Safety and Adverse Events of Medialization Thyroplasty: A Systematic Review.

INTRODUCTION: Unilateral vocal fold paralysis or paresis (UVFP) is a condition that causes significant morbidity due to dysphonia, dysphagia, and aspiration. Type I medialization thyroplasty (MT) is the current mainstay surgical treatment for UVFP. Though widely considered a safe procedure, concerns exist over possible airway complications which can lead to overnight observation. Herein, we report a systematic review of the safety and adverse events of MT to aid in determining the safety of same-day discharge. DATA SOURCES: PubMed and Embase databases. REVIEW METHODS: Our search identified studies investigating complications associated with MT. Articles were selected if published between January 1, 1989 and March 15, 2023. Abstracts were screened, and data were extracted from included studies. Only Type I MT procedures were included; case reports were excluded. Participant characteristics, intervention details, results, and adverse events were extracted. RESULTS: The database query identified 751 abstracts, of which 46 studies met eligibility criteria. A total of 2426 patients underwent MT. The most common implant was Silastic (n = 898, 37.0%) followed by Gore-Tex (n = 664, 27.4%). There were 254 (10.5%) total complications reported; 110 (4.5%) were considered major. The most common complication was nonobstructive hematoma (n = 59, 2.4%) followed by hemorrhage (n = 36, 1.5%). Implant extrusion (n = 24, 0.99%) or displacement (n = 15, 0.62%) occurred mostly in Silastic and Gore-Tex implants. Same-day discharge occurred with 429 patients and was not associated with adverse events. CONCLUSIONS: UVFP can be reliably improved by MT with a low risk of complications. Outpatient MT is a promising treatment with a favorable safety profile. Laryngoscope, 134:1994-2004, 2024.

Treatments for Age-related Vocal Atrophy: A Systematic Review.

OBJECTIVE: Age-related vocal atrophy (ARVA) can dramatically affect voice, communication, and quality of life. The objectives of this systematic review were to (1) determine whether treatments for ARVA were superior to controls (2) compare the relative efficacy of procedural and behavioral treatments (3) review the various types of outcome measures, and (4) evaluate the quality of studies. REVIEW METHODS: The literature was searched using strategies designed by a medical librarian (2/18/21, updated 3/9/22). Studies investigating treatments for bilateral vocal atrophy were included. Studies involving unilateral atrophy, presbyphonia (without endoscopic findings), or an absent comparator group were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist was used to guide this study. RESULTS: After applying the inclusion/exclusion criteria, 8 articles remained, including 4 randomized trials and 4 cohort studies, and a narrative synthesis was performed. Surgical and behavioral treatments for ARVA appeared to be superior to control groups, based on specific outcome measures. However, the superiority of these treatments over controls was not uniformly observed across multiple outcome measures. When comparing different treatments, superiority could not be established based on the quality and completeness of the studies included in the systematic review. Outcome measures also varied between individual studies. Finally, the risk of bias was analyzed and scored. Consistent point deductions among reviewed studies were noted. CONCLUSIONS: When comparing treatments for ARVA. Surgery and voice therapy were both superior to control groups based on specific outcome measures from different domains. Superiority of one treatment could not be established. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:2846-2855, 2023.

Broadly neutralizing antibody-mediated protection against simian-HIV infection among macaques with vaginal sexually transmitted infections.

