Assessing the Effect of Quality-Improvement Strategies for Organization of Care in Type 2 Diabetes Outcomes in Adults: Aim-Strait.

OBJECTIVES: To observe the effect of an organization-of-care improvement process on the achievement of therapeutic goals for people with type 2 diabetes mellitus (T2DM). METHODS: This single-arm cohort study analyzed the electronic medical records of patients with T2DM in 5 primary care practices in Ontario, Canada, before and 2 years after implementation of an individualized quality-improvement program. The primary outcome was the change in glycated hemoglobin (A1C) between baseline and follow up, with secondary analyses including change in other metabolic parameters, medication patterns and clinic visits. Prespecified subgroup analysis of patients with baseline values above guideline therapeutic targets was performed. RESULTS: In the overall population of 1,886 patients, A1C improved from 7.1% (baseline) to 7.0% (follow up) (p<0.001); low-density lipoprotein-cholesterol (LDL-C) improved from 2.1 to 1.9 mmol/L (p<0.001); and diastolic blood pressure (BP) improved from 75 to 74 mmHg (p<0.001), with no significant change observed in systolic BP. Of those patients who were above guideline-recommended therapeutic targets at baseline, improvements were observed at follow-up: A1C 8.3±1.3% to 7.8±1.3% (p<0.001), LDL-C 2.9±0.7 mmol/L to 2.4±0.9 mmol/L (p<0.001), systolic BP 144±11 to 134±16 mmHg (p<0.001) and diastolic BP 80±10 to 75±11 mmHg (p<0.001), with the percentages of patients achieving target at follow up being 32% for A1C, 40% for LDL-C and 49% for systolic BP. Overall, 22% of patients achieved all 3 targets at baseline compared to 28% at follow up (p<0.001). CONCLUSIONS: The implementation of an organization-of-care improvement program in primary care was associated with improved metabolic control, which was most pronounced in patients with baseline levels above guideline-recommended therapeutic targets.

Characteristics of Adults With Type 2 Diabetes Mellitus by Category of Chronic Kidney Disease and Presence of Cardiovascular Disease in Alberta Canada: A Cross-Sectional Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an excess risk of cardiovascular disease (CVD) and chronic kidney disease (CKD). Although CVD, CKD, and use of antihyperglycemic treatments are all key drivers of the costs and consequences experienced by people with diabetes, no recent Canadian data describe these characteristics among adults with diabetes. OBJECTIVE: To describe prevalence of CVD, CKD, and use of antihyperglycemic treatments among adults with diabetes. DESIGN: Retrospective population-based, cross-sectional study. SETTING: Alberta, Canada. PATIENTS: All adults with T2DM as of March 31, 2017. MEASUREMENTS: We described the demographic and clinical characteristics by CKD stage and CVD status and type. CKD stage was categorized according to international guidelines and based on estimated glomerular filtration rate (eGFR) and severity of albuminuria. METHODS: Clinical and demographic characteristics were defined using provincial administrative data; medication use was based on data from the provincial drug plan. Additional analyses examined subgroups based on demographic characteristics, clinical characteristics, and medication use. RESULTS: There were 260 903 participants, all of whom had T2DM. Median age was 64 years; 53.6% were male; and 10.9% lived in rural communities. Median duration of diabetes was 7.7 years. Half of the participants had A1C <7%. Overall, 33.0% had CKD; among these most had eGFR <60 mL/min/1.73 m2; 11.1%, 5.6%, and 2.9% had CKD stages 3a, 3b, and 4/5, respectively. The overall prevalence of CVD (prior myocardial infarction, stroke/transient ischemic attack, or peripheral artery disease) was 22.5%; prevalence increased in parallel with the presence of CKD: 14.4%, 28.8%, 35.7%, 44.3%, and 50.9% for stages 1, 2, 3a, 3b, and 4/5, respectively. Prescriptions for antihyperglycemic medications were more common in people with CKD as compared with those without. However, the use of all antihyperglycemic medications except insulin and meglitinide was progressively lower in the presence of more severe CKD. LIMITATIONS: The study is based on administrative data; therefore, the findings could be influenced by measurement error (eg, accuracy of diagnostic and procedural codes and prescription drug codes used). CONCLUSIONS: These findings will be useful to policy makers seeking to understand the burden of diabetes-related kidney disease as well as the potential budget implications and potential clinical benefits of expanded use of antihyperglycemic use in this population.

