Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial.

Objectives: In the phase III SOLO1 trial (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation who were in response after platinum-based chemotherapy. We analyzed the timing, duration and grade of the most common hematologic and non-hematologic adverse events in SOLO1.

Methods: Eligible patients were randomized to olaparib tablets 300 mg twice daily (N = 260) or placebo (N = 131), with a 2-year treatment cap in most patients.

Molecular and clinical predictors of improvement in progression-free survival with maintenance PARP inhibitor therapy in women with platinum-sensitive, recurrent ovarian cancer: A meta-analysis.

Background: The authors performed a meta-analysis to better quantify the benefit of maintenance poly(ADP-ribose) polymerase inhibitor (PARPi) therapy to inform practice in platinum-sensitive, recurrent, high-grade ovarian cancer for patient subsets with the following characteristics: germline BRCA mutation (gBRCAm), somatic BRCA mutation (sBRCAm), wild-type BRCA but homologous recombinant-deficient (HRD), homologous recombinant-proficient (HRP), and baseline clinical prognostic characteristics.

Methods: Randomized trials comparing a PARPi versus placebo as maintenance treatment were identified from electronic databases. Treatment estimates of progression-free survival were pooled across trials using the inverse variance weighted method.

Machine learning and wearable sensors at preoperative assessments: Functional recovery prediction to set realistic expectations for knee replacements.

Unmet expectations contribute to a high patient dissatisfaction rate following total knee replacement but clinicians currently do not have the tools to confidently adjust expectations. In this study, supervised machine learning was applied to multi-variate wearable sensor data from preoperative timed-up-and-go tests. Participants (n=82) were instrumented three months after surgery and patients showing relevant improvement were designated as "responders" while the remainder were labelled "maintainers".

Machine Learning Predicts the Fall Risk of Total Hip Arthroplasty Patients Based on Wearable Sensor Instrumented Performance Tests.

Background: The prevalence of falls affects the wellbeing of aging adults and places an economic burden on the healthcare system. Integration of wearable sensors into existing fall risk assessment tools enables objective data collection that describes the functional ability of patients. In this study, supervised machine learning was applied to sensor-derived metrics to predict the fall risk of patients following total hip arthroplasty.

Monitoring daily shoulder activity before and after reverse total shoulder arthroplasty using inertial measurement units.

Background: The purpose of this study was to use at-home, portable, continuous monitoring technologies to record arm motion and activity preoperatively and postoperatively after reverse total shoulder arthroplasty (RTSA).

Methods: Thirty-three patients indicated for RTSA were monitored preoperatively and 3 and 12 months postoperatively. Inertial measurement units were placed on the sternum and upper arm of the operative limb, recording humeral motion relative to the torso for the duration of a waking day.

Setup error with and without image guidance using two canine intracranial positioning systems for radiation therapy.

Daily image guidance reduces inter-fractional variation in patient position for intracranial radiation therapy. However, the ability to detect and correct positioning errors is limited below a certain level. Because of these limitations, the accuracy achieved with a positioning system prior to image guidance may affect the error remaining after image guidance (the residual setup error).

Residual setup error in the canine intracranial region after megavoltage, kilovoltage, or cone-beam computed tomographic image guidance for radiation therapy.

Sources of residual setup error after image guidance include image localization accuracy, errors associated with image registration, and inability of some treatment couches to correct submillimeter translational errors and/or pitch and roll errors. The purpose of this experimental study was to measure setup error after image-guided correction of the canine intracranial region, using a four degrees-of-freedom couch capable of 1 mm translational moves. Six cadaver dogs were positioned 45 times as for clinical treatment using a vacuum deformable body cushion, a customizable head cushion, a thermoplastic mask and an indexed maxillary plate with a dental mould.

Automatic emotion and attention analysis of young children at home: a ResearchKit autism feasibility study.

Current tools for objectively measuring young children's observed behaviors are expensive, time-consuming, and require extensive training and professional administration. The lack of scalable, reliable, and validated tools impacts access to evidence-based knowledge and limits our capacity to collect population-level data in non-clinical settings. To address this gap, we developed mobile technology to collect videos of young children while they watched movies designed to elicit autism-related behaviors and then used automatic behavioral coding of these videos to quantify children's emotions and behaviors.

Machine Learning Groups Patients by Early Functional Improvement Likelihood Based on Wearable Sensor Instrumented Preoperative Timed-Up-and-Go Tests.

Background: Wearable sensors permit efficient data collection and unobtrusive systems can be used for instrumenting knee patients for objective assessment. Machine learning can be leveraged to parse the abundant information these systems provide and segment patients into relevant groups without specifying group membership criteria. The objective of this study is to examine functional parameters influencing favorable recovery outcomes by separating patients into functional groups and tracking them through clinical follow-ups.

Repeatability of measuring knee flexion angles with wearable inertial sensors.

