COSMIC-dFBA: A novel multi-scale hybrid framework for bioprocess modeling.

Metabolism governs cell performance in biomanufacturing, as it fuels growth and productivity. However, even in well-controlled culture systems, metabolism is dynamic, with shifting objectives and resources, thus limiting the predictive capability of mechanistic models for process design and optimization. Here, we present Cellular Objectives and State Modulation In bioreaCtors (COSMIC)-dFBA, a hybrid multi-scale modeling paradigm that accurately predicts cell density, antibody titer, and bioreactor metabolite concentration profiles. Using machine-learning, COSMIC-dFBA decomposes the instantaneous metabolite uptake and secretion rates in a bioreactor into weighted contributions from each cell state (growth or antibody-producing state) and integrates these with a genome-scale metabolic model. A major strength of COSMIC-dFBA is that it can be parameterized with only metabolite concentrations from spent media, although constraining the metabolic model with other omics data can further improve its capabilities. Using COSMIC-dFBA, we can predict the final cell density and antibody titer to within 10% of the measured data, and compared to a standard dFBA model, we found the framework showed a 90% and 72% improvement in cell density and antibody titer prediction, respectively. Thus, we demonstrate our hybrid modeling framework effectively captures cellular metabolism and expands the applicability of dFBA to model the dynamic conditions in a bioreactor.

Screening for older inpatients at risk for long length of stay: which clinical tool to use?

BACKGROUND: Screening for inpatients at risk for long length of stay (LOS) is the first step of an effective hospital care plan for older inpatients. This study aims, in older adults admitted to a geriatric acute care ward, to examine and compare the 6-item brief geriatric assessment (BGA) and the "Programme de Recherche sur l'Intégration des Services pour le Maintien de l'Autonomie" (PRISMA-7) risk levels with long LOS, and to establish their performance criteria (i.e., sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios) for LOS. METHODS: Based on an observational, retrospective, cohort design, 166 inpatients aged ≥75 admitted to a geriatric acute care ward of a McGill University-affiliated hospital (Montreal, Quebec, Canada) were recruited. The risk levels of the 6-item BGA (low, moderate and high) and the PRISMA-7 (low versus high) were calculated from a baseline assessment. The LOS was subsequently calculated in number of days. RESULTS: Only the 6-item BGA high risk level was associated with a long LOS (Odds ratio = 1.1 with P = 0.028 and Hazard ratio = 2.1 with P = 0.004). Kaplan-Meier distributions showed that there was no significant difference in the delay of hospital discharge between the low and high-risk level reported by the PRISMA-7 (P = 0.381), whereas the 6-item BGA three risk levels differed significantly (P = 0.008), with individuals at high risk levels being discharged later when compared to those with low (P = 0.001) and moderate (P = 0.019) risk levels. Both tools' performance criteria were poor (i.e., < 0.70), except for PRISMA-7's sensitivity which was 100%. CONCLUSION: The 6-item BGA risk levels were associated with LOS, low risk-level being associated with short LOS and high-risk level with long LOS, but no association was reported with the PRISMA-7 risk levels. Both tools had poor performance criteria for long LOS, suggesting that they cannot be used as prognostic tools with current scientific knowledge.

Decreased risk of falls in patients attending music sessions on an acute geriatric ward: results from a retrospective cohort study.

BACKGROUND: Music has been shown to improve health and quality of life. It was suggested that music may also have an impact on gait stability and fall risk. Yet, few studies have exploited music in the hospital setting, and even less so in the geriatric population. Our objective was to examine the influence of music listening on the risk of falls by comparing the Morse Fall Scale score in patients admitted to a Geriatric Assessment Unit (GAU) who attended music listening sessions and in patients who did not attend music sessions. METHODS: This was a retrospective cohort study (mean follow-up 13.3 ± 6.8 days) which took place in a GAU, St. Mary's Hospital Center, Montreal. A total of 152 charts of participants, with a mean age of 85.7 ± 6.4 years and 88.2% female were reviewed and included. There were 61 participants exposed to the music listening sessions group and 91 in the non-exposed group matched for age, sex, cause and season of admission, and living situation. One-hour music sessions were provided to the patients by volunteer musicians. The Morse Fall Scale score upon admission and discharge as well as its variation (change from before to after exposure) were used as outcomes. Age, sex, living situation, reason for admission, season of admission, Mini Mental Status Examination score, number of therapeutic classes taken daily upon admission, use of psychoactive drugs upon admission and length of stay were used as covariates. RESULTS: The Morse Fall Scale score decreased significantly in the exposed group compared to the non-exposed group (p = 0.025) and represented a small to medium-sized effect, d = 0.395. The multiple linear regression model showed a significant association between the decrease of the Morse Fall Scale score and music exposure (B = - 17.1, p = 0.043). CONCLUSION: Participating in music listening sessions was associated with a decreased risk of falls in patients admitted to a GAU. Further controlled research is necessary to confirm these findings and to determine the mechanisms by which music listening impacts fall risk. TRIAL REGISTRATION: Clinical trial registry: ClinicalTrials.gov . Registration number: NCT03348657 (November 17th, 2017). Retrospectively registered.

