The Yale Center for Biomedical Innovation and Technology (CBIT): One Model to Accelerate Impact From Academic Health Care Innovation.

The process of translating academic biomedical advances into clinical care improvements is difficult, risky, expensive, and poorly understood. Notably, many clinicians who identify health care problems do not have the time or expertise to solve the problems, and many academic researchers are unaware of important gaps in clinical care to which their expertise may apply.Recognizing an opportunity to connect people who can identify health care problems with those who can solve them, the Yale Center for Biomedical Innovation and Technology (CBIT) was established in 2014 to educate and enhance the impact of health care innovators. The authors review other health care innovation centers and describe best practices borrowed by Yale CBIT, which tailored its activities and approach to its unique ecosystem.In four years, Yale CBIT has affected over 3,000 people and established a health care innovation cycle as an efficient strategy to guide translational research. Yale CBIT has created or supported graduate and undergraduate courses, clinical immersion programs for industry partners, and large health care hackathon events. Over 200 projects have been submitted to CBIT for mentorship, and some of those projects have been commercialized and raised millions of dollars of follow-on funding.The authors present Yale CBIT as one model of accelerating the impact of academic medicine on clinical practice and outcomes. The project advising strategy is intended to be a template to maximize the efficiency of biomedical innovation and ultimately improve the outcomes and experiences of future patients.

International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis.

BACKGROUND: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

A Systems Approach to Healthcare Innovation Using the MIT Hacking Medicine Model.

MIT Hacking Medicine is a student, academic, and community-led organization that uses systems-oriented "healthcare hacking" to address challenges around innovation in healthcare. The group has organized more than 80 events around the world that attract participants with diverse backgrounds. These participants are trained to address clinical needs from the perspective of multiple stakeholders and emphasize utility and implementation viability of proposed solutions. We describe the MIT Hacking Medicine model as a potential method to integrate collaboration and training in rapid innovation techniques into academic medical centers. Built upon a systems approach to healthcare innovation, the time-compressed but expertly guided nature of the events could enable more widely accessible preliminary training in systems-level innovation methodology, as well as creating a structured opportunity for interdisciplinary congregation and collaboration.

Gluten sensitivity: fact or fashion statement?

PURPOSE OF REVIEW: In recent years, the concern over food sensitivities in general and gluten intolerance in particular has sharply increased. Patients and medical providers are awash in various claims about the potential implications of including or excluding gluten from the diet. RECENT FINDINGS: Three main conditions are described with respect to gluten: wheat allergy, celiac disease, and nonceliac gluten sensitivity (NCGS). Wheat allergy is a type 1 hypersensitivity reaction to nongluten proteins within wheat. Celiac disease is an autoimmune reaction to the gluten protein resulting in damage to the small intestine with genetic associations. NCGS is a diagnosis of exclusion and, to date, no biomarkers have been identified for this condition. SUMMARY: When evaluating and treating patients with potential reactions to gluten, it is important to distinguish among wheat allergy, celiac disease, and NCGS. Each condition has distinct dietary and treatment implications.

Association of Vitamin D Status and Acute Rhinosinusitis: Results From the United States National Health and Nutrition Examination Survey 2001-2006.

Although vitamin D status may be a modifiable risk factor for various respiratory ailments, limited data exists regarding its role in sinonasal infections. Our goal was to investigate the association of 25-hydroxyvitamin D (25OHD) levels with acute rhinosinusitis (ARS) in a large, nationally representative sample of non-institutionalized individuals from the United States. In this cross-sectional study of individuals ≥ 17 years from the National Health and Nutrition Examination Survey 2001-2006, we used multivariable regression analysis to investigate the association of 25OHD levels with ARS, while adjusting for season, demographics (age, sex, race, and poverty-to-income ratio), and clinical data (smoking, asthma, chronic obstructive pulmonary disease, diabetes mellitus, and neutropenia). A total of 3921 individuals were included in our analyses. Median 25OHD level was 22 (interquartile range 16-28) ng/mL. Overall, 15.8% (95% confidence interval [CI] 14.4-17.7) of participants reported ARS within the 24 hours leading up to their survey participation. After adjusting for season, demographics, and clinical data, 25OHD levels were associated with ARS (odds ratio 0.88, 95% CI 0.78-0.99 per 10 ng/mL). When vitamin D status was dichotomized, 25OHD levels < 20 ng/mL were associated with 33% higher odds of ARS (odds ratio 1.33, 95% CI 1.03-1.72) compared with levels ≥ 20 ng/mL. Our analyses suggest that 25OHD levels are inversely associated with ARS. Randomized, controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of sinonasal infections.

