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Amiodarone is a class III antiarrhythmic medication used to treat atrial and ventricular tachyarrhythmias. Pulmonary fibrosis from amiodarone use is a well-documented side effect. Pre-COVID-19 pandemic studies have shown that amiodarone-induced pulmonary fibrosis occurs in 1%-5% of patients and usually occurs between 12 to 60 months after initiation. The risk factors associated with amiodarone-induced pulmonary fibrosis include a high total cumulative dose (treatment longer than two months) and high maintenance dose (>400 mg/day). COVID-19 infection is also a known risk factor for developing pulmonary fibrosis and occurs in approximately 2%-6% of patients after a moderate illness. This study aims to assess the incidence of amiodarone in COVID-19 pulmonary fibrosis (ACPF). This is a retrospective cohort study with 420 patients with COVID-19 diagnoses between March 2020 and March 2022, comparing two populations, COVID-19 patients with exposure to amiodarone (N=210) and COVID-19 patients without amiodarone exposure (N=210). In our study, pulmonary fibrosis occurred in 12.9% of patients in the amiodarone exposure group compared to 10.5% of patients in the COVID-19 control group (p=0.543). In multivariate logistic analysis, which controlled for clinical covariates, amiodarone use in COVID-19 patients did not increase the odds of developing pulmonary fibrosis (odds ratio (OR): 1.02, 95% confidence interval (CI): 0.52-2.00). The clinical factors associated with the development of pulmonary fibrosis in both groups included a history of preexisting interstitial lung disease (ILD) (p=0.001), exposure to prior radiation therapy (p=0.021), and higher severity of COVID-19 illness (p<0.001). In conclusion, our study found no evidence that amiodarone use in COVID-19 patients increased the odds of developing pulmonary fibrosis at six-month follow-up. However, long-term amiodarone usage in the COVID-19 population should be based on the physician's discretion., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Money et al.)

Cancer treatment-induced toxicities may restrict maximal effective dosing for treatment and cancer survivors' quality of life. It is critical to develop novel strategies that mitigate treatment-induced toxicity without affecting the efficacy of anti-cancer therapies. Rapamycin is a macrolide with anti-cancer properties, but its clinical application has been hindered, partly by unfavorable bioavailability, pharmacokinetics, and side effects. As a result, significant efforts have been undertaken to develop a variety of nano-delivery systems for the effective and safe administration of rapamycin. While the efficacy of nanostructures carrying rapamycin has been studied intensively, the pharmacokinetics, biodistribution, and safety remain to be investigated. In this study, we demonstrate the potential for rapamycin perfluorocarbon (PFC) nanoparticles to mitigate cisplatin-induced acute kidney injury with a single preventative dose. Evaluations of pharmacokinetics and biodistribution suggest that the PFC nanoparticle delivery system improves rapamycin pharmacokinetics. The safety of rapamycin PFC nanoparticles was shown both in vitro and in vivo. After a single dose, no disturbance was observed in blood tests or cardiac functional evaluations. Repeated dosing of rapamycin PFC nanoparticles did not affect overall spleen T cell proliferation and responses to stimulation, although it significantly decreased the number of Foxp3 + CD4 + T cells and NK1.1 + cells were observed.

This study describes the clinical features of a cohort of imported cases of strongyloidiasis and the performance of standard diagnostic techniques for this condition. A total of 413 cases were identified, of whom 86 had microscopically proven infection. In proven cases, 23% had normal eosinophil counts, 19% had negative Strongyloides -specific serology, and 9.3% had normal blood counts and were seronegative. Serological testing was less sensitive for returning travelers (46.2%) than for migrants (89.7%). Immunosuppression, including human T-cell lymphotropic virus 1, was significantly associated with proven infection after controlling for age, presence of symptoms, duration of infection, and eosinophilia (OR 5.60, 95% CI 1.54-20.4). Patients with proven infection had lower serology values than those diagnosed with strongyloidiasis on the basis of positive serology and eosinophilia alone ( P = 0.016). Symptomatic patients were significantly younger, had a shorter presumed duration of infection, and lower serology values. These data suggest a correlation between immunologic control of strongyloidiasis and the amplitude of the humoral response.

