Can dopamine prevent the renal side effects of indomethacin? A prospective randomized clinical study.

BACKGROUND: Indomethacin therapy for closure of a patent ductus arteriosus in preterm neonates is responsible for transient renal insufficiency. Dopamine theoretically reduces the renal side effects of indomethacin therapy. PATIENTS: 33 neonates with a mean gestational age of 28.5 weeks who received indomethacin for treatment of a symptomatic PDA were included in a prospective randomized controlled clinical study. METHOD: 15 patients were treated with indomethacin alone (control group), 18 patients with indomethacin and dopamine (study group). Indomethacin was given in a dose of 0.2 mg/kg/dose intravenously, all patients received three doses with intervall of 12 hours. The dose of dopamine was in all patients 4 micrograms/kg per minute commencing 2 hours prior to the first dose of indomethacin and continuing for 12 hours after the third dose. RESULTS: Indomethacin induced a significant increase in serum creatinin (76.3 mumol/l vs 99.7 mumol/l for the control group, and 70.7 mumol/l vs 93.0 mumol/l for the study group), and weight (1259 g vs 1316 g for the control group, and 1187 g vs 1221 g for the study group). The increase systolic blood pressure (61 mmHg vs 65.7 mmHg) in the study group was significant (p < 0.05) but remained unchanged in the control group. The changes between the study group and the control group were not significant either in serum creatinin, fractional excretion of sodium, or weight gain. The failure rate of ductal closure was not different between the two groups. CONCLUSION: The additional use of dopamine does not reduce the renal side effects of indomethacin.

Syndromic algorithms for detection of gambiense human african trypanosomiasis in South Sudan.

BACKGROUND: Active screening by mobile teams is considered the best method for detecting human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense but the current funding context in many post-conflict countries limits this approach. As an alternative, non-specialist health care workers (HCWs) in peripheral health facilities could be trained to identify potential cases who need testing based on their symptoms. We explored the predictive value of syndromic referral algorithms to identify symptomatic cases of HAT among a treatment-seeking population in Nimule, South Sudan. METHODOLOGY/PRINCIPAL FINDINGS: Symptom data from 462 patients (27 cases) presenting for a HAT test via passive screening over a 7 month period were collected to construct and evaluate over 14,000 four item syndromic algorithms considered simple enough to be used by peripheral HCWs. For comparison, algorithms developed in other settings were also tested on our data, and a panel of expert HAT clinicians were asked to make referral decisions based on the symptom dataset. The best performing algorithms consisted of three core symptoms (sleep problems, neurological problems and weight loss), with or without a history of oedema, cervical adenopathy or proximity to livestock. They had a sensitivity of 88.9-92.6%, a negative predictive value of up to 98.8% and a positive predictive value in this context of 8.4-8.7%. In terms of sensitivity, these out-performed more complex algorithms identified in other studies, as well as the expert panel. The best-performing algorithm is predicted to identify about 9/10 treatment-seeking HAT cases, though only 1/10 patients referred would test positive. CONCLUSIONS/SIGNIFICANCE: In the absence of regular active screening, improving referrals of HAT patients through other means is essential. Systematic use of syndromic algorithms by peripheral HCWs has the potential to increase case detection and would increase their participation in HAT programmes. The algorithms proposed here, though promising, should be validated elsewhere.

