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To determine the most common reasons for Institutional Review Boards deferral of biomedical research proposals.Cross-sectional study administered to chairs, vice-chairs, and co-chairs of IRBs at NIH-funded institutions.Data forms were distributed to IRB chairs at 21 of 25 NIH-funded institutions (four declined to participate), with an institutional response rate of 86% (18/21). Overall, ethical considerations were more likely than scientific merit to be a reason for protocol deferral. Common ethical considerations for deferral were inadequate informed consent, inadequate detail for risk assessment, insufficient protection of participant safety, and inadequate minimization of risks. Important elements of scientific merit were appropriate research design, adequate adverse event reporting, and the importance of knowledge to be gained. Nonsponsored, investigator-initiated proposals (including those receiving internal funding) were more likely to be deferred (66%), usually due to inadequate protocol development (43%), less external vetting and oversight (20%), and submissions from inexperienced faculty (16%).Deferrals may be avoided by careful compliance with ethical considerations, and by ensuring sufficient scientific merit of the proposal, with research design optimized for participant safety. Those submitting investigator-initiated proposals may consider obtaining at least partial funding to decrease the risk of deferral.

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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.

Purpose Setup deviations of a craniospinal irradiation (CSI) patient cohort previously treated with helical tomotherapy were used to derive the optimal planning target volume (PTV) margin for CSI patients treated in the supine position. Methods and Materials The daily setup shifts of 27 CSI tomotherapy patients as determined using pretreatment megavoltage computed tomography verification for a total of 454 fractions were evaluated. Translational displacements in the mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) directions were used to assess the systematic and random setup errors, and to derive the PTV margin required when daily image guidance is unavailable. Results The individual patient mean shifts and the corresponding standard deviations in the ML, CC, and AP directions were −0.5 ± 2.1 mm, 1.0 ± 2.7 mm, and 0.7 ± 1.1 mm, respectively. The random errors in the corresponding directions were 1.9 mm, 1.9 mm, and 2.2 mm. The PTV margins required in the absence of daily imaging were 3.7 mm to the right, 4.7 mm to the left, 4.4 mm inferior, 6.4 mm superior, 1.6 mm posterior, and 3.0 mm anterior. Conclusions The current PTV margin of 3.0 mm is sufficient to ensure clinical target volume coverage for CSI tomotherapy patients treated with daily megavoltage computed tomography imaging. When pretreatment verification imaging is not used to lower the setup uncertainty, a larger PTV margin of up to 6.4 mm in the CC direction will be needed.

Background Facial erythema is a common symptom that responds to vascular laser treatment, but there are few comparative studies. Objective We sought to compare the effectiveness of microsecond 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with nonpurpuragenic 595-nm pulsed dye laser (PDL) for diffuse facial erythema. Methods This was a split-face, double-blind randomized controlled trial. Bilateral cheeks received 4 treatments each at one month intervals with PDL or Nd:YAG. Spectrophotometer measurements, digital photographs, pain scores, and patient preferences were recorded. Results Sixteen patients enrolled and 2 dropped out. Fourteen patients, all skin types I to III, 57% women, mean age 42 years, completed the study and were analyzed. Spectrophotometer readings changed after both PDL (8.9%) and Nd:YAG (2.5%), but varied by treatment type, with PDL reducing facial redness 6.4% more from baseline than Nd:YAG ( P = .0199; 95% confidence interval −11.6 to −1.2). Pain varied ( P = .0028), with Nd:YAG associated with less pain, at 3.07, than PDL at 3.87. Subjects rated redness as improved by 52% as a result of PDL, and 34% as a result of Nd:YAG ( P = .031; 95% confidence interval −34.6 to −1.94). No serious adverse events were observed. Limitations Lasers settings are not standardized across devices. Conclusion Facial erythema is safely and effectively treated with PDL and Nd:YAG. Nonpupuragenic PDL may be more effective for lighter-skinned patients, but microsecond Nd:YAG may be less painful.

Background Botulinum toxin injections and suction-curettage have been separately shown to be effective in treating axillary hyperhidrosis but have not been compared in the same patients. Objective We sought to compare effectiveness of suction-curettage versus neurotoxin for the treatment of axillary hyperhidrosis. Methods Each of 20 patients was randomized to receive toxin injections to one axilla and suction-curettage to the contralateral axilla. The primary outcome measure was reduction of sweat rate measured by gravimetry, and the secondary measure was quality of life as measured by a patient-directed questionnaire. Results At 3 months posttreatment, toxin injections decreased baseline resting sweat production by 72.1% versus 60.4% ( P = .29) for suction-curettage, and baseline exercise-induced sweat production by 73.8% versus 58.8% ( P = .10). When patients were stratified into the categories of light and heavy sweaters, there was a difference among heavy sweaters, with exercise-induced sweat production lower by 10.48 mg/min or 34.3% ( P = .0025) at toxin-treated sites. Compared with suction-curettage, toxin also resulted in greater improvements in quality of life by 0.80 points ( P = .0002) and 0.90 points ( P = .0017) at 3 and 6 months posttreatment, respectively, as measured by the patient questionnaire. Limitations The follow-up period was limited to 6 months. Conclusions By objective measures 3 months after treatment, neurotoxin injections are nominally more effective than suction-curettage in all cases, and markedly more effective in heavy sweaters. Patients have a very significant preference for neurotoxin injections at 3 months, and this is maintained at 6 months.

