Assessing health systems for type 1 diabetes in sub-Saharan Africa: developing a 'Rapid Assessment Protocol for Insulin Access'

BACKGROUND: In order to improve the health of people with Type 1 diabetes in developing countries, a clear analysis of the constraints to insulin access and diabetes care is needed. We developed a Rapid Assessment Protocol for Insulin Access, comprising a series of questionnaires as well as a protocol for the gathering of other data through site visits, discussions, and document reviews. METHODS: The Rapid Assessment Protocol for Insulin Access draws on the principles of Rapid Assessment Protocols which have been developed and implemented in several different areas. This protocol was adapted through a thorough literature review on diabetes, chronic condition management and medicine supply in developing countries. A visit to three countries in sub-Saharan Africa and meetings with different experts in the field of diabetes helped refine the questionnaires. Following the development of the questionnaires these were tested with various people familiar with diabetes and/or healthcare in developing countries. The Protocol was piloted in Mozambique then refined and had two further iterations in Zambia and Mali. Translations of questionnaires were made into local languages when necessary, with back translation to ensure precision. RESULTS: In each country the protocol was implemented in 3 areas – the capital city, a large urban centre and a predominantly rural area and their respective surroundings. Interviews were carried out by local teams trained on how to use the tool. Data was then collected and entered into a database for analysis. CONCLUSION: The Rapid Assessment Protocol for Insulin Access was developed to provide a situational analysis of Type 1 diabetes, in order to make recommendations to the national Ministries of Health and Diabetes Associations. It provided valuable information on patients' access to insulin, syringes, monitoring and care. It was thus able to sketch a picture of the health care system with regards to its ability to care for people with diabetes. In all countries where this tool was used the involvement of local stakeholders resulted in the process acting as a catalyst in bringing diabetes to the attention of the health authorities

Cyanobacteria blooms cannot be controlled by effective microorganisms (EM) from mud- or Bokashi-balls

In controlled experiments, the ability of ‘‘Effective Microorganisms (EM, in the form of mudballs or Bokashi-balls)’’ was tested for clearing waters from cyanobacteria. We found suspensions of EM-mudballs up to 1 g l-1 to be ineffective in reducing cyanobacterial growth. In all controls and EM-mudball treatments up to 1 g l-1 the cyanobacterial chlorophyll-a (Chl-a) concentrations increased within 4 weeks from&120 to 325–435 lg l-1. When pieces of EM-mudballs (42.5 g) were added to 25-l lake water with cyanobacteria, no decrease of cyanobacteria as compared to untreated controls was observed. In contrast, after 4 weeks cyanobacterial Chl-a concentrations were significantly higher in EM-mudball treatments (52 lg l-1) than in controls (20 lg l-1). Only when suspensions with extremely high EM-mudball concentrations were applied (i.e., 5 and 10 g l-1), exceeding the recommended concentrations by orders of magnitude, cyanobacterial growth was inhibited and a bloom forming concentration was reduced strongly. In these high dosing treatments, the oxygen concentration dropped initially to very low levels of 1.8 g l-1. This was most probably through forcing strong light limitation on the cyanobacteria caused by the high amount of clay and subsequent high turbidity of the water. Hence, this study yields no support for the hypothesis that EM is effective in preventing cyanobacterial proliferation or in terminating blooms. We consider EM products to be ineffective because they neither permanently bind nor remove phosphorus from eutroficated systems, they have no inhibiting effect on cyanobacteria, and they could even be an extra source of nutrients

A transgenic cell line with inducible transcription for studying (CGG)n repeat expansion mechanisms

There are more than 30 inherited human disorders connected with repeat expansion (myotonic dystrophy type I, Huntington’s disease, Fragile X syndrome). Fragile X syndrome is the most common reason for inherited intellectual disability in the human population. The ways of the expansion development remain unclear. An important feature of expanded repeats is the ability to form stable alternative DNA secondary structures. There are hypotheses about the nature of repeat instability. It is proposed that these DNA secondary structures can block various stages of DNA metabolism processes, such as replication, repair and recombination and it is considered as the source of repeat instability. However, none of the hypotheses is fully conf irmed or is the only valid one. Here, an experimental system for studying (CGG)n repeat expansion associated with transcription and TCR­-NER is proposed. It is noteworthy that the aberrations of transcription are a poorly studied mechanism of (CGG)n instability. However, the proposed systems take into account the contribution of other processes of DNA metabolism and, therefore, the developed systems are universal and applicable for various studies. Transgenic cell lines carrying a repeat of normal or premutant length under the control of an inducible promoter were established and a method for repeat instability quantif ication was developed. One type of the cell lines contains an exogenous repeat integrated into the genome by the Sleeping Beauty transposon; in another cell line, the vector is maintained as an episome due to the SV40 origin of replication. These experimental systems can serve for f inding the causes of instability and the development of therapeutic agents. In addition, a criterion was developed for the quantif ication of exogenous (CGG)n repeat instability in the transgenic cell lines’ genome

Follow-up of breast cancer in primary care vs specialist care: results of an economic evaluation

A randomized controlled trial (RCT) comparing primary-care-centred follow-up of breast cancer patients with the current standard practice of specialist-centred follow-up showed no increase in delay in diagnosing recurrence, and no increase in anxiety or deterioration in health-related quality of life. An economic evaluation of the two schemes of follow-up was conducted concurrent with the RCT. Because the RCT found no difference in the primary clinical outcomes, a cost minimization analysis was conducted. Process measures of the quality of care such as frequency and length of visits were superior in primary care. Costs to patients and to the health service were lower in primary care. There was no difference in total costs of diagnostic tests, with particular tests being performed more frequently in primary care than in specialist care. Data are provided on the average frequency and length of visits, and frequency of diagnostic testing for breast cancer patients during the follow-up period. © 1999 Cancer Research Campaig

Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source of these mediators. We conclude that adipose tissue eosinophils play a key role in the regulation of normal PVAT anti-contractile function

Impact of diabetes duration and cardiovascular risk factors on mortality in type 2 diabetes: the Hoorn Study

Background. Several studies have reported differences in the mortality risk between diabetic subjects detected by screening and known diabetic patients. We studied mortality in relation to diabetes duration, and the contribution of other cardiovascular risk factors to the elevated risk. Materials and methods. Participants were type 2 diabetic subjects (n = 174) of a population-based cohort study. Of these, 95 were diagnosed by screening. Known diabetic subjects were grouped into two categories of diabetes duration, with a median duration of 2.4 and 11.2 years, respectively. We assessed the contribution of classical cardiovascular risk factors (dyslipidaemia, hypertension, and prior myocardial infarction), and of new cardiovascular risk factors (microalbuminuria, von Willebrand factor, sVCAM-1 and C-reactive protein) to the mortality risk during nearly 10 years of follow up. Cox's proportional hazards model was used to study the association of diabetes duration and mortality. Results. The age- and sex-adjusted relative risks of mortality were 2.06 (95% C.I. 1.04-4.10) and 3.19 (1.64-6.20) for the patients with short- and long-term diabetes compared with the screening-detected diabetic subjects, respectively. Adjustment for cardiovascular risk factors resulted in a reduction of mortality risk in both groups: 1.13 (0.51-2.50) and 2.39 (1.18-4.83), respectively. Mortality risk significantly increased with increasing diabetes duration, even after multiple adjustment (P-value for trend ranged from < 0.001-0.018). Conclusions. Mortality risk increased with increasing diabetes duration. In subjects with short diabetes duration the mortality risk could largely be attributed to other risk factors. In subjects with a longer diabetes duration, however, the elevated mortality risk was independent of these cardiovascular risk factors

Rosiglitazone Decreases C-Reactive Protein to a Greater Extent Relative to Glyburide and Metformin Over 4 Years Despite Greater Weight Gain: Observations from A Diabetes Outcome Progression Trial (ADOPT)

OBJECTIVE: C-reactive protein (CRP) is closely associated with obesity and cardiovascular disease in both diabetic and nondiabetic populations. In the short term, commonly prescribed antidiabetic agents have different effects on CRP; however, the long-term effects of those agents are unknown. RESEARCH DESIGN AND METHODS: In A Diabetes Outcome Progression Trial (ADOPT), we examined the long-term effects of rosiglitazone, glyburide, and metformin on CRP and the relationship among CRP, weight, and glycemic variables in 904 subjects over 4 years. RESULTS: Baseline CRP was significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR), A1C, BMI, waist circumference, and waist-to-hip ratio. CRP reduction was greater in the rosiglitazone group by -47.6% relative to glyburide and by -30.5% relative to metformin at 48 months. Mean weight gain from baseline (at 48 months) was 5.6 kg with rosiglitazone, 1.8 kg with glyburide, and -2.8 kg with metformin. The change in CRP from baseline to 12 months was correlated positively with change in BMI in glyburide (r = 0.18) and metformin (r = 0.20) groups but not in the rosiglitazone (r = -0.05, NS) group. However, there was no longer a significant correlation between change in CRP and change in HOMA-IR, A1C, or waist-to-hip ratio in any of the three treatment groups. CONCLUSIONS: Rosiglitazone treatment was associated with durable reductions in CRP independent of changes in insulin sensitivity, A1C, and weight gain. CRP in the glyburide and metformin groups was positively associated with changes in weight, but this was not the case with rosiglitazone

Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction

Background: The association of plasma fibrinogen with myocardial infarction (MI) may (like that of C-reactive protein, CRP) be a marker of subclinical inflammation, mediated by cytokines such as interleukin-6 (IL-6). There are well- recognized discrepancies between commonly performed fibrinogen assays. Increased ratio of clottable fibrinogen to intact fibrinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional fibrinogen, and is elevated in acute MI.&lt;br/&gt; Objective: To compare the associations of intact fibrinogen and four routine fibrinogen assays (two von Clauss assays; one prothrombin-time derived; and one immunonephelometric) in a case-control study of previous MI. Patients/methods: Cases (n = 399) were recruited 3-9 months after their event; 413 controls were age- and sex-matched from the case-control study local population. Intact fibrinogen was measured in 50% of subjects. Results: All routine fibrinogen assays showed high intercorrelations (r = 0.82-0.93) and significant (P lt 0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact fibrinogen (r = 0.45-0.62), while intact fibrinogen showed only a small, nonsignificant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact fibrinogen assay was significantly higher (P lt 0.0003) in cases vs. controls. Each fibrinogen assay correlated with plasma levels of CRP and IL-6 (which were also elevated in cases vs. controls). Each routine fibrinogen assay remained significantly elevated in cases vs. controls after further adjustment for C-reactive protein and interleukin-6. Conclusions: These data provide evidence for acquired, increased hyperfunctional plasma fibrinogen in MI survivors, which is not associated with markers of inflammatory reactions. The causes and significance of these results remain to be established in prospective studies