OBJECTIVE: Sexually transmitted infections (STIs) increase mucosal HIV infection risk and have the potential to reduce preexposure prophylaxis efficacy. Clinical trials of a broadly neutralizing antibody (bNAb) provided proof-of-concept that passive immunization against HIV can be efficacious in people. We sought to evaluate preclinically the protective efficacy of passive bNAb immunization against simian-human immunodeficiency virus (SHIV) infection in the context of concurrent vaginal STIs. DESIGN: Using a macaque model of combined ulcerative and nonulcerative vaginal STIs caused by Treponema pallidum , Chlamydia trachomatis , and Trichomonas vaginalis , we determined the protection that passively administered bNAb 10-1074 conferred against repeated vaginal SHIV challenges and compared correlates of protection to contemporaneous and historical controls without STIs. METHODS: Plasma viremia was monitored via RT-qPCR assay. Concentrations of 10-1074 were determined longitudinally in plasma samples via TZM-bl pseudovirus neutralization assay. RESULTS: Among macaques with vaginal STIs, a single subcutaneous injection of 10-1074 durably protected against vaginal SHIV acquisition, as compared with untreated controls. Interestingly, the median plasma concentration of 10-1074 at the time of SHIV breakthrough among macaques with STIs was significantly higher (10-fold) than that previously observed among 10-1074-treated macaques in the absence of STIs. CONCLUSION: Passive immunization with 10-1074 conferred significant protection against repeated vaginal SHIV challenges among macaques harboring vaginal STIs. However, our findings suggest that higher bNAb concentrations may be required for prophylaxis when STIs are present. Our findings potentially impact dose selection for the clinical development of bNAbs and highlight the importance of additional preclinical efficacy testing in STI models.

A Novel Grading System for Supraglottic Stenosis Based on Morphology and Functional Status.

OBJECTIVE: Currently, no classification system exists to grade the severity of supraglottic stenosis. The aim of this investigation was to (1) develop a novel grading system for supraglottic stenosis that can both enhance communication between providers and relay information about patient functional status and (2) determine the reliability of the grading system. METHODS: A retrospective analysis of patients with supraglottic stenosis at three institutions from 2010-2021 was conducted. After demographic data were collected, two focus group meetings of five laryngologists were held to develop a grading system based on functional status and morphology of stenosis seen on laryngoscopy. Three laryngologists then used the grading system to rate 20 case examples of supraglottic stenosis. Quadratic-weighted kappa coefficients were calculated to assess inter-rater and intra-rater reliabilities of the novel grading system. RESULTS: Twenty-eight patients were included. Epiglottic and arytenoid fixation were morphological features associated with worse functional outcomes such as requiring a G-tube or a tracheostomy, respectively. Inter-rater reliability was substantial to almost perfect (Kw = 0.79-0.81) and intra-rater reliability was almost perfect for all raters (0.88-1.0) when using the novel grading system. CONCLUSION: A grading system for supraglottic stenosis has been proposed with strong inter-rater and intra-rater reliabilities. The proposed system has the advantage of being descriptive of both patient functionality and morphology of the stenosis. LEVEL OF EVIDENCE: 3-According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 3 evidence Laryngoscope, 133:1442-1447, 2023.

Dynamics of lidocaine in topical anesthesia for office-based laryngeal procedures: A pilot study.

OBJECTIVES: To study topical lidocaine for office-based laryngeal procedures recording onset, duration, and subjective experience of topical anesthesia. STUDY DESIGN: Nine healthy volunteers were anesthetized with 4 % lidocaine endoscopically. Laryngeal sensitivity prior to and during anesthesia was recorded until normal sensation returned measured by air-puff sensory testing. Subjective experience of the process was recorded. METHODS: Questionnaires regarding subjective experience were completed prior to, during, and after anesthesia. Laryngeal sensitivity via air-pulse trigger of the laryngeal adductor reflex (LAR) prior to and after 3 mL shower of 4 % lidocaine was recorded at 30 second intervals until the larynx was insensate with no LAR at 10 mmHg. Time to anesthesia was recorded and post-endoscopy questionnaire was given. Upon subjective change in sensation, sensitivity via air-pulse trigger of the LAR was recorded until baseline sensation returned. A post-anesthesia questionnaire recorded the subjective experience. RESULTS: Average time to full anesthesia was 110 s (±31.2). Subjective return of sensation was noted at 10 min (±2.5), however time to return to normal LAR was 22 min (±5.8). Based on three standard deviations, 99.7 % of the population will be anesthetized at 3.4 min, report subjective change at 18.2 min and regain full sensation at 40 min. CONCLUSIONS: Office-based laryngeal procedures should be performed at least 2 min following topical 4 % lidocaine with a window for manipulation of at least 16 min. Oral intake should be delayed for over 45 min to ensure complete return of sensation. The laryngeal shower of lidocaine is subjectively tolerated. LEVEL OF EVIDENCE: 2C Outcomes Research.

Safety and Predictors of 30-Day Adverse Events of Laryngeal Framework Surgery: An Analysis of ACS-NSQIP data.

