Four subgroups based on tau levels in Alzheimer's disease observed in two independent cohorts

BackgroundAs Alzheimer's disease (AD) pathology presents decades before dementia manifests, unbiased biomarker cut-points may more closely reflect presence of pathology than clinically defined cut-points. Currently, unbiased cerebrospinal fluid (CSF) tau cut-points are lacking.MethodsWe investigated CSF t-tau and p-tau cut-points across the clinical spectrum using Gaussian mixture modelling, in two independent cohorts (Amsterdam Dementia Cohort and ADNI).ResultsIndividuals with normal cognition (NC) (total n =1111), mild cognitive impairment (MCI) (total n =1213) and Alzheimer's disease dementia (AD) (total n =1524) were included. In both cohorts, four CSF t- and p-tau distributions and three corresponding cut-points were identified. Increasingly high tau subgroups were characterized by steeper MMSE decline and higher progression risk to AD (cohort/platform-dependent HR, t-tau 1.9-21.3; p-tau 2.2-9.5).LimitationsThe number of subjects in some subgroups and subanalyses was small, especially in the highest tau subgroup and in tau PET analyses.ConclusionsIn two independent cohorts, t-tau and p-tau levels showed four subgroups. Increasingly high tau subgroups were associated with faster clinical decline, suggesting our approach may aid in more precise prognoses

Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis

Background:The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains.Methods and Findings:As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters.Conclusions:The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added

T Lymphocytes Promote the Antiviral and Inflammatory Responses of Airway Epithelial Cells

T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV)

Cationic Host Defence Peptides:Potential as Antiviral Therapeutics

There is a pressing need to develop new antiviral treatments; of the 60 drugs currently available, half are aimed at HIV-1 and the remainder target only a further six viruses. This demand has led to the emergence of possible peptide therapies, with 15 currently in clinical trials. Advancements in understanding the antiviral potential of naturally occurring host defence peptides highlights the potential of a whole new class of molecules to be considered as antiviral therapeutics. Cationic host defence peptides, such as defensins and cathelicidins, are important components of innate immunity with antimicrobial and immunomodulatory capabilities. In recent years they have also been shown to be natural, broad-spectrum antivirals against both enveloped and non-enveloped viruses, including HIV-1, influenza virus, respiratory syncytial virus and herpes simplex virus. Here we review the antiviral properties of several families of these host peptides and their potential to inform the design of novel therapeutics

A Case Study of the Implementation of a Competency-based Curriculum in a Caribbean Teaching Hospital

Objective: Several teaching hospitals are currently modifying their curriculum to comply with the changing demands in medical education. As a result, we decided to evaluate whether a competency-based curriculum implemented in a Caribbean teaching hospital fulfilled the requirements as defined by the CanMEDS framework. Methods: We made use of a triangulation method in the survey to obtain information on the educational process. Two separate methods were used consisting of site visits by visiting professors and a medical educator. The focus was on the structure, content and assessments of the educational activities. Results: Major recommendations included increased involvement of medical specialists in the educational activities in the clinical workplace. There was need for improvement of communication between medical specialists, patients, nurses, trainees and residents. Overall, improvements were observed in the structure of clinical rotations and content of the training programme. Conclusion: The implemented assessment programme provided necessary information for effective evaluation of the competency-based curriculum. We were able to identify new and feasible methods for improving the curriculum in our educational setting. Keywords: Assessment, competency-based curriculum, teaching hospita

Understanding the impact of interprofessional collaboration on the quality of care: a case report from a small-scale resource limited health care environment

