evaluation

Within-Trial Evaluation of Medical Resources, Costs, and Quality of Life Among Patients With Type 2 Diabetes Participating in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)

OBJECTIVE

To compare medical resource use, costs, and health utilities for 14,752 patients with type 2 diabetes who were randomized to once-weekly exenatide (EQW) or placebo in addition to usual diabetes care in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

RESEARCH DESIGN AND METHODS

Medical resource use data and responses to the EuroQol 5-Dimension (EQ-5D) instrument were collected at baseline and throughout the trial. Medical resources and medications were assigned values by using U.S. Medicare payments and wholesale acquisition costs, respectively. Secondary analyses used English costs.

RESULTS

Patients were followed for an average of 3.3 years, during which time those randomized to EQW experienced 0.41 fewer inpatient days (7.05 vs. 7.46 days; relative rate ratio 0.91; P = 0.05). Rates of outpatient medical visits were similar, as were total inpatient and outpatient costs. Mean costs for nonstudy diabetes medications over the study period were ~$1,600 lower with EQW than with placebo (P = 0.01). Total within-study costs, excluding study medication, were lower in the EQW arm than in the placebo arm ($28,907 vs. $30,914; P ≤ 0.01). When including the estimated cost of EQW, total mean costs were significantly higher in the EQW group than in the placebo group ($42,697 vs. $30,914; P < 0.01). With English costs applied, mean total costs, including exenatide costs, were £1,670 higher in the EQW group than the placebo group (£10,874 vs. £9,204; P < 0.01). There were no significant differences in EQ-5D health utilities between arms over time.

CONCLUSIONS

Medical costs were lower in the EQW arm than the placebo arm, but total costs were significantly higher once the cost of branded exenatide was incorporated.




evaluation

What Parents Need to Know About the Special Education Evaluation


I spend most days of my life working with various students who are at different parts in the sped referral process. I attend Child Study Meetings where we decide if we are going to evaluate a student. I observe and screen children and talk with parents and teachers to help the committee make a good decision about whether we should do a special education evaluation.   I evaluate those students (this includes Psychological testing, observations, talking with student/teacher/parent, doing rating scales, etc.). I attend eligibility meetings where we determine if the student is eligible for for special education services. All of this is second nature to me and sometimes I need to stop and remember when a parent comes in, that this is NEW.

When I talk to parents, I find that many parents do not fully understand the special education referral process, even when they nod and act like they do. We as school staff need to do a better job of helping the parents understand the process. Parents also need to speak up and ask questions when there is not understanding.

This is a guide for parents to understand the process of special education testing, the testing components, and some of the test data. It is important to note that schools systems and states will vary to some degree. If you have any questions about the process in your school system, ask your school psychologist, teacher, or principal. Parents have every right to ask questions and usually school personnel are happy to help make this process less anxiety-provoking for you. It is important for parents to understand their rights during the special education process.


Special Education Process

After data shows that interventions have been attempted and if a student is suspected of having a disability, a referral is made to evaluate him or her for special education testing. Once the parents sign the Permission for Testing Forms, timelines begin and the schools have 65 business days to complete the assessments and hold the eligibility meeting. Some states may have a different timeline.

During these 65 days, several testing components will be completed with you and your child. The evaluators will write reports and a copy will be given to parents at the eligibility meeting. However, schools are required to have a copy available for parents to pick up two days before the eligibility meeting. It is advised, that parents take advantage of this and read reports before the meeting to help get familiar with the information and to formulate questions. The reports hold a lot of information that can be overwhelming if you are not familiar with this type of testing. Read Understanding Test Scores to understand the types of tests used and what the scores mean.

Additionally, the meeting is likely to bring forth strong emotions as your child’s difficulties are discussed openly. It can be overwhelming for parents, especially when not prepared. When parents do not read the reports prior to the eligibility meeting, they are the only people at the table who come to the meeting not knowing what to expect.


What if My Child is Found ELIGIBLE for Special Education Services?

