Treating 4,000 diabetic patients in Cambodia, a high-prevalence but resource-limited setting: a 5-year study

BACKGROUND: Despite the worldwide increasing burden of diabetes, there has been no corresponding scale-up of treatment in developing countries and limited evidence of program effectiveness. In 2002, in collaboration with the Ministry of Health of Cambodia, Médecins Sans Frontières initiated an outpatient program of subsidized diabetic care in two hospital-based chronic disease clinics in rural settings. We aimed to describe the outcomes of newly and previously diagnosed diabetic patients enrolled from 2002 to 2008. METHODS: We calculated the mean and proportion of patients who met the recommended treatment targets, and the drop from baseline values for random blood glucose (RBG), hemoglobin A1c (HbA1c), blood pressure (BP), and body mass index (BMI) at regular intervals. Analysis was restricted to patients not lost to follow-up. We used the t test to compare baseline and subsequent paired values. RESULTS: Of 4404 patients enrolled, 2,872 (65%) were still in care at the time of the study, 24 (0.5%) had died, and 1,508 (34%) were lost to follow-up. Median age was 53 years, 2,905 (66%) were female and 4,350 (99%) had type 2 diabetes. Median (interquartile range (IQR)) follow-up was 20 months (5 to 39.5 months). A total of 24% (51/210) of patients had a HbA1c concentration of <7% and 35% (709/1,995) had a RBG <145 mg/dl within 1 year. There was a significant drop of 109 mg/dl (95% confidence interval (CI) 103.1 to 114.3) in mean RBG (P < 0.001) and a drop of 2.7% (95% CI 2.3 to 3.0) in mean HbA1c (P < 0.001) between baseline and month 6. In all, 45% (327/723) and 62% (373/605) of patients with systolic or diastolic hypertension at baseline, respectively, reached = 130/80 mm Hg within 1 year. There was a drop of 13.5 mm Hg (95% CI 12.1 to 14.9) in mean systolic blood pressure (SBP) (P < 0.001), and a drop of 11.7 mm Hg (95% CI 10.8 to 12.6) in mean diastolic blood pressure (DBP) (P < 0.001) between baseline and month 6. Only 22% (90/401) patients with obesity at baseline lowered their BMI <27.5 kg/m2 after 1 year. Factors associated with loss to follow-up were male sex, age >60 years, living outside the province, normal BMI on admission, high RBG on last visit, and coming late for the last consultation. CONCLUSION: Significant and clinically important improvements in glycemia and BP were observed, but a relatively low proportion of diabetic patients reached treatment targets. These results and the high loss to follow-up rate highlight the challenges of delivering diabetic care in rural, resource-limited settings

Modeling the differentiation of A- and C-type baroreceptor firing patterns

The baroreceptor neurons serve as the primary transducers of blood pressure for the autonomic nervous system and are thus critical in enabling the body to respond effectively to changes in blood pressure. These neurons can be separated into two types (A and C) based on the myelination of their axons and their distinct firing patterns elicited in response to specific pressure stimuli. This study has developed a comprehensive model of the afferent baroreceptor discharge built on physiological knowledge of arterial wall mechanics, firing rate responses to controlled pressure stimuli, and ion channel dynamics within the baroreceptor neurons. With this model, we were able to predict firing rates observed in previously published experiments in both A- and C-type neurons. These results were obtained by adjusting model parameters determining the maximal ion-channel conductances. The observed variation in the model parameters are hypothesized to correspond to physiological differences between A- and C-type neurons. In agreement with published experimental observations, our simulations suggest that a twofold lower potassium conductance in C-type neurons is responsible for the observed sustained basal firing, whereas a tenfold higher mechanosensitive conductance is responsible for the greater firing rate observed in A-type neurons. A better understanding of the difference between the two neuron types can potentially be used to gain more insight into the underlying pathophysiology facilitating development of targeted interventions improving baroreflex function in diseased individuals, e.g. in patients with autonomic failure, a syndrome that is difficult to diagnose in terms of its pathophysiology.Comment: Keywords: Baroreflex model, mechanosensitivity, A- and C-type afferent baroreceptors, biophysical model, computational mode

Vascular Remodeling in Health and Disease

The term vascular remodeling is commonly used to define the structural changes in blood vessel geometry that occur in response to long-term physiologic alterations in blood flow or in response to vessel wall injury brought about by trauma or underlying cardiovascular diseases.1, 2, 3, 4 The process of remodeling, which begins as an adaptive response to long-term hemodynamic alterations such as elevated shear stress or increased intravascular pressure, may eventually become maladaptive, leading to impaired vascular function. The vascular endothelium, owing to its location lining the lumen of blood vessels, plays a pivotal role in regulation of all aspects of vascular function and homeostasis.5 Thus, not surprisingly, endothelial dysfunction has been recognized as the harbinger of all major cardiovascular diseases such as hypertension, atherosclerosis, and diabetes.6, 7, 8 The endothelium elaborates a variety of substances that influence vascular tone and protect the vessel wall against inflammatory cell adhesion, thrombus formation, and vascular cell proliferation.8, 9, 10 Among the primary biologic mediators emanating from the endothelium is nitric oxide (NO) and the arachidonic acid metabolite prostacyclin [prostaglandin I2 (PGI2)], which exert powerful vasodilatory, antiadhesive, and antiproliferative effects in the vessel wall

