Prevention of mother-to-child transmission of HIV: a cross-sectional study in Malawi.

OBJECTIVE: To estimate the use and outcomes of the Malawian programme for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). METHODS: In a cross-sectional analysis of 33 744 mother-infant pairs, we estimated the weighted proportions of mothers who had received antenatal HIV testing and/or maternal antiretroviral therapy and infants who had received nevirapine prophylaxis and/or HIV testing. We calculated the ratios of MTCT at 4-26 weeks postpartum for subgroups that had missed none or at least one of these four steps. FINDINGS: The estimated uptake of antenatal testing was 97.8%; while maternal antiretroviral therapy was 96.3%; infant prophylaxis was 92.3%; and infant HIV testing was 53.2%. Estimated ratios of MTCT were 4.7% overall and 7.7% for the pairs that had missed maternal antiretroviral therapy, 10.7% for missing both maternal antiretroviral therapy and infant prophylaxis and 11.4% for missing maternal antiretroviral therapy, infant prophylaxis and infant testing. Women younger than 19 years were more likely to have missed HIV testing (adjusted odds ratio, aOR: 4.9; 95% confidence interval, CI: 2.3-10.6) and infant prophylaxis (aOR: 6.9; 95% CI: 1.2-38.9) than older women. Women who had never started maternal antiretroviral therapy were more likely to have missed infant prophylaxis (aOR: 15.4; 95% CI: 7.2-32.9) and infant testing (aOR: 13.7; 95% CI: 4.2-83.3) than women who had. CONCLUSION: Most women used the Malawian programme for the prevention of MTCT. The risk of MTCT increased if any of the main steps in the programme were missed.

Registration and management of community patients with tuberculosis in north-west China.

OBJECTIVES: To describe the registration, management and characteristics of patients with tuberculosis (TB) in north-west China, and investigate whether patients with TB were diagnosed and treated in a timely manner. STUDY DESIGN: Health-facility-based retrospective data were collected from district patient registers and case reports for all patients with TB registered from January 2009 to December 2011 in Xinjiang Uygur Autonomous Region, north-west China. METHODS: Patient characteristics and clinical data were collected from the national TB epidemic reporting system using standardized case reporting forms for diagnosis, treatment and outcome. Data were collected and entered by trained health staff in the regional TB clinics. RESULTS: In total, data for 20,396 patients with TB were collected; of these, 78.5% were farmers. The age peaks were 20-44 years and 60-74 years. Average health-seeking and diagnostic delays were 32 days and two days, respectively. More than half (54.7%) of the patients with smear-negative TB were diagnosed by chest x-ray. Moreover, 94.3% of patients with TB were treated successfully. From 2009 to 2011, the health-seeking delay decreased significantly (P < 0.05), and the diagnostic delay increased significantly (P < 0.05). A significant decreasing trend in smear-positive TB was observed (P < 0.05), along with an increasing trend in treatment success (P < 0.05). CONCLUSIONS: In north-west China, there is a need to focus on key high-risk populations for prevention and control of TB, such as those aged 20-44 years and 60-74 years, males and farmers. Delays in diagnosis and treatment have a negative effect on cure rates and make it more difficult to control the propagation of TB.

The Cardioprotective Effects of Semaglutide Exceed Those of Dietary Weight Loss in Mice With HFpEF.

Obesity-related heart failure with preserved ejection fraction (HFpEF) has become a well-recognized HFpEF subphenotype. Targeting the unfavorable cardiometabolic profile may represent a rational treatment strategy. This study investigated semaglutide, a glucagon-like peptide-1 receptor agonist that induces significant weight loss in patients with obesity and/or type 2 diabetes mellitus and has been associated with improved cardiovascular outcomes. In a mouse model of HFpEF that was caused by advanced aging, female sex, obesity, and type 2 diabetes mellitus, semaglutide, compared with weight loss induced by pair feeding, improved the cardiometabolic profile, cardiac structure, and cardiac function. Mechanistically, transcriptomic, and proteomic analyses revealed that semaglutide improved left ventricular cytoskeleton function and endothelial function and restores protective immune responses in visceral adipose tissue. Strikingly, treatment with semaglutide induced a wide array of favorable cardiometabolic effects beyond the effect of weight loss by pair feeding. Glucagon-like peptide-1 receptor agonists may therefore represent an important novel therapeutic option for treatment of HFpEF, especially when obesity-related.

Viewpoint: Why do we need a point-of-care CD4 test for low-income countries?

