Clinical outcomes and adverse events in patients hospitalised with COVID-19, treated with off-label hydroxychloroquine and azithromycin.

AIMS: To assess clinical outcomes and adverse drug events in patients hospitalised with COVID-19 treated with off-label hydroxychloroquine (HCQ) and azithromycin (Az). METHODS: We performed a retrospective analysis of hospitalised patients who had a positive polymerase chain reaction test for SARS-CoV-2 and received HCQ plus Az or no targeted therapy. The primary end point was clinical improvement on day 7 defined as either hospital discharge or an improvement of 2 points on a 6-category ordinal scale. Secondary outcomes included mortality at day 28, intensive care admission, requirement for mechanical ventilation and incidence of adverse events. RESULTS: Data from a total of 134 patients were evaluated; 82 patients received HCQ/Az and 52 patients received no targeted therapy. Clinical improvement was seen in 26.8% of patients who received HCQ/Az but this was not significant. The rates of intensive care transfer and mechanical ventilation were higher in the treatment group, but these differences were not significant. Mortality at day 28 was significantly higher in the treatment group (P = .03). Hypoglycaemia elevated liver function tests and QT prolongation were monitored in both groups. The risk of QT prolongation was significantly higher in the treatment group. Treatment was stopped early in 6 (7.3%) patients due to adverse events. CONCLUSION: Although patients who received HCQ/Az were more severely ill the administration of these repurposed drugs did not result in clinical improvement and was associated with a significant increase in toxicity. This descriptive study highlights the importance of monitoring all repurposed agents for adverse events.

The effects of intrinsic enrichment on captive felids.

Environmental enrichment is a well-known technique, which has been used to enhance the welfare of captive animals. The aim of this study is to investigate how three different forms of intrinsic enrichment, namely, a hay ball without scent, a hay ball with catnip, and a hay ball with cinnamon, influenced the behavior of six cheetah and two Sumatran tigers at Fota Wildlife Park, Ireland. Enrichment-directed behaviors, as well as pacing, locomotion, inactive, and exploratory behaviors were investigated. The results indicated that the three forms of enrichment had similar effects, in terms of enrichment-directed behavior, with cinnamon resulting in the highest levels of enrichment-directed behaviors. The cinnamon treatment resulted in a significant decrease in pacing behavior when compared with baseline observations. No evidence of habituation (i.e., a significant reduction in enrichment-directed behaviors) was observed for any of the three enrichments. This means that these low cost, easy to apply, practical forms of enrichment could be frequently applied for these species as part of an enrichment regime.

The effects of environmental and visitor variables on the behavior of free-ranging ring-tailed lemurs (Lemur catta) in captivity.

The effect of the zoo environment on captive animals is an increasingly studied area of zoo research, with visitor effects and exhibit design recognized as two of the factors that can contribute to animal welfare in captivity. It is known that in some situations, visitors may be stressful to zoo-housed primates, and this may be compounded by environmental factors such as the weather, the time of day, and zoo husbandry routines. Exhibit design and proximity of the public are also known to influence behavioral response of primates to visitors; however, there is minimal research on free-ranging zoo animals, even though they are potentially subjected to intense interactions with visitors. The current study explores the effect of the zoo environment, several visitor variables and specific animal-visitor interactions on the behavior of free-ranging ring-tailed lemurs (Lemur catta) at Fota Wildlife Park, Ireland. Data were obtained through scan samples collected over 18 months (n = 12,263) and analyzed using a range of statistical tests, including general estimating equations (GEE). Results demonstrate that the free-ranging lemurs' behavior at Fota Wildlife Park is affected by season, weather and time of day. Similarities in feeding behavior exist between the free-ranging group and lemurs in the wild when resources are plentiful. Visitor variables had a limited effect on lemur behavior and behavioral diversity level. Lemurs rarely reacted to visitors when specific interactions were considered. Generally, the results indicate that the ring-tailed lemurs in this study have adapted well to the zoo environment and habituated to visitors.

An investigation into the prevalence of exploratory behavior in captive cheetahs (Acinonyx jubatus).

