Instrumentos de avaliação multidimensional de fragilidade para uso no cuidado de idosos com doença cardiovascular / Multidimensional frailty assessment tools for use in the care of older adults with cardiovascular disease / Instrumentos de evaluación multidimensional de la fragilidad en la atención de adultos mayores con enfermedad cardiovascular

Objetivo: identificar quais os instrumentos disponíveis para avaliação multidimensional da fragilidade em idosos com doença cardiovascular, potencialmente aplicáveis durante a realização do Processo de Enfermagem. Método: revisão sistemática conduzida em oito bases de dados/portais, para identificação de estudos que apresentassem instrumentos multidimensionais de avaliação de fragilidade em idosos com doença cardiovascular e que fossem aplicáveis ao processo de enfermagem. Resultados: foram incluídos 19 instrumentos multidimensionais. O Brief Frailty Index for Coronary Artery Disease foi desenvolvido para uso no cuidado cardiovascular de idosos. O Frailty Index for Adults e o Maastricht Frailty Screening Tool for Hospitalized Patients foram desenvolvidos para uso no Processo de Enfermagem. Conclusão: apesar de apenas um instrumento ter sido desenvolvido para o idosos com doença cardiovascular e apenas dois serem aplicáveis ao processo de enfermagem, a maioria deles tem potencial de adaptação e validação para uso nesta população durante a avaliação de enfermagem.

Objective: to identify which tools are available for multidimensional frailty assessment of older adult with cardiovascular disease and which are potentially applicable during the Nursing Process. Method: a systematic review conducted in eight databases/portals to identify studies that presented multidimensional frailty assessment tools for older adult with cardiovascular disease and that were applicable to the nursing process. Results: a total of 19 multidimensional tools were included. The Brief Frailty Index for Coronary Artery Disease was developed for use in the cardiovascular care of older adult. The Frailty Index for Adults and the Maastricht Frailty Screening Tool for Hospitalized Patients were developed for use in the Nursing Process. Conclusion: although only one tool was developed for older adults with cardiovascular disease and only two are applicable to the nursing process, most of them have the potential to be adapted and validated for use in this population during nursing assessment.

Objetivo: identificar qué instrumentos están disponibles para la evaluación multidimensional de la fragilidad en personas mayores con enfermedad cardiovascular, que se puedan aplicar en el Proceso de Enfermería. Método: revisión sistemática realizada en ocho bases de datos/portales, para identificar estudios que presentaran instrumentos multidimensionales para la evaluación de la fragilidad en adultos mayores con enfermedad cardiovascular y que fueran aplicables al proceso de enfermería. Resultados: se incluyeron 19 instrumentos multidimensionales. El Brief Frailty Index for Coronary Artery Disease se desarrolló para usarlo en el cuidado cardiovascular de las personas mayores. El Frailty Index for Adults y la Maastricht Frailty Screening Tool for Hospitalized Patients se elaboraron para ser usados en el Proceso de Enfermería. Conclusión: aunque sólo se elaboró un instrumento para adultos mayores con enfermedad cardiovascular y sólo dos son aplicables al proceso de enfermería, la mayoría de ellos tienen el potencial para ser adaptados y validados para ser usados en esa población en la evaluación de enfermería.

The utility of website-based quality improvement tools for health professionals: a systematic review.

