Publications by authors named "Sarah Logan"

66 Publications

Post-COVID-19 assessment in a specialist clinical service: a 12-month, single-centre, prospective study in 1325 individuals.

BMJ Open Respir Res 2021 11;8(1)

University College London Hospitals NHS Foundation Trust, London, UK

Introduction: Post-COVID-19 complications require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated post-COVID-19 clinical service to include hospitalised and non-hospitalised patients.

Methods: In a single-centre, observational analysis, we report the demographics, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation of 1325 individuals assessed at the University College London Hospitals post-COVID-19 service between April 2020 and April 2021, comparing by referral route: posthospitalised (PH), non-hospitalised (NH) and post emergency department (PED). Symptoms associated with poor recovery or inability to return to work full time were assessed using multivariable logistic regression.

Results: 1325 individuals were assessed (PH: 547, 41.3%; PED: 212, 16%; NH: 566, 42.7%). Compared with the PH and PED groups, the NH group were younger (median 44.6 (35.6-52.8) years vs 58.3 (47.0-67.7) years and 48.5 (39.4-55.7) years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be of ethnic minority (30.9%, 52.7% and 41.0%) or seen later after symptom onset (median (IQR): 194 (118-298) days, 69 (51-111) days and 76 (55-128) days; all p<0.0001). All groups had similar rates of onward specialist referral (NH 18.7%, PH 16.1% and PED 18.9%, p=0.452) and were more likely to require support for breathlessness (23.7%, 5.5% and 15.1%, p<0.001) and fatigue (17.8%, 4.8% and 8.0%, p<0.001). Hospitalised patients had higher rates of pulmonary emboli, persistent lung interstitial abnormalities and other organ impairment. 716 (54.0%) individuals reported <75% optimal health (median 70%, IQR 55%-85%). Less than half of employed individuals could return to work full time at first assessment.

Conclusion: Post-COVID-19 symptoms were significant in PH and NH patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.
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http://dx.doi.org/10.1136/bmjresp-2021-001041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587466PMC
November 2021

Rituximab 500 mg 6-monthly infusions is an option in maintenance therapy of ANCA-associated vasculitis.

Rheumatol Adv Pract 2021 16;5(2):rkab039. Epub 2021 Jul 16.

Institute of Clinical Sciences, Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, UK.

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http://dx.doi.org/10.1093/rap/rkab039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496757PMC
July 2021

Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate.

J Infect 2021 06 11;82(6):276-316. Epub 2021 Mar 11.

Hospital for Tropical Diseases, Division of Infection, University College London Hospitals NHS Foundation Trust, London, NW1 2BU, United Kingdom; Institute for Global Health, University College London, London, WC1E 6BT, United Kingdom; MRC Clinical Trials Unit, University College London, London, WC1V 6LJ, United Kingdom. Electronic address:

Objective: Our objective was to describe the characteristics of patients admitted, discharged and readmitted, due to COVID-19, to a central London acute-care hospital during the second peak, in particular in relation to corticosteroids use.

Methods: We reviewed patients admitted from the community to University College Hospital (UCH) with COVID-19 as their primary diagnosis between 1st-31st December 2020. Re-attendance and readmission data were collected for patients who re-presented within 10 days following discharge. Data were retrospectively collected.

Results: 196 patients were admitted from the community with a diagnosis of COVID-19 and discharged alive in December 2020. Corticosteroids were prescribed in hospital for a median of 5 days (IQR 3-8). 20 patients (10.2%) were readmitted within 10 days. 11/20 received corticosteroids in the first admission of which 10 had received 1-3 days of corticosteroids. Readmission rate in those receiving 1-3 days of corticosteroids was 25%.

Conclusions: Most international guidelines have recommended providing up to 10 days of corticosteroids for severe COVID-19 but stopping on discharge. Our findings show shorter courses of corticosteroids during admission are associated with an increased risk of being readmitted and support continuing the course of corticosteroids after hospital discharge monitored in the virtual ward setting.
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http://dx.doi.org/10.1016/j.jinf.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948670PMC
June 2021

COVID-19 emergency department discharges: an outcome study.

Clin Med (Lond) 2021 03 8;21(2):e126-e131. Epub 2021 Jan 8.

University College London Hospitals NHS Foundation Trust, London, UK.

