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Background: Individuals frequently turning to social media to discuss medical conditions and medication, sharing their experiences and information and asking questions among themselves. These online discussions can provide valuable insights into individual perceptions of medical treatment, and increasingly, studies are focusing on the potential use of this information to improve health care management. Objective: The objective of this infodemiology study was to identify social media posts mentioning paracetamol-containing products to develop a better understanding of patients’ opinions and perceptions of the drug. Methods: Posts between January 2003 and March 2019 containing at least one mention of paracetamol were extracted from 18 French forums in May 2019 with the use of the Detec’t (Kap Code) web crawler. Posts were then analyzed using the automated Detec’t tool, which uses machine learning and text mining methods to inspect social media posts and extract relevant content. Posts were classified into groups: Paracetamol Only, Paracetamol and Opioids, Paracetamol and Others, and the Aggregate group. Results: Overall, 44,283 posts were analyzed from 20,883 different users. Post volume over the study period showed a peak in activity between 2009 and 2012, as well as a spike in 2017 in the Aggregate group. The number of posts tended to be higher during winter each year. Posts were made predominantly by women (14,897/20,883, 71.34%), with 12.00% (2507/20,883) made by men and 16.67% (3479/20,883) by individuals of unknown gender. The mean age of web users was 39 (SD 19) years. In the Aggregate group, pain was the most common medical concept discussed (22,257/37,863, 58.78%), and paracetamol risk was the most common discussion topic, addressed in 20.36% (8902/43,725) of posts. Doliprane was the most common medication mentioned (14,058/44,283, 31.74%) within the Aggregate group, and tramadol was the most commonly mentioned drug in combination with paracetamol in the Aggregate group (1038/19,587, 5.30%). The most common unapproved indication mentioned within the Paracetamol Only group was fatigue (190/616, with 16.32% positive for an unapproved indication), with reference to dependence made by 1.61% (136/8470) of the web users, accounting for 1.33% (171/12,843) of the posts in the Paracetamol Only group. Dependence mentions in the Paracetamol and Opioids group were provided by 6.94% (248/3576) of web users, accounting for 5.44% (342/6281) of total posts. Reference to overdose was made by 245 web users across 291 posts within the Paracetamol Only group. The most common potential adverse event detected was nausea (306/12843, 2.38%) within the Paracetamol Only group. Conclusions: The use of social media mining with the Detec’t tool provided valuable information on the perceptions and understanding of the web users, highlighting areas where providing more information for the general public on paracetamol, as well as other medications, may be of benefit.

Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival. This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries. 18 695 patients with previously manifest or increased risk of vascular disease were randomly assigned to receive either rimonabant 20 mg (n=9381) or matching placebo (n=9314). Randomisation was stratified by centre, implemented with an independent interactive voice response system, and all study personnel and participants were masked to group assignment. The primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke, as determined via central adjudication. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00263042. At a mean follow-up of 13·8 months (95% CI 13·6–14·0), the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant. All randomised participants were analysed. At the close of the trial (Nov 6, 2008), the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 364 (3·9%) patients assigned to rimonabant and 375 (4·0%) assigned to placebo (hazard ratio 0·97, 95% CI 0·84–1·12, p=0·68). With rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]), neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious psychiatric side-effects (232 [2·5%] vs 120 [1·3%]) were significantly increased compared with placebo. Four patients in the rimonabant group and one in the placebo group committed suicide. The premature termination of this trial has important lessons for drug development. A drug that was being marketed for weight loss, but being tested for improving cardiovascular outcomes, induced a level of serious neuropsychiatric effects that was deemed unacceptable by regulatory authorities, and both the drug and the trial were abruptly terminated. Sanofi-Aventis.

ObjectiveThe aim of this trial was to determine whether obese patients benefit from treatment with rimonabant in terms of progression of carotid atherosclerosis. Rimonabant, a selective cannabinoid-1 receptor blocker, reduces body weight and improves cardiometabolic risk factors in patients who are obese.Design, setting, patients, interventions and resultsA prospective, double-blind, placebo-controlled trial (Atherosclerosis Underlying Development assessed by Intima–media Thickness in patients On Rimonabant (AUDITOR)) randomised 661 patients with abdominal obesity and metabolic syndrome to rimonabant or placebo for 30 months of treatment. The absolute change in the average value for six segments of far wall carotid intima–media thickness from baseline to month 30 was 0.010±0.095 mm in the rimonabant group and 0.012±0.091 mm in the placebo group (p=0.67). The annualised change was an increase of 0.005±0.042 mm for the rimonabant-treated group and 0.007±0.043 mm for the placebo-treated group (p=0.45).ConclusionsThere was no difference in atherosclerosis progression between patients receiving rimonabant for 30 months and those receiving placebo for the primary efficacy measure (absolute change in carotid intima–media thickness). These findings are consistent with a similar study using coronary intravascular ultrasound and another study evaluating the occurrence of cardiovascular events. Our findings suggest that a 5% loss of body weight over a 30-month period with rimonabant is insufficient to modify atherosclerosis progression in the carotid artery in obese patients with metabolic syndrome.Clinical trial registration informationclinicaltrials.gov Identifier: NCT00228176.