BACKGROUND: As technology continues to advance, it is important to understand how website-based tools can support quality improvement. Website-based tools refer to resources such as toolkits that users can access and use autonomously through a dedicated website. This review examined how website-based tools can support healthcare professionals with quality improvement, including the optimal processes used to develop tools and the elements of an effective tool. METHODS: A systematic search of seven databases was conducted to include articles published between January 2012 and January 2024. Articles were included if they were peer reviewed, written in English, based in health settings and reported the development or evaluation of a quality improvement website-based tool for professionals. A narrative synthesis was conducted using NVivo. Risk of bias was assessed using the Mixed Methods Appraisal Tool. All papers were independently screened and coded by two authors using a six-phase conceptual framework by Braun and Clarke. RESULTS: Eighteen studies met the inclusion criteria. Themes identified were tool development processes, quality improvement mechanisms and barriers and facilitators to tool usage. Digitalising existing quality improvement processes (n = 7), identifying gaps in practice (n = 6), and contributing to professional development (n = 3) were common quality improvement aims. Tools were associated with reported enhancement of accuracy and efficiency in clinical tasks, improvement in adherence to guidelines, facilitation of reflective practice and provision of tailored feedback for continuous quality improvement. Common features were educational resources (n = 7) and assisting the user to assess current practices against standards/recommendations (n = 6), which supported professionals in achieving better clinical outcomes, increased professional satisfaction and streamlined workflow in various settings. Studies reported facilitators to tool usage including relevance to practice, accessibility and facilitating multidisciplinary action, making these tools practical and time-efficient for healthcare. However, barriers such as being time consuming, irrelevant to practice, difficult to use and lack of organisational engagement were reported. Almost all tools were co-developed with stakeholders. The co-design approaches varied, reflecting different levels of stakeholder engagement and adoption of co-design methodologies. It is noted that the quality of included studies was low. CONCLUSIONS: These findings offer valuable insights for future development of quality improvement website-based tools in healthcare. Recommendations include ensuring tools are co-developed with healthcare professionals, focusing on practical usability and addressing common barriers to enhance engagement and effectiveness in improving healthcare quality. Randomised controlled trials are warranted to provide objective evidence of tool efficacy. FUNDING: This work was supported by the Prevention Research Support Program, funded by the New South Wales Ministry of Health, Australia. REGISTRATION: This review was registered with PROSPERO, no. CRD42023451346.

Web-based prognostic tools for oral tongue cancer: An analysis of online predictors.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) often presents with aggressive clinical behaviour that may require multimodality treatment based on reliable prognostication. We aimed to evaluate the prognostic ability of five online web-based tools to predict the clinical behaviour of OTSCC resection and biopsy samples. METHODS: A total of 135 OTSCC resection cases and 33 OTSCC biopsies were included to predict recurrence and survival. Area under the receiver operating characteristic curves (AUC), χ2 tests, and calibration plots constructed to estimate the prognostic power of each tool. RESULTS: The tool entitled 'Prediction of risk of Locoregional Recurrences in Early OTSCC' presented an accuracy of 82%. The tool, 'Head & Neck Cancer Outcome Calculator' for 10-year cancer-related mortality had an accuracy 77% and AUC 0.858. The other tool entitled 'Cancer Survival Rates' for 5-year mortality showed an accuracy of 74% and AUC of 0.723. For biopsy samples, 'Cancer Survival Prediction Calculators' predicted the recurrence free survival with an accuracy of 70%. CONCLUSIONS: Web-based tools can aid in clinical decision making of OTSCC. Three of five online web-based tools could predict recurrence risk and cancer-related mortality in resected OTSCC and one tool could help in clinical decision making for biopsy samples.

The synergistic impact of incentive and regulatory environmental policies on firms' environmental performance.

The imperative to enhance corporate environmental performance is not only pivotal for a company's growth but also crucial for fulfilling societal responsibilities and protecting global environmental interests. Recognizing the inadequacies of standalone environmental policies, our study delves into the synergistic effects of incentive-based and regulatory approaches on the environmental performance of listed firms in China. We meticulously examine the interplay between environmental punishment and subsidies over the period of 2015-2019. Our analysis reveals that a strategic combination of punishment and subsidies can substantially improve firms' environmental performance. This effect intensifies with the increasing amounts of fines and subsidies. Additionally, we explore the dynamic effects of policy implementation. Our results indicate that subsidies implemented either a year before or after the imposition of punishment might diminish the effectiveness of standalone environmental penalty policies. Furthermore, our findings suggest that diverse regulatory policies enhance firm environmental performance by promoting investments in environmental protection and fostering green innovation. This discovery highlights the need for a nuanced understanding of policy mixes and their implications for corporate environmental strategies.

Health literacy in medical imaging: a scoping review of current evidence and future directions.

