WHO Essential Medicines Policies and Use in Developing and Transitional Countries: An Analysis of Reported Policy Implementation and Medicines Use Surveys

Background

Suboptimal medicine use is a global public health problem. For 35 years the World Health Organization (WHO) has promoted essential medicines policies to improve quality use of medicines (QUM), but evidence of their effectiveness is lacking, and uptake by countries remains low. Our objective was to determine whether WHO essential medicines policies are associated with better QUM.

Methods and Findings

We compared results from independently conducted medicines use surveys in countries that did versus did not report implementation of WHO essential medicines policies. We extracted survey data on ten validated QUM indicators and 36 self-reported policy implementation variables from WHO databases for 2002–2008. We calculated the average difference (as percent) for the QUM indicators between countries reporting versus not reporting implementation of specific policies. Policies associated with positive effects were included in a regression of a composite QUM score on total numbers of implemented policies. Data were available for 56 countries. Twenty-seven policies were associated with better use of at least two percentage points. Eighteen policies were associated with significantly better use (unadjusted p<0.05), of which four were associated with positive differences of 10% or more: undergraduate training of doctors in standard treatment guidelines, undergraduate training of nurses in standard treatment guidelines, the ministry of health having a unit promoting rational use of medicines, and provision of essential medicines free at point of care to all patients. In regression analyses national wealth was positively associated with the composite QUM score and the number of policies reported as being implemented in that country. There was a positive correlation between the number of policies (out of the 27 policies with an effect size of 2% or more) that countries reported implementing and the composite QUM score (r = 0.39, 95% CI 0.14 to 0.59, p = 0.003). This correlation weakened but remained significant after inclusion of national wealth in multiple linear regression analyses. Multiple policies were more strongly associated with the QUM score in the 28 countries with gross national income per capita below the median value (US$2,333) (r = 0.43, 95% CI 0.06 to 0.69, p = 0.023) than in the 28 countries with values above the median (r = 0.22, 95% CI −0.15 to 0.56, p = 0.261). The main limitations of the study are the reliance on self-report of policy implementation and measures of medicine use from small surveys. While the data can be used to explore the association of essential medicines policies with medicine use, they cannot be used to compare or benchmark individual country performance.

Conclusions

WHO essential medicines policies are associated with improved QUM, particularly in low-income countries. Please see later in the article for the Editors'' Summary     

Patent and Exclusivity Status of Essential Medicines for Non-Communicable Disease

Objective

The threat of non-communicable diseases (“NCDs”) is increasingly becoming a global health crisis and are pervasive in high, middle, and low-income populations resulting in an estimated 36 million deaths per year. There is a need to assess intellectual property rights (“IPRs”) that may impede generic production and availability and affordability to essential NCD medicines.

Methods

Using the data sources listed below, the study design systematically eliminated NCD drugs that had no patent/exclusivity provisions on API, dosage, or administration route. The first step identified essential medicines that treat certain high disease burden NCDs. A second step examined the patent and exclusivity status of active ingredient, dosage and listed route of administration using exclusion criteria outlined in this study.

Materials

We examined the patent and exclusivity status of medicines listed in the World Health Organization’s (“WHO”) Model List of Essential Drugs (Medicines) (“MLEM”) and other WHO sources for drugs treating certain NCDs. i.e., cardiovascular and respiratory disease, cancers, and diabetes. We utilized the USA Food and Drug Administration Orange Book and the USA Patent and Trademark Office databases as references given the predominant number of medicines registered in the USA.

Results

Of the 359 MLEM medicines identified, 22% (79/359) address targeted NCDs. Of these 79, only eight required in-depth patent or exclusivity assessment. Upon further review, no NCD MLEM medicines had study patent or exclusivity protection for reviewed criteria.

Conclusions

We find that ensuring availability and affordability of potential generic formulations of NCD MLEM medicines appears to be more complex than the presence of IPRs with API, dosage, or administration patent or exclusivity protection. Hence, more sophisticated analysis of NCD barriers to generic availability and affordability should be conducted in order to ensure equitable access to global populations for these essential medicines.     

Access to Diagnostic Tests and Essential Medicines for Cardiovascular Diseases and Diabetes Care: Cost,Availability and Affordability in the West Region of Cameroon

Objective

To assess the availability and affordability of medicines and routine tests for cardiovascular disease (CVD) and diabetes in the West region of Cameroon, a low-income setting.

