Brian Chen

A tale of two citizens: A state attorney general and a hematologist facilitate translation of research into us food and drug administration actions-a sonar report

PURPOSE Pharmaceutical safety is a public health issue. In 2005, the Connecticut Attorney General (AG) raised concerns over adverse drug reactions in off-label settings, noting that thalidomide was approved to treat a rare illness, but more than 90% of its use was off label. A hematologist had reported thalidomide with doxorubicin or dexamethasone was associated with venous thromboembolism (VTE) rates of 25%. We review US Food and Drug Administration (FDA) and manufacturer responses to a citizen petition filed to address these thalidomide safety issues. METHODS Case study. RESULTS The AG petitioned the FDA requesting thalidomide-related safety actions. Coincidentally, the manufacturer submitted a supplemental New Drug Approval (sNDA), requesting approval to treat multiple myeloma with thalidomide-dexamethasone. FDA safety officers reviewed the petition and the literature and noted that VTE risks with thalidomide were not appropriately addressed in the existing package insert. In the sNDA application, the manufacturer reported thalidomide-associated toxicities for multiple myeloma were primarily somnolence and neurotoxicity, and a proposed package insert did not focus on VTE risks. In October, the FDA informed the Oncology Drug Division that VTE risks with thalidomide were poorly addressed in the existing label. After reviewing this memorandum, an Oncology Drug Division reviewer informed the manufacturer that approval of the sNDA would be delayed until several thalidomide-associated VTE safety actions, including revisions of the package insert, were implemented. The manufacturer and FDA agreed on these actions, and the sNDA was approved. CONCLUSION New approaches addressing off-label safety are needed. The conditions that facilitated the successful response to this citizen petition are uncommon.

Subcutaneous infiltration of carbon dioxide (carboxytherapy) for abdominal fat reduction: A randomized clinical trial

Background Noninvasive fat removal is preferred because of decreased downtime and lower perceived risk. It is important to seek new noninvasive fat removal treatments that are both safe and efficacious. Objective To assess the extent to which carboxytherapy, which is the insufflation of carbon dioxide gas into subcutaneous fat, results in reduction of fat volume. Methods In this randomized, sham‐controlled, split‐body study, adults (body mass index, 22‐29 kg/m2) were randomized to receive 5 weekly infusions of 1000 cm3 of CO2 to 1 side of the abdomen, and 5 sham treatments to the contralateral side. The primary outcome measures were ultrasound measurement of fat layer thickness and total circumference before and after treatment. Results A total of 16 participants completed the study. Ultrasound measurement indicated less fat volume on the side treated with carboxytherapy 1 week after the last treatment (P = .011), but the lower fat volume was not maintained at 28 weeks. Total circumference decreased nominally but not significantly at week 5 compared with baseline (P = .0697). Participant body weights did not change over the entire course of the study (P = 1.00). Limitations Limitations included modest sample size and some sources of error in the measurement of circumference and fat layer. Conclusion Carboxytherapy provides a transient decrease in subcutaneous fat that may not persist. Treatment is well tolerated.

Effects of the US Food and Drug Administration Boxed Warning of Erythropoietin-Stimulating Agents on Utilization and Adverse Outcome

Purpose In March 2007, a US Food and Drug Administration boxed warning was issued for erythropoietin-stimulating agents (ESAs) regarding serious adverse events, such as venous thromboembolism (VTE). We evaluated the US Food and Drug Administrations boxed warning of ESAs used to treat chemotherapy-induced anemia because evidence on the effectiveness of boxed warnings remains inconclusive. Patients and Methods Using 2004 to 2009 SEER-Medicare data, we exploited a natural experiment to examine the effects of ESA boxed warnings on utilization and risk of VTE. The intervention group included Medicare fee-for-services patients diagnosed with colorectal, breast, or lung cancers targeted by this warning and undergoing chemotherapy; the control group included patients with myelodysplastic syndromes not targeted by this warning. The period from January 2004 to September 2006 was used as the prewarning period; the period from April 2007 to September 2009 was used as the postwarning period. The two binary dependent variables included ESA use and hospitalized VTE. Linear probability models with a difference-in-differences specification were used for estimation. Results Our sample consisted of 45,319 unique patients between 2004 and 2009. The trends in ESA use remained similar between the intervention and control groups before the warning, but started declining sharply in the intervention group only after the warning. The trends in hospitalized VTE were relatively stable. Regressions showed that the ESA boxed warning was associated with a 20.2-percentage-point reduction ( P < .001) in the likelihood of ESAs being used to treat cancers targeted by the warning, but not significantly associated with the likelihood of hospitalized VTE. Conclusion Our study showed that the warning was effective in reducing ESA utilization. Future studies should examine other regulatory drug safety actions, such as the Risk Evaluation and Mitigation Strategy initiative, whose effectiveness remains unknown.