Stepwise management of asthma.

BACKGROUND: Stepwise management of asthma remains an area of evolving research. Asthma is one of the most expensive chronic diseases in the United States; stepwise management is an important area of focus, with several recent guidelines recommending management. METHODS: This is a review of published English language literature, focusing on management guidelines for asthma in adult and pediatric patients. RESULTS: Asthma is a chronic disease whose assessment of severity allows for therapeutic goals to match the impairment noted. Good evidence exists to aid risk reduction, leading to decreased emergency room visits, preventing loss of lung function in adults and lung growth in children, and optimizing pharmacotherapy with reduced side effects profile. CONCLUSION: Recent asthma management guidelines incorporate 4 components of asthma care including: monitoring of severity, patient education, controlling external triggers, and medications, including recent attention to medication adherence. Asthma is an expensive chronic disease with preventive measures leading to reduced healthcare costs. Future targeted cytokine therapy to decrease serum and blood eosinophils may become an integral part of asthma management.

Clinical practice guideline: Bell's palsy.

OBJECTIVE: Bell's palsy, named after the Scottish anatomist, Sir Charles Bell, is the most common acute mono-neuropathy, or disorder affecting a single nerve, and is the most common diagnosis associated with facial nerve weakness/paralysis. Bell's palsy is a rapid unilateral facial nerve paresis (weakness) or paralysis (complete loss of movement) of unknown cause. The condition leads to the partial or complete inability to voluntarily move facial muscles on the affected side of the face. Although typically self-limited, the facial paresis/paralysis that occurs in Bell's palsy may cause significant temporary oral incompetence and an inability to close the eyelid, leading to potential eye injury. Additional long-term poor outcomes do occur and can be devastating to the patient. Treatments are generally designed to improve facial function and facilitate recovery. There are myriad treatment options for Bell's palsy, and some controversy exists regarding the effectiveness of several of these options, and there are consequent variations in care. In addition, numerous diagnostic tests available are used in the evaluation of patients with Bell's palsy. Many of these tests are of questionable benefit in Bell's palsy. Furthermore, while patients with Bell's palsy enter the health care system with facial paresis/paralysis as a primary complaint, not all patients with facial paresis/paralysis have Bell's palsy. It is a concern that patients with alternative underlying etiologies may be misdiagnosed or have unnecessary delay in diagnosis. All of these quality concerns provide an important opportunity for improvement in the diagnosis and management of patients with Bell's palsy. PURPOSE: The primary purpose of this guideline is to improve the accuracy of diagnosis for Bell's palsy, to improve the quality of care and outcomes for patients with Bell's palsy, and to decrease harmful variations in the evaluation and management of Bell's palsy. This guideline addresses these needs by encouraging accurate and efficient diagnosis and treatment and, when applicable, facilitating patient follow-up to address the management of long-term sequelae or evaluation of new or worsening symptoms not indicative of Bell's palsy. The guideline is intended for all clinicians in any setting who are likely to diagnose and manage patients with Bell's palsy. The target population is inclusive of both adults and children presenting with Bell's palsy. ACTION STATEMENTS: The development group made a strong recommendation that (a) clinicians should assess the patient using history and physical examination to exclude identifiable causes of facial paresis or paralysis in patients presenting with acute-onset unilateral facial paresis or paralysis, (b) clinicians should prescribe oral steroids within 72 hours of symptom onset for Bell's palsy patients 16 years and older, (c) clinicians should not prescribe oral antiviral therapy alone for patients with new-onset Bell's palsy, and (d) clinicians should implement eye protection for Bell's palsy patients with impaired eye closure. The panel made recommendations that (a) clinicians should not obtain routine laboratory testing in patients with new-onset Bell's palsy, (b) clinicians should not routinely perform diagnostic imaging for patients with new-onset Bell's palsy, (c) clinicians should not perform electrodiagnostic testing in Bell's palsy patients with incomplete facial paralysis, and (d) clinicians should reassess or refer to a facial nerve specialist those Bell's palsy patients with (1) new or worsening neurologic findings at any point, (2) ocular symptoms developing at any point, or (3) incomplete facial recovery 3 months after initial symptom onset. The development group provided the following options: (a) clinicians may offer oral antiviral therapy in addition to oral steroids within 72 hours of symptom onset for patients with Bell's palsy, and (b) clinicians may offer electrodiagnostic testing to Bell's palsy patients with complete facial paralysis. The development group offered the following no recommendations: (a) no recommendation can be made regarding surgical decompression for patients with Bell's palsy, (b) no recommendation can be made regarding the effect of acupuncture in patients with Bell's palsy, and (c) no recommendation can be made regarding the effect of physical therapy in patients with Bell's palsy.