Once a child is eligible for special education services, the schools have 30 days to develop an Individualized Education Plan (IEP) for the student. This will consist of accommodations, goals, and describe the services offered. Parents are part of a committee to help create this document. Once it is signed, schools are legally required to follow it. It is reviewed once a year, unless parents or teachers feel that changes are necessary. Every three years, the committee will determine if the student should be reevaluated. This is called a triennial evaluation. Sometimes another full evaluation will be conducted, other times a review of records and updated teacher information is used.


What if My Child is Found INELIGIBLE for Special Education Services?

If your child was found ineligible for special education services and you agree with the eligibility findings, then your child will not receive special education. He or she was evaluated because of a problem that still needs to be addressed within regular education. Ask for a separate meeting with your teacher or a team to determine what accommodations or strategies can be used to help.

If you believe that your child requires special education services and has a disability, but was found ineligible for services, make an appointment to meet with the special education director. If an agreement cannot be reached, you may be able to have an Independent Evaluation at the expense of the school. The results of that testing will be brought back to an eligibility meeting. A child MUST have 2 things before they can receive special education services: They must have a disability and there must be a documented educational impact that the student requires special education services to be successful.






evaluation

New York Takes Final Step to Separate State Test Scores From Teacher Evaluations

The New York state legislature passed a bill that would make the use of state test scores in these evaluations optional, leaving the decision up to districts and making it subject to collective bargaining.




evaluation

Tennessee Teachers Have Warmed to Evaluation System, But Not State Tests

Tennessee improved its teacher evaluation and training systems by integrating data and teacher voice, according to a new report. But value-added measures that evaluate teachers based on student test scores remain controversial.




evaluation

Ex-Obama Adviser Who Championed Teacher Evaluations to Seek Senate Seat

Can a Democrat with a record of tying test scores to teacher evaluations win a U.S. Senate seat in Colorado? Mike Johnston, a former Obama campaign adviser, wants to find out.




evaluation

Teacher Evaluation in Washington, D.C.

Unless students are randomly assigned to teachers, it's unfair to label teachers.




evaluation

Basin Plan Evaluation 2017 - social and economic technical overview.

Implementing the Basin Plan requires the Murray Darling Basin Authority to evaluate the economic, social and environmental outcomes directly attributable to the Basin Plan. This report draws together all the data and modelling used to separate the Basin Plan effects (both positive and negative) from all the other drivers of change at the community scale in the southern Basin. This work built upon the analysis undertaken by the MDBA to support the Northern Basin Review. The community-level analysis adopted by the MDBA complements the industry and broad Basin-scale summary of social and economic conditions presented in the 2017 Basin Plan Evaluation report. A strong reliance is placed on the community outcomes as this represents the finer scale relationships between the types of irrigated production and local businesses, and between the towns and the surrounding farming communities. Further work is required to align these community-level outcomes with the observed regional, industry and Basin scale changes.




evaluation

2019-2020 Annual Evaluation Work Plan.




evaluation

Annual Evaluation Work Plan : Indigenous Advancement Strategy.




evaluation

Australian government response to the Senate Finance and Public Administration References Committee inquiry report : the appropriateness and effectiveness of the objectives, design, implementation and evaluation of the Community Development Program (CDP)




evaluation

The community development programme : evaluation of participation and employment outcomes / Department of the Prime Minister and Cabinet.




evaluation

Transition to Work Interim Evaluation Report.




evaluation

An evaluation of bicycle passing distances in the ACT / JRR Mackenzie, JK Dutschke, G Ponte.

To evaluate bicycle passing distances in the Australian Capital Territory (ACT), specialised passing distance measurement devices (PDMDs) were installed on a sample of 23 cyclists who ride in the ACT. Passing distance data and GPS data was collected by cyclists using the PDMDs for a four week period, during a trial phase of a newly legislated minimum passing distance (MPD) rule The MPD rule requires drivers to provide more than 1 metre of space when passing a cyclist on a road with a speed limit of 60 km/h or below, and 1.5 meters of space when passing a cyclist on a road with a speed limit above 60 km/h.-- Abstract.




evaluation

An evaluation of the California civil addict program / by William H. McGlothlin, M. Douglas Anglin, Bruce D. Wilson.

