A new case manager for diabetic patients: a pilot observational study of the role of community pharmacists and pharmacy services in the case management of diabetic patients

The adherence of type 2 diabetes mellitus (DM2) patients with an individual care plan (ICP) is often not satisfactory, nor does it allow for a significant improvement in outcome, because of poor accessibility to services, poor integration of pathway articulations, poor reconciliation with the patient's life, or the lack of a constant reference person. The purpose of this study was to evaluate the contribution of community pharmacists and pharmacy services in improving adherence with periodic controls in DM2. The study was conducted at a rural pharmacy. A sample of 40 patients was calculated with respect to a historical cohort and subsequently enrolled. Clinical and personal data were collected in an electronic case report form. Pharmacists acting as a case manager followed patients carrying out their ICP developed by an attending physician. Some of the activities foreseen by the ICP, such as electrocardiogram, fundus examination, and self-analysis of blood and urine, were carried out directly in the pharmacy by the pharmacist through the use of telemedicine services and point of care units. Activities that could not be performed in the pharmacy were booked by the pharmacist at the accredited units. Examination results were electronically reported by the pharmacist to the attending physician. The primary endpoint was the variation in patient adherence with the ICP compared to a historical cohort. Secondary endpoints were variation in waiting time for the examinations, mean percentage change in glycated hemoglobin (HbA1c) and low-density lipoprotein (LDL) cholesterol levels and blood pressure, impact on healthcare-related costs, and perceived quality of care. Adherence to the ICP significantly increased. Waiting times were reduced and clinical outcomes improved with conceivable effects on costs. Patients appreciated the easier access to services. Community pharmacists and pharmacy services represent ideal actors and context that, integrated in the care network, can really favor ICP adherence and obtain daily morbidity reduction and cost savings through proper disease control and an early diagnosis of complications

ProNGF Is a Cell-Type-Specific Mitogen for Adult Hippocampal and for Induced Neural Stem Cells

The role of proNGF, the precursor of Nerve Growth Factor (NGF), on the biology of adult neural stem cells (aNSCs) is still unclear. Here I analyzed adult hippo-campal neurogenesis in AD11 transgenic mice, in which the constitutive expression of anti-NGF antibody leads to an imbalance of proNGF over mature NGF. I found in-creased proliferation of progenitors but a reduced neurogenesis in the AD11 DG- hippocampus (HP-DG). Also in vitro, AD11 hippocampal neural stem cells (NSCs) pro-liferated more but were unable to differentiate into morphologically mature neu-rons. By treating wild-type (WT) hippocampal progenitors with the uncleavable form of proNGF (proNGF-KR) I demonstrated that proNGF acts as mitogen on aNSCs at low concentration. The mitogenic effect of proNGF was specifically addressed to the radial glia-like (RGL) neural stem cells through the induction of cyclin D1 expression. These cells express high level of p75NTR, as demonstrated by immunofluorescence analyses performed ex vivo on RGL cells isolated from freshly-dissociated HP-DG or selected in vitro from NSCs by LIF (leukemia inhibitory factor). Clonogenic assay per-formed in the absence of mitogens showed that RGLs respond to proNGF-KR by re-activating their proliferation and thus leading to neurospheres formation. The mito-genic effect of proNGF was further exploited in the expansion of mouse induced Neural Stem Cells (iNSCs). Chronic exposure of iNSCs to proNGF-KR increased their proliferation. Altogether, I demonstrated that proNGF acts as mitogen on hippo-campal and induced neural stem cells.The role of proNGF, the precursor of nerve growth factor (NGF), in the biology of adult neural stem cells (aNSCs) is still unclear. Here, we analyzed adult hippocampal neurogenesis in AD11 transgenic mice, in which the constitutive expression of anti-NGF antibody leads to an imbalance of proNGF over mature NGF. We found increased proliferation of progenitors but a reduced neurogenesis in the AD11 dentate gyrus (DG)-hippocampus (HP). Also in vitro, AD11 hippocampal neural stem cells (NSCs) proliferated more, but were unable to differentiate into morphologically mature neurons. By treating wild-type hippocampal progenitors with the uncleavable form of proNGF (proNGF-KR), we demonstrated that proNGF acts as mitogen on aNSCs at low concentration. The mitogenic effect of proNGF was specifically addressed to the radial glia-like (RGL) stem cells through the induction of cyclin D1 expression. These cells express high levels of p75NTR, as demonstrated by immunofluorescence analyses performed ex vivo on RGL cells isolated from freshly dissociated HP-DG or selected in vitro from NSCs by leukemia inhibitory factor. Clonogenic assay performed in the absence of mitogens showed that RGLs respond to proNGF-KR by reactivating their proliferation and thus leading to neurospheres formation. The mitogenic effect of proNGF was further exploited in the expansion of mouse-induced neural stem cells (iNSCs). Chronic exposure of iNSCs to proNGF-KR increased their proliferation. Altogether, we demonstrated that proNGF acts as mitogen on hippocampal and iNSCs. Stem Cells 2019;37:1223–1237