Clinical practice guideline: Bell's Palsy executive summary.

The American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Bell's Palsy. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 11 recommendations developed encourage accurate and efficient diagnosis and treatment and, when applicable, facilitate patient follow-up to address the management of long-term sequelae or evaluation of new or worsening symptoms not indicative of Bell's palsy. There are myriad treatment options for Bell's palsy; some controversy exists regarding the effectiveness of several of these options, and there are consequent variations in care. In addition, there are numerous diagnostic tests available that are used in the evaluation of patients with Bell's palsy. Many of these tests are of questionable benefit in Bell's palsy. Furthermore, while patients with Bell's palsy enter the health care system with facial paresis/paralysis as a primary complaint, not all patients with facial paresis/paralysis have Bell's palsy. It is a concern that patients with alternative underlying etiologies may be misdiagnosed or have an unnecessary delay in diagnosis. All of these quality concerns provide an important opportunity for improvement in the diagnosis and management of patients with Bell's palsy.

Outcomes of sinus surgery in ambulatory patients with immune dysfunction.

BACKGROUND: Previous outcomes studies of patients with chronic rhinosinusitis (CRS) have mostly excluded subjects with immunodeficiency or autoimmune disease. Although expert opinion suggests these patients are often refractory to therapy, outcomes after endoscopic sinus surgery (ESS) are not well delineated. We evaluated improvement in objective and quality of life (QoL) measures after ESS in adult patients treated in the ambulatory setting with immune dysfunction including immunodeficiency and autoimmune diseases. METHODS: Patients with CRS associated with immune dysfunction (n = 22) were evaluated and matched 1:1 with control subjects from a prospective cohort in a nested case-control design. Preoperative computed tomography (CT) and pre-/postoperative endoscopic findings were recorded. Disease-specific QoL instruments (the Rhinosinusitis Disability Index [RSDI] and Chronic Sinusitis Survey [CSS]) were administered pre- and postoperatively. RESULTS: Mean postoperative follow-up was similar for both cases (18.6 +/- 6.6 months) and controls (18.4 +/- 8.7 months). Preoperative CT and endoscopy scores (i.e., disease severity) were similar in both cases and controls. Postoperative endoscopy scores were significantly improved for both cases (p < 0.001) and controls (p = 0.012). Both groups had similar preoperative and postoperative scores on the CSS; however, control subjects reported significantly worse RSDI baseline scores. Immunodeficiency and autoimmune cases and CRS controls experienced significant improvement in QoL after surgery (p < or = 0.041). CONCLUSION: Immunodeficiency and autoimmune cases, in the ambulatory setting, present with similar severity of disease when compared with controls with CRS. We found similar improvements in both objective and QoL outcomes for case subjects and control subjects, suggesting that patients with immune dysfunction may experience similar benefit from ESS.