Partial and no recovery from delirium after hospital discharge predict increased adverse events.

Background: The implications of partial and no recovery from delirium after hospital discharge are not clear. We sought to explore whether partial and no recovery from delirium among recently discharged patients predicted increased adverse events (emergency room visits, hospitalisations, death) during the subsequent 3 months. Method: Prospective study of recovery from delirium in older hospital inpatients. The Confusion Assessment Method was used to diagnose delirium in hospital and determine recovery status after discharge (T0). Adverse events were determined during the 3 months T0. Survival analysis to the first adverse event and counting process modelling for one or more adverse events were used to examine associations between recovery status (ordinal variable, 0, 1 or 2 for full, partial or no recovery, respectively) and adverse events. Results: Of 278 hospital inpatients with delirium, 172 were discharged before the assessment of recovery status (T0). Delirium recovery status at T0 was determined for 152: 25 had full recovery, 32 had partial recovery and 95 had no recovery. Forty-four patients had at least one adverse event during the subsequent 3 months. In multivariable analysis of one or more adverse events, poorer recovery status predicted increased adverse events; the hazard ratio (HR) (95% confidence interval, CI) was 1.72 (1.09, 2.71). The association of recovery status with adverse events was stronger among patients without dementia. Conclusion: Partial and no recovery from delirium after hospital discharge appear to predict increased adverse events during the subsequent 3 months These findings have potentially important implications for in-hospital and post-discharge management and policy.

Frequency of full, partial and no recovery from subsyndromal deliriumin older hospital inpatients.

OBJECTIVES: To determine the frequencies of full, partial and no recovery from subsyndromal delirium (SSD) in older hospital inpatients. A secondary objective was to compare the recovery status of patients with SSD or delirium. METHODS: SSD was defined as acute onset of one or more Confusion Assessment Method core symptoms of delirium (fluctuation, inattention, disorganized thinking and altered level of consciousness) not meeting criteria for delirium and not progressing to delirium. The recovery status of medical or surgical inpatients aged 65 and older with SSD was assessed approximately 1 and 3 months after enrolment. Primary outcome categories were full recovery (no core symptoms of delirium), partial recovery (presence of one or more core symptoms but fewer symptoms than at enrolment), no recovery (same number of core symptoms as at enrolment) or death. Nominal logistic regression was used to compare the recovery status of patients with SSD or delirium. RESULTS: Twenty-eight patients with SSD were enrolled. At the first follow-up, the frequencies of full, partial and no recovery and death were 40%, 12%, 32% and 16%, respectively; at the second follow-up, the frequencies were 54%, 8%, 21% and 17%, respectively. The frequency of full recovery was much higher in patients with SSD than delirium. CONCLUSION: Small study sample size notwithstanding, the majority (54%) of patients with SSD recovered fully, but a substantial proportion (29%) had a protracted course. It may be important to monitor the longer-term course of SSD and develop strategies to ensure full recovery in all patients.

Improving Transitional Care for Older Adults: Results of a Patient-Centred Quality Improvement Intervention.

The objective of this study was to evaluate the implementation and outcomes of a quality improvement intervention for older adults discharged from hospital to home, that used a patient-centred discharge education tool called the Patient-Centered Discharge Plan (PCAP). We conducted a pre-post evaluation of PCAP implementation among patients 65 years and older and discharged home from an acute medical or geriatric admission at two general hospitals. Two patient cohorts, PRE and POST, were analysed using administrative data (n = 3,309) and post-discharge structured interviews in a subset of patients (n = 326). Outcomes were 90-day readmissions and return emergency department (ED) visits, and transition experiences (10-item scale). The PCAP was provided to 20 per cent of 1,683 patients. Transition experience scores increased from PRE to POST at both hospitals (adjusted beta 1.3; 95% CI: 0.8, 1.7), and return ED visits declined in one of the two hospitals (adjusted decline 1.3%; 95% CI: -3.7, 6.2). In conclusion, dedicated resources are needed to support future PCAP implementation.

Taking the pulse of bioprocesses: at-line and in-line monitoring of mammalian cell cultures.

