Off-label drug use during the COVID-19 pandemic in Africa: topic modelling and sentiment analysis of ivermectin in South Africa and Nigeria as a case study.

Although rejected by the World Health Organization, the human and even veterinary formulation of ivermectin has widely been used for prevention and treatment of COVID-19. In this work we leverage Twitter to understand the reasons for the drug use from ivermectin supporters, their source of information, their emotions, their gender demographics, and location information, in Nigeria and South Africa. Topic modelling is performed on a Twitter dataset gathered using keywords 'ivermectin' and 'ivm'. A model is fine-tuned on RoBERTa to find the stance of the tweets. Statistical analysis is performed to compare the stance and emotions. Most ivermectin supporters either redistribute conspiracy theories posted by influencers, or refer to flawed studies confirming ivermectin efficacy in vitro. Three emotions have the highest intensity, optimism, joy and disgust. The number of anti-ivermectin tweets has a significant positive correlation with vaccination rate. All the provinces in South Africa and most of the provinces of Nigeria are pro-ivermectin and have higher disgust polarity. This work makes the effort to understand public discussions regarding ivermectin during the COVID-19 pandemic to help policy-makers understand the rationale behind its popularity, and inform more targeted policies to discourage self-administration of ivermectin. Moreover, it is a lesson to future outbreaks.

A general swimming response in exhausted obligate swimming fish.

Marine organisms normally swim at elevated speeds relative to cruising speeds only during strenuous activity, such as predation or escape. We measured swimming speeds of 29 ram ventilating sharks from 10 species and of three Atlantic bluefin tunas immediately after exhaustive exercise (fighting a capture by hook-and-line) and unexpectedly found all individuals exhibited a uniform mechanical response, with swimming speed initially two times higher than the cruising speeds reached approximately 6 h later. We hypothesized that elevated swimming behaviour is a means to increase energetic demand and drive the removal of lactate accumulated during capture via oxidation. To explore this hypothesis, we estimated the mechanical work that must have been spent by an animal to elevate its swim speed and then showed that the amount of lactate that could have been oxidized to fuel it comprises a significant portion of the amount of lactate normally observed in fishes after exhaustive exercise. An estimate for the full energetic cost of the catch-and-release event ensued.

Higher rates of COVID-19 but less severe infections reported for patients on Dupilumab: a Big Data analysis of the World Health Organization VigiBase.

OBJECTIVE: Dupilumab (Dupixent®) is a monoclonal antibody that inhibits IL-4 and IL-13 signaling used for the treatment of allergic diseases. Whilst biologic therapy is traditionally regarded as immunosuppressive and capable to increase the infectious risk, Dupilumab does not display these characteristics and may be even protective in certain cases. We investigated the link between Dupilumab therapy and SARS-CoV-2 infection. MATERIALS AND METHODS: We carried out a comprehensive data mining and disproportionality analysis of the WHO global pharmacovigilance database. One asymptomatic COVID-19 case, 106 cases of symptomatic COVID-19, and 2 cases of severe COVID-19 pneumonia were found. RESULTS: Dupilumab treated patients were at higher risk of COVID-19 (with an IC0.25 of 3.05), even though infections were less severe (IC0.25 of -1.71). The risk of developing COVID-19 was significant both among males and females (with an IC0.25 of 0.24 and 0.58, respectively). The risk of developing COVID-19 was significant in the age-group of 45-64 years (with an IC0.25 of 0.17). CONCLUSIONS: Dupilumab use seems to reduce COVID-19 related severity. Further studies are needed to better understand the immunological mechanisms and clinical implications of these findings. Remarkably, the heterogenous nature of the reports and the database structure did not allow to establish a cause-effect link, but only an epidemiologically decreased risk in the patients subset treated with dupilumab.

Safety profile of Dupilumab during pregnancy: a data mining and disproportionality analysis of over 37,000 reports from the WHO individual case safety reporting database (VigiBase™).