OBJECTIVES/HYPOTHESIS: To characterize and identify predictors of 30-day adverse events in patients undergoing laryngeal framework surgery (LFS). STUDY DESIGN: This study is a retrospective analysis of the National Surgical Quality Improvement dataset. METHODS: LFS cases were identified from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database from 2008 to 2018. Demographic variables, patient comorbidities, and perioperative outcomes (any adverse event, 30-day readmission, 30-day reoperation, and unplanned intubation) were extracted. Patient-specific and surgery-specific factors associated with perioperative adverse events were examined using descriptive statistics and univariate logistic regression (LR). RESULTS: Of 283 patients who underwent LFS, 225 underwent laryngoplasty medialization, 56 underwent laryngoplasty medialization with arytenoidectomy or arytenoidopexy via an external approach, and 2 underwent local myocutaneous or fasciocutaneous advancement flap along with laryngoplasty. Medical comorbidities were present in 33.6% of patients and 57.9% were American Society of Anesthesiologists (ASA) Class III/IV (57.9%). LFS was performed as same-day surgery in 30.7% of cases. Fourteen patients (4.9%) suffered an adverse condition within 30 days following surgery. In univariate LR, ASA Class III or IV (odds ratio [OR] 4.6, 95% confidence interval [CI] 1.2-30.1) was the only predictor associated with any adverse event. Arytenoid adduction (AA) was associated with increased risk of reoperation within 30 days of the initial surgery (OR 6.4, 95% CI 1.0-49). CONCLUSIONS: LFS is a generally safe procedure with infrequent perioperative adverse events. In the ACS-NSQIP database, ASA classification of III or IV was associated with a higher risk for any 30-day adverse event and AA was associated with a higher risk for 30-day reoperation. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1414-1420, 2022.

Assessing the Clinical Utility of the Early Postoperative Pharyngogram in Hypopharyngeal Surgery for Dysphagia.

OBJECTIVES/HYPOTHESIS: To evaluate the clinical utility of postoperative contrast x-ray pharyngograms (XRP) for detecting pharyngoesophageal leaks following hypopharyngeal dysphagia surgery. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records were reviewed of patients undergoing endoscopic (E-) or open (O-) Zenker's diverticulectomy (-ZD) with cricopharyngeal myotomy (-CPM) and CPM alone from 2008 to 2020 at one academic institution. Exclusion criteria were patients who were fed enterally or underwent repair of epiphrenic diverticula or O-CPM during laryngectomy. XRP clinical indication, impact on clinical care, and factors associated with use patterns were examined using descriptive statistics and logistic regression (LR). RESULTS: Of 152 subjects, 52% underwent O-ZD, 30% O-CPM, 15% E-ZD, and 3% E-CPM. An XRP was ordered for 65% of subjects, mostly routinely (94%). Among the four clinically apparent leaks observed in this cohort, early postoperative XRP confirmed one. It did not identify any clinically silent leaks. In univariate LR, undergoing XRP was associated with increasing day of diet advancement (odds ratio [OR] 4.7, 95% confidence interval [CI] 2.5-10.5) and hospital stay duration (OR 3.2, 95% CI 2.1-5.2), as well as surgeon specialty of otolaryngology compared to general surgery (OR 12.8, 95% CI 4.8-40.8) and procedure sub-type (O-CPM: OR 0.03, 95% CI 0.002-0.16). In multivariate LR, the following variables were significantly associated with XRP use: hospital stay (OR 1.7; 95% CI 1.1-3.0), otolaryngology (OR 105; 95% CI 15.4-2193), O-CPM (OR 0.03; 95% CI 0.002-0.16), and E-CPM (OR 0.04, 95% CI 0.002-0.60). CONCLUSIONS: Prospective, multi-institutional studies are needed to confirm the low clinical utility we observed of early, postoperative XRP following hypopharyngeal surgery for dysphagia. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:272-277, 2022.

Broadly neutralizing antibody-mediated protection of macaques against repeated intravenous exposures to simian-human immunodeficiency virus.

