Comprehensive functional characterization of complement factor I rare variant genotypes identified in the SCOPE geographic atrophy cohort.

Rare variants (RVs) in the gene encoding the regulatory enzyme complement factor I (CFI; FI) that reduce protein function or levels increase age-related macular degeneration risk. A total of 3357 subjects underwent screening in the SCOPE natural history study for geographic atrophy secondary to age-related macular degeneration, including CFI sequencing and serum FI measurement. Eleven CFI RV genotypes that were challenging to categorize as type I (low serum level) or type II (normal serum level, reduced enzymatic function) were characterized in the context of pure FI protein in C3b and C4b fluid phase cleavage assays and a novel bead-based functional assay (BBFA) of C3b cleavage. Four variants predicted or previously characterized as benign were analyzed by BBFA for comparison. In all, three variants (W51S, C67R, and I370T) resulted in low expression. Furthermore, four variants (P64L, R339Q, G527V, and P528T) were identified as being highly deleterious with IC50s for C3b breakdown >1 log increased versus the WT protein, while two variants (K476E and R474Q) were ∼1 log reduced in function. Meanwhile, six variants (P50A, T203I, K441R, E548Q, P553S, and S570T) had IC50s similar to WT. Odds ratios and BBFA IC50s were positively correlated (r = 0.76, p < 0.01), while odds ratios versus combined annotation dependent depletion (CADD) scores were not (r = 0.43, p = 0.16). Overall, 15 CFI RVs were functionally characterized which may aid future patient stratification for complement-targeted therapies. Pure protein in vitro analysis remains the gold standard for determining the functional consequence of CFI RVs.

Effectiveness of a postoperative disposition protocol for sleep apnea surgery.

PURPOSE: 1) Evaluate the effectiveness of a postoperative disposition protocol for upper airway surgery in patients with sleep apnea. 2) Compare the cost-effectiveness of outpatient and overnight observational sleep apnea surgery versus surgical intensive care admission determined by preoperative screening criteria. MATERIALS AND METHODS: A new preoperative protocol for sleep apnea surgery was instituted at the Durham Veterans Affairs Medical Center in 2008 to triage patients undergoing sleep apnea surgery to one of three postoperative dispositions: intensive care, routine ward bed, or discharge home. An Institutional Review Board approved retrospective chart review of patients undergoing sleep apnea surgery between May 2008 and January 2012 was performed. Postoperative complications and cost comparisons were assessed between each of the three postoperative disposition groups. RESULTS: 115 patients underwent sleep apnea surgery between July 2008 and January 2012. 11 patients were excluded leaving 104 patients in the final analysis. Median follow-up was 1.25months. Overall complication rate was 12.5%. Eight complications occurred in the group triaged to intensive care, and 5 occurred in those triaged to lesser levels of postoperative care. All serious complications occurred during the immediate postoperative period. Based on only room charges, $125,275 was saved over the 3.6years of this study. CONCLUSION: A post operative disposition protocol can be effectively used to triage patients to less than intensive postoperative care. In institutions like the Durham VA, where sleep apnea patients were routinely triaged to intensive care, postoperative resources will be more efficiently utilized.

Qualities of residency applicants: comparison of otolaryngology program criteria with applicant expectations.

OBJECTIVES: To evaluate the criteria used by otolaryngology programs in ranking residency candidates and to compare residency candidate ranking criteria among otolaryngology programs and applicant expectations. DESIGN: Cross-sectional, anonymous survey administered during the 2009 and 2010 match cycles. SETTING: Otolaryngology residency programs. PARTICIPANTS: Otolaryngology residency program applicants (PAs) and otolaryngology program directors (PDs). MAIN OUTCOME MEASURES: The PDs were asked to rank the importance of 10 criteria in choosing a residency candidate on a 20-point scale (with 1 indicating utmost importance; 20, not important at all). The PAs were asked to express their expectations of how candidates should be ranked using those same criteria. RESULTS: The interview and personal knowledge of the applicant (mean rank, 3.63) were the most important criteria to PDs, whereas the interview and letters of recommendation (mean rank, 3.65) were the most important criteria among PAs. Likelihood to rank program highly and ethnicity/sex were the least valued by PDs and PAs. CONCLUSIONS: Although PDs and PAs agree on the least important criteria for ranking otolaryngology residency candidates, they disagree on the most important criteria. This information provides insight into how programs select residency candidates and how this compares with applicant expectations. Furthermore, this information will assist applicants in understanding how they might be evaluated by programs. Improved understanding of the match process may increase the likelihood of having a good fit between otolaryngology programs and matched applicants.

Comparison of applicant criteria and program expectations for choosing residency programs in the otolaryngology match.

OBJECTIVE: To evaluate criteria used by residency applicants in ranking otolaryngology residency programs and to compare applicant criteria with program expectations of ranking otolaryngology residency programs. STUDY DESIGN: Cross-sectional survey. SETTING: 2009 and 2010 match cycles. SUBJECTS AND METHODS: Program applicants and otolaryngology program directors. MAIN OUTCOME MEASURES: Applicants were asked to rank the importance of 10 criteria in choosing a residency program (1 = criterion was of the utmost importance and 20 = not important at all). Program directors were asked to express expectations of how applicants should rank programs using those same criteria. The Mann-Whitney U test was used to analyze responses between groups. RESULTS: Comprehensiveness of subspecialties and resident satisfaction were the most important criteria for both groups; salary, call schedule, and likelihood to rank the resident highly were least valued. Four criteria were significantly different between groups. Applicants significantly valued location (4.36 vs 8.9, P < .0001) and call schedule (9.85 vs 12.73, P = .002) more than program directors did. Program directors valued didactic schedule (6.1 vs 9.18, P < .0001) and comprehensiveness of subspecialties (2.53 vs 3.02, P = .007) more than applicants did. Forty-one of 105 (39%) program directors completed the survey. CONCLUSION: While applicants and program directors agree on the most and least important criteria for ranking residency programs, there are several significant differences in these criteria. This study provides insight on ranking criteria that may improve the resident match process and subsequent training experience. However, the ability to generalize the results is limited by the low response rate.