Methods

A survey was conducted on the availability and cost of twelve routine tests and twenty medicines for CVD and diabetes in eight health districts (four urban and four rural) covering over 60% of the population of the region (1.8 million). We analyzed the percentage of tests and medicines available, the median price against the international reference price (median price ratio) for the medicines, and affordability in terms of the number of days’ wages it would cost the lowest-paid unskilled government worker for initial investigation tests and procurement for one month of treatment.

Results

The availability of tests varied between 10% for the ECG to 100% for the fasting blood sugar. The average cost for the initial investigation using the minimum tests cost 29.76 days’ wages. The availability of medicines varied from 36.4% to 59.1% in urban and from 9.1% to 50% in rural settings. Only metformin and benzathine-benzylpenicilline had a median price ratio of ≤1.5, with statins being largely unaffordable (at least 30.51 days’ wages). One month of combination treatment for coronary heart disease costs at least 40.87 days’ wages.

Conclusion

The investigation and management of patients with medium-to-high cardiovascular risk remains largely unavailable and unaffordable in this setting. An effective non-communicable disease program should lay emphasis on primary prevention, and improve affordable access to essential medicines in public outlets.     

Quantifying the Impoverishing Effects of Purchasing Medicines: A Cross-Country Comparison of the Affordability of Medicines in the Developing World

Background

Increasing attention is being paid to the affordability of medicines in low- and middle-income countries (LICs and MICs) where medicines are often highly priced in relation to income levels. The impoverishing effect of medicine purchases can be estimated by determining pre- and postpayment incomes, which are then compared to a poverty line. Here we estimate the impoverishing effects of four medicines in 16 LICs and MICs using the impoverishment method as a metric of affordability.

Methods and Findings

Affordability was assessed in terms of the proportion of the population being pushed below US$1.25 or US$2 per day poverty levels because of the purchase of medicines. The prices of salbutamol 100 mcg/dose inhaler, glibenclamide 5 mg cap/tab, atenolol 50 mg cap/tab, and amoxicillin 250 mg cap/tab were obtained from facility-based surveys undertaken using a standard measurement methodology. The World Bank''s World Development Indicators provided household expenditure data and information on income distributions. In the countries studied, purchasing these medicines would impoverish large portions of the population (up to 86%). Originator brand products were less affordable than the lowest-priced generic equivalents. In the Philippines, for example, originator brand atenolol would push an additional 22% of the population below US$1.25 per day, whereas for the lowest priced generic equivalent this demographic shift is 7%. Given related prevalence figures, substantial numbers of people are affected by the unaffordability of medicines.

Conclusions

Comparing medicine prices to available income in LICs and MICs shows that medicine purchases by individuals in those countries could lead to the impoverishment of large numbers of people. Action is needed to improve medicine affordability, such as promoting the use of quality assured, low-priced generics, and establishing health insurance systems. Please see later in the article for the Editors'' Summary     

Peer Support and Exclusive Breastfeeding Duration in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis

Objective

To examine the effect of peer support on duration of exclusive breastfeeding (EBF) in low and middle-income countries (LMICs).

Data Sources

Medline, EMBASE, and Cochrane Central Register for Controlled Trials were searched from inception to April 2012.

Methods

Two authors independently searched, reviewed, and assessed the quality of randomized controlled trials utilizing peer support in LMICs. Meta-analysis and metaregression techniques were used to produce pooled relative risks and investigate sources of heterogeneity in the estimates.

Results

Eleven randomized controlled trials conducted at 13 study sites met the inclusion criteria for systematic review. We noted significant differences in study populations, peer counselor training methods, peer visit schedule, and outcome ascertainment methods. Peer support significantly decreased the risk of discontinuing EBF as compared to control (RR: 0.71; 95% CI: 0.61–0.82; I² = 92%). The effect of peer support was significantly reduced in settings with >10% community prevalence of formula feeding as compared to settings with <10% prevalence (p = 0.048). There was no evidence of effect modification by inclusion of low birth weight infants (p = 0.367) and no difference in the effect of peer support on EBF at 4 versus 6 months postpartum (p = 0.398).

