Global Burden of Double Malnutrition: Has Anyone Seen It?

Background

Low- to middle-income countries (LMICs) are believed to be characterized by the coexistence of underweight and overweight. It has also been posited that such coexistence is appearing among the low socioeconomic status (SES) groups.

Methods

We conducted a cross-sectional analysis of nationally representative samples of 451321 women aged 20–49 years drawn from 57 Demographic and Health Surveys conducted between 1994 and 2008. Body Mass Index (BMI in kg/m²), was used to define underweight and overweight following conventional cut-points. Covariates included age, household wealth, education, and residence. We estimated multinomial multilevel models to assess the extent to which underweight (BMI<18.5 kg/m²) and overweight (BMI≥25.0 kg/m²) correlate at the country-level, and at the neighborhood-level within each country.

Results

In age-adjusted models, there was a strong negative correlation between likelihood of being underweight and overweight at country- (r = −0.79, p<0.001), and at the neighborhood-level within countries (r = −0.51, P<0.001). Negative correlations ranging from −0.11 to −0.90 were observed in 46 of the 57 countries at the neighborhood-level and 29/57 were statistically significant (p≤0.05). Similar negative correlations were observed in analyses restricted to low SES groups. Finally, the negative correlations across countries, and within-countries, appeared to be stable over time in a sub-set of 36 countries.

Conclusion

The explicitly negative correlations between prevalence of underweight and overweight at the country-level and at neighborhood-level suggest that the hypothesized coexistence of underweight and overweight has not yet occurred in a substantial manner in a majority of LMICs.     

The Global Burden of Disease Assessments—WHO Is Responsible?

The Global Burden of Disease (GBD) concept has been used by the World Health Organization (WHO) for its reporting on health information for nearly 10 years. The GBD approach results in a single summary measure of morbidity, disability, and mortality, the so-called disability-adjusted life year (DALY). To ensure transparency and objectivity in the derivation of health information, WHO has been urged to use reference groups of external experts to estimate burden of disease. Under the leadership and coordination of WHO, expert groups have been appraising and abstracting burden of disease information. Examples include the Child Health Epidemiology Reference Group (CHERG), the Malaria Monitoring and Evaluation Reference Group (MERG), and the recently established Foodborne Disease Burden Epidemiology Reference Group (FERG). The structure and functioning of and lessons learnt by these groups are described in this paper. External WHO expert groups have provided independent scientific health information while operating under considerable differences in structure and functioning. Although it is not appropriate to devise a single "best practice" model, the common thread described by all groups is the necessity of WHO's leadership and coordination to ensure the provision and dissemination of health information that is to be globally accepted and valued.     

The Global Burden of Childhood Coeliac Disease: A Neglected Component of Diarrhoeal Mortality?

Objectives

Coeliac disease has emerged as an increasingly recognised public health problem over the last half-century, and is now coming to be seen as a global phenomenon, despite a profound lack of globally representative epidemiological data. Since children with coeliac disease commonly present with chronic diarrhoea and malnutrition, diagnosis is often overlooked, particularly in poorer settings where children often fail to thrive and water-borne infectious diarrhoeas are common. This is the first attempt to make global estimates of the burden of coeliac disease in childhood.

Methods

We built a relatively crude model of childhood coeliac disease, incorporating estimates of population prevalence, probability of non-diagnosis, and likelihood of mortality among the undiagnosed across all countries from 1970 to 2010, based around the few available data. All our assumptions are stated in the paper and the model is available as a supplementary file.

Findings

Our model suggests that in 2010 there were around 2.2 million children under 5 years of age living with coeliac disease. Among these children there could be 42,000 deaths related to coeliac disease annually. In 2008, deaths related to coeliac disease probably accounted for approximately 4% of all childhood diarrhoeal mortality.