OBJECTIVE: The importance of health literacy in medical imaging is well recognized, yet the current landscape remains inadequately understood. This study aims to explore the extent of health literacy studies contextualized to medical imaging. STUDY DESIGN: Scoping review. METHODS: A scoping review was conducted using three online bibliographic databases namely, PubMed, ScienceDirect, and CINAHL. We have adopted the concept of health literacy, as a clinical risk and personal asset, to guide this review. RESULTS: Of 311 unique articles, 39 met our selection criteria. Five themes (categories) were identified by the authors: appropriate communication with patients who receive medical imaging test results, appropriate usage of medical imaging, classes and characteristics of eHealth literacy, disease/deterioration prevention, and patient education. Additionally, 17 health literacy assessment tools were identified, including 11 original creations. Finally, 11 recommendations have emerged from this scoping review, offering valuable insights into methods, considerations, and strategies for promoting health literacy. CONCLUSIONS: Health literacy studies in medical imaging cover both clinical and public health perspectives, benefiting diverse populations, regardless of underlying medical conditions. Notably, the majority of assessment tools used in these studies were author-generated, hindering cross-study comparisons. Given the innate capacity of medical images to convey intuitive information, those images do not solely benefit the patients who are given medical imaging examinations, but they also hold significant potential to enhance public health literacy. Health literacy and medical imaging are closely associated and mutually reinforce each other.

Acceptability of data linkage to identify women at risk of postnatal complication for the development of digital risk prediction tools and interventions to better optimise postnatal care, a qualitative descriptive study design.

BACKGROUND: Pregnancy acts as a cardiovascular stress test. Although many complications resolve following birth, women with hypertensive disorder of pregnancy have an increased risk of developing cardiovascular disease (CVD) long-term. Monitoring postnatal health can reduce this risk but requires better methods to identity high-risk women for timely interventions. METHODS: Employing a qualitative descriptive study design, focus groups and/or interviews were conducted, separately engaging public contributors and clinical professionals. Diverse participants were recruited through social media convenience sampling. Semi-structured, facilitator-led discussions explored perspectives of current postnatal assessment and attitudes towards linking patient electronic healthcare data to develop digital tools for identifying postpartum women at risk of CVD. Participant perspectives were gathered using post-it notes or a facilitator scribe and analysed thematically. RESULTS: From 27 public and seven clinical contributors, five themes regarding postnatal check expectations versus reality were developed, including 'limited resources', 'low maternal health priority', 'lack of knowledge', 'ineffective systems' and 'new mum syndrome'. Despite some concerns, all supported data linkage to identify women postnatally, targeting intervention to those at greater risk of CVD. Participants outlined potential benefits of digitalisation and risk prediction, highlighting design and communication needs for diverse communities. CONCLUSIONS: Current health system constraints in England contribute to suboptimal postnatal care. Integrating data linkage and improving education on data and digital tools for maternal healthcare shows promise for enhanced monitoring and improved future health. Recognised for streamlining processes and risk prediction, digital tools may enable more person-centred care plans, addressing the gaps in current postnatal care practice.

CogWatch: An open-source platform to monitor physiological indicators for cognitive workload and stress.

Cognitive workload is a measure of the mental resources a user is dedicating to a given task. Low cognitive workload produces boredom and decreased vigilance, which can lead to an increase in response time. Under high cognitive workload the information processing burden of the user increases significantly, thereby compromising the ability to effectively monitor their environment for unexpected stimuli or respond to emergencies. In cognitive workload and stress monitoring research, sensors are used to measure applicable physiological indicators to infer the state of user. For example, electrocardiography or photoplethysmography are often used to track both the rate at which the heart beats and variability between the individual heart beats. Photoplethysmography and chest straps are also used in studies to track fluctuations in breathing rate. The Galvanic Skin Response is a change in sweat rate (especially on the palms and wrists) and is typically measured by tracking how the resistance of two probes at a fixed distance on the subject's skin changes over time. Finally, fluctuations in Skin Temperature are typically tracked with thermocouples or infrared light (IR) measuring systems in these experiments. While consumer options such a smartwatches for health tracking often have the integrated ability to perform photoplethysmography, they typically perform significant processing on the data which is not transparent to the user and often have a granularity of data that is far too low to be useful for research purposes. It is possible to purchase sensor boards that can be added to Arduino systems, however, these systems generally are very large and obtrusive. Additionally, at the high end of the spectrum there are medical tools used to track these physiological signals, but they are often very expensive and require specific software to be licensed for communication. In this paper, an open-source solution to create a physiological tracker with a wristwatch form factor is presented and validated, using conventional off-the-shelf components. The proposed tool is intended to be applied as a cost-effective solution for research and educational settings.

ChlorTox scale assessment, greenness, and whiteness evaluation of selective spectrophotometric analysis of dimenhydrinate and cinnarizine.

