Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer.

CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar transcriptome profiling across different types of cancer in comparison with healthy tissue-resident T-cells. Thus, we analyzed the single cell transcriptome of five tumor-infiltrating CD4-T, CD8-T and Treg cells obtained from different types of cancer to identify specific pathways for each subset in malignant environments. An in silico analysis was performed from single-cell RNA-sequencing data available in public repositories (Gene Expression Omnibus) including breast cancer, melanoma, colorectal cancer, lung cancer and head and neck cancer. After dimensionality reduction, clustering and selection of the different subpopulations from malignant and nonmalignant datasets, common genes across different types of cancer were identified and compared to nonmalignant genes for each T-cell subset to identify specific pathways. Exclusive pathways in CD4+ cells, CD8+ cells and Tregs, and common pathways for the tumor-infiltrating T-cell subsets were identified. Finally, the identified pathways were compared with RNAseq and proteomic data obtained from T-cell subsets cultured under malignant environments and we observed that cytokine signaling, especially Th2-type cytokine, was the top overrepresented pathway in Tregs from malignant samples.

The Epidemiology of Abortion And Its Prevention in Chile.

Mortality by abortion has continuously decreased over the past fifty years in Chile. In fact, maternal death as a result of an induced abortion has become an exceptionally rare phenomenon in epidemiological terms (a risk of 1 in 4 million pregnant women of fertile age or 0.4 per 100,000 life births for abortion of any type, excluding ectopic pregnancy). After abortion became illegal in 1989, deaths related to abortion continued to decrease from 10.8 to 0.39 per 100,000 live births. This scientific fact challenges the common notion that less permissive abortion laws lead to greater mortality associated with abortion.

[Influence of psychosocial factors on adherence to antihypertensive drug therapy: results from a Cardiovascular Health Program cohort followed in the Metropolitan Region of Santiago, Chile]. / Influencia de factores psicosociales en la adherencia al tratamiento farmacológico antihipertensivo: Resultados de una cohorte del Programa de Salud Cardiovascular de la Región Metropolitana, Chile.

BACKGROUND: Inadequate blood pressure control in hypertensive patients remains a persistent health problem in Chile and worldwide. Poor adherence to antihypertensive drug therapy is one of the frequently cited factors. OBJECTIVES: To determine the influence of psychosocial factors in the adherence to drug therapy in hypertensive patients followed through a Cardiovascular Health Program (CHP) that provides free access to primary care centers located in the Metropolitan Region of Santiago, Chile. METHODS: Cross sectional study. A randomized sample of 513 hypertensive patients (30 to 68 years) was obtained from a universe of 1.484 patients. Adherence to treatment was determined by the Morisky-Green-Levine test. Demographic, socioeconomic and average values of blood pressure were recorded. Validated questionnaires were utilized to assess the patient-physician relationship, awareness of being hypertensive, patient perception of social support, family cohesion, patient self-health assessment and symptoms of emotional stress and depression. RESULTS: The drug therapy adherence was 36.6%, higher in women (38.4% vs 28.9%; p < 0.001). After multivariate analysis, absence of adherence was associated with male gender (OR: 1.76 [95% CI 1.21-2.56]), low education (OR: 1.72 [95% CI 1.18 to 2.53]), inadequate patient-physician relationship (OR: 1.56 [95% CI 1.13 to 2.27]), and high level of emotional stress and depression (OR: 1.93 [95% CI 1.27 to 2.94]). CONCLUSIONS: Our study highlights the influence of inadequate patient-physician relation, high level of emotional stress and depression, low education level and income and male gender in the lack of adherence to antihypertensive drug therapy in hypertensive patients followed throughout the CHP.

Effects of emerging SARS-CoV-2 on total and cause-specific maternal mortality: A natural experiment in Chile during the peak of the outbreak, 2020-2021.

