Low efficacy of the combination artesunate plus amodiaquine for uncomplicated falciparum malaria among children under 5 years in Kailahun, Sierra Leone.

OBJECTIVE: In 2004, Sierra Leone adopted artesunate plus amodiaquine as first-line antimalarial treatment. We evaluated the efficacy of this combination in Kailahun, where a previous study had shown 70.2% efficacy of amodiaquine in monotherapy. METHODS: Method and outcome classification of the study complied with WHO guidelines. Children 6-59 months with uncomplicated malaria were followed-up for 28 days. PCR genotyping was used to distinguish recrudescence from reinfection. Reinfections were reclassified as cured. RESULTS: Of 172 children who were referred to the study clinic, 126 satisfied inclusion criteria and were enrolled. No early treatment failures were reported. The day 14, efficacy was 98.2% (95% CI: 93.8-99.8). Of 65 recurrent parasitaemias analysed by PCR, 17 were recrudescences. The PCR-adjusted day 28 efficacy was 84.5% (95% CI: 76.4-90.7). All true failures occurred in the last 8 days of follow-up. Of 110 children who completed the 28-day follow-up, 54 (49.1%) experienced a novel infection. CONCLUSION: The efficacy of this combination was disappointing. The high reinfection rate suggested little prophylactic effect. In Kailahun a more efficacious combination might be necessary in the future. The efficacy of AS + AQ needs to be monitored in Kailahun and in the other regions of Sierra Leone

A Statistical Approach to Evaluate the Tephra Deposit and Ash Concentration from Puff Model Forecasts

In this paper we present a new statistical approach able to provide tephra deposit load and ash concentration using PUFF, a lagrangian model widely used to forecast volcanic ash dispersal during volcanic crisis. We perform a parametric study in order to analyze the influence of each input parameter on model outputs. For this test, we simulate two eruptive scenarios like to the 2001 (Scenario 1) and 1998 (Scenario 2) Etna eruptions using high resolution weather data and a domain of 170 x 170 km. Results show that for both scenarios, we are able to calculate the tephra deposit load and ash concentration but the use of millions of particles is required. Specifically, up to 33 and 220 millions of particles were necessary to accurately predict the tephra deposit and ash concentration in air, respectively. This is approximately two orders of magnitude larger than values typically considered running PUFF. The parametric study shows that the horizontal diffusion coefficient, the time step of the simulations, the topography and the standard deviation of the particle distribution greatly affect the model outputs. We also validate the model by best fit procedures. Results show a good comparison between field data of the 2001 Etna eruption and PUFF simulations, being inside 5 and 1/5 times the observed data, comparable with results of Eulerian models. This work will allow to reliably outlining the areas of contaminated airspace using PUFF or any other lagrangian model in order to define the No Fly Zone and ensure the safety to aviation operations as required after the Eyjafjallajökull eruption

Size matters but when, why and for whom?

Pack size of tobacco products, including factory-made cigarettes and loose tobacco, is an important but neglected aspect of tobacco control policy. Understanding the nature of the relationship between pack size and consumption, as well as the underlying mechanisms, is key for informing effective policy and reducing smoking prevalenc

Dry eye in systemic sclerosis patients: Novel methods to monitor disease activity

Background: In systemic sclerosis (SSc) patients, dry eye syndrome (DES) is the most frequent ocular feature. The aim of this study was to investigate ocular DES-related SSc patients and to establish any correlation with the severity of the disease. Methods: Retrospectively, data from 60 patients with SSc underwent ophthalmic examination, where non-invasive film tear break-up time (NIF-TBUT), tear film lipid layer thickness (LLT), anesthetic-free Schirmer test I, tear osmolarity measurement (TearLab System), and modified Rodnan skin score (mRSS) data were collected. The visual analog scale (VAS) and Symptom Assessment in Dry Eye (SANDE) methods were utilized. The results were correlated with mRSS and the duration of SSc. Results: Severe DES occurred in 84% of cases, and was more severe in women. The eyelids were involved in 86.6%, secondary to meibomian gland disease (MGD). A direct correlation was found between the tear osmolarity (mean 328.51 ± 23.8 SD) and skin score (mRSS) (r = 0.79; p < 0.01). Significantly reduced NIF-TBUT, LLT, and Schirmer test I values were observed in the case of severe skin involvement. Conclusions: SSc patients show lipid tear dysfunction related to the severity and duration of the disease due to inflammation and the subsequent atrophy of the meibomian glands

Exposure-based risk assessment and emergency management associated with the fallout of large clasts at Mount Etna

