717. Lefamulin (LEF) vs. Moxifloxacin (MOX) in Patients With Community-Acquired Bacterial Pneumonia (CABP) at Risk for Poor Efficacy or Safety Outcomes: Pooled Subgroup Analyses From the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Noninferiority Clinical Trials

Abstract Background In the United States, CABP is the second most common cause of hospitalization and a leading cause of infectious death. Patients with chronic obstructive pulmonary disease (COPD)/asthma or diabetes are at risk for CABP and associated mortality. Similarly, patients with underlying cardiac or liver disease are at risk for potential cardiac or liver toxicities, respectively, associated with CABP antimicrobials, and patients aged ≥65 years are at risk for both efficacy/safety concerns. We report pooled efficacy/safety outcomes in at-risk subgroups from the LEAP 1 and 2 phase 3 trials. Methods In LEAP 1, patients with CABP (PORT III–V) received IV LEF 150 mg q12h for 5–7 days or MOX 400mg q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, patients with CABP (PORT II–IV) received oral LEF 600 mg q12h for 5 days or MOX 400 mg q24h for 7 days. Both studies assessed early clinical response (ECR; 96 ± 24 hours after first dose) in the intent-to-treat (ITT; all randomized patients) population (FDA primary endpoint) and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (≥1 study drug dose) and clinically evaluable (met predefined evaluability criteria) populations (EMA coprimary endpoints). Pooled analyses used a 10% noninferiority margin. Safety was assessed in all randomized and treated patients. Results 1289 ITT patients were randomized to LEF (n = 646) or MOX (n = 643); of whom, 297 (23.0%) were aged 65–74 years and 220 (17.1%) were ≥75 years; 232 patients (18.0%) had COPD/asthma and 168 (13.0%) had diabetes mellitus (DM). At baseline, 501 patients (38.9%) had history of hypertension, 73 (5.7%) had history of arrhythmia, and 263 (20.4%) had transaminitis. The figure shows efficacy by age and in COPD/asthma and DM patients. Treatment-emergent adverse events, electrocardiogram assessments, and laboratory results in patients at risk for cardiac and hepatic safety concerns are shown in Tables 1 and 2. Conclusion In pooled analyses of LEAP 1 and 2, LEF efficacy was high and similar to MOX in patients at risk of efficacy concerns and LEF showed a safety profile similar to that of MOX in patients at risk of safety concerns. LEF is a promising new option for IV/oral monotherapy of CABP in patients at risk of poor outcomes due to CABP or to antimicrobial therapy for CABP. Disclosures All authors: No reported disclosures.

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A Phase-3 Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults with Community-acquired Bacterial Pneumonia (DEFINE-CABP)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz514 ◽

2019 ◽

Cited By ~ 2

Author(s):

Juan P Horcajada ◽

Robert A Salata ◽

Rodolfo Álvarez-Sala ◽

Floarea Mimi Nitu ◽

Laura Lawrence ◽

...

Keyword(s):

Clinical Response ◽

Bacterial Pneumonia ◽

Study Drug ◽

The United States ◽

Efficacy And Safety ◽

Success Rates ◽

Phase 3 ◽

Double Blind ◽

Atypical Pathogens ◽

Intent To Treat

Abstract Background The clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin’s shape and charge profile uniquely impacts its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin to moxifloxacin for the treatment of CABP. Methods A randomized, double-blind, comparator-controlled, multicenter, global Phase 3 study compared the efficacy and safety of delafloxacin 300 mg BID or moxifloxacin 400 mg QD in adults with CABP. The primary endpoint was early clinical response (ECR) defined as improvement at 96 (± 24) hours after first dose of study drug. Clinical response at test of cure (TOC) and microbiologic response were also assessed. Results In the intent-to-treat analysis population (ITT), ECR rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group. Noninferiority of delafloxacin compared with moxifloxacin was demonstrated. At TOC in the ITT population, the success rates were similar between groups. Treatment-emergent adverse events considered at least possibly related to the study drug occurred in 65 subjects (15.2%) in the delafloxacin group and 54 (12.6%) in the moxifloxacin group. Conclusions IV/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for grampositive, gramnegative, and atypical pathogens.