OBJECTIVE: The opioid epidemic has increased parentally acquired HIV infection. To inform the development of a long-acting prevention strategy, we evaluated the protective efficacy of broadly neutralizing antibodies (bNAbs) against intravenous simian-human immunodeficiency virus (SHIV) infection in macaques. DESIGN: Five cynomolgus macaques were injected once subcutaneously with 10-1074 and 3BNC117 (10 mg each kg-1) and were repeatedly challenged intravenously once weekly with SHIVAD8-EO (130 TCID50), until infection was confirmed via plasma viral load assay. Two control macaques, which received no antibody, were challenged identically. METHODS: Plasma viremia was monitored via RT-qPCR assay. bNAb concentrations were determined longitudinally in plasma samples via TZM-bl neutralization assays using virions pseudotyped with 10-1074-sensitive (X2088_c9) or 3BNC117-sensitive (Q769.d22) HIV envelope proteins. RESULTS: Passively immunized macaques were protected against a median of five weekly intravenous SHIV challenges, as compared to untreated controls, which were infected following a single challenge. Of the two bNAbs, 10-1074 exhibited relatively longer persistence in vivo. The median plasma level of 10-1074 at SHIV breakthrough was 1.1 µg ml-1 (range: 0.6-1.6 µg ml-1), whereas 3BNC117 was undetectable. Probit modeling estimated that 6.6 µg ml-1 of 10-1074 in plasma corresponded to a 99% reduction in per-challenge infection probability, as compared to controls. CONCLUSIONS: Significant protection against repeated intravenous SHIV challenges was observed following administration of 10-1074 and 3BNC117 and was due primarily to 10-1074. Our findings extend preclinical studies of bNAb-mediated protection against mucosal SHIV acquisition and support the possibility that intermittent subcutaneous injections of 10-1074 could serve as long-acting preexposure prophylaxis for persons who inject drugs.

Recurrent Respiratory Papillomatosis Office versus Operating Room: Systematic Review and Meta-Analysis.

OBJECTIVES: Recurrent respiratory papillomatosis can be treated in the office or operating room (OR). The choice of treatment is based on several factors, including patient and surgeon preference. However, there is little data to guide the decision-making. This study examines the available literature comparing operative treatment in-office versus OR. METHODS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews guidelines. Of 2,864 articles identified, 78 were reviewed full-length and 18 were included. Outcomes of interest were recurrence and complication rates, number of procedures, time interval between procedures, and cost. RESULTS: Only one study compared outcomes of operative in-office to OR treatments. The weighted average complication rate for OR procedures was 0.02 (95% confidence interval [CI] 0.00-0.32), n = 8, and for office procedures, 0.17 (95% CI 0.08-0.33), n = 6. The weighted average time interval between OR procedures was 10.59 months (5.83, 15.35) and for office procedures 5.40 months (3.26-7.54), n = 1. The weighted average cost of OR procedures was $10,105.22 ($5,622.51-14,587.83), n = 2 versus $2,081.00 ($1,987.64-$2,174.36), n = 1 for office procedures. CONCLUSION: Only one study compares office to OR treatment. The overall data indicate no differences aside from cost and imply that office procedures may be more cost-effective than OR procedures. However, the heterogeneous data limits any strong comparison of outcomes between office and OR-based treatment of laryngeal papillomas. More studies to compare the two treatment settings are warranted.

Prospective Randomized Trial Comparing Opioids versus Nonsteroidal Antiinflammatory Drugs for Postoperative Analgesia in Outpatient Rhinoplasty.

