Frequency Of Discontinuation Research Articles

Les orthèses d’avancées mandibulaires chez les patients souffrant d’un SAHOS sévère. Éfficacité à court et long terme, facteurs prédictifs d’efficacité

Mandibular advancement devices, more simply known as Oral Appliances (OAs), represent one of the current treatments for Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS). The primary objective of the study was to measure their efficacy in the severe OSAHS population. The secondary objectives were to determine predictive factors for the OA efficacy and to determine the tolerance and frequency of treatment discontinuation. OA efficacy outcomes based on Apnea-Hypopnea Index (AHI) reduction, complications, and discontinuation rates were collected from 271 prospectively followed severe OSAHS patients treated with OAs. OA treatment reduced the AHI by a mean 21.5 respiratory events/h, P<10-5. The complete response rate was 19.3%. With their OAs, 70.7% of patients presented AHI reduction>50% and 58.5% of patients exhibited AHI less than 15/h. The effectiveness of OA on AHI did not vary significantly over time (P=0.0936). OA was discontinued by 9.6% of patients, mainly due to its ineffectiveness, and more rarely because of intolerance. Mandibular advancement orthosis is an effective and well-tolerated treatment for severe OSAHS. In 70.7% of the cases studied, the oral appliance reduced AHI by at least 50%, and it should be more systematically proposed in the event of failure or refusal of CPAP treatment.

Postoperative Adjuvant Chemoradiotherapy Versus Chemotherapy Alone for Stage III Endometrial Cancer: A Multicenter Retrospective Study

IntroductionWe aimed to evaluate the efficacy and toxicity of the combination of 6 cycles of chemotherapy and radiation therapy compared with chemotherapy alone as postoperative adjuvant therapy for patients with stage III endometrial cancer.MethodsThis retrospective cohort study included patients with stage III endometrial cancer who received postoperative chemoradiotherapy or chemotherapy alone at 6 hospitals between January 2009 and December 2019. The progression-free survival (PFS) and overall survival (OS) for each treatment group were analyzed using the Kaplan–Meier method. We also assessed differences in toxicity profiles between the treatment groups.ResultsA total of 133 patients met the inclusion criteria. Of these, 80 patients (60.2%) received adjuvant chemoradiotherapy and 53 (39.8%) received chemotherapy alone. The PFS and OS did not differ significantly between the groups. For patients with stage IIIC endometrioid subtype, the chemoradiotherapy group had significantly longer PFS rate than did the chemotherapy alone group (log-rank test, P = .019), although there was no significant difference in the OS (log-rank test, P = .100). CRT was identified as a favorable prognostic factor for PFS in multivariate analysis (adjusted HR, .37; 95% CI, .16-.87; P = .022). Patients treated with chemoradiotherapy more frequently suffered from grade 4 neutropenia (73.8% vs 52.8%; P = .018) and grade 3 or worse thrombocytopenia (36.3% vs 9.4%; P = .001) compared with the chemotherapy alone group. There were no differences between the 2 treatment groups in the frequency of toxicity-related treatment discontinuation or dose reduction.ConclusionWe confirmed that chemoradiotherapy yields longer progression-free survival than does chemotherapy alone for patients with stage IIIC endometrioid endometrial cancer, with an acceptable toxicity profile.

Rates of discontinuation and non-publication of trials for the pharmacologic treatment of alcohol use disorder