Iron deficiency is highly prevalent in pre-school children in developing countries and an important health problem in sub-Saharan Africa. A debate exists on the possible protective effect of iron deficiency against malaria and other infections; yet consensus is lacking due to limited data. Recent studies have focused on the risks of iron supplementation but the effect of an individual's iron status on malaria risk remains unclear. Studies of iron status in areas with a high burden of infections often are exposed to bias. The aim of this study was to assess the predictive value of baseline iron status for malaria risk explicitly taking potential biases into account. We prospectively assessed the relationship between baseline iron deficiency (serum ferritin <30 µg/L) and malaria risk in a cohort of 727 Malawian preschool children during a year of follow-up. Data were analyzed using marginal structural Cox regression models and confounders were selected using causal graph theory. Sensitivity of results to bias resulting from misclassification of iron status by concurrent inflammation and to bias from unmeasured confounding were assessed using modern causal inference methods. The overall incidence of malaria parasitemia and clinical malaria was 1.9 (95% CI 1.8-2.0) and 0.7 (95% CI 0.6-0.8) events per person-year, respectively. Children with iron deficiency at baseline had a lower incidence of malaria parasitemia and clinical malaria during a year of follow-up; adjusted hazard ratio's 0.55 (95%-CI:0.41-0.74) and 0.49 (95%-CI:0.33-0.73), respectively. Our results suggest that iron deficiency protects against malaria parasitemia and clinical malaria in young children. Therefore the clinical importance of treating iron deficiency in a pre-school child should be weighed carefully against potential harms. In malaria endemic areas treatment of iron deficiency in children requires sustained prevention of malaria.

A reliable diagnostic biomarker of iron status is required for severely anemic children living in malarious areas because presumptive treatment with iron may increase their infection risk if they are not iron deficient. Current biomarkers are limited because they are altered by host inflammation. In this study hepcidin concentrations were assessed in severely anemic children living in a highly malarious area of Malawi and evaluated against bone marrow iron in order to determine the usefulness of hepcidin as a point of care test. 207 severely anemic children were assessed for levels of hepcidin, ferritin, serum transferrin receptor, erythropoietin, hematological indices, C-reactive protein, interleukin-6, malaria parasites and HIV infection. Deficiency of bone marrow iron stores was graded and erythroblast iron incorporation estimated. Interaction of covariates was assessed by structural-equation-modeling. Hepcidin was a poor predictor of bone marrow iron deficiency (sensitivity 66.7%; specificity 48.5%), and of iron incorporation (sensitivity 54.2%; specificity 61.8%), and therefore would have limitations as a point of care test in this category of children. As upregulation of hepcidin by inflammation and iron status was blunted by erythropoietin in this population, enhanced iron absorption through the low hepcidin values may increase infection risk. Current recommendations to treat all severely anemic children living in malarious areas with iron should therefore be reconsidered.

The World Health Organization guidelines for treating severe anemia in African children deal principally with malaria, folate deficiency, and iron deficiency. In this study of Malawian preschool children with severe anemia, deficiencies of folate and iron were infrequent, and multiple infectious agents in addition to malaria parasites were contributing causes. In this study of Malawian preschool children with severe anemia, deficiencies of folate and iron were infrequent and multiple infectious agents in addition to malaria parasites were contributing causes. Severe anemia (hemoglobin concentration less than 5.0 g per deciliter) is a major cause of sickness and death among children in sub-Saharan Africa. 1 – 4 In various settings, 12 to 29% of hospitalized children are severely anemic, 1 – 4 and the in-hospital case fatality rate in these children is 8 to 17%. 1 , 3 , 4 Little is known about the causes of severe anemia in African children. Most studies have been confined to the anemia associated with malaria 5 or with other individual factors. 1 , 2 , 6 As a result, the treatment guidelines advocated by the World Health Organization (WHO) deal specifically with malaria, folate . . .