This study estimated the effects of the COVID-19 pandemic on maternal mortality in Chile between 2020 and 2021. A natural experiment was conducted using official data on maternal deaths and live births (LBs) between 1997 and 2021. The effects of the SARS-CoV-2 outbreak were evaluated using interrupted time series (ITS) and an autoregressive integrated moving average (ARIMA) model to forecast the expected rates on MMR and 95% confidence intervals (95% CI). In Chile, following World Health Organization suggestions, maternal deaths aggravated by SARS-CoV-2 are assigned to code O98.5 (non-respiratory infectious indirect) accompanied by code U07.1 or U07.2, depending on confirmation of the presence or absence of the virus. ITS analysis revealed that the SARS-CoV-2 outbreak impacted the MMR due to indirect causes, with a greater increase in indirect nonrespiratory causes than respiratory causes. The ARIMA forecast was consistent with ITS, showing that the expected MMR for indirect causes (3.44 in 2020 and 1.55 in 2021) was substantially lower than the observed rates (9.65 in 2020 and 7.46/100.000 LBs in 2021). For nonrespiratory indirect causes, the observed values of the MMR for 2020 (8.77/100.000 LBs) and 2021 (7.46/100.000 LBs) were double the predicted values of 4.02 (95% CI: 0.44-7.61) and 3.83 (95% CI: -0.12-7.79), respectively. A lower effect was observed on direct obstetrical deaths. During 2020-2021, there was a rise in the MMR in Chile attributable to SARS-CoV-2. The pandemic contributed to an escalation in the MMR due to indirect causes, particularly nonrespiratory and infectious causes. MMR due to direct obstetric causes were less affected. This suggests that the pandemic disproportionately affected maternal health by exacerbating conditions unrelated to pregnancy, childbirth, or postpartum, more than those directly linked to obstetric complications.

Inorganic Polyphosphate Affects Biofilm Assembly, Capsule Formation, and Virulence of Hypervirulent ST23 Klebsiella pneumoniae.

The emergence of hypervirulent Klebsiella pneumoniae (hvKP) strains poses a significant threat to public health due to high mortality rates and propensity to cause severe community-acquired infections in healthy individuals. The ability to form biofilms and produce a protective capsule contributes to its enhanced virulence and is a significant challenge to effective antibiotic treatment. Polyphosphate kinase 1 (PPK1) is an enzyme responsible for inorganic polyphosphate synthesis and plays a vital role in regulating various physiological processes in bacteria. In this study, we investigated the impact of polyP metabolism on the biofilm and capsule formation and virulence traits in hvKP using Dictyostelium discoideum amoeba as a model host. We found that the PPK1 null mutant was impaired in biofilm and capsule formation and showed attenuated virulence in D. discoideum compared to the wild-type strain. We performed a proteomic analysis to gain further insights into the underlying molecular mechanism. The results revealed that the PPK1 mutant had a differential expression of proteins involved in capsule synthesis (Wzi-Ugd), biofilm formation (MrkC-D-H), synthesis of the colibactin genotoxin precursor (ClbB), as well as proteins associated with the synthesis and modification of lipid A (ArnB-LpxC-PagP). These proteomic findings corroborate the phenotypic observations and indicate that the PPK1 mutation is associated with impaired biofilm and capsule formation and attenuated virulence in hvKP. Overall, our study highlights the importance of polyP synthesis in regulating extracellular biomolecules and virulence in K. pneumoniae and provides insights into potential therapeutic targets for treating K. pneumoniae infections.

Impact of reproductive laws on maternal mortality: the chilean natural experiment.

Improving maternal health and decreasing morbidity and mortality due to induced abortion are key endeavors in developing countries. One of the most controversial subjects surrounding interventions to improve maternal health is the effect of abortion laws. Chile offers a natural laboratory to perform an investigation on the determinants influencing maternal health in a large parallel time-series of maternal deaths, analyzing health and socioeconomic indicators, and legislative policies including abortion banning in 1989. Interestingly, abortion restriction in Chile was not associated with an increase in overall maternal mortality or with abortion deaths and total number of abortions. Contrary to the notion proposing a negative impact of restrictive abortion laws on maternal health, the abortion mortality ratio did not increase after the abortion ban in Chile. Rather, it decreased over 96 percent, from 10.8 to 0.39 per 100,000 live births. Thus, the Chilean natural experiment provides for the first time, strong evidence supporting the hypothesis that legalization of abortion is unnecessary to improve maternal health in Latin America.

Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome.

Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

[Overestimation of the ocurrence of induced abortions in Colombia and other Latinoamerican countries]. / Sobrestimación del aborto inducido en Colombia y otros países latinoamericanos.

