Scottish Index of Multiple Deprivation (SIMD) indicators as predictors of mortality among patients hospitalised with COVID-19 disease in the Lothian Region, Scotland during the first wave: a cohort study.

Background: Sars-CoV-2, the causative agent of COVID-19, has led to more than 226,000 deaths in the UK and multiple risk factors for mortality including age, sex and deprivation have been identified. This study aimed to identify which individual indicators of the Scottish Index of Multiple Deprivation (SIMD), an area-based deprivation index, were predictive of mortality.

Methods: This was a prospective cohort study of anonymised electronic health records of 710 consecutive patients hospitalised with Covid-19 disease between March and June 2020 in the Lothian Region of Southeast Scotland.

Distinctive hospital and community resistomes in Scottish urban wastewater: Metagenomics of a paired wastewater sampling design.

The wastewater microbiome contains a multitude of resistant bacteria of human origin, presenting an opportunity for surveillance of resistance in the general population. However, wastewater microbial communities are also influenced by clinical sources, such as hospitals. Identifying signatures of the community and hospital resistome in wastewater is needed for interpretation and risk analysis.

Performance status: A key factor in predicting mortality in the first wave of COVID-19 in South-East Scotland.

Background: COVID-19 mortality risk factors have been established in large cohort studies; long-term mortality outcomes are less documented.

Methods: We performed multivariable logistic regression to identify factors associated with in-patient mortality and intensive care unit (ICU) admission in symptomatic COVID-19 patients admitted to hospitals in South-East Scotland from 1st March to 30th June 2020. One-year mortality was reviewed.

Secrets of the Hospital Underbelly: Patterns of Abundance of Antimicrobial Resistance Genes in Hospital Wastewater Vary by Specific Antimicrobial and Bacterial Family.

Hospital wastewater is a major source of antimicrobial resistance (AMR) outflow into the environment. This study uses metagenomics to study how hospital clinical activity impacts antimicrobial resistance genes (ARGs) abundances in hospital wastewater. Sewage was collected over a 24-h period from multiple wastewater collection points (CPs) representing different specialties within a tertiary hospital site and simultaneously from community sewage works.

Segmentation and shielding of the most vulnerable members of the population as elements of an exit strategy from COVID-19 lockdown.

This study demonstrates that an adoption of a segmenting and shielding strategy could increase the scope to partially exit COVID-19 lockdown while limiting the risk of an overwhelming second wave of infection. We illustrate this using a mathematical model that segments the vulnerable population and their closest contacts, the 'shielders'. Effects of extending the duration of lockdown and faster or slower transition to post-lockdown conditions and, most importantly, the trade-off between increased protection of the vulnerable segment and fewer restrictions on the general population are explored.

Diagnostic performance of the combined nasal and throat swab in patients admitted to hospital with suspected COVID-19.

Background: Accurate diagnosis in patients with suspected coronavirus disease 2019 (COVID-19) is essential to guide treatment and limit spread of the virus. The combined nasal and throat swab is used widely, but its diagnostic performance is uncertain.

Methods: In a prospective, multi-centre, cohort study conducted in secondary and tertiary care hospitals in Scotland, we evaluated the combined nasal and throat swab with reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in consecutive patients admitted to hospital with suspected COVID-19.

Risk factors for carbapenemase-producing organisms among inpatients in Scotland: A national matched case-control study.

Objective: To determine risk factors for carbapenemase-producing organisms (CPOs) and to determine the prognostic impact of CPOs.

Design: A retrospective matched case-control study.

Patients: Inpatients across Scotland in 2010-2016 were included.

'The Mould that Changed the World': Quantitative and qualitative evaluation of children's knowledge and motivation for behavioural change following participation in an antimicrobial resistance musical.

Background: A primary school musical ("The Mould that Changed the World") was developed as a unique public engagement strategy to combat antimicrobial resistance (AMR) by engaging children in the story of the discovery of antibiotics, the risks of drug-resistant infections and the importance of prudent antibiotic use.

Methods: The musical intervention was implemented in two UK primary schools by music specialists through a series of workshops, associated learning resources and performances to relatives. Participating children (n = 182), aged 9 to 11 years, were given an online questionnaire in the classroom before rehearsals began and at two weeks post-performance with a six-month evaluation in one school.

Successful reintroduction of tumour necrosis factor-alpha inhibition after treatment of disseminated Lyme borreliosis.

The importance of tumour necrosis factor-alpha (TNF-α) in the human immune response to Borrelia burgdorferi is uncertain. Murine models suggest a critical role, including spirochaete reactivation following TNF-α inhibition. Our case, combined with a review of the clinical and scientific literature, provides reassurance that TNF-α inhibition can be safely reinstituted after treatment of disseminated borreliosis with standard duration antimicrobial chemotherapy.

Arsenic exposure and outcomes of antimonial treatment in visceral leishmaniasis patients in Bihar, India: a retrospective cohort study.

Background: In the late twentieth century, emergence of high rates of treatment failure with antimonial compounds (SSG) for visceral leishmaniasis (VL) caused a public health crisis in Bihar, India. We hypothesize that exposure to arsenic through drinking contaminated groundwater may be associated with SSG treatment failure due to the development of antimony-resistant parasites.

Methods: A retrospective cohort design was employed, as antimony treatment is no longer in routine use.

Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.

The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm).

The R enantiomer of the antitubercular drug PA-824 as a potential oral treatment for visceral Leishmaniasis.

The novel nitroimidazopyran agent (S)-PA-824 has potent antibacterial activity against Mycobacterium tuberculosis in vitro and in vivo and is currently in phase II clinical trials for tuberculosis (TB). In contrast to M. tuberculosis, where (R)-PA-824 is inactive, we report here that both enantiomers of PA-824 show potent parasiticidal activity against Leishmania donovani, the causative agent of visceral leishmaniasis (VL).

Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412.

Six healthy young male volunteers at a contract research organization were enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist anti-CD28 monoclonal antibody that directly stimulates T cells. Within 90 minutes after receiving a single intravenous dose of the drug, all six volunteers had a systemic inflammatory response characterized by a rapid induction of proinflammatory cytokines and accompanied by headache, myalgias, nausea, diarrhea, erythema, vasodilatation, and hypotension. Within 12 to 16 hours after infusion, they became critically ill, with pulmonary infiltrates and lung injury, renal failure, and disseminated intravascular coagulation.