CONTEXTE: Le diabète de type 2 (DB2) est associé à un risque accru de maladie cardiovasculaire (MCV) et d'insuffisance rénale chronique (IRC). Bien que les MCV, l'IRC et la prise d'agents antihyperglycémiants soient des indicateurs importants des coûts et des conséquences pour les personnes diabétiques, il n'existe pas de données récentes au Canada décrivant ces caractéristiques chez les adultes atteints de diabète. OBJECTIF: Documenter la prévalence des MCV, de l'IRC et la prise d'antihyperglycémiants chez les diabétiques adultes. TYPE D'ÉTUDE: Étude transversale rétrospective représentative de la population. CADRE: Alberta, Canada. SUJETS: Tous les adultes atteints de DB2 au 31 mars 2017. MESURES: Nous avons défini les caractéristiques démographiques et cliniques selon le stade de l'IRC, de même que par le type de MCV et la gravité de l'atteinte. Le stade de l'IRC a été catégorisé selon les lignes directrices internationales, le débit de filtration glomérulaire estimé et la quantité d'albuminurie. MÉTHODOLOGIE: Les caractéristiques démographiques et cliniques ont été définies par l'entremise des données administratives provinciales; et les données sur la médication provenaient du Régime provincial d'assurance-médicaments. Des analyses supplémentaires ont examiné des sous-groupes de sujets sur la base des caractéristiques démographiques, des caractéristiques cliniques et sur la prise de médicaments. RÉSULTATS: L'étude porte sur 260 903 adultes atteints de DB2. L'âge médian se situait à 64 ans; 53,6 % étaient des hommes et 10,9 % vivaient en milieu rural. Les sujets étaient atteints de diabète depuis 7,7 ans (médiane). La moitié des participants présentaient une hémoglobine glyquée (HbA1C) inférieure à 7 %. Dans l'ensemble, 33,0 % des sujets étaient atteints d'IRC; dont la plupart présentaient un DFGe inférieur à 60 mL/min/1,73 m2; quant au stade de l'IRC, 11,1 % des sujets étaient classés au stade 3a, 5,6 % au stade 3 b et 2,9 % aux stades 4/5. La prévalence générale de maladies cardiovasculaires (antécédents d'infarctus du myocarde, d'accident vasculaire cérébral (AVC)/accident ischémique transitoire ou d'artériopathie périphérique) s'établissait à 22,5 %; un pourcentage croissant parallèlement à la présence d'IRC, soit de 14,4 % au stade 1, de 28,8 % au stade 2, de 35,7 % au stade 3a, de 44,3 % au stade 3 b et de 50,9 % aux stades 4/5. Les ordonnances d'agents antihyperglycémiants ont été plus fréquentes chez les sujets atteints d'IRC que chez les autres. Toutefois, la prise d'agents antihyperglycémiants, à l'exception de l'insuline et du méglitinide, s'est avérée progressivement plus faible en présence d'IRC plus grave. LIMITES: L'étude est fondée sur des données administratives, les résultats pourraient ainsi être influencés par des erreurs de mesures, notamment en ce qui concerne la précision du diagnostic ou la nomenclature des codes de procédure et des codes de prescription utilisés. CONCLUSION: Ces résultats serviront aux responsables de l'élaboration de politiques qui cherchent à comprendre le fardeau des néphropathies liées au diabète, de même que les potentielles répercussions budgétaires et les avantages cliniques de l'utilisation accrue d'agents antihyperglycémiants dans cette population de patients.

Glycated Hemoglobin Level Goal Achievement in Adults With Type 2 Diabetes in Canada: Still Room for Improvement.