Nausea and vomiting are considered common series side effects induced by chemotherapy treatment in cancer patients. This annoying side effect can impair the patient's compliance to cancer treatment and affect their quality of life. Dimenhydrinate and cinnarizine in combined pharmaceutical dosage form is used to control chemotherapy induced nausea and vomiting in cancer patients. For safety, selective spectrophotometric methods based on novel dual resolution strategies were introduced to estimate dimenhydrinate and cinnarizine in presence of their harmful impurities namely benzophenone and 1- (diphenylmethyl)piperazine, respectively. These methods namely, dual ratio difference (DRD), dual ratio extraction (DRE) and dual absorbance extraction coupled with dual ratio extraction (DAE-DRE) were successfully performed to simultaneously analyze the drug of interests dimenhydrinate and cinnarizine in their pure form, synthetic mixtures and in market dosage form. Linearity ranges were 6.0-60.0 µg/mL and 3.0-30.0 µg/mL for dimenhydrinate and cinnarizine, respectively with good recovery% of Mean ± SD for all the proposed methods 99.82 ± 0.48, 99.79 ± 0.40, 100.14 ± 0.82, 100.03 ± 0.69, respectively. ICH guidelines were adhered in accordance with confirming validation of the proposed methods where fulfilling results were accomplished. Various unified greenness and whiteness assessment tools, such as the chlorTox scale, greenness index via spider chart, AGREE (The Analytical Greenness Metric), green certificate, and the RGB12 algorithm were employed in this research to assess the greenness and sustainability of the introduced UV-spectrophotometric methods in comparison to the reported HPLC method. As a result, these methods hold significant potential for utilization in the quality control department of pharmaceutical companies, contributing to enhanced pharmaceutical product analysis and overall sustainability practices.

EHR-Driven Delivery of EPA Assessments Significantly Improves Participation.

INTRODUCTION: Digital education tools are a cornerstone in the evolution to CBME through EPAs. Successful implementation requires understanding the variable impacts of EHR-driven delivery of EPAs, flexible digital device access to EPAs, and user-behavior trends. METHODS: Through a HIPAA compliant, flexible-device accessible, surgical education platform, general surgery training programs at 21 institutions collected EPA from July 2023 to April 2024. At 5 EHR-integrated institutions (EHR+), EPA were created for clinical activities based on the OR schedule, automatically pushed to attendings and residents with built in completion reminders. At 16 institutions without EHR integration (EHR-), EPA were initiated manually. To improve user experience, care phases were bundled (cEPA). We compared the EHR+ and EHR- groups, computing descriptive statistics on the cEPAs completed and user behavior metrics. RESULTS: We collected 4187 cEPAs in total, with 82% at EHR+ institutions and 18% at EHR- institutions. Platform triggering dramatically drove cEPA completion for both faculty and residents, 88% and 81%, respectively. Only 3% were initiated by the faculty or resident. Faculty at EHR+ institutions strongly preferred the automated OR-triggered workflow to start their EPAs (Chi-squared test, p ≈ 0). Faculty completed all 3 care phases nearly 80% of the time. Time reminders specifically drive EPA completion for residents and faculty on weekdays and build habits on weekends. 71% of cEPAs completed were by computer, and 29% by phone. More comments were provided when computers were used. Residents reviewed feedback with a median lag of 1 hour and 29 min after results were available. CONCLUSIONS: EHR-driven delivery of EPA leads to a 4.6-fold increase in EPAs completed. EPA initiation is the most critical phase in the workflow and EHR-data driven alerts drive this action. These alerts are also effective drivers of habit formation. Flexible device access is important to increase EPAs completed and improve the usefulness through comments for residents.

From the Intensive Care Unit to Recovery: Managing Post-intensive Care Syndrome in Critically Ill Patients.