Conclusions

Peer support increases the duration of EBF in LMICs; however, the effect appears to be reduced in formula feeding cultures. Future studies are needed to determine the optimal timing of peer visits, how to best integrate peer support into packaged intervention strategies, and the effectiveness of supplemental interventions to peer support in formula feeding cultures.     

Is Serum Zinc Associated with Pancreatic Beta Cell Function and Insulin Sensitivity in Pre-Diabetic and Normal Individuals? Findings from the Hunter Community Study

Aim

To determine if there is a difference in serum zinc concentration between normoglycaemic, pre-diabetic and type-2 diabetic groups and if this is associated with pancreatic beta cell function and insulin sensitivity in the former 2 groups.

Method

Cross sectional study of a random sample of older community-dwelling men and women in Newcastle, New South Wales, Australia. Beta cell function, insulin sensitivity and insulin resistance were calculated for normoglycaemic and prediabetes participants using the Homeostasis Model Assessment (HOMA-2) calculator.

Result

A total of 452 participants were recruited for this study. Approximately 33% (N = 149) had diabetes, 33% (N = 151) had prediabetes and 34% (N = 152) were normoglycaemic. Homeostasis Model Assessment (HOMA) parameters were found to be significantly different between normoglycaemic and prediabetes groups (p<0.001). In adjusted linear regression, higher serum zinc concentration was associated with increased insulin sensitivity (p = 0.01) in the prediabetic group. There was also a significant association between smoking and worse insulin sensitivity.

Conclusion

Higher serum zinc concentration is associated with increased insulin sensitivity. Longitudinal studies are required to determine if low serum zinc concentration plays a role in progression from pre-diabetes to diabetes.     

The Impact of WHO Essential Medicines Policies on Inappropriate Use of Antibiotics

Background

Inappropriate overuse of antibiotics contributes to antimicrobial resistance (AMR), yet policy implementation to reduce inappropriate antibiotic use is poor in low and middle-income countries.

Aims

To determine whether public sector inappropriate antibiotic use is lower in countries reporting implementation of selected essential medicines policies.

Materials and Methods

Results from independently conducted antibiotic use surveys in countries that did, and did not report implementation of policies to reduce inappropriate antibiotic prescribing, were compared. Survey data on four validated indicators of inappropriate antibiotic use and 16 self-reported policy implementation variables from WHO databases were extracted. The average difference for indicators between countries reporting versus not reporting implementation of specific policies was calculated. For 16 selected policies we regressed the four antibiotic use variables on the numbers of policies the countries reported implementing.

Results

Data were available for 55 countries. Of 16 policies studied, four (having a national Ministry of Health unit on promoting rational use of medicines, a national drug information centre and provincial and hospital drugs and therapeutics committees) were associated with statistically significant reductions in antibiotic use of ≥20% in upper respiratory infection (URTI). A national strategy to contain antibiotic resistance was associated with a 30% reduction in use of antibiotics in acute diarrheal illness. Policies seemed to be associated with greater effects in antibiotic use for URTI and diarrhea compared with antibiotic use in all patients. There were negative correlations between the numbers of policies reported implemented and the percentage of acute diarrhoea cases treated with antibiotics (r = -0.484, p = 0.007) and the percentage of URTI cases treated with antibiotics (r = -0.472, p = 0.005). Major study limitations were the reliance on self-reported policy implementation data and antibiotic use data from linited surveys.

Conclusions

Selected essential medicines policies were associated with lower antibiotic use in low and middle income countries.     

Use of Medical Services and Medicines Attributable to Diabetes in Sub-Saharan Africa

Background

Although the large majority of persons with diabetes and other non-communicable diseases (NCDs) lives and dies in low- and middle-income countries, the prevention and treatment of diabetes and other NCDs is widely neglected in these areas. A contributing reason may be that, unlike the impacts of acute and communicable diseases, the demands on resources imposed by diabetes is not superficially obvious, and studies capable of detecting these impacts have not be done.

Methods

To ascertain recent use of medical services and medicines and other information about the impact of ill-health, we in 2008–2009 conducted structured, personal interviews with 1,780 persons with diagnosed diabetes (DMs) and 1,770 matched comparison subjects (MCs) without diabetes in Cameroon, Mali, Tanzania and South Africa. We sampled DMs from diabetes registries and, in Cameroon and South Africa, from attendees at outpatient diabetes clinics. To recruit MCs, we asked subjects with diabetes to identify five persons living nearest to them who were of the same sex and approximate age. We estimated diabetes impact on medical services use by calculating ratios and differences between DMs and MCs, testing for statistical significance using two-stage multivariable hurdle models.