BACKGROUND: The misuse and abuse of opioids, including overprescription, has led to the current opioid epidemic and national crisis. There is a national effort to eliminate the unnecessary prescription of opioids for analgesia. METHODS: Seventy patients were randomized to receive postoperative analgesia with either 5 mg hydrocodone with 325 mg acetaminophen (opioid control group) or 400 mg of ibuprofen [nonsteroidal antiinflammatory drug (NSAID) experimental group]. Pain levels were assessed on postoperative days 1, 2, and 7. Outcome measures included numeric pain rating scores and assessments of frequency and amount of analgesic used. RESULTS: There was no significant difference in gender (p = 0.81) or age (p = 0.61) between groups. On postoperative day 0, the NSAID group (mean ± SD, 2.54 ± 1.57) was found to be noninferior to the opioid group (mean ± SD, 3.14 ± 1.75; p = 0.003). On postoperative day 1, the NSAID group showed a lower mean pain score (mean ± SD, 1.84 ± 1.29) than the opioid group (mean ± SD, 2.46 ± 1.90; p = 0.01). However, on postoperative day 7, the difference in pain scores between the NSAID (mean ± SD, 3.29 ± 2.14) and opioid (mean ± SD, 3.14 ± 2.12; p = 0.17) groups lost statistical significance. There was no significant difference in mean day of medication cessation between the NSAID (mean ± SD, 4.73 ± 1.57) and opioid (mean ± SD, 4.28 ± 2.23; p = 0.26) groups. Seventy-six percent of patients who were prescribed opioids took fewer than eight tablets. Five patients escalated from NSAIDs to opioids. There were no adverse effects related to NSAID use. CONCLUSIONS: NSAIDs are an acceptable and safe alternative to opioids for postoperative analgesia in rhinoplasty and potentially lead to better overall pain control in some patients. Significantly reducing or eliminating opioid prescriptions may be considered in light of the current opioid epidemic. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Durable protection against repeated penile exposures to simian-human immunodeficiency virus by broadly neutralizing antibodies.

Penile acquisition of HIV accounts for most infections among men globally. Nevertheless, candidate HIV interventions for men advance to clinical trials without preclinical efficacy data, due primarily to a paucity of relevant animal models of penile HIV infection. Using our recently developed macaque model, we show that a single subcutaneous administration of broadly neutralizing antibody (bNAb) 10-1074 conferred durable protection against repeated penile exposures to simian-human immunodeficiency virus (SHIVSF162P3). Macaques co-administered bNAbs 10-1074 and 3BNC117, or 3BNC117 alone, also exhibited significant protection against repeated vaginal SHIVAD8-EO exposures. Regression modeling estimated that individual plasma bNAb concentrations of 5 µg ml-1 correlated with ≥99.9% relative reduction in SHIV infection probability via penile (10-1074) or vaginal (10-1074 or 3BNC117) challenge routes. These results demonstrate that comparably large reductions in penile and vaginal SHIV infection risk among macaques were achieved at clinically relevant plasma bNAb concentrations and inform dose selection for the development of bNAbs as long-acting pre-exposure prophylaxis candidates for use by men and women.

Long-Acting Cabotegravir Protects Macaques Against Repeated Penile Simian-Human Immunodeficiency Virus Exposures.

We used a novel penile simian-human immunodeficiency virus (SHIV) transmission model to investigate whether long-acting cabotegravir (CAB LA) prevents penile SHIV acquisition in macaques. Twenty-two macaques were exposed to SHIV via the foreskin and urethra once weekly for 12 weeks. Of these, 6 received human-equivalent doses of CAB LA, 6 received oral emtricitabine/tenofovir disoproxil fumarate, and 10 were untreated. The efficacy of CAB LA was high (94.4%; 95% confidence interval, 58.2%-99.3%) and similar to that seen with oral emtricitabine/tenofovir disoproxil fumarate (94.0%; 55.1%-99.2%). The high efficacy of CAB LA in the penile transmission model supports extending the clinical advancement of CAB LA preexposure prophylaxis to heterosexual men.

Decreased Tongue Volume Post Radiation.

OBJECTIVES: To evaluate volume changes within the tongue post chemoradiation therapy (CRT). STUDY DESIGN: Retrospective review. SETTING: Academic Medical Center. SUBJECTS AND METHODS: Subjects included 19 patients that received CRT as the primary treatment for tonsillar or hypopharynx squamous cell carcinoma. Tongue volumes were calculated by three raters from thin slice computed tomography images collected before treatment and up to 29 months post-CRT. Body mass index (BMI) was also collected at each time point. RESULTS: Inter-rater reliability was high with an ICC of 0.849 (95% CI = 0.773, 0.905). Linear mixed effects modeling showed a mean decrease of 0.45 cm3 (standard error of the mean [SEM] = 0.11) in tongue volume per month post-CRT (P < .001). However, the addition of BMI to the model was significant (χ2 (4) = 25.0, P < .001), indicating that BMI was a strong predictor of tongue volume, with a mean decrease of 1.75 cm3 (SEM = 0.49) in tongue volume per unit decrease in BMI (P < .001) and reducing the post-CRT effect on tongue volume decrease per month to 0.23 cm3 (P = .02). BMI significantly (P < .001) decreased by 0.11 units (SEM = 0.02) per month post radiation. CONCLUSION: Tongue dysfunction and decreased tongue strength are significant contributors to the dysphagia that patients experience after receiving CRT. In this study, both tongue volume and BMI decreased post-CRT; therefore, BMI could potentially be used as a predictor of tongue volume post-CRT.