OBJECTIVES: To describe the clinical histories and management of adults with type 2 diabetes who were not reaching their target glycated hemoglobin (A1C) levels and to identify barriers to achieving therapeutic goals. METHODS: Practice assessment surveys and practice audits were completed by 88 primary care physicians (PCPs) in the Diabetes Mellitus Assessment of Clinical managemenT In ONtario (DM-ACTION) program and by 56 diabetes specialists in the Diabetes Mellitus IMproving PAtient Care in our communiTies (DM-IMPACT) program. The DM-ACTION audit analyzed data from 1,173 adults with A1C levels ≥7.3% who were not prescribed insulin; the DM-IMPACT audit included 135 individuals with similar characteristics. RESULTS: Most PCPs (92%) and specialists (88%) stated that they typically recommend A1C levels of ≤7.0%; more than 90% indicated that they adjusted antihyperglycemic therapy within 3 months if suboptimal A1C targets endured. Among the DM-ACTION patients, the median A1C level was 7.8%; the median time between the last 2 A1C tests was 5 months; 58% were taking ≤2 noninsulin antihyperglycemic agents; and adjustment of glucose-lowering therapy was noted for only 56%. The corresponding values for the DM-IMPACT patients were 8.0%, 4 months, 43% and 68%, respectively. PCPs and specialists attributed patients' factors and patients' adherence as primary causes of poor achievement of guideline-recommended targets. PCPs perceived patients' factors as the predominant barrier to optimizing care, but the specialists believed that therapeutic inertia stems from a wide range and a varied combination of patient-centric factors. CONCLUSIONS: Type 2 diabetes remains a health-care challenge in Canada and globally. Primary care physicians and specialists attributed patients' factors as principal obstacles to optimal diabetes management. However, physician-associated therapeutic inertia may also be an important barrier to unmet therapeutic goals.

Insights Into the Current Management of Older Adults With Type 2 Diabetes in the Ontario Primary Care Setting.

OBJECTIVE: The Goal Oriented controL of Diabetes in the Elderly populatioN (GOLDEN) Program assessed the management of older persons with type 2 diabetes in Canadian primary care. METHODS: Data were extracted from the records of 833 consecutively identified persons 65 years of age or older who had type 2 diabetes and were taking 1 antihyperglycemic agent or more; they were managed by 64 physicians from 36 Ontario clinics. RESULTS: More than half (53%) had glycated hemoglobin (A1C) levels of 7.0% or lower, 41% had blood pressure levels below 130/80 mm Hg, and 73% had low-density lipoprotein levels of 2.0 mmol/L or lower; 19% met all 3 criteria. Over the past year, 11% had been assessed for frailty, 16% for cognitive dysfunction and 19% for depression; 88% were referred for eye checkups, and 83% had undergone foot examinations. One-tenth were taking 4 or more antihyperglycemic agents, 87% statins and 52% an angiotensin-converting enzyme inhibitor. More than half of those with high clinical complexity had A1C levels of 7.0% or lower; of these, one-third were taking a sulfonylurea, and one-fifth were taking insulin. In the patients with A1C levels of 7.0% or above and low clinical complexity, there was often no up-titration or initiation of additional antihyperglycemic agents. CONCLUSIONS: Older persons with type 2 diabetes often have multiple comorbidities. Unlike eye and foot examinations, there was less emphasis on evaluating for frailty, cognitive dysfunction and depression. The GOLDEN patients had generally well-controlled glycemic, blood pressure and cholesterol profiles, but whether these would be reflected in a "sicker" population is not known. Personalized strategies are necessary to avoid undertreatment of "healthy" older patients and overtreatment of the frail elderly.

Palliative sedation challenging the professional competency of health care providers and staff: a qualitative focus group and personal written narrative study.