Rockville, Maryland : National Institute on Drug Abuse, 1977.




evaluation

Evaluation of drug abuse treatments : based on first year followup : national followup study of admissions to drug abuse treatments in the DARP during 1969-1972.

Rockville, Maryland : National Institute on Drug Abuse, 1978.




evaluation

Medical evaluation of long-term methadone-maintained clients / edited by Herbert D. Kleber, Frank Slobetz and Marjorie Mezritz.

Rockville, Maryland : National Institute on Drug Abuse, 1980.




evaluation

Evaluation of the NIDA drug abuse prevention campaign, 1983-1984 : final report.

[United States] : National Technical Information Service, United States Department of Commerce, 1984.




evaluation

Drug abuse treatment evaluation : strategies, progress, and prospects / editors Frank M. Tims, Jacqueline P. Ludford.

Springfield, Virginia. : National Technical Information Service, 1984.




evaluation

Evaluation of treatment programs for abusers of nonopiate drugs : problems and approaches. Volume 3 / Wynne Associates for Division of Research, National Institute on Drug Abuse, Alcohol, Drug Abuse and Mental Health Administration, Department of Health,

Washington, D.C. : Wynne Associates, [1974]




evaluation

Monitoring and evaluation : alcoholism and other drug dependence services.

Chicago, Ill. : Joint Commission on Accreditation of Healthcare Organizations, 1987.




evaluation

Evaluation of the 'progress' pilot projects "from recovery into work" / by Stephen Burniston, Jo Cutter, Neil Shaw, Michael Dodd.

York : York Consulting, 2001.




evaluation

Reference and Document Aware Semantic Evaluation Methods for Korean Language Summarization. (arXiv:2005.03510v1 [cs.CL])

Text summarization refers to the process that generates a shorter form of text from the source document preserving salient information. Recently, many models for text summarization have been proposed. Most of those models were evaluated using recall-oriented understudy for gisting evaluation (ROUGE) scores. However, as ROUGE scores are computed based on n-gram overlap, they do not reflect semantic meaning correspondences between generated and reference summaries. Because Korean is an agglutinative language that combines various morphemes into a word that express several meanings, ROUGE is not suitable for Korean summarization. In this paper, we propose evaluation metrics that reflect semantic meanings of a reference summary and the original document, Reference and Document Aware Semantic Score (RDASS). We then propose a method for improving the correlation of the metrics with human judgment. Evaluation results show that the correlation with human judgment is significantly higher for our evaluation metrics than for ROUGE scores.




evaluation

A stochastic user-operator assignment game for microtransit service evaluation: A case study of Kussbus in Luxembourg. (arXiv:2005.03465v1 [physics.soc-ph])

This paper proposes a stochastic variant of the stable matching model from Rasulkhani and Chow [1] which allows microtransit operators to evaluate their operation policy and resource allocations. The proposed model takes into account the stochastic nature of users' travel utility perception, resulting in a probabilistic stable operation cost allocation outcome to design ticket price and ridership forecasting. We applied the model for the operation policy evaluation of a microtransit service in Luxembourg and its border area. The methodology for the model parameters estimation and calibration is developed. The results provide useful insights for the operator and the government to improve the ridership of the service.




evaluation

Study finds nearly 40% drop in stroke evaluations during COVID-19 pandemic

The number of people evaluated for signs of stroke at U.S. hospitals has dropped by nearly 40% during the COVID-19 pandemic, according to a study led by researchers from Washington University School of Medicine in St. Louis who analyzed stroke evaluations at more than 800 hospitals across 49 states and the District of Columbia.




evaluation

Community Asthma Initiative: Evaluation of a Quality Improvement Program for Comprehensive Asthma Care

Comprehensive home visits conducted by Community Health Workers including environmental remediation and office-based nurse case management improve asthma outcomes.

Implementation of a comprehensive quality improvement program as part of enhanced care of pediatric asthma patients with a history of hospitalizations or emergency department visits can improve health outcomes and be cost-effective as well as reduce health disparities. (Read the full article)




evaluation

Discomfort and Pain in Newborns With Myelomeningocele: A Prospective Evaluation

Active termination of life in newborns with myelomeningocele because of assumed suffering in these newborns has been extensively discussed. However, the level of discomfort and pain in these newborns has never been substantially assessed.

