Population-based assessment of cardiovascular complications of rheumatic heart disease in Fiji: a record-linkage analysis

Objective: To determine population-based rates of nonfatal complications of rheumatic heart disease (RHD). Design: Retrospective cohort study based on multiple sources of routine clinical and administrative data amalgamated by probabilistic record-linkage. Setting: Fiji, an upper-middle-income country, where most of the population has access to government-funded health care services. Participants: National cohort of 2,116 patients with clinically apparent RHD aged 5-69 years during 2008-2012. Primary and secondary outcome measures: The primary outcome was hospitalisation for any of heart failure, atrial fibrillation, ischaemic stroke and infective endocarditis. Secondary outcomes were first hospitalisation for each of the complications individually in the national cohort as well as in hospital (n=1300) and maternity (n=210) subsets. Information on outcomes was obtained from discharge diagnoses coded in the hospital patient information system. Population-based rates were obtained using relative survival methods with census data as the denominator. Results: Among 2,116 patients in the national cohort (median age, 23.3 years; 57.7% female), 546 (25.8%) were hospitalised for an RHD complication, a substantial proportion of all cardiovascular admissions in the country during this period in those aged 0–40 years (heart failure, 210/454, 46.2%; ischaemic stroke 31/134, 23.3%). Absolute numbers of RHD complications peaked during the third decade of life with higher population-based rates in women compared to men (incidence rate ratio 1.4, 95% CI 1.3–1.6, P<0.001). Hospitalisation for any RHD complication was associated with substantially increased risk of death (hazard ratio, 5.4, 95% CI, 3.4–8.8, P<0.001), especially after the onset of heart failure (hazard ratio, 6.6, 95% CI, 4.8–9.1, P<0.001). Conclusions: Our study defines the burden of RHD-attributable morbidity in the general population of Fiji, potentially reflecting the situation in low- and middle-income countries worldwide. Hospitalisation for an RHD complication is associated with markedly increased risk of death, re- emphasising the importance of effective early prevention

Comparative prebiotic activity of mixtures of cereal grain polysaccharides

The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential

Influence of acute pancreatitis on the in vitro responsiveness of rat mesenteric and pulmonary arteries

<p>Abstract</p> <p>Background</p> <p>Acute pancreatitis is an inflammatory disease characterized by local tissue injury and systemic inflammatory response leading to massive nitric oxide (NO) production and haemodynamic disturbances. Therefore, the aim of this work was to evaluate the vascular reactivity of pulmonary and mesenteric artery rings from rats submitted to experimental pancreatitis.</p> <p>Male Wistar rats were divided into three groups: saline (SAL); tauracholate (TAU) and phospholipase A₂(PLA₂). Pancreatitis was induced by administration of TAU or PLA₂from <it>Naja mocambique mocambique </it>into the common bile duct of rats, and after 4 h of duct injection the animals were sacrificed. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PHE) in isolated mesenteric and pulmonary arteries were obtained. Potency (pEC₅₀) and maximal responses (E_MAX) were determined. Blood samples were collected for biochemical analysis.</p> <p>Results</p> <p>In mesenteric rings, the potency for ACh was significantly decreased from animals treated with TAU (about 4.2-fold) or PLA₂(about 6.9-fold) compared to saline group without changes in the maximal responses. Neither pEC₅₀nor E_MAXvalues for Ach were altered in pulmonary rings in any group. Similarly, the pEC₅₀and the E_MAXvalues for SNP were not changed in both preparations in any group. The potency for PHE was significantly decreased in rat mesenteric and pulmonary rings from TAU group compared to SAL group (about 2.2- and 2.69-fold, for mesenteric and pulmonary rings, respectively). No changes were seen in the E_MAXfor PHE. The nitrite/nitrate (NO_x^-) levels were markedly increased in animals submitted to acute pancreatitis as compared to SAL group, approximately 76 and 68% in TAU and PLA₂protocol, respectively.</p> <p>Conclusion</p> <p>Acute pancreatitis provoked deleterious effects in endothelium-dependent relaxing response for ACh in mesenteric rings that were strongly associated with high plasma NO_x^-levels as consequence of intense inflammatory responses. Furthermore, the subsensitivity of contractile response to PHE in both mesenteric and pulmonary rings might be due to the complications of this pathological condition in the early stage of pancreatitis.</p

Preterm birth and small for gestational age in relation to alcohol consumption during pregnancy: stronger associations among vulnerable women? Results from two large Western-European studies

Pfinder M, Kunst AE, Feldmann R, van Eijsden M, Vrijkotte TGM. Preterm birth and small for gestational age in relation to alcohol consumption during pregnancy: stronger associations among vulnerable women? Results from two large Western-European studies. BMC Pregnancy and Childbirth. 2013;13(1): 49.BACKGROUND: Inconsistent data on the association between prenatal alcohol exposure and a range of pregnancy outcomes, such as preterm birth (PTB) and small for gestational age (SGA) raise new questions. This study aimed to assess whether the association between low-moderate prenatal alcohol exposure and PTB and SGA differs according to maternal education, maternal mental distress or maternal smoking. METHODS: The Amsterdam Born Children and their Development (ABCD) Study (N=5,238) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (N=16,301) are both large studies. Women provide information on alcohol intake in early pregnancy, 3 months postpartum and up to 17 years retrospectively. Multivariate logistic regression analyses and stratified regression analyses were performed to examine the association between prenatal alcohol exposure and PTB and SGA, respectively. RESULTS: No association was found between any level of prenatal alcohol exposure (non-daily, daily, non-abstaining) and SGA. The offspring of daily drinkers and non-abstainers had a lower risk of PTB [ABCD: odds ratio (OR) 0.31, 95% confidence interval (CI) 0.13, 0.77; KiGGS: OR 0.75, 95% CI 0.57, 0.99]. Interactions with maternal education, maternal distress or maternal smoking were not significant. CONCLUSIONS: Although these results should be interpreted with caution, both studies showed no adverse effects of low-moderate prenatal alcohol exposure on PTB and SGA, not even in the offspring of women who were disadvantaged in terms of low education, high levels of distress, or smoking during pregnancy