Surgery for chronic rhinosinusitis may improve sleep and sexual function.

OBJECTIVES/HYPOTHESIS: This study was designed to evaluate the impact of surgery on the sexual function and sleep function of patients with chronic rhinosinusitis (CRS). STUDY DESIGN: A retrospective review of a cohort of prospectively enrolled patients with chronic rhinosinusitis who have undergone endoscopic sinus surgery. METHODS: Each patient completed the Rhinosinusitis Disability Index (RSDI) prior to surgery and at least nine months following endoscopic sinus surgery, and the preoperative and postoperative scores for the questions related to sleep and sexual activity were evaluated. Wilcoxon signed-rank test was used to assess the magnitude and direction of change between observation points. RESULTS: Mean response scores regarding sexual activity between preoperative (1.1 +/- 1.0) and postoperative scores (0.7 +/- 0.8) are significantly different (P < .001). Mean response scores regarding sleep dysfunction between preoperative (2.4 +/- 1.0) and postoperative scores (1.5 +/- 1.1) are also significantly different (P < .001). For both questions, a higher frequency of subjects responded "never" and "almost never" in the postoperative period compared with preoperative measures. CONCLUSIONS: Using the questions from the RSDI, there is an improvement in scores of sexual function and sleep after surgery for patients with chronic rhinosinusitis. Further, more in-depth evaluations of these potential benefits are needed.

Fracture of bony lamellae within the frontal recess after balloon catheter dilatation.

BACKGROUND: The precise manner in which balloon catheter dilatation (BCD) alters the dimensions of the frontal recess and frontal sinus outflow tract is not well characterized. The purpose of this investigation was to determine whether BCD within the frontal recess is associated with reproducible patterns of fracture in bony lamellae, to characterize changes between pre- and postintervention measurements of the frontal sinus outflow tract, and to compare the degree of change seen with endoscopic Draf I dissection. METHODS: Eight cadaver heads underwent pre- and postintervention endoscopic visualization and computed tomography (CT) of the frontal recess and frontal sinus outflow tract. Frontal recesses were assigned for either BCD or Draf I dissection. CT scans were evaluated by two reviewers (principal investigator and neuroradiologist). RESULTS: Inter-rater reliability was strong for all measures (r > 0.77; p < 0.001). The sagittal and coronal dimensions of the frontal sinus outflow tract increased significantly after BCD and Draf I dissection (p < 0.028). Significantly less change was noted in average coronal dimensions of the frontal sinus outflow tract after BCD compared with Draf I dissection (0.9 +/- 0.5 mm versus 2.6 +/- 0.6 mm; p < 0.018). Mean change in the sagittal dimension was significantly less after BCD compared with Draf I dissection (1.0 +/- 0.8 mm versus 4.0 +/- 1.2 mm; p < 0.018). The anterior face of the ethmoid bulla was the most frequently fractured lamella after BCD (56%). CONCLUSION: The sagittal and coronal dimensions of the frontal sinus outflow tract increased significantly after BCD and Draf I dissection. A significantly greater change in dimensions of the frontal sinus outflow tract is observed after Draf I dissection compared with BCD. No orbital or skull base injury was noted with either technique.

Outcomes of sinus surgery in adults with cystic fibrosis.