The use of pediatric flexible bronchoscopy in the COVID-19 pandemic era

On March 11, 2020, the World Health Organization (WHO) declared the pandemic because of a novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In January 2020, the first transmission to healthcare workers (HCWs) was described. SARS-CoV-2 is transmitted between people because of contact, droplets, and airborne. Airborne transmission is caused by aerosols that remain infectious when suspended in air over long distances and time. In the clinical setting, airborne transmission may occur during aerosol generating procedures like flexible bronchoscopy. To date, although the role of children in the transmission of SARS-CoV-2 is not clear the execution of bronchoscopy is associated with a considerably increased risk of SARS-CoV-2 transmission to HCWs. The aim of this overview is to summarize available recommendations and to apply them to pediatric bronchoscopy. We performed systematic literature searches using the MEDLINE (accessed via PubMed) and Scopus databases. We reviewed major recommendations and position statements published at the moment by the American Association for Bronchology and Interventional Pulmonology, WHO, European Center for Disease Prevention and Control and expert groups on the management of patients with COVID-19 to limit transmission among HCWs. To date there is a lack of recommendations for safe bronchoscopy during the pandemic period. The main indications concern adults and little has been said about children. We have summarized available recommendations and we have applied them to pediatric bronchoscopy

Modelling Hospital Medical Wards to Address Patient Complexity: A Case-Based Simulation-Optimization Approach

In this paper we focus on patient flows inside Internal Medicine Departments, with the aim of supporting new organizational models taking into account the patient relevant characteristics such as complexity and frailty. The main contribution of this paper is to develop a Discrete Event Simulation model to describe in detail the pathways of complex patients through medical hospital wards. The model has been applied to reproduce a case study of an Italian middle size hospital. The objective is quantifying the impact on resource use and outcome of introducing a new organizational model for medical departments. The re-organization is mainly focused on changing the available beds assignment among the wards to better address the complexity of care of patients with comorbidities. Following a patient-centered approach, patients are segmented considering the clinical characteristics (i.e. the pathology, proxy of Diagnoses Related Groups classification) and sub-grouped considering other characteristics, such as comorbidities and ward of admission. Then, an optimization component embedded into the model chooses the best pooling strategy to reorganize medical wards, determining the corresponding number of beds able to improve process indicators, such as length of stay. The simulation model is presented, and preliminary results are analyzed and discussed

Drug design and synthesis of first in class PDZ1 targeting NHERF1 inhibitors as anticancer agents

Targeted approaches aiming at modulating NHERF1 activity, rather than its overall expression, would be preferred to preserve the normal functions of this versatile protein. We focused our attention on the NHERF1/PDZ1 domain that governs its membrane recruitment/displacement through a transient phosphorylation switch. We herein report the design and synthesis of novel NHERF1 PDZ1 domain inhibitors. These compounds have potential therapeutic value when used in combination with antagonists of β-catenin to augment apoptotic death of colorectal cancer cells refractory to currently available Wnt/β-catenin-targeted agents

