Unsupervised Online Paired Associates Learning Task from the Cambridge Neuropsychological Test Automated Battery (CANTAB®) in the Brain Health Registry.

BACKGROUND: Unsupervised online cognitive assessments have demonstrated promise as an efficient and scalable approach for evaluating cognition in aging, and Alzheimer's disease and related dementias. OBJECTIVES: The aim of this study was to evaluate the feasibility, usability, and construct validity of the Paired Associates Learning task from the Cambridge Neuropsychological Test Automated Battery® in adults enrolled in the Brain Health Registry. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: The Paired Associates Learning task was administered to Brain Health Registry participants in a remote, unsupervised, online setting. In this cross-sectional analysis, we 1) evaluated construct validity by analyzing associations between Paired Associates Learning performance and additional participant registry data, including demographics, self- and study partner-reported subjective cognitive change (Everyday Cognition scale), self-reported memory concern, and depressive symptom severity (Patient Health Questionnaire-9) using multivariable linear regression models; 2) determined the predictive value of Paired Associates Learning and other registry variables for identifying participants who self-report Mild Cognitive Impairment by employing multivariable binomial logistic regressions and calculating the area under the receiver operator curve; 3) investigated feasibility by looking at task completion rates and statistically comparing characteristics of task completers and non-completers; and 4) evaluated usability in terms of participant requests for support from BHR related to the assessment. RESULTS: In terms of construct validity, in participants who took the Paired Associates Learning for the first time (N=14,528), worse performance was associated with being older, being male, lower educational attainment, higher levels of self- and study partner-reported decline, more self-reported memory concerns, greater depressive symptom severity, and self-report of Mild Cognitive Impairment. Paired Associates Learning performance and Brain Health Registry variables together identified those with self-reported Mild Cognitive Impairment with moderate accuracy (areas under the curve: 0.66-0.68). In terms of feasibility, in a sub-sample of 29,176 participants who had the opportunity to complete Paired Associates Learning for the first time in the registry, 14,417 started the task. 11,647 (80.9% of those who started) completed the task. Compared to those who did not complete the task at their first opportunity, those who completed were older, had more years of education, more likely to self-identify as White, less likely to self-identify as Latino, less likely to have a subjective memory concern, and more likely to report a family history of Alzheimer's disease. In terms of usability, out of 8,395 received requests for support from BHR staff via email, 4.4% (n=374) were related to PAL. Of those, 82% were related to technical difficulties. CONCLUSIONS: Our findings support moderate feasibility, good usability, and construct validity of cross-sectional Paired Associates Learning in an unsupervised online registry, but also highlight the need to make the assessment more inclusive and accessible to individuals from ethnoculturally and socioeconomically diverse communities. A future, improved version could be a scalable, efficient method to assess cognition in many different settings, including clinical trials, observational studies, healthcare, and public health.

The Heart Failure Optimization Study (HF-OPT): rationale and design.

BACKGROUND: According to the current guidelines, implantable cardioverter-defibrillators (ICD) for primary prevention in patients with heart failure and reduced ejection fraction (HFrEF) should not be considered until optimal guideline-directed medical therapy (GDMT) has been achieved for a minimum of 3 months. Optimization of GDMT often needs time beyond 3 months after diagnosis. The aim of the Heart Failure Optimization Study (HF-OPT) is to evaluate the recovery of left ventricular function beyond 3 months after diagnosis of newly diagnosed HFrEF. METHODS: The HF-OPT multicenter study is comprised of two non-randomized phases (registry and study). During the first 90 days a wearable cardioverter-defibrillator (WCD) is prescribed and patients are enrolled in an observational pre-study registry. Registry subjects meeting inclusion criteria for the study portion at day 90 have ongoing left ventricular ejection fraction (LVEF) reassessment at 90, 180 and 360 days after the index hospital discharge, regardless of continued WCD use. Approximately 600 subjects will be enrolled in the study portion. Of those, one-third are anticipated to start the study phase at day 90 with reduced LVEF. The primary objective of this study is to observe the rate of recovery of LVEF > 35% between 90 and 180 days, while key secondary endpoints include mortality and WCD recorded arrhythmias and shocks. DISCUSSION: The HF-OPT study will provide important information on the rate of additional recovery of LVEF > 35%, between 90 and 180 days, in newly diagnosed HF with reduced LVEF patients being titrated with GDMT. The results of the study may impact indications for primary prophylactic ICD implantation.

Optimization by uniform design U8 (83 ) approach for enhanced caffeine degradation in synthetic wastewater in bioreactor.