Objective: With approximately 15 million individuals in the United States meeting criteria for Alcohol Use Disorder (AUD), advancing effective medication-assisted treatment options is crucial. This advancement stems from the publication of clinical trial (CT) results. The primary objective of this study was to assess the rates of discontinuation and non-publication of results in CTs focused on the pharmacologic treatment of AUD and to assess associated factors. Design: A cross-sectional study was completed after acquiring trials focused on AUD within the ClinicalTrials.gov database. Inclusion criteria for CTs were the use of a pharmaceutical intervention with an outcome measure of alcohol intake or craving, conducted between October 2008 through September 2018. The primary outcome measures were the frequency of trial discontinuation and non-publication. Discontinuation was assessed as the listed status on ClinicalTrials.gov. Publications were identified through verification of listings on ClinicalTrials.gov, or via searches of PubMed, Embase, and Google Scholar. If publications were not found, correspondence to trial contacts were sent. Data analysis occurred on December 5th, 2020. Results: Of 235 trials returned from the search, 87 met inclusion criteria. Our study found that 12.6% (11) of CTs involving pharmaceutical treatments for AUD were prematurely terminated, and 39.1% (34) had no published results. Recruitment and lower cutoff of targeted age groups were significantly associated with discontinuation and non-publication, respectively. Conclusions: Scientific evidence advances faster when all results are known—furthering the progress of positive studies, while avoiding duplicative efforts to test the same hypotheses with the same methods, thereby reducing scientific waste. Given the number of unpublished AUD trials, potentially useful information regarding treatment for individuals with AUD may be inaccessible to clinicians while also adding to the abundance of research waste. Key points Question: What are the rates of discontinuation or non-publication of clinical trials for pharmacological treatments for AUD and associated factors? Findings: Among 87 trials, 11 (12.6%) were prematurely terminated and 34 (39.1%) did not reach publication, with trials that included participants 21 years and older more likely to reach publication than those with younger participants. Meaning: Low publication rates of CTs for pharmacological treatments of AUD may (1) stunt the advancement of AUD research, (2) decrease the value in funding AUD research from government entities, and (3) needlessly expose participants to potentially harmful interventions.

Reasons and Associated Factors of Early Discontinuation of Implanon: A Follow-up Study from Lahore, Pakistan

Background: Family planning is needed at this time when the world population is rapidly increasing. Etonogestrel sub-dermal implant is a highly effective long-acting and reversible sub-dermal contraceptive implant. Despite its success and enhancement in usage, it is stopped by a proportion of users prior to its expiration date. Objective: To ascertain the frequency of discontinuation of Implanon during one year period and uncover its reasons and associated factors among women consulting obstetrics and gynecological clinics for contraception methods and opting for Implanon among the available options. Methodology: This prospective observational study was conducted in Services Hospital, Lahore. All of the women who underwent Implanon insertion from July to December 2020 were enrolled in the study. The outcome variable is early discontinuation of the inserted implant within one year of its insertion. Results: 350 women receiving sub-dermal Implanon for contraception purposes were included in this study. Their median age and BMI were 28(IQR= 25.8-31) years and 24.3 (IQR=23.6-25) Kg/m2 respectively. The early discontinuation rate was 49.1%. Reasons for removal were menstrual problems (100%), headache (19%), weight gain (12%), pain in the arm (5%), desire to conceive (1.7%) and spouse death (0.3%). Younger age, increasing body mass index, rural residence and shorter marriage duration were found to be significantly associated with early removal. Conclusion: This study found a high early discontinuation rate. Premature removal was most commonly caused by menstrual issues. Early removal was independently predicted by an early age, length of the marriage, rising BMI, and residence in a rural location. An awareness campaign should be created specifically for rural areas to address their concerns and reduce the early discontinuation rate. Further research should be conducted to understand the menstrual problems in women undergoing implanon insertion.

Tolerability of Lithium: A Naturalistic Discontinuation Study in Older Adults (≥60 Years)

Lithium is one of the most effective treatment options in both bipolar disorder and treatment-resistant depression. The use of lithium in older adults declined during the last decades, probably resulting in undertreatment of older adults. To investigate how well lithium is tolerated in old age, we aimed to determine the frequency, reasons and possible predictors of discontinuation due to adverse effects in a cohort of hospitalized adults aged 60 years or older who had started with lithium. We performed a retrospective cohort study based on chart reviews. Participants were in treatment at Parnassia Group at The Hague, the Netherlands. After inclusion (between January 2010 and December 2016), participants were followed until April 2017, when we performed data extraction and analysis. In our sample of 135 patients (median age 69 years, median follow-up duration 18 months), 49 (36.3%) participants discontinued lithium. Only a minority (11 (8.1%)) of the participants discontinued solely due to adverse effects. The majority discontinued lithium due to psychiatric (18,5%) reasons, (most commonly mentioned within this subgroup: lack of effectiveness and non-compliance) or a combination of reasons (7.4%). None of the factors we studied (age, gender, Charlson Comorbidity Index (CCI), polypharmacy, renal function and neurological history) were significantly associated with discontinuation due to adverse effects. The frequency of lithium discontinuation in our cohort was in range with frequencies reported in younger patients. Older age itself should not be a reason to withhold lithium treatment.