Recently, the Guttmacher Institute estimated a number of 400,400 clandestine abortions for Colombia. Because of the strong implications that such brief could have in different areas of interest, a full revision of the methodology of estimation was performed. The methodology used by the Guttmacher Institute was as follows: first, the authors estimated the losses from spontaneous and induced abortions from the opinion of 289 subjects who work in an equal number of Colombian health institutions through the opinion survey entitled "Health Facilities Survey". Subsequently, an expansive multiplier (x3, x4, x5, etc.) was applied to the numbers obtained by this survey that also emerges from a subjective opinion of another 102 respondents of the "Health Professional Survey" selected by convenience. There is no objective data based on real vital events, the whole estimate is based on imagining/numbers underlying mere opinions. Even as public opinion survey, the sampling technique introduced serious selection bias in the gathering of information. Valid epidemiological methods using standardized rates, choosing the paradigmatic cases of Chile and Spain as standard populations, it was observed that Guttmacher Institute methodology overestimates more than 9 times the complications due to induced abortion in hospital discharges and more than 18 times the total number of induced abortions. In other Latin American countries where the same methodology was applied including Argentina, Brazil, Chile, Mexico, Peru, Guatemala, and Dominican Republic, the number of induced abortions was also largely overestimated. These results call for caution with this type of reports that alarm public opinion.

Impact of emerging virus pandemics on cause-specific maternal mortality time series: a population-based natural experiment using national vital statistics, Argentina 1980-2017.

Background: Emerging pandemic viruses may have multiple deleterious effects on maternal health. This study examines the effects of a pandemic influenza virus on cause-specific maternal mortality time series, using Argentinian vital statistics. Methods: We conducted a population-based natural experiment from national vital records of maternal deaths between 1980 and 2017. Joinpoint regression models were used to model time series of the maternal mortality ratio (MMR). The sensitivity of the registry to detect the effects of the pandemic H1N1 2009 influenza virus on cause-specific MMR was analysed using a panel of parallel interrupted time series (ITS). Findings: Over this 38-year study, the MMR decreased by 58·6% (69·5 to 28·8 deaths/100,000 live births), transitioning from direct obstetric causes (67·0 to 21·1/100,000 live births; 68·4% decrease) to indirect causes (2·6 to 7·7/100,000 live births; 196·2% increase). The regression analysis showed an average reduction of -2·2%/year (95% CI: -2·9 to -1·4) with 2 join points in the total trend (1998 and 2009). Parallel ITS analyses revealed the pandemic H1N1 virus had an increasing effect on mortality from the respiratory system- and sepsis-related complications (level change 4·7 and 1·6/100,000 live births respectively), reversing after the outbreak. No effect was found on MMR from hypertensive disorders, haemorrhage, abortive outcomes, other direct obstetric causes, and indirect non-respiratory comorbidities. Interpretation: The Argentinian maternal death registry appears sensitive to detect different effects of emerging infectious epidemics on maternal health. In a population-based natural experiment, pandemic H1N1 virus impacted maternal mortality almost exclusively from the respiratory system- and sepsis-related complications. Funding: Supported by FISAR www.fisarchile.org.

Proteogenomic analysis in an early onset diffuse gastric cancer patient revealed alterations in PIK3R1, TP53, SMAD4 and a potential role of the PI3K-AKT and EGFR pathways: a case report.

Background: Early-onset gastric cancers (EOGC) are poor prognosis hard-to treat malignancies that affect young individuals (<45 years old). Case Description: Herein we describe the case of a 26-year-old female EOGC patient that initially displayed stable disease after first-line CAPOX plus immunotherapy. However, patient eventually developed progressive disease and was consecutively switched to paclitaxel plus ramucirumab, and palliative irinotecan. In search for therapeutic alternatives a proteo-genomic analysis was performed in a tissue biopsy taken after the first progression. Our analyses found a total of 18 somatic mutations, including TP53 and PIK3R1, and a previously unreported germline alteration in the tumor suppressor SMAD4. Also, our proteomic analysis found 62 proteins previously documented as "enriched in stomach cancer" and AKT/mTOR and EGFR as pathways with therapeutic potential. Unfortunately, the clinical utility of AKT/mTOR inhibitors or EGFR targeted therapies could not be assessed. Conclusions: As explained above EOGC is a growing health concern that affects young individuals. Furthermore, the reported case displayed a poor response to standard therapy including checkpoint inhibitors and chemotherapy despite the presence of biomarkers that predict a favorable outcome. Future studies should adopt alternative approaches to find novel, more effective therapies.