Automatic synchronisation of the cell cycle in budding yeast through closed-loop feedback control

The cell cycle is the process by which eukaryotic cells replicate. Yeast cells cycle asynchronously with each cell in the population budding at a different time. Although there are several experimental approaches to synchronise cells, these usually work only in the short-term. Here, we build a cyber-genetic system to achieve long-term synchronisation of the cell population, by interfacing genetically modified yeast cells with a computer by means of microfluidics to dynamically change medium, and a microscope to estimate cell cycle phases of individual cells. The computer implements a controller algorithm to decide when, and for how long, to change the growth medium to synchronise the cell-cycle across the population. Our work builds upon solid theoretical foundations provided by Control Engineering. In addition to providing an avenue for yeast cell cycle synchronisation, our work shows that control engineering can be used to automatically steer complex biological processes towards desired behaviours similarly to what is currently done with robots and autonomous vehicles

Dissemination of patient blood management practices in Swiss intensive care units: a cross-sectional survey

BACKGROUND Patient blood management (PBM) promotes the routine detection and treatment of anaemia before surgery, optimising the management of bleeding disorders, thus minimising iatrogenic blood loss and pre-empting allogeneic blood utilisation. PBM programmes have expanded from the elective surgical setting to nonsurgical patients, including those in intensive care units (ICUs), but their dissemination in a whole country is unknown. METHODS We performed a cross-sectional, anonymous survey (10 October 2018 to 13 March 2019) of all ordinary medical members of the Swiss Society of Intensive Care Medicine and the registered ICU nurses from the 77 certified adult Swiss ICUs. We analysed PBM-related interventions adopted in Swiss ICUs and related them to the spread of PBM in Swiss hospitals. We explored blood test ordering policies, blood-sparing strategies and red blood cell-related transfusion practices in ICUs. RESULTS A total of 115 medical doctors and 624 nurses (response rates 27% and 30%, respectively) completed the surveys. Hospitals had implemented a PBM programme according to 42% of physicians, more commonly in Switzerland's German-speaking regions (Odds Ratio [OR] 3.39, 95% confidence interval [CI] 1.23-9.35; p = 0.018) and in hospitals with more than 500 beds (OR 3.91, 95% CI 1.48-10.4; p = 0.006). The PBM programmes targeted the detection and correction of anaemia before surgery (79%), minimising perioperative blood loss (94%) and optimising anaemia tolerance (98%). Laboratory tests were ordered in 70.4% by the intensivist during morning rounds; the nurses performed arterial blood gas analyses autonomously in 48.4%. Blood-sparing techniques were used by only 42.1% of nurses (263 of 624, missing: 6) and 47.0% of physicians (54 of 115). Approximately 60% of respondents used an ICU-specific transfusion guideline. The reported haemoglobin threshold for the nonbleeding ICU population was 70 g/l and, therefore, was at the lower limit of current guidelines. CONCLUSIONS Based on this survey, the estimated proportion of the intensivists working in hospitals with a PBM initiative is 42%, with significant variability between regions and hospitals of various sizes. The risk of iatrogenic anaemia is relevant due to liberal blood sample collection practices and the underuse of blood-sparing techniques. The reported transfusion threshold suggests excellent adherence to current international ICU-specific transfusion guidelines