Leveraging the Client-Provider Interaction to Address Contraceptive Discontinuation: A Scoping Review of the Evidence That Links Them.

Despite considerable investment and effort, unmet need for contraception remains an obstacle to improved family planning outcomes. One influencing factor is the frequency of contraceptive discontinuation among users who desire to prevent pregnancy, often due to method-related concerns and side effects. Contraceptive users have the right to be supported during counseling to voluntarily choose methods that align with their individual needs and preferences. Contraceptive counseling, as a key component of quality of care, is particularly important for providers to reduce unmet need among their clients. This scoping review examined the state of the evidence on contraceptive counseling and its impact on discontinuation. The review first examines the association between quality of care and contraceptive discontinuation, then looks to what the current body of evidence suggests are women's contraceptive counseling priorities, and lastly, explores whether specific counseling tools and approaches have been evaluated with discontinuation as an outcome. The results identified general principles and priorities for good counseling including person-centeredness, client-tailored information exchange, clear and concise information on side effects and bleeding changes, reducing providers' implicit and explicit biases, and trust and respect between the client and provider. The review of the literature also found that evidence to support the use of specific counseling tools and approaches to reduce contraceptive discontinuation is insufficient; research should be designed to determine which specific elements of the client-provider interaction can be improved to significantly impact contraceptive discontinuation. This evidence could inform how the global community of practice might improve and leverage specific counseling approaches and tools to address the most common predictors of discontinuation.

Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease: A National Alliance of Sickle Cell Centers Study

Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease: A National Alliance of Sickle Cell Centers Study

Continuously Tunable and Energy-Enhanced Injection Pulse-Seeded Terahertz Parametric Generator Based on KTP Crystal

A continuously tunable, energy-enhanced injection, pulse-seeded THz parametric generator based on a KTP crystal (KTP ips-TPG) has been demonstrated in this paper. Theoretical analysis denotes that improving the initial Stokes intensity is favorable to achieve a continuously tunable, high-energy THz generation in a KTP crystal, which is clarified to originate from the enhancement of stimulated polariton scattering (SPS) process in the photon-like region of polariton and parametric amplification process in the phonon-like region of polariton. In the experiment, the THz continuously tunable range was from 2.93 to 6.21 THz, and the THz energies were 6.27, 2.62, 5.43, 4.59, and 5.88 μJ at the output peaks of 3.33, 3.83, 4.41, 4.85, and 5.69 THz, respectively. Compared with the traditional KTP THz parametric oscillator (KTP TPO) with discontinuous frequency tuning, the KTP ips-TPG has great improvement in terms of continuous frequency tuning range and THz output energy, where the enhancement ratios of THz output energy were 6.88× at 3.36 THz, 5.25× at 4.35 THz, 18.21× at 4.79 THz, and 1.82× at 5.69 THz. This injection pulse-seeded THz parametric source based on a KTP crystal is not only suitable to the practical applications in THz high frequency range, but also provides a technical solution for the KTP-family crystals to achieve a continuously tunable and high energy THz generation in a wide THz region.

A Game-Theoretical Learning Approach for Spectrum Trading in Cognitive Satellite-Terrestrial Networks

This letter investigates the bandwidth allocation problem for discontinuous frequency bands in cognitive satellite-terrestrial networks (CSTNs). Different from existing studies, we take the realistic assumption that the available idle spectrum bands are disconnected. Most of the existing works focused on the continuous bandwidth allocation problem and proposed corresponding algorithms optimizing continuous variables, which cannot directly solve the bandwidth allocation problem for discontinuous frequency bands. Besides, we also take the individual bandwidth requirement, the priority of terrestrial cognitive users, and the limitation on the total available bandwidth into consideration. The bandwidth allocation for discontinuous frequency bands is formulated as a bandwidth auction game, which is proven to have at least one pure strategy Nash Equalization (NE) solution. Furthermore, an improved best response learning algorithm based on exploration and exploitation (BREE) is proposed to achieve satisfying performance. Finally, simulations are conducted to verify the convergence and superiority of the proposed BREE algorithm.