Popperian epidemiology and the logic of bi-conditional modus tollens arguments for refutational analysis of randomised controlled trials.

Popperian epidemiology is a biomedical science tool based on the hypothesis-deductive method and the falsifiability of scientific hypotheses. This article explores the applicability of the refutationist logic tools in the analysis of a randomised controlled trial (RCT), the randomised Aldactone evaluation study (RALES). This was carried out by using bi-conditional modus-tollens arguments of the type (i) P-then-Q(n) and (ii) Q(n)-If-X(P), X(P) being a set of potential falsifiers of Q(n) as part of the explicit falsity-content of P. In this model, P is the main hypothesis and Q(n) one or more logical predictions to be tested. The X(P) argument represents inclusion criteria, exclusion criteria and conditional criteria of the RCT so every P-then-X(P) argument should be fulfilled in canonical form to corroborate P-then-Q(n). Thus, falsifiability of a RCT would be determined by the empirical content of the conditional argument Q(n)-If-X(P) and its external validity would be determined by the empirical content of X(P). In this way it would be possible to mathematically assess the external validity of a RCT if the observational predicates of the X(P) argument in a given population are known. According to this popperian model, applicability of the RCT results to clinical practice implies transferring of all its empirical content, in other words, the totality of its truth and falsity contents. Thus, to ignore the explicit falsity-content of a RCT such as RALES may jeopardise its potential benefits in clinical practice as suggested by recent studies.

A landmark for popperian epidemiology: refutation of the randomised Aldactone evaluation study.

In 1999 a great multi-site clinical trial known as the randomised Aldactone evaluation study (RALES) showed that the use of spironolactone importantly reduced complications attributable to chronic heart failure without major negative side effects. Recently, RALES has been questioned by a large scale observational study in the Ontario population. In contrast with predictions, the complications and mortality increased dramatically because of hyperkalaemia, reaching dimensions that from a public health perspective are comparable to an epidemic. This review analyses both researches in the light of Karl Popper's science theory applying the modus tollens syllogism to the reality proposed by the main empirical enunciations that ensue from its epidemiological designs. RALES is deductively refuted because of the non-fulfillment of auxiliary assumptions that would act as reciprocal potential falsifiers in both studies, taking the logical form of a bi-conditional argument of the type: (a) P-then-Q and (b) Q-if-X(P), X(P) being a set of potential falsifiers of Q as part of the explicit falsity content of P. From this popperian model, implications for clinical research are discussed.

Abortion legislation, maternal healthcare, fertility, female literacy, sanitation, violence against women and maternal deaths: a natural experiment in 32 Mexican states.

OBJECTIVE: To test whether there is an association between abortion legislation and maternal mortality outcomes after controlling for other factors thought to influence maternal health. DESIGN: Population-based natural experiment. SETTING AND DATA SOURCES: Official maternal mortality data from 32 federal states of Mexico between 2002 and 2011. MAIN OUTCOMES: Maternal mortality ratio (MMR), MMR with any abortive outcome (MMRAO) and induced abortion mortality ratio (iAMR). INDEPENDENT VARIABLES: Abortion legislation grouped as less (n=18) or more permissive (n=14); constitutional amendment protecting the unborn (n=17); skilled attendance at birth; all-abortion hospitalisation ratio; low birth weight rate; contraceptive use; total fertility rates (TFR); clean water; sanitation; female literacy rate and intimate-partner violence. MAIN RESULTS: Over the 10-year period, states with less permissive abortion legislation exhibited lower MMR (38.3 vs 49.6; p<0.001), MMRAO (2.7 vs 3.7; p<0.001) and iAMR (0.9 vs 1.7; p<0.001) than more permissive states. Multivariate regression models estimating effect sizes (ß-coefficients) for mortality outcomes showed independent associations (p values between 0.001 and 0.055) with female literacy (ß=-0.061 to -1.100), skilled attendance at birth (ß=-0.032 to -0.427), low birth weight (ß=0.149 to 2.166), all-abortion hospitalisation ratio (ß=-0.566 to -0.962), clean water (ß=-0.048 to -0.730), sanitation (ß=-0.052 to -0.758) and intimate-partner violence (ß=0.085 to 0.755). TFR showed an inverse association with MMR (ß=-14.329) and MMRAO (ß=-1.750) and a direct association with iAMR (ß=1.383). Altogether, these factors accounted for (R(2)) 51-88% of the variance among states in overall mortality rates. No statistically independent effect was observed for abortion legislation, constitutional amendment or other covariates. CONCLUSIONS: Although less permissive states exhibited consistently lower maternal mortality rates, this finding was not explained by abortion legislation itself. Rather, these differences were explained by other independent factors, which appeared to have a more favourable distribution in these states.