A Tractable Experimental Model for Study of Human and Animal Scabies

Scabies, a neglected parasitic disease caused by the microscopic mite Sarcoptes scabiei, is a major driving force behind bacterial skin infections in tropical settings. Aboriginal and Torres Strait Islander peoples are nearly twenty times more likely to die from acute rheumatic fever and rheumatic heart disease than individuals from the wider Australian community. These conditions are caused by bacterial pathogens such as Group A streptococci, which have been linked to underlying scabies infestations. Community based initiatives to reduce scabies and associated disease have expanded, but have been threatened in recent years by emerging drug resistance. Critical biological questions surrounding scabies remain unanswered due to a lack of biomedical research. This has been due in part to a lack of either a suitable animal model or an in vitro culture system for scabies mites. The pig/mite model reported here will be a much needed resource for parasite material and will facilitate in vivo studies on host immune responses to scabies, including relations to associated bacterial pathogenesis, and more detailed studies of molecular evolution and host adaptation. It represents the missing tool to extrapolate emerging molecular data into an in vivo setting and may well allow the development of clinical interventions

Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol

<p>Abstract</p> <p>Background</p> <p>After more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide, we lack good evidence to guide our everyday decisions in conducting antidepressant treatment of patients with major depression. First we did not know which antidepressant to use as first line treatment. Second we do not know which dosage we should be aiming at with that antidepressant. Because more than half of the patients with major depression starting treatment do not remit after adequate trial with the first agent, they will need a second line treatment. Dose escalation, augmentation and switching are the three often recommended second line strategies but we do not know which is better than the others. Moreover, we do not know when to start considering this second line treatment.</p> <p>The recently published multiple-treatments meta-analysis of 12 new generation antidepressants has provided some partial answers to the first question. Starting with these findings, this proposed trial aims to establish the optimum 1st line and 2nd line antidepressant treatment strategy among adult patients with a non-psychotic unipolar major depressive episode.</p> <p>Methods</p> <p>SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multi-centre randomised controlled trial. Step I is a cluster-randomised trial comparing titration up to the minimum vs maximum of the recommended dose range among patients starting with sertraline. The primary outcome is the change in the Patient Health Questionnaire (PHQ)-9 scores administered by a blinded rater via telephone at week 1 through 3. Step II is an individually randomised trial comparing staying on sertraline, augmentation of sertraline with mirtazapine, and switching to mirtazapine among patients who have not remitted on the first line treatment by week 3. The primary outcome is the change in the PHQ-9 scores at week 4 through 9. Step III represents a continuation phase to Steps I and II and aims to establish longer-term effectiveness and acceptability of the above-examined treatment strategies up to week 25. The trial is supported by the Grant-in-Aid by the Ministry of Health, Labour and Welfare, Japan.</p> <p>Discussion</p> <p>SUN(^_^)D promises to be a pragmatic large trial to answer important clinical questions that every clinician treating patients with major depression faces in his/her daily practices concerning its first- and second-line treatments.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01109693">NCT01109693</a></p

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

Hookworm-Related Anaemia among Pregnant Women: A Systematic Review

Anaemia affects large numbers of pregnant women in developing countries and increases their risk of dying during pregnancy and delivering low birth weight babies, who in turn are at increased risk of dying. Human hookworm infection has long been recognized among the major causes of anaemia in poor communities, but understanding of the benefits of the management of hookworm infection in pregnancy has lagged behind the other major causes of maternal anaemia. Low coverage of anthelmintic treatment in maternal health programmes in many countries has been the result. After systematically reviewing the available literature we observed that increasing hookworm infection intensity is associated with lower haemoglobin levels in pregnant women. We also estimate that between a quarter and a third of pregnant women in sub-Saharan Africa are infected with hookworm and at risk of preventable hookworm-related anaemia. However, all identified intervention studies showed a benefit of deworming for maternal or child health and we argue that increased efforts should be made to increase the coverage of anthelmintic treatment among pregnant women

Pancreatitis and pancreatic cancer in two large pooled case–control studies

The association between duration of pancreatitis and pancreatic cancer has not been well characterized in large population-based studies. We conducted detailed analyses to determine the association between pancreatitis onset and pancreatic cancer risk. Data from two case–control studies of pancreatic cancer (n = 4515) in the San Francisco Bay Area and the M.D. Anderson Cancer Center were pooled for analysis (1,663 cases, 2,852 frequency-matched controls). Adjusted odds ratios (OR) were estimated using a random-effects model. In the pooled multivariable model, history of pancreatitis was associated with a 7.2-fold increased risk estimate for pancreatic cancer [95% confidence interval (CI): 4.0, 13]. The risk estimate was nearly 10-fold in participants aged &lt;55 years (OR = 9.9, 95% CI: 3.5, 28). A shorter temporal history of pancreatitis was more closely associated with pancreatic cancer than was a longer temporal history: &lt;3 years (OR = 29, 95% CI: 12, 71), 3–10 years (OR = 2.6, 95% CI: 1.5, 5.6), and &gt;10 years (OR = 1.8, 95% CI: 0.7, 4.5, p trend &lt; 0.001). A short temporal history of pancreatitis was highly associated with pancreatic cancer, suggesting that pancreatitis may be an early manifestation of pancreatic cancer in some individuals. Pancreatic cancer should be considered in the differential diagnosis of individuals with an episode of pancreatitis