Canadian multidisciplinary expert consensus on the use of biologics in upper airways: a Delphi study.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. METHODS: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1-9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures-kappa coefficient ([Formula: see text]) value > 0.61. RESULTS: After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. CONCLUSION: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

Wound healing in endoscopic sinus surgery: Phase 1 clinical trial evaluating the role of Chitogel with adjuvants.

OBJECTIVES: This study aimed to determine the safety and efficacy of Chitogel, with and without Deferiprone (Def) and Gallium Protoporphyrin (GaPP), as a promoter of wound healing to improve surgical outcomes after endoscopic sinus susgery. DESIGN: A double-blinded, randomised control human clinical trial was conducted in patients undergoing ESS as a treatment for chronic rhinosinusitis. Participants underwent functional ESS or FESS with drill out as required and were randomised to receive test product Chitogel, Chitogel in combination with Def or Def-GaPP versus no packing (control). SETTING: Ostial stenosis and persistent inflammation are the main reasons for revision endoscopic sinus surgery (ESS). Post-operative (PO) dressings can improve PO wound healing and patient outcomes after ESS. PARTICIPANTS: Eighty two patients were included in this study with 79 patients completing the study with 40 undergoing full house FESS and 39 FESS plus frontal drillout. MAIN OUTCOME MEASURES: Patients were followed up at 2, 6 and 12 weeks PO, and outcome scores such as SNOT-22, VAS and LKS, pre and post-surgery (12 weeks) were compared. RESULTS: Seventy nine patients completed the study, there was a significant reduction in SNOT-22 score and improvement of VAS at 12 weeks in patients treated with Chitogel compared to control (p < .05). In those patients, the mean ostium area for the Chitogel and the Chitogel + Def + GaPP groups was higher across all three sinuses compared to the no-treatment control group, without statistical significance. Sphenoid sinus ostium was significantly more patent in patients treated with Chitogel compared to the control at the 12-week time point (p < .05). CONCLUSION: Chitogel as a PO dressing after ESS results in the best patient-reported symptom scores and objective measurements. The combination of Def and GaPP to Chitogel though proving safe, had no effect on the ostium patency or mucosal healing.

Heart rate as an early predictor of severe cardiomyopathy and increased mortality in peripartum cardiomyopathy.

BACKGROUND: Delays in diagnosis of peripartum cardiomyopathy (PPCM) are common and are associated with worse outcomes; however, few studies have addressed methods for improving early detection. HYPOTHESIS: We hypothesized that easily accessible data (heart rate [HR] and electrocardiograms [ECGs]) could identify women with more severe PPCM and at increased risk of adverse outcomes. METHODS: Clinical data, including HR and ECG, from patients diagnosed with PPCM between January 1998 and July 2016 at our institution were collected and analyzed. Linear and logistic regression were used to analyze the relationship between HR at diagnosis and the left ventricular ejection fraction (LVEF) at diagnosis. Outcomes included overall mortality, recovery status, and major adverse cardiac events. RESULTS: Among 82 patients meeting inclusion criteria, the overall mean LVEF at diagnosis was 26 ± 11.1%. Sinus tachycardia (HR > 100) was present in a total of 50 patients (60.9%) at the time of diagnosis. In linear regression, HR significantly predicted lower LVEF (F = 30.00, p < .0001). With age-adjusted logistic regression, elevated HR at diagnosis was associated with a fivefold higher risk of overall mortality when initial HR was >110 beats per minute (adjusted odds ratio 5.35, confidence interval 1.23-23.28), p = .025). CONCLUSION: In this study, sinus tachycardia in women with PPCM was associated with lower LVEF at the time of diagnosis. Tachycardia in the peripartum period should raise concern for cardiomyopathy and may be an early indicator of adverse prognosis.

Vascular Anatomy of the Inferior Turbinate and Its Clinical Implications.

