Expanding Access to Contraceptive Services in a Family Medicine Residency Clinic: The Rapid Access to Contraception Clinic Model.

BACKGROUND AND OBJECTIVES: Learning to provide long-acting reversible contraception (LARC) during family medicine residency is an important step in building capacity for the primary care workforce to meet the reproductive health care needs of communities. We aimed to measure the impact of adding a contraceptive visit type (CVT) allowing for rapid access to contraception (RAC) on family medicine resident LARC procedure numbers. METHODS: Our program created a CVT in which patients were seen only for contraceptive services. We added the CVT to third-year family medicine resident continuity clinic schedules and a block of CVTs (the RAC clinic) to the third-year gynecology rotation. Residents self-reported LARC procedure numbers performed throughout residency, and the totals were compared for graduating residents from 2023 (post-RAC cohort) to 2022 graduates and 2018-2022 graduates (pre-RAC cohort). RESULTS: Post-RAC cohort residents reported a statistically significant increase in intrauterine device (IUD; P=.015) and contraceptive implant (P=.010) removals compared to the 2022 pre-RAC cohort. Insertions of IUDs and contraceptive implants were unchanged when compared to the pre-RAC cohort. IUD removals (P=.004) and insertions (P=.034), and contraceptive implant removals (P=.028) were significantly increased for post-RAC compared to 2022 graduates, with no difference in contraceptive implant insertions (P=.211). CONCLUSIONS: The addition of the CVT and RAC clinic contributed to an increase in LARC removals in both comparisons, and IUD insertions between 2022 and 2023. This clinic model offers an opportunity for other family medicine residency programs to improve access to contraceptive services and increase resident training in LARC management.

Keeping Things Positive: Affect as a Mediator between Physical Activity and Psychological Functioning.

Higher physical activity is generally associated with more favorable psychological functioning. However, the role of positive and negative affect in such associations is unclear. Accordingly, this cross-sectional study explored whether affect mediated the relationship of physical activity with psychological well-being (PWB) and psychological dysfunctioning (PD). Young Iranian adults (N = 200) completed self-rating questionnaires covering physical activity, positive and negative affect, and proxies of PWB and PD. Regression analyses indicated that higher physical activity levels and higher positive and lower negative affect predicted proxies of PWB. The same (albeit in the opposite direction) applied to proxies of PD. Structural equation modeling indicated that positive and negative affect mediated the relationship between physical activity and PWB/PD. Accordingly, change in affect might be an important mechanism behind the association of physical activity and PWB/PD. Future research should further explore this across target populations and cultural contexts. Longitudinal and/or experimental studies are needed to disentangle causality.

Differential Effects of a Behavioral Treatment Probe on Social Gaze Behavior in Fragile X Syndrome and Non-Syndromic Autism Spectrum Disorder.

The purpose of this study was to examine potential differences in social learning between individuals with fragile X syndrome (FXS), the leading known inherited cause of intellectual disability, and individuals with non-syndromic autism spectrum disorder (ASD). Thirty school-aged males with FXS and 26 age and symptom-matched males with non-syndromic ASD, were administered a behavioral treatment probe designed to improve levels of social gaze during interactions with others. The treatment probe was administered by a trained behavior therapist over two days in our laboratory and included reinforcement of social gaze in two alternating training conditions - looking while listening and looking while speaking. Prior to each session, children in each group were taught progressive muscle relaxation and breathing techniques to counteract potential increased hyperarousal. Measures included the rate of learning in each group during treatment, in addition to levels of social gaze and heart rate obtained during administration of a standardized social conversation task administered prior to and following the treatment probe. Results showed that learning rates obtained during administration of the treatment probe were significantly less steep and less variable for males with FXS compared to males with non-syndromic ASD. Significant improvements in social gaze were also observed for males with FXS during the social conversation task. There was no effect of the treatment probe on heart rate in either group. These data reveal important differences in social learning between the two groups and have implications for early interventions in the two conditions.

A Scoping Review of Behavioral Interventions for Promoting Social Gaze in Individuals with Autism Spectrum Disorder and Other Developmental Disabilities.

