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"Sheikh, Fatima"
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Fabrication and Evaluation of Voriconazole Loaded Transethosomal Gel for Enhanced Antifungal and Antileishmanial Activity
Voriconazole (VRC) is a broad-spectrum antifungal agent belonging to BCS class II (biopharmaceutical classification system). Despite many efforts to enhance its solubility, this primary issue still remains challenging for formulation scientists. Transethosomes (TELs) are one of the potential innovative nano-carriers for improving the solubility and permeation of poorly soluble and permeable drugs. We herein report voriconazole-loaded transethosomes (VRCT) fabricated by the cold method and followed by their incorporation into carbopol 940 as a gel. The prepared VRCT were evaluated for % yield, % entrapment efficiency (EE), surface morphology, possible chemical interaction, particle size, zeta potential, and polydispersity index (PDI). The optimized formulation had a particle size of 228.2 nm, a zeta potential of −26.5 mV, and a PDI of 0.45 with enhanced % EE. Rheology, spreadability, extrudability, in vitro release, skin permeation, molecular docking, antifungal, and antileishmanial activity were also assessed for VRCT and VRC loaded transethosomal gel (VTEG). Ex-vivo permeation using rat skin depicted a transdermal flux of 22.8 µg/cm2/h with enhanced efficiency up to 4-fold. A two-fold reduction in inhibitory as well as fungicidal concentration was observed against various fungal strains by VRCT and VTEG besides similar results against L-donovani. The development of transethosomal formulation can serve as an efficient drug delivery system through a topical route with enhanced efficacy and better patient compliance.
Journal Article
Factors associated with access to post-sepsis care: a scoping review protocol
IntroductionThe objective of this scoping review is to identify and describe factors that affect access to post-sepsis care. Considering the burden faced by sepsis survivors, it is important to understand the facilitators and barriers to accessing post-sepsis care to facilitate the design and implementation of patient-centred and equitable pathways to care.Methods and analysisThis scoping review will include studies that consider individuals who have experienced sepsis and any factors that may affect access to care, including comorbidities, discharge setting and social determinants of health. A comprehensive search of MEDLINE, Embase, Emcare, HealthSTAR and Scopus will be conducted. The extracted data will be summarised and presented thematically.Ethics and disseminationApproval from a research ethics board is not required for this review as it is a synthesis of information from studies where the primary investigators have already received approval from their respective ethics boards. Once complete, the review will be submitted for publication in a peer-reviewed journal, and the findings will be shared to local and national forums.Trial registration detailsThis review has been uploaded and registered under Open Science Framework. https://doi.org/10.17605/OSF.IO/JMFW2
Journal Article
The prognostic utility of protein C as a biomarker for adult sepsis: a systematic review and meta-analysis
Background
Sepsis, the dysregulated host response to infection, triggers abnormal pro-coagulant and pro-inflammatory host responses. Limitations in early disease intervention highlight the need for effective diagnostic and prognostic biomarkers. Protein C’s role as an anticoagulant and anti-inflammatory molecule makes it an appealing target for sepsis biomarker studies. This meta-analysis aims to assess the diagnostic and prognostic value of protein C (PC) as a biomarker for adult sepsis.
Methods
We searched MEDLINE, PubMed, EMBASE, CINAHL and Cochrane Library from database inception to September 12, 2021. We included prospective observational studies of (1) adult patients (> 17) with sepsis or suspicion of sepsis that; (2) measured PC levels with 24 h of study admission with; and (3) the goal of examining PC as a diagnostic or prognostic biomarker. Two authors screened articles and conducted risk of bias (RoB) assessment, using the Quality in Prognosis Studies (QUIPS) and the Quality Assessment in Diagnostic Studies-2 (QUADAS-2) tools. If sufficient data were available, meta-analysis was conducted to estimate the standardized mean difference (SMD) between patient populations.
Results
Twelve studies were included, and 8 were synthesized for meta-analysis. Pooled analysis demonstrated moderate certainty of evidence that PC levels were less reduced in sepsis survivors compared to non-survivors (6 studies, 741 patients, SMD = 0.52, 95% CI 0.24–0.81,
p
= 0.0003,
I
2
= 55%), and low certainty of evidence that PC levels were less reduced in septic patients without disseminated intravascular coagulation (DIC) compared to those with DIC (3 studies, 644 patients, SMD = 0.97, 95% CI 0.62–1.32,
p
< 0.00001, I
2
= 67%). PC could not be evaluated as a diagnostic tool due to heterogeneous control populations between studies.
