Clinical impact of an individualised clinical pharmacy programme into the memory care pathway of older people: an observational study.

BACKGROUND: In older patients, medication exposure [i.e. polypharmacy, potentially inappropriate medications (PIMs), medications with anticholinergic and/or sedative properties] is a modifiable risk factor associated with cognitive iatrogenic risk and dementia. AIM: To assess the potential clinical impact of the implementation of an individualised clinical pharmacy programme at the initiation of the Memory care pathway in older patients with a cognitive complaint. METHOD: This prospective observational study included older patients with high-risk of adverse drug event (HR) admitted in a French geriatric university hospital to explore the cognitive complaint or the cognitive disorder between January and November 2021. Drug-related problems (DRPs) were identified during a medication review performed in HR patients, and pharmaceutical interventions (PIs) notified in the patient's hospitalisation report were collected. The clinical impact of PIs was assessed by an expert panel (geriatricians and clinical pharmacists) using the Clinical, Economic, and Organisational (CLEO) tool. RESULTS: Overall, 326 patients were eligible and 207 (63.5%) were considered as HR patients. Among HR patients, 88.9% (n = 184) were treated using at least 5 medications (polypharmacy), and 36.7% (n = 76) received at least one PIM with cognitive iatrogenic risk. During the medication review, 490 PIs were provided and their clinical impact was rated as minor for 57.3% (n = 281), moderate for 26.7% (n = 131), and major for 2.5% (n = 12). CONCLUSION: The integration of clinical pharmacist secured the Memory care pathway of older patients with a cognitive complaint by identifying an important number of DRPs and PIMs with potential cognitive iatrogenic risk.

Identifying core global mental health professional competencies: A multi-sectoral perspective.

Concerned with sustainably alleviating mental distress and promoting the right to health worldwide, global mental health (GMH) is practised across various contexts spanning the humanitarian-development-peace nexus. The inherently intersectoral and multidisciplinary nature of GMH calls for competency frameworks and training programmes that embody diversity, decolonisation and multiprofessionalism. Existing competency frameworks have failed to capture the multi-sectoral, inter-professional nature of contemporary GMH practice. In response to these needs, a qualitative content analysis of relevant job advertisements was conducted to distil a comprehensive set of professional competencies in contemporary GMH practice. Approximately 200 distinct skills and competencies were extracted from 70 job advertisements and organised into four meta-dimensions: 'skills', 'sector', 'self' and 'subject'. The first known systematic attempt at a multi-sectoral GMH competency framework, it offers a springboard for exploring vital yet overlooked professional competencies such as resilience, self-reflection, political skills and entrepreneurialism. On this basis, recommendations for building a competent, agile and effective GMH workforce with diversified and future-proof skillsets are proposed. The framework can also inform inter-professional training and curriculum design, and capacity-building initiatives aimed at early-career professional development, particularly in low- and middle-income settings.

Exploratory Assessment of Galectin-1, -3, and -9 in Non-Small Cell Lung Cancer.

Galectins play a pivotal role in lung cancer oncogenic pathways, influencing apoptosis, angiogenesis, and tumor metastasis. Biomarkers that diagnose, prognose, and guide cancer treatment are crucial, with galectins having the biomarker potential for non-small cell lung cancer (NSCLC). Using enzyme-linked immunosorbent assay (ELISA), we assessed serum galectin-1, -3, and -9 levels in NSCLC patients. A retrospective chart review was performed to examine patient demographics, cancer stage, tumor biology, cancer treatment, and patient outcomes. Galectin levels were then compared across these factors. In this exploratory analysis, galectin-3 levels were significantly lower in patients with squamous cell lung cancer (p = 0.0019) and in patients exposed to chemotherapy (p = 0.0375). Galectin-1 levels were significantly lower in patients with previous metastasis but had no correlation with future metastasis. Abnormal galectin-1 levels were significantly correlated with decreased overall survival (OS) in NSCLC (p = 0.0357) and specifically in patients with surgically resectable NSCLC (p = 0.0112). However, abnormal galectin-1 levels were not found to correlate with decreased OS in multivariable analysis (p = 0.0513). These findings may have clinical implications as galectin-3 inhibitors are in trials for NSCLC. Additionally, they suggest that galectin-1 has potential as a prognostic marker for surgically resectable NSCLC.