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Identifying Foot and Ankle Patients at Risk to Fall Based on Patient Reported Outcomes Assessments

Foot & Ankle Orthopaedics ◽

10.1177/2473011418s00026 ◽

2018 ◽

Vol 3 (3) ◽

pp. 2473011418S0002

Author(s):

Judith Baumhauer ◽

Jack Teitel ◽

Allison McIntyre ◽

David Mitten ◽

Jeff Houck

Keyword(s):

At Risk ◽

Effect Size ◽

Fall Risk ◽

Patient Reported Outcomes ◽

The United States ◽

Foot And Ankle ◽

Falls Risk ◽

Orthopaedic Patients ◽

Patient Reported ◽

Patients At Risk

Category: Other Introduction/Purpose: Each year approximately 30-40% of people over the age of 65 fall. Approximately one half of these falls result in an injury with the estimated annual direct medical costs of $30 billion. Pain, mobility issues, neuropathy and post-operative weight bearing limitations make foot and ankle patients particularly vulnerable to falls. Current approaches to determine at risk patients are cumbersome and time consuming requiring performance testing and “hands on” clinical assessment. The efficiency of obtaining PRO, such as PROMIS, in the clinical arena has been well documented. The purpose of this study is determine if patient reported outcomes (PROMIS) can identify orthopaedic and specifically foot and ankle patients at risk to fall. Methods: Prospective patient reported outcomes (PROMIS CAT physical function, pain interference and depression and CMS fall risk assessment questions) and patient demographics were collected for all patients at each clinic visit from an academic orthopaedic multi-specialty practice between January 2015 and November 2017. Standardized yes/no validated self-reported fall risk questions include: “Have you fallen in the last year?” and “Do you feel you are at risk of falling?” Histograms, t-tests, confidence intervals and effect size were used to determine the fall risk “YES” patients were different than the “NO” for ALL orthopaedic patients and specifically foot and ankle patients. Logistic Regression was used to determine if age, gender, height, weight, and PROMIS scales predicted self-reported falls risk. Results: 94,761 orthopaedic patients comprising 315,273 visits (44% male, mean age 53.7+/-17 years) and 13,720 foot/ankle patients comprising 33,480 visits (37% male, mean age 52.7+/-16.1 years) had complete data for analysis. Table 1 provides the means/SD/p-values/effect sizes for patient self-identifying at risk to fall stratified by PROMIS PF/ PI/Dep t-scores. Although all PROMIS scores demonstrated significant impairment between patients at risk designation (yes/no), PROMIS PF had the largest effect size for ALL Ortho and FOOT AND ANKLE patients (0.8 and 0.7 respectively). Patients who are at risk to fall have PROMIS PF t-scores >1.5 lower than the United States normative population while the patients not at risk are less <1 SD. In the adjusted regression models gender and PROMIS PF had the largest coefficients. Conclusion: Falls are a major threat to quality of life and independence yet prevention/treatment strategies are difficult to implement across a health system. There is also a tremendous societal cost with orthopaedic surgeons often the recipient of these debilitated patients. PROMIS assessments are part of the AOFAS OFAR initiative to track patient recovery with treatment and can additional be used to fulfill a quality indicator requirement by CMS. This study demonstrates these assessments (PROMIS threshold values) can also be linked to self-report falls risk (yes/no) and may identify patients at risk with no face to face time required from the provider.

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Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkx382 ◽

2017 ◽

Vol 72 (12) ◽

pp. 3501-3501 ◽

Cited By ~ 6

Author(s):

Oliver A Cornely ◽

Michael N Robertson ◽

Shariq Haider ◽

Andrew Grigg ◽

Michelle Geddes ◽

...

Keyword(s):

At Risk ◽

Invasive Fungal Disease ◽

Fungal Disease ◽

Open Label ◽

Phase 3 ◽

Open Label Study ◽

Label Study ◽

Patients At Risk

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Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An Evidence-Based Review

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.0177 ◽

2008 ◽

Vol 26 (16) ◽

pp. 2767-2778 ◽

Cited By ~ 406

Author(s):

Bertrand Coiffier ◽

Arnold Altman ◽

Ching-Hon Pui ◽

Anas Younes ◽

Mitchell S. Cairo

Keyword(s):

At Risk ◽

High Risk ◽

Tumor Lysis Syndrome ◽

The United States ◽

Standards Of Care ◽

Close Monitoring ◽

Tumor Lysis ◽

High Risk Patients ◽

Patients At Risk ◽

Risk Patients

PurposeTumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS.MethodsA panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used.ResultsNew guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involves similar recommendations, with the addition of aggressive hydration and diuresis, plus allopurinol or rasburicase for hyperuricemia. Alkalinization is not recommended. Although guidelines for rasburicase use in adults are provided, this agent is currently only approved for use in pediatric patients in the United States.ConclusionThe potential severity of complications resulting from TLS requires measures for prevention in high-risk patients and prompts treatment in the event that symptoms arise. Recognition of risk factors, monitoring of at-risk patients, and appropriate interventions are the key to preventing or managing TLS. These guidelines should assist in the prevention of TLS and improve the management of patients with established TLS.