Conclusions

Although coeliac disease may only account for a small proportion of diarrhoeal mortality, these deaths are not preventable by applying normal diarrhoea treatment guidelines, which may even involve gluten-based food supplements. As other causes of diarrhoeal mortality decline, coeliac disease will become a proportionately increasing problem unless consideration is given to trying gluten-free diets for children with chronic diarrhoea and malnutrition.     

Adult Moyamoya Disease: A Burden of Intracranial Stenosis in East Asians?

Background

Both Moyamoya disease (MMD) and intracranial atherosclerotic stenosis (ICAS) are more prevalent in Asians than in Westerners. We hypothesized that a substantial proportion of patients with adult-onset MMD were misclassified as having ICAS, which may in part explain the high prevalence of intracranial atherosclerotic stroke in Asians.

Method

We analyzed 352 consecutive patients with ischemic events within the MCA distribution and relevant intracranial arterial stenosis, but no demonstrable carotid or cardiac embolism sources. Conventional angiography was performed in 249 (70.7%) patients, and the remains underwent MRA. The occurrence of the c.14429G>A (p.Arg4810Lys) variant in ring finger protein 213 (RNF213) was analyzed. This gene was recently identified as a susceptibility gene for MMD in East Asians.

Results

The p.Arg4810Lys variant was observed in half of patients with intracranial stenosis (176 of 352, 50.0%), in no healthy control subjects (n = 51), and in 3.2% of stroke control subjects (4 of 124 patients with other etiologies). The presence of basal collaterals, bilateral involvement on angiography, and absence of diabetes were independently associated with the presence of the RNF213 variant. Among 131 patients who met all three diagnostic criteria and were diagnosed with MMD, three-fourths (75.6%) had this variant. However, a significant proportion of patients who met two criteria (57.7%), one criterion (28.6%), or no criteria (20.0%) also had this variant. Some of them developed typical angiographic findings of MMD on follow-up angiography.

Conclusions

Careful consideration of MMD is needed when diagnosing ICAS because differential therapeutic strategies are required for these diseases and due to the limitations of the current diagnostic criteria for MMD.     

The Burden of OASIS Increases along with Socioeconomic Position – Register-Based Analysis of 980,733 Births in Finland

Background

Obstetric anal sphincter injury (OASIS) has been identified as a major preventable risk factor for anal incontinence.

Objective

Aim was to measure national variation in incidence of OASIS by socioeconomic status (SES).

Methods

A retrospective population based case-control study using the data derived from the Finnish Medical Birth Register for the years 1991–2010. A total population of singleton vaginal births was reviewed. We calculated unadjusted incidences of OASIS stratified by SES and vaginal parity, and adjusted risks for OASIS in each social class, after controlling for parity, birthweight, mode of delivery, maternal age and maternal smoking. SES was recorded into five categories based on mother’s occupation at time of birth; upper white-collar workers such as physicians, lower white-collar workers such as nurses, blue-collar workers such as cleaners, others such as students, and cases with missing information.

Results

Seven per thousand (6,404 of 980,733) singleton births were affected by OASIS. In nulliparae the incidence of OASIS was 18% higher (adjusted OR 1.18 95% CI 1.04−1.34) for upper white-collar workers and 12% higher (adjusted OR 1.12 95% CI 1.02−1.24) for lower white-collar workers compared with blue-collar workers. Among women in these higher SES groups, 40% of the excess OASIS risk was explained by age, non-smoking, birthweight and mode of delivery. Despite the large effect of SES on OASIS, inclusion of SES in multivariable models caused only small changes in estimated adjusted effects for other established risk factors.

Conclusions

OASIS at the first vaginal delivery demonstrates a strong positive social gradient. Higher SES is associated with a number of risk factors for OASIS, including higher birthweight and non-smoking, but only 40% of the excess incidence is explained by these known risk factors. Further research should address other underlying causes including differences in lifestyle or environmental factors, and inequalities in healthcare provision.     

The Burden of Acute Disease in Mahajanga,Madagascar – A 21 Month Study

Background

Efforts to develop effective and regionally-appropriate emergency care systems in sub-Saharan Africa are hindered by a lack of data on both the burden of disease in the region and on the state of existing care delivery mechanisms. This study describes the burden of acute disease presenting to an emergency unit in Mahajanga, Madagascar.

