitudinal, integrated curriculum. The authors compare the knowledge, skills, and attitudes of students completing the CIC with those of students completing traditional third-year clerkships. Method The authors compared 27 students completing the first three years of the CIC (2004–2007) with 45 students completing clerkships at other Harvard teaching hospitals during the same period. At baseline, no significant between-group differences existed (Medical College Admission Test and Step 1 scores, second-year objective structured clinical examination [OSCE] performance, attitudes toward patient-centered care, and plans for future practice) in any year. The authors compared students’ National Board of Medical Examiners Subject and Step 2 Clinical Knowledge scores, OSCE performance, perceptions of the learning environment, and attitudes toward patient-centeredness. Results CIC students performed as well as or better than their traditionally trained peers on measures of content knowledge and clinical skills. CIC students expressed higher satisfaction with the learning environment, more confidence in dealing with numerous domains of patient care, and a stronger sense of patient-centeredness. Conclusions CIC students are at least as well as and in several ways better prepared than their peers. CIC students also demonstrate richer perspectives on the course of illness, more insight into social determinants of illness and recovery, and increased commitment to patients. These data suggest that longitudinal integrated clerkships offer students important intellectual, professional, and personal benefits.

Hazards of Hindsight — Monitoring the Safety of Nutritional Supplements

Americans spend more than

Assessing supplement safety--the FDA's controversial proposal.

32 billion a year on dietary supplements, which do not require premarketing approval before they reach store shelves. Under current law, the FDA must identify and remove dangerous supplements only after they have caused harm.

A methamphetamine analog (N,α-diethyl- phenylethylamine) identified in a mainstream dietary supplement

By law, dietary supplements whose ingredients were not sold in the United States before 1994 require demonstration of a “reasonable expectation of safety” — a currently unenforced requirement. Will the FDAs proposed new guidance in this area be adequate?

Presence of Banned Drugs in Dietary Supplements Following FDA Recalls

Pharmaceuticals and banned substances have been detected in hundreds of purportedly natural supplements. Recently, several athletes have been disqualified from competition after testing positive for the methamphetamine analog N,α-diethyl-phenylethylamine (N,α-DEPEA). Athletes have claimed they unknowingly consumed the banned stimulant in workout supplements. Three samples from different lot numbers of Craze, a workout supplement, were analyzed to detect the presence and concentration of N,α-DEPEA. Two labs independently identified N,α-DEPEA in the supplement using ultra high performance liquid chromatography (UHPLC) coupled to an LTQ Orbitrap XL mass spectrometer and UHPLC-quadruple-time-of-flight mass (Q-TOF) spectrometer, respectively. The identity of N,α-DEPEA was confirmed using nuclear magnetic resonance and reference standards. Manufacturer recommended servings were estimated to provide 21 to 35 mg of N,α-DEPEA. N,α-DEPEA has never been studied in humans. N,α-DEPEA is a methamphetamine analog; however, its stimulant, addictive and other adverse effects in humans are entirely unknown. Regulatory agencies should act expeditiously to warn consumers and remove N,α-DEPEA from all dietary supplements.

DMAA as a Dietary Supplement Ingredient

Presence of Banned Drugs in Dietary Supplements Following FDA Recalls The US Food and Drug Administration (FDA) initiates class I drug recalls when products have the reasonable possibility of causing serious adverse health consequences or death.1 Recently, the FDA has used class I drug recalls in an effort to remove dietary supplements adulterated with pharmaceutical ingredients from US markets. Approximately half of all FDA class I drug recalls since 2004 have involved dietary supplements adulterated with banned pharmaceutical ingredients.2,3 Prior research has found that even after FDA recalls, dietary supplements remain available on store shelves.4 However, it is not known if the supplements on sale after FDA recalls are free of the adulterants. In the present study, dietary supplements purchased at least 6 months after FDA recalls were analyzed to determine if banned drugs were still present.

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

vider will have this discussion include their understanding of the risks of medical imaging, the amount of time that is available with the patient prior to ordering a test, concerns related to prior false-negative imaging examination findings, and unfavorable outcomes related to a past approach to an incidentaloma. We found that most frontline providers in our study had very little training in the potential radiation risks from medical imaging and that these providers felt uncomfortable discussing the risks with patients. Alternatively, providers who feel comfortable may choose not to discuss the risks with patients for other reasons, such as relatively small perceived risk compared with the perceived benefits or time limitations. As further dialogue ensues about how to communicate with patients about the risks of medical testing, consideration should be given to the infrequency of these discussions in current practice. Future studies should investigate other potential reasons that providers are not engaging in these discussions and evaluate interventions to increase the frequency and efficacy of these discussions.

Imported Fenproporex-based Diet Pills from Brazil: A Report of Two Cases

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

A new approach to determining pharmacologic adulteration of herbal weight loss products

Banned amphetamine-based anorectics are illicitly imported into the United States (US), but little is known regarding the harm these diet pills pose to US residents. A 26-year-old woman using imported diet pills presented with a two-year history of intermittent chest pains, palpitations, headaches and insomnia. Urine toxicology screen detected amphetamines and benzodiazepines. Fenproporex and chlordiazepoxide were detected in her pills. Her symptoms resolved after she stopped using diet pills. A 38-year-old man using imported diet pills presented after his occupational urine screen was significantly positive for amphetamine. Fenproporex and fluoxetine were detected in his pills. These cases illustrate the potential harm from imported prescription diet pills that combine fenproporex with benzodiazepines, antidepressants, diuretics, laxatives and other substances. Increasing physicians’ awareness of imported diet pill use may improve care of patients suffering from the pills’ many adverse effects.

A synthetic stimulant never tested in humans, 1,3‐dimethylbutylamine (DMBA), is identified in multiple dietary supplements

Pharmaceutical adulterants are commonly found in herbal weight loss products, and analytical techniques for detecting these adulterants have become increasingly important to the public health community. Previously we reported a novel analytical method for the determination of adulterants in herbal formulations by capillary electrophoresis with contactless conductivity detection. The current study refines this previously described technique by testing if anxiolytics, diuretics, and laxatives interfered with the detection of anorectics and antidepressants. A survey of herbal weight loss products sold by compounding pharmacies in Brazil were analysed to determine the presence of pharmaceutical adulterants. A total of 106 herbal products, collected from 73 pharmacies in nine Brazilian states, were analysed for amfepramone, sibutramine, fenproporex, fluoxetine, paroxetine, sertraline and bupropion using the new analytical method. The method permitted the rapid and selective screening for the seven adulterants. Of the 106 weight loss products sampled, four (3.8%) were found to be adulterated by fenproporex or sibutramine. The adulterated samples were compounded by four different pharmacies located in three different Brazilian states. The novel capillary electrophoresis method we developed may be a useful tool for public health organisations tasked with analysing herbal weight loss products.