Background: Individuals diagnosed with autism spectrum disorder (ASD) commonly experience difficulties maintaining social gaze with others during interactions. Although behavioral interventions targeted to promote social gaze in ASD are evident in the literature, to our knowledge, no review of the literature has been conducted to summarize and evaluate the evidence for these interventions. Methods: We reviewed and summarized behavioral intervention studies designed to promote social gaze in individuals diagnosed with ASD and other developmental disabilities published in English between 1977 and January 2022 using PsychINFO and PubMed databases. Results: 41 studies met the inclusion criteria describing interventions conducted on 608 individuals. A variety of intervention strategies were employed to promote social gaze in these individuals including discrete trial instruction, prompting, modeling, and imitation. Most studies employed single-case research designs and reported successful outcomes, but limited data were available concerning the generalization, maintenance and social validity of these interventions. An increasing number of studies utilized technology-based procedures including computer application gameplay, gaze-contingent eye tracking devices and humanoid robots. Conclusions: The present review indicates that behavioral interventions can be successfully employed to promote social gaze in individuals with ASD and other developmental disabilities. However, future research is needed to establish the generalization, maintenance and social validity of these interventions. There are also important ethical issues to be addressed given the increasing divide between treatment advocates and proponents of the neurodiversity movement.

ROAR ED-SANE: A Retrospective Observational Assessment Review of an Emergency Department Sexual Assault Nurse Examiner Program's Adherence to Centers for Disease Control and Prevention Guidelines for Sexually Transmitted Infections.

BACKGROUND: Sexual assault survivors are at increased risk for sexually transmitted infections. Sexual Assault Nurse Examiner programs guide sexually transmitted infection treatment, monitoring, and follow-up scheduling according to guidelines by the Centers for Disease Control and Prevention (CDC). Reported low rates of provider adherence to CDC treatment guidelines and patient adherence to follow-up necessitate a review of medication prescribing and follow-up scheduling practices, especially at smaller community hospitals in the United States. METHODS: A retrospective medical record review was conducted to assess adherence rates to CDC guidelines for prescribing practices, scheduling, and follow-up of sexual assault survivors. We included pediatric and adult patients presenting to the emergency department (ED) and participating in the ED Sexual Assault Nurse Examiner program at a rural, community-based teaching hospital in La Crosse, WI, from January 2018 to December 2021. Descriptive statistics were used to evaluate results. RESULTS: Analysis included 103 patients. Prescribing adherence to CDC guidelines was >80% for all except human immunodeficiency virus (53.4%), trichomoniasis (68.1%), and hepatitis B (69%). Of the 38 patients who had a follow-up scheduled during their ED encounter, 78.9% attended their scheduled follow-up and 94.7% of those appointments were scheduled within the CDC-recommended time frame, leading to an overall adherence of 40%. CONCLUSIONS: Adherence rates were high for most prescribing practices, and attendance of scheduled follow-up was higher than expected. Opportunities to improved adherence to CDC guidelines were identified in prescribing for 3 disease states (human immunodeficiency virus, trichomoniasis, and hepatitis B) and in scheduling of follow-up.

Brief intensive social gaze training reorganizes functional brain connectivity in boys with fragile X syndrome.

Boys with fragile X syndrome (FXS), the leading known genetic cause of autism spectrum disorder (ASD), demonstrate significant impairments in social gaze and associated weaknesses in communication, social interaction, and other areas of adaptive functioning. Little is known, however, concerning the impact of behavioral treatments for these behaviors on functional brain connectivity in this population. As part of a larger study, boys with FXS (mean age 13.23 ± 2.31 years) and comparison boys with ASD (mean age 12.15 ± 2.76 years) received resting-state functional magnetic resonance imaging scans prior to and following social gaze training administered by a trained behavior therapist in our laboratory. Network-agnostic connectome-based predictive modeling of pretreatment resting-state functional connectivity data revealed a set of positive (FXS > ASD) and negative (FXS < ASD) edges that differentiated the groups significantly and consistently across all folds of cross-validation. Following administration of the brief training, the FXS and ASD groups demonstrated reorganization of connectivity differences. The divergence in the spatial pattern of reorganization response, based on functional connectivity differences pretreatment, suggests a unique pattern of response to treatment in the FXS and ASD groups. These results provide further support for implementing targeted behavioral treatments to ameliorate syndrome-specific behavioral features in FXS.

Transfusion-Transmitted Cache Valley Virus Infection in a Kidney Transplant Recipient With Meningoencephalitis.

BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the fall of 2020, a patient developed encephalitis 6 weeks following kidney transplantation and receipt of multiple blood transfusions. METHODS: After ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens using reverse-transcription polymerase chain reaction (RT-PCR), the plaque reduction neutralization test, cell culture, and whole-genome sequencing. RESULTS: CVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole-genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation. CONCLUSIONS: Our investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients.

