"Right Into the Center": A Semantic Analysis of Direction in Operating Room Instruction.

OBJECTIVE: In our previous work, teaching surgeons used potentially ambiguous language in the OR 12.3 times per minute. Our objectives were to examine ambiguous examples featuring Directional Frame of Reference (DFoR), which involves instructions containing directional terms like "up" or "left," and to uncover what contributes to understanding or misunderstanding of such instruction. DESIGN: We videorecorded the critical moments of 6 surgeries, as chosen by the surgeons. With a semanticist, we applied constructs from formal semantics to choose potentially ambiguous DFoR terms commonly flagged in our previous work. We separately interviewed attending and resident surgeons, asking each to describe the meaning of those DFoR terms while they viewed case recordings alongside transcripts. We compared their responses, analyzing them for agreement in direction. We performed thematic analysis on case and interview transcripts for themes related to DFoR. SETTING: Midwestern academic university teaching hospital. PARTICIPANTS: Six attending and 6 resident surgeons. RESULTS: Attending and resident surgeons disagreed on direction in 9 of the 26 (34.6%) DFoR examples. Misunderstanding arose from using linear direction to describe three-dimensional space, e.g., "up" for anterior/cephalad/right. It also arose when combining degree modifiers with DfoR, e.g., "we're far enough back" combines the ambiguities of "back" (DfoR) and "far enough" (degree modifier). Use of axial parts (noun-like directional terms), e.g., "bottom," and confusing "left" for "right" also provoked misunderstanding. Misunderstanding was associated with lack of experience and mitigated by pointing with a finger or instrument, concurrent with speech. CONCLUSIONS: Use of ambiguous language with DFoR incurs a high potential for misunderstanding, especially with novice surgeons. We recommend avoiding linear directions and axial parts, and instead physically pointing to represent complex 3D directions. Degree modifiers can be replaced with exact distances e.g., replace "little more anterior" with "1 centimeter anterior," and semaphores can be used to clarify direction.

Validation of Minimal Clinically Important Difference (MCID) for University of Pennsylvania Smell Identification Test (UPSIT).

BACKGROUND: The University of Pennsylvania Smell Identification Test is widely used to measure change in olfactory function, but a minimal clinically important difference (MCID) has not been well-established. A study published in 1997 regarding patients with head trauma reported an MCID of 4 but did not detail the methods used in the calculation. OBJECTIVE: To validate the MCID for UPSIT in patients with postviral, sinusitis, and procedure-associated olfactory loss. METHODS: This was a secondary analysis of prospectively collected data from 5 clinical research studies related to olfactory function. Three studies included subjects with COVID-19-related olfactory dysfunction, one with chronic sinusitis subjects, and one with subjects undergoing transsphenoidal surgery. All subjects had completed a baseline and follow-up UPSIT, baseline and follow-up Clinical Global Impression-Severity (CGI-Severity), and a follow-up CGI-Improvement. Both distribution- and anchor-based methods were used to determine the MCID of UPSIT. Distribution-based method calculated MCID using half standard deviation of baseline UPSIT and delta UPSIT scores. Clinical-anchor method determined MCID by comparing delta UPSIT scores between consecutive CGI-I clinical categories ranging from very much better to very much worse. RESULTS: The study population comprised 295 subjects. Subjects had a mean (SD) baseline UPSIT score of 27 (7.5), and follow-up score of 28 (7.9), and a mean UPSIT change of 0.6 (5.8). Half the baseline UPSIT SD was 3.75 and half the delta UPSIT SD was 2.9. With the anchor-based approach, an MCID of 4 was defined as clinically meaningful by exploring the relationship between delta UPSIT and CGI-Improvement. Using a more conservative approach based on the MCID values identified from both methods, we determined that a change of 4 or greater is the appropriate MCID for UPSIT. CONCLUSION: Investigators in the future should use 4 as MCID for UPSIT and report the percentage of study subjects who achieve a clinically meaningful difference. LEVEL OF EVIDENCE: III.

Efficacy of Gabapentin For Post-COVID-19 Olfactory Dysfunction: The GRACE Randomized Clinical Trial.