Cardiovascular Symptoms, Dysautonomia, and Quality of Life in Adult and Pediatric Patients with Hypermobile Ehlers-Danlos Syndrome: A Brief Review.

BACKGROUND: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder characterized by joint hypermobility and other systemic manifestations, such as cardiovascular symptoms, musculoskeletal pain, and joint instability. Cardiovascular symptoms, such as lightheadedness and palpitations, and types of dysautonomia, including postural orthostatic tachycardia syndrome (POTS), are frequently reported in adults with hEDS and have been shown to negatively impact quality of life (QoL). OBJECTIVE: This brief review will be an overview of co-occurring symptoms in POTS and hEDS to inform potential cardiovascular screening procedures. RESULTS: While many patients with hEDS report cardiovascular symptoms, few have structural abnormalities, suggesting that dysautonomia is likely responsible for these symptoms. One validated screening measure for dysautonomia symptom burden is the Composite Autonomic Symptom Scale (COMPASS-31). Studies have found that adults with POTS, hEDS, and both POTS and hEDS have higher COMPASS-31 scores than the general population, suggesting a high symptom burden due to dysautonomia, which leads to impaired QoL. CONCLUSION: While studies have examined cardiovascular symptoms and the impact of dysautonomia in adults with and without hEDS, there is scant literature on dysautonomia in pediatric patients with hEDS. Therefore, more studies on cardiovascular symptoms and dysautonomia, as they relate to the quality of life in pediatric patients with hEDS, are needed. This brief review summarizes the current literature on dysautonomia and cardiovascular symptoms in pediatric and adult populations with hEDS.

Pragmatic Expansion of a Neonatal Antibiotic Stewardship Program in a Community Health Care System.

BACKGROUND: Previously published neonatal antibiotic stewardship efforts have been primarily implemented in single centers. Piedmont Athens Regional began work to decrease antibiotic use in the NICU with spread to the newborn nursery (NBN) and, subsequently, 13 other NICUs and NBNs throughout a health care system over a 4-year period. METHODS: This quality improvement initiative was conducted in the context of a multicenter learning collaborative from 2016 to 2019. The primary aim was a 10% reduction in antibiotic days per 1000 patient days (antibiotic utilization rate [AUR]) among newborns in the NICU and NBN at each hospital by December 2018. Change ideas were implemented by using plan-do-study-act cycles. The primary outcome measure was AUR with a balancing measure of antibiotic restarts. RESULTS: Piedmont Athens Regional decreased the NICU AUR by 46% and NBN AUR by 83%. Piedmont Healthcare decreased the NICU AUR by 40% and NBN AUR by 74%. Seven of 8 NICUs and 5 of 7 NBNs achieved a >10% reduction in AUR and 8 of 8 intervention hospitals showed a sustained drop in AUR in the NBN, NICU, or both during the 1.5-year postobservation period. Decreases in antibiotic initiation resulted in 335 fewer antibiotic courses in the NICU and 189 fewer infants started on antibiotics in the NBN in 2020 versus 2017. CONCLUSIONS: This initiative achieved reductions in AUR across multiple hospitals in the network. The system-wide approach facilitated information technology (IT) and electronic health record modifications. Common drivers of NICU improvement were involvement for at least 2 years, multidisciplinary teams, and the highest baseline AUR. The common driver of nursery improvement was the implementation of a neonatal sepsis risk calculator.