Examining Phenotypic Differences in Gaze Avoidance Between Autism Spectrum Disorder and Fragile X Syndrome.

We examined potential phenotypic differences in eye gaze avoidance exhibited by boys with autism spectrum disorder (ASD) and boys with fragile X syndrome (FXS). In Study 1, the Eye Contact Avoidance Scale (ECAS) was administered to caregivers of boys aged 7-18 years with FXS (n = 148), ASD (n = 168), and mixed developmental disabilities (MDD; n = 128). In Study 2, subsets of boys with FXS (n = 31) and boys with ASD (n = 25) received a brief behavioral treatment probe to improve eye contact. Results showed that boys with FXS obtained significantly higher scores on the ECAS compared to boys with ASD and MDD. Exposure to the brief behavioral treatment probe resulted in significant decreases in scores for boys with FXS, but not for boys with ASD.

Long-term follow-up of telehealth-enabled behavioral treatment for challenging behaviors in boys with fragile X syndrome.

BACKGROUND: A significant proportion of boys with fragile X syndrome (FXS), the most common known genetic cause of intellectual disability, exhibit challenging behaviors such as aggression and self-injury that can cause significant distress to families. Recent evidence suggests that coaching caregivers to implement functional communication training (FCT) with their child via telehealth can help to ameliorate these behaviors in FXS. In the present study, we followed families who had participated in our previous randomized controlled trial of FCT to evaluate the longer-term effects of FCT on challenging behaviors in this population. METHODS: In study 1, follow-up emails, phone calls, text messages, and letters were sent to caregivers of 48 boys with FXS who had completed our previous study conducted between 2016 and 2019. The main outcome measures administered at follow-up were the Aberrant Behavior Checklist-Community (ABC-C) and the Parenting Stress Index, 4th Edition (PSI-4). In study 2, families who had received FCT treatment but whose child exhibited challenging behaviors daily at follow-up received a 1-h parent training booster session to determine whether the intervention effect could be recovered. RESULTS: Sixteen (66.7%) of 24 families who had received FCT treatment and 18 (75.0%) of 24 families who had received treatment as usual were traced and consented between March and August 2021. The mean follow-up time was 3.1 years (range, 1.4 to 4.2 years). Longitudinal mixed effects analyses indicated that boys who had received FCT were more likely to show improvements on the irritability and lethargy/social withdrawal subscales of the ABC-C over the follow-up interval compared to boys who had continued with treatment as usual. Four of the six boys who had received the booster parent training session via telehealth were reported to exhibit fewer forms of challenging behavior at a 4-week follow-up. CONCLUSIONS: Empowering parents to implement behavior analytic treatments with their child in their own home can have durable effects on maintaining low levels of challenging behaviors in boys with FXS. These data further support the need to implement parent-mediated interventions for challenging behaviors in this population at an early age. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03510156 . Registered 27 April 2018.

Curbing the Delta Surge: Clinical Outcomes After Treatment With Bamlanivimab-Etesevimab, Casirivimab-Imdevimab, or Sotrovimab for Mild to Moderate Coronavirus Disease 2019.

OBJECTIVE: To describe and compare the clinical outcomes of bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab treatment of mild to moderate coronavirus disease 2019 (COVID-19) during the severe acute respiratory coronavirus 2 (SARS-CoV-2) B.1.617.2 Delta surge. METHODS: This is a retrospective study of high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 between August 1, 2021, and December 1, 2021. Rates of severe disease, hospitalization, intensive care unit admission, and death were assessed. RESULTS: Among 10,775 high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for mild to moderate COVID-19 during the Delta surge, 287 patients (2.7%) developed severe disease that led to hospitalization, oxygen supplementation, or death within 30 days after treatment. The rates of severe disease were low among patients treated with bamlanivimab-etesevimab (1.2%), casirivimab-imdevimab (2.9%), and sotrovimab (1.6%; P<.01). The higher rate of severe outcomes among patients treated with casirivimab-imdevimab may be related to a significantly lower COVID-19 vaccination rate in that cohort. Intensive care unit admission was comparable among patients treated bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab (1.0%, 1.0%, and 0.4%, respectively). CONCLUSION: This real-world study of a large cohort of high-risk patients shows low rates of severe disease, hospitalization, intensive care unit admission, and mortality after treatment with bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 during the SARS-CoV-2 Delta surge.

