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.

Risk factors for antimicrobial resistance in patients with bacteraemia related to urinary tract infection.

Introduction: NHS Lothian policy has recently changed to avoid first-line use of trimethoprim for uncomplicated urinary tract infections (UTI) in patients with risk factors for trimethoprim resistance, in line with national guidance. This study aimed to identify risk factors for antimicrobial resistance in bacteraemia related to UTI.

Methods: A retrospective cohort study of 687 patients with bacteraemia related to UTI in NHS Lothian from 01/02/18 to 29/02/20 was undertaken.

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.

HIV testing in secondary care: a multicentre longitudinal mixed methods electronic survey of non-HIV specialist hospital physicians in South-East Scotland and Northern England.

Background: Increasing the uptake of HIV testing in people who may have undiagnosed HIV is essential to reduce the morbidity associated with late HIV diagnosis.

Methods: We conducted a multicentre, longitudinal, mixed-methods study, surveying the attitudes, knowledge and practice of non-HIV specialist hospital physicians in South-East Scotland and North-East England with respect to HIV testing.

Results: We found that although awareness of indications for HIV testing had improved over time, only 13% of clinicians recognised all of the surveyed HIV indicator conditions.

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.

Staff and patient perceptions of a community urinary catheter service.

Introduction: Urinary catheters are used extensively throughout healthcare for various reasons including management of urinary tract dysfunction. The purpose of this study was to simultaneously explore both catheter user experience and staff perception of catheter services within community urinary catheter care.

Methods: A questionnaire was conducted to investigate the views of community nursing staff.

How youth mentoring relationships end and why it matters: a mixed-methods, multi-informant study.

Scant empirical attention has been devoted to understanding endings in youth mentoring relationships, despite the frequency with which they occur. This study examined data from a mixed-methods study of mentoring relationship endings in which youth mentees, the youth's parents or guardians, mentors, and program staff were surveyed about the closure process, and a subsample of program staff, mentors, and parents or guardians also participated in in-depth qualitative interviews. Findings from a descriptive analysis detailing the perceptions of multiple stakeholders in the closure process as reported in surveys are presented along with case studies derived from a case-based analysis of in-depth qualitative interview data.

Pig Exposure and Health Outcomes in Hospitalized Infectious Disease Patients in Vietnam.

Many infectious diseases have a zoonotic origin, and several have had major public health implications. Contact with animals is a known risk factor for zoonotic infections, although there are limited data on disease symptoms and pathogens associated with contact with different animal species. The rise in pig production in Southeast Asia has contributed to the emergence and re-emergence of zoonotic infections caused by contact with pigs and pig products.

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.

A phase I trial of ANG1/2-Tie2 inhibitor trebaninib (AMG386) and temsirolimus in advanced solid tumors (PJC008/NCI♯9041).

Background: There is crosstalk between the ANG-Tie2 and the PI3K/Akt/mTOR pathways. Combined ANG1/2 and mTOR blockade may have additive anti-cancer activity. The combination of trebananib, an inhibitor of ANG1/2-Tie2 interaction, with temsirolimus was evaluated in patients with advanced solid tumors to determine tolerability, maximum tolerated dose (MTD), and preliminary antitumor activity.

Arsenic, antimony, and Leishmania: has arsenic contamination of drinking water in India led to treatment- resistant kala-azar?

Background: In Bihar state, India, the cure rate of antimonial compounds (eg, sodium stibogluconate) in the treatment of visceral leishmaniasis (VL) has fallen from more than 85% to less than 50%. This reduction has been attributed to long-term, widespread misuse of antimonial drugs within the Indian private health-care system. We aimed to test the hypothesis that exposure to arsenic in drinking water in this region has resulted in antimony-resistant Leishmania parasites.

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).

Longitudinal language outcomes following intrathecal chemotherapy for acute lymphoblastic leukaemia.

Intrathecal chemotherapy (ITC) is the treatment option for acute lymphoblastic leukaemia (ALL). Neurocognitive deficits have been described following ITC, but language status post-treatment is yet to be clarified. This study examined the language skills of nine children following ITC for ALL (mean age 7;8 years and 3;2 years post-diagnosis at baseline measurement) and nine age- and sex-matched controls, at baseline then 2 years later, using a battery of tests assessing general language skills.

HIV testing: getting the message across--a survey of knowledge, attitudes and practice among non-HIV specialist physicians.

Introduction: 26% of people living with HIV in the UK remain undiagnosed and over 50% of adults with HIV are significantly immunocompromised at the time of diagnosis. Current guidelines recommend routine testing in all patients presenting with a range of conditions in low prevalence areas (< 2/1000).

Methods: The authors conducted an online survey of the knowledge, attitudes and practice of non-HIV specialist physicians with regard to HIV testing in two areas of the UK with a lower prevalence of HIV.

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.