Post-intensive care syndrome (PICS) is the term used to describe the decline in the physical, cognitive, and/or mental condition of individuals who have been discharged from the intensive care unit (ICU). This complication could result in a significant reduction in quality of life, with some patients experiencing symptoms of prolonged weakness, depression, anxiety, and post-traumatic stress disorder (PTSD). Intensive care advancement over the years has resulted in an increase in ICU survival rates and a proportional increase in PICS, creating a need for more in-depth research into the prevention and management of the disease. Hence, this study aims to examine the present body of literature on PICS, encompassing its underlying physiological processes and elements that contribute to its development, methods for evaluating and diagnosing the condition, current treatment choices as well as potential new approaches, and the constraints in managing PICS and the necessity for further investigation. In this article, studies were compiled from several databases, including, but not limited to, Google Scholar, PubMed, and Cochrane Library. These studies were reviewed, and their data were used to highlight important aspects regarding the efficacy of current PICS screening tools, the optimization and limitations of both pharmacologic and non-pharmacologic treatment methods, and the feasibility and safety of emerging treatments and technologies. The major conclusions of this review were centered around the need for multidisciplinary management of PICS. From pharmacological management using analgesia to non-pharmacological management using early mobilization and exercise therapy, the effective treatment of PICS requires a multifaceted approach. Patient follow-up and its importance were touched upon, including strategies and policies to bolster proper follow-up, thereby increasing favorable outcomes. Lastly, the importance of family involvement and the increased need for research into this topic were highlighted.

DigiTRAC: Qualitative insights from knowledge users to inform the development of a Digital Toolkit for enhancing resilience among multiple sclerosis caregivers.

BACKGROUND: Resilience-promoting resources are critically needed to support positive caregiving experiences for multiple sclerosis (MS) caregivers. A digital toolkit offers a flexible way to access and use evidence-based resources that align with MS caregivers' interests and needs over time. OBJECTIVE: We explored the perspectives of key knowledge users regarding content areas, features, and other considerations to inform an MS caregiver resilience digital toolkit. METHODS: Twenty-two individuals completed a demographic survey as part of this study: 11 MS family caregivers, 7 representatives of organizations providing support services for people with MS and/or caregivers, and 4 clinicians. We conducted nine semi-structured individual interviews and two focus groups. Data were analyzed using content analysis. RESULTS: Participants recommended that a digital toolkit should include content focused on promoting MS caregivers' understanding of the disease, its trajectory and available management options, and enhancing caregiving skills and caregivers' ability to initiate and maintain behaviours to promote their own well-being. Features that allow for tracking and documenting care recipients' and caregivers' experiences, customization of engagement, and connectivity with other sources of support were also recommended. Participants suggested a digital toolkit should be delivered through an app with web browser capabilities accessible on smartphones, tablets, or laptops. They also acknowledged the need to consider how users' previous technology experiences and issues related to accessibility, usability, privacy and security could influence toolkit usage. CONCLUSION: These findings will guide future toolkit development and evaluation. More broadly, this study joins the chorus of voices calling for critical attention to the well-being of MS family caregivers.

Measuring the adoption of internet and communication technologies among practitioners in routine disability services: a stepped inclusive approach.

PURPOSE: Existing measurements of the use of information and communication technologies (ICTs) among practitioners in disability services often treat ICT adoption as a monolithic concept, overlooking its multifaceted nature within the disability field. This study introduces a stepped, inclusive approach to capturing this complexity, elucidating disparities in the utilization of various ICT dimensions, the present vs. anticipated use, and variations among different clinical-demographic groups. MATERIALS AND METHODS: A cross-sectional survey was conducted in Hong Kong, gathering valid data from 324 practitioners spanning diverse disciplines and disability services. RESULTS: Data analysis produced a three-factor model categorizing ICT tools into (1) information and communication tools, (2) screening and monitoring tools, and (3) treatment and rehabilitation tools. The first category was identified as the predominant ICT utilized currently, with significant projected growth in the latter two categories' usage. Variances in current ICT adoption were influenced by practitioners' roles, clientele, positions, affiliating agencies, and educational attainments. CONCLUSIONS: This research provides a deeper understanding of the key dimensions of ICT adoption within disability services. It underscores the importance of devising specific and customized strategies for the effective integration of ICTs, ensuring a more tailored approach to meeting the unique demands of the disability field.

Future studies focusing on information and communication technologies (ICTs) adoption or relevant concepts, such as e-health and telerehabilitation may consider employing similar methodological approaches accustomed to one's local context.Future attention and investment in ICT adoption in disability services should focus more on domains directly relevant to clinical and rehabilitation practice, tailoring strategies to the specific needs of the field.There exists an urgent imperative to enhance ICT training, especially for psychosocial and medical professionals, while also increasing investments in non-governmental organizations.Such support needs to be gender- and age-inclusive, ensuring it meets the diverse needs of practitioners at all organizational levels.