Integrated clinical pharmacy activities into the pediatric kidney graft pathway / Activités de pharmacie clinique intégrées dans le parcours du patient de greffe rénale pédiatrique

The pediatric renal graft pathway is at risk of care discontinuation, even though therapeutic adherence is essential. The objective is to evaluate the integration of clinical pharmacy activities into this care pathway. This feasibility study is divided into three stages: structuring, implementing and evaluation. In pre-transplant, immediate and remote post-transplant, interviews were proposed as well as the pharmaceutical analysis of medication prescriptions. In 8 months duration, 32 patients were included. All patients included in pre-transplant and immediate post-transplant benefited from the activities. At M0, all the prescriptions analyzed resulted in at least one problem detected. Half of the transplanted patients benefited from M1 maintenance, one patient from M3 maintenance and no M6 follow-up could be carried out. This work concludes with the good feasibility and integration of clinical pharmacy activities within the care pathway.

Le parcours de greffe rénale pédiatrique est à risque de rupture de soins car les patients sont polymédiqués alors même que l'adhésion thérapeutique est essentielle. L'objectif est d'évaluer l'intégration d'activités de pharmacie clinique dans ce parcours de soins. Cette étude de faisabilité se décline en trois étapes : structuration, mise en œuvre et évaluation. En pré-greffe, post-greffe immédiate et post-greffe à distance, des entretiens ont été proposés ainsi que l'analyse pharmaceutique des prescriptions médicamenteuses. En huit mois, 32 patients ont été inclus. Tous les patients inclus en pré-greffe et en post-greffe immédiate ont bénéficié des activités. À M0, toutes les prescriptions analysées ont abouti à au moins un problème détecté. La moitié des patients greffés ont bénéficié de l'entretien à M1, un patient de l'entretien à M3 et aucun suivi à M6 n'a pu être réalisé. Ce travail conclut à la bonne faisabilité et intégration des activités de pharmacie clinique au sein du parcours de soins.

Research protocol of the Laval-ROSA Transilab: a living lab on transitions for people living with dementia.

BACKGROUND: The Laval-ROSA Transilab is a living lab that aims to support the Laval Integrated Health and Social Services Centres (Quebec, Canada) in consolidating the Quebec Alzheimer Plan. It aims to improve care transitions between different settings (Family Medicine Groups, home care, and community services) and as such improve the care of people living with dementia and their care partners. Four transition-oriented innovations are targeted. Two are already underway and will be co-evaluated: A) training of primary care professionals on dementia and interprofessional collaboration; B) early referral process to community services. Two will be co-developed and co-evaluated: C) developing a structured communication strategy around the dementia diagnosis disclosure; D) designation of a care navigator from the time of dementia diagnosis. The objectives are to: 1) co-develop a dashboard for monitoring transitions; 2) co-develop and 3) co-evaluate the four targeted innovations on transitions. In addition, we will 4) co-evaluate the impact and implementation process of the entire Laval-ROSA Transilab transformation, 5) support its sustainability, and 6) transfer it to other health organizations. METHODS: Multi-methods living lab approach based on the principles of a learning health system. Living labs are open innovation systems that integrate research co-creation and knowledge exchange in real-life settings. Learning health systems centers care improvement on developing the organization's capacity to learn from their practices. We will conduct two learning cycles (data to knowledge, knowledge to practice, and practice to data) and involve various partners. We will use multiple data sources, including health administrative databases, electronic health records data, surveys, semi-structured interviews, focus groups, and observations. DISCUSSION: Through its structuring actions, the Laval-ROSA Transilab will benefit people living with dementia, their care partners, and healthcare professionals. Its strategies will support sustainability and will thus allow for improvements throughout the care continuum so that people can receive the right services, at the right time, in the right place, and from the right staff.

"We Are All in This Together": Which Memorable Moral Messages Guided Student Responses to the COVID-19 Pandemic?