BACKGROUND: Despite recent advances in palliative medicine, sedating a terminally ill patient is regarded as an indispensable treatment to manage unbearable suffering. With the prospect of widespread use of palliative sedation, the feelings and representations of health care providers and staff (carers) regarding sedation must be carefully explored if we are to gain a better understanding of its impact and potential pitfalls. The objective of the study was to provide a comprehensive description of the opinions of carers about the use of sedation practices in palliative care units (PCU), which have become a focus of public attention following changes in legislation. METHODS: Data were collected using a qualitative study involving multi-professional focus groups with health care providers and staff as well as personal narratives written by physicians and paramedical staff. A total of 35 medical and paramedical providers volunteered to participate in focus group discussions in three Palliative Care Units in two French hospitals and to write personal narratives. RESULTS: Health care provider and staff opinions had to do with their professional stance and competencies when using midazolam and practicing sedation in palliative care. They expressed uncertainty regarding three aspects of the comprehensive care: biomedical rigour of diagnosis and therapeutics, quality of the patient/provider relationship and care to be provided. Focusing on the sedative effect of midazolam and continuous sedation until death, the interviewed health care providers examined the basics of their professional competency as well as the key role played by the health care team in terms of providing support and minimizing workplace suffering. Nurses were subject to the greatest misgivings about their work when they were called upon to sedate patients. CONCLUSIONS: The uncertainty experienced by the carers with regard to the medical, psychosocial and ethical justification for sedation is a source of psychological burden and moral distress, and it has proved to be a major source of suffering in the workplace. Lastly, the study shows the uncertainty can have the positive effect of prompting the care team to devise ways to deal with it.

Sequential occurrence of dyspnea at the end of life in palliative care, according to the underlying cancer.

Dyspnea is a symptom that severely affects the quality of life of terminally ill patients. Its frequency differs considerably between studies. We aimed to characterize the frequency of dyspnea in a palliative care hospital (PCH) and to identify factors predisposing to dyspnea, particularly during the very last days of life, as a function of the underlying disease. Episodes of dyspnea were identified by the computerized extraction of prospectively collected data from the reports of care assistants or from medical observations recorded in the medical files for all stays at our PCH during the last 6 years. There were 6455 hospital stays, 88% ending in the death of the patient; 13,282 episodes of dyspnea were recorded during 2608 hospital stays (40%). Dyspnea was more frequently observed in cases of cancer than in other conditions (RR = 1.30; 95% CI: 1.14-1.48). Pulmonary metastasis increased the risk of dyspnea from 37% to 51% (RR = 1.37; 95% CI: 1.29-1.46). Dyspnea frequency varied with the primary cancer site, from 24% (brain cancer) to 60% (esophageal cancer). The data for cancer patients staying for more than 6 days who subsequently died indicated that 8% of patients experienced dyspnea exclusively during the last 4 days of the life, independently of the site of the primary cancer. Dyspnea during the last few days of life requires systematic assessment. Exclusively terminal dyspnea should be distinguished from more precocious dyspnea, as the pathophysiological mechanisms and treatments of these two forms are probably different.

Death wishes and explicit requests for euthanasia in a palliative care hospital: an analysis of patients files.

BACKGROUND: In the current public debate in France about end-of-life and legalization of euthanasia, palliative care is considered as a suitable answer or an alternative or even a supplement to euthanasia. The debate is based on opinion surveys, partly because there is a lack of objective data about the incidence of euthanasia requests (ER) in palliative care settings. The aim of this study was to collect, classify and quantify the expressions of wishes to die (WD), based on computerized files for patients admitted to an 81-bed palliative care hospital (PCH) in Paris during 2010-2011. METHODS: Two researchers analyzed the carers' notes extracted on the basis of containing the words "wish to die", "euthanasia" or any expressions relating to death. Notes related to WD and the corresponding patients were then classified in the order: ER, suicidal thought (ST) and other wish to die (OWD). Repeated ER were qualitatively analyzed according to a grid. RESULTS: We found that 195 of the 2157 patients (9%) expressed a WD: 61 (3%) expressed an ER; 15 (1%) described ST and 119 (6%) expressed an OWD without requiring acting. The WD group was predominantly female, stayed longer in the hospital (median 24 vs. 13 days), and consumed more anxiolytics and antidepressants. None of age, disease or marital status was associated with ER. More women and widows expressed an OWD. Twenty-six ER patients also expressed an OWD and two a ST. Six patients repeated their ER: all had poorly controlled symptoms with repercussions for their mental state. CONCLUSION: Our data show the existence of various expressions of WD with a low incidence of ER in a French PCH. The observation of WD including ER is suggestive of good communication between the patients and the care teams. Independent of the changeability of expressions of WD, their very existence should lead to a consideration of the dynamic changes in these WD, and to care staff paying additional attention to the individual, their suffering and the context.