Gravity-driven slug motion in capillary tubes

The velocity of a liquid slug falling in a capillary tube is lower than predicted for Poiseuille flow due to presence of menisci, whose shapes are determined by the complex interplay of capillary, viscous, and gravitational forces. Due to the presence of menisci, a capillary pressure proportional to surface curvature acts on the slug and streamlines are bent close to the interface, resulting in enhanced viscous dissipation at the wedges. To determine the origin of drag-force increase relative to Poiseuille flow, we compute the force resultant acting on the slug by integrating Navier-Stokes equations over the liquid volume. Invoking relationships from differential geometry we demonstrate that the additional drag is due to viscous forces only and that no capillary drag of hydrodynamic origin exists (i.e., due to hydrodynamic deformation of the interface). Requiring that the force resultant is zero, we derive scaling laws for the steady velocity in the limit of small capillary numbers by estimating the leading order viscous dissipation in the different regions of the slug (i.e., the unperturbed Poiseuille-like bulk, the static menisci close to the tube axis and the dynamic regions close to the contact lines). Considering both partial and complete wetting, we find that the relationship between dimensionless velocity and weight is, in general, nonlinear. Whereas the relationship obtained for complete-wetting conditions is found in agreement with the experimental data of Bico and Quere [J. Bico and D. Quere, J. Colloid Interface Sci. 243, 262 (2001)], the scaling law under partial-wetting conditions is validated by numerical simulations performed with the Volume of Fluid method. The simulated steady velocities agree with the behavior predicted by the theoretical scaling laws in presence and in absence of static contact angle hysteresis. The numerical simulations suggest that wedge-flow dissipation alone cannot account for the entire additional drag and that the non-Poiseuille dissipation in the static menisci (not considered in previous studies) has to be considered for large contact angles.

The fallacy of slimming products: a case analysis in Switzerland

Introduction: Many people desire to lose weight. This favors the marketing of "miracle" products with overemphasized slimming capacities. To our knowledge, no study regarding the claimed performances of slimming products has ever been conducted in Switzerland. Objectives: To assess weight loss claims of slimming products available in Switzerland by analyzing their corresponding advertisements. Methods: Between May 2008 and February 2013, 31 advertisements for 13 different slimming products from a single producer were collected. Weight loss claims and text of the advertisement were analyzed. Results: Weight loss claims ranged between 7 and 31 kg, with an estimated daily weight loss ranging between 300 g and 1 kg. 84% of the advertisements targeted women (by including the photograph of a woman), 61% showed a picture of a person before and after using the product, and 51% claimed that the product had improved marital relationships. The terms "natural", "miracle/extraordinary" and "scientific" were present in 92%, 77%, and 31% of the products, respectively. Free gifts were provided to buyers for 69% of the products. Cost was very similar for all 13 products (range: 49 to 59 CHF, with 8 products costing the same amount) and no correlation was found between cost of the product and weight loss claims. No differences were found for weight loss claims according to presence or absence of a picture or of the terms ".natural", ".miracle/extraordinary" and ".scientific" Finally, the yearly costs for advertising such products (French-speaking Switzerland) ranged between 56,000 and 126,000 CHF, suggesting that the gains obtained were higher than this value. Conclusion: In Switzerland, advertisements for slimming products use positive and reassuring terms to attract consumers, which are lured by unreachable, false promises of rapid and easy weight loss. Taking into account the costs of advertising, the gains obtained appear to be significant. Legislation on advertising of such products is urgently needed.

Metabolism of oral glucose in children born small for gestational age : evidence for an impaired whole body glucose oxidation

Résumé Les études épidémiologiques indiquent que la restriction intra-utérine confère un risque accru de développement de diabète de type 2 au cours de la vie. Certaines études ont documenté la présence d'une résistance à l'insuline chez les jeunes adultes ou les adolescents nés petits pour l'âge gestationnel. Comme la plupart des études ont impliqués des individus post-pubères et comme la puberté influence de manière marquée le métabolisme énergétique, nous avons évalué le devenir du glucose administré oralement dans un groupe incluant essentiellement des enfants pré-pubères ou en début de puberté avec restriction intra-utérine, et chez des enfants matchés pour l'âge et pour le poids. Tous les enfants ont eu une évaluation de leur composition corporelle par mesure des plis cutanés. Ils ont ensuite été étudiés dans des conditions standardisées et ont reçu 4 charges consécutives orales de glucose à raison de 180 mg/kg de poids corporel jusqu'à atteindre un état d'équilibre relatif. La dépense énergétique et l'oxydation des substrats ont été évaluées durant la quatrième heure par calorimétrie indirecte. Comparativement avec les enfants matchés pour l'âge et le poids, les enfants nés petits pour l'âge gestationnel avaient une plus petite stature. Leur dépense énergétique n'était pas significativement abaissée, mais leur oxydation du glucose était plus basse. Ces résultats indiquent que des altérations métaboliques sont présentes précocement chez les enfants nés petits pour l'âge gestationnel, et qu'elles sont possiblement reliées à des altérations de la composition corporelle. Abstract: Epidemiological studies indicate that intrauterine growth restriction confers an increased risk of developing type 2 diabetes mellitus in subsequent life. Several studies have further documented the presence of insulin resistance in young adults or adolescent children born small for gestational age. Since most studies addressed postpubertal individuals, and since puberty markedly affects energy metabolism, we evaluated the disposal of oral glucose in a group including mainly prepubertal and early pubertal children with intrauterine growth restriction and in healthy age- and weight-matched control children. All children had an evaluation of their body composition by skinfold thickness measurements. They were then studied in standardized conditions and received 4 consecutive hourly loads of 180 mg glucose/kg body weight to reach a near steady state. Energy expenditure and substrate oxidation were evaluated during the fourth hour by indirect calorimetry. Compared to both age- and weight-matched children, children born small for gestational age had lower stature. Their energy expenditure was not significantly decreased, but they had lower glucose oxidation rates. These results indicate that metabolic alterations are present early in children born small for gestational age, and are possibly related to alterations of body composition.