Management of Iatrogenic Cervical Esophageal Perforations: A Narrative Review.

Importance: Esophageal perforations are difficult to diagnose and have a high mortality rate. Cervical esophageal perforations (CEPs) are the second most common anatomic type of esophageal perforations and are most often due to iatrogenic injury. They are often managed more conservatively than thoracic perforations. The current literature on CEPs is mostly observational, with a paucity of prospective controlled studies. In addition, there is scarce literature focusing specifically on iatrogenic CEPs (iCEPs) as an entity of their own. Observations: The existing studies on esophageal perforations address treatment by anatomic location and by cause, but few focus specifically on iCEPs. The cricopharynx is the most common site for injury in diagnostic endoscopy. The standard treatment is generally conservative management with drainage unless the perforation is greater than 2 cm, the diagnosis is delayed, or the patient shows signs of sepsis, which would prompt surgical intervention, most commonly in the form of primary repair via open or endoscopic approach. An open approach has been the mainstay of therapy; however, use of endoscopic clips, stents, and suturing is increasingly on the rise. Guideline recommendations on the optimal therapeutic approach for iCEPs are lacking. The most consistent recommendation in the literature is immediate and individualized treatment. Conclusions and Relevance: The management of iCEPs is controversial. There is a need for additional prospective studies comparing treatment options for iCEPs to establish a gold standard treatment and to assess for the expanding role of endoscopic interventions.

Implementation of a three-tiered approach to identify and characterize anti-drug antibodies raised against HIV-specific broadly neutralizing antibodies.

The ability to detect, quantify, and interrogate the properties of immune responses raised against biological therapeutics is not only important to our understanding of these molecules, but also to their success in the clinic. A tiered assay approach to identify the presence, specificity, and titer of anti-drug antibody (ADA) responses has been adopted as a gold standard by industry leaders, the FDA, and the EMA. In order to support pre-clinical and clinical trials, these assays must be standardized, and their performance sufficiently characterized to ensure the accuracy and reproducibility of results under relevant testing conditions. Here we present implementation of electrochemiluminiscence assays that fit into the tiered paradigm of ADA testing for five HIV broadly neutralizing antibodies (3BNC117, 3BNC117-LS, 10-1074, PGT121, and PGDM1400) in compliance with Good Clinical Laboratory practices. Assay sensitivities and matrix effects were evaluated and used to inform the development of positivity cut points. Once cut points were established, assay precision, specificity, free-drug tolerance, and robustness were defined. In all cases, assay characteristics met or surpassed recommendations set forth by the FDA. To further evaluate the performance of these assays and the tiered approach, samples from non-human primates that had received a subset of the five therapeutics were evaluated. In sum, this study reports qualification of a set of ADA assays available to the scientific community as pre-clinical and clinical trials of broadly HIV-neutralizing antibodies proceed, and a framework that is easily adapted as new drug products are advanced in the clinic.

Improving On-time Discharge in Otolaryngology Admissions.