The COVID-19 pandemic has revealed lessons about the moral bases of student compliance with pandemic health messaging, which is a vital concern for educational institutions where students learn and live in close proximity. Existing theoretical and empirical work suggests that audiences may be receptive when prescribed behavior aligns with memorable moral messages (MMM) received from family members or other valued sources. We report the results of two studies that examined the nature of MMM that students found relevant in the fall of 2020 and the moral values they appeared to invoke. In the first, focus group interviews and qualitative thematic analysis were used to identify underlying moral themes. Findings indicated that students were influencegd by MMM focused on empathy/caring, those that addressed communal versus individual responsibilities, and messages that prioritized virtues that were needed (e.g., patience) during the pandemic. During this first phase of the research, we also collected a verbatim list of MMM that students reported recalling and using. To determine if quantitative evidence supported the three-part categorization scheme, a second study asked a sample of 327 students to rate the influence of the MMM reported in Study One. Exploratory factor analysis largely confirmed Study One, with consideration for others, self-determination, and communal responsibility emerging as primary moral considerations. Findings of the two studies are interpreted as partial support for moral foundations theory and consistent with the expectations of negotiated morality theory. Recommendations for health educators and experts are offered, including framing compliance guidelines in a manner consistent with MMM received from family members and helping students navigate the moral tension between self and communal interests.

Prognostic factors after acute mesenteric ischemia: which patients require specific management?

PURPOSE: Diagnosis and treatment of AMI are a real issue for implicating physicians. In the literature, only one AMI stroke center has reported its results so far, with increasing survival rates. Our aim was to analyze acute mesenteric ischemia (AMI) related mortality and predictive factors, in a single academic center, before creating a dedicated intestinal stroke center. METHODS: All the patients with an AMI, between January 2015 and December 2020, were retrospectively included. They were divided into 2 groups according to the early mortality: death during the first 30 days and alive. The 2 groups were compared. RESULTS: 173 patients (57% of men), were included, with a mean age of 68 ± 16 years. Overall mortality rate was 61%. Mortality occurred within the first 30 days in 78% of dead cases. Dead patients were significantly older, more frequently admitted from intensive care, with more serious clinical, laboratory and radiological characteristics. We have identified 3 protective factors - history of abdominal surgery (Odd Ratio = 0.1; 95%CI = 0.01-0.8, p = 0.03), medical management with curative anticoagulation (OR = 0.09; 95%CI = 0.02-0.5, p = 0.004) and/or antiplatelets (OR = 0.04; 95%CI = 0.006-0.3, p = 0.001)-, and 2 predictive factors of mortality - age > 70 years (OR = 7; 95%CI = 1.4-37, p = 0.02) and previous history of coronaropathy (OR = 13; 95%CI = 1.7-93, p = 0.01). CONCLUSIONS: AMI is a severe disease with high morbidity and mortality rates. Even if its diagnosis is still difficult because of non-specific presentation, its therapeutic management needs to be changed in order to improve survival rates, particularly in patients older than 70 years with history of coronaropathy. Developing a dedicated organization would improve the diagnosis and the management of patients with AMI.

Oncology Nurses Can Build Patient-Centered Outcomes Research Partnerships.

Nurses can inform and lead patient-centered outcomes research (PCOR) projects that address care-related questions prioritized by patients. However, PCOR projects may fail to materialize because time constraints create barrier.

Pattern Analysis of Serum Galectins-1, -3, and -9 in Breast Cancer.

Galectins have been shown to have roles in cancer progression via their contributions to angiogenesis, metastasis, cell division, and the evasion of immune destruction. This study analyzes galectin-1, -3, and -9 serum concentrations in breast cancer patients through enzyme-linked immunosorbent assay (ELISA) against the characteristics of the patient and the tumor such as stage, molecular subtype, and receptor expression. Galectin-9 was found to be statistically significantly increased in HER2-enriched tumors and reduced in patients with hormone-receptor-positive tumors. Galectin-1 was found to be statistically significantly increased in the serum of patients who had undergone hormonal, immunotherapy, or chemotherapy. These findings provide insight into the changes in galectin levels during the progress of cancer, the response to treatment, and the molecular phenotype. These findings are valuable in the further understanding of the relationships between galectin and tumor biology and can inform future research on therapeutic targets for galectin inhibitors and the utility of galectin biomarkers.

Comprehensive and User-Analytics-Friendly Cancer Patient Database for Physicians and Researchers.