Tuberculose miliaire chez une personne âgée: diagnostic inattendu à l'autopsie [Miliary tuberculosis: unexpected autopsy finding in an elderly person].

Miliary tuberculosis is a rare disease that is difficult to diagnose because of its non-specific presentation. It should be suspected in elderly patients who complaint of failure to thrive, unexplained fatigue and weight loss. Using a clinical situation where the diagnosis was made only at autopsy, we briefly review the epidemiology of miliary tuberculosis and propose recommendations for the diagnosis and the prophylaxis of latent tuberculosis. Finally, we discuss criteria to perform epidemiological investigations among close contacts in this situation.

Elevated hypertension risk for African-origin populations in biracial societies : Modeling the Epidemiologic Transition Study.

OBJECTIVES: Blood pressures in persons of African descent exceed those of other racial/ethnic groups in the United States. Whether this trait is attributable to the genetic factors in African-origin populations, or a result of inadequately measured environmental exposures, such as racial discrimination, is not known. To study this question, we conducted a multisite comparative study of communities in the African diaspora, drawn from metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. METHODS: At each site, 500 participants between the age of 25 and 49 years, with approximately equal sex balance, were enrolled for a longitudinal study of energy expenditure and weight gain. In this study, we describe the patterns of blood pressure and hypertension observed at baseline among the sites. RESULTS: Mean SBP and DBP were very similar in the United States and South Africa in both men and women, although among women, the prevalence of hypertension was higher in the United States (24 vs. 17%, respectively). After adjustment for multiple covariates, relative to participants in the United States, SBP was significantly higher among the South Africans by 9.7 mmHg (P < 0.05) and significantly lower for each of the other sites: for example, Jamaica: -7.9 mmHg (P = 0.06), Ghana: -12.8 mmHg (P < 0.01) and Seychelles: -11.1 mmHg (P = 0.01). CONCLUSION: These data are consistent with prior findings of a blood pressure gradient in societies of the African diaspora and confirm that African-origin populations with lower social status in multiracial societies, such as the United States and South Africa, experience more hypertension than anticipated based on anthropometric and measurable socioeconomic risk factors.

Mortality risk associated with underweight : a census-linked cohort of 31,578 individuals with up to 32 years of follow-up