Conclusion and relevance
Our review demonstrates that PC levels were significantly higher in sepsis survivors compared to non-survivors and patients with sepsis but not disseminated intravascular coagulation (DIC). Our evaluation is limited by high RoB in included studies and poor reporting of the sensitivity and specificity of PC as a sepsis biomarker. Future studies are needed to determine the sensitivity and specificity of PC to identify its clinical significance as a biomarker for early sepsis recognition.
Trial Registration
PROSPERO registration number: CRD42021229786. The study protocol was published in BMJ Open.
Journal Article
Evaluating N95 respirator designs: A mixed-methods pilot and feasibility study
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a global impact, underscoring the importance of personal protective equipment (PPE). Use of N95s reduces the risk of airborne infection; however, in the absence of equitable designs, health care workers (HCWs) who do not fit the average White male head and face are at an increased risk of airborne infectious diseases.
Primary: Feasibility of a mixed-method study, with a sample size of 100, 50% of participants self-identifying as non-White and having at least one characteristic of interest. Secondary: (1) Generate quantitative evidence on N95 fit using a PortaCount fit test, (2) describe participant-reported feelings on fit and breathability, and (3) evaluate the impacts of the pandemic on a HCW's physical and mental well-being.
This was a mixed-method prospective pilot and feasibility study. Quantitative fit was assessed using a TSI PortaCount test and measurements of bizygomatic breadth and Menton-Sellion length. A survey was administered to collect sociodemographic information, HCWs' assessment of N95 fit, comfort, and the impact of PPE-related challenges on well-being.
This study was limited by a small sample size, as COVID-19 pandemic restrictions prevented adequate recruitment to detect differences between groups. We describe key findings that should inform analyses of the impact of gender and ethnicity on N95 respirator fit. Following a study amendment to increase eligible sites, 37 of the 41 (90.2%) approached HCWs consented to participate. Compared to other HCWs, non-White females had the lowest mean fit factor. Differences in Menton-Sellion length and bizygomatic breadth were observed between males, females, and White and non-White HCWs. Most HCWs reported physical discomfort and negative impacts on their psychological well-being.
We identified gender and ethnicity as key factors in the fit of N95s. Differences in gender, ethnicity, and anthropometric measures must be considered in respirator designs.
Journal Article
Impacts of patient advisory councils on recovery for sepsis survivors: a case study
Sepsis is a life-threatening condition with significant long-term impacts for survivors and their families. The known benefits of patient engagement have led to increased efforts globally to involve survivors in sepsis research. This study aimed to characterize the experiences of sepsis survivors and their families in patient advisory councils (PACs) for two Canadian sepsis research networks (Action on Sepsis and Sepsis Canada) and explore how PAC involvement supports long-term recovery.
This mixed-methods cross-sectional study consisted of a structured survey, ten interviews, and one focus group discussion. All current members of the Sepsis Canada and Action on Sepsis PACs (n = 29) were invited to participate. The results of the survey were analyzed descriptively and used to inform the development of the semi-structured interview guide. Qualitative data were analyzed using a thematic approach.
Overall, 16 PAC members participated. The majority of participants were women and over 40 years old. Survey scores showed that most participants felt meaningfully engaged, while the qualitative findings highlighted how PACs supported recovery and fostered community connections between survivors, families, and researchers. Major themes included sepsis experience, recovery journey, characteristics of PACs, characteristics of PAC participation, and impacts of PAC involvement.
Our findings demonstrate that PACs provide critical benefits that extend beyond feeling valued or appreciated for contributing to a specific project. These findings highlight the value of patient-oriented research in shaping evidence-based practices and policies and emphasize the need for trauma-informed approaches and improved post-sepsis care pathways to enhance recovery outcomes.
Journal Article
Social determinants of health associated with the development of sepsis in adults: a scoping review protocol
IntroductionSepsis, the life-threatening immune response to infection, affects millions of people annually. Understanding of the factors associated with the development of sepsis is crucial for improving population health and public health efforts; in particular, literature exploring the relationship between sepsis and social determinants of health is lacking. This review seeks to establish and amalgamate existing evidence of the relationships between sepsis and the following social determinants: frailty, registration with a family physician, mental illness, alcohol abuse, social support levels, smoking status, illicit drug use disorders, socioeconomic status, gender and race/ethnicity.Methods and analysisThis study will analyse qualitative and quantitative studies using standard processes. The selected social determinants of health and their potential link to adult sepsis will be analysed separately under distinct headings. Findings will be consolidated in a final discussion. PubMed and Medline will be searched for articles published between 1970 and 2020 using search strings combining ‘sepsis’ and other variations, such as ‘septicaemia’ with each social determinant of interest. ‘Sepsis’ and at least one social determinant of interest must be present in a study’s title for inclusion in the review; the results of the initial search will be filtered based on predetermined inclusion and exclusion criteria. Evidence from this scoping review will provide information on the impact of social determinants of health on the risk of developing adult sepsis, which can inform clinicians of the various risk factors to consider when admitting patients.Ethics and disseminationApproval from a research ethics board is not needed for this amalgamation of information from studies for which the primary investigators have obtained their own, respective ethics board approval. Once completed, the review will be submitted for publication in a peer-reviewed journal, and findings will be presented in local and national forums.