PCBs have long been known to affect dopamine (DA) function in the brain. The current study used an amphetamine behavioral sensitization paradigm in rats developmentally exposed to PCBs. Long–Evans rats were given perinatal exposure to 0, 3, or 6 mg/kg/day PCBs and behavioral sensitization to d -amphetamine (AMPH) was assessed in one adult male and female/litter. Non-exposed (control) males showed increasing locomotor activity to repeated injections of 0.5 mg/kg AMPH, typical of behavioral sensitization. PCB-exposed males showed greater activation to the initial acute AMPH injection, but sensitization occurred later and was blunted relative to controls. Sensitization in control females took longer to develop than in the males, but no exposure-related differences were observed. Analysis of whole brain and serum AMPH content following a final IP injection of 0.5 mg/kg revealed no differences among the exposure groups. Overall, these results indicated developmental PCB exposure can alter the motor-stimulating effects of repeated AMPH injections. Males developmentally exposed to PCBs appeared to be pre-sensitized to AMPH, but quickly showed behavioral tolerance to the same drug dose. Results also revealed the behavioral effect was not due to exposure-induced alterations in AMPH metabolism following PCB exposure.

Patients with diabetic nephropathy (DN) have increased plasma fasting triglyceride (TG) levels, and most prospective studies report that elevated TG precedes DN. TG-rich lipoprotein particles might promote progression of DN. To test the hypothesis that elevated TG levels contribute to the development of DN, one may examine whether a polymorphism strongly associated with TG levels affects DN risk. The apolipoprotein A5 (apoA5) −1131T→C polymorphism has a large effect on the TG level, and all three genotypes are relatively common in East Asians. Therefore, we sought to examine the association of this polymorphism with DN. We genotyped the apoA5 −1131T→C polymorphism in a case-control study involving 367 Chinese Type 2 diabetes patients with DN and 382 without DN, as well as 198 subjects without diabetes. Mean fasting TG levels were higher in CC than in TT carriers by 41%, 54%, and 62% in each of the three subject groups, respectively. However, the genotype distributions did not differ between patients with and without nephropathy ( P =.69). Therefore, these results weigh against the hypothesis that high fasting TG per se causes DN. The strong association between TG level and DN may be due to a factor that is usually closely linked to TG level but that is not affected by the apoA5 polymorphism.

Cardiac hypertrophy and remodeling in relation to ACE and angiotensinogen genes genotypes in Chinese dialysis patients. Background Genetic polymorphisms of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes are associated with increased risk of hypertension and left ventricular hypertrophy (LVH) in hypertensive subjects. However, the extent to which these polymorphisms are related to LVH and remodeling in dialysis patients remains unknown. Methods Two hundred and forty-six end-stage renal disease (ESRD) patients on peritoneal dialysis and 183 control subjects, all of Chinese origin, were genotyped for the ACE insertion/deletion (I/D) and the AGT M235T gene polymorphisms. Left ventricular mass index (LVMi) and relative wall thickness were measured using echocardiography. Results Prevalence of ACE DD and AGT TT genotype was 14% and 83%, respectively, in ESRD patients and did not differ significantly from controls. A total percentage of 95% of our patients had LVH (171 with concentric and 63 with eccentric hypertrophy). Adjusting for age, gender, body mass index, duration of dialysis, diabetes, renal diagnosis, hematocrit, systolic and diastolic blood pressure, dialysis urea clearance, residual glomerular filtration rate, and use of converting enzyme inhibitors or angiotensin receptor blockers, AGT TT genotype remained independently associated with greater LVMi (coefficient = 28.73; 95% CI, 5.72 to 51.75; P = 0.015) and relative wall thickness (coefficient = 0.072; 95% CI, 0.022 to 0.122; P = 0.005) than MT/MM genotypes. LVMi and relative wall thickness did not differ significantly among patients with DD, DI, and II genotypes. No statistical significant interaction was noted between ACE and AGT gene polymorphism in relation to LVMi and relative wall thickness. Conclusion Polymorphism of the AGT M235T gene but not ACE I / D gene is associated with greater LVMi and relative wall thickness, indicating more concentric LVH, in Chinese peritoneal dialysis patients. Possible synergistic effects between AGT and ACE gene polymorphism require further evaluation in a larger population.