Jamiu O Busari,1,2 Franka M Moll,3 Ashley J Duits3-5 1Department of Educational Development and Research, Faculty of Health, Medicine and Life Sciences, University of Maastricht, Maastricht, the Netherlands; 2Department of Pediatrics, Zuyderland Medical Center, Heerlen, the Netherlands; 3Department of Medical Education, St. Elisabeth Hospital, Willemstad, Curaçao; 4Institute for Medical Education, University Medical Center Groningen, Groningen, the Netherlands; 5Red Cross Blood Bank Foundation, Willemstad, Curaçao Background: A critical assessment of current health care practices, as well as the training needs of various health care providers, is crucial for improving patient care. Several approaches have been proposed for defining these needs with attention on communication as a key competency for effective collaboration. Taking our cultural context, resource limitations, and small-scale ­setting into account, we researched the applicability of a mixed focus group approach for analysis of the communication between doctors and nurses, as well as the measures for improvement. Study objective: Assessment of nurse-physician communication perception in patient care in a Caribbean setting. Methods: Focus group sessions consisting of nurses, interns, and medical specialists were conducted using an ethnographic approach, paying attention to existing communication, risk evaluation, and recommendations for improvement. Data derived from the focus group sessions were analyzed by thematic synthesis method with descriptive themes and development of analytic themes. Results: The initial focus group sessions produced an extensive list of key recommendations which could be clustered into three domains (standardization, sustainment, and collaboration). Further discussion of these domains in focus groups showed nurses’ and physicians’ domain perspectives and effects on patient care to be broadly similar. Risks related to lack of information, knowledge sharing, and professional respect were clearly described by the participants. Conclusion: The described mixed focus group session approach for effectively determining current interprofessional communication and key improvement areas seems suitable for our small‑scale, limited resource setting. The impact of the cultural context should be further ­evaluated by a similar study in a different cultural context. Keywords: interprofessional communication, focus group sessions, nurses’ perspective, cultural context, quality of car

Health care transformation in a resource-limited environment: exploring the determinants of a good climate for change

Tessa A van Boekholt,1 Ashley J Duits,2–4 Jamiu O Busari5,6 1Department of Public Health, United Nations High Commissioner for Refugees Uganda Operation, Arua, Uganda; 2Department of Medical Education, St. Elisabeth Hospital, Willemstad, Curaçao; 3Institute for Medical Education, University Medical Center Groningen, Groningen, The Netherlands; 4Red Cross Blood Bank Foundation, Willemstad, Curaçao; 5Department of Educational Development and Research, Faculty of Health, Medicine and Life Sciences, University of Maastricht, Maastricht, The Netherlands; 6Department of Pediatrics, Zuyderland Medical Center, Heerlen, The Netherlands Purpose: In a continued effort to improve the health care services, a project was set up to develop and implement a care pathway for the effective management of pressure ulcers in the St Elisabeth Hospital in Curaçao, the Dutch Caribbean. To ensure the effective implementation of our intervention, we decided to investigate what factors define the implementation climate of a health care institution within a resource-limited environment. Methods: We used a participatory tool approach in this study, where a mixed team of health professionals worked on two parts of a health improvement project, namely: 1) workforce leadership development through a clinical leadership training program; and 2) health care quality improvement through the pressure ulcer care pathway development. In-depth interviews were held with ten participants to gain insight into their experiences of the implementation climate in the hospitals and inductive analysis was used to identify the (sub)themes. Results: Identified themes that described the implementation climate included: 1) the attitude of staff toward policy changes; 2) vision of the organization; 3) collaboration; 4) transparency and communication; 5) personal development; and 6) resources. These factors were interrelated and associated with several potential consequences such as loss of motivation among staff, loss of creativity to solve issues, the emergence of the feeling “us” vs “them”, short-term solutions to problems, and a sense of suspicion/frustration among staff members. Conclusion: From this study, positive subconstructs for a favorable implementation climate in a hospital organization were lacking and those that were identified were suboptimal. The inability to satisfy all the subconstructs seemed to be the consequence of insufficient resources and infrastructure within the current health system. A favorable implementation climate in a resource-limited environment is closely tied to the availability of health care resources and infrastructure. Keywords: care pathway, implementation, health care, leadership, Caribbean, pressure ulcer, interprofessional collaboratio