Findings

DMs consumed 12.95 times more days of inpatient treatment, 7.54 times more outpatient visits, and 5.61 times more medications than MCs (all p<0.001). DMs used an estimated 3.44 inpatient days per person per year, made 10.72 outpatient visits per person per year (excluding traditional healers), and were taking an average of 2.49 prescribed medicines when interviewed.

Conclusions

In Sub-Saharan Africa, the relative incremental use of medical care and medicines associated with diagnosed diabetes is much greater than in industrialized countries and in China. Published calculations of the health-system impact of diabetes in Africa are dramatic underestimates. Although non-communicable diseases like diabetes are commonly thought to be minor problems for health systems and patients in Africa, our data demonstrate the opposite.     

Observational Study of the Association of First Insulin Type in Uncontrolled Type 2 Diabetes with Macrovascular and Microvascular Disease

Aims

To compare the risk of vascular disease, HbA1c and weight change, between first prescribed insulins in people with type 2 diabetes.

Methods

People included in THIN United Kingdom primary care record database who began insulin (2000–2007) after poor control on oral glucose-lowering agents (OGLD) were grouped by the number of OGLDs in their treatment regimen immediately before starting insulin (n = 3,485). Within OGLD group, Cox regression compared macrovascular (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and microvascular disease (peripheral neuropathy, nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A_1c (HbA_1c) and weight change.

Results

Mean follow-up was 3.6 years. Rates of incident macrovascular events were similar when basal insulin was compared to pre-mix or NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH 1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32, 1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus basal after 3 OGLDs, adjusted hazard ratio1.87 (1.04, 3.36), was not seen after two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs, weight increase was less with basal compared with pre-mix. After three OGLDs, mean HbA_1c had reduced less in basal versus pre-mix or NPH at 6–8 and at 9–11 months, and versus pre-mix at 12–14 months.

Conclusion

We found no difference in the risk of macrovascular events between first insulins in the medium term when started during poor glycaemia control. The increased risk of microvascular events with NPH warrants further study. In certain groups, first use of basal insulin was associated with less gain in weight and decrease in HbA_1c compared to other insulins.     

A Review of the Evidence to Support Influenza Vaccine Introduction in Countries and Areas of WHO's Western Pacific Region

Background

Immunization against influenza is considered an essential public health intervention to control both seasonal epidemics and pandemic influenza. According to the World Health Organization (WHO), there are five key policy and three key programmatic issues that decision-makers should consider before introducing a vaccine. These are (a) public health priority, (b) disease burden, (c) efficacy, quality and safety of the vaccine, (d) other inventions, (e) economic and financial issues, (f) vaccine presentation, (g) supply availability and (h) programmatic strength. We analyzed the body of evidence currently available on these eight issues in the WHO Western Pacific Region.

Methodology/Principal Findings

Studies indexed in PubMed and published in English between 1 January 2000 and 31 December 2010 from the 37 countries and areas of the Western Pacific Region were screened for keywords pertaining to the five policy and three programmatic issues. Studies were grouped according to country income level and vaccine target group. There were 133 articles that met the selection criteria, with most (90%) coming from high-income countries. Disease burden (n = 34), vaccine efficacy, quality and safety (n = 27) and public health priority (n = 27) were most frequently addressed by studies conducted in the Region. Many studies assessed influenza vaccine policy and programmatic issues in the general population (42%), in the elderly (24%) and in children (17%). Few studies (2%) addressed the eight issues relating to pregnant women.

Conclusions/Significance

The evidence for vaccine introduction in countries and areas in this Region remains limited, particularly in low- and middle-income countries that do not currently have influenza vaccination programmes. Surveillance activities and specialized studies can be used to assess the eight issues including disease burden among vaccine target groups and the cost-effectiveness of influenza vaccine. Multi-country studies should be considered to maximize resource utilization for cross-cutting issues such as vaccine presentation and other inventions.     