Background: As assessment with inertial-measurement-units (IMUs) increases in research and in clinics, it is important to be aware of the repeatability of these sensors. The objectives of this experiment were to evaluate the measurement repeatability of IMU joint angles using a repeatable robot controller and an anthropomorphic leg phantom and to determine effects of joint speed and sensor positioning on the angles collected by these sensors. Comparisons to an electro-goniometer and three-dimensional (3D) motion capture cameras were also completed.

Exaggeration of PFS by blinded, independent, central review (BICR).

Background: Recent published studies have shown meaningful discrepancies between local investigator and blinded, independent, central review (BICR) assessed median progression-free survival (PFS). When the local review but not BICR shows progression, generally, no further assessments are carried out and patients are censored in the BICR analysis, leading to violation of the statistical assumptions of independence between censoring and outcome used in survival analysis methods.

Methods: We carried out a simulation study to assess methodological reasons behind these discrepancies and corroborated our findings in a case study of three BRCA-mutated ovarian cancer trials.

Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.

Background: Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain.

Methods: We conducted an international, randomized, double-blind, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients with newly diagnosed advanced (International Federation of Gynecology and Obstetrics stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both ( BRCA1/2) who had a complete or partial clinical response after platinum-based chemotherapy.

Proposal and Validation of a Knee Measurement System for Patients With Osteoarthritis.

Objective: Currently most measurements of knee joint function are obtained through observation and patient-reported outcomes. This paper proposes an implementation and validation of a knee monitor to measure quantitative joint data in multiple degrees of freedom. The proposed system is configurable with minimal patient interaction and no frame-alignment calibration procedure is required for measurement after visually placing/replacing sensors on patients.

Pharmacologic Treatment of Hypertensive Urgency in the Outpatient Setting: A Systematic Review.

Background: Hypertensive urgency (HU), defined as acute severe uncontrolled hypertension without end-organ damage, is a common condition. Despite its association with long-term morbidity and mortality, guidance regarding immediate management is sparse. Our objective was to summarize the evidence examining the effects of antihypertensive medications to treat.

The role of core and accessory type IV pilus genes in natural transformation and twitching motility in the bacterium Acinetobacter baylyi.

Here we present an examination of type IV pilus genes associated with competence and twitching in the bacterium Acinetobacter baylyi (strain ADP1, BD413). We used bioinformatics to identify potential competence and twitching genes and their operons. We measured the competence and twitching phenotypes of the bioinformatically-identified genes.

Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.

Background: Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2) mutation using a tablet formulation of olaparib.

Methods: This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy.

The Digital Drag and Drop Pillbox: Design and Feasibility of a Skill-based Education Model to Improve Medication Management.

Objective: We present the design and feasibility testing for the "Digital Drag and Drop Pillbox" (D-3 Pillbox), a skill-based educational approach that engages patients and providers, measures performance, and generates reports of medication management skills.

Methods: A single-cohort convenience sample of patients hospitalized with heart failure was taught pill management skills using a tablet-based D-3 Pillbox. Medication reconciliation was conducted, and aptitude, performance (% completed), accuracy (% correct), and feasibility were measured.

Opening the Duke electronic health record to apps: Implementing SMART on FHIR.

Objective: Recognizing a need for our EHR to be highly interoperable, our team at Duke Health enabled our Epic-based electronic health record to be compatible with the Boston Children's project called Substitutable Medical Apps and Reusable Technologies (SMART), which employed Health Level Seven International's (HL7) Fast Healthcare Interoperability Resources (FHIR), commonly known as SMART on FHIR.

Methods: We created a custom SMART on FHIR-compatible server infrastructure written in Node.js that served two primary functions.

Which Moral Foundations Predict Willingness to Make Lifestyle Changes to Avert Climate Change in the USA?

Jonathan Haidt's Moral Foundations Theory identifies five moral axes that can influence human motivation to take action on vital problems like climate change. The theory focuses on five moral foundations, including compassion, fairness, purity, authority, and ingroup loyalty; these have been found to differ between liberals and conservatives as well as Democrats and Republicans. Here we show, based on the Cornell National Social Survey (USA), that valuations of compassion and fairness were strong, positive predictors of willingness to act on climate change, whereas purity had a non-significant tendency in the positive direction (p = 0.

Extended-release guanfacine hydrochloride in 6-17-year olds with ADHD: a randomised-withdrawal maintenance of efficacy study.

Background: Extended-release guanfacine hydrochloride (GXR), a selective α2A-adrenergic agonist, is a nonstimulant medication for attention-deficit/hyperactivity disorder (ADHD). This phase 3, double-blind, placebo-controlled, randomised-withdrawal study evaluated the long-term maintenance of GXR efficacy in children/adolescents with ADHD.

Methods: Children/adolescents (6-17 years) with ADHD received open-label GXR (1-7 mg/day).

Prone position for acute respiratory failure in adults.

Background: Acute hypoxaemia de novo or on a background of chronic hypoxaemia is a common reason for admission to intensive care and for provision of mechanical ventilation. Various refinements of mechanical ventilation or adjuncts are employed to improve patient outcomes. Mortality from acute respiratory distress syndrome, one of the main contributors to the need for mechanical ventilation for hypoxaemia, remains approximately 40%.