Treatment Persistence of Renin-Angiotensin-Aldosterone-System Inhibitors Over Time in Heart Failure with Reduced Ejection Fraction

Clinical practice guidelines support sustained use of renin-angiotensin-aldosterone-system (RAAS) inhibitors over time in heart failure with reduced ejection fraction, yet few data are available regarding the frequency, timing or predictors of early treatment discontinuation in clinical practice. Among prevalent or new users of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs) in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, we estimated the frequency and independent predictors of treatment discontinuation during follow-up. Among sites with > 5 users of a given RAAS inhibitor, we evaluated practice variation in the proportion of patients with treatment discontinuation. Over median follow-up of 18 months, frequency of drug discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.7% (444 of 3509 users), 10.4% (140 of 1352 users), and 20.4% (435 of 2129 users), respectively. An additional, 149 (11.0%) of ARNI users were switched to ACEis/ARBs, and 447 (12.7%) of ACEi/ARB users were switched to ARNIs during follow-up. Across sites, the median proportion of discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.5% (25th-75th percentiles 6.9%-18.9%), 18.8% (25th-75th percentiles 12.5%-28.6%), and 19.6% (25th-75th percentiles 10.7%-27.0%), respectively. Chronic kidney disease was the only independent predictor of increased risk of discontinuation of each of the RAAS inhibitor classes (P < 0.02 for all). Higher Kansas City Cardiomyopathy Questionnaire overall summary scores independently predicted lower risk of discontinuation of ACEis/ARBs and ARNIs (both P < 0.001) but not of MRAs. Investigator clinical experience was predictive of lower risks of discontinuation of ACEis/ARBs and MRAs (P < 0.02) but not of ARNIs. All other independent predictors of discontinuation were unique to individual therapeutic classes. One in 10 patients discontinue ACEis/ARBs or ARNIs, and 1 in 5 discontinue MRAs in routine clinical practice of heart failure with reduced ejection fraction. Unique patient-level and clinician/practice-level factors are associated with premature discontinuation of individual RAAS inhibitors, which may help to guide structured efforts to promote treatment persistence in clinical care.

Efficacy and Safety of Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Mantle Cell Lymphoma in the Phase 2 ACE-LY-004 Study

Efficacy and Safety of Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Mantle Cell Lymphoma in the Phase 2 ACE-LY-004 Study

Characterizing opioid agonist treatment discontinuation trends in British Columbia, Canada, 2012–2018

BackgroundGiven the elevated risk of mortality immediately following opioid agonist treatment (OAT) discontinuation, determining the frequency and timing of OAT discontinuation can help guide the planning of services to facilitate uninterrupted OAT. We sought to describe weekly and monthly trends in OAT episode discontinuations in British Columbia to determine the potential resource needs for implementing support services. MethodsThis population-based retrospective study utilized a provincial-level linkage of health administrative databases to identify all people with opioid use disorder (PWOUD) who received OAT between 01/2012−08/2018. We defined OAT episodes as continuous medication dispensations without interruptions in prescribed doses lasting ≥5 days for methadone and ≥6 days for buprenorphine/naloxone. We derived the percentage of PWOUD discontinuing OAT every month and we considered weekly discontinuations between 09/2017−08/2018, accounting for weeks during which monthly income assistance payments from social service programs occurred. ResultsOur study included 37,207 PWOUD discontinuing 158,027 OAT episodes. Discontinuations were relatively stable month-to-month, increasing from 10.6 % to 14.9 % (2012–2018). The monthly percentage of discontinuations was 21.2 % for buprenorphine/naloxone and 10.0 % for methadone. Weekly discontinuations were greater in income disbursement weeks (816; IQR: 752, 901) compared to other weeks (655; IQR: 615, 683; p < 0.01). ConclusionsWe identified a high, and stable rate of monthly OAT discontinuations and a consistently higher rate of discontinuing treatment among PWOUD accessing buprenorphine/naloxone. There is an urgent need to develop the evidence base for interventions to support OAT engagement and to improve clinical management of OUD to address the opioid-related overdose crisis.