The link between multiple sclerosis and depression.

Depression--be it a formal diagnosis based on consensus clinical criteria, or a collection of symptoms revealed by a self-report rating scale--is common in patients with multiple sclerosis (MS) and adds substantially to the morbidity and mortality associated with this disease. This Review discusses the prevalence and epidemiology of depression in patients with MS, before covering aetiological factors, including genetics, brain pathology, immunological changes, dysregulation of the hypothalamic-pituitary-adrenal axis, and psychosocial influences. Treatment options such as antidepressant drugs, cognitive-behavioural therapy, mindfulness-based therapy, exercise and electroconvulsive therapy are also reviewed in the context of MS-related depression. Frequent comorbid conditions, namely pain, fatigue, anxiety, cognitive dysfunction and alcohol use, are also summarized. The article then explores three key challenges facing researchers and clinicians: what is the optimal way to define depression in the context of diseases such as MS, in which the psychiatric and neurological symptoms overlap; how can current knowledge about the biological and psychological underpinnings of MS-related depression be used to boost the validity of this construct; and can intervention be made more effective through use of combination therapies with additive or synergistic effects, which might exceed the modest benefits derived from their individual components?

CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis.

BACKGROUND: Granulocytes generally exert protective roles in the central nervous system (CNS), but recent studies suggest that they can be detrimental in experimental autoimmune encephalomyelitis (EAE), the most common model of multiple sclerosis. While the cytokines and adhesion molecules involved in granulocyte adhesion to the brain vasculature have started to be elucidated, the required chemokines remain undetermined. METHODS: CXCR2 ligand expression was examined in the CNS of mice suffering from EAE or exposed to bacterial toxins by quantitative RT-PCR and in situ hybridization. CXCL1 expression was analyzed in IL-6-treated endothelial cell cultures by quantitative RT-PCR and ELISA. Granulocytes were counted in the brain vasculature after treatment with a neutralizing anti-CXCL1 antibody using stereological techniques. RESULTS: CXCL1 was the most highly expressed ligand of the granulocyte receptor CXCR2 in the CNS of mice subjected to EAE or infused with lipopolysaccharide (LPS) or pertussis toxin (PTX), the latter being commonly used to induce EAE. IL-6 upregulated CXCL1 expression in brain endothelial cells by acting transcriptionally and mediated the stimulatory effect of PTX on CXCL1 expression. The anti-CXCL1 antibody reduced granulocyte adhesion to brain capillaries in the three conditions under study. Importantly, it attenuated EAE severity when given daily for a week during the effector phase of the disease. CONCLUSIONS: This study identifies CXCL1 not only as a key regulator of granulocyte recruitment into the CNS, but also as a new potential target for the treatment of neuroinflammatory diseases such as multiple sclerosis.

Crawling phagocytes recruited in the brain vasculature after pertussis toxin exposure through IL6, ICAM1 and ITGαM.