Exploratory behavior in the wild is fundamentally linked to an animal's survival and natural life history. The ability to gather information about their environment, establish territories, assert dominance, communicate information regarding reproductive status and locate mates are closely associated with a range of exploratory behaviors. Understanding how these behaviors are performed within the captive setting is crucial in order to create a captive environment in which these behaviors can be expressed, and their function conserved. The objective of this research was to highlight the factors of captive husbandry and management that influence the occurrence of exploratory behaviour of cheetahs (Acinonyx jubatus) in captivity. One hundred and twelve cheetahs in 88 enclosures across nine zoological institutions in five countries were the subjects of this study. The presence of raised areas, number of movements between enclosures, group composition, sex and an interaction between group composition and the ability to view cheetahs in adjacent enclosures, all significantly influenced the prevalence of exploratory behavior in captive cheetahs. The presence of raised areas and an increasing number of movements between enclosures significantly increased the probability of observing exploratory behaviour, while this probability was significantly decreased for female cheetahs, when cheetahs were able to view conspecifics in adjacent enclosures, and were maintained in groups. A number of recommendations are discussed in relation to promoting exploratory behavior in captive cheetahs.

Evaluation and interpretation of the effects of environmental enrichment utilizing varying degrees of sampling effort.

Documenting the effects of novel forms of enrichment is becoming increasingly important within the field of environmental enrichment. Appropriate documentation and evaluation must accompany any enrichment research project in order for accurate results to be obtained. The objective of the present study was to provide an example of how the level of effort in documenting the effect of enrichment is linked to how it is evaluated. This study was carried out on eight cheetahs (Acinonyx jubatus) at Fota Wildlife Park, Ireland. Temporal feeding variation was the enrichment type used during this study. Behavior data were collected in five different ways in order to simulate varying degrees of effort. Randomization tests were utilized to analyze behavior data. Significant behavioral differences were observed in the first four sampling methods with patterns of behavior remaining similar in all five methods. However, only the most time intensive method concurred with findings previously published utilizing this form of enrichment. No significant differences in behavior were detected when the least time intensive method was used. Between 1 and 2 hr of data collection daily is necessary to evaluate temporal feeding variation accurately. However, 30-45 min of data collection also gave an insight into the effectiveness of the enrichment. Methods of evaluation can influence the interpretations of the strength of the enriching effect of the treatment. Appropriate evaluation and accurate reporting of enrichment is crucial for the future development of the environmental enrichment field.

A comparative study of the speeds attained by captive cheetahs during the enrichment practice of the "cheetah run".

The enrichment practice of the "cheetah run" is becoming increasingly popular within zoological institutions as a method to enrich captive cheetahs. A lure moving at speed represents an artificial prey item that the cursorial cheetah can pursue, therefore allowing it to perform an important hunting behavior within a captive setting. This study was conducted in order to highlight how employing different forms of this type of enrichment may influence its efficacy. This is important in relation to the future development of an optimum type of "cheetah run" enrichment which maximizes the potential beneficial effects and therefore positively impacts upon cheetah welfare in captivity. Video recordings were carried out at three separate institutions (Fota Wildlife Park, Ireland; Ann van Dyk Cheetah Centre, South Africa; Cheetah Conservation Fund, Namibia). Randomization tests were carried out to compare the highest speeds attained between males and females, trained and untrained cheetahs and also between the three institutions. Females and trained individuals reached significantly higher speeds compared with males and untrained individuals, respectively. The only significant difference between the three institutions was between the Ann van Dyk Cheetah Centre and the Cheetah Conservation Fund, where cheetahs at the Ann van Dyk center reached significantly higher speeds. The current study represents the first detailed study of any aspect of the "cheetah run" across multiple institutions. It also includes the first quantification of the speed of cheetahs in captivity in relation to differing enrichment practices.

A comprehensive investigation of negative visitor behaviour in the zoo setting and captive animals' behavioural response.

Negative visitor behaviour in zoos such as banging, shouting and feeding animals are unwanted, but under-studied, visitor actions. It is not known how prevalent negative behaviour is, which species or enclosure type receives the most negative behaviour or how these behaviours affect zoo-housed animals. In this study, a comprehensive assessment of negative visitor behaviour, using an innovative methodology, was conducted at 25 different enclosures at Fota Wildlife Park, Ireland. Additionally, animal activity level and out of sight behaviour was observed. Descriptive statistics and general linear models were used to investigate which variables affected behaviour. Banging was the most common negative behaviour, while Humboldt penguins, lion-tailed macaques and Sumatran tigers were the most harassed species. Negative actions increased as visitor number increased and at traditional-style viewing areas. Active animal behaviour and out of sight animals were effected as negative visitor behaviours increased, but there appeared to be a tolerance threshold before a behavioural response was observed. By understanding negative behaviours, zoos can strive to reduce them and promote positive animal welfare.

Kocuria rhizophila prosthetic hip joint infection.