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700. Safety and Efficacy of Omadacycline in Patients with Diabetes in Phase 3 Clinical Studies

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.768 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S316-S317

Author(s):

Manjunath P Pai ◽

Mark H Wilcox ◽

Marla Curran ◽

Surya Chitra ◽

Lynne Garrity-Ryan ◽

...

Keyword(s):

Clinical Response ◽

Medical History ◽

Clinical Success ◽

Oral Medication ◽

Phase 3 ◽

Safety And Efficacy ◽

Skin Structure ◽

Patients With Diabetes ◽

Poor Treatment ◽

History Of

Abstract Background The risk of serious infections and poor treatment outcomes is reported to be higher in patients with diabetes compared with the general population. Omadacycline (OMC) is an intravenous (IV) and oral aminomethylcycline antibiotic approved in the US to treat acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) in adults. Here we assessed safety and efficacy results from OMC Phase 3 studies (ABSSSI: Omadacycline in Acute Skin and skin structure Infections Study [OASIS]-1 and OASIS-2; CABP: Omadacycline for Pneumonia Treatment In the Community study [OPTIC]), by diabetes history. Methods In OASIS-1 (IV to optional oral medication) and OASIS-2 (oral only), patients were randomized to OMC or linezolid (LZD) for 7–14 days. In OPTIC, patients were randomized to IV OMC or moxifloxacin (MOX) for 7–14 days, with optional transition to oral medication. Data from OASIS-1 and OASIS-2 were pooled, and patient subgroups were defined by any medical history of diabetes (type 1, type 2, or unspecified), or no medical history of diabetes. Efficacy outcomes were early clinical response (ECR) and investigator’s assessment of clinical response at post-treatment evaluation (PTE), as defined for each indication. Safety was assessed by treatment-emergent adverse events (TEAEs) and laboratory measures, and data were pooled across the three studies. Results A total of 2,150 patients were included, of whom 238 (11.1%) had any history of diabetes (n = 105 for ABSSSI, n = 133 for CABP). In the pooled ABSSSI studies and the CABP study, clinical success at ECR and PTE was similar between patients with or without diabetes, and between OMC and the respective comparator (figure). TEAEs and serious TEAEs, respectively, were reported in similar numbers of OMC-, LZD-, and MOX-treated patients with diabetes (41.8–49.3%, 4.5–7.0%) and without (41.2–48.3%, 1.6–6.9%). Rates of nausea and vomiting, respectively, in patients with diabetes were similar across treatment arms: OMC (5.0%, 5.0%), LZD (7.5%, 6.0%), MOX (7.0%, 2.8%). Conclusion Omadacycline efficacy and safety were similar and consistent in patients with or without diabetes. Disclosures All authors: No reported disclosures.

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Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkx263 ◽

2017 ◽

Vol 72 (12) ◽

pp. 3406-3413 ◽

Cited By ~ 28

Author(s):

Oliver A Cornely ◽

Michael N Robertson ◽

Shariq Haider ◽

Andrew Grigg ◽

Michelle Geddes ◽

...

Keyword(s):

At Risk ◽

Invasive Fungal Disease ◽

Fungal Disease ◽

Open Label ◽

Phase 3 ◽

Open Label Study ◽

Label Study ◽

Patients At Risk

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Reversible Thrombocytopenia after Gabapentin in an HIV-Positive Patient

Case Reports in Psychiatry ◽

10.1155/2018/5927065 ◽

2018 ◽

Vol 2018 ◽

pp. 1-2

Author(s):

Mohammed Basith ◽

Andrew Francis ◽

Alfredo Bellon

Keyword(s):