Fundamental discrepancies in abortion estimates and abortion-related mortality: A reevaluation of recent studies in Mexico with special reference to the International Classification of Diseases.

In countries where induced abortion is legally restricted, as in most of Latin America, evaluation of statistics related to induced abortions and abortion-related mortality is challenging. The present article reexamines recent reports estimating the number of induced abortions and abortion-related mortality in Mexico, with special reference to the International Classification of Diseases (ICD). We found significant overestimations of abortion figures in the Federal District of Mexico (up to 10-fold), where elective abortion has been legal since 2007. Significant overestimation of maternal and abortion-related mortality during the last 20 years in the entire Mexican country (up to 35%) was also found. Such overestimations are most likely due to the use of incomplete in-hospital records as well as subjective opinion surveys regarding induced abortion figures, and due to the consideration of causes of death that are unrelated to induced abortion, including flawed denominators of live births. Contrary to previous publications, we found important progress in maternal health, reflected by the decrease in overall maternal mortality (30.6%) from 1990 to 2010. The use of specific ICD codes revealed that the mortality ratio associated with induced abortion decreased 22.9% between 2002 and 2008 (from 1.48 to 1.14 deaths per 100,000 live births). Currently, approximately 98% of maternal deaths in Mexico are related to causes other than induced abortion, such as hemorrhage, hypertension and eclampsia, indirect causes, and other pathological conditions. Therefore, only marginal or null effects would be expected from changes in the legal status of abortion on overall maternal mortality rates. Rather, maternal health in Mexico would greatly benefit from increasing access to emergency and specialized obstetric care. Finally, more reliable methodologies to assess abortion-related deaths are clearly required.

Overcoming barriers in the management of hypertension: the experience of the cardiovascular health program in chilean primary health care centers.

Objective. To assess the blood pressure control and cardiovascular risk factors (CVRFs) in a population of hypertensive patients with access to care under a government-financed program, the Cardiovascular Health Program (CHP). Design. A cross-sectional and multicenter study. Setting. 52 primary care centers, metropolitan area of Santiago, Chile. Participants. 1,194 patients were selected by a systematic random sampling from a universe of 316,654 hypertensive patients. Key Measurements. Demographic information, blood pressure (BP) measurements, and CVRF were extracted from medical records of patients followed for a 12-month period. Results. 59.7% of patients reached target BP <140/90 mmHg. More women were captured in the sampling (2.1 : 1), achieving better BP control than men. Diabetic patients (26.4%) had worse BP control than nondiabetics. Antihypertensive medications were used in 91.5%, with multidrug therapy more frequent in patients with higher BP and more difficult control. Conclusions. The success in improving the BP control to values <140/90 mmHg from 45.3% to 59.7% underscores the contribution of this program in the Chilean primary care cardiovascular preventive strategies. However, fewer hypertensive men than women were captured by this program, and it is of concern the underperforming of BP control observed in diabetics.

Women's education level, maternal health facilities, abortion legislation and maternal deaths: a natural experiment in Chile from 1957 to 2007.