This is the first study presenting quantitative data on discomfort and pain in newborns with myelomeningocele. Therefore, it can be of guidance in the choice of treatment: either active treatment or palliative care in the context of end-of-life decisions. (Read the full article)




evaluation

Evaluation of a Clinical Dehydration Scale in Children Requiring Intravenous Rehydration

Evaluating dehydration severity is a challenging task. Clinical dehydration scores that combine multiple clinical findings are promising. One clinical dehydration scale score has been developed and subsequently evaluated; however, few participants in the derivation and validation studies were significantly dehydrated.

In children requiring intravenous rehydration, the dehydration scale displayed moderate reliability and weak associations with objective measures. Thus, although the scale can assist in assessing dehydration, it should not be used in isolation to dictate interventions (eg, intravenous rehydration, hospitalization). (Read the full article)




evaluation

Economic Evaluation of Strategies to Reduce Sudden Cardiac Death in Young Athletes

Sudden cardiac death in young athletes is an uncommon but devastating event. Addition of routine electrocardiogram (ECG) screening to standard preparticipation care may reduce the number of sudden deaths. Lack of data regarding effectiveness and costs has prevented widespread implementation.

Adding ECG screening to current preparticipation evaluation is not cost-effective. Cost is driven primarily by the evaluation of the large number of false-positive findings. An ECG-only screening strategy is more cost-effective. (Read the full article)




evaluation

An Evaluation of Mother-Centered Anticipatory Guidance to Reduce Obesogenic Infant Feeding Behaviors

Childhood obesity occurs in 20% of children before they enter kindergarten. Treatment is difficult, making prevention desirable, but little is known about effective methods using anticipatory guidance to prevent obesity in pediatric primary care.

This study provides a comparison of 2 approaches versus usual care using anticipatory guidance to improve infant feeding during the first year of life, and demonstrates positive specific feeding behavior differences at 1 year in the intervention groups. (Read the full article)




evaluation

Evaluation of Interobserver Agreement of Apgar Scoring in Preterm Infants

The Apgar score is a convenient method to rapidly assess the clinical status of the newborn infant. Recent literature suggests Apgar scores vary widely in preterm infants.

The Apgar signs for respiratory effort, grimace, and muscle tone demonstrated considerable disagreement in preterm infants ≤28 weeks’ gestation. Disagreement exists despite the level of respiratory intervention, continuous positive airway pressure, or intubation, and is likely independent of gestational age. (Read the full article)




evaluation

Retrospective Evaluation of a New Neonatal Trigger Score

Trigger scores and early warning systems provide an objective measure of a patient’s condition, allowing earlier recognition of severe illness and adaptation of care. Such scores are established in adult and pediatric populations but remain unevaluated and rarely used in neonates.

This newly designed Neonatal Trigger Score provides an objective adjunct to multidisciplinary clinical assessment in detecting unwell neonates. It is more sensitive and specific than previously validated pediatric early warning system scores. (Read the full article)




evaluation

Evaluation of an Office Protocol to Increase Exclusivity of Breastfeeding

A gap exists with lack of programs to help mothers breastfeed. The 2012 American Academy of Pediatrics' "Policy Statement on Breastfeeding and the Use of Human Milk" re-emphasized breastfeeding as an important public health initiative rather than a lifestyle choice.

Families who receive care in a primary care setting that has implemented a "breastfeeding-friendly" office protocol may have increased rates of exclusive breastfeeding. This study evaluated an accepted clinical protocol in a large, diverse pediatric primary care setting. (Read the full article)




evaluation

Blood Cultures in the Evaluation of Uncomplicated Skin and Soft Tissue Infections

Blood cultures are a common investigation in children admitted to the hospital with skin and soft tissue infections. The yield of blood cultures in this condition is unknown.