A Transdiagnostic, Hierarchical Taxonomy of Psychopathology Following Traumatic Brain Injury (HiTOP-TBI).

Psychopathology, including depression, anxiety, and post-traumatic stress, is a significant yet inadequately addressed feature of moderate-severe traumatic brain injury (TBI). Progress in understanding and treating post-TBI psychopathology may be hindered by limitations associated with conventional diagnostic approaches, specifically the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). The Hierarchical Taxonomy of Psychopathology (HiTOP) offers a promising, transdiagnostic alternative to psychiatric classification that may more effectively capture the experiences of individuals with TBI. However, HiTOP lacks validation in the TBI population. To address this gap, we administered a comprehensive questionnaire battery, including 56 scales assessing homogeneous symptom components and maladaptive traits within HiTOP, to 410 individuals with moderate-severe TBI. We evaluated the reliability and unidimensionality of each scale and revised those with psychometric problems. Using a top-down, exploratory latent variable approach (bass-ackwards modeling), we subsequently constructed a hierarchical model of psychopathological dimensions tailored to TBI. The results showed that, relative to norms, participants with moderate-severe TBI experienced greater problems in the established HiTOP internalizing and detachment spectra, but fewer problems with thought disorder and antagonism. Fourteen of the 56 scales demonstrated psychometric problems, which often appeared reflective of the TBI experience and associated disability. The Hierarchical Taxonomy of Psychopathology Following Traumatic Brain Injury (HiTOP-TBI) model encompassed broad internalizing and externalizing spectra, splitting into seven narrower dimensions: Detachment, Dysregulated Negative Emotionality, Somatic Symptoms, Compensatory and Phobic Reactions, Self-Harm and Psychoticism, Rigid Constraint, and Harmful Substance Use. This study presents the most comprehensive empirical classification of psychopathology after TBI to date. It introduces a novel, TBI-specific transdiagnostic questionnaire battery and model, which addresses the limitations of conventional DSM and ICD diagnoses. The empirical structure of psychopathology after TBI largely aligned with the established HiTOP model (e.g., a detachment spectrum). However, these constructs need to be interpreted in relation to the unique experiences associated with TBI (e.g., considering the injury's impact on the person's social functioning). By overcoming limitations of conventional diagnostic approaches, the HiTOP-TBI model has the potential to accelerate our understanding of the causes, correlates, consequences, and treatment of psychopathology after TBI.

Geospatial insights into Alphonso mango cultivation: a comprehensive land suitability study in the coastal belt of Maharashtra, India.

Land suitability assessment is integral to the advancement of precision agriculture. This inquiry is focused on identifying optimal regions for cultivating Alphonso mango in the coastal belt of Maharashtra, spanning across Palghar, Raigad, Thane, Ratnagiri, and Sindhudurg districts. Employing a GIS-based Analytic Hierarchy Process (AHP) methodology, 10 crucial parameters have been considered, encompassing climatic, physical, and chemical soil characteristics: cation exchange capacity, organic carbon, slope, rainfall, soil pH, soil texture, mean annual soil temperature, base saturation, soil drainage, and soil depth. Weights are assigned to these parameters based on expert opinions and existing literature to determine their significance in developing a soil suitability map. The study reveals distinct land suitability zones for Alphonso mango cultivation. The land suitability map designates 25.78% of the study area as highly suitable, while 9.18% is considered unsuitable for Alphonso mango cultivation. To validate the study, the Receiver Operating Characteristic (ROC) curve has been employed, indicating an 83% approval rate for the reliability and performance of the soil suitability. The results categorise soil suitability classes, providing valuable insights for farmers and agricultural planners to make informed decisions regarding Alphonso mango cultivation in similar geoenvironmental regions.

Modulating metabolism through synthetic biology: Opportunities for two-stage fermentation.

Bio-based production of fuels, chemicals and materials is needed to replace current fossil fuel based production. However, bio-based production processes are very costly, so the process needs to be as efficient as possible. Developments in synthetic biology tools has made it possible to dynamically modulate cellular metabolism during a fermentation. This can be used towards two-stage fermentations, where the process is separated into a growth and a production phase, leading to more efficient feedstock utilization and thus potentially lower costs. This article reviews the current status and some recent results in application of synthetic biology tools towards two-stage fermentations, and compares this approach to pre-existing ones, such as nutrient limitation and addition of toxins/inhibitors.

