Investigation of the corneal frequency response to modulated sound excitation

Purpose : To investigate the possibility of determining the eye's intraocular pressure (IOP), biomechanical parameters (BM), and geometrical distortion through its frequency response to acoustic excitation as measured by phase-sensitive swept source optical coherence tomography (PhS-ssOCT). Methods : Experimental (E): Freshly enucleated porcine eyes (<45h) were mounted in front of a PhS-ssOCT at 15mmHg IOP. A loudspeaker was placed 10mm to the corneal apex, and a frequency sweep (0-1000Hz) was applied at sound pressure levels of 0.88Pa. Resonance amplitude and frequency were measured for different corneal treatments: 1) de-epithelized, 2) applied photosensitizer Riboflavin (RF), 3) cross-linked (CXL, Dresden protocol), and different measurement set-ups: a) at/around apex, b) IOP 15 - 30 mmHg, c) eye mounted on artificial orbital fat, mimicked by silicone. Simulations (S): Nonlinear hyperelastic FE models of porcine eyes were built and subjected to a modulated pressure, equal to (E). The frequency response was determined by monitoring the apex displacement over time then using fast Fourier transformation (FFT) analysis to determine the frequency peaks. Resonance frequency and amplitudes were determined across corneal meridians for homogeneous BM and for corneas with local BM variations. For both (E) and (S), resonance frequencies were defined at the positions of peak amplitudes. Results : (S) and (E) results were in good correspondence and both showed resonance frequencies of 370Hz. An increase of 15 mmHg in IOP resulted in a decrease of the resonance amplitude of up to 1.24±0.61μm (E) and a frequency shift of up to 22.7± 9.3Hz (E). BM changes produced by CXL led to a decrease in amplitude of 2.19±0.78μm, without significant frequency shifts (E). (S) supported these trends, but showed up to 13Hz higher frequency shifts with IOP increase. Additionally, (S) showed that localized BM changes could be detected by examining asymmetries of the resonance amplitude across opposite corneal meridians. Presence of artificial orbital fat resulted in a damping of the resonance amplitude of >50% for (E) and (S). Conclusions : Sound-coupled OCT measurements made it possible to detect corneal resonance frequencies. IOP and BM could be decoupled, due to differential dependencies of amplitude and resonance frequency on IOP and BM

Tailored lighting intervention (TLI) for improving sleep-wake cycles in older adults living with dementia

Introduction: Sleep disturbance is a hallmark of Alzheimer’s disease and related dementias, and caregiver stress caused by patients’ nighttime wandering, injuries, and agitation are frequently at the root of decisions to move them to assisted living facilities, where typically dim institutional lighting can further exacerbate their sleep problems. This study explored the effects of a circadian-effective lighting intervention on actigraphic sleep measures and subjective assessments of sleep disturbance, depression, and sleep-disturbed behaviors.Methods: Fourteen older adult (≥60 years) participants (11 females, mean age = 84.1 [SD 8.9]), all diagnosed with moderate to severe dementia and sleep disturbance, were recruited from 3 assisted living and memory care facilities. Following a crossover, placebo-controlled design, 3 different lighting modes were used to deliver high levels of circadian stimulus to the participants’ eyes for two 8-week intervention periods in a counter balanced order with a 4-week washout between the study’s 2 conditions (dim light control vs. active intervention). Actigraphy and questionnaire data were collected over 7-day assessment periods that preceded (baseline weeks 1 and 9) and concluded (post-intervention week 9 and 22) the intervention periods. Actigraphic outcomes included sleep duration, sleep time, sleep efficiency, sleep start time, and sleep end time. Subjective assessments included the Cornell Scale for Depression in Dementia (CSDD), Pittsburgh Sleep Quality Index (PSQI), and Sleep Disorders Inventory (SDI) instruments.Results: Under the active condition, sleep duration significantly (p = 0.018) increased and sleep start time significantly (p = 0.012) advanced after the intervention compared to baseline. Also under the active condition, PSQI (p = 0.012), CSDD (p = 0.007), Sleep Disorders Inventory frequency (p = 0.015), and SDI severity (p = 0.015) scores were significantly lower after the intervention compared to baseline.Discussion: This study demonstrates that a circadian-effective lighting intervention delivering bright days and dark nights improves measures of sleep and mood in dementia patients living in controlled environments

Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas

Abstract Aim This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS). Methods Patients were randomly assigned (1:1) to receive trabectedin 1.5mg/m 2 24-h intravenous (i.v.) infusion every 3weeks (q3wk) ( Arm A ), or doxorubicin 75mg/m 2 i.v. q3wk, or doxorubicin 60mg/m 2 i.v. plus ifosfamide (range, 6–9g/m 2 ) i.v. q3wk ( Arm B ). Progression-free survival (PFS) by independent review was the primary efficacy end-point. Results One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p =0.9573; hazard ratio=0.86, p =0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm. Conclusion Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma

Developing Symptom Lists for People with Cancer Treated with Targeted Therapies

Background: Targeted Therapies (TTs) have revolutionised cancer treatment with their enhanced specificity of action. Compared with conventional therapies, TTs are delivered over a longer period and often have unusual symptom profiles. Patient reported outcome measures such as symptom side-effect lists need to be developed in a time-efficient manner to enable a rapid and full evaluation of new treatments and effective clinical managementObjective: the aim of this study is to develop a set of TT-related symptoms and identify the optimal method for developing symptom lists. Patients and Methods: symptoms from TT treatment in the context of Chronic Myeloid Leukaemia (CML), HER2 positive breast cancer, or Gastrointestinal Stromal Tumours (GIST) were identified through literature reviews, interviews with health care professionals (HCPs) and patients, and patient focus groups. The symptom set was then pilot tested in patients across the three cancer diagnoses: The number of items derived from each source (literature, patients, or HCPs) were compared. Results: a total of 316 patients and 86 HCPs from 16 countries participated. An initial set of 209 symptoms was reduced to 61 covering 12 symptom categories. Patient interviews made the greatest contribution to the item set.Conclusions: symptom lists should be created based on input from patients. The item set described will be applicable to the assessment of new TTs, and in monitoring treatment.<br/