In this paper, we discuss the reasons why we urgently need a point-of-care (POC) CD4 test, elaborate the problems we have experienced with the current technology which hampers CD4-count coverage and highlight the ideal characteristics of a universal CD4 POC test. It is high-time that CD4 technology is simplified and adapted for wider use in low-income countries to change the current paradigm of restricted access once and for all.

Author Correction: The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unreponsive to standard heart failure therapy.

Phospholamban (PLN) plays a role in cardiomyocyte calcium handling as primary inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). The p.(Arg14del) pathogenic variant in the PLN gene results in a high risk of developing dilated or arrhythmogenic cardiomyopathy with heart failure. There is no established treatment other than standard heart failure therapy or heart transplantation. In this study, we generated a novel mouse model with the PLN-R14del pathogenic variant, performed detailed phenotyping, and tested the efficacy of established heart failure therapies eplerenone or metoprolol. Heterozygous PLN-R14del mice demonstrated increased susceptibility to ex vivo induced arrhythmias, and cardiomyopathy at 18 months of age, which was not accelerated by isoproterenol infusion. Homozygous PLN-R14del mice exhibited an accelerated phenotype including cardiac dilatation, contractile dysfunction, decreased ECG potentials, high susceptibility to ex vivo induced arrhythmias, myocardial fibrosis, PLN protein aggregation, and early mortality. Neither eplerenone nor metoprolol administration improved cardiac function or survival. In conclusion, our novel PLN-R14del mouse model exhibits most features of human disease. Administration of standard heart failure therapy did not rescue the phenotype, underscoring the need for better understanding of the pathophysiology of PLN-R14del-associated cardiomyopathy. This model provides a great opportunity to study the pathophysiology, and to screen for potential therapeutic treatments.

Anemia prevalence among pregnant women and birth weight in five areas in China.

OBJECTIVES: To investigate the current prevalence of anemia among pregnant women in different areas of China and the association with birth weight and educational level. METHODS: A total of 6,413 women aged 24-37 in the third trimester of pregnancy from five areas were randomly selected from all gravidas who gave birth in the hospitals from 1999 to 2003. Blood hemoglobin concentration (Hb) was measured by the cyanomethemoglobin method; Hb <110 g/l was considered as anemia. RESULTS: The overall prevalence of anemia was 58.6%, ranging from 48.1 to 70.5% in the five areas. There was a significant difference in the prevalence of anemia between women who have mental jobs and those who have physical jobs (52.3 vs. 61.1%, p < 0.01). The prevalence of anemia depended on the level of education: with 52.9, 62.4 and 66.5%, for college, secondary school and primary education, respectively, and the difference was statistically significant (p = 0.005). Results showed that higher birth weight was associated with Hb concentrations ranging from 90 to 140 g/l, whereas lower birth weight occurred below 80 g/l and above 140 g/l Hb. CONCLUSIONS: The prevalence of anemia in Chinese pregnant women was high both in rural areas and towns. Area of residence, education level and type of job influenced the prevalence of anemia. Low maternal Hb concentrations influenced birth weight.

Outcomes in HIV-infected patients who develop tuberculosis after starting antiretroviral treatment in Malawi.

A retrospective review was conducted of patients starting antiretroviral treatment (ART) at Mzuzu Central Hospital, Malawi, to identify those who developed tuberculosis (TB) within 6 months of commencing ART and document their treatment outcomes. Of 2933 patients, 22 (0.75%) developed active TB, 17 (77%) of whom had commenced ART as a result of unexplained weight loss and/or fever. Of those who developed TB, 41% successfully completed anti-tuberculosis treatment, with lower survival probabilities than patients who did not develop TB. Easier methods are needed to diagnose TB in human immunodeficiency virus-infected patients and to prevent patients from developing TB while on ART.

Plasma levels of heart failure biomarkers are primarily a reflection of extracardiac production.