Importance: The COVID-19 pandemic affected millions of people and has become a dominant etiology of olfactory dysfunction (OD). No interventions with definitive clinical utility exist. Gabapentin represents a potential therapy for COVID-19-induced OD. Objective: To evaluate the efficacy of oral gabapentin on olfactory function and olfaction-related quality of life in patients with COVID-19-induced OD. Design, Setting, and Participants: This pilot double-blinded, placebo-controlled randomized clinical trial (RCT) was conducted at Washington University School of Medicine in St Louis from January 7, 2022, to February 3, 2023. Adults with at least 3 months of OD after COVID-19 infection were eligible for inclusion. Participants with a history of other causes of OD or contraindications to gabapentin were excluded. Intervention: Patients were randomized 1:1 to oral gabapentin or placebo. All patients underwent titration to a maximum tolerable dose, which was maintained during an 8-week fixed-dose (FD) phase then tapered off. Participants were monitored for 4 weeks following cessation of study medication. Main Outcomes and Measures: Outcomes were assessed following the 8-week FD phase and 4 weeks after taper completion. The primary outcome measure was the response rate determined by subjective improvement in OD on the Clinical Global Impression of Improvement (CGI-I) after the FD phase. Other subjective and objective measures of olfactory function were also assessed as secondary outcome measures. Results: Sixty-eight participants were enrolled (34 randomized to each arm), a total of 44 participants completed the FD period and 20 (45.4%) reported response to treatment with at least slight improvement in olfaction from baseline. Of those randomized, 51 (75%) were women and 56 were White (82%) with a mean (SD) age of 43 (13.5) years. Baseline demographic features including age, sex, and race and ethnicity were not significantly different between the groups. Of the 18 participants in the gabapentin group, 8 (44%) were responders and of the 26 participants in the placebo group, 12 (46%) reported response to treatment (percent difference, 1.7%; 95% CI, -31.6% to 28.2%). Mixed-model analysis of all secondary outcome measures demonstrated no clinically meaningful or statistically significant difference between the gabapentin and placebo groups throughout the trial. There were no serious adverse events. Conclusions and Relevance: In this randomized clinical trial, gabapentin was not associated with statistically significant or clinically meaningful benefit over placebo and likely is not an efficacious therapy for COVID-19-induced OD. Trial Registration: ClinicalTrials.gov Identifier: NCT05184192.

Development and Psychometric Validation of the Olfactory Dysfunction Outcomes Rating.

Importance: Olfactory dysfunction (OD) is an increasingly common and morbid condition, especially given the ongoing COVID-19 pandemic. Thus, the ability to reproducibly measure smell loss-associated quality of life (QOL) and its response to treatment is paramount. Objective: To develop and validate a concise and visually appealing smell loss-associated QOL patient-reported outcome measure for OD. Design, Setting, and Participants: A secondary analysis of comments to an online survey by 1000 patients with olfactory dysfunction published in 2013 was used as the primary source to generate items of the Olfactory Dysfunction Outcomes Rating (ODOR). In addition, 30 patients with OD enrolled in 2 clinical studies at a tertiary care medical center (Washington University) were asked to identify their main concerns associated with smell loss. And finally, 4 otolaryngologists reviewed the items generated from the online survey and the patients' interviews to identify any additional items. Prospective study design was used for data collection from the 30 patients and 4 otolaryngologists. Prospective study design was used for survey validation. Validation of the ODOR was performed with 283 patients enrolled in several prospective studies at a single institution that completed the ODOR as an outcome measure. Main Outcomes and Measures: Item generation and selection were the outcomes of ODOR development. The psychometric and clinimetric measures evaluated for validation were internal consistency, test-retest reliability, face and content validity, concurrent validity, and discriminant validity. Minimal clinically important difference was also determined. Results: The ODOR is a 28-item instrument with each item scored as either no difficulty or very rarely bothered (0) to complete difficulty or very frequently bothered (4) with a total instrument score range of 0 to 112 points. Higher scores indicate higher degree of dysfunction and limitation. Validation in the cohort of 283 patients (mean [SD] age, 47.0 [14.4] years; 198 female participants [73%]; 179 White participants [80%]) revealed that the instrument has high internal consistency (Cronbach α = 0.968), test-retest reliability (r = 0.90 [95% CI, 0.81-0.95]), face validity, content validity, concurrent validity (r = 0.87 [95% CI, 0.80-0.91] compared with the Questionnaire of Olfactory Disorders-Negative Statements; ρ = -0.76 [95% CI, -0.81 to -0.71] compared with a patient-reported symptom severity scale), and divergent validity (mean score difference, -33.9 [95% CI, -38.3 to -29.6] between normosmic patients and hyposmic/anosmic patients). The minimal clinically important difference was 15 points. The estimated time for survey completion was approximately 5 minutes. Conclusions and Relevance: In this survey creation and validation study, the ODOR was shown to be a novel, concise, reliable, and valid patient-reported outcome measure of OD-associated QOL. It can be used to measure physical problems, functional limitations, and emotional consequences associated with OD and how they change after a given intervention, which is clinically applicable and particularly pertinent given the growing burden of OD associated with COVID-19.