BACKGROUND: In contrast to obesity, information on the health risks of underweight is sparse. We examined the long-term association between underweight and mortality by considering factors possibly influencing this relationship. METHODS: We included 31,578 individuals aged 25-74 years, who participated in population based health studies between 1977 and 1993 and were followed-up for survival until 2008 by record linkage with the Swiss National Cohort (SNC). Body Mass Index (BMI) was calculated from measured (53% of study population) or self-reported height and weight. Underweight was defined as BMI < 18.5 kg/m2. Cox regression models were used to determine mortality Hazard Ratios (HR) of underweight vs. normal weight (BMI 18.5- < 25.0 kg/m2). Covariates were study, sex, smoking, healthy eating proxy, sports frequency, and educational level. RESULTS: Underweight individuals represented 3.0% of the total study population (n = 945), and were mostly women (89.9%). Compared to normal weight, underweight was associated with increased all-cause mortality (HR: 1.37; 95% CI: 1.14-1.65). Increased risk was apparent in both sexes, regardless of smoking status, and mainly driven by excess death from external causes (HR: 3.18; 1.96-5.17), but not cancer, cardiovascular or respiratory diseases. The HR were 1.16 (0.88-1.53) in studies with measured BMI and 1.59 (1.24-2.05) with self-reported BMI. CONCLUSIONS: The increased risk of dying of underweight people was mainly due to an increased mortality risk from external causes. Using self-reported BMI may lead to an overestimation of mortality risk associated with underweight.

Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial.

BACKGROUND: One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes. METHODS: We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m(2) cisplatin and 85 mg/m(2) docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030771. FINDINGS: From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12·8 months (95% CI 9·7-22·9) in the chemoradiotherapy group and 11·6 months (8·4-15·2) in the chemotherapy group (p=0·67). Median overall survival was 37·1 months (95% CI 22·6-50·0) with radiotherapy, compared with 26·2 months (19·9-52·1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery. INTERPRETATION: Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi.

Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial.

BACKGROUND: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. METHODS: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. RESULTS: Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. CONCLUSIONS: Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

Maladie de Whipple: quand y penser [Whipple's disease, when to think about it?].

Whipple's disease is a chronic, systemic, bacterial infection caused by Tropheryma whipplei. Its cardinal symptoms include intermittent and recurrent arthralgia or arthritis together with chronic diarrhoea, abdominal pain and weight loss. It may mimick many chronic inflammatory diseases, and the diagnosis remains a challenge. Salivary and faecal quantitative PCR for T. whipplei should be ensued, if positive, by an upper endoscopy for duodenal biopsies. The treatment consists of a combination of oral doxycycline and hydroxychloroquine for 12 months followed by life-long doxycycline. Whipple's disease, although rare, is an entity that should be considered regularly, as its progression may be fatal if left untreated.

Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants.

BACKGROUND: Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries. METHODS: We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18·5 kg/m(2) [underweight], 18·5 kg/m(2) to <20 kg/m(2), 20 kg/m(2) to <25 kg/m(2), 25 kg/m(2) to <30 kg/m(2), 30 kg/m(2) to <35 kg/m(2), 35 kg/m(2) to <40 kg/m(2), ≥40 kg/m(2) [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue. FINDINGS: We used 1698 population-based data sources, with more than 19·2 million adult participants (9·9 million men and 9·3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21·7 kg/m(2) (95% credible interval 21·3-22·1) in 1975 to 24·2 kg/m(2) (24·0-24·4) in 2014 in men, and from 22·1 kg/m(2) (21·7-22·5) in 1975 to 24·4 kg/m(2) (24·2-24·6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21·4 kg/m(2) in central Africa and south Asia to 29·2 kg/m(2) (28·6-29·8) in Polynesia and Micronesia; for women the range was from 21·8 kg/m(2) (21·4-22·3) in south Asia to 32·2 kg/m(2) (31·5-32·8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13·8% (10·5-17·4) to 8·8% (7·4-10·3) in men and from 14·6% (11·6-17·9) to 9·7% (8·3-11·1) in women. South Asia had the highest prevalence of underweight in 2014, 23·4% (17·8-29·2) in men and 24·0% (18·9-29·3) in women. Age-standardised prevalence of obesity increased from 3·2% (2·4-4·1) in 1975 to 10·8% (9·7-12·0) in 2014 in men, and from 6·4% (5·1-7·8) to 14·9% (13·6-16·1) in women. 2·3% (2·0-2·7) of the world's men and 5·0% (4·4-5·6) of women were severely obese (ie, have BMI ≥35 kg/m(2)). Globally, prevalence of morbid obesity was 0·64% (0·46-0·86) in men and 1·6% (1·3-1·9) in women. INTERPRETATION: If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world's poorest regions, especially in south Asia. FUNDING: Wellcome Trust, Grand Challenges Canada.