Plasma heart failure (HF) biomarkers, like natriuretic peptides, are important in diagnosis, prognosis and HF treatment. Several novel HF biomarkers have been identified, including Gal-3, GDF-15 and TIMP-1, but their clinical potential remains vague. Here we investigated plasma biomarker levels in relation to tissue expression and structural and functional cardiac changes. Methods: Cardiac remodeling, cardiac function, and plasma and tissue biomarker levels were investigated in mice after myocardial infarction induced by temporal and permanent LAD ligation (tLAD and pLAD). In addition, a pressure overload model induced by transverse aortic constriction (TAC) and an obese/hypertensive HFpEF-like mouse model were investigated. Results: Plasma levels of ANP and its cardiac expression were strictly associated with cardiac remodeling and function. Gal-3, GDF-15 and TIMP-1 cardiac expressions were also related to cardiac remodeling and function, but not their plasma levels. Only directly after myocardial infarction could elevated plasma levels of Gal-3 and TIMP-1 be detected. Eight weeks after infarction, plasma levels were not elevated despite enhanced cardiac expression and low EF (18.3±3.3%, pLAD). Plasma levels of TIMP-1 and GDF-15 were elevated after TAC, but this also correlated with increased lung expression and congestion. In obese-hypertensive mice, elevated plasma levels of Gal-3, GDF-15 and TIMP1 were associated with increased adipose tissue expression and not with cardiac function. Conclusions: The Gal-3, GDF-15 and TIMP-1 plasma pool levels are hardly influenced by dynamic changes in cardiac expression. These biomarkers are not specific for indices of cardiac remodeling, but predominantly reflect stress in other affected tissues and hence provide health information beyond the heart.

Outcomes of HIV-infected children with tuberculosis who are started on antiretroviral therapy in Malawi.

SETTING: Mzuzu Central Hospital, in the northern region of Malawi, which provides free antiretroviral therapy (ART) to human immunodeficiency virus (HIV) infected adults and children, including those with tuberculosis (TB). OBJECTIVES: To compare outcomes in HIV-infected children who have been started on ART because of 1) active TB, 2) a past history of TB in the last 2 years and 3) a non-TB diagnosis. DESIGN: Retrospective data collection using ART patient master cards and ART patient registers. RESULTS: Between July 2004 and September 2006, 439 (11%) children of a total 3908 patients were started on ART. There were 29 with active TB, 56 with a past history of TB in the last 2 years and 354 with a non-TB diagnosis. The three groups were similar in nutritional indices and CD4-lymphocyte percentages. The 6-month probability of survival was 0.86 in the active TB group, 0.94 in the past history of TB group and 0.89 in the non-TB group. 12-month survival probability for the same groups was 0.86, 0.86 and 0.88, respectively. CONCLUSION: HIV-infected children with active and previous TB who are started on ART have good outcomes that are similar to those of children started on ART due to a non-TB diagnosis.

Outcomes of tuberculosis patients who start antiretroviral therapy under routine programme conditions in Malawi.

SETTING: Public sector facilities in Malawi providing antiretroviral therapy (ART) to human immunodeficiency virus (HIV) positive patients, including those with tuberculosis (TB). OBJECTIVES: To compare 6-month and 12-month cohort treatment outcomes of HIV-positive TB patients and HIV-positive non-TB patients treated with ART. DESIGN: Retrospective data collection using ART patient master cards and ART patient registers. RESULTS: Between July and September 2005, 7905 patients started ART, 6967 with a non-TB diagnosis and 938 with a diagnosis of active TB. 6-month cohort outcomes of non-TB and TB patients censored on 31 March 2006 showed significantly more TB patients alive and on ART (77%) compared with non-TB patients (71%) (P < 0.001). Between January and March 2005, 4580 patients started ART, 4179 with a non-TB diagnosis and 401 with a diagnosis of active TB. 12-month cohort outcomes of non-TB and TB patients censored on 31 March 2006 showed significantly more TB patients alive and on ART (74%) compared with non-TB patients (66%) (P < 0.001). Other outcomes of default and transfer out were also significantly less frequent in TB compared with non-TB patients. CONCLUSION: HIV-positive TB patients on ART in Malawi have generally good treatment outcomes, and more patients need to access this HIV treatment.

Alcohol, smoking, and physical activity related to respiratory infections in elderly people.

OBJECTIVE: Elderly people show an increased risk of acute respiratory infections and their complications. This increased susceptibility may be the result of immunosenescence. If lifestyle factors could influence the risk of the infections, this could result in great public health relevance. We investigated the relation between alcohol consumption, smoking, and physical activity with acute respiratory infections. DESIGN: Prospective observational analysis. SETTING: The study took place between September 1998 - June 2000, in the Wageningen area of The Netherlands. PARTICIPANTS: In total 652 relatively healthy elderly people participated. Participants were noninstitutionalized and 60 years and older. MEASUREMENTS: The lifestyle factors were assessed at baseline by means of standardized and validated questionnaires in the participants. Self-reported respiratory infections were assessed from 1998-2000 by nurse telephone contact, and home visits, and were evaluated by microbiological tests in a subset. RESULTS: We detected 1024 acute respiratory infections among 443 participants, the overall incidence rate (IR) was 1.6 infections per person per year. IR ratio (95% confidence interval) of the infections was 1.31 (1.01, 1.70) for occasional (superior 0 glasses/day < 1), 1.22 (0.92, 1.64) for light (1 < glasses/day < 3 (men) and 1< glasses/day < 2 (women)), and 1.33 (1.04, 1.83) at moderate/heavy (superior 3 (men) or superior 2 (women) glasses/day) alcohol consumption after adjustment for age and sex. Alcohol intake was not related to illness severity. Smoking and physical activity were not related to the incidence and severity of the infections. All results remained unaltered after adjustment for lifestyle factors and for other potential risk factors for respiratory infections. CONCLUSION: Our findings suggest that only alcohol intake may be unfavorably associated with the frequency of acute respiratory infections in apparently healthy elderly people. Until our results are confirmed in trials, it is not warranted to recommend elderly people to change their habits of life, such as alcohol consumption, smoking and physical activity in order to reduce the risk of acute respiratory infections.