Blood cultures are not useful in children admitted to the hospital with uncomplicated skin and soft tissue infections, and they may be associated with increased length of hospital stay. (Read the full article)




evaluation

Evaluation of an Early Risk Screener for PTSD in Preschool Children After Accidental Injury

Unintentional injuries lead to a significant number of children suffering from long-lasting posttraumatic stress symptoms. Therefore, early identification of individuals at risk is crucial to provide preventative interventions. However, currently, no early screener has been evaluated in preschool-aged children.

Good sensitivity (85%) and acceptable specificity (63%) were found for an early screening measure for preschool-aged children after accidental injury. Hence, the 21-item Pediatric Emotional Distress Scale–Early Screener, a reliable and valid early screening instrument, is suggested for use within a stepped-care model. (Read the full article)




evaluation

Development and Evaluation of Global Child Health Educational Modules

Global health is of increasing interest and relevance to North American pediatric trainees. Opportunities for resident global health training and exposure are most often limited to electives or trainees in dedicated global health tracks.

A series of short, structured, participatory global child health modules improved knowledge and were well received and integrated within academic programs. Such modules enable global health learning for all residents, including those who never intend to practice overseas. (Read the full article)




evaluation

Prospective Evaluation of a Clinical Pathway for Suspected Appendicitis

Although appendicitis is the most common surgical cause of abdominal pain in pediatrics, its diagnosis remains elusive. When evaluated independently, clinical scoring systems and ultrasonography have been shown to have low to moderate sensitivity in the diagnosis of appendicitis.

Our study evaluated the accuracy of a clinical practice guideline combining the Samuel’s pediatric appendicitis score and selective ultrasonography as the primary imaging modality for children with suspected appendicitis. Our clinical pathway demonstrated high sensitivity and specificity. (Read the full article)




evaluation

Economic Evaluation of the Routine Childhood Immunization Program in the United States, 2009

The first evaluation of the economic impact of all vaccines in the routine US childhood immunization schedule assessed the 2001 schedule (excluding pneumococcal conjugate and influenza vaccines) and documented substantial cost savings over the lifetimes of the cohort of children born in 2001.

This report updates our previous evaluation, and estimates the costs and benefits of vaccinating the cohort of children born in 2009. We include vaccines routinely recommended for children in 2009. (Read the full article)




evaluation

Use of Modified Acute Concussion Evaluation Tools in the Emergency Department

Concussions in youth are a common injury evaluated in the emergency department (ED). Early recognition and active management of this mild traumatic brain injury are important to safe recovery. Tools to assess and manage concussion in the ED are lacking.

Acute Concussion Evaluation tools, modified for ED use, improved reported follow-up with primary care or concussion specialists and adherence to recommendations. Barriers to follow-up remain and the importance of ongoing outpatient management should be stressed. (Read the full article)




evaluation

The Pediatric AIDS Corps: A 5-Year Evaluation

Demographic data concerning health care providers working long-term in resource-limited areas with religious groups or other government or nongovernment organizations are limited. Health outcomes from these programs vary with the focus of the individual program.

This study describes the composition and evaluation of a long-term global health corps program. Other groups interested in long-term physician placement in resource-limited areas will be able to use these data while developing their program. (Read the full article)




evaluation

Neuroimaging in the Evaluation of Neonatal Encephalopathy

Computed tomography is commonly used for neuroimaging in newborn infants with neonatal encephalopathy despite concerns over potential harm from radiation exposure. Alternative neuroimaging options include MRI and cranial ultrasound.

Using a very large, international, multicenter database, we demonstrate utilization rates and compare diagnostic findings of computed tomography, MRI, and cranial ultrasound in the evaluation of neonatal encephalopathy. (Read the full article)




evaluation

Motor Performance After Neonatal Extracorporeal Membrane Oxygenation: A Longitudinal Evaluation

After neonatal extracorporeal membrane oxygenation treatment, children are at risk for neurodevelopmental problems including delayed motor function. So far this has only been studied cross-sectionally until age 7 years.