Real-time and near real-time monitoring of cell culture processes are critical to the evolving process analytical technology (PAT) paradigm for upstream bioprocessing. The responses measured from these analytical instruments can enable rapid feedback to perturbations that can otherwise lead to batch failures. Historically, real-time monitoring of bioreactor processes has been relegated to parameters such as pH, dissolved oxygen, and temperature. Other analytical results, such as cell growth and metabolites, are provided through manual daily sampling. In order to reduce sample error and increase throughput, real-time and near real-time instruments have been developed. Here we discuss recent advances in these technologies. This article aims to focus on other developing at-line and in-line technologies that enable monitoring of bioreactor processes, including dielectric spectroscopy, NIR, off-gas spectrometry, integrated at-line HPLC, and nanofluidic devices for monitoring cell growth and health, metabolites, titer, and product quality.

Clinical and Cost-effectiveness of a Comprehensive geriatric assessment and management for Canadian elders with Cancer-the 5C study: a study protocol for a randomised controlled phase III trial.

INTRODUCTION: Geriatric assessment and management is recommended for older adults with cancer referred for chemotherapy but no randomised controlled trial has been completed of this intervention in the oncology setting. TRIAL DESIGN: A two-group parallel single blind multi-centre randomised trial with a companion trial-based economic evaluation from both payer and societal perspectives with process evaluation. PARTICIPANTS: A total of 350 participants aged 70+, diagnosed with a solid tumour, lymphoma or myeloma, referred for first/second line chemotherapy, who speak English/French, have an Eastern Collaborative Oncology Group Performance Status 0-2 will be recruited. All participants will be followed for 12 months. INTERVENTION: Geriatric assessment and management for 6 months. The control group will receive usual oncologic care. All participants will receive a monthly healthy ageing booklet for 6 months. OBJECTIVE: To study the clinical and cost-effectiveness of geriatric assessment and management in optimising outcomes compared with usual oncology care. RANDOMISATION: Participants will be allocated to one of the two arms in a 1:1 ratio. The randomisation will be stratified by centre and treatment intent (palliative vs other). OUTCOME: Quality of life. SECONDARY OUTCOMES: (1) Cost-effectiveness, (2) functional status, (3) number of geriatric issues successfully addressed, (4) grades3-5 treatment toxicity, (5) healthcare use, (6) satisfaction, (7) cancer treatment plan modification and (8) overall survival. PLANNED ANALYSIS: For the primary outcome we will use a pattern mixture model using an intent-to-treat approach (at 3, 6 and12 months). We will conduct a cost-utility analysis alongside this clinical trial. For secondary outcomes 2-4, we will use a variety of methods. ETHICS AND DISSEMINATION: Our study has been approved by all required REBs. We will disseminate our findings to stakeholders locally, nationally and internationally and by publishing the findings. TRIAL REGISTRATION NUMBER: NCT03154671.

Predicting a long hospital stay after admission to a geriatric assessment unit: Results from an observational retrospective cohort study.

OBJECTIVE: Morbidities and related disabilities often lead to older inpatients having a long hospital stay. The aim of this study was to examine whether the 6-item brief geriatric assessment (BGA), developed and validated in France to determine a priori levels of risk of a long hospital stay (i.e.; low, moderate, high), could be successfully used with patients admitted to a geriatric assessment unit (GAU) in Quebec. STUDY DESIGN: Observational retrospective cohort design. SETTING: A GAU of a McGill University affiliated hospital (Montreal, Quebec, Canada). PARTICIPANTS: 499 inpatients (84.7 ±â€¯7.2 years; 73.3% female) recruited upon their admission. MAIN OUTCOME MEASURES: The BGA comprises 6 items: age > 85 years, male gender, ≥ 5 drugs per day, use of home-help support, history of falls and temporal disorientation. It was administered at baseline and a priori levels of risk of a long hospital stay (i.e., low, moderate, high) were determined. Length of hospital stay (LHS, in days) was calculated using the hospital registry. The association between a priori levels of risk from the BGA and LSH was examined using regression models and Kaplan-Meier curves. RESULTS: The LHS increased with the 6-item BGA a priori level of risk (P = 0.010). High-risk (Hazard ratio (HR) = 1.68 with P < 0.001) and moderate-risk (HR = 1.24 with P = 0.039) of a long hospital stay successfully predicted a long stay. Kaplan-Meier distributions of time to discharge showed that inpatients classified as having high and moderate risk levels for a long hospital stay were discharged later than those with a low risk level (P < 0.001 and P = 0.013). CONCLUSION: The 6-item BGA a priori levels of risk for a long hospital stay successfully predicted a long stay among patients admitted to a GAU in Quebec.