Treatment Strategy for Patients with HR-Positive HER2-Negative Metastatic Breast Cancer That Progressed on CDK4/6 Inhibitors

Background/Aims: The study aim was to evaluate if mTOR inhibitors can be considered as a treatment option for HR+ HER2− metastatic breast cancer (MBC) after progression on CDK4/6 inhibitors in clinical practice. Methods: We retrospectively collected the clinicopathological data of patients with HR+ HER2− MBC treated with CDK4/6 inhibitors and subsequent therapies at our institution between 2014 and 2020. The patients were divided into 3 groups according to the type of subsequent treatment: (A) exemestane plus everolimus, (B) endocrine monotherapy, and (C) chemotherapy. Overall survival (OS) was estimated by using the Kaplan-Meier method and compared by using the log-rank test. The efficacy and adverse events (AEs) of each subsequent treatment were assessed by using Fisher’s exact tests. Results: Eighty-six patients (34 in group A, 20 in group B, 32 in group C) were included. The most common endocrine therapy in group B was fulvestrant (40%). The major chemotherapy regimen in group C was eribulin (25%). The median OS times after stopping CDK4/6 inhibitors were 34.5 months (95% confidence interval, 17.2 to NA), 13.6 months (3.9 to NA), and 19.5 months (18.8 to NA) in group A, group B, and group C, respectively. The only significant difference in OS was observed between group A and group B (20.9 months; p = 0.003). There was no difference in the incidence of grade 3 AEs between groups A and C or in the frequency of treatment discontinuation because of AEs among the 3 groups. Conclusion: Our study shows that mTOR inhibitors might be an effective treatment option for patients with HR+ HER2− MBC previously treated with CDK4/6 inhibitors.

O10 Characteristics of patients who discontinued baricitinib treatment within 12 months and reasons for discontinuation: real-world data

Abstract Background/Aims Baricitinib is an oral targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) recommended by the National Institute for Health and Care Excellence (NICE) in the UK for severe rheumatoid arthritis (RA) either as mono- or combination therapy. We wanted to observe the frequency of discontinuation in a real-world setting, the characteristics of patients who stop taking baricitinib, and the reasons for discontinuation. Objective: To describe the characteristics of patients who discontinue baricitinib treatment and the reasons for discontinuation. Methods A real-world retrospective observational study of baricitinib use in RA patients at University Hospital Southampton using local advanced therapy database for data collection. We described the characteristics of patients discontinuing baricitinib therapy and divided patients into two groups. Group 1 (those who discontinued therapy within the first 12 months of use) and group 2 (who continued therapy beyond 12 months) Results From October 2017 to July 2020, a total of 83 patients started baricitinib and were recorded in the database, 55 (66.27%) remain on treatment to date. Among 28 (33.74%) patients who stopped baricitinib, 21 had stopped within 12 months. The reasons for discontinuation were lack of efficacy (64.28%) and AEs (28.57% - 1 tooth infection, 1 urinary tract infection, 1 discitis, 2 chest infection, 1 personality change, 1 deranged liver function and 1 lymphoma). In group 1, the mean (±SD) age was 49.00 (13.65) years, 66.67% were female and 85.71% were previously biologic inadequate responders (IR), 42.86% were receiving monotherapy, with 57.14% being on combination therapy with a csDMARD and 9.52% were using a glucocorticoid. In group 2, 82.26% were female, 61.52 (10.94) years of age and 83.87% were previously biologic IR, 41.94% were on monotherapy and 58.06% on combination therapy with a csDMARD. Patients who discontinued appeared more likely to be younger and male. However, there was no significant difference regarding mono- or combination therapy, disease duration or seropositivity (p-value &amp;gt; 0.05) (Table 1). Conclusion In a real-world setting, baricitinib appears efficacious and well-tolerated in the first year of use by two-thirds of patients. Characteristics such as older age and female gender were associated with continued use. Disclosure M. Lwin: None. C. Holroyd: Honoraria; Lily. Member of speakers’ bureau; Lily. C.J. Edwards: Honoraria; Abbvie, Biogen, BMS, Celgene, Fresenius, GSK, Janssen, Lilly, Mundipharma, Pfizer, Roche, Sanofi, UCB. Member of speakers’ bureau; Abbvie, Biogen, BMS, Celgene, Janssen, Lilly, Sanofi, Pfizer, Roche. Grants/research support; Abbvie, Biogen, Pfizer.