BACKGROUND: Published reports on the vascular anatomy of the inferior turbinate (IT) are limited. Historical papers report the IT artery as a tributary off the posterior lateral nasal artery (PLNA), but this has not been our clinical experience. OBJECTIVE: The purpose of this study was to examine the arterial blood supply to and the branching pattern within the IT. We discuss this is the context of IT surgery and relate it to postoperative bleeding complication rates. METHODS: Endoscopic dissection was performed on 16 cadaver heads (24 sides) to determine the origin of the IT artery. Intraoperative surgical videos were analyzed in 50 patients to uncover the vascular branching pattern within the IT. A retrospective review of bleeding complications in patients undergoing IT reduction surgery was also conducted. RESULTS: In 17 of 24 sides (70.8%), the IT artery arose either exclusively (54.2%) or partly (16.6%) off the descending palatine artery (DPA). As a branch off the DPA, the IT artery exited the pterygopalatine fossa through a foramen located 7.7 ± 3.0 mm from posterior edge of the IT, 8.4 ± 3.1 mm above the nasal floor and 1.6 ± 2.1 mm below the insertion of the IT bone onto the lateral nasal wall. The mean number of arteries cascading within the IT was 2.7 ± 0.5. Moreover, 112 patients underwent IT reduction surgery and 2 (1.8%) experienced postoperative epistaxis. CONCLUSION: The IT artery has major contributions from the DPA. Most commonly 3 arteries branch within the IT. Knowledge of this vascular anatomy may minimize bleeding associated with IT reduction surgery.

The effectiveness of topical colloidal silver in recalcitrant chronic rhinosinusitis: a randomized crossover control trial.

BACKGROUND: Recalcitrant chronic rhinosinusitis without polyposis (CRSsP) is a challenging condition to manage as traditional medical therapies and surgery fail to provide satisfactory clinical improvements. Colloidal silver (CS), a widely used naturopathic agent, has recently shown anti-biofilm properties both in vitro and within a rhinosinusitis animal model. To date, no trials involving humans have been published in world literature. The purpose of this study was to assess the efficacy of CS as a topical nasal spray in patients with refractory CRSsP. METHODS: A prospective cohort study was conducted using a convenience sample of 20 randomized patients with crossover methodology, comparing nasal sprays with CS versus saline. Patients sprayed twice daily for six weeks with the first intervention and then switched to the second for the next six weeks, with measurements made at baseline and each time point. Primary outcomes were changes in SNOT-22 and Lund-Kennedy (LK) endoscopic scores. All analysis was non-parametric and was conducted using STATA 14. RESULTS: Twenty-two patients were enrolled in the study with 20 completing the entire protocol. Mean 6-week change in SNOT-22 scores were -2.8 and 1.0 for saline and CS, respectively (p = 0.373). Similarly, mean 6-week change in LK scores were -1.4 and -1.1 for saline and CS, respectively (p = 0.794). Significant period effects were observed with the SNOT-22 score between the randomized groups. No participants experienced negative health effects directly attributable to the administration of intranasal CS. CONCLUSION: Commercially available CS nasal spray did not demonstrate any meaningful subjective or objective improvements in patients with recalcitrant CRSsP. TRIAL REGISTRATION: NCT02403479 . Registered on March 1, 2015.

Office-based rhinologic surgery: A modern experience with operative techniques under local anesthetic.

BACKGROUND: Office-based rhinologic procedures have become popularized in recent years with the advent of several minimally invasive techniques. There is a paucity of literature, however, that supports more robust in-clinic procedures, e.g., true endoscopic sinus surgery (ESS). There is a high volume of this work being done at our center, and the objective of this article was to review the safety and tolerability of in-clinic surgeries. METHODS: A retrospective chart review was conducted. All the adult patients who underwent in-clinic sinonasal procedures and surgery with a minimum of 3 months of follow-up were included. Information regarding intra- and postoperative complications and revision procedures were recorded. For the ESS procedures, the indication, sinuses operated on, and type of revision were also collected. RESULTS: A total of 315 patients met the inclusion criteria. There were 166 turbinoplasties, 118 ESS, 35 septoplasties, 34 rhinoplasties, and 4 septorhinoplasties performed. For the ESS procedures, 74 (62.7%) were bilateral, and experience was had operating in all paranasal sinuses. All ESS work involved opening diseased ostia and was more than just polypectomies. The mean follow-up for the ESS cases was 13.4 months (range, 12-65 months). Complication rates and tolerability measures were comparable with those of other reported in-office sinonasal procedures performed with the patient under local anesthetic. CONCLUSION: Office-based rhinologic surgery was safe and well tolerated by the patients. The need for revision ESS in our series was low when considering the extent of surgery that was performed. An in-clinic procedure may avoid a general anesthetic in the operating room for appropriately selected patients.