Comparable Outcomes for Bebtelovimab and Ritonavir-Boosted Nirmatrelvir Treatment in High-Risk Patients With Coronavirus Disease-2019 During Severe Acute Respiratory Syndrome Coronavirus 2 BA.2 Omicron Epoch.

The effectiveness of bebtelovimab in real-world settings has not been assessed. In this retrospective cohort study of 3607 high-risk patients, bebtelovimab was used more commonly than nirmatrelvir-ritonavir for treatment of coronavirus disease 2019 (COVID-19) among older patients, immunosuppressed patients, and those with multiple comorbid conditions. Despite its use in patients with multiple comorbid conditions, the rate of progression to severe disease after bebtelovimab (1.4% [95% confidence interval, 1.2%-1.7%]) was not significantly different from that for nirmatrelvir-ritonavir treatment (1.2% [.8%-1.5%]). Our findings support the emergency use authorization of bebtelovimab for treatment of COVID-19 during the Omicron epoch dominated by BA.2 and subvariants.

Rates of Severe Outcomes After Bamlanivimab-Etesevimab and Casirivimab-Imdevimab Treatment of High-Risk Patients With Mild to Moderate Coronavirus Disease 2019.

Bamlanivimab-etesevimab and casirivimab-imdevimab are authorized by the US Food and Drug Administration for emergency treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk persons. There has been no study comparing their clinical efficacy. In this retrospective study of 681 patients with mild to moderate COVID-19 during a period dominated by severe acute respiratory syndrome coronavirus 2 wild-type and alpha variants, 25 patients (3.7%) had progression to a severe outcome requiring hospitalization and oxygen supplementation within 30 days after monoclonal antibody infusion. Severe outcome was significantly higher among the 181 patients who were treated with casirivimab-imdevimab when compared with the 500 patients who received bamlanivimab-etesevimab (21 [6.6%] vs 13 [2.6%]; P=.01). Patients treated with casirivimab-imdevimab had higher odds of severe outcomes compared with those who received bamlanivimab-etesevimab (odds ratio, 2.67; 95% CI, 1.17 to 6.06). The demographic and clinical characteristics, and the time to monoclonal antibody infusion, of the 2 treatment cohorts were not significantly different. The reason behind this significant difference in the clinical outcomes is unclear, but our observations emphasize potential efficacy differences among antispike monoclonal antibodies against COVID-19. Further clinical studies using larger cohorts of patients are needed to confirm or refute these observations.

Implementing Automated Nonparametric Statistical Analysis on Functional Analysis Data: A Guide for Practitioners and Researchers.

Functional analysis (FA) is an integral component of behavioral assessment and treatment given that clinicians design behavioral treatments based on FA results. Unfortunately, the interrater reliability of FA data interpretation by visual analysis can be inconsistent, potentially leading to ineffective treatment implementation. Hall et al. (2020) recently developed automated nonparametric statistical analysis (ANSA) to facilitate the interpretation of FA data and Kranak et al. (2021) subsequently extended and validated ANSA by applying it to unpublished clinical data. The results of both Hall et al. and Kranak et al. support ANSA as an emerging statistical supplement for interpreting FA data. In the present article, we show how ANSA can be applied to interpret FA data collected in clinical settings in multielement and pairwise designs. We provide a detailed overview of the calculations involved, how to use ANSA in practice, and recommendations for its implementation. A free web-based application is available at https://ansa.shinyapps.io/ansa/. Supplementary Information: The online version contains supplementary material available at 10.1007/s40614-021-00290-2.

Effects of X Chromosome Monosomy and Genomic Imprinting on Observational Markers of Social Anxiety in Prepubertal Girls with Turner Syndrome.

Previous studies have suggested that girls with Turner syndrome (TS) exhibit symptoms of social anxiety during interactions with others. However, few studies have quantified these behaviors during naturalistic face-to-face social encounters. In this study, we coded observational markers of social anxiety in prepubertal girls with TS and age-matched controls during a 10-min social encounter with an unfamiliar examiner. Results showed that girls with TS exhibited significantly higher levels of gaze avoidance compared to controls. Impairments in social gaze were particularly increased in girls with a maternally retained X chromosome (Xm), suggesting a genomic imprinting effect. These data indicate that social gaze avoidance may be a critical behavioral marker for identifying early social dysfunction in young girls with TS.

Identification of Risk Factors for Acute Kidney Injury from Intravenous Ketorolac in Geriatric Trauma Patients.