Background: Understanding geographic and temporal trends in imported infections is key to the management of unwell travellers. Many tropical infections can be managed as outpatients, with admission reserved for severe cases., Methods: We prospectively recorded the diagnosis and travel history of patients admitted between 2000 and 2015. We describe the common tropical and non-tropical infectious diseases and how these varied based on region, reason for travel and over time., Results: A total of 4362 admissions followed an episode of travel. Falciparum malaria was the most common diagnosis (n=1089). Among individuals who travelled to Africa 1206/1724 (70.0%) had a tropical diagnosis. The risk of a tropical infection was higher among travellers visiting friends and relatives than holidaymakers (OR 2.8, p<0.001). Among travellers to Asia non-tropical infections were more common than tropical infections (349/782, 44.6%), but enteric fever (117, 33.5%) of the tropical infections and dengue (70, 20.1%) remained important. The number of patients admitted with falciparum malaria declined over the study but those of enteric fever and dengue did not., Conclusions: Most of those arriving from sub-Saharan Africa with an illness requiring admission have a classical tropical infection, and malaria still predominates. In contrast, fewer patients who travelled to Asia have a tropical diagnosis but enteric fever and dengue remain relatively common. Those visiting friends and relatives are most likely to have a tropical infection., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Malaria is the commonest imported infection in the UK. Malaria requiring ICU admission has a reported mortality of up to 25%. The relationship between ethnicity, immunity, and risk of malaria is complex. The Malaria Score for Adults (MSA) and Coma Acidosis Malaria (CAM) score have recently been proposed to risk stratify patients with malaria., Methods: Retrospective study of patients with WHO severe falciparum malaria admitted to ICU at the Hospital for Tropical Diseases, London, UK. The relationship between clinical variables and risk of death or a prolonged ICU stay were examined with logistic regression. The predictive value of the MSA and CAM score were calculated., Results: 124 patients were included. Cerebral malaria and acute kidney injury occurred earlier (median day 1) than acute respiratory distress syndrome (median day 3). Six patients had community acquired bacterial co-infection. Eight patients were co-infected with HIV, five of whom were newly diagnosed. The positive predictive value of a CAM score ≥2 or an MSA ≥5 for death were 12% and 22% respectively. Five patients died. No variable was significantly associated with risk of death. There were no significant differences between individuals raised in endemic countries compared to non-endemic countries., Conclusions: Mortality in patients managed in a specialist centre was low. Patients who died succumbed to complications associated with a prolonged stay on ICU rather than malaria per se. The clinical usefulness of the MSA and CAM score was limited. Co-infection with HIV was relatively common but compared to studies in children, bacteraemia was uncommon. The relationship between ethnicity and immunity to severe disease is complex.