At Risk ◽

Human Immunodeficiency Virus ◽

Psychiatric Care ◽

Hiv Positive ◽

Inpatient Psychiatric Care ◽

Immunodeficiency Virus ◽

The Us ◽

Patients At Risk ◽

History Of ◽

Severe Anxiety

Gabapentin has become increasingly used in psychiatric practice specifically for anxiety disorders. Even though gabapentin is not approved by the US Food and Drug Administration to treat anxiety, physicians sometimes use it as an alternative to benzodiazepines in patients with a history of substance abuse. Gabapentin is also prescribed when individuals are at risk of thrombocytopenia which is not considered a side effect. Among patients at risk of thrombocytopenia are those positive for human immunodeficiency virus (HIV). Here we present a case of an HIV-positive man who presented for inpatient psychiatric care with severe anxiety and a history of alcohol and benzodiazepine abuse. In this patient, gabapentin worsened thrombocytopenia after repeated exposure to this medication. We suggest caution when considering gabapentin for patients with preexisting low platelet counts, as there seems to be a risk for worsening thrombocytopenia with this antiepileptic in the presence of HIV infection.

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Alternative Education

Encyclopedia of Social Work ◽

10.1093/acrefore/9780199975839.013.1228 ◽

2017 ◽

Author(s):

Cynthia Franklin ◽

Linda Webb ◽

Hannah Szlyk

Keyword(s):

At Risk ◽

Alternative Education ◽

Task Force ◽

At Risk Students ◽

The United States ◽

School Curriculum ◽

Drop Out ◽

Effective Strategies ◽

History Of ◽

Solution Focused

This article will cover the current best practices in designing and establishing alternative programs for at-risk students and suggest how social workers can assist in program development and sustainability. At-risk students are youth considered more likely than others to drop out of school due to various factors, including truancy, poor grades, disruptive behaviors, pregnancy, and repeated expulsions or suspensions. The history of alternative education in the United States will be reviewed and the types of alternative educations programs in practice outlined. How the framework of an alternative school differs from that of a disciplinary program will be examined along with initial steps toward development and implementation. Effective strategies explained include establishing a task force, involving the greater community, and implementing evidence-based interventions such as Response to Intervention (RTI) into the school curriculum. An example of a sustainable public alternative education program grounded in solution-focused brief therapy (SFBT) is presented.

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Severe Pertussis Infections in the United States, 2011–2015

Clinical Infectious Diseases ◽

10.1093/cid/ciy889 ◽

2018 ◽

Vol 69 (2) ◽

pp. 218-226 ◽

Cited By ~ 9

Author(s):

Sarah A Mbayei ◽

Amanda Faulkner ◽

Christine Miner ◽

Karen Edge ◽

Victor Cruz ◽

...

Keyword(s):

United States ◽

Treatment Options ◽

Age Groups ◽

The United States ◽

Hospitalized Patients ◽

Chronic Obstructive ◽

Emerging Infections ◽

Older Children ◽

Pertussis Infection ◽

History Of

Abstract Background The incidence of pertussis in the United States has increased in recent years. While characteristics of severe pertussis infection have been described in infants, fewer data are available in older children and adults. In this analysis, we characterize pertussis infections in hospitalized patients of all ages. Methods Cases of pertussis with cough onset from 1 January 2011 through 31 December 2015 from 7 US Emerging Infections Program Network states were reviewed. Additional information on hospitalized patients was obtained through abstraction of the inpatient medical record. Descriptive and multivariable analyses were conducted to characterize severe pertussis infection and identify potential risk factors. Results Among 15942 cases of pertussis reported, 515 (3.2%) were hospitalized. Three hospitalized patients died. Infants aged <2 months accounted for 1.6% of all pertussis cases but 29.3% of hospitalizations. Infants aged 2–11 months and adults aged ≥65 years also had high rates of hospitalization. Infants aged <2 months whose mothers received acellular pertussis during the third trimester and children aged 2 months to 11 years who were up to date on pertussis-containing vaccines had a 43%–66% reduced risk of hospitalization. Among adolescents aged 12–20 years, 43.5% had a history of asthma, and among adults aged ≥65 years, 26.8% had a history of chronic obstructive pulmonary disease. Conclusions Individuals at the extreme ends of life may be the most vulnerable to severe pertussis infections, though hospitalization was reported across all age groups. Continued monitoring of severe pertussis infections will be important to help guide prevention, control, and treatment options.

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