A gold standard dataset and evaluation of methods for lineage abundance estimation from wastewater.

During the SARS-CoV-2 pandemic, genome-based wastewater surveillance sequencing has been a powerful tool for public health to monitor circulating and emerging viral variants. As a medium, wastewater is very complex because of its mixed matrix nature, which makes the deconvolution of wastewater samples more difficult. Here we introduce a gold standard dataset constructed from synthetic viral control mixtures of known composition, spiked into a wastewater RNA matrix and sequenced on the Oxford Nanopore Technologies platform. We compare the performance of eight of the most commonly used deconvolution tools in identifying SARS-CoV-2 variants present in these mixtures. The software evaluated was primarily chosen for its relevance to the CDC wastewater surveillance reporting protocol, which until recently employed a pipeline that incorporates results from four deconvolution methods: Freyja, kallisto, Kraken 2/Bracken, and LCS. We also tested Lollipop, a deconvolution method used by the Swiss SARS-CoV-2 Sequencing Consortium, and three additional methods not used in the C-WAP pipeline: lineagespot, Alcov, and VaQuERo. We found that the commonly used software Freyja outperformed the other CDC pipeline tools in correct identification of lineages present in the control mixtures, and that the VaQuERo method was similarly accurate, with minor differences in the ability of the two methods to avoid false negatives and suppress false positives. Our results also provide insight into the effect of the tiling primer scheme and wastewater RNA extract matrix on viral sequencing and data deconvolution outcomes.

Twenty years of herpes simplex virus type 2 (HSV-2) research in low-income and middle-income countries: systematic evaluation of progress made in addressing WHO prioritiesfor research in HSV-2 epidemiology and diagnostics.

INTRODUCTION: Low-income and middle-income countries (LMICs) have a high burden of herpes simplex virus type 2 (HSV-2) infection, which has been strongly associated with HIV. In 2001, the WHO hosted a workshop to set research priorities for HSV-2 in LMICs. Periodic re-evaluation of research priorities is essential to ensure effective allocation of resources. This study describes the progress made between 2000 and 2020 in addressing the priorities identified in two of the five thematic areas that were the workshop's focus: HSV-2 epidemiology and diagnostics. The remaining areas are addressed in a companion paper. METHODS: A systematic search of MEDLINE, CINAHL, Global Health and Cochrane databases was carried out. Relevant primary and secondary research studies conducted in LMICs, written in English and published from 2000-2020 were included. Two independent researchers screened, identified papers and extracted preidentified variables from study texts. Data were organised into an Excel spreadsheet and analysed using IBM SPSS V.26. RESULTS: Overall, 4445 discrete papers were identified, of which 165 publications were eligible for inclusion. The highest general population HSV-2 prevalence was reported in South and West Africa. Prevalence was higher among women than men and increased with age. HSV-2 prevalence studies among key populations were few, and the majority were in East and South Asia. Cohort studies of HSV-2 incidence among younger populations (mean age=25 years) and HSV-2 infection prevalence in North Africa and the Middle East were few. The most researched topic in HSV-2 diagnostics addressed serological techniques and direct molecular biology. Studies of point-of-care testing were also few. CONCLUSION: HSV-2 research identified in LMICs has mainly addressed the epidemiology and diagnostics priorities identified by the 2001 WHO workshop. Unaddressed priorities include point-of-care testing, antiviral resistance and exploration of HSV-2 epidemiology in neglected geographical settings and population subgroups.

Assessment of the utilization of real-time prescription benefits for patient cost savings within an outpatient setting.