We describe, in a nationwide evaluation, the longitudinal course of motor function development after neonatal extracorporeal membrane oxygenation with persisting problems up to 12 years. At risk are children with congenital diaphragmatic hernia and those with chronic lung disease. (Read the full article)




evaluation

Automated Urinalysis and Urine Dipstick in the Emergency Evaluation of Young Febrile Children

Urinary tract infection is the most common serious bacterial illness among febrile infants and young children. Automated urine cytometry may supplant traditional urinalysis, but diagnostic performance at unique pediatric cutpoints has not been described for this labor-saving technique.

We describe new, clinically useful cutpoints for automated leukocyte and bacterial counts. The sensitivity and specificity of bacterial counts ≥250 cells/μL exceed those of other methods. However, point-of-care dipstick tests for leukocyte esterase or nitrite have acceptable performance. (Read the full article)




evaluation

State-Specific Differences in School Sports Preparticipation Physical Evaluation Policies

Preparticipation physical evaluations (PPEs) are considered necessary for a high standard of care for US scholastic athletes. However, important questions remain regarding consistency of implementation and content of cardiovascular screening practices among states.

Our results show that PPE policies are variable among US states, and adoption of current PPE-4 best practices is slow, demonstrating the need for nationwide PPE standardization. (Read the full article)




evaluation

Unrecognized Celiac Disease in Children Presenting for Rheumatology Evaluation

Associations have been reported between celiac disease (CD) and numerous autoimmune conditions in adults and children. However, current screening guidelines do not consider patients with rheumatic diseases to be at high risk for CD.

The prevalence of CD in children presenting for rheumatology evaluation was found to be 2% by routine serologic screening. The majority of screening-detected CD cases had no CD-associated symptoms. Gluten restriction was found to relieve some musculoskeletal complaints. (Read the full article)




evaluation

Critical Elements in the Medical Evaluation of Suspected Child Physical Abuse

Previous research has described important variability in the medical evaluation of suspected child physical abuse. This variability may contribute to bias and reduce reliability in the medical diagnosis of abuse.

A panel of child abuse pediatricians participated in a Delphi Process, defining critical elements for the medical evaluation of suspected physical abuse in children. Results can be used to reduce practice variability that may contribute to potential bias in evaluation. (Read the full article)




evaluation

Evaluation for Occult Fractures in Injured Children

Screening for occult fractures is a key component of the medical evaluation for young victims of suspected physical abuse. Little is known about adherence to occult fracture evaluation guidelines in children with suspected abuse cared for at non-pediatric-focused hospitals.

Occult fracture evaluations were performed in half of young children diagnosed with abuse or injuries concerning for abuse in a large cohort of hospitals. Evaluations were more common at hospitals caring for higher volumes of young, injured children. (Read the full article)




evaluation

No, Mentoring a Student-Teacher Won't Hurt Your Evaluation Score, Study Suggests

Mentoring a student-teacher won't hurt a teacher's district evaluation score—in fact, it might even give it a boost, according to a working study.




evaluation

Evaluation of the efficacy of antibiotic combinations against multidrug-resistant Pseudomonas aeruginosa in automated time-lapse microscopy and static time-kill experiments [Clinical Therapeutics]

Objectives: Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Yet, data of which combinations are most effective is lacking. This study aimed to evaluate the in vitro efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR Pseudomonas aeruginosa.

Methods: We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, meropenem, minocycline, rifampicin, temocillin, thiamphenicol or trimethoprim by automated time-lapse microscopy using predefined cut-off values indicating inhibition of growth (≤106 CFU/mL) at 24 h. Promising combinations were subsequently evaluated in static time-kill experiments.

Results: All strains were intermediate or resistant to polymyxin B, anti-pseudomonal β-lactams, ciprofloxacin and amikacin. Genes encoding β-lactamases (e.g., blaPAO and blaOXA-50) and mutations associated with permeability and efflux were detected in all strains. In the time-lapse microscopy experiments, positive interactions were found with 39 of 52 antibiotic combination/bacterial strain setups. Enhanced activity was found against all four strains with polymyxin B used in combination with aztreonam, cefepime, fosfomycin, minocycline, thiamphenicol and trimethoprim. Time kill experiments showed additive or synergistic activity with 27 of the 39 tested polymyxin B combinations, most frequently with aztreonam, cefepime, and meropenem.