Symptom Burden of Patients with Dry Eye Disease: A Four Domain Analysis

Purpose

To determine which sensory (symptom persistence and intensity) and reactive (activity and affective interference) domains of symptom analysis are essential for assessing symptom burden in dry eye disease (DED) patients.

Methods

A symptom domain tool was developed to investigate all four symptom domains in DED. In a cross-sectional pilot study, we administered the symptom burden tool and the Ocular Surface Disease Index (OSDI) questionnaire to 48 DED patients. Total and domain scores from the symptom burden tool and the OSDI were normalized to achieve comparability. Spearman correlation coefficients were calculated to measure the relationship between domains and subscales. Agreement between the symptom burden tool and OSDI was assessed by Bland-Altman plot. Assigned treatments were compared by symptom burden to determine whether treatment aggressiveness is linked to symptom intensity.

Results

There was high agreement between the symptom burden tool and the OSDI. Symptom persistence had a stronger correlation with affective interference (r  =  0.62 for the symptom burden tool and r = 0.73 for the OSDI) than activity interference (r = 0.58 for the symptom burden tool and r = 0.60 for the OSDI). Symptom intensity correlated weakly with affective interference (r = 0.38) and activity interference (r = 0.37) in the symptom burden tool (OSDI does not have a subscale for intensity). In patients with equal persistence of symptoms, those having high symptom intensity were receiving more aggressive treatment (66.7%) than those with lower symptom intensity (33.3%).

Conclusions

Persistence of symptoms correlates better with affective interference than activity interference. Intensity of symptoms may be important for treatment decisions.     

Maternal Microchimerism: Increased in the Insulin Positive Compartment of Type 1 Diabetes Pancreas but Not in Infiltrating Immune Cells or Replicating Islet Cells

Background

Maternal microchimeric cells (MMc) transfer across the placenta during pregnancy. Increased levels of MMc have been observed in several autoimmune diseases including type 1 diabetes but their role is unknown. It has been suggested that MMc are 1) effector cells of the immune response, 2) targets of the autoimmune response or 3) play a role in tissue repair. The aim of this study was to define the cellular phenotype of MMc in control (n = 14) and type 1 diabetes pancreas (n = 8).

Methods

Using sex chromosome-based fluorescence in-situ hybridization, MMc were identified in male pancreas and their phenotype determined by concomitant immunofluorescence.

Results

In normal pancreas, MMc positive for endocrine, exocrine, duct and acinar markers were identified suggesting that these cells are derived from maternal progenitors. Increased frequencies of MMc were observed in type 1 diabetes pancreas (p = 0.03) with particular enrichment in the insulin positive fraction (p = 0.01). MMc did not contribute to infiltrating immune cells or Ki67+ islet cell populations in type 1 diabetes.

Conclusion

These studies provide support for the hypothesis that MMc in human pancreas are derived from pancreatic precursors. Increased frequencies of MMc beta cells may contribute to the initiation of autoimmunity or to tissue repair but do not infiltrate islets in type 1 diabetes.     

Cancer Incidence and Mortality in Patients with Type 2 Diabetes Treated with Human Insulin: A Cohort Study in Shanghai

Aim

The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes.

Methods

We recruited 8,774 insulin-naïve diabetes patients from the Shanghai Diabetes Registry (SDR). The follow-up rate was 85.4%. All subjects were divided into the insulin use cohort (n = 3,639) and the non-insulin use cohort (n = 5,135). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. Cox proportional hazards model was used to estimate the relative risk (RR) of cancer and mortality.

Results

We observed 98 cancer events in the insulin use cohort and 170 in the non-insulin use cohort. Cancer incidence rates were 78.6 and 74.3 per 10,000 patients per year in the insulin users and the non-insulin users, respectively. No significant difference in cancer risk was observed between the two cohorts (adjusted RR = 1.20, 95% CI 0.89–1.62, P = 0.228). Regarding site-specific cancers, only the risk of liver cancer was significantly higher in the insulin users compared to that in the non-insulin users (adjusted RR = 2.84, 95% CI 1.12–7.17, P = 0.028). The risks of overall mortality (adjusted RR = 1.89, 95% CI 1.47–2.43, P<0.0001) and death from cancer (adjusted RR = 2.16, 95% CI 1.39–3.35, P = 0.001) were all significantly higher in the insulin users than in the non-insulin users.