Fallout of ballistic blocks and bombs ejected from eruptive vents represents a well-known hazard in areas proximal to volcanoes (mostly &lt;5&thinsp;km from the vent). However, fallout of large clasts sedimenting from plume margins that extend to medial areas and have the potential to produce severe injuries to people and cause damage to infrastructure, is often overlooked. Recent eruptive events at Mount Etna (Italy) provide a clear example where large-clast fallout from plume margins (&gt;5&thinsp;cm) has posed a real threat both to the many visitors reaching the summit area and to local infrastructure, and, therefore, has been selected as a case study. To quantify this hazard, a new particle sedimentation model was calibrated with field data and then used for probabilistic hazard assessments. For a fully probabilistic scenario the hazard zone covered 72&thinsp;km2 and included some 125&thinsp;km of paths and roads, as well as 15 buildings. Evacuation on foot to a safe area was estimated at almost 4&thinsp;h, but this could be reduced to less than 3&thinsp;h if two shelters were provided. Our results show the importance of integrating probabilistic hazard analysis of large-clast fallout within effective strategies of risk management and reduction, especially in the case of volcanoes where visitors can reach the summit areas.</p

Cigarette pack size and consumption: an adaptive randomised controlled trial.

BackgroundObservational evidence suggests that cigarette pack size - the number of cigarettes in a single pack - is associated with consumption but experimental evidence of a causal relationship is lacking. The tobacco industry is introducing increasingly large packs, in the absence of maximum cigarette pack size regulation. In Australia, the minimum pack size is 20 but packs of up to 50 cigarettes are available. We aimed to estimate the impact on smoking of reducing cigarette pack sizes from ≥25 to 20 cigarettes per pack.MethodA two-stage adaptive parallel group RCT in which Australian smokers who usually purchase packs containing ≥25 cigarettes were randomised to use only packs containing either 20 (intervention) or their usual packs (control) for four weeks. The primary outcome, the average number of cigarettes smoked per day, was measured through collecting all finished cigarette packs, labelled with the number of cigarettes participants smoked. An interim sample size re-estimation was used to evaluate the possibility of detecting a meaningful difference in the primary outcome.ResultsThe interim analysis, conducted when 124 participants had been randomised, suggested 1122 additional participants needed to be randomised for sufficient power to detect a meaningful effect. This exceeded pre-specified criteria for feasible recruitment, and data collection was terminated accordingly. Analysis of complete data (n = 79) indicated that the mean cigarettes smoked per day was 15.9 (SD = 8.5) in the intervention arm and 16.8 (SD = 6.7) among controls (difference - 0.9: 95%CI = - 4.3, 2.6).ConclusionIt remains unclear whether reducing cigarette pack sizes from ≥25 to 20 cigarettes reduces cigarette consumption. Importantly, the results of this study provide no evidence that capping cigarette pack sizes would be ineffective at reducing smoking. The limitations identified in this study can inform a more efficient RCT, which is urgently required to address the dearth of experimental evidence on the impact of large cigarette pack sizes on smoking.Trial registrationhttps://doi.org/10.1186/ISRCTN34202533

Modelling Future Coronary Heart Disease Mortality to 2030 in the British Isles.

OBJECTIVE: Despite rapid declines over the last two decades, coronary heart disease (CHD) mortality rates in the British Isles are still amongst the highest in Europe. This study uses a modelling approach to compare the potential impact of future risk factor scenarios relating to smoking and physical activity levels, dietary salt and saturated fat intakes on future CHD mortality in three countries: Northern Ireland (NI), Republic of Ireland (RoI) and Scotland. METHODS: CHD mortality models previously developed and validated in each country were extended to predict potential reductions in CHD mortality from 2010 (baseline year) to 2030. Risk factor trends data from recent surveys at baseline were used to model alternative future risk factor scenarios: Absolute decreases in (i) smoking prevalence and (ii) physical inactivity rates of up to 15% by 2030; relative decreases in (iii) dietary salt intake of up to 30% by 2030 and (iv) dietary saturated fat of up to 6% by 2030. Probabilistic sensitivity analyses were then conducted. RESULTS: Projected populations in 2030 were 1.3, 3.4 and 3.9 million in NI, RoI and Scotland respectively (adults aged 25-84). In 2030: assuming recent declining mortality trends continue: 15% absolute reductions in smoking could decrease CHD deaths by 5.8-7.2%. 15% absolute reductions in physical inactivity levels could decrease CHD deaths by 3.1-3.6%. Relative reductions in salt intake of 30% could decrease CHD deaths by 5.2-5.6% and a 6% reduction in saturated fat intake might decrease CHD deaths by some 7.8-9.0%. These projections remained stable under a wide range of sensitivity analyses. CONCLUSIONS: Feasible reductions in four cardiovascular risk factors (already achieved elsewhere) could substantially reduce future coronary deaths. More aggressive polices are therefore needed in the British Isles to control tobacco, promote healthy food and increase physical activity