Pressure on acute medical services in the pandemic mandated an assertive emergency department (ED) discharge policy. Given the potential for subsequent deterioration and growing appreciation of complications relating to COVID-19 infection, this follow up study was instigated to provide clinical reassurance that discharged patients had followed a safe clinical course. 199 patients discharged from the ED of our central London hospital were identified over a 20-day period at the height of the pandemic in April 2020. 44 had already reattended ED and 12 had been admitted. At 2-week telephone follow-up, 14 patients were identified who required urgent recall for assessment. At 4-week telephone follow-up, 87 patients were identified with persistent symptoms requiring face to face review. A COVID-19 follow-up clinic was therefore established to provide multi-professional review and diagnostics. 65 patients attended for this assessment. This is the first report on outcomes in COVID-19 infected patients discharged from an ED. It highlights the importance of safety-netting after discharge, the difficulty in predicting which patients might deteriorate and the need for appropriate follow up services.
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http://dx.doi.org/10.7861/clinmed.2020-0817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002789PMC
March 2021

Implementation and evaluation of a COVID-19 rapid follow-up service for patients discharged from the emergency department.

Clin Med (Lond) 2021 Jan 18;21(1):e57-e62. Epub 2020 Dec 18.

Hospital for Tropical Diseases, London, UK

The COVID-19 pandemic has necessitated rapid adaptation of healthcare providers to new clinical and logistical challenges. Following identification of high levels of emergency department (ED) reattendance among patients with suspected COVID-19 at our centre, we piloted a rapid remote follow-up service for this patient group. We present our service framework and evaluation of our pilot cohort of 192 patients. We followed up patients by telephone within 36 hours of their ED attendance. Pulse oximetry was used for remote monitoring of a subset of patients. Patients required between one and six consecutive telephone assessments, dependent on illness severity, and 23 patients were recalled for in-person assessment. Approximately half of patients with confirmed or probable COVID-19 required onward referral for respiratory follow-up. This framework reduced unplanned ED reattendances in comparison with a retrospective comparator cohort (4.7% from 22.6%). We reproduced these findings in a validation cohort with a high prevalence of acute COVID-19, managed through the clinic in September-October 2020, where we identified an unplanned ED reattendance rate of 5.2%. We propose that rapid remote follow-up is a mechanism by which ambulatory patients can be clinically supported during the acute phase of illness, with benefits both to patient care and to health service resilience.
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http://dx.doi.org/10.7861/clinmed.2020-0816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850184PMC
January 2021

Delayed healthcare seeking and prolonged illness in healthcare workers during the COVID-19 pandemic: a single-centre observational study.

BMJ Open 2020 11 26;10(11):e040216. Epub 2020 Nov 26.

COVID-19 Response Team, Department of Infectious Diseases, University College London Hospitals NHS Foundation Trust, Hospital for Tropical Diseases, London, UK.

Objectives: To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19.

Design: A cross-sectional, single-centre study.

Setting: A large, teaching hospital based in Central London with tertiary infection services.

Participants: 236 HCWs completed a survey distributed by internal staff email bulletin. 167 were women and 65 men.

Measures: Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report.

Results: The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020 Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110/138, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off.

Conclusion: There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Subsequent serology studies at the same hospital study site have confirmed sero-positivity for COVID-19 up to 45% by the end of April 2020 in frontline HCWs. The study revealed a concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This study also highlighted anosmia as a key symptom of COVID-19 early in the pandemic, prior to this symptom being more widely recognised as a feature of COVID-19.
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http://dx.doi.org/10.1136/bmjopen-2020-040216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692003PMC
November 2020

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids.

Transl Psychiatry 2020 10 13;10(1):347. Epub 2020 Oct 13.

Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, 53226, WI, USA.