Methods and Findings

Handwritten patient registries on all emergency department patients presenting between 1 January 2011 and 30 September 2012 were reviewed and data entered into a database. Data included age, sex, diagnosis, and disposition. We classified diagnoses into Clinical Classifications Software (CCS) multi-level categories. The population was 53.5% male, with a median age of 31 years. The five most common presenting conditions were 1) Superficial injury; contusion, 2) Open wounds of head; neck; and trunk, 3) Open wounds of extremities, 4) Intracranial injury, and 5) Unspecified injury and poisoning. Trauma accounted for 48%, Infectious Disease for 15%, Mental Health 6.1%, Noncommunicable 29%, and Neoplasms 1.2%. The acuity seen was high, with an admission rate of 43%. Trauma was the most common reason for admission, representing 19% of admitted patients.

Conclusions

This study describes the burden of acute disease at a large referral center in northern Madagascar. The Centre Hôpitalier Universitaire de Mahajanga sees a high volume of acutely ill and injured patients. Similar to other reports from the region, trauma is the most common pathology observed, though infectious disease was responsible for the majority of adult mortality. Typhoid fever other intestinal infections were the most lethal CCS-coded pathologies. By utilizing a widely understood classification system, we are able to highlight contrasts between Mahajanga’s acute and overall disease burden as well as make comparisons between this region and the rest of the globe. We hope this study will serve to guide the development of context-appropriate emergency medicine systems in the region.     

Overexpression of Heparanase Lowers the Amyloid Burden in Amyloid-β Precursor Protein Transgenic Mice

Heparan sulfate (HS) and HS proteoglycans (HSPGs) colocalize with amyloid-β (Aβ) deposits in Alzheimer disease brain and in Aβ precursor protein (AβPP) transgenic mouse models. Heparanase is an endoglycosidase that specifically degrades the unbranched glycosaminoglycan side chains of HSPGs. The aim of this study was to test the hypothesis that HS and HSPGs are active participators of Aβ pathogenesis in vivo. We therefore generated a double-transgenic mouse model overexpressing both human heparanase and human AβPP harboring the Swedish mutation (tgHpa*Swe). Overexpression of heparanase did not affect AβPP processing because the steady-state levels of Aβ_1–40, Aβ_1–42, and soluble AβPP β were the same in 2- to 3-month-old double-transgenic tgHpa*Swe and single-transgenic tgSwe mice. In contrast, the Congo red-positive amyloid burden was significantly lower in 15-month-old tgHpa*Swe brain than in tgSwe brain. Likewise, the Aβ burden, measured by Aβ_x-40 and Aβ_x-42 immunohistochemistry, was reduced significantly in tgHpa*Swe brain. The intensity of HS-stained plaques correlated with the Aβ_x-42 burden and was reduced in tgHpa*Swe mice. Moreover, the HS-like molecule heparin facilitated Aβ_1–42-aggregation in an in vitro Thioflavin T assay. The findings suggest that HSPGs contribute to amyloid deposition in tgSwe mice by increasing Aβ fibril formation because heparanase-induced fragmentation of HS led to a reduced amyloid burden. Therefore, drugs interfering with Aβ-HSPG interactions might be a potential strategy for Alzheimer disease treatment.     

The Impact of IPTi and IPTc Interventions on Malaria Clinical Burden – In Silico Perspectives

Background

Clinical management of malaria is a major health issue in sub-Saharan Africa. New strategies based on intermittent preventive treatment (IPT) can tackle disease burden by simultaneously reducing frequency of infections and life-threatening illness in infants (IPTi) and children (IPTc), while allowing for immunity to build up. However, concerns as to whether immunity develops efficiently in treated individuals, and whether there is a rebound effect after treatment is halted, have made it imperative to define the effects that IPTi and IPTc exert on the clinical malaria scenario.