BACKGROUND: Ketorolac is an effective analgesic but the potential for acute kidney injury (AKI) is concerning, particularly in geriatric "G-60 trauma" patients. The objectives of this study are to report the incidence of AKI in patients who receive ketorolac, identify risk factors for AKI, and develop a risk factor-guided algorithm for safe utilization. METHODS: This retrospective cohort study included trauma patients age 60 years and older who received intravenous ketorolac. The primary endpoint was the incidence of AKI. RESULTS: Among 316 patients evaluated, the incidence of AKI was 2.5%. Patients with AKI received more nephrotoxins, had more comorbidities, and higher use of loop diuretics or vasopressors. Loop diuretic therapy and number of comorbidities were independent predictors of AKI. CONCLUSIONS: Risk for AKI with ketorolac was low, being more prevalent with comorbidities or receipt of loop diuretics.

Conducting In-Home Functional Analyses of Aggression and Self-Injury Exhibited by Boys with Fragile X Syndrome.

OBJECTIVE: Boys with fragile X syndrome (FXS) are at increased risk for exhibiting aggression and self-injury that can be extremely disruptive to families. Few studies, however, have examined the extent to which social-environmental factors can influence these behaviors, particularly in home settings. METHODS: Caregivers of 32 boys with FXS, aged 3 to 10 years, were coached by a board-certified behavior analyst to implement a functional analysis (FA) with their child in their home over 2 days. The functions identified in the FAs were validated by behavioral interventions conducted through telehealth over 12 weeks. RESULTS: Social functions for aggression and self-injury were identified in 29 (90.6%) cases, with the most common functions identified being escape from demands/transitions and/or tangible reinforcement. Subsequent function-based behavioral interventions (i.e., functional communication training) implemented for 22 cases by telehealth resulted in decreased rates of aggression and self-injury by 74% to 100%. CONCLUSION: These data underscore the significant impact that social-environmental factors can have on the development and maintenance of aggression and self-injury in FXS. Conducting early home-based behavioral interventions designed to increase functional communication skills may therefore be an effective solution for the treatment of aggression and self-injury in FXS in the long term.

N-acetylcysteine (NAC) for methamphetamine dependence: A randomised controlled trial.

BACKGROUND: Methamphetamine dependence is a significant global health concern for which there are no approved medications. The cysteine prodrug, N-acetylcysteine (NAC), has been found to ameliorate glutamate dysregulation in addiction, and to reduce craving for methamphetamine and other drugs. We evaluated the efficacy and safety of NAC as a pharmacotherapy for methamphetamine dependence. METHODS: A parallel double-blind randomised placebo-controlled trial of people dependent on methamphetamine recruited from Geelong, Melbourne and Wollongong, Australia, between July 2018 and December 2019. Participants were randomised to receive either 12 weeks of oral NAC (2400 mg/day) or matched placebo, delivered as a take-home medication. The primary outcome was methamphetamine use, measured in two ways: (a) change in days of use in the past 4 weeks from baseline to weeks 4, 8 and 12, assessed using the Timeline Followback; and (b) methamphetamine-positive oral fluid samples taken weekly. Analyses were intention-to-treat and based on imputed data. Secondary outcomes were craving, severity of dependence, withdrawal severity and psychiatric symptoms (depression, suicidality, hostility and psychotic symptoms). Significance levels were p < 0.025 for primary outcomes and p < 0.01 for secondary outcomes. Adverse events were compared between groups by system organ class. The study was prospectively registered, ACTRN12618000366257. RESULTS: Participants (N = 153; 59% male, mean [SD] age 38 [8]) were randomised to placebo (n = 77) or NAC (n = 76). Both groups had a median (IQR) of 24 (15-28) days of methamphetamine use in the 4 weeks prior to baseline. Both groups significantly reduced methamphetamine use (mean [SE] reduction of 7.3 [1.2]) days for placebo, 6.8 [1.2] for NAC) but NAC did not reduce days of methamphetamine use more than placebo (group difference of 0.5 days, 97.5% CI -3.4-4.3). There was no significant effect of NAC on methamphetamine-positive oral fluid samples (placebo 79%, NAC 76%; mean difference -2.6, 97.5% CI -12.6-7.4). NAC did not significantly reduce craving, severity of dependence, withdrawal, suicidality, depression, hostility or psychotic symptoms relative to placebo. Adverse events did not differ significantly between placebo and NAC groups. INTERPRETATION: These findings suggest that take-home oral NAC has no significant effect on methamphetamine use or most clinically related outcomes amongst people who are dependent on the drug.