Traditionally, crop production in sub-Saharan Africa (SSA) depends primarily on mining soil nutrients. Integrated Soil Fertility Management (ISFM) is an approach for intensifying agriculture in SSA that aims at maximizing the agronomic efficiency (AE) of applied nutrient inputs. ISFM contains the following essential components: proper fertilizer management, use of improved varieties, the combined application of organic inputs and fertilizer, and adaptation of input application rates to within-farm soil fertility gradients where these are important. This paper evaluates, through meta-analysis, the impact of these components on the AE of fertilizer N (N-AE), defined as extra grain yield per kg fertilizer N applied, in maize-based systems in SSA. Since N-AE is low for excessive fertilizer N application rates or when fertilizer is applied on fertile, unresponsive soil, as was confirmed by scatter plots against control yields and fertilizer N application rates, such values were removed from the database in order to focus on and elucidate the more variable and complex responses under less than ideal conditions typical for SSA. Compared with local varieties, the use of hybrid maize varieties significantly increased N-AE values (17 and 26 kg (kg N)⁻¹, respectively) with no differences observed between local and improved, open-pollinated varieties. Mixing fertilizer with manure or compost resulted in the highest N-AE values [36 kg (kg N)⁻¹] while organic inputs of medium quality also showed significantly higher N-AE values compared with the sole fertilizer treatment but only at low organic input application rates (40 and 23 kg (kg N)⁻¹, respectively). High quality organic inputs (Class I) and those with a high C-to-N ratio (Class III) or high lignin content (Class IV) did not affect N-AE values in comparison with the sole fertilizer treatment. Application of N fertilizer on infields resulted in significantly higher N-AE values [31 kg (kg N)⁻¹] compared with the outfields [17 kg (kg N)⁻¹]. The obtained information indicates that N-AE is amenable to improved management practices and that the various components embedded in the ISFM definition result in improvements in N-AE.

The objective of the present study was to estimate whether physical activity on one day was associated with both sleep quality and quantity the following night and to examine to what extent sleep on one night was associated with physical activity the next day. We collected data from 33 young adults who were overweight or obese and consistently wore a Fitbit Charge 3. A total of 7094 days and nights were analyzed. Person-specific models were conducted to test the bi-directional associations for each participant separately. Results suggest an absence of association between steps and sleep efficiency in the two directions. More heterogeneous results were observed for the association between steps and total sleep time, with 19 participants (58%) showing a negative association between total sleep time and next day steps, and 9 (27%) showing a negative association between steps and next day total sleep time. Taken together, these results suggest a potential conflicting association between total sleep time and physical activity for some participants. Pre- and post-print doi: https://doi.org/10.31236/osf.io/nfjqv; supplemental material: https://osf.io/y7nxg/.

Hookworm infections are an important cause of (severe) anemia and iron deficiency in children in the tropics. Type of hookworm species (Ancylostoma duodenale or Necator americanus) and infection load are considered associated with disease burden, although these parameters are rarely assessed due to limitations of currently used diagnostic methods. Using multiplex real-time PCR, we evaluated hookworm species-specific prevalence, infection load and their contribution towards severe anemia and iron deficiency in pre-school children in Malawi. A. duodenale and N. americanus DNA loads were determined in 830 fecal samples of pre-school children participating in a case control study investigating severe anemia. Using multiplex real-time PCR, hookworm infections were found in 34.1% of the severely anemic cases and in 27.0% of the non-severely anemic controls (p<0.05) whereas a 5.6% hookworm prevalence was detected by microscopy. Prevalence of A. duodenale and N. americanus was 26.1% and 4.9% respectively. Moderate and high load A. duodenale infections were positively associated with severe anemia (adjusted odds ratio: 2.49 (95%CI 1.16-5.33) and 9.04 (95%CI 2.52-32.47) respectively). Iron deficiency (assessed through bone marrow examination) was positively associated with intensity of A. duodenale infection (adjusted odds ratio: 3.63 (95%CI 1.18-11.20); 16.98 (95%CI 3.88-74.35) and 44.91 (95%CI 5.23-385.77) for low, moderate and high load respectively). This is the first report assessing the association of hookworm load and species differentiation with severe anemia and bone marrow iron deficiency. By revealing a much higher than expected prevalence of A. duodenale and its significant and load-dependent association with severe anemia and iron deficiency in pre-school children in Malawi, we demonstrated the need for quantitative and species-specific screening of hookworm infections. Multiplex real-time PCR is a powerful diagnostic tool for public health research to combat (severe) anemia and iron deficiency in children living in resource poor settings.

Background: Self-reported physical activity is often inaccurate. Wearable devices utilizing multiple sensors are now widespread. The aim of this study was to determine acceptability of Fitbit Charge HR for children and their families, and to determine best practices for processing its objective data. Methods: Data were collected via Fitbit Charge HR continuously over the course of 3 weeks. Questionnaires were given to each child and their parent/guardian to determine the perceived usability of the device. Patterns of data were evaluated and best practice inclusion criteria recommended. Results: Best practices were established to extract, filter, and process data to evaluate device wear, r and establish minimum wear time to evaluate behavioral patterns. This resulted in usable data available from 137 (89%) of the sample. Conclusions: Activity trackers are highly acceptable in the target population and can provide objective data over longer periods of wear. Best practice inclusion protocols that reflect physical activity in youth are provided.