FDA’S Perspectives on Cardiovascular Devices

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, §903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 ). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA’s review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.     

The impact of cystic fibrosis on recovery from orthopedic trauma: A case study

Cystic Fibrosis has effects on many body systems, including the skeletal system. In this case, we describe the impact of respiratory and endocrine disease on bone healing following orthopedic trauma in a 22-year-old woman. Limitations to mobility resulting from trauma complicated her respiratory condition. Disease-related effects on bone health and healing delayed her recovery from the trauma. It is important to recognize the multisystemic nature of CF, even when managing acute orthopedic injuries.     

Effect of short-term erythropoietin therapy in anemic premature infants.

OBJECTIVE: To determine the effectiveness of a 10-day subcutaneous erythropoietin (rHuEpo) course of 300 units per kg per dose plus oral iron compared to oral iron alone in anemic infants during their convalescent phase of illness. STUDY DESIGN: Prospective, randomized trial performed at a 40-bed, teaching, referral, level III, neonatal intensive care unit. Infants with a gestational age at birth of less than 32 weeks, hematocrit of less than or equal to 28% with a corrected reticulocyte count of less than or equal to 5%, postconceptual age of less than 48 weeks or 5 months chronological age, and a diagnosis of anemia of prematurity were considered for inclusion. Major outcome parameters included hematocrit, corrected reticulocyte count and red cell transfusion requirements. RESULTS: A total of 60 infants were enrolled (n=30 per group). Infants randomized to rHuEpo had a significantly higher post-treatment hematocrit and corrected reticulocyte count than infants in the iron only group (p<0.001). There was a trend towards fewer red cell requirements in the rHuEpo group. CONCLUSIONS: The rHuEpo regimen studied here was associated with an acute improvement in hematocrit and corrected reticulocyte counts. This study did not demonstrate a statistically significant decrease in transfusion therapy, in part related to increased subsequent use of rHuEpo in the control group. Taken together, these data demonstrate that this regimen can effectively treat anemia in convalescent premature infants.     

Baseline characteristics and treatment preferences of oral surgery patients.

PURPOSE: Patient preferences for treatment choices may depend on patient characteristics. Using standard gamble (SG) and willingness to pay (WTP), this study compares preferences for treatment of mandibular fracture among patients in a low-income urban area. PATIENTS AND METHODS: Surveys of African-American and Hispanic adults receiving treatment at King/Drew Medical Center for either mandibular fracture (n = 98) or third molar removal (n = 105) were used to investigate differences in patient characteristics across treatment groups (third molar vs fracture) and treatment preference (wiring vs surgery). RESULTS: The fracture patients were willing to pay more to restore function without scarring or nerve damage than were the third molar patients. Patients who chose surgery were willing to accept a greater risk of possible nerve damage or scarring than those who chose wiring. Among 15 potential predictors of SG and WTP studied in 4 subgroups defined by actual treatment and treatment preference, significant predictors varied, with associations for education and clinical experience for SG and associations with income and psychosocial predictors for WTP. CONCLUSIONS: SG and WTP capture different domains of health values in patients. There is considerable heterogeneity in relationships among patient characteristics and patient preferences across subgroups defined by actual treatment and treatment preferences.     

Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

Inadequate dietary calcium and vitamin D intakes in renal-transplant recipients in Ireland.

OBJECTIVE: To quantify the dietary calcium and vitamin D intake in adult renal-transplant recipients attending at a large teaching hospital in Ireland for follow-up. SETTING: Outpatient renal-transplant follow-up clinic. SUBJECTS: Fifty-nine adult renal transplant recipients (58% male) with a mean age of 46 years, a median transplant duration of 6 years, and a mean estimated glomerular filtration rate (eGFR) of 50 mL/min per 1.73 m2. Fifty-three percent were at National Kidney Foundation stage 3 chronic kidney disease, and 14% had stage 4 chronic kidney disease. INTERVENTION: This cross-sectional, observational study used a tailored food frequency questionnaire specific for calcium and vitamin D intake in Irish adults, which was completed during a face-to-face interview with each subject. MAIN OUTCOME MEASURE: The main outcome measure was the average daily dietary and supplemented calcium and vitamin D intake. RESULTS: The median interquartile range (IQR) dietary calcium intake was 820 mg/day (range, 576-1,177 mg/day), and was similar in men and women (recommended intake > or = 1,000 mg/day in adult men and nonmenopausal adult women, > or = 1,500 mg/day in menopausal women). Five participants received calcium supplementation. Overall, 59% of men and 64% of women had total calcium intakes below the recommended amounts. The median IQR estimated dietary vitamin D intake was 5.2 microg/day (range, 2.4-6.4 microg/day) in women, and 4.6 microg/day (range, 2.2-6.6 microg/day) in men (recommended intake, > or = 10 microg/day). Six subjects received vitamin D supplementation. Total vitamin D intakes were suboptimal in 91% of men and 87% of women. Dietary calcium and vitamin D intakes significantly correlated with each other, but neither was significantly related to eGFR category, and was similarly low in both presumed menopausal women and in the initial year posttransplantation. CONCLUSION: These findings suggest that dietary and total calcium and vitamin D intakes in adult renal-transplant patients are in many cases inadequate.