Hypertension management research priorities from patients,caregivers, and healthcare providers: A report from the Hypertension Canada Priority Setting Partnership Group

Patient‐ and stakeholder‐oriented research is vital to improving the relevance of research. The authors aimed to identify the 10 most important research priorities of patients, caregivers, and healthcare providers (family physicians, nurses, nurse practitioners, pharmacists, and dietitians) for hypertension management. Using the James Lind Alliance approach, a national web‐based survey asked patients, caregivers, and care providers to submit their unanswered questions on hypertension management. Questions already answered from randomized controlled trial evidence were removed. A priority setting process of patient, caregiver, and healthcare providers then ranked the final top 10 research priorities in an in‐person meeting. There were 386 respondents who submitted 598 questions after exclusions. Of the respondents, 78% were patients or caregivers, 29% lived in rural areas, 78% were aged 50 to 80 years, and 75% were women. The 598 questions were distilled to 42 unique questions and from this list, the top 10 research questions prioritized included determining the combinations of healthy lifestyle modifications to reduce the need for antihypertensive medications, stress management interventions, evaluating treatment strategies based on out‐of‐office blood pressure compared with conventional (office) blood pressure, education tools and technologies to improve patient motivation and health behavior change, management strategies for ethnic groups, evaluating natural and alternative treatments, and the optimal role of different healthcare providers and caregivers in supporting patients with hypertension. These priorities can be used to guide clinicians, researchers, and funding bodies on areas that are a high priority for hypertension management research for patients, caregivers, and healthcare providers. This also highlights priority areas for improved knowledge translation and delivering patient‐centered care.     

High‐resolution CT pulmonary findings in idiopathic ankylosing spondylitis: correlations with clinical assessment,plain chest X‐ray and pulmonary function tests

Aim: The aim of this study is to evaluate pulmonary manifestations of ankylosing spondylitis on high‐resolution computed tomography (CT) scan and to correlate these findings with clinical assessment, plain chest X‐ray and pulmonary function tests. Methods: The study comprised 32 patients (26 males [81.3%], 6 females [18.8%]) who met the modified New York criteria for diagnosis of idiopathic ankylosing spondylitis; in addition 10 normal subjects not complaining of any respiratory symptoms and matched for age and sex served as a control group. All patients were subjected to full history‐taking, full clinical examination, chest X‐ray, high‐resolution computed tomography (HRCT) chest and pulmonary function tests. Results: The abnormalities on HRCT included evidence of apical lung fibrosis in two patients (6.3%), interstitial lung disease in six (18.8%), minor interstitial abnormalities in eight (25%), bronchiectasis in four (12.5%), lung nodules in three (6.3%) and pleural thickening in five patients (6.3%). Nine patients (28.1%) showed negative findings by chest X‐ray which revealed positive findings on HRCT. Five patients (15.6%) showed positive findings on both HRCT and plain chest X‐ray, and 18 patients (56.3%) showed no findings on both HRCT and chest X‐ray. Four patients (12.5%) showed normal pulmonary function tests, 25 (78.13%) showed restrictive pattern, 17 (53.13%) had obstructive pattern and 26 patients (81.3%) had diffusion defects. Conclsuion: The identification of non‐apical minor basal interstitial lung disease in our study which was previously reported in other studies, raises a possible association to ankylosing spondylitis. High‐resolution CT scan is more sensitive than chest X‐rays in detection of such minor interstitial lung disease (ILD), and other parenchymal lung changes.     

When patients refuse assessment of decision-making capacity: how should clinicians respond?

When patients refuse beneficial treatment, the assessment of decision-making capacity plays a key role in determining the best course of action. However, situations in which patients refuse to explain their reasons occur. This can make an assessment of capacity impossible. In such cases, clinicians find themselves in difficult situations without clear ethical guidance. Refusal to give reasons for refusing beneficial treatment has been seen as pointing to the absence of decision-making capacity. However, the reasons given for this are either unsatisfactory or insufficient to eliminate cases of genuine uncertainty. This article argues that although it cannot be concluded that such patients are incompetent, there are reasons to treat them as if they were. The basis of this possibility, however, points to several obligations for clinicians before such a situation can be said to exist.     

Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway

Migration toward pathology is the first critical step in stem cell engagement during regeneration. Neural stem cells (NSCs) migrate through the parenchyma along nonstereotypical routes in a precise directed manner across great distances to injury sites in the CNS, where they might engage niches harboring local transiently expressed reparative signals. The molecular mechanisms for NSC mobilization have not been identified. Because NSCs seem to home similarly to pathologic sites derived from disparate etiologies, we hypothesized that the inflammatory response itself, a characteristic common to all, guides the behavior of potentially reparative cells. As proof of concept, we show that human NSCs migrate in vivo (including from the contralateral hemisphere) toward an infarcted area (a representative CNS injury), where local astrocytes and endothelium up-regulate the inflammatory chemoattractant stromal cell-derived factor 1alpha (SDF-1alpha). NSCs express CXC chemokine receptor 4 (CXCR4), the cognate receptor for SDF-1alpha. Exposure of SDF-1alpha to quiescent NSCs enhances proliferation, promotes chain migration and transmigration, and activates intracellular molecular pathways mediating engagement. CXCR4 blockade abrogates their pathology-directed chain migration, a developmentally relevant mode of tangential migration that, if recapitulated, could explain homing along nonstereotypical paths. Our data implicate SDF-1alpha/CXCR4, representative of the inflammatory milieu characterizing many pathologies, as a pathway that activates NSC molecular programs during injury and suggest that inflammation may be viewed not simply as playing an adverse role but also as providing stimuli that recruit cells with a regenerative homeostasis-promoting capacity. CXCR4 expression within germinal zones suggests that NSC homing after injury and migration during development may invoke similar mechanisms.     

Molecular Epidemiology of Rabies in Wild Canidae in Tunisia

Rabies is a viral zoonosis that is transmissible to humans via domestic and wild animals. There are two epidemiological cycles for rabies, the urban and the sylvatic cycles. In an attempt to study the epidemiological role of wild canidae in rabies transmission, the present study aimed to analyze the genetic characteristics of virus isolates and confirm prior suggestions that rabies is maintained through a dog reservoir in Tunisia. Virus strains isolated from wild canidae were subject to viral sequencing, and Bayesian phylogenetic analysis was performed using Beast2 software. Essentially, the virus strains isolated from wild canidae belonged to the Africa-1 clade, which clearly diverges from fox-related strains. Our study also demonstrated that genetic characteristics of the virus isolates were not as distinct as could be expected if a wild reservoir had already existed. On the contrary, the geographic landscape is responsible for the genetic diversity of the virus. The landscape itself could have also acted as a natural barrier to the spread of the virus.     

Oxygen-dependent mutagenesis in Escherichia coli lacking superoxide dismutase.

Escherichia coli double mutants (sodA sodB) completely lacking superoxide dismutase (SOD) have greatly enhanced mutation rates during aerobic growth. Single mutants lacking manganese SOD (MnSOD) but possessing iron SOD (FeSOD) have a smaller increase, and single mutants lacking FeSOD but possessing MnSOD do not show such an increase. The enhancement of mutagenesis is completely dependent on the presence of oxygen, and treatments that increase the flux of superoxide radicals produce even higher levels of mutagenesis. The presence of a plasmid overproducing either form of SOD reduces the level of mutagenesis to that of wild type, showing that the O2-dependent enhancement results from a lack of SOD. The enhancement of mutagenesis is RecA-independent, and a complete lack of SOD does not induce the SOS response during aerobic growth. However, the enhanced mutagenesis in aerobically grown sodA sodB mutants is largely dependent on functional exonuclease III, suggesting that the increased flux of superoxide radicals results in DNA lesions that can be acted on by this enzyme, leading to mutations.     

Minimal residual disease after allogeneic bone marrow transplantation for chronic myeloid leukaemia: a metaphase-FISH study

Metaphase-FISH was adopted for the detection of proliferating Philadelphia-positive (Ph⁺) residual leukaemic cells in 25 patients with chronic myeloid leukaemia treated with allogeneic bone marrow transplantation (BMT). Patients were followed up during their clinical remission for 4–50 months (median 17 months) after BMT. 80 bone marrow samples were studied. For most of the cases no fewer than 1000 metaphases were analysed. Six patients (24%) showed residual Ph⁺ cells during the first 6 months and two others by the end of the first year after BMT. Three patients relapsed during the study and in two of them residual Ph⁺ cells were detected during the first 6 months after BMT. In 17 patients no Ph⁺ cells were detected at any stage of follow-up and 16 (94.1%) of them continue in complete clinical and haematological remission. Our results indicate that metaphase-FISH is a reliable tool in the quantitation of proliferating residual leukaemic cells. We suggest that consecutive findings of equal amounts of residual leukaemic cells do not necessarily predict a relapse. However, their presence calls for follow-up at shorter intervals where an increasing number of these cells predicts an ensuing relapse.