Nuanced cancer patient care is needed, as the development and clinical course of cancer is multifactorial with influences from the general health status of the patient, germline and neoplastic mutations, co-morbidities, and environment. To effectively tailor an individualized treatment to each patient, such multifactorial data must be presented to providers in an easy-to-access and easy-to-analyze fashion. To address the need, a relational database has been developed integrating status of cancer-critical gene mutations, serum galectin profiles, serum and tumor glycomic profiles, with clinical, demographic, and lifestyle data points of individual cancer patients. The database, as a backend, provides physicians and researchers with a single, easily accessible repository of cancer profiling data to aid-in and enhance individualized treatment. Our interactive database allows care providers to amalgamate cohorts from these groups to find correlations between different data types with the possibility of finding "molecular signatures" based upon a combination of genetic mutations, galectin serum levels, glycan compositions, and patient clinical data and lifestyle choices. Our project provides a framework for an integrated, interactive, and growing database to analyze molecular and clinical patterns across cancer stages and subtypes and provides opportunities for increased diagnostic and prognostic power.

Regulators of male and female sexual development are critical for the transmission of a malaria parasite.

Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify genes essential for the formation of either male or female sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of ten mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in the determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain as well as the protein interactors of a female-determining zinc-finger protein indicate that germ-granule-like ribonucleoprotein complexes complement transcriptional processes in the regulation of both male and female development of a malaria parasite.

The Barriers and Facilitators to Decentralised Nurse-Led Mental Health Service Delivery in Sierra Leone.

In 2009, 98.0% of people with mental illness in Sierra Leone were not receiving treatment, partly due to the absence of public psychiatric facilities outside the capital. In response to this situation, the Ministry of Health and Sanitation rolled out nurse-led mental health units (MHUs) to every district. This study evaluates the barriers and facilitators to mental health service delivery in decentralised MHUs in Sierra Leone using key informant interviews and focus group discussions with 13 purposefully sampled clinical staff and senior management personnel. The interviews were audio-recorded, translated from Krio if necessary, transcribed, and analysed using manifest content analysis. The findings suggest that factors affecting nurse-led mental health service delivery include small workforce and high workload, culture and beliefs, risks, lack of safety measures and required resources, outdated policies, poor salaries, lack of funds for medication, distance, power, influence, and stigma. Factors that could facilitate nurse-led mental health services include: increasing motivation, increasing the workforce, knowledge sharing, mentorship, availability of medication, passion and modern psychiatry. The findings contribute towards understanding the challenges and opportunities faced by the recently established nurse-led decentralised mental health services across Sierra Leone, in order to address the large mental health treatment gap. We hope the findings will inform further policy and planning to improve the quality of decentralised mental healthcare.

The Effect of Preoperative Carbohydrate Intake on Length of Stay and Postoperative Recovery Following Laparoscopic Living Donor Nephrectomy.

OBJECTIVE: Enhanced Recovery After Surgery (ERAS) protocols are applied in many surgical procedures and often involve preoperative carbohydrate intake. Research surrounding the utility of ERAS in living donor nephrectomy is limited. The objective of this study was to identify whether living kidney donors who received preoperative oral carbohydrates experienced a difference in length of hospital stay (LOS), duration of time required to resume regular oral food and fluid intake, and incidence of gastrointestinal (GI) complications following laparoscopic nephrectomy compared to historical control donors who underwent preoperative fasting. METHODS: This study was a retrospective analysis of data from adult subjects at one transplant center who underwent laparoscopic living donor nephrectomy. A total of 55 ERAS subjects who received preoperative carbohydrates and 93 historical control subjects who underwent preoperative fasting were included in the final analysis. The following variables were compared between groups: LOS, time to tolerating a regular oral diet postoperatively, time to meeting 50% of estimated fluid needs by oral intake postoperatively, and incidence of postoperative GI complications. RESULTS: No significant differences between the ERAS and historical control groups in age, weight, body mass index, sex distribution, or estimated fluid needs were identified. Both groups consisted of predominantly female subjects. ERAS subjects experienced a shorter LOS (2.8 days versus 3.9 days, P < .001), time to tolerating a regular oral diet (36.5 hours versus 68.2 hours, P < .001), and time to meeting 50% of estimated fluid needs (25.3 hours versus 44.6 hours, P < .001) after laparoscopic nephrectomy compared to historical control subjects. No significant difference between groups in the incidence of postoperative GI complications (nausea, vomiting, or ileus) was identified. CONCLUSION: Our findings demonstrate the advantages of ERAS in living kidney donors undergoing laparoscopic nephrectomy and support ERAS implementation within this patient population.