We present the first case report of prosthetic joint infection (PJI) caused by Kocuria rhizophila. Our patient is a 74-year-old male who underwent primary total hip replacement for right hip pain. His recovery was uneventful until 6 weeks postoperatively when he presented to his routine outpatient appointment with significant erythema, swelling, and tenderness over his right hip wound. Based on the acuity of his symptoms and the radiological findings, it was determined that the patient should undergo debridement, antibiotics, and implant retention (DAIR procedure). A consensus decision was also made at our PJI multidisciplinary meeting to treat him with 12 weeks of IV antibiotics. After completing this 12 weeks course of IV Vancomycin, his inflammatory markers returned to normal limits. At 6 months follow-up, our patient was mobilizing independently without any signs of infection recurrence. His radiographs showed the implant was in a satisfactory position with no evidence of loosening. This case adds to an emerging body of literature describing invasive infections associated with Kocuria species. We have demonstrated the effectiveness of managing this condition with debridement, implant retention, and IV Vancomycin therapy for 12 weeks.

An International Investigation of the Prevalence of Negative Visitor Behaviour in the Zoo.

Negative visitor behaviour is an understudied area of zoo research, even though negative actions can have serious implications for animal welfare. This research project investigated the prevalence of negative visitor behaviours at four different zoos. It included observations of visitors at seven different taxa exhibits and three different types of enclosures. A modified version of behaviour sampling was used to record visitor behaviour and the activity of the animals, while a negative binomial regression was conducted to test the significance of several predictor variables against the number of negative behaviours observed. Negative visitor behaviour was relatively common, occurring in 57% of observations. Banging was the most commonly observed negative action. Negative behaviours were influenced by zoo (p < 0.001), species (p < 0.001) and the number of visitors present (p < 0.001). The charismatic species were the most harassed animals included in the study, while children were the most likely to engage in negative behaviour. Negative visitor behaviours occurred more frequently when animals were active and in close proximity to visitors. It is imperative for zoos to understand visitors' behaviour so that they can effectively communicate with their visitors to minimise negative actions and promote better animal welfare.

Assessing the potential for invasive species introductions and secondary spread using vessel movements in maritime ports.

Global shipping facilitates the introduction of invasive species and parasites via ballast water and hull fouling. Regional management of invasives may be strengthened by identifying the major routes in a network, to allow for targeted ship inspections. This study used cargo shipping records to establish the connectivity of shipping routes between ports in Ireland and other nations. 9291 records were analysed, investigating vessel residence and journey times. On average, vessels spent up to five days in port and less than five days at sea. However, there was strong variation, with general cargo ships recording up to 13 days in port. A horizon scan for species likely to invade in Ireland was incorporated for five species and their associated parasites: American razor clam, Asian shore crab, Brush clawed shore crab, Chinese mitten crab and American slipper limpet. Routes of concern are highlighted and a general framework for effective management is outlined.

A Service Evaluation of Adherence with Antimicrobial Guidelines in the Treatment of Community-Acquired Pneumonia Before and During the SARS-CoV-2 Outbreak.

Antimicrobial stewardship is essential to reducing antimicrobial resistance, reducing costs, and, crucially, ensuring good patient care. Community-acquired pneumonia (CAP) is a common medical condition, the symptoms of which show a significant overlap with those of COVID-19. Following the COVID-19 outbreak in Ireland, patients presenting to our hospital with features of a respiratory infection were more commonly reviewed within 24 hours (24h) of admission by an infectious disease (ID) or respiratory specialist. We aimed to assess how the change in service provision, involving frequent specialist reviews of patients admitted with features of CAP during the first wave of the COVID-19 pandemic, affected antimicrobial stewardship and prescribing practices. Patients admitted under general medical teams treated for CAP from March-April 2020 were included. Retrospective data including demographics, CURB-65 score, and antimicrobial therapy were collected, as well as information on whether the patient had undergone specialist review by an ID or respiratory physician. Data were compared to a similar cohort treated for CAP between November 2019 and January 2020, though in this cohort, before the era of COVID-19, none of the patients had undergone specialist review. Seventy-six patients were included from the March-April 2020 cohort, with 77 from November 2019-January 2020 for comparison. An ID or respiratory specialist reviewed 35 patients from the March-April cohort within 24 h of admission. There was a higher rate of appropriate escalation, de-escalation, and continuation of antibiotics among those reviewed. Less than 20% of patients were started on antibiotics in accordance with CAP guidelines on admission, though the antibiotics initiated were frequently deemed appropriate in the clinical setting. Specialist review increases rates of appropriate antimicrobial prescribing and adherence with hospital guidelines in patients with CAP.

Severe COVID-19 is characterised by inflammation and immature myeloid cells early in disease progression.