Objectives: To establish the clinical reasons for inpatient admissions among injecting drug users. To determine the frequency of behavioural issues during their care and to estimate the financial implications of injecting drug use to the health service., Methods: Retrospective cohort study at University College London Hospital. Clinical, laboratory and financial data were extracted from case notes and electronic records. The cost of each admission was compared to the income received for the period of care., Results: 124 injecting drug users required 191 admissions between 2005 and 2009. Skin and soft tissue infections (58%) and pneumonia (18%) were the commonest reasons for admission. Bacteraemia at admission was often not accompanied by an inflammatory response. Exposure to HIV (4%), hepatitis B (49%) and C (84%) was common. Drug misuse (16%) during admission was frequent. The cost to the NHS of treating soft tissue infections in drug users was approximately £77 million per annum. After a median follow-up of 40 months, 10 patients (8%) had died. All deaths were attributable to drug use., Conclusions: Bacterial and viral infections are largely responsible for the significant mortality and morbidity of injecting drug users presenting to secondary care. The financial burden to the NHS is substantial., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Treatment of acute malaria caused by Plasmodium falciparum may include long-half-life drugs, such as the antifolate combination sulfadoxine-pyrimethamine (SP), to provide posttreatment chemoprophylaxis against parasite recrudescence or delayed emergence from the liver. An unusual case of P. falciparum recrudescence in a returned British traveler who received such a regimen, as well as a series of 44 parasite isolates from the same hospital, was analyzed by PCR and direct DNA sequencing for the presence of markers of parasite resistance to chloroquine and antifolates. The index patient harbored a mixture of wild-type and resistant pfdhfr and pfdhps alleles upon initial presentation. During his second malaria episode, he harbored only resistant parasites, with the haplotypes IRNI (codons 51, 59, 108, and 164) and SGEAA (codons 436, 437, 540, 581, and 613) at these two loci, respectively. Analysis of isolates from 44 other patients showed that the pfdhfr haplotype IRNI was common (found in 81% of cases). The SGEAA haplotype of pfdhps was uncommon (found only in eight cases of East African origin [17%]). A previously undescribed mutation, I431V, was observed for seven cases of Nigerian origin, occurring as one of two haplotypes, VAGKGS or VAGKAA. The presence of this mutation was also confirmed in isolates of Nigerian origin from the United Kingdom Malaria Reference Laboratory. The presence of the pfdhps haplotype SGEAA in P. falciparum parasites of East African origin appears to compromise the efficacy of treatment regimens that include SP as a means to prevent recrudescence. Parasites with novel pfdhps haplotypes are circulating in West Africa. The response of these parasites to chemotherapy needs to be evaluated.

Objectives: We sought to identify chloroquine-resistant Plasmodium falciparum parasites among 66 travellers who presented in the UK with malaria., Methods: A multiplex real-time PCR assay was devised to identify wild-type and two distinct chloroquine-resistance-associated alleles of the pfcrt gene., Results: Those with documented use of chloroquine/proguanil prophylaxis were more likely to carry parasites with resistance-associated alleles of pfcrt than were patients who had been using antimalarials other than chloroquine (92.9% versus 37.5%; P = 0.011). We also found evidence that people reporting optimum compliance with chloroquine prophylaxis during malaria exposure were more common among malaria cases than were those reporting optimum compliance with other regimens (OR 3.85, 95% CI 1.61-9.69; P = 0.0008)., Conclusions: Chloroquine, known to be failing as therapy for falciparum malaria worldwide, is also failing to provide adequate malaria prophylaxis for travellers.

Just more than 2,000 cases of Plasmodium falciparum malaria are reported in the United Kingdom annually, with a mortality rate of approximately 1%. Some studies suggest that patients with malaria who originate from disease-endemic areas are less likely to develop severe disease; such patients are often treated at home. We have prospectively examined 99 patients with imported P. falciparum malaria and categorized them according to severity as defined by World Health Organization criteria. There was no significant difference between those who developed severe disease and those who did not in terms of their ethnicity, residence in a malaria-endemic area, or history of previous episodes of malaria. To assume a patient has clinical immunity to malaria simply because they originate from or have lived for a long time in a malaria-endemic area may be inappropriate and unsafe.

A double-blind, community-randomized, placebo-controlled trial was conducted in a rural area of The Gambia between June and December 1999 to test whether a reduction in the infectious reservoir can reduce malaria transmission. Overall 14,017 (85%) individuals living in the study area were treated with either placebo or sulfadoxine-pyrimethamine (SP) combined with a single dose of artesunate (AS). Following the mass drug administration (MDA) 1375 children aged 6 months to 10 years were kept under surveillance for clinical malaria in 18 villages throughout the 1999 malaria transmission season. During a 20-week surveillance period 637 episodes of malaria were detected. The mean incidence rate was 2.5/100 child-weeks in the placebo villages, and 2.3/100 child-weeks in villages that received SP + AS. The mean rate ratio, adjusted for individual and village-level covariates, was 0.91 (95% CI 0.68-1.22, P = 0.49). During the first 2 months of surveillance, the malaria incidence was lower in treated villages. After 2 months the incidence was slightly higher in the MDA group but this was not statistically significant. Overall, no benefit of the MDA could be detected. The reason for the absence of an impact on malaria transmission is probably the very high basic reproductive number of malaria, and the persistence of mature gametocytes, which are not affected by AS treatment.