The cerebral vasculature is constantly patrolled by rod-shaped leukocytes crawling on the luminal endothelial surface. These cells are recruited in greater numbers after exposure to bacterial lipopolysaccharide (LPS) by a mechanism involving tumor necrosis factor (TNF), interleukin-1ß (IL1ß) and angiopoietin-2 (Angpt2). Here, we report that the population of crawling leukocytes, consisting mainly of granulocytes, is also increased in the brains of mice suffering from experimental autoimmune encephalomyelitis (EAE) or injected with pertussis toxin (PTX), which is commonly used to induce EAE. However, this recruitment occurs through an alternative mechanism, independent of Angpt2. In a series of experiments using DNA microarrays, knockout mice and neutralizing antibodies, we found that PTX acts indirectly on the endothelium in part through IL6, which is essential for the post-transcriptional upregulation of intercellular adhesion molecule 1 (ICAM1) in response to PTX but not to LPS. We also found that phagocytes adhere to brain capillaries through the interaction of integrin αM (ITGαM) with ICAM1 and an unidentified ligand. In conclusion, this study supports the concept that PTX promotes EAE, at least in part, by inducing vascular changes necessary for the recruitment of patrolling leukocytes.

Rod-Shaped monocytes patrol the brain vasculature and give rise to perivascular macrophages under the influence of proinflammatory cytokines and angiopoietin-2.

The nervous system is constantly infiltrated by blood-derived sentinels known as perivascular macrophages. Their immediate precursors have not yet been identified in situ and the mechanism that governs their recruitment is mostly unknown. Here, we provide evidence that CD68(+)GR1(-) monocytes can give rise to perivascular macrophages in mice suffering from endotoxemia. After adhesion to the endothelium, these monocytes start to crawl, adopt a rod-shaped morphology when passing through capillaries, and can manifest the ability to proliferate and form a long cytoplasmic protuberance. They are attracted in greater numbers during endotoxemia by a combination of vasoregulatory molecules, including TNF (tumor necrosis factor), interleukin-1beta, and angiopoietin-2. After a period of several hours, some of them cross the endothelium to expand the population of perivascular macrophages. Depletion of adherent monocytes and perivascular macrophages can be achieved by injection of anti-angiopoietin-2 peptide-Fc fusion protein. This study extends our understanding of the behavior of monocytes at the blood-brain interface and provides a way to block their infiltration into the nervous tissue under inflammatory conditions.

A cross-cultural investigation of the use of teaching styles.

Teacher beliefs are a major influence on teacher actions. Because context influences beliefs, it was the purpose of this study to explore teachers' beliefs about Mosston's Spectrum of Teaching Styles from an international perspective. Over 1,400 teachers from 7 countries completed a survey related to their self-reported use of and beliefs about various teaching styles. Data suggested a shared core of reproduction teaching style use. The use of and beliefs about the production styles of teaching were more varied. Teachers' use of styles was significantly related to their beliefs about the styles.

Transcytosis of iota-toxin across polarized CaCo-2 cells.

Iota-toxin from Clostridium perfringens type E is a binary toxin consisting of two independent proteins, an enzymatic Ia and binding Ib component. Ia catalyses ADP-ribosylation of actin monomers, thus disrupting the actin cytoskeleton. In this report, we show that Ia plus Ib applied apically or basolaterally induce a rapid decrease in the transepithelial resistance (TER) of CaCo-2 cell monolayers and disorganization of actin filaments as well as the tight and adherens junctions. Ib alone, on the apical or basolateral side, slowly decreased the TER without affecting the actin cytoskeleton, possibly via pore formation. Interestingly, the two iota-toxin components inoculated separately on each cell surface induced cytopathic effects and a TER decrease. Anti-Ib sera, raised against the whole molecule or the Ia docking domain and applied to the opposite cell side versus Ib, neutralized the TER decrease. In addition, radioactive Ib incubated in the basolateral compartment was detected on the apical side by selective cell surface biotinylation. This argues for a transcytotic routing of Ib to mediate internalization of Ia from the opposite cell surface. Bafilomycin A1 also prevented the cytopathic effects of Ia and Ib applied separately to each cell side, possibly by blocking translocation of Ia into the cytosol and/or the intracellular transport of Ib. Ib is either routed into the cell independently of Ia, trans-cytosed and permanently exposed on the opposite cell surface or continuously recycled between an endosomal compartment and the cell surface.