Postoperative Hypocalcemia following Non-Cardiac Surgical Procedures in Children with 22q11.2 Deletion Syndrome.

The guidelines for management of children with 22q11.2 deletion syndrome (22q11DS) highlight the risk for developing hypocalcemia after surgery and recommend monitoring calcium perioperatively. Despite this guidance, little has been published on postoperative hypocalcemia and 22q11DS. Our goals were to evaluate the frequency of perioperative calcium monitoring and examine how often postoperative hypocalcemia was identified. This is a retrospective chart review of patients in our 22q Center's repository. Inclusion criteria were a diagnosis of 22q11DS and a history of a non-cardiac surgical procedure. Data collected included all non-cardiac surgeries and perioperative calcium labs. In total, 68 patients were included and underwent 305 on-cardiac surgeries. Patients in only 17% of these surgeries had postoperative calcium testing, but of those tested, 58% showed hypocalcemia. Patients with history of hypocalcemia at the time of chart review undergoing non-cardiac surgeries were tested postoperatively 40% of the time; however, 67% of these had hypocalcemia. Similarly, for patients without history of hypocalcemia, postoperative testing occurred 60% of the time, with 52% of these having hypocalcemia. This study demonstrates that postoperative hypocalcemia in children with 22q11DS following non-cardiac surgeries is common and affects patients both with and without prior history of hypocalcemia. These data support establishing a protocol for perioperative testing/management of hypocalcemia for patients with 22q11DS.

High prevalence of sternal foramina in indigenous Bolivians compared to Midwest Americans and indigenous North Americans (sternal foramina in indigenous Bolivians).

The sternal foramen, usually an asymptomatic osteological defect, can lead to catastrophic consequences if not recognized prior to certain medical procedures. This study reports the prevalence of a sternal foramen in two South Amerindian populations compared with other published populations. We evaluated the presence of sternal foramina using thoracic computed tomography scans of 1334 (48% female) participants from two indigenous populations of Bolivia (n = 900 Tsimane, 434 Moseten). The prevalence of sternal foramina was compared to two U.S. populations of similar sex/age distribution (n = 572 Midwest Americans, 131 self-identified Native North Americans) via similar CT scans. A sternal foramen was significantly more common in the two Bolivian populations (prevalence ranging from 12.8 to 13.4%), compared to 4.4-5.1% in the two U.S. groups, consistent with prior estimates in studies from industrialized populations. Males had higher frequency of a sternal foramen compared to females in each of the four groups (OR = 1.904, 95% CI: 1.418-2.568, p < 0.001). Age was not associated with sternal foramen presence. These data show both a higher rate of sternal foramina in the South Amerindian populations versus comparator populations in North America and the highest rate of any studied living population. Although it is not possible to determine from our data the relative contribution of genetics versus early life or environmental causes to the higher rates of sternal foramen, we note that small prior studies have likewise demonstrated a higher prevalence in lower income countries. Further determination of the contributing factors warrants greater investigation and research.