OBJECTIVES: Adults with cystic fibrosis (CF) represent a challenging subset of patients with chronic rhinosinusitis (CRS). While data suggest that endoscopic sinus surgery (ESS) may benefit pediatric CF patients, there remains a paucity of data regarding the impact of endoscopic sinus surgery on adult CF patients with CRS. Our purpose was to evaluate objective and quality-of-life measures in adult CF patients with CRS following ESS. STUDY DESIGN: Nested case-control study. SETTING: Tertiary care center. METHODS: Twenty patients with CF were evaluated and matched to 20 controls without concomitant CF. Preoperative CT and preoperative/postoperative endoscopic findings were recorded as objective measures. Changes in two disease-specific quality-of-life (QoL) instruments were also evaluated both preoperatively and postoperatively. RESULTS: Mean postoperative follow-up was similar for cases and controls (13.1 +/- 7.9 months vs 14.0 +/- 6.0 months, respectively). Preoperative CT scores (16.9 +/- 4.5 vs 10.9 +/- 5.9, P = 0.001) and endoscopy scores (9.3 +/- 5.8 vs 5.7 +/- 4.6, P = 0.049) were significantly worse in CF patients. Postoperative endoscopy scores were significantly worse for CRS patients with CF (P = 0.001), although the degree of improvement on endoscopy within each group was no different (P = 0.071). Additionally, both groups experienced similar improvement in QoL after ESS (all P > or = 0.134). CONCLUSIONS: While baseline measures of disease severity are worse in the CF population, our data support objective and QoL improvements for adult patients with comorbid CF comparable to patients without CF.

Middle turbinate hinge flap for frontal recess obliteration following prior cranialization.

Frontal sinus cranialization is an established procedure utilized in instances wherein the posterior table has been irreversibly compromised. A known complication of this procedure is pneumocephalus, which may develop if the frontal recess has not been fully separated from the cranialized sinus. We report 3 cases wherein massive pneumocephalus developed after cranialization of the frontal sinus. In each case, a novel endoscopic repair was undertaken utilizing a middle turbinate hinge flap to obliterate the frontal recess. In each instance, obliteration of the frontal recess resulted in durable resolution of pneumocephalus.

Accuracy and definitive interpretation of preoperative technetium 99m sestamibi imaging based on the discipline of the reader.

BACKGROUND: Technetium 99m sestamibi scans have become a principal means of localizing parathyroid adenomas. Its accuracy and reliability has allowed for the proliferation of minimal access parathyroidectomy. Localizing interpretation of these scans often drives referral of hyperparathyroid patients for surgery. Interpretation of these scans may differ between nuclear medicine physicians and surgeons. METHODS: We reviewed patients (N = 65) with digital images from an academic medical center with the diagnosis of primary hyperparathyroidism. We assessed the willingness to define an adenoma's location, the interrater reliability, and the accuracy of technetium (Tc-99m) sestamibi read by a surgeon and a nuclear medicine physician. RESULTS: There was poor correlation between both readers for assessment of quality of images (k = 0.54, 0.07) but very good correlation for adenoma location (k = 0.81). CONCLUSION: Both readers had good accuracy in predicting the location of the parathyroid adenoma. The surgeon was more likely to call a scan positive.

Physiologic alterations in the murine model after nasal fungal antigenic exposure.

OBJECTIVE: To determine whether a recently developed murine model of fungus-induced sinonasal inflammation demonstrated alterations in ciliary activity and expression of inflammatory cytokines. STUDY DESIGN: A prospective randomized controlled study of rhinosinusitis after fungal antigenic sensitization was performed with intraperitoneal aspergillus antigen injection followed by intranasal antigen challenge for 4 weeks. Saline solution was used in a parallel fashion for control animals. SUBJECTS AND METHODS: Six mice were used to validate the model. Additional 15 mice were used for ciliary beat frequency (CBF) analysis and cytokine expression with multiplex technology. Mean values for degree of inflammation, secretory hyperplasia, CBF, and cytokine expression were compared. RESULTS: Histologic analyses demonstrated dense chronic inflammation in aspergillus-challenged animals versus sparse inflammatory cells in controls. Significant differences in mean of aspergillus-challenged versus control animals were observed in degree of inflammation (P < 0.01), secretory hyperplasia (P < 0.01), CBF (P < 0.00002), IL-1alpha (P < 0.0002), IL-1beta (P < 0.0003), IL-4 (P < 0.02), TNF-alpha (P < 0.02), and RANTES (P < 0.01). CONCLUSION: Alteration in baseline CBF accompanied by increased expression of specific inflammatory cytokines was observed in aspergillus-challenged mice.

Prevalence of biofilm-forming bacteria in chronic rhinosinusitis.