Oral corticosteroid prescribing habits for rhinosinusitis: The American Rhinologic Society membership.

BACKGROUND: In the field of otolaryngology, oral corticosteroids (OCS) are widely prescribed for rhinosinusitis. Although there is evidence in the literature regarding specific OCS dosing protocols, it is not known to what extent these recommendations are being followed. OBJECTIVE: To examine the current state of OCS prescribing habits for rhinosinusitis by American Rhinologic Society members. METHODS: An anonymous online survey was sent to all American Rhinologic Society members. Dosing, frequency, tapering, and overall prescribing habits for OCS were assessed in chronic rhinosinusitis with polyposis (CRSwP) and in chronic rhinosinusitis without polyposis and acute bacterial rhinosinusitis. The CRSwP group was subdivided into aspirin-exacerbated respiratory disease, allergic fungal sinusitis, and not otherwise specified. Results were compared with current guidelines. Descriptive statistics were used to analyze data. RESULTS: Ninety-three surveys were completed (response rate, 12.9%). Prednisone was the most common OCS prescribed. In the CRSwP-aspirin-exacerbated respiratory disease group (n = 86), the median starting dose was 60 mg (range, 4-80 mg) and the average duration was 8 days (range, 2-28 days). In the CRSwP-allergic fungal sinusitis group (n = 81), the median starting dose was 50 mg (range, 20-60 mg), and the average duration was 6 days (range, 2-35 days). In the CRSwP-not otherwise specified group (n = 84), the median starting dose was 50 mg (range, 20-80 mg) and the average duration was 5 days (range, 1-21 days). OCS were prescribed for chronic rhinosinusitis without polyposis and acute bacterial rhinosinusitis by 66.0 and 62.4% of respondents, respectively. CONCLUSION: Significant heterogeneity existed in OCS prescribing habits for rhinosinusitis. Discrepancies were observed between survey results and evidence-based recommendations. Developing standardized OCS treatment protocols for rhinosinusitis may improve the quality of care by optimizing clinical outcomes and reducing the risk of complications.

Evaluating the referral preferences and consultation requests of primary care physicians with otolaryngology - head and neck surgery.

BACKGROUND: No literature exists which examines referral preferences to, or the consultation process with, Otolaryngology. In a recent Canadian Medical Association nation-wide survey of General Practitioners and Family Physicians, Otolaryngology was listed as the second-most problematic specialty for referrals. The purpose of this study was to learn about and improve upon the referral process between primary care physicians (PCPs) and Otolaryngology at an academic centre in Southwestern Ontario. METHODS: PCPs who actively refer patients to Otolaryngology within the catchment area of Western University were asked to complete a short paper-based questionnaire. Data was analyzed using descriptive statistics. RESULTS: A total of 50 PCPs were surveyed. Subspecialty influenced 90.0% of the referrals made. Specialist wait times altered 58.0% of referrals. All PCPs preferred to communicate via fax. Half of those surveyed wanted clinical notes from every encounter. Seventy-four percent of respondents wanted inappropriate referrals forwarded to the proper specialist automatically. Twenty-two percent of those surveyed were satisfied with current wait times. A central referral system was favored by 74% of PCPs. CONCLUSION: Improvements could help streamline the referral and consultation practices with Otolaryngology in Southwestern Ontario. A central referral system and reduction in the frequency of consultative reports can be considered.

Synthesis and biodistribution of 8-iodo-11-(4-methylpiperazino)-5H-dibenzo[b,e][1,4]-diazepine: Iozapine.

8-Iodo-11-(4-methylpiperazino)-5H-dibenzo[b,e][1,4]-diazepine: Iozapine, a potential D(4)-receptor ligand was synthesized using oxidative iodo-destannylation reaction. The preliminary biodistribution studies of radioiodinated iozapine have shown that the compound is taken up in the brains of mice and rabbits.

Episiotomy and vaginal trauma.