Journal Article
Diagnostic and prognostic accuracy of Protein C in adult patients with sepsis: protocol for a systematic review and meta-analysis
IntroductionSepsis is a dysregulated host response to infection characterised by activation of proinflammatory and procoagulant mechanisms. Protein C (PC)’s activity as an anticoagulant and antiinflammatory molecule makes it an appealing target for sepsis biomarker studies. To date, there has been no systematic review of PC as a sepsis biomarker.ObjectivesTo evaluate the diagnostic accuracy and prognostic strength of PC as a biomarker for adult sepsis.Methods and analysisMedline, Embase, Cochrane Library, PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be searched from inception through 20 January 2021 for prospective observational studies that evaluate the use of PC as a diagnostic or prognostic biomarker for adult sepsis. Title and abstract screening, full-text screening and data extraction will be conducted in duplicate. Risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies and Quality in Prognostic Studies tools. If sufficient data are available, a meta-analysis will be conducted. The standardised mean difference and 95% CI will be calculated for prognostic and diagnostic studies. If possible, a hierarchical summary receiver operator characteristic curve will be generated to assess overall prognostic and diagnostic biomarker accuracy. I2 statistics will be used to assess heterogeneity. Sensitivity analysis will be performed by removing studies with a high risk of bias and re-examining the meta-analysis results.Ethics and disseminationGiven this is a systematic review and meta-analysis, there is no requirement for ethics approval. Findings will be disseminated through a peer-reviewed publication and social media.PROSPERO registration numberCRD42021229786.
Journal Article
Internal Medicine Residents’ Views About Care Transitions: Results of an Educational Intervention
Problem:
Suboptimal care transitions can lead to re-hospitalizations.
Intervention:
We developed a 2-week “Transitions of Care Curriculum” to train first-year internal medicine residents to improve their knowledge and skills to deliver optimal transitional care. Our objective was to use reflective writing essays to evaluate the impact of the curriculum on the residents.
Methods:
The rotation included: Transition of Care Teaching modules, Transition Audit, Transitional Care Site Visits, and Transition of Care Conference. Residents performed the above elements of care transitions during the curriculum and wrote reflective essays about their experiences. These essays were analyzed to assess for the overall impact of the curriculum on the residents.
Qualitative analysis of reflective essays was used to evaluate the impact of the curriculum. Of the 20 residents who completed the rotation, 18 reflective essays were available for qualitative analysis.
Results:
Five major themes identified in the reflective essays for improvement were: discharge planning, patient-centered care, continuity of care, goals of care discussions, and patient safety. The most discussed theme was continuity of care, with following subthemes: fragmentation of the healthcare system, disjointed care to the patients, patient specific factors contributing to lack of continuity of care, lack of primary care provider role as a coordinator of care, and challenges during discharge process. Residents also identified system-based gaps and suggested solutions to overcome these gaps.
Conclusions:
This experiential learning and use of reflective writing enhanced the residents’ self-identified awareness of gaps in care transitions and prompted them to generate ideas for systems improvement and personal actions to improve their practice during care transitions.
Journal Article
Sepsis policy, guidelines and standards in Canada: a jurisdictional scoping review protocol
IntroductionTo our knowledge, this study is the first to identify and describe current sepsis policies, clinical practice guidelines, and health professional training standards in Canada to inform evidence-based policy recommendations.Methods and analysisThis study will be designed and reported according to the Arksey and O’Malley framework for scoping reviews and the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews. EMBASE, CINAHL, Medline, Turning Research Into Practice and Policy Commons will be searched for policies, clinical practice guidelines and health professional training standards published or updated in 2010 onwards, and related to the identification, management or reporting of sepsis in Canada. Additional sources of evidence will be identified by searching the websites of Canadian organisations responsible for regulating the training of healthcare professionals and reporting health outcomes. All potentially eligible sources of evidence will be reviewed for inclusion, followed by data extraction, independently and in duplicate. The included policies will be collated and summarised to inform future evidence-based sepsis policy recommendations.Ethics and disseminationThe proposed study does not require ethics approval. The results of the study will be submitted for publication in a peer-reviewed journal and presented at local, national and international forums.
Journal Article