Background: This study evaluates the impact of Real-Time Prescription Benefits (RTPB), a tool integrated into electronic health records (EHRs), on patient out-of-pocket costs in an academic institution. RTPB provides prescribers with alternative, less expensive medications based on insurance plans. The primary measure was cost-savings, defined as the difference between the out-of-pocket cost of the prescribed medication and its alternative. Methods: A retrospective analysis of prescriptions from outpatient clinics in a university-based health system was conducted between May 2020 and July 2021. Prescriptions were analyzed at the 2nd level of the Anatomical Therapeutic Chemical (ATC) classification system. Costs were standardized to a 30-day supply. Standardized cost and total cost per prescription, and overall savings for the top 20 medication classes at the 2nd ATC level were calculated. The overall impact of RTPB was estimated based on selecting the least expensive alternative suggested by RTPB. Results: The study found that RTPB information was provided for 22% of prescriptions, with suggested alternatives for 1.26%. Among prescriptions with an alternative selected, the standardized average cost saving was $38.83. The study realized $15,416 in patient total cost savings. If the least expensive RTPB-suggested alternative were chosen for all prescriptions, an estimated $276,386 could have been saved. Psychoanaleptic and psycholeptic medications were the most prescribed with an alternative, with most savings in specialty drugs like anthelmintic and immunostimulant medications. Conclusion: The study highlights the importance of RTPB in reducing patient costs. It reports patient cost-savings with RTPB in prescribing decisions. Future research could explore the impact of RTPB on medication adherence using pharmacy claims data.

Defining a screening tool for post-traumatic stress disorder in East Africa: a penalized regression approach.

Background: Scalable PTSD screening strategies must be brief, accurate and capable of administration by a non-specialized workforce. Methods: We used PTSD as determined by the structured clinical interview as our gold standard and considered predictors sets of (a) Posttraumatic Stress Checklist-5 (PCL-5), (b) Primary Care PTSD Screen for the DSM-5 (PC-PTSD) and, (c) PCL-5 and PC-PTSD questions to identify the optimal items for PTSD screening for public sector settings in Kenya. A logistic regression model using LASSO was fit by minimizing the average squared error in the validation data. Area under the receiver operating characteristic curve (AUROC) measured discrimination performance. Results: Penalized regression analysis suggested a screening tool that sums the Likert scale values of two PCL-5 questions-intrusive thoughts of the stressful experience (#1) and insomnia (#21). This had an AUROC of 0.85 (using hold-out test data) for predicting PTSD as evaluated by the MINI, which outperformed the PC-PTSD. The AUROC was similar in subgroups defined by age, sex, and number of categories of trauma experienced (all AUROCs>0.83) except those with no trauma history- AUROC was 0.78. Conclusion: In some East African settings, a 2-item PTSD screening tool may outperform longer screeners and is easily scaled by a non-specialist workforce.

Computer-aided design and implementation of efficient biosynthetic pathways to produce high added-value products derived from tyrosine in Escherichia coli.

Developing efficient bioprocesses requires selecting the best biosynthetic pathways, which can be challenging and time-consuming due to the vast amount of data available in databases and literature. The extension of the shikimate pathway for the biosynthesis of commercially attractive molecules often involves promiscuous enzymes or lacks well-established routes. To address these challenges, we developed a computational workflow integrating enumeration/retrosynthesis algorithms, a toolbox for pathway analysis, enzyme selection tools, and a gene discovery pipeline, supported by manual curation and literature review. Our focus has been on implementing biosynthetic pathways for tyrosine-derived compounds, specifically L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine, with significant applications in health and nutrition. We selected one pathway to produce L-DOPA and two different pathways for dopamine-one already described in the literature and a novel pathway. Our goal was either to identify the most suitable gene candidates for expression in Escherichia coli for the known pathways or to discover innovative pathways. Although not all implemented pathways resulted in the accumulation of target compounds, in our shake-flask experiments we achieved a maximum L-DOPA titer of 0.71 g/L and dopamine titers of 0.29 and 0.21 g/L for known and novel pathways, respectively. In the case of L-DOPA, we utilized, for the first time, a mutant version of tyrosinase from Ralstonia solanacearum. Production of dopamine via the known biosynthesis route was accomplished by coupling the L-DOPA pathway with the expression of DOPA decarboxylase from Pseudomonas putida, resulting in a unique biosynthetic pathway never reported in literature before. In the context of the novel pathway, dopamine was produced using tyramine as the intermediate compound. To achieve this, tyrosine was initially converted into tyramine by expressing TDC from Levilactobacillus brevis, which, in turn, was converted into dopamine through the action of the enzyme encoded by ppoMP from Mucuna pruriens. This marks the first time that an alternative biosynthetic pathway for dopamine has been validated in microbes. These findings underscore the effectiveness of our computational workflow in facilitating pathway enumeration and selection, offering the potential to uncover novel biosynthetic routes, thus paving the way for other target compounds of biotechnological interest.