The era of routine episiotomy is gradually ending. Previously perceived benefits gradually have been disproved as evidence-based scientific clinical studies have shown the detrimental effects of episiotomy; however, circumstances always will exist in which prudent clinical judgment may dictate the necessity for an episiotomy. In most of these situations, however, an episiotomy often can be avoided. Perhaps more hospital perinatal review committees should evaluate episiotomy rates and strive to convince their staff to reduce their rates. We can learn to be more patient and allow the natural forces of labor to gradually stretch the perineum. In reviewing the extensive volume of published literature on episiotomy and perineal-vaginal trauma, the best advice lies in the dictum "Don't just do something, sit there!"

Cesarean delivery for fetal distress: rate and risk factors.

UNLABELLED: The objective of this article was to review the recent English language literature on cesarean delivery for fetal distress to determine its incidence, diagnostic tests, and the contributing factors to this obstetric complications. A PubMed search (1990-2000) with items of "cesarean, fetal distress," "cesarean, non-reassuring fetal heart rate," "cesarean, neonatal acidosis," and "cesarean, umbilical arterial pH," was undertaken. Reports, letters to the editor, focus on anomalous fetuses, and papers not specifically focused on this topic were excluded. Of the 392 articles that the search yielded, 169 met the inclusion criteria. Based on 37 reports with more than 1,000 patients each, the overall risk of prompt cesarean delivery for fetal concern was 3.1% (43,340 of 13,989,74). The risk exceeded 20% in patients with moderate/severe asthma, severe hypothyroidism, severe preeclampsia, and postterm or fetal growth restricted fetuses with abnormal Doppler studies. Use of likelihood ratios suggests that Doppler of the umbilical artery is a superior diagnostic test to amniotic fluid index in identifying parturients at risk for cesarean for non-reassuring fetal heart rate tracing. Although several risk factors increase the need for cesarean delivery for fetal distress, in general, most are unpreventable. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to estimate the incidence of cesarean delivery for non-reassuring fetal heart rate tracing, outline potential diagnostic tests that are useful for the detection of fetal distress, and summarize medical and obstetric conditions that place patients at risk for cesarean delivery for fetal distress.

Emergency cesarean delivery for nonreassuring fetal heart rate tracings. Compliance with ACOG guidelines.

OBJECTIVE: To review the English-language literature from 1990 to 2000 on cesarean delivery for "fetal distress" and assess compliance with American College of Obstetricians and Gynecologists (ACOG) guidelines. STUDY DESIGN: A PubMed search with the search items cesarean, fetal distress, cesarean, nonreassuring fetal heart rate, cesarean, neonatal acidosis and cesarean, umbilical arterial pH was undertaken. Excluded from the search were case reports, letters to the editor, focus on fetal anomaly, combinations with other reasons for operative delivery (either abdominally or vaginally) or absence of pertinent information. RESULTS: Among 392 articles from the search, 169 met the inclusion criteria. Three reports provided detailed information on use of scalp pH; use occurred in 5% (60/1,128) of emergency cesareans. Three reports provided data on the use of tocolytics for intrauterine resuscitation; the combined result was 16% (201/1,261). Five reports assessed the decision-to-incision interval within 30 minutes; in 59% (262/446) of cases it was achieved. Five reports contained cord pH information on 340 emergency cesarean deliveries; umbilical arterial pH was < 7.00 in 10%. CONCLUSION: Physician use of, and compliance with, ACOG guidelines for emergency cesarean deliveries is difficult to assess, and incomplete compliance appears commonplace.

Rapidly progressive amyloid polyneuropathy associated with a novel variant transthyretin serine 25.

We report a 52-year-old woman with a novel transthyretin (TTR) variant serine replacing alanine at residue 25 [Ala25Ser (Serine 25)], who showed a unique clinical picture with a relatively acute onset neuropathy within a few days of an influenza vaccination, progressing to a severe degree within 2 years. Sural nerve biopsy revealed amyloid deposition in the endoneurium. Sequencing of the proband's DNA revealed a G to T transversion at the first position of codon 25 of TTR gene. DNA analysis of this family showed the same mutation in her older sister and a niece, but her parents did not have the mutation. Haplotype analysis revealed the mutation to be clearly linked to haplotype III allele inherited from the proband's father. These results indicate this novel Serine 25 mutation originated in the paternal germline mosaicism. It is possible that the vaccination had an influence on the unique clinical picture, but this remains uncertain.