Maternal alcohol exposure during pregnancy can substantially impact the development of the fetus, causing a range of symptoms, known as fetal alcohol spectrum disorders (FASDs), such as cognitive dysfunction and psychiatric disorders, with the pathophysiology and mechanisms largely unknown. Recently developed human cerebral organoids from induced pluripotent stem cells are similar to fetal brains in the aspects of development and structure. These models allow more relevant in vitro systems to be developed for studying FASDs than animal models. Modeling binge drinking using human cerebral organoids, we sought to quantify the downstream toxic effects of alcohol (ethanol) on neural pathology phenotypes and signaling pathways within the organoids. The results revealed that alcohol exposure resulted in unhealthy organoids at cellular, subcellular, bioenergetic metabolism, and gene expression levels. Alcohol induced apoptosis on organoids. The apoptotic effects of alcohol on the organoids depended on the alcohol concentration and varied between cell types. Specifically, neurons were more vulnerable to alcohol-induced apoptosis than astrocytes. The alcohol-treated organoids exhibit ultrastructural changes such as disruption of mitochondria cristae, decreased intensity of mitochondrial matrix, and disorganized cytoskeleton. Alcohol exposure also resulted in mitochondrial dysfunction and metabolic stress in the organoids as evidenced by (1) decreased mitochondrial oxygen consumption rates being linked to basal respiration, ATP production, proton leak, maximal respiration and spare respiratory capacity, and (2) increase of non-mitochondrial respiration in alcohol-treated organoids compared with control groups. Furthermore, we found that alcohol treatment affected the expression of 199 genes out of 17,195 genes analyzed. Bioinformatic analyses showed the association of these dysregulated genes with 37 pathways related to clinically relevant pathologies such as psychiatric disorders, behavior, nervous system development and function, organismal injury and abnormalities, and cellular development. Notably, 187 of these genes are critically involved in neurodevelopment, and/or implicated in nervous system physiology and neurodegeneration. Furthermore, the identified genes are key regulators of multiple pathways linked in networks. This study extends for the first time animal models of binge drinking-related FASDs to a human model, allowing in-depth analyses of neurotoxicity at tissue, cellular, subcellular, metabolism, and gene levels. Hereby, we provide novel insights into alcohol-induced pathologic phenotypes, cell type-specific vulnerability, and affected signaling pathways and molecular networks, that can contribute to a better understanding of the developmental neurotoxic effects of binge drinking during pregnancy.
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http://dx.doi.org/10.1038/s41398-020-01029-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553959PMC
October 2020

Isolation and Culture of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoid Cells.

Methods Mol Biol 2020 Oct 8. Epub 2020 Oct 8.

Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.

The advent of human-induced pluripotent stem cell (iPSC)-derived three-dimensional (3D) cerebral organoids provides unprecedented opportunities of modeling human brains in states of health and disorder. Emerging data supports that cerebral organoids allow for more relevant in vitro systems for studying the human brain system and diseases than the current widely used 2D monolayer cell culture. Thus, the ability to isolate, culture, and maintain human brain cells from cerebral organoids is highly needed, particularly for studies on organoid-derived cell-type-specific signaling and their electrophysiological properties. Here we present a protocol to isolate and culture brain cells from 2-month human iPSC-derived cerebral organoids. The dissociation and plating of cells from organoids takes 3-4 h. The dissociated cells can be maintained in culture for up to at least 3 weeks. Some cells expressed the neuron-specific marker microtubule-associated protein 2 and exhibited spontaneous action potentials.
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http://dx.doi.org/10.1007/7651_2020_328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030126PMC
October 2020

Psychological and self-management support for people with vasculitis or connective tissue diseases: UK health professionals' perspectives.

Rheumatol Adv Pract 2020 27;4(2):rkaa016. Epub 2020 May 27.

Department of Nursing and Midwifery, Faculty of Health and Applied Science, University of the West of England.

Objectives: CTD and systemic vasculitis impact on health-related quality of life. Treatment can be complex, involving multiple medical specialities. The aim of this study was to investigate psychological and self-management support for patients in secondary care.

Methods: An online survey of health professionals in the UK, including 45 multiple-choice and free-text questions, was analysed descriptively. Free-text survey responses were analysed thematically to identify health professionals' perceptions of best practice and unmet needs.

Results: The online survey included 120 health professionals (34% specialist nurses, 51% doctors and 12% allied health professionals), predominantly working in rheumatology (52.9%) and nephrology (21.5%) departments. Access to self-management programmes or clinics for people with CTD or vasculitis was available in 23% of rheumatology and 8% of nephrology departments. In response to 'How well is your team providing self-management support to people with CTD or vasculitis?', 38% of respondents reported 'not very well' or 'not well at all'. Direct access to psychological support was available in 76.9% of nephrology and 32.8% of rheumatology departments. More than 80% of respondents would like additional training. Key themes from the qualitative data (free-text survey responses) included the importance of: dedicated psychological support and self-management programmes for people with CTD and vasculitis, a whole-team approach (specialist teams empowering people to manage their own care), staff training (e.g. brief psychological interventions) and signposting to resources, including patient charities.

Conclusion: People with CTD and vasculitis have complex needs, and improvements in self-management and psychological support are required in UK rheumatology and nephrology departments.
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http://dx.doi.org/10.1093/rap/rkaa016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494082PMC
May 2020

Hyperkeratotic Plaque on the Thigh of an Immunosuppressed Patient: Challenge.