Cervical spinal cord injuries in patients with refractory epilepsy.

The incidence of cervical spinal cord injuries (c-SCI) in patients with refractory epilepsy is 30-40 times higher than in the normal population. The injuries occur after seizure-related falls. Risk factors and pitfalls in diagnosis are discussed. Awareness of the risk within this population of developing c-SCI should receive more widely recognition, especially in centres that treat this population.

Consumption of fermented milk products and breast cancer: a case-control study in The Netherlands.

In a case-control study in The Netherlands, we observed a significantly lower consumption of fermented milk products (predominantly yogurt and buttermilk) among 133 incident breast cancer cases as compared to 289 population controls (mean +/- SD among users only, 116 +/- 100 versus 157 +/- 144 g/day; P less than 0.01). The age-adjusted odds ratio of daily consumption of 1.5 glasses (greater than or equal to 225 g) of fermented milk versus none was 0.50 (95% confidence interval, 0.23-1.08). When fermented milk was entered as a continuous variable (per g) in either age-adjusted or multivariate analysis, the odds ratio expressed per 225 g was 0.63 (multivariate-adjusted 95% confidence interval, 0.41-0.96). After multivariate adjustment for intake of fat and other confounders, a statistically significant decrease in breast cancer risk was also observed for increasing intake of Gouda cheese. The multivariate-adjusted odds ratio expressed per 60 g of this fermented product was 0.56 (95% confidence interval, 0.33-0.95). For daily intake of milk, no statistically significant differences were observed between cases and controls. These results support the hypothesis that high consumption of fermented milk products may protect against breast cancer.

Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis Risk In Communities.

BACKGROUND: Low heart rate variability (HRV) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease (CHD) in the general population. METHODS AND RESULTS: We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD, aged 45 to 65, by using the case-cohort design. At baseline, in 1987 to 1989, 2-minute rhythm strips were recorded. Time-domain measures of HRV were determined in a random sample of 900 subjects, for all subjects with incident CHD (395 subjects), and for all deaths (443 subjects) that occurred through 1993. Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design. Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death. The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors. CONCLUSIONS: Low HRV was associated with increased risk of CHD and death from several causes. It is hypothesized that low HRV is a marker of less favorable health.

QTc duration is associated with levels of insulin and glucose intolerance. The Zutphen Elderly Study.

Prolongation of heart rate-adjusted QT length (corrected QT interval [QTc]) is associated with elevated risk of coronary heart disease and sudden death. This may have to do with autonomic cardiac control. Because insulin is known to stimulate sympathetic activity, we studied the association of insulin level and glucose tolerance with QTc. In 1990, 383 elderly men 70-89 years of age without previous myocardial infarctions or known diabetes had a 12-lead electrocardiogram recorded and glucose tolerance determined in the frame of an ongoing follow-up study. QTc was significantly associated with fasting glucose, insulin, and C-peptide and glucose levels 60 and 120 min after an oral glucose load. For fasting C-peptide and the area under the glucose curve (AUGC), this association could not be explained by the concomitant occurrence of other risk factors of coronary heart disease. Furthermore, fasting C-peptide and the AUGC were independently additive predictors of QTc duration. The difference in QTc between men in the extreme quintiles of both variables was 22 ms. QTc prolongation seems to be part of the insulin resistance syndrome. The association may be explained by increased sympathetic activity induced by high insulin levels. An additional explanation could be an effect of high insulin, impaired glucose utilization, or both on membrane activity of myocardial cells.

ST segment and T wave characteristics as indicators of coronary heart disease risk: the Zutphen Study.

