The household economic burden of non-communicable diseases in 18 countries

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. METHODS: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. RESULTS: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. CONCLUSIONS: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs. (AU)

Amino acid and hyaluronic acid mixtures differentially regulate extra cellular matrix genes in cultured human fibroblasts.

The aim of this screening study was to evaluate the efficacy of different proprietary mixtures of amino acid and hyaluronic acid (HA) in stimulating the production of extracellular matrix (ECM) components, particularly the neo-synthesis of elastin, and in promoting a more efficient deposition of elastic fibres (elastogenesis), while at the same time maintaining the stimulation of collagen. The study has allowed identification of the optimal ratios between the amino acids (AA) for the production of collagen and elastin. Human primary dermal fibroblasts from a 44-year-old female donor were used as a test system in an experimental design based on the evaluation of the expression of relevant ECM genes using a transcriptomic dynamic approach. The expression of ECM genes was evaluated by RTqPCR from 24 to 120 hours in the presence of the test items. Moreover, the production of ECM proteins was verified by Western blot analysis after a 120 h treatment period. In addition to elastin, collagen IV, a fundamental structural component of the basal lamina responsible for epithelial and connective tissue anchoring, was analysed as potential target for the modulation of ECM protein production by human fibroblast. The first phase of the study demonstrated that alanine and valine are essential to promote production of elastin, of which they are important constituents. The second phase of the study, which was conducted to clarify the interactions between the different clusters of AA, demonstrated that it is necessary to choose a mixture that contains specific amounts of amino acids of both proteins, collagen and elastin, to give a significant response and a significant production of both. This also proves the existence of a ratio between the 2 clusters (AA elastin/AA collagen) that guarantees an adequate and balanced response to gene expression and production by fibroblasts, collagen and elastin. The study has allowed identification of the optimal ratios between the AA for the production of collagen and elastin.

The environmental profile of a community's health: a cross-sectional study on tobacco marketing in 16 countries

To examine and compare tobacco marketing in 16 countries while the Framework Convention on Tobacco Control requires parties to implement a comprehensive ban on such marketing.METHODS:Between 2009 and 2012, a kilometre-long walk was completed by trained investigators in 462 communities across 16 countries to collect data on tobacco marketing. We interviewed community members about their exposure to traditional and non-traditional marketing in the previous six months. To examine differences in marketing between urban and rural communities and between high-, middle- and low-income countries, we used multilevel regression models controlling for potential confounders.FINDINGS:Compared with high-income countries, the number of tobacco advertisements observed was 81 times higher in low-income countries (incidence rate ratio, IRR: 80.98; 95% confidence interval, CI: 4.15-1578.42) and the number of tobacco outlets was 2.5 times higher in both low- and lower-middle-income countries (IRR: 2.58; 95% CI: 1.17-5.67 and IRR: 2.52; CI: 1.23-5.17, respectively). Of the 11,842 interviewees, 1184 (10%) reported seeing at least five types of tobacco marketing. Self-reported exposure to at least one type of traditional marketing was 10 times higher in low-income countries than in high-income countries (odds ratio, OR: 9.77; 95% CI: 1.24-76.77). For almost all measures, marketing exposure was significantly lower in the rural communities than in the urban communities.CONCLUSION:Despite global legislation to limit tobacco marketing, it appears ubiquitous. The frequency and type of tobacco marketing varies on the national level by income group and by community type, appearing to be greatest in low-income countries and urban communities.

Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study

BACKGROUND:Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a simple, quick, and inexpensive means of stratifying an individual's risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries.METHODS:The Prospective Urban-Rural Epidemiology (PURE) study is a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years and if household members intended to stay at that address for another 4 years. Participants were assessed for grip strength, measured using a Jamar dynamometer. During a median follow-up of 4.0 years (IQR 2.9-5.1), we assessed all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia or chronic obstructive pulmonary disease (COPD), hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury due to fall, and fracture. Study outcomes were adjudicated using source documents by a local investigator, and a subset were adjudicated centrally.FINDINGS:Between January, 2003, and December, 2009, a total of 142,861 participants were enrolled in the PURE study, of whom 139,691 with known vital status were included in the analysis. During a median follow-up of 4.0 years (IQR 2.9-5.1), 3379 (2%) of 139,691 participants died. After adjustment, the association between grip strength...

Impact of age on viral kinetics of peginterferon alfa-2a/ribavirin in chronic hepatitis C: final analysis from the PROPHESYS cohort.