SARS-CoV-2 infection causes a wide spectrum of disease severity. Identifying the immunological characteristics of severe disease and the risk factors for their development are important in the management of COVID-19. This study aimed to identify and rank clinical and immunological features associated with progression to severe COVID-19 in order to investigate an immunological signature of severe disease. One hundred and eight patients with positive SARS-CoV-2 PCR were recruited. Routine clinical and laboratory markers were measured, as well as myeloid and lymphoid whole-blood immunophenotyping and measurement of the pro-inflammatory cytokines IL-6 and soluble CD25. All analysis was carried out in a routine hospital diagnostic laboratory. Univariate analysis demonstrated that severe disease was most strongly associated with elevated CRP and IL-6, loss of DLA-DR expression on monocytes and CD10 expression on neutrophils. Unbiased machine learning demonstrated that these four features were strongly associated with severe disease, with an average prediction score for severe disease of 0.925. These results demonstrate that these four markers could be used to identify patients developing severe COVID-19 and allow timely delivery of therapeutics.

On the diversity and distribution of a data deficient habitat in a poorly mapped region: The case of Sabellaria alveolata L. in Ireland.

Data that can be used to monitor biodiversity through time are essential for conservation and management. The reef-forming worm, Sabellaria alveolata (L. 1767) is currently classed as 'Data Deficient' due to an imbalance in the spread of data on its distribution. Little is known about the distribution of this species around Ireland. Using data archaeology, we collated past and present distribution records and discovered that S. alveolata has a discontinuous distribution with large gaps between populations. Many regions lack data and should be targeted for sampling. Biodiversity surveys revealed that S. alveolata supported diverse epibiotic algal communities. Retrograding (declining) reefs supported greater infaunal diversity than prograding (growing) reefs or sand, suggesting that S. alveolata is a dynamic ecosystem engineer that has a lasting legacy effect. Similar research should be carried out for other Data Deficient species, habitats and regions. Such data are invaluable resources for management and conservation.

Late presentation of 'Lemierre's syndrome': how a delay in seeking healthcare and reduced access to routine services resulted in widely disseminated Fusobacterium necrophorum infection during the global COVID-19 pandemic.

The SARS-CoV-2 outbreak has disrupted the delivery of routine healthcare services on a global scale. With many regions suspending the provision of non-essential healthcare services, there is a risk that patients with common treatable illnesses do not receive prompt treatment, leading to more serious and complex presentations at a later date. Lemierre's syndrome is a potentially life-threatening and under-recognised sequela of an oropharyngeal or dental infection. It is characterised by septic embolisation of the gram-negative bacillus Fusobacterium necrophorum to a variety of different organs, most commonly to the lungs. Thrombophlebitis of the internal jugular vein is frequently identified. We describe an atypical case of Lemierre's syndrome involving the brain, liver and lungs following a dental infection in a young male who delayed seeking dental or medical attention due to a lack of routine services and concerns about the SARS-CoV-2 outbreak.

Bacterial pneumonia coinfection and antimicrobial therapy duration in SARS-CoV-2 (COVID-19) infection.

BACKGROUND: Bacterial respiratory coinfection in the setting of SARS-CoV-2 infection remains poorly described. A description of coinfection and antimicrobial usage is needed to guide ongoing antimicrobial stewardship. OBJECTIVES: To assess the rate of empirical antimicrobial treatment in COVID-19 cases, assess the rate and methods of microbiological sampling, assess the rate of bacterial respiratory coinfections and evaluate the factors associated with antimicrobial therapy in this cohort. METHODS: Inpatients with positive SARS-CoV-2 PCR were recruited. Antibiotic prescription, choice and duration were recorded. Taking of microbiological samples (sputum culture, blood culture, urinary antigens) and culture positivity rate was also recorded. Linear regression was performed to determine factors associated with prolonged antimicrobial administration. RESULTS: A total of 117 patients were recruited; 84 (72%) were prescribed antimicrobial therapy for lower respiratory tract infections. Respiratory pathogens were identified in seven (6%) patients. The median duration of antimicrobial therapy was 7 days. C-reactive protein level, oxygen requirement and positive cultures were associated with prolonged duration of therapy. CONCLUSIONS: The rate of bacterial coinfection in SARS-CoV-2 is low. Despite this, prolonged courses of antimicrobial therapy were prescribed in our cohort. We recommend active antimicrobial stewardship in COVID-19 cases to ensure appropriate antimicrobial prescribing.

Erratum to: Bacterial pneumonia coinfection and antimicrobial therapy duration in SARS-CoV-2 (COVID-19) infection.

[This corrects the article DOI: 10.1093/jacamr/dlaa071.].

Intrapopulational distribution of Meiogymnophallus minutus (Digenea, Gymnophallidae) infections in its first and second intermediate host.