OBJECTIVES: This study evaluated the predictive value of T wave amplitude and ST segment level on lead I for angina pectoris, a first myocardial infarction, sudden death and coronary heart disease death in middle-aged and elderly men. BACKGROUND: Certain ST-T wave characteristics may reflect favorable autonomic cardiac control. Slight ST segment elevation has been reported to indicate a low risk of coronary heart disease mortality. METHODS: A total of 876 men, born between 1900 and 1920, participated in periodic medical examinations and were followed up with respect to morbidity and mortality from 1960 to 1985. In 1985, the remaining cohort was extended to 836 elderly men from the same birth cohort who were followed up until 1990. Relative risks in categories of T wave amplitude and ST segment level were estimated by survival analysis. RESULTS: Both middle-aged and elderly men with T wave amplitudes > or = 0.15 mV had a lower risk of myocardial infarction, coronary heart disease death and sudden death than men with T wave amplitudes 0.05 to 0.15 mV. The adjusted relative risk of coronary heart disease death was 0.5 (95% confidence interval [CI] 0.2 to 1.0); in men with T wave amplitude < or = 0.05 mV, relative risk was 2.0 (95% CI 1.3 to 3.1). Slight ST segment elevation was also associated with decreased risk: relative risk 0.5 (95% CI 0.3 to 1.0) compared with the isoelectric ST segment level. In men with ST segment depression, relative risk was 2.2 (95% CI 1.4 to 3.4). The association of T wave amplitude and ST segment level were independent of each other. CONCLUSIONS: In addition to the elevated risk of coronary heart disease that is associated with ST-T wave abnormalities, we observed that normal variations in repolarization characteristics are predictive of future heart disease.

Scaling up antiretroviral therapy in Africa: learning from tuberculosis control programmes--the case of Malawi.

The rapid and massive scale-up of antiretroviral drug therapy (ART) so needed in sub-Saharan Africa will not be possible using a 'medicalised' model. A more simple approach is required. DOTS has been used now for many years to provide successful anti-tuberculosis treatment to millions of patients in poor countries of the world, and many of the established concepts can be used for the delivery of ART. Malawi, a small and impoverished country in sub-Saharan Africa, is embarking on a national scale-up of ART. In this review we describe how we have adopted several of the principles of DOTS for delivering ART in Malawi: case finding and registration, treatment, monitoring, drug procurement, staffing and the issue of free drugs. We also discuss ART for HIV-infected TB patients. We hope that by using the DOTS approach we will be able to deliver ART to large numbers of HIV-infected patients under controlled conditions, and minimise the risk of developing drug resistance.

Scaling up HIV/AIDS and joint HIV-TB services in Malawi.

Two country-wide surveys were undertaken to assess progress in scaling up human immunodeficiency virus/ acquired immune-deficiency syndrome (HIV/AIDS) and HIV-tuberculosis (TB) services in the public health sector in Malawi between 2002 and 2003. In 2003, 118 sites were performing counselling and HIV testing compared with 70 in 2002. There were 215 269 HIV tests carried out in 2003 compared with 149 540 in 2002, the largest increases being in pregnant women (from 5059 to 26791), patients with TB (from 2130 to 3983) and patients/clients attending health facilities (from 35 407 to 79 584). In 2003, 3703 patients with AIDS were started on antiretroviral therapy compared with 1220 patients in 2002.

Netherlands research programme weight gain prevention (NHF-NRG): rationale, objectives and strategies.

OBJECTIVE: To outline the rationale, objectives and strategies used in a systematically designed research programmme to study specific weight gain-inducing behaviours, their social-psychological as well as environmental determinants, and the effects of interventions aimed at the prevention of weight gain. DESIGN: The evidence for potential behavioural determinants and strategies to prevent weight gain was reviewed, and the methods applied within the Netherlands Research programme weight gain prevention (NHF-NRG) project were described. The project is designed according to the Intervention Mapping protocol. SETTING: The Netherlands. SUBJECTS: The main target groups are (a) adolescents (12-16 y) in secondary school, (b) young adults (20-40 y) at the workplace and (c) recently retired people (55-65 y) at home. INTERVENTIONS: Each intervention includes an individual component, in which computer-tailored information is provided. Additionally, interventions are aimed at changing environmental components. RESULTS: The short-term results of this project can be expected by the beginning of 2005. Guidelines for nationwide weight gain prevention, based on this research programme, will become available in 2007. CONCLUSIONS: Based on the few interventions that were evaluated to date, no robust conclusions can be drawn regarding the effectiveness of obesity prevention. The systematic and multidisciplinary design of the NHF-NRG programme enables the identification of potentially effective methods and strategies for the prevention of weight gain.