Methods and Findings

Here, we simulate several schemes of intervention under different transmission settings, while varying immunity build up assumptions. Our model predicts that infection risk and effectiveness of acquisition of clinical immunity under prophylactic effect are associated to intervention impact during treatment and follow-up periods. These effects vary across regions of different endemicity and are highly correlated with the interplay between the timing of interventions in age and the age dependent risk of acquiring an infection. However, even when significant rebound effects are predicted to occur, the overall intervention impact is positive.

Conclusions

IPTi is predicted to have minimal impact on the acquisition of clinical immunity, since it does not interfere with the occurrence of mild infections, thus failing to reduce the underlying force of infection. On the contrary, IPTc has a significant potential to reduce transmission, specifically in areas where it is already low to moderate.     

The Financial Burden of Morbidity in HIV-Infected Adults on Antiretroviral Therapy in C?te d'Ivoire

Background

Large HIV care programs frequently subsidize antiretroviral (ARV) drugs and CD4 tests, but patients must often pay for other health-related drugs and services. We estimated the financial burden of health care for households with HIV-infected adults taking antiretroviral therapy (ART) in Côte d''Ivoire.

Methodology/Principal Findings

We conducted a cross-sectional survey. After obtaining informed consent, we interviewed HIV-infected adults taking ART who had consecutively attended one of 18 HIV care facilities in Abidjan. We collected information on socioeconomic and medical characteristics. The main economic indicators were household capacity-to-pay (overall expenses minus food expenses), and health care expenditures. The primary outcome was the percentage of households confronted with catastrophic health expenditures (health expenditures were defined as catastrophic if they were greater than or equal to 40% of the capacity-to-pay). We recruited 1,190 adults. Median CD4 count was 187/mm³, median time on ART was 14 months, and 72% of subjects were women. Mean household capacity-to-pay was $213.7/month, mean health expenditures were $24.3/month, and 12.3% of households faced catastrophic health expenditures. Of the health expenditures, 75.3% were for the study subject (ARV drugs and CD4 tests, 24.6%; morbidity events diagnosis and treatment, 50.1%; transportation to HIV care centres, 25.3%) and 24.7% were for other household members. When we stratified by most recent CD4 count, morbidity events related expenses were significantly lower when subjects had higher CD4 counts.

Conclusions/Significance

Many households in Côte d''Ivoire face catastrophic health expenditures that are not attributable to ARV drugs or routine follow-up tests. Innovative schemes should be developed to help HIV-infected patients on ART face the cost of morbidity events.     

Is Cadmium Exposure Associated with the Burden,Vulnerability and Rupture of Human Atherosclerotic Plaques?

The general population is exposed to cadmium from food and smoking. Cadmium is a widely spread toxic pollutant that seems to be associated with cardiovascular diseases, although little is known if it contributes to the occurrence of atherosclerotic plaques and the process whereby plaques become vulnerable and are prone to rupture. We tested the hypotheses that cadmium exposure is associated not only with an increased subclinical burden of atherosclerotic plaques in different vascular territories and early signs of plaque vulnerability, but also with cadmium content and plaque-rupture in the clinical phase of the disease. Ultrasound technique was used to measure plaque prevalence and echogenicity in the carotid and femoral arteries in a population sample of women (n = 599) in whom blood cadmium was measured. In addition cadmium was measured in snap-frozen endarterectomies and whole blood obtained from patients who were referred to surgery because of symptomatic carotid plaques (n = 37). Sixteen endarterectomies were divided into three parts corresponding to different flow conditions and plaque vulnerability. In the population sample blood cadmium was associated with the number of vascular territories with plaques (p = 0.003 after adjustment for potential confounders). The cadmium concentrations in symptomatic plaques were 50-fold higher in plaque tissue than in blood. Cadmium levels in blood and plaque correlated, also after adjustment for smoking and other cardiovascular risk factors (p<0.001). Compared with the other parts of the plaque, the cadmium content was double as high in the part where plaque rupture usually occurs. In conclusion, the results show that cadmium exposure is associated with the burden of subclinical atherosclerosis in middle-aged women with different degrees of glucose tolerance, and that the content of cadmium in symptomatic plaques in patients is related to that in blood, but much higher, and preferentially located in the part of plaque where rupture often occurs.     