Coffee wastewater contains large amounts of caffeine which affects microflora and seed development to great extent. Although several physio-chemical methods available for caffeine degradation, they are not preferred for large-scale treatment. In this study, we optimized induced cell concentration, aeration and agitation rate for maximizing caffeine degradation rate in bioreactor using Uniform design. Maximum caffeine degradation rate of 23·59 mg L-1 h-1 was achieved. The reduction in chemical oxygen demand, biological oxygen demand and total organic carbon removal were found to be 72, 78 and 72% respectively. Mathematical model was developed through regression analysis and predicted maximum caffeine degradation rate of 24·2 mg L-1 h-1 under optimal conditions of 0·35 g L-1 biomass, 395 rev min-1 and 1·62 vvm. Experimental validation at optimum condition resulted in 22 mg L-1 h-1 of caffeine degradation rate. This is the first-ever bioreactor study showing highest caffeine degradation rate in synthetic coffee wastewater with limited experimental runs.

A rapid LC-PDA method for the simultaneous quantification of metformin, empagliflozin and linagliptin in pharmaceutical dosage form.

OBJECTIVE: The objective of the present study is to develop and validate a simple, rapid stability indicating high performance liquid chromatography method for the simultaneous quantification of metformin, empagliflozin, linagliptin in bulk and pharmaceutical dosage form. MATERIALS AND METHODS: The chromatographic separation was achieved on C18 X-bridge phenyl column (250×4.6mm, 5µm particle size). The pharmaceutical analytes were quantified by diode array detector in HPLC, eluted with acetonitrile and triethylamine (70:30) as mobile phase, monitored at 240nm over a runtime of 7min. RESULTS: The method was linear in the range of 50-750µg/mL (r2=0.999) for metformin, 0.5-7.5µg/mL (r2=0.999) for empagliflozin, 0.25-3.75µg/mL (r2=0.999) for linagliptin. The percentage recoveries of these 3 drugs were within acceptable limits (99.2-100.8). The method was found to be precise as % RSD<2. Forced degradation studies were conducted under acidic, basic, oxidative, reductive, photolysis, thermal conditions and showed degradation within (19.4-32.4%). CONCLUSION: The validated (as per ICH guidelines) rapid method can be routinely used in quality control lab for the quantification of metformin, empagliflozin and linagliptin in raw materials as well as in pharmaceutical dosage form.

A simple stability indicating RP-HPLC-DAD method for concurrent analysis of Tenofovir Disoproxil Fumarate, Doravirine and Lamivudine in pure blend and their combined film coated tablets.

OBJECTIVES: The main aim of the study was to develop an economical, insightful, accurate and simple RP-HPLC-DAD method with high precision and good sensitivity for concurrent determination of Tenofovir disoproxil fumarate, Doravirine and Lamivudine in blended bulk form and their combined tablet form. MATERIAL AND METHODS: A method with Ascentis C18 (150×4.6mm, 5µm) column, mobile phase ratio of 0.1% ortho phosphoric acid and Acetonitrile in 70:30 (v/v), 1mL/min flow rate and detection wavelength of 260nm was highly proficient in effective separation of all three drugs. The developed method was validated in accordance with ICH specifications. RESULTS: The retention times of Doravirine, Lamivudine and Tenofovir disoproxil fumarate observed were 2.4, 2.9, and 3.6min, respectively. The linear responses were observed for Doravirine, Lamivudine and Tenofovir disoproxil fumarate in the range of 12.5-75µg/mL, 75-225µg/mL and 75-225µg/mL, respectively. The limit of detection and quantification values were calculated to be 0.36µg/mL and 0.11µg/mL for Lamivudine, 0.55µg/mL and 1.66µg/mL for Tenofovir disoproxil fumarate and 0.03µg/mL and 0.09µg/mL for Doravirine. The % RSD values of the intra-day and inter-day precision were calculated in the range of 0.134-1.749. The mean percentage recovery of all three analytes was in the range of 98.85-100.18%. The statistical results of the validation parameters ensured that the method was accurate, specific, and precise with good sensitivity. Investigation of analytes under different stressed conditions ensures the stability of analytes reflecting the stability indication of the method. The developed method has high proficiency in separation of Tenofovir disoproxil fumarate, Doravirine and Lamivudine. The degradation products generated due to stress conditions also separated with good resolution. CONCLUSION: The current method is a stability-indicating assay method consisting of appropriate specificity, accuracy, precision and sensitivity. The developed method has a good potential to be adopted by the pharmaceutical industrial sector.