Conclusion

There was no excess risk of overall cancer in patients with type 2 diabetes who were treated with human insulin. However, a significantly higher risk of liver cancer was found in these patients. Moreover, insulin users showed higher risks of overall and cancer mortality. Considering that individuals treated with insulin were more likely to be advanced diabetic patients, caution should be used in interpreting these results.     

Left Ventricular Hypertrophy and Insulin Resistance in Adults from an Urban Community in the Gambia: Cross-Sectional Study

Objective

To determine the association between left ventricular hypertrophy and insulin resistance in Gambians.

Design

Cross-sectional study.

Setting

Outpatient clinics of Royal Victoria Teaching Hospital and Medical Research Council Laboratories in Banjul.

Participants

Three hundred and sixteen consecutive patients were enrolled from outpatient clinics. The data of 275 participants (89 males) were included in the analysis with a mean (± standard deviation) age of 53.7 (±11.9) years.

Interventions

A questionnaire was filled and anthropometric measurements were taken. 2-D guided M-mode echocardiography, standard 12-1ead electrocardiogram, fasting insulin and the oral glucose tolerance test were performed.

Main Outcome Measures

The Penn formula was used to determine the left ventricular mass index, 125 g/m² in males and 110 g/m² in females as the cut-off for left ventricular hypertrophy. Using the fasting insulin and fasting glucose levels, the insulin resistance was estimated by the homeostatic model assessment formula. Logistic regression analysis was used to determine the association between left ventricular hypertrophy and insulin resistance.

Results

The mean Penn left ventricular mass index was 119.5 (±54.3) and the prevalence of Penn left ventricular mass index left ventricular hypertrophy was 41%. The mean fasting glucose was 5.6 (±2.5) mmol/l, fasting insulin was 6.39 (±5.49) μU/ml and insulin resistance was 1.58 (±1.45). There was no association between Penn left ventricular mass index left ventricular hypertrophy and log of insulin resistance in univariate (OR = 0.98, 95% CI = 0.80 – 1.19, p = 0.819) and multivariate logistic regression (OR = 0.93, 95% CI = 0.76–1.15, p = 0.516) analysis.

Conclusion

No association was found in this study between left ventricular hypertrophy and insulin resistance in Gambians and this does not support the suggestion that insulin is an independent determinant of left ventricular hypertrophy in hypertensives.     

Financing of U.S. Biomedical Research and New Drug Approvals across Therapeutic Areas

Background

We estimated U.S. biomedical research funding across therapeutic areas, determined the association with disease burden, and evaluated new drug approvals that resulted from this investment.

Methodology/Principal Findings

We calculated funding from 1995 to 2005 and totaled Food and Drug Administration approvals in eight therapeutic areas (cardiovascular, endocrine, gastrointestinal, genitourinary, HIV/AIDS, infectious disease excluding HIV, oncology, and respiratory) primarily using public data. We then calculated correlations between funding, published estimates of disease burden, and drug approvals.Financial support for biomedical research from 1995 to 2005 increased across all therapeutic areas between 43% and 369%. Industry was the principal funder of all areas except HIV/AIDS, infectious disease, and oncology, which were chiefly sponsored by the National Institutes of Health (NIH). Total (ρ = 0.70; P = .03) and industry funding (ρ = 0.69; P = .04) were correlated with projected disease burden in high income countries while NIH support (ρ = 0.80; P = .01) was correlated with projected disease burden globally. From 1995 to 2005 the number of new approvals was flat or declined across therapeutic areas, and over an 8-year lag period, neither total nor industry funding was correlated with future approvals.

Conclusions/Significance

Across therapeutic areas, biomedical research funding increased substantially, appears aligned with disease burden in high income countries, but is not linked to new drug approvals. The translational gap between funding and new therapies is affecting all of medicine, and remedies must include changes beyond additional financial investment.     

Eosinophil Inversely Associates with Type 2 Diabetes and Insulin Resistance in Chinese Adults

Context

Limited population-based study focused on relationship between eosinophil and type 2 diabetes (T2D).

Objectives

We aimed to evaluate the relationship between peripheral eosinophil percentage and glucose metabolism and insulin resistance in a large sample size of Chinese population aged 40 and older.