Phytoremediation of agriculture runoff by filamentous algae poly-culture for biomethane production, and nutrient recovery for secondary cultivation of lipid generating microalgae.

An integrated system was implemented for water phytoremediation and biofuel production through sequential cultivation of filamentous algae followed by cultivation of lipid-producing microalgae Chlorella sorokiniana. Natural poly-culture of filamentous algae was grown in agricultural stormwater using the Algal Turf Scrubber®, harvested and subjected for lipid extraction and/or methane production using anaerobic digestion (AD). While filamentous algae lipid content was too low for feasible biodiesel production (<2%), both whole biomass and lipid-extracted algal residues (LEA) yielded ∼0.2LmethanepergVS at loading rates up to 5gVS/L-day. Importantly, essential macro-nutrients and trace elements captured from stormwater were released into the AD effluent as soluble nutrients and were successfully tested as fertilizer replacement for cultivation of lipid-accumulating C. sorokiniana in a subsequent stage. Accordingly, filamentous algae poly-culture was exploited for waste nutrient capturing and biofuel feedstock generation. These nutrients were recovered and reused as a concentrated supplement for potentially high-value microalgae.

Partial and No Recovery from Delirium in Older Hospitalized Adults: Frequency and Baseline Risk Factors.

OBJECTIVES: To determine the frequency and baseline risk factors for partial and no recovery from delirium in older hospitalized adults. DESIGN: Cohort study with assessment of recovery status approximately 1 and 3 months after enrollment. SETTING: University-affiliated, primary, acute-care hospital. PARTICIPANTS: Medical or surgical inpatients aged 65 and older with delirium (N = 278). MEASUREMENTS: The Mini-Mental State Examination (MMSE), Confusion Assessment Method (CAM), Delirium Index (DI), and activities of daily living (ADLs) were completed at enrollment and each follow-up. Primary outcome categories were full recovery (absence of CAM core symptoms of delirium), partial recovery (presence of ≥1 CAM core symptoms but not meeting criteria for delirium), no recovery (met CAM criteria for delirium), or death. Secondary outcomes were changes in MMSE, DI, and ADL scores between the baseline and last assessment. Potential risk factors included many clinical and laboratory variables. RESULTS: In participants with dementia, frequencies of full, partial, and no recovery and death at first follow-up were 6.3%, 11.3%, 74.6%, and 7.7%, respectively; in participants without dementia, frequencies were 14.3%, 17%, 50.9%, and 17.9%, respectively. In participants with dementia, frequencies at the second follow-up were 7.9%, 15.1%, 57.6%, and 19.4%, respectively; in participants without dementia, frequencies were 19.2%, 20.2%, 31.7%, and 28.8%, respectively. Frequencies were similar in participants with prevalent and incident delirium and in medical and surgical participants. The DI, MMSE, and ADL scores of many participants with partial and no recovery improved. Independent baseline risk factors for delirium persistence were chart diagnosis of dementia (odds ratio (OR) = 2.51, 95% confidence interval (CI) =1.38, 4.56), presence of any malignancy (OR = 5.79, 95% CI = 1.51, 22.19), and greater severity of delirium (OR =9.39, 95% CI = 3.95, 22.35). CONCLUSION: Delirium in many older hospitalized adults appears to be much more protracted than previously thought, especially in those with dementia, although delirium symptoms, cognition, and function improved in many participants with partial and no recovery. It may be important to monitor the longer-term course of delirium in older hospitalized adults and develop strategies to ensure full recovery.

Learning while having fun: the use of video gaming to teach geriatric house calls to medical students.

Although most health professionals perform home visits, there is not a structured method for performing them. In addition, in-training health professionals' exposure to home visits is limited for logistical reasons. A new method for medical students to learn how to perform an effective home visit was developed using an instructional video game. It was expected that students would learn the principles of a home visit using a video game while identifying the usefulness of video gaming (edutainment) in geriatrics education. A video game was created simulating a patient's house that the students were able to explore. Students played against time and distracters while being expected to click on those elements that they considered to be risk factors for falls or harmful for the patient. At the end of the game, the students received feedback on the chosen elements that were right or wrong. Finally, evaluation of the tool was obtained using pre- and posttests and pre- and postexposure feedback surveys. Fifty-six fourth-year medical students used the video game and completed the tests and the feedback surveys. This method showed a high level of engagement that is associated with improvement in knowledge. Additionally, users' feedback indicated that it was an innovative approach to the teaching of health sciences. In summary, this method provides medical students with a fun and structured experience that has an effect not only on their learning, but also on their understanding of the particular needs of the elderly population.