Health Disparities from Economic Burden of Diabetes in Middle-income Countries: Evidence from México

The rapid growth of diabetes in middle-income countries is generating disparities in global health. In this context we conducted a study to quantify the health disparities from the economic burden of diabetes in México. Evaluative research based on a longitudinal design, using cost methodology by instrumentation. For the estimation of epidemiological changes during the 2010–2012 period, several probabilistic models were developed using the Box-Jenkins technique. The financial requirements were obtained from expected case management costs by disease and the application of an econometric adjustment factor to control the effects of inflation. Comparing the economic impact in 2010 versus 2012 (p<0.05), there was a 33% increase in financial requirements. The total amount for diabetes in 2011 (US dollars) was $7.7 billion. It includes $3.4 billion in direct costs and $4.3 in indirect costs. The total direct costs were $.4 billion to the Ministry of Health (SSA), serving the uninsured population; $1.2 to the institutions serving the insured population (Mexican Institute for Social Security–IMSS-, and Institute for Social Security and Services for State Workers-ISSSTE-); $1.8 to users; and $.1 to Private Health Insurance (PHI). If the risk factors and the different health care models remain as they currently are in the analyzed institutions, health disparities in terms of financial implications will have the greatest impact on users’ pockets. In middle-income countries, health disparities generated by the economic burden of diabetes is one of the main reasons for catastrophic health expenditure. Health disparities generated by the economic burden of diabetes suggests the need to design and review the current organization of health systems and the relevance of moving from biomedical models and curative health care to preventive and socio-medical models to meet expected challenges from diseases like diabetes in middle-income countries.     

Bronchiectasis-Associated Hospitalizations in Germany, 2005–2011: A Population-Based Study of Disease Burden and Trends

Background

Representative population-based data on the epidemiology of bronchiectasis in Europe are limited. The aim of the present study was to investigate the current burden and the trends of bronchiectasis-associated hospitalizations and associated conditions in Germany in order to inform focused patient care and to facilitate the allocation of healthcare resources.

Methods

The nationwide diagnosis-related groups hospital statistics for the years 2005–2011 were used in order to identify hospitalizations with bronchiectasis as any hospital discharge diagnosis according to the International Classification of Diseases, 10th revision, code J47, (acquired) bronchiectasis. Poisson log-linear regression analysis was used to assess the significance of trends. In addition, the overall length of hospital stay (LOS) and the in-hospital mortality in comparison to the nationwide overall mortality due to bronchiectasis as the primary diagnosis was assessed.

Results

Overall, 61,838 records with bronchiectasis were extracted from more than 125 million hospitalizations. The average annual age-adjusted rate for bronchiectasis as any diagnosis was 9.4 hospitalizations per 100,000 population. Hospitalization rates increased significantly during the study period, with the highest rate of 39.4 hospitalizations per 100,000 population among men aged 75–84 years and the most pronounced average annual increases among females. Besides numerous bronchiectasis-associated conditions, chronic obstructive pulmonary disease (COPD) was most frequently found in up to 39.2% of hospitalizations with bronchiectasis as the primary diagnosis. The mean LOS was comparable to that for COPD. Overall, only 40% of bronchiectasis-associated deaths occurred inside the hospital.

Conclusions

The present study provides evidence of a changing epidemiology and a steadily increasing prevalence of bronchiectasis-associated hospitalizations. Moreover, it confirms the diversity of bronchiectasis-associated conditions and the possible association between bronchiectasis and COPD. As the major burden of disease may be managed out-of-hospital, prospective patient registries are needed to establish the exact prevalence of bronchiectasis according to the specific underlying condition.     