BACKGROUND: The aim of this study was to assess the main factors related to maternal mortality reduction in large time series available in Chile in context of the United Nations' Millennium Development Goals (MDGs). METHODS: Time series of maternal mortality ratio (MMR) from official data (National Institute of Statistics, 1957-2007) along with parallel time series of education years, income per capita, fertility rate (TFR), birth order, clean water, sanitary sewer, and delivery by skilled attendants were analysed using autoregressive models (ARIMA). Historical changes on the mortality trend including the effect of different educational and maternal health policies implemented in 1965, and legislation that prohibited abortion in 1989 were assessed utilizing segmented regression techniques. RESULTS: During the 50-year study period, the MMR decreased from 293.7 to 18.2/100,000 live births, a decrease of 93.8%. Women's education level modulated the effects of TFR, birth order, delivery by skilled attendants, clean water, and sanitary sewer access. In the fully adjusted model, for every additional year of maternal education there was a corresponding decrease in the MMR of 29.3/100,000 live births. A rapid phase of decline between 1965 and 1981 (-13.29/100,000 live births each year) and a slow phase between 1981 and 2007 (-1.59/100,000 live births each year) were identified. After abortion was prohibited, the MMR decreased from 41.3 to 12.7 per 100,000 live births (-69.2%). The slope of the MMR did not appear to be altered by the change in abortion law. CONCLUSION: Increasing education level appears to favourably impact the downward trend in the MMR, modulating other key factors such as access and utilization of maternal health facilities, changes in women's reproductive behaviour and improvements of the sanitary system. Consequently, different MDGs can act synergistically to improve maternal health. The reduction in the MMR is not related to the legal status of abortion.

Early life and adult socioeconomic influences on mortality risk: preliminary report of a 'pauper rich' paradox in a Chilean adult cohort.

PURPOSE: The inverse relationship between early life and adult socioeconomic measures and mortality risk has been well established in developed countries, but remains practically unexplored in Latin American societies. The setting was Chile; the study included 11,600 adults living in the urban center of San Francisco de Mostazal. This was a prospective cohort study of a weighted random sample of 795 subjects followed up during 8 years. METHODS: Education (elementary, high school and college), height (percentiles 50 and 75), and income (population quartiles) were assessed at baseline. Relative risks of all-cause mortality were computed in Cox regression models adjusting for age, gender, body mass index, smoking status, and joint effects of the socioeconomic measures. RESULTS: A graded inverse relationship with all-cause mortality was observed for education (risk: 1.0, 0.67, and 0.30, p for trend < 0.01) and height (risk: 1.0, 0.75, and 0.56, p for trend < 0.01), but not for income (p for trend = 0.94). CONCLUSIONS: These findings suggest a 'pauper rich' paradox in transitioning Latin American economies. Income level does not seem sufficient to improve survival in cohorts exposed to adverse early life influences reflected by education and height.

Influencia de factores psicosociales en la adherencia al tratamiento farmacológico antihipertensivo: Resultados de una cohorte del Programa de Salud Cardiovascular de la Región Metropolitana, Chile / Influence of psychosocial factors on adherence to antihypertensive drug therapy: Results from a Cardiovascular Health Program cohort followed in the Metropolitan Region of Santiago, Chile

Background: Inadequate blood pressure control in hypertensive patients remains a persistent health problem in Chile and worldwide. Poor adherence to antihypertensive drug therapy is one of the frequently cited factors. Objectives: To determine the influence of psychosocial factors in the adherence to drug therapy in hypertensive patients followed through a Cardiovascular Health Program (CHP) that provides free access to primary care centers located in the Metropolitan Region of Santiago, Chile. Methods: Cross sectional study. A randomized sample of 513 hypertensive patients (30 to 68 years) was obtained from a universe of 1.484 patients. Adherence to treatment was determined by the Morisky-Green-Levine test. Demographic, socioeconomic and average values of blood pressure were recorded. Validated questionnaires were utilized to assess the patient-physician relationship, awareness of being hypertensive, patient perception of social support, family cohesion, patient self-health assessment and symptoms of emotional stress and depression. Results: The drug therapy adherence was 36.6%, higher in women (38.4% vs 28.9%; p < 0.001). After multivariate analysis, absence of adherence was associated with male gender (OR: 1.76 [95% CI 1.21-2.56]), low education (OR: 1.72 [95% CI 1.18 to 2.53]), inadequate patient-physician relationship (OR: 1.56 [95% CI 1.13 to 2.27]), and high level of emotional stress and depression (OR: 1.93 [95% CI 1.27 to 2.94]). Conclusions: Our study highlights the influence of inadequate patient-physician relation, high level of emotional stress and depression, low education level and income and male gender in the lack of adherence to antihypertensive drug therapy in hypertensive patients followed throughout the CHP.