The population of patients with chronic hepatitis C viral infection is ageing; however, elderly, hepatitis C-infected patients are understudied and less frequently treated. This subanalysis of data from the multinational PROPHESYS study examined associations between age (≤65 vs >65 years), on-treatment virological response and sustained virological response (SVR) in patients treated with peginterferon alfa-2a (40KD)/ribavirin in accordance with local licences. PROPHESYS comprised three cohorts studied in 19 countries according to country-specific legal and regulatory requirements. This subanalysis includes treatment-naive HCV mono-infected patients assigned to receive peginterferon alfa-2a (40KD)/ribavirin, with 6276 individuals aged ≤65 years and 349 aged >65 years. Rapid virological response (RVR) rates by Week 4 were consistently lower in older genotype (G) 1 (21.6% vs 27.2% in younger patients), G2 (80.7% vs 85.1%) and G3 (60.0% vs 74.2%) patients. SVR rates were significantly lower (29.8% vs 43.0%) and relapse rates significantly higher (43.1% vs 26.7%) in older G1 patients (P = 0.0002 vs ≤65 years). In contrast, SVR and relapse rates were similar in G2 and G3 patients regardless of age. The positive predictive value of RVR for SVR was comparable in older and younger G1 patients (66.7% vs 68.6%, respectively) and higher in older G2 (80.7% vs 75.6%) and G3 (77.8% vs 66.8%) patients. Virological response rates are generally lower in elderly CHC patients, and RVR is a reliable positive predictor of SVR in patients >65 years.

Early kinetics of innate and adaptive immune responses during hepatitis B virus infection.

BACKGROUND AND AIMS: Innate immunity appears to be silent in acutely hepatitis B virus (HBV)-infected chimpanzees, as shown by microarray analysis of intrahepatic gene expression. Whether this observation also applies to HBV pathogenesis in man remains undefined. The aim of this study was thus to characterise natural killer (NK) and CD56(+) natural T (NT) cell responses early after human HBV infection and their relationship to the induction of adaptive immunity. METHODS: Two HBV-seronegative blood donors who became hepatitis B surface antigen (HBsAg) and HBV DNA positive but had persistently normal alanine aminotransferase (ALT) were followed from a very early stage of HBV infection. The phenotype (CD69 and NKG2D) and function (cytotoxicity and interferon gamma (IFN gamma) production) of NK and NT cells were analysed. CD4- and CD8-mediated responses were studied in parallel with overlapping peptides covering the entire HBV sequence by ex vivo intracellular cytokine staining (ICS) for IFN gamma, interleukin 2 (IL2), IL4 and IL10, and by ex vivo Elispot for IFN gamma. Healthy subjects, and patients with chronic and acute HBV infection were studied for comparison. RESULTS: An early induction of both innate and adaptive responses was observed. NK and NT cells showed faster kinetics than HBV-specific T cells with an earlier peak of activity, while CD4(+) and CD8(+) cell responses were mounted with a similar profile, with higher frequencies of IFN gamma-producing CD8(+) cells at the peak of the response. CONCLUSIONS: The innate immune system is able to sense HBV infection, as shown by the early development of NK and NT cell responses, which probably contribute to contain the HBV infection and to allow timely induction of adaptive responses.

Speciation study of the anti-inflammatory drug tenoxicam (Htenox) with Cu(II): X-ray crystal structure of [Cu(tenox)(2)(py)(2)].EtOH.

A speciation study was carried out in aqueous solution of the anti-inflammatory drug tenoxicam (Htenox), under quasi-physiological conditions (temperature of 37 degrees C and ionic strength 0.15 M NaCl) in order to determine the acidity constants from spectrophotometric studies, the pK(a) values found being pK(1)=1.143+/-0.008 and pK(2)=4.970+/-0.004. Subsequently, the spectrophotometrical speciation of the different complexes of Cu(II) with the drug was performed under the same conditions of temperature and ionic strength, observing the formation of Cu(Htenox)(2)(2+) with log beta(212)=20.05+/-0.01, Cu(tenox)(2) with log beta(012)=13.6+/-0.1, Cu(Htenox)(2+) with log beta(111)=10.52+/-0.08, as well as Cu(tenox)(+) with log beta(011)=7.0+/-0.2, all of them in solution, and solid species Cu(tenox)(2)(s) with an estimated value of log beta(012)(s) approximately 18.7. The crystalline structure of the complex [Cu(tenox)(2)(py)(2)]. EtOH, was also determined, and it was observed that tenoxicam employs the oxygen of the amide group and the pyridyl nitrogen to bond to the cation.

Urinary excretion of glucagon-like peptide 1 (GLP-1) 7-36 amide in human type 2 (non-insulin-dependent) diabetes mellitus.