Acute mesenteric ischemia: which predictive factors of delayed diagnosis at emergency unit?

PURPOSE: Acute mesenteric ischemia (AMI) is frequently diagnosed late, leading to a poor prognosis. Our aims were to identify predictive factors of delayed diagnosis and to analyze the outcomes of patients with AMI admitted in emergency units. METHODS: All the patients with AMI (2015-2020), in two Emergency units, were retrospectively included. Two groups were defined according to the time of diagnosis between the arrival at emergency unit and the CT scan: ≤ 6 h (early), > 6 h (delayed). RESULTS: 119 patients (mean age = 71 ± 7 years) were included. The patients with a delayed diagnosis (n = 33, 28%) were significantly associated with atypical presentation, including lower rates of abdominal pain (73 vs 89%, p = 0.003), abdominal tenderness (33 vs 43%, p = 0.03), and plasma lactate (4 ± 2 vs 6 ± 7 mmol/l, p = 0.03) when compared with early diagnosis. After multivariate analysis, the absence of abdominal pain was the only independent predictive factor of delayed diagnosis (Odd Ratio = 0.17; 95% CI = 0.03-0.88, p = 0.03). Patients with delayed diagnosis tended to be associated to lower rates of revascularization (9 vs 17%, p = 0.4), higher rates of major surgical morbidity (90 vs 57%, p = 0.1), longer length of stay (16 ± 23 vs 13 ± 15 days, p = 0.4) and, at the end of follow-up, higher rate of short small bowel syndrome (18 vs 7%, p = 0.095). CONCLUSION: AMI is a challenge for emergency physicians. History of patient, physical exam, biological data are not sufficient to diagnose AMI. New biomarkers, and awareness of emergency physicians should improve and accelerate the diagnosis of AMI.

LRP-1-dependent control of calpain expression and activity: A new mechanism regulating thyroid carcinoma cell adhesion.

The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor mediating the clearance of various molecules from the extracellular matrix. LRP1 also regulates cell surface expression of matrix receptors by modulating both extracellular and intracellular signals, though current knowledge of the underlying mechanisms remains partial in the frame of cancer cells interaction with matricellular substrates. In this study we identified that LRP1 downregulates calpain activity and calpain 2 transcriptional expression in an invasive thyroid carcinoma cell model. LRP1-dependent alleviation of calpain activity limits cell-matrix attachment strength and contributes to FTC133 cells invasive abilities in a modified Boyden chamber assays. In addition, using enzymatic assays and co-immunoprecipitation experiments, we demonstrated that LRP1 exerts post-translational inhibition of calpain activity through PKA-dependent phosphorylation of calpain-2. This LRP-1 dual mode of control of calpain activity fine-tunes carcinoma cell spreading. We showed that LRP1-mediated calpain inhibition participates in talin-positive focal adhesions dissolution and limits ß1-integrin expression at carcinoma cell surface. In conclusion, we identified an additional and innovative intracellular mechanism which demonstrates LRP-1 pro-motile action in thyroid cancer cells. LRP-1 ability to specifically control calpain-2 expression and activity highlights a novel facet of its de-adhesion receptor status.

Tixagevimab-Cilgavimab: COVID-19 Pre-Exposure Prophylaxis.

Tixagevimab-cilgavimab is the only nonvaccine drug currently authorized in the United States for the prevention of COVID-19 infection in individuals who are moderately to severely immunocompromised or unable to receive COVI.