Efficacité différentielle de l'aprotinine et de l'acide tranexamique selon le type de chirurgie cardiaque

Objective: To analyse the effectiveness and toxicity of aprotinin compared with tranexamic acid according to the type of cardiac surgery: coronary artery bypass or valve surgery. Setting: A French general hospital of 700 acute beds. Method: A retrospective study of benefit/risk ratio of aprotinin in adult cardiac surgery, which compare two periods (2000 vs. 2005) where mainly only anti-fibrinolytic treatment changed. Aprotinin was compared with tranexamic acid according to the type of surgery: coronary artery bypass or valve surgery. This study was conducted before the marketing application authorization of aprotinin was suspended. Main outcome measure: Blood loss during the first 24 h after intervention. The second outcome measures were mortality and spontaneous declaration of adverse drug effects. Results: Six hundred and seventy-six patients were included in our study. For coronary artery bypass, aprotinin appeared to be more effective than tranexamic acid to reduce blood loss after intervention (719 ± 41 mL vs. 947 ± 34 mL; p < 0.0001 during the first 24 h). For valvular surgery, there was no difference between the two anti-fibrinolytic drugs to decrease postoperative bleeding. No acute toxic effects were reported through the data bank of the department of cardiovascular surgery. Conclusions: Our preliminary results indicated that tolerance to aprotinin was as good as for tranexamic acid. Concerning its effectiveness, results differed according to the type of surgery. The benefit/risk ratio of aprotinin in our study was positive for coronary artery bypass surgery, but the use of tranexamic acid in valve surgery was as efficient and much less expensive than aprotinin. Our data suggest that even if the marketing application authorization of aprotinin was suspended, this drug should have clinical benefit for coronary artery bypass surgery. Therefore, our study shows that it is difficult to reach an unequivocal result about the use of aprotinin. Further investigations of aprotinin must be conducted in different types of cardiac surgery and among different patients populations like in pediatrics in which its efficiency and safety profiles are not clear. © 2010 Elsevier Masson SAS. All rights reserved.Objectifs Étude de l’efficacité et de la toxicité de l’aprotinine comparativement à l’acide tranexamique selon deux types de chirurgie : pontage coronarien ou chirurgie valvulaire. Contexte Centre hospitalier français de 700 lits. Patients et méthode Étude rétrospective mesurant le rapport bénéfice/risque de l’aprotinine utilisée chez l’adulte en chirurgie cardiaque comparant deux périodes (2000 versus 2005) dont les changements en pratique concernaient essentiellement les traitements hémostatiques. L’aprotinine a été comparée à l’acide tranexamique selon deux types de chirurgie : le pontage coronarien et la chirurgie valvulaire. Cette étude a été effectuée avant le retrait de commercialisation de l’aprotinine. Principal critère d’évaluation Volume de perte sanguine durant les premières 24 heures après l’intervention. Les critères secondaires d’évaluation étaient le taux de mortalité et d’effets indésirables. Résultats Six cent soixante-seize patients ont été inclus dans l’étude. Dans le cas du pontage coronarien, l’aprotinine semblait diminuer les pertes sanguines plus efficacement que l’acide tranexamique (719 ± 41 mL versus 947 ± 34 mL ; p < 0,0001 durant les premières 24 heures). En chirurgie valvulaire, aucune différence significative n’a été observée entre les deux hémostatiques quant à la diminution des saignements postopératoires. Aucun effet indésirable aigu n’a été relevé dans la base de données du département de chirurgie cardiaque. Conclusions Cette étude a montré que l’aprotinine et l’acide tranexamique ont un profil de tolérance similaire. Concernant l’efficacité, nos résultats diffèrent selon le type de chirurgie. Le ratio bénéfice/risque est en faveur de l’aprotinine pour le pontage coronarien, mais l’utilisation de l’acide tranexamique en chirurgie valvulaire est aussi efficace mais beaucoup moins chère que l’aprotinine. Nos résultats suggèrent que même si l’aprotinine a été retirée du marché, elle pouvait présenter un intérêt clinique dans le pontage coronarien. Par conséquent, notre étude a montré qu’il est difficile d’aboutir à un résultat univoque concernant l’utilisation de l’aprotinine. D’autres investigations seraient nécessaires afin d’étudier l’aprotinine dans d’autres types de chirurgie cardiaque et chez différentes populations de patients, notamment chez les enfants dont les profils d’efficacité et de tolérance de l’aprotinine ne sont pas encore établis