Host size and age are generally assumed to play a pivotal role in digenean trematode infection patterns, accounting for much of the variation found within intermediate host populations. However, knowledge is based on a limited number of studied host-parasite systems. We investigated the shell length class distribution of Meiogymnophallus minutus infections within populations of the first intermediate host Scrobicularia plana and second intermediate host Cerastoderma edule. Infections occurred very early in the life of the two intermediate hosts. Both prevalence and intensity of infections increased with host shell length and displayed extremely high values amongst large individuals. Whilst metacercarial infection patterns in juvenile C. edule could be best explained by differences in host shell length, in adult cockles, the effect of host age on infection levels prevailed. The microsporidian hyperparasite Unikaryon legeri, occurring in the metacercarial stage of M. minutus, was particularly abundant in aged cockles, strongly influencing infection patterns of the gymnophallid. Our results are consistent with the intrapopulational distribution reported from other digenean trematode parasites. The relative influence of both host size and age and the underlying mechanisms as well as the impact of hyperparasitism on M. minutus infection patterns are discussed.

Tetanus - A Rare But Real Threat.

Tetanus is a potentially fatal disease of the nervous system arising from toxins produced by Clostridium tetani, an anaerobic bacterium found in soil [1]. Characterized by muscular rigidity, spasms and autonomic dysregulation its identification and, importantly, its prevention remain critical to the welfare of at risk patients. We present the case of a twenty two year old woman who presented to hospital with trismus and generalized muscle spasms three days following a dog bite to the right hand. Here, we discuss the presentation of generalized tetanus and the use of neurophysiology to facilitate its diagnosis.

In vivo exposure to microcystins induces DNA damage in the haemocytes of the zebra mussel, Dreissena polymorpha, as measured with the comet assay.

The Comet assay was used to investigate the potential of the biotoxin microcystin (MC) to induce DNA damage in the freshwater zebra mussel, Dreissena polymorpha. Mussels maintained in the laboratory were fed daily, over a 21-day period, with one of four strains of the cyanobacterium, Microcystis aeruginosa. Three of the strains produced different profiles of MC toxin, while the fourth strain did not produce MCs. The mussels were sampled at 0, 7, 14, and 21 days by withdrawing haemocytes from their adductor muscle. In addition, a positive control was performed by exposing a subsample of the mussels to water containing cadmium chloride (CdCl(2)). Cell viability, measured with the Fluorescein Diacetate/Ethidium Bromide test, indicated that the MC concentrations, to which the mussels were exposed, were not cytotoxic to the haemocytes. The Comet assay performed on the haemocytes indicated that exposure to CdCl(2) produced a dose-responsive increase in DNA damage, demonstrating that mussel haemocytes were sensitive to DNA-damaging agents. DNA damage, measured as percentage tail DNA (%tDNA), was observed in mussels exposed to the three toxic Microcystis strains, but not in mussels exposed to the nontoxic strain. Toxin analysis of the cyanobacterial cultures confirmed that the three MC-producing strains exhibit different toxin profiles, with the two MC variants detected being MC-LF and MC-LR. Furthermore, the DNA damage that was observed appeared to be strain-specific, with high doses of MC-LF being associated with a higher level of genotoxicity than low concentrations of MC-LR. High levels of MC-LF also seemed to induce relatively more persistent DNA damage than small quantities of MC-LR. This study is the first to demonstrate that in vivo exposure to MC-producing strains of cyanobacteria induces DNA damage in the haemocytes of zebra mussels and confirms the sublethal toxicity of these toxins.

Fatigue and Activity Management Education for Individuals with Systemic Lupus Erythematosus.

BACKGROUND: Fatigue and Activity Management Education (FAME) is a six-week occupational therapy-led programme focusing on fatigue and stress management, exercise, nutrition, and joint protection. Each session consists of education and goal setting. OBJECTIVES OF STUDY: To assess the impact of FAME on occupational participation and fatigue management. METHODS: Three programmes were facilitated with twenty-one women with SLE. A mixed methods design was used. Quantitative data were collected using self-reported questionnaires administered before, immediately after, and eight weeks after intervention. Data were analysed using descriptive and nonparametric inferential statistics. Qualitative data were collected through focus groups and interviews. Thematic analysis was carried out on the qualitative data. FINDINGS: There was a statistically significant improvement in depression as measured by the Hospital Anxiety and Depression Scale and categories of "burden to others" and "fatigue" in the LupusQoL. There were nonsignificant improvements in fatigue, occupational participation, self-efficacy, and anxiety. Participants reported an improved understanding of fatigue and the impact of stress on fatigue. They also identified self-management strategies they were using on a daily basis.