Tolerability of lithium: A naturalistic discontinuation study in older inpatients (≥60 years).

Lithium is one of the most effective treatment options in both bipolar disorder and treatment-resistant depression. The use of lithium in older patients declined during the last decades, probably resulting in undertreatment of older patients. To investigate how well lithium is tolerated in old age, we aimed to determine the frequency, reasons, and possible predictors of discontinuation due to adverse effects in a cohort of inpatients ≥60 years who had started with lithium. We performed a retrospective cohort study based on chart reviews. Participants were in treatment at Parnassia Group at The Hague, The Netherlands. After inclusion (between January 2010 and December 2016), participants were followed until April 2017, when we performed data extraction and analysis. In our sample of 135 patients (median age 69 years, median follow-up duration 18 months), 49 (36.3%) participants discontinued lithium. Only a minority (11 [8.1%]) of the participants discontinued solely due to adverse effects. The majority discontinued lithium due to psychiatric (18, 5%) reasons (most commonly mentioned within this subgroup: lack of effectiveness and noncompliance) or a combination of reasons (7.4%). None of the factors we studied (age, gender, Charlson Comorbidity Index, polypharmacy, renal function, and neurological history) were significantly associated with discontinuation due to adverse effects. The frequency of lithium discontinuation in our cohort was in range with frequencies reported in younger patients. Older age itself should not be a reason to withhold lithium treatment.

Real-world effectiveness and tolerability of carbamazepine and oxcarbazepine in 354 patients with trigeminal neuralgia.

It is widely agreed that carbamazepine and oxcarbazepine are highly effective in the long-term treatment of trigeminal neuralgia. However, the tolerability of these drugs across the different aetiologies of trigeminal neuralgia is still undetermined. In this retrospective, real-world study, we assessed the effectiveness and tolerability of carbamazepine and oxcarbazepine in a large cohort of patients with classical (254 patients), secondary (60 patients) and idiopathic (40 patients) trigeminal neuralgia. We analysed data using a propensity score analysis to account for selection bias; frequencies of side effects associated with carbamazepine and oxcarbazepine were calculated by adjusting data with the inverse probability of treatment weighting. The initial proportion of responders was 88.3% with carbamazepine, and 90.9% with oxcarbazepine. The number of refractory patients was significantly higher in idiopathic (15%) and secondary forms (27%) than in classical trigeminal neuralgia (6%; p<.05). In 53 patients treated with carbamazepine (29.6%) and in 22 treated with oxcarbazepine (12.6%), major side effects caused treatment interruption or dosage reduction to an unsatisfactory level. Side effects occurred more frequently in patients treated with carbamazepine (43.6%) than with oxcarbazepine (30.3%, p<.0001). The frequency of treatment discontinuation was higher in patients with secondary and idiopathic forms than in those with classical trigeminal neuralgia (p<.05). Our real-world study shows that carbamazepine and oxcarbazepine are effective in most patients with trigeminal neuralgia; nevertheless, side effects are still a major issue, particularly in patients with secondary and idiopathic trigeminal neuralgia. Although carbamazepine and oxcarbazepine are effective in most patients with trigeminal neuralgia, their side effects are still a major issue, thus necessitating the development of better-tolerated drugs.

Bed Utilization and Overcrowding in a High-Volume Tertiary Level Pediatric Emergency Department

To measure bed utilization rate and overcrowding in a high-volume tertiary level pediatric emergency department (ED) and correlate with outcome. All children beyond neonatal age attending the 22-bedded emergency were prospectively enrolled from February to December, 2019. Number of daily admissions, boarders, discharges, ward transfers, length of stay (LOS) and unfavorable outcomes (care discontinuation and deaths) were recorded. Daily bed occupancy rate (BOR) was calculated and correlated with unfavorable outcome. A total of 17,463 children visited the ED during the study period. The median (IQR) daily attendance and admission rate was 58 (51,65) and 22 (17,26) patients, respectively. The median (IQR) number of boarders and BOR was 48 (40-58) and 218% (181-263%), respectively. The median (IQR) LOS was 42.7 (23-71.4) hours. Unfavorable outcome correlated positively with number of boarders and BOR (P<0.001). Overcrowding of the ED was associated with increased frequency of care discontinuation and mortality. This data calls for systemic changes to tackle overcrowding.