Atopic dermatitis, known also as atopic eczema, represents a commonly diagnosed, chronic or recurrent/relapsing inflammatory disorder. From a clinical point of view, it is characterized by acute flare-ups of intense itching, eczematous pruritic lesions involving dry skin. Dupilumab is the only biologic agent approved to treat moderate to severe course of atopic dermatitis, which can be particularly severe during pregnancy causing distress and impacting on maternal and fetal health. However, there is a dearth of data concerning the safety profile of Dupilumab during gestation. Therefore, we took advantage of a large global pharmacovigilance database. From inception up to March 9, 2021, 94,065 adverse drug reactions (ADRs) from 37,848 unique reports were retrieved. Of these, 36 reports related to pregnancy, puerperium and perinatal ADR could be extracted from the pharmacovigilance database. More than half of reports (n = 21; 58.3%) were spontaneous abortion, followed by other events, including exposure to the drug during the pregnancy (n = 8; 22.2%). Two cases of abortion were reported. No studied pregnancy, puerperium and perinatal ADR was found to be associated with the use of Dupilumab. The only OR significantly greater than 1 was the OR associated with the risk of developing heterotopic pregnancy (21.66 [95% CrI 2.95-159.02]) even if the IC was highly imprecise (1.45 [95% CrI from -2.34 to 3.09]), probably because of the single case of heterotopic pregnancy reported. In conclusion, Dupilumab use appears safe during gestation. Further studies are needed, especially to better understand the mechanisms underlying the pharmacological actions and ADR of Dupilumab.

Cost and social distancing dynamics in a mathematical model of COVID-19 with application to Ontario, Canada.

A mathematical model of COVID-19 is presented where the decision to increase or decrease social distancing is modelled dynamically as a function of the measured active and total cases as well as the perceived cost of isolating. Along with the cost of isolation, we define an overburden healthcare cost and a total cost. We explore these costs by adjusting parameters that could change with policy decisions. We observe that two disease prevention practices, namely increasing isolation activity and increasing incentive to isolate do not always lead to optimal health outcomes. We demonstrate that this is due to the fatigue and cost of isolation. We further demonstrate that an increase in the number of lock-downs, each of shorter duration can lead to minimal costs. Our results are compared with case data in Ontario, Canada from March to August 2020 and details of expanding the results to other regions are presented.

[Clinical value of the early use of ulinastatin in patients with moderately severe or severe acute pancreatitis].

Objective: To observe the clinical efficacy and the effects on serum inflammatory factors of early use of ulinastatin in patients with moderately severe or severe acute pancreatitis (MSAP/SAP). Methods: This prospective, randomized, controlled trial was conducted in the First Affiliated Hospital of Soochow University from September 2013 to May 2016. A total of 42 cases were enrolled and assigned into either observation group or conventional treatment group (n=21 each). The conventional treatment group received somatostatin, while the observation group received somatostatin combined with ulinastatin. After treatment, clinical characteristics, serum indicators, clinical complications and serum level of inflammatory factors were analyzed. Results: Intra-abdominal pressure and relief time of abdominal pain were significantly decreased in observation group [ (10.4±2.1) cmH(2)O; (2.5±1.2) d ] compared with the conventional treatment group [ (11.7±2.2) cmH(2)O; (3.33± 1.2) d ], P<0.05. White blood cells (WBC) were lower in observation group than those in conventional treatment group [ (11.2±1.8) ×10(9)/L vs (12.5±2.3) ×10(9)/L; P<0.05 ]. After treatment serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α(TNF-α) in observation group [ (30.5±3.3), (34.7± 6.5), (22.6±4.0) µg/L] were significantly lower than those in conventional treatment group [ (39.6±4.0), (40.9±3.4), (33.1±6.6) µg/L], P<0.05. There were no differences between the two groups in modified CT severity index (MCTSI), recovery time of defecation, ICU length of stay, serum amylase, C-reactive protein (CRP) and incidence rates of clinical complications. Conclusions: The early use of ulinastatin in the patients with MSAP/SAP can down-regulated the levels of TNF-α, IL-6 and IL-8, reduce the inflammatory response, decrease intra-abdominal pressure and shorten abdominal pain time. It was beneficial and worthy of wider popularization.