Conclusion: Positive interactions were frequently found with the tested combinations, also against strains that harboured several resistance mechanisms to the single drugs and with antibiotics that are normally not active against P. aeruginosa. Further study is needed to explore the clinical utility of these combinations.




evaluation

Evaluation of the effect of contezolid (MRX-I) on the corrected QTc interval: a randomized, double-blind, placebo- and positive-controlled crossover study in healthy Chinese volunteers [Clinical Therapeutics]

Contezolid (MRX-I), a new oxazolidinone, is an antibiotic in development for treating complicated skin and soft tissue infections (cSSTI) caused by resistant Gram-positive bacteria. This was a thorough QT study conducted in 52 healthy subjects who were administered oral contezolid at a therapeutic (800 mg) dose, a supratherapeutic (1600 mg) dose, placebo, and oral moxifloxacin 400 mg in 4 separate treatment periods. The pharmacokinetic profile of contezolid was also evaluated. Time-point analysis indicated that the upper bounds of the two-sided 90% confidence interval (CI) for placebo-corrected change-from-baseline QTc (QTc) were <10 ms for the contezolid therapeutic dose at each time point. The upper bound of the 90% CI for QTc were slightly more than 10 ms with the contezolid supratherapeutic dose at 3 and 4 hours postdose, and the prolongation effect on the QT/QTc interval was less than that of the positive control, moxifloxacin 400 mg. At 3 and 4 h after the moxifloxacin dose, the moxifloxacin group met the assay sensitivity criteria outlined in ICH Guidance E14 with having a lower confidence bound ≥5 ms. The results of a linear exposure-response model which were similar to that of a time point analysis demonstrated a slightly positive relationship between contezolid plasma levels and QTcF interval with a slope of 0.227 ms per mg/L (90% CI: 0.188 to 0.266). In summary, contezolid did not prolong the QT interval at a therapeutic dose and may have a slight effect on QT interval prolongation at a supratherapeutic dose.




evaluation

Phase 2a Pharmacokinetic, Safety, and Exploratory Efficacy Evaluation of Oral Gepotidacin (GSK2140944) in Female Participants With Uncomplicated Urinary Tract Infection (Acute Uncomplicated Cystitis) [Clinical Therapeutics]

Gepotidacin, a triazaacenaphthylene bacterial type II topoisomerase inhibitor, is in development for treatment of uncomplicated urinary tract infection (uUTI). This Phase 2a study in female participants with uUTI evaluated the pharmacokinetics (primary objective), safety, and exploratory efficacy of gepotidacin. Eligible participants (N = 22) were confined to the clinic at baseline, received oral gepotidacin 1,500 mg twice daily for 5 days (on-therapy; Days 1 to 5), and returned to the clinic for test-of-cure (Days 10 to 13) and follow-up (Day 28±3). Pharmacokinetic, safety, clinical, and microbiological assessments were performed. Maximum plasma concentrations were observed approximately 1.5 to 2 hours postdose. Steady state was attained by Day 3. Urinary exposure over the dosing interval increased from 3,742 μg.h/ml (Day 1) to 5,973 μg.h/ml (Day 4), with trough concentrations of 322 to 352 μg/ml from Day 3 onward. Gepotidacin had an acceptable safety-risk profile with no treatment-limiting adverse events and no clinically relevant safety trends. Clinical success was achieved in 19 (86%) and 18 (82%) of 22 participants at test-of-cure and follow-up, respectively. Eight participants had a qualifying baseline uropathogen (growth; ≥105 CFU/ml). A therapeutic (combined clinical and microbiological [no growth; <103 CFU/ml]) successful response was achieved in 6 (75%) and 5 (63%) of 8 participants at test-of-cure and follow-up, respectively. Plasma area under the free-drug concentration-time curve over 24 hours at steady state divided by the MIC (fAUC0-24/MIC) and urine AUC0-24/MIC ranged from 6.99 to 90.5 and 1,292 to 121,698, respectively. Further evaluation of gepotidacin in uUTI is warranted. (NCT03568942)