The urinary excretion of insulinotropic glucagon-like peptide 1 (GLP-1) was investigated as an indicator of renal tubular integrity in 10 healthy subjects and in 3 groups of type 2 diabetic patients with different degrees of urinary albumin excretion rate. No significant difference emerged between the groups with respect to age of the patients, known duration of diabetes, metabolic control, BMI, or residual beta-cell pancreatic function. Endogenous creatinine clearance was significantly reduced under conditions of overt diabetic nephropathy, compared with normo and microalbuminuric patients (p < 0.01). Urinary excretion of GLP-1 was significantly higher in normoalbuminuric patients compared to controls (490.4 +/- 211.5 vs. 275.5 +/- 132.1 pg/min; p < 0.05), with further increase under incipient diabetic nephropathy conditions (648.6 +/- 305 pg/min; p < 0.01). No significant difference resulted, in contrast, between macroproteinuric patients and non-diabetic subjects. Taking all patients examined into account, a significant positive relationship emerged between urinary GLP-1 and creatinine clearance (p = 0.004). In conclusion, an early tubular impairment in type 2 diabetes would occur before the onset of glomerular permeability alterations. The tubular dysfunction seems to evolve with the development of persistent microalbuminuria. Finally, the advanced tubular involvement, in terms of urinary GLP1 excretion, under overt diabetic nephropathy conditions would be masked by severe concomitant glomerular damage with the coexistence of both alterations resulting in a peptide excretion similar to control subjects.

Beryllium(II) complexes of the Kläui tripodal ligand cyclopentadienyltris(diethylphosphito-p)cobaltate(-).

The interactions of the beryllium(II) ion with the cyclopentadienyltris(diethylphosphito-P)cobaltate monoanion, L(-), have been investigated, in aqueous solution, by synthetic methods, potentiometry, ESMS, and (1)H, (31)P, and (9)Be NMR spectroscopy. L(-) has been found able to displace either two or three water molecules in the beryllium(II) coordination sphere, to form mononuclear, dinuclear, and trinuclear derivatives, in which the metal ion is pseudotetrahedrally coordinated. The species [BeL(H(2)O)](+) and [Be(2)L(2)(mu-OH)](+) have been identified in solution while complexes of formula BeL(2) and [Be(3)L(4)](ClO(4))(2) have been isolated as solid materials. The species [BeL(OPPh(2))](+), closely related to [BeL(H(2)O)](+), has been characterized in acetone solution and isolated as tetraphenylborate salt. The structure of the unusual trimeric complex [Be(3)L(4)](2+) has been elucidated by an unprecedented 2D (9)Be-(31)P NMR correlation spectrum showing the presence of a single central beryllium nucleus and two equivalent terminal beryllium nuclei. The three beryllium centers are held together by four cobaltate ligands, which display two different bonding modes: two ligands are terminally linked with all the three oxygen donors to one terminal beryllium, and the other two bridge two metal centers, sharing the oxygen donors between central and terminal beryllium atoms.

Spinal dysraphism in an elderly patient.

Spinal dysraphisms are diagnosed more frequently at birth or in infancy. We report a spinal malformation compatible with lipomyeloschisis in an elderly patient presenting with symptoms and signs of myelopathy. Magnetic resonance imaging revealed an intraspinal mass continuous with a subcutaneous lipoma. Three-dimensional computed tomography reconstructions better showed the spinal dysraphism; dermal sinus was also evident. Neuroimaging can define the precise diagnosis also in elderly patients presenting with myelopathy and can provide valuable structural details.

Effect of nutrient ingestion on glucagon-like peptide 1 (7-36 amide) secretion in human type 1 and type 2 diabetes.

Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2 diabetic patients, resulting the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect. GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients, suggesting an impairment of the entero-insular axis in both diabetic conditions. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1 concentrations, both at fasting and in response to nutrient ingestion, in 16 type 1 diabetic patients (age = 40.5 +/- 14yr, HbA1C = 7.8 +/- 1.5%), 14 type 2 diabetics (age = 56.5 +/- 13yr, HbA1C = 8.1 +/- 1.8%), and 10 matched controls. In postabsorptive state, a mixed breakfast (230 KCal) was administered to all subjects and blood samples were collected for plasma glucose, insulin, C-peptide and GLP-1 determination during the following 3 hours. In normal subjects, the test meal induced a significant increase of GLP-1 (30', 60': p < 0.01), returning the peptide values towards basal concentrations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to controls (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion failed to increase plasma peptide levels, which even decreased during the test (p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1 diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 pg/ml). With respect to controls, the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60' (p < 0.01). In conclusion, either in condition of insulin resistance or insulin deficiency chronic hyperglycemia, which is a common feature of both metabolic disorders, could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation.

Usefulness of pharmacologic stress echocardiography in a chest pain center.

We tested the value of a stress echocardiography-based algorithm used in a chest pain center. The algorithm had superlative negative predictive value for cardiac events, allowing an early discharge.

Acute cardiac rupture during dobutamine-atropine echocardiography stress test.

We report an acute cardiac rupture during dobutamine-atropine echocardiography stress test on the sixth day after admission for an inferoposterior acute myocardial infarction complicated with mild pericardial effusion.