Photography in Dermatologic Surgery: Selection of an Appropriate Camera Type for a Particular Clinical Application

BACKGROUND Photographs are an essential tool for the documentation and sharing of findings in dermatologic surgery, and various camera types are available. OBJECTIVE To evaluate the currently available camera types in view of the special functional needs of procedural dermatologists. METHODS Mobile phone, point and shoot, digital single-lens reflex (DSLR), digital medium format, and 3-dimensional cameras were compared in terms of their usefulness for dermatologic surgeons. For each camera type, the image quality, as well as the other practical benefits and limitations, were evaluated with reference to a set of ideal camera characteristics. Based on these assessments, recommendations were made regarding the specific clinical circumstances in which each camera type would likely be most useful. RESULTS Mobile photography may be adequate when ease of use, availability, and accessibility are prioritized. Point and shoot cameras and DSLR cameras provide sufficient resolution for a range of clinical circumstances, while providing the added benefit of portability. Digital medium format cameras offer the highest image quality, with accurate color rendition and greater color depth. Three-dimensional imaging may be optimal for the definition of skin contour. CONCLUSION The selection of an optimal camera depends on the context in which it will be used.

Effect of Post-Injection Facial Exercise on Time of Onset of Botulinum Toxin for Glabella and Forehead Wrinkles: A Randomized Controlled, Crossover Clinical Trial

Men, % 98.0 96.9 .65 Race, white, % 94.9 94.8 .97 Average age, y 70 67 .03 Average Breslow thickness, mm 3.9* 0.76 \.01 Lesion identified by patient, % 38.5 22.2 .01 VA primary care physician visit in preceding 6 months, % 85.0 92.9 .05 VA dermatology visit in preceding 6 months, % 20.0 34.2 .03 Age-appropriate colonoscopy screening, % 47.0 73.7 \.01 History of skin cancer, % 38.9 51.3 .08 History of other noncutaneous malignancy, % 20.0 34.0 .04

Tale of Two Erythropoiesis-Stimulating Agents: Utilization, Dosing, Litigation, and Costs of Darbepoetin and Epoetin Among South Carolina Medicaid-Covered Patients With Cancer and Chemotherapy-Induced Anemia

PURPOSE The US Food and Drug Administration (FDA) has approved epoetin and darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and darbepoetin dosing schedules were three times per week and weekly, respectively, although off-label, less frequent scheduling was common. In 2004, 2007, and 2008, a US Food and Drug Administration Advisory Committees warned of risks associated with erythropoiesis-stimulating agents. During this period, lawsuits alleging illegal darbepoetin marketing practices have concluded, resulting in

Photography in Dermatologic Surgery: Selection of an Appropriate Lighting Solution for a Particular Clinical Application

1.1 billion in fines and settlements and one criminal conviction. No prior study, to our knowledge, has reported on the use of darbepoetin versus epoetin for CIA. METHODS We evaluated the dosing, utilization, and costs of erythropoiesis-stimulating agents among 3,761 South Carolina Medicaid patients with CIA. RESULTS Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10% and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per-administration epoetin and darbepoetin doses were 40,983 IU and 191 µg, respectively, in 2003 and 47,753 IU and 369 µg, respectively, in 2010. Mean monthly patient costs for epoetin and darbepoetin were

Quantitative evaluation of skin shrinkage associated with non-invasive skin tightening: a simple method for reproducible linear measurement using microtattoos

1,030 and

Investigating Serious Adverse Drug Reactions in Patients Receiving Erythropoiesis-Stimulating Agents: A Root Cause Analysis Using the “ANTICIPATE” Framework

981, respectively, in 2003 and

Are preclinical research findings replicable: An empirical analysis based on EpoR studies in cancer.

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