The effects of concurrent oral paliperidone or risperidone use with paliperidone long-acting injection.

IntroductionDosing recommendations for paliperidone long-acting injectable antipsychotic (LAIA) do not include oral antipsychotic (OAP) overlap; however, OAPs are often given concurrently despite limited evidence describing both the risks and benefits of this practice.MethodsA retrospective chart review was conducted in patients initiated on paliperidone palmitate (PP) during a psychiatric hospitalization to compare patients who received OAP overlap versus those who did not. The primary outcome is the proportion of patients who receive prescription claims for benztropine, a medication commonly prescribed for extrapyramidal symptoms, at the time of LAIA discontinuation and 6 months postdischarge. Secondary outcomes include prescription claims for beta blockers and diphenhydramine, number of psychiatric emergency visits and hospitalizations, length of stay of the index hospitalization, frequency of LAIA discontinuation and the time to LAIA discontinuation.ResultsThere is a significant difference in the proportion of benztropine prescription claims in the OAP overlap group versus the no-overlap group at the time of LAIA discontinuation (30% vs 0%, P = .046) but not at 6 months postdischarge. There are also significant differences in the number of psychiatric emergency visits (0.7 vs 0.1, P = .02) and psychiatric hospitalizations (0.6 vs 0.1, P = .029) at the time of LAIA discontinuation. No other differences are observed in defined secondary outcomes.DiscussionPatients who receive OAP overlap while receiving PP receive more benztropine and have more psychiatric emergency visits and hospitalizations than those treated without OAP. Larger studies with better control for confounding variables are needed to confirm these results.

406. Utility of Tracheal Aspirates in Guiding Antibiotic Use in Mechanically Ventilated Patients with COVID-19

BackgroundIn critically ill patients with COVID-19 it is difficult to determine the presence of bacterial co-infection. Many patients receive antibiotics until a bacterial infection can be ruled out. To minimize aerosolization of SARS-CoV-2, non-invasive sampling, such as endotracheal aspiration (ETA), is preferred over invasive techniques. The purpose of this study is to determine the diagnostic yield of ETA and effect of ETA on antibiotic management in patients with COVID-19.MethodsThis retrospective analysis included patients admitted to the intensive care unit (ICU) from March 1 to May 31, 2020 who tested positive for SARS-CoV-2. Patients who did not receive mechanical ventilation were excluded. Data were extracted from electronic medical records. When ETA was performed, records were manually reviewed to determine diagnostic yield and effect on antibiotic management. Diagnostic yield was defined as ETA result with a plausible respiratory pathogen in a quantity of moderate or many. Plausible respiratory pathogens exclude normal flora, yeast, coagulase-negative Staphylococcus sp and Enterococcus sp. The primary outcome is the frequency of initiation, change, no change, or discontinuation of antibiotics based on ETA results.Results124 patients with COVID-19 were admitted to the ICU; 76 met inclusion criteria. The average age was 58 years and 75% were male. Hispanic or Latino ethnicity made up the majority of the patient population (63%). Antibiotics were administered to 97% of patients for a median of 11 days of therapy (IQR 7, 21). There were 100 ETAs performed on 55 patients for a diagnostic yield of 21%. ETA led to a change in antibiotic management 47% of the time it was performed. Antibiotic changes include de-escalation (29), discontinuation (7), escalation (6), and initiation (5). ConclusionThe diagnostic yield of ETA in mechanically ventilated patients with COVID-19 was low. Furthermore, ETA results led to a change in antibiotics less than half of the time. The use of ETA to diagnose bacterial co-infection and guide antibiotic therapy in patients with COVID-19 should be weighed against the risk of using a more invasive sampling technique vs the benefit of potential for increased diagnostic yield. Another conclusion may be to forgo ETA if the result is unlikely to change management.Disclosures All Authors: No reported disclosures

Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to 1 Aug 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.