Superficial siderosis of the central nervous system and anticoagulant therapy: a case report.

Superficial siderosis of the central nervous system is a rare condition characterized by deposition of haemosiderin in the leptomeninges and in the subpial layers of the brain and spinal cord. With the widespread use of magnetic resonance imaging, an increasing number of cases of superficial siderosis are being discovered, secondary forms being more frequent than idiopathic ones. We report a 78-year-old man in oral anticoagulant therapy, who presented neurosensory hearing loss, gait ataxia and spastic paraparesis. Magnetic resonance imaging suggested the diagnosis of superficial siderosis of the central nervous system, without an evident bleeding source.

Platelet activating factor is elevated in cerebral spinal fluid and plasma of patients with relapsing-remitting multiple sclerosis.

Platelet-activating factor (PAF) is a phospholipid mediator of inflammation with a wide range of biological activities, including the alteration of barrier function of endothelium. A biological assay combined with high pressure liquid chromatography-tandem mass spectrometry showed that plasma and cerebral spinal fluid (CSF) PAF levels in 20 patients with relapsing/remitting or secondary progressive multiple sclerosis (MS) studied by magnetic resonance imaging (MRI) were significantly higher than in healthy controls (plasma: 3.29+/-4.52 vs. 0.48+/-0.36 ng/ml, p < 0.002; CSF: 4.95+/-6.22 ng/ml vs. 0.01+/-0.04 ng/ml, p < 0.0001). Values were also significantly higher in relapsing/remitting than in secondary progressive (plasma: 5.10+/-4.97 vs. 0.52+/-0.85 ng/ml, p < 0.005; CSF: 8.59+/-6.39 vs. 0.55+/-0.68 ng/ml, p < 0.002). It was also found that both plasma (R2: 0.65) and CSF (R2:0.72) levels were correlated with the MRI number of gadolinium enhancing lesions, which are markers of blood-brain barrier (BBB) injury, whereas their peaks were not correlated with the MRI number of white matter lesions, nor with the expanded disability status score (EDSS) according to Kurtze [Kurtze, J.F., 1983. Rating neurological impairment in multiple sclerosis: an expanded disability scale (EDSS). Neurology 33, 1444-1452]. Both plasma and CSF in patients with relapsing/remitting MS and marked gadolinium enhancement contained the two major molecular species of PAF: 1-0-hexadecyl- (C16:O) and 1-0-octadecyl-sn-glycero-3-phosphocholine (C18:O). The ratio of the two molecular species was different in the two biological fluids, being PAF C18:0 more abundant in CSF and PAF C16:0 in plasma, indicating a different cellular origin of PAF or different enzymatic processing. These findings suggest that PAF is a significant mediator of BBB injury in the early stages of MS, rather than a marker of its progression and severity.

Mechanism of liver allograft rejection: the indirect recognition pathway.

Transplant rejection is mediated by the direct and indirect pathways. To explore the role of the indirect recognition pathway in the rejection of liver allografts, T cells obtained from peripheral blood were expanded in medium containing IL-2 and tested in LDA for reactivity to synthetic peptides corresponding to the hypervariable regions of the mismatched HLA-DR antigen(s) of the donor. Serial investigations of 17 recipients showed that T-cell reactivity to donor HLA-DR peptides was strongly associated with acute rejection episodes. In recipients carrying a graft that was mismatched by two HLA-DR alleles, a single donor antigen was targeted during primary rejection, although allopeptide reactivity against the second HLA-DR antigen was observed during subsequent episodes of acute rejection. The finding that allopeptide reactivity occurs early following transplantation and is predictive of rejection is consistent with the notion that processing of donor alloantigens by recipient APCs activates the indirect T-cell recognition pathway that plays a major role in initiating and amplifying allograft rejection.

Personality traits and metabolic control: a study in insulin-dependent diabetes mellitus patients.

BACKGROUND: In the present study the authors evaluated the relationship between personality traits (according to DSM-III-R) and poor metabolic control in an adult onset insulin-dependent diabetes mellitus sample (n = 77). METHODS: Personality traits were assessed with the Personality Diagnostic Questionnaire--Revised. Metabolic control was evaluated through glycosilated hemoglobin (HbA1c): poor metabolic control was defined as HbA1c > or = 9% (normal values < 6.0%). RESULTS: Principal Component Analysis revealed three personality profiles: 'Cluster A/C Mixed', 'Cluster B Dependent' and 'Cluster B Aggressive'. Oneway ANCOVA, using sex as covariate, revealed a significant association (p = 0.01) only between poor metabolic control and Cluster B Dependent profile. No correlation was found between HbA1c and the other profiles. CONCLUSION: These data suggest that a specific personality profile is associated with poor metabolic control.