OBJECTIVE: We conducted a quality improvement project to increase the rate of discharges before noon (DBN) in the otolaryngology department at a tertiary care center. METHODS: Based on a Plan-Do-Study-Act framework, monthly discharge data and observed-to-expected (O:E) length of stay were collected and shared with the department members monthly. A target of 43% DBN was predetermined by the center (Plan). The following interventions were implemented (Do): discharge planning starting at the time of admission, focus on early attending-to-resident team communication, placement of discharge order prior to rounding, and weekly reminders to the entire department. RESULTS: Discharges were monitored for 3 years. For the year prior to this study, a minority of patients were discharged before noon (12 months: 75 of 190, 36%). During the first 6 months of monitoring (Study), no significant improvement was identified (34 of 95, 36%). After interventions, performance significantly improved (31 months: 250 of 548, 68%). The performance was consistently above the predetermined target of 43%. During the study time, O:E length of stay remained below the predetermined target (O:E ratio, 0.90; hospital target, 0.93). DISCUSSION: Comprehensive discharge planning beginning at the time of admission, weekly reminders, and improved communication (Act) can help to prioritize DBN and increase the percentage of discharges before noon. IMPLICATIONS FOR PRACTICE: By utilizing a quality improvement framework, significant improvements in timely discharge can be achieved and sustained with changes in workflow and departmental culture. These changes can be achieved without increases in resources or prolonging the length of stay.

Optimization and qualification of a functional anti-drug antibody assay for HIV-1 bnAbs.

The recent identification of human monoclonal antibodies with broad and potent neutralizing activity against HIV-1 (bnAbs) has resulted in substantial efforts to develop these molecules for clinical use in the prevention and treatment of HIV-1 infection. As with any protein therapeutic drug product, it is imperative to have qualified assays that can accurately detect and quantify anti-drug antibodies (ADA) that may develop in patients receiving passive administration of HIV-1 bnAbs. Here, we have optimized and qualified a functional assay to assess the potential of ADA to inhibit the neutralizing function of HIV-1 bnAbs. Using a modified version of the validated TZM-bl HIV-1 neutralization assay, murine anti-idiotype antibodies were utilized to optimize and evaluate parameters of linearity, range, limit of detection, specificity, and precision for measuring inhibitory ADA activity against multiple HIV-1 bnAbs that are in clinical development. We further demonstrate the utility of this assay for detecting naturally occurring ADA responses in non-human primates receiving passive administration of human bnAbs. This functional assay format complements binding-antibody ADA strategies being developed for HIV-1 bnAbs, and when utilized together, will support a multi-tiered approach for ADA testing that is compliant with Good Clinical Laboratory Practice (GCLP) procedures and FDA guidance.

Impact of Q-Griffithsin anti-HIV microbicide gel in non-human primates: In situ analyses of epithelial and immune cell markers in rectal mucosa.

Natural-product derived lectins can function as potent viral inhibitors with minimal toxicity as shown in vitro and in small animal models. We here assessed the effect of rectal application of an anti-HIV lectin-based microbicide Q-Griffithsin (Q-GRFT) in rectal tissue samples from rhesus macaques. E-cadherin+ cells, CD4+ cells and total mucosal cells were assessed using in situ staining combined with a novel customized digital image analysis platform. Variations in cell numbers between baseline, placebo and Q-GRFT treated samples were analyzed using random intercept linear mixed effect models. The frequencies of rectal E-cadherin+ cells remained stable despite multiple tissue samplings and Q-GRFT gel (0.1%, 0.3% and 1%, respectively) treatment. Whereas single dose application of Q-GRFT did not affect the frequencies of rectal CD4+ cells, multi-dose Q-GRFT caused a small, but significant increase of the frequencies of intra-epithelial CD4+ cells (placebo: median 4%; 1% Q-GRFT: median 7%) and of the CD4+ lamina propria cells (placebo: median 30%; 0.1-1% Q-GRFT: median 36-39%). The resting time between sampling points were further associated with minor changes in the total and CD4+ rectal mucosal cell levels. The results add to general knowledge of in vivo evaluation of anti-HIV microbicide application concerning cellular effects in rectal mucosa.

A Novel, Minimally Invasive Approach to Replacing Missing Teeth: Two Case Reports.

For the replacement of missing teeth, resin-bonded fixed partial dentures (RBFPDs) are a routine, minimally invasive option clinicians can use on patients who either cannot or will not move forward with surgical interventions. Advances in materials and design have greatly improved the longevity and prognoses for these prostheses. In some patients, however, debonding remains a clinical problem. In this clinical report, novel RBFPD designs are presented with the aim of improving retention and esthetics while offering short treatment time and minimal preparation without the need for local anesthesia.