Design and Methods

A cross-sectional study was performed among 9,111 Chinese adults including 3,561 men and 5,550 women. The glucose metabolism status was confirmed by 75-g oral glucose tolerance test. Homeostasis model assessment of insulin resistance index and serum insulin levels were used to evaluate insulin resistance. Homeostasis model assessment-B was used to evaluate β cell function.

Results

The average age of participants was 58.5 years. The prevalence of T2D decreased across the tertiles of eosinophil percentage (21.3%, 18.2% and 16.9%, P<0.0001). Each one tertile increase of eosinophil percentage inversely associated with risk of T2D when referred not only to normal glucose tolerance (NGT) (odds ratio (OR) 0.81, 95% CI 0.76–0.87, P< 0.0001), but also to impaired glucose regulation (OR 0.89, 95% CI 0.83–0.97, P = 0.006), respectively, after adjustment for the confounding factors. Compared with the first tertile, the third tertile of eosinophil percentage associated with a 23% decrease of insulin resistance in NGT participants after full adjustments (P = 0.005). Each 1-standard deviation of increment of eosinophil percentage associated with a 37% decrease of insulin resistance (P = 0.005).

Conclusions

Higher peripheral eosinophil percentage was associated with decreased risk of T2D. The inverse relation to insulin resistance was detected in NGT participants.     

Cognitive Functions in Middle Aged Individuals Are Related to Metabolic Disturbances and Aerobic Capacity: A Cross-Sectional Study

Aims

Metabolic disturbances may contribute to cognitive dysfunction in patients with type 2 diabetes. We investigated the relation between cognitive impairment and metabolic deteriorations, low physical fitness, low-grade inflammation and abdominal obesity in middle aged individuals.

Methods

We conducted a cross-sectional study including 40 to 65 year-old patients with type 2 diabetes and limited co morbidity (N = 56), age-matched individuals with impaired glucose tolerance (N = 56) as well as age-matched controls with normal glucose tolerance (N = 72). Specific cognitive functions were assessed with focus on verbal memory, processing speed, executive functions, and a composite overall mean score. Oral glucose tolerance test, VO₂max test, systemic inflammation, DXA scanning and abdominal MRI were measured.

Results

Multiple linear regression analyses adjusting for age, gender and verbal intelligence demonstrated that a low score in processing speed, executive functions and overall cognitive function were related to high fasting C-peptide, as well as low insulin sensitivity, beta-cell function and VO₂max. Measurements of blood glucose, obesity and inflammation were not associated with cognitive function.

Conclusion

Low cognitive scores are seen in middle aged individuals with hyperinsulinemia, low insulin sensitivity, beta-cell function and low aerobic capacity. These findings emphasize the importance of appropriate lifestyle and not only blood glucose control in prevention of cognitive disability.     

Risks of Breast and Endometrial Cancer in Women with Diabetes: A Population-Based Cohort Study

Objective

We investigated the overall and age-specific risks of developing breast and endometrial cancer among women with diabetes in a population-based cohort study.

Methods

Women with diabetes (n = 319310) and age-matched controls (n = 319308), selected from ambulatory care claims and beneficiary registry in 2000, respectively were linked to the in-patient claims (2000–2008) to identify admissions due to breast (ICD-9-CM: 174) and endometrial (ICD-9-CM: 182) cancer. The person-year approach with Poisson assumption was used to estimate the incidence density rate. The age-specific hazard ratios (HRs) of above malignancies in relation to diabetes with multivariate Cox proportional hazard regression.

Results

The overall incidence density rate of breast and endometrial cancer was estimated at 1.21 and 0.21 per 10,000 patient-years, respectively, for diabetes. The corresponding figures for controls were lower at 1.00 and 0.14 per 10,000 patient-years. Compared with the controls, the covariate adjusted HR for breast and endometrial cancer was 1.42 (95% confidence interval (CI) 1.34–1.50) and 1.71 (95% CI 1.48–1.97), respectively in women with diabetes. Elderly (> = 65 years) diabetes had the highest HR (1.61) of breast cancer, while the highest HR (1.85) of endometrial cancer was observed in diabetes aged < = 50 years.

Conclusions

Diabetes may significantly increase the risks of breast and endometrial cancer in all age stratifications. Health education for strict adherence of cancer screening program in women with diabetes is essential.