BACKGROUND: Recently, biofilms have been implicated in the pathogenesis of recalcitrant chronic rhinosinusitis (CRS). We sought to determine the prevalence of biofilm-forming cultures obtained from patients with CRS and clinical factors that may contribute to biofilm formation. METHODS: Endoscopically guided sinonasal cultures were obtained in duplicate from CRS patients with evidence of mucopurulence. Bacterial swabs were sent for microbiological characterization and were simultaneously evaluated for biofilm-forming capacity by a modified Calgary Biofilm Detection Assay. Biofilm formation was based on concomitant values of biofilm-forming Pseudomonas aeruginosa O1 (PAO1) (positive control) and non-biofilm-forming mutants sad-31 (type IV pili) and sad-36 (flagella K; negative control). Samples, with growth greater than the sad-31 mutant, were designated as biofilm formers. RESULTS: Sinonasal cultures were obtained from 157 consecutive patients (83 female patients) over a 4-month period. Forty-five samples (28.6%) showed biofilm formation. Among patients with a prior history of functional endoscopic sinus surgery (FESS), 30.7% (n = 42) showed biofilm growth. For patients naive to surgical intervention (n = 20), only 15% showed biofilm formation. A positive, statistically significant correlation existed between biofilm formation and number of prior FESS procedures. Polymicrobial cultures, Pseudomonas aeruginosa, and/or Staphylococcus aureus comprised 71% of samples. Chi-squared analysis showed an association with prior infections, but not with any pharmacologic therapy or comorbidies. CONCLUSION: We show a high percentage of CRS patients (28.6%) whose sinonasal mucopurulence has biofilm-forming capacity. Postsurgical patients had a high prevalence of biofilm-forming bacteria, a possible reflection of the severe nature of their disease. Additional studies are warranted.

Fine-needle aspiration biopsy versus ultrasound-guided fine-needle aspiration biopsy: cost-effectiveness as a frontline diagnostic modality for solitary thyroid nodules.

BACKGROUND: Ultrasound-guided fine-needle aspiration biopsy (ultrasound-guided FNAB) is considered the diagnostic test of choice when a fine-needle aspiration biopsy (FNAB) returns an inconclusive diagnosis because of cytologic ambiguity or paucity of specimen. METHODS: Cost-effectiveness analysis utilizing a decision tree was used to model the diagnostic strategies. The decision analysis model was parameterized using costs from a large, academic medical center and probabilities from existing literature. Outcomes included the incremental cost per additional case correctly diagnosed. RESULTS: All data are reported as frontline ultrasound-guided FNAB strategy versus FNAB strategy-expected cost: $1329 versus $1312; expected number of cases correctly diagnosed (per 1000 biopsies): 980 versus 920; incremental cost per additional correctly diagnosed case: $289. CONCLUSION: The use of ultrasound-guided FNAB as the initial modality for tissue biopsy of a thyroid nodule is more effective than traditional FNAB at an additional cost of $289 per additional correct diagnosis.

Color doppler ultrasonography is a reliable predictor of free tissue transfer outcomes in head and neck reconstruction.

OBJECTIVE: The purpose of our investigation was to report our experience with a color flow doppler (CFD) ultrasonography for postoperative monitoring of free tissue transfers. METHODS: A retrospective analysis of head and neck free tissue transfers at a single institution between 2000 and 2005 (n = 84; 80 successful, 4 failures). CFD measured blood flow velocity (cm/sec) and resistance to flow in the pedicle vein and artery on postoperative days 1, 3, and 7. RESULTS: Analysis of artery/vein ratio revealed vascular congestion by postoperative day 3 which later resolved. In flap failures, there was a significant reduction (P < 0.05) in venous blood flow by postoperative day 3. Waveform morphology representing vascular resistance and origin of donor flap did not correlate with flap outcome (r(2) = 0.23 and 0.44 respectively). CONCLUSION: Postoperative monitoring of free tissue transfers may allow for detection of poor perfusion. CFD is an objective method of studying blood flow postoperatively. EBM RATING: C-4.