Reduced Peripheral Expression of the Glucocorticoid Receptor α Isoform in Individuals with Posttraumatic Stress Disorder: A Cumulative Effect of Trauma Burden

Background

Posttraumatic stress disorder (PTSD) is a serious psychiatric condition that was found to be associated with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis and changes in glucocorticoid (GC) responsiveness. The physiological actions of GCs are primarily mediated through GC receptors (GR) of which isoforms with different biological activities exist. This study aimed to investigate whether trauma-experience and/or PTSD are associated with altered expression of GR splice variants.

Methods

GRα and GRβ mRNA expression levels were determined by real-time quantitative PCR in whole blood samples of individuals with chronic and severe forms of PTSD (n = 42) as well as in ethnically matched reference subjects (non-PTSD, n = 35).

Results

Individuals suffering from PTSD exhibited significantly lower expression of the predominant and functionally active GRα isoform compared to non-PTSD subjects. This effect remained significant when accounting for gender, smoking, psychotropic medication or comorbid depression. Moreover, the GRα expression level was significantly negatively correlated with the number of traumatic event types experienced, both in the whole sample and within the PTSD patient group. Expression of the less abundant and non-ligand binding GRβ isoform was comparable between patient and reference groups.

Conclusions

Reduced expression of the functionally active GRα isoform in peripheral blood cells of individuals with PTSD seems to be a cumulative effect of trauma burden rather than a specific feature of PTSD since non-PTSD subjects with high trauma load showed an intermediate phenotype between PTSD patients and individuals with no or few traumatic experiences.     

Long-Term Burden and Respiratory Effects of Respiratory Syncytial Virus Hospitalization in Preterm Infants—The SPRING Study

The health status of premature infants born 32¹-35⁰ weeks’ gestational age (wGA) hospitalized for RSV infection in the first year of life (cases; n = 125) was compared to that of premature infants not hospitalized for RSV (controls; n = 362) through 6 years. The primary endpoints were the percentage of children with wheezing between 2-6 years and lung function at 6 years of age. Secondary endpoints included quality of life, healthcare resource use, and allergic sensitization. A significantly higher proportion of cases than controls experienced recurrent wheezing through 6 years of age (46.7% vs. 27.4%; p = 0.001). The vast majority of lung function tests appeared normal at 6 years of age in both cohorts. In children with pulmonary function in the lower limit of normality (FEV₁ Z-score [-2; -1]), wheezing was increased, particularly for cases vs. controls (72.7% vs. 18.9%, p = 0.002). Multivariate analysis revealed the most important factor for wheezing was RSV hospitalization. Quality of life on the respiratory subscale of the TAPQOL was significantly lower (p = 0.001) and healthcare resource utilization was significantly higher (p<0.001) in cases than controls. This study confirms RSV disease is associated with wheezing in 32-35 wGA infants through 6 years of age.     

Potato Glycoalkaloids: A Burden or a Blessing?

Steroidal glycoalkaloids (SGAs) are produced following the general steroid biosynthesis pathway, starting from acetyl-coenzyme A and followed by the intermediates mevalonic acid, squalene, cycloartenol, and cholesterol. α-Chaconine and α-solanine are the main SGAs of the cultivated potato (Solanum tuberosum), whereas many other SGAs are known in the wild potato species. Low concentrations of SGAs improve the taste of potato, but concentrations greater than 200 mg/kg can have toxic effects on animals and humans. SGAs have antimicrobial activity and confer resistance to some insects, but many such pests of potato are not greatly affected. Certain environmental conditions and wounding enhance SGA accumulation in tubers in the field and storage. Low production of SGAs is a dominant character inherited in a relatively simple manner and can be selected for in potato-breeding programs, whereas the use of wild potato germplasm tends to increase the SGA accumulation in the breeding lines. Further efforts are likely to be directed toward the reduction of the SGA content in the edible potato products through breeding and biotechnological methodologies, whereas potato genotypes with high SGA production may be developed for use in the pharmaceutical industry.