Dislocated College Students and the Pandemic: Back Home Under Extraordinary Circumstances.

OBJECTIVE: This research examines college students' experiences of dislocation during the COVID-19 pandemic. BACKGROUND: Due to governmental stay-at-home orders during the pandemic, families with "dislocated" (compelled to return home) college students would likely encounter unique stressors while also being limited in their normal ways of coping. METHODS: Using an online survey, the current study sought to discover how diverse individual characteristics and family living situations of 323 dislocated students associated with varying homelife experiences (e.g., intrusive parenting, students making an extra effort to spend time with family), and how such experiences associated with relationship changes during the quarantine. RESULTS: Analyses detected some differences in the students' homelife experiences based on background and living situations, especially related to being a first-year student, having been excited about returning home, and feeling accepted by parents about being home. Negative family relationship quality during the quarantine was most predicted by negative attitudes from students and parents about students being home, the student feeling less adultlike (based on treatment and own identity conception), and having low autonomy. CONCLUSION: Returning home for quarantine was challenging for most students, and circumstances and attitudes appeared to contribute to how such challenges associated with family relationship changes. IMPLICATIONS: Implications for practitioners and universities are discussed in regard to preparing college students and their families for similar conditions.

Optimizing outcomes using vancomycin therapeutic drug monitoring in patients with MRSA bacteremia: trough concentrations or area under the curve?

BACKGROUND: Vancomycin therapeutic drug monitoring is routinely performed but the specific measure used in practice is variable. OBJECTIVE: To evaluate the relationship between the first measured vancomycin trough, area-under-the-curve (AUC), and failure in patients with MRSA bacteremia. METHODS: This retrospective, cohort study included adult non-neutropenic patients with MRSA bacteremia who received vancomycin. The primary outcome was treatment failure. Initial trough and AUC values were compared between the failure and success groups. Classification and regression tree analysis was used to identify thresholds associated with failure. Multivariate analysis was performed to control for identified confounders. RESULTS: There were 89 patients. Failure occurred in 23 (26%). Trough and AUC values associated with failure were < 10.6 mg/L (39% vs. 13%; P = 0.006) and AUC < 410mg*h/L (40% vs. 17%; P = 0.014). Both remained significant after controlling covariates (trough < 10.6 mg/L, OR [95% CI] = 4.91 [1.6-15]; AUC<410mg*h/L, OR [95% CI] = 3.13 [1.14-8.62]). Only AUC was predictive of nephrotoxicity. CONCLUSION: Failure was more common with troughs < 10.6 mg/L or AUC < 410 mg*h/L. Supratherapeutic AUCs, but not trough, were associated with nephrotoxicity.

Sublesional Bevacizumab Injection for Recurrent Respiratory Papillomatosis: Evaluation of Utility in a Typical Clinical Practice.

OBJECTIVES: The goal of this study was to evaluate the benefit of sublesional bevacizumab injection for recurrent respiratory papillomatosis (RRP) as used in a typical clinical practice. METHODS: A retrospective review of patients with RRP treated between 2011 and 2016 was undertaken. All patients were treated with in-office potassium titanyl phosphate (KTP) laser photoablation. Sublesional bevacizumab injection was used based on joint patient-physician decision making. Papilloma burden was objectively measured on prior recordings by 2 blinded reviewers and described as vocal fold segments affected (VFSA) by papilloma. Each patient served as their own control by comparing times when bevacizumab was or was not used. Mixed model for longitudinal data was used to determine if the previous use of bevacizumab decreased the disease burden. RESULTS: A total of 19 patients met inclusion criteria and all prior laryngoscopic exams were reviewed for VFSA as described above. The mean (SD) number of VFSA when bevacizumab was not used at the prior procedure was 15 (14) as compared to 8 (11) when bevacizumab was used. When adjusted for age, time from initial presentation and baseline disease burden, mixed model showed a decrease of 11 VFSA (95% CI 6.5, 15.5, P < .0001) when bevacizumab was used as compared to when bevacizumab was not used at the prior procedure. In mixed model analysis, there was not a significant association between bevacizumab dose used and VFSA at the subsequent visit (P = .8). CONCLUSION: Using sublesional bevacizumab intermittently based on clinical findings appears to be effective in improving disease control. Papilloma burden is significantly decreased at the subsequent clinical follow-up following injection of sublesional bevacizumab. The beneficial effect of sublesional bevacizumab may be not be dose-dependent.