International survey of COVID-19 management strategies

Background: While individual countries have gained considerable knowledge and experience in coronavirus disease of 2019 (COVID-19) management, an international, comparative perspective is lacking, particularly regarding the measures taken by different countries to tackle the pandemic. This paper elicits the views of health system staff, tapping into their personal expertise on how the pandemic was initially handled. Methods: From May to July 2020, we conducted a cross-sectional, online, purpose-designed survey comprising 70 items. Email lists of contacts provided by the International Society for Quality in Health Care, the Italian Network for Safety in Health Care and the Australian Institute of Health Innovation were used to access healthcare professionals and managers across the world. We snowballed the survey to individuals and groups connected to these organizations. Key outcome measures were attitudes and information about institutional approaches taken; media communication; how acute hospitals were re-organized; primary health organization; personal protective equipment; and staffing and training. Results: A total of 1131 survey participants from 97 countries across the World Health Organization (WHO) regions responded to the survey. Responses were from all six WHO regions; 57.9% were female and the majority had 10 or more years of experience in healthcare; almost half (46.5%) were physicians; and all other major clinical professional groups participated. As the pandemic progressed, most countries established an emergency task force, developed communication channels to citizens, organized health services to cope and put in place appropriate measures (e.g. pathways for COVID-19 patients, and testing, screening and tracing procedures). Some countries did this better than others. We found several significant differences between the WHO regions in how they are tackling the pandemic. For instance, while overall most respondents (71.4%) believed that there was an effective plan prior to the outbreak, this was only the case for 31.9% of respondents from the Pan American Health Organization compared with 90.7% of respondents from the South-East Asia Region (SEARO). Issues with swab testing (e.g. delay in communicating the swab outcome) were less frequently reported by respondents from SEARO and the Western Pacific Region compared with other regions. Conclusion: The world has progressed in its knowledge and sophistication in tackling the pandemic after early and often substantial obstacles were encountered. Most WHO regions have or are in the process of responding well, although some countries have not yet instituted widespread measures known to support mitigation, for example, effective swab testing and social control measures

Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer’s Disease

Retina and optic nerve are sites of extra-cerebral manifestations of Alzheimer’s Disease (AD). Amyloid-β (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau protein are detected in eyes from AD patients and transgenic animals in correlation with inflammation, reduction of synapses, visual deficits, loss of retinal cells and nerve fiber. However, neither the pathological relevance of other post-translational tau modifications—such as truncation with generation of toxic fragments—nor the potential neuroprotective action induced by their in vivo clearance have been investigated in the context of AD retinal degeneration. We have recently developed a monoclonal tau antibody (12A12mAb) which selectively targets the neurotoxic 20–22 kDa NH2-derived peptide generated from pathological truncation at the N-terminal domain of tau without cross-reacting with its full-length normal protein. Previous studies have shown that 12A12mAb, when intravenously (i.v.)-injected into 6-month-old Tg2576 animals, markedly improves their AD-like, behavioural and neuropathological syndrome. By taking advantage of this well-established tau-directed immunization regimen, we found that 12A12mAb administration also exerts a beneficial action on biochemical, morphological and metabolic parameters (i.e. APP/Aβ processing, tau hyperphosphorylation, neuroinflammation, synaptic proteins, microtubule stability, mitochondria-based energy production, neuronal death) associated with ocular injury in the AD phenotype. These findings prospect translational implications in the AD field by: (1) showing for the first time that cleavage of tau takes part in several pathological changes occurring in vivo in affected retinas and vitreous bodies and that its deleterious effects are successfully antagonized by administration of the specific 12A12mAb; (2) shedding further insights on the tight connections between neurosensory retina and brain, in particular following tau-based immunotherapy. In our view, the parallel response we detected in this preclinical animal model, both in the eye and in the hippocampus, following i.v. 12A12mAb injection opens novel diagnostic and therapeutic avenues for the clinical management of cerebral and extracerebral AD signs in human beings

Analysis of the RLMS Adaptive Beamforming Algorithm Implemented with Finite Precision

This paper studies the influence of the use of finite wordlength on the operation of the RLMS adaptive beamformingalgorithm. The convergence behavior of RLMS, based on the minimum mean square error (MSE), is analyzed for operation with finite precision. Computer simulation results verify that a wordlength of nine bits is sufficient for the RLMS algorithm to achieve performance close to that provided by full precision. The performance measures used include residual MSE, rate of convergence, error vector magnitude (EVM), and beam pattern. Based on all these measures, it is shown that the RLMS algorithm outperforms other earlier algorithms, such as least mean square (LMS), recursive least square (RLS), modified robust variable step size (MRVSS) and constrained stability LMS (CSLMS)