Am J Dermatopathol 2020 Aug;42(8):e118-e119

Department of Dermatology, Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, United Kingdom.

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http://dx.doi.org/10.1097/DAD.0000000000001619DOI Listing
August 2020

Hyperkeratotic Plaque on the Thigh of an Immunosuppressed Patient: Answer.

Am J Dermatopathol 2020 Aug;42(8):618-619

Department of Dermatology, Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, United Kingdom.

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http://dx.doi.org/10.1097/DAD.0000000000001620DOI Listing
August 2020

Experience of a novel community testing programme for COVID-19 in London: Lessons learnt.

Clin Med (Lond) 2020 09 17;20(5):e165-e169. Epub 2020 Jul 17.

London North West University Healthcare NHS Trust, Harrow, UK

We describe the London community testing programme developed for COVID-19, audit its effectiveness and report patient acceptability and patient adherence to isolation guidance, based upon a survey conducted with participants.Any patients meeting the Public Health England (PHE) case definition for COVID-19 who did not require hospital admission were eligible for community testing. 2,053 patients with suspected COVID-19 were tested in the community between January and March 2020. Of those tested, 75 (3.6%) were positive. 88% of patients that completed a patient survey felt safe and 82% agreed that community testing was preferable to hospital admission. 97% were able to remain within their own home during the isolation period but just 41% were able to reliably isolate from other members of their household.The London community testing programme allowed widespread testing for COVID-19 while minimising patient transport, hospital admissions and staff exposures. Community testing was acceptable to patients and preferable to admission to hospital. Patients were able to reliably isolate in their home but not from household contacts. The authors believe in the importance, feasibility and acceptability of community testing for COVID-19 as a part of a package of interventions to mitigate a second wave of infection.
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http://dx.doi.org/10.7861/clinmed.2020-0436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539734PMC
September 2020

Dynamic Characterization of Structural, Molecular, and Electrophysiological Phenotypes of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids, and Comparison with Fetal and Adult Gene Profiles.

Cells 2020 05 23;9(5). Epub 2020 May 23.

Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Background: The development of 3D cerebral organoid technology using human-induced pluripotent stem cells (iPSCs) provides a promising platform to study how brain diseases are appropriately modeled and treated. So far, understanding of the characteristics of organoids is still in its infancy. The current study profiled, for the first time, the electrophysiological properties of organoids at molecular and cellular levels and dissected the potential age equivalency of 2-month-old organoids to human ones by a comparison of gene expression profiles among cerebral organoids, human fetal and adult brains.

Results: Cerebral organoids exhibit heterogeneous gene and protein markers of various brain cells, such as neurons, astrocytes, and vascular cells (endothelial cells and smooth muscle cells) at 2 months, and increases in neural, glial, vascular, and channel-related gene expression over a 2-month differentiation course. Two-month organoids exhibited action potentials, multiple channel activities, and functional electrophysiological responses to the anesthetic agent propofol. A bioinformatics analysis of 20,723 gene expression profiles showed the similar distance of gene profiles in cerebral organoids to fetal and adult brain tissues. The subsequent Ingenuity Pathway Analysis (IPA) of select canonical pathways related to neural development, network formation, and electrophysiological signaling, revealed that only calcium signaling, cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling in neurons, glutamate receptor signaling, and synaptogenesis signaling were predicted to be downregulated in cerebral organoids relative to fetal samples. Nearly all cerebral organoid and fetal pathway phenotypes were predicted to be downregulated compared with adult tissue.

Conclusions: This novel study highlights dynamic development, cellular heterogeneity and electrophysiological activity. In particular, for the first time, electrophysiological drug response recapitulates what occurs in vivo, and neural characteristics are predicted to be highly similar to the human brain, further supporting the promising application of the cerebral organoid system for the modeling of the human brain in health and disease. Additionally, the studies from these characterizations of cerebral organoids in multiple levels and the findings from gene comparisons between cerebral organoids and humans (fetuses and adults) help us better understand this cerebral organoid-based cutting-edge platform and its wide uses in modeling human brain in terms of health and disease, development, and testing drug efficacy and toxicity.
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http://dx.doi.org/10.3390/cells9051301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291286PMC
May 2020

Routine Outpatient Parenteral Antimicrobial Therapy Clinic Review Minimizes Inpatient Readmission.

Clin Infect Dis 2020 12;71(10):2771-2773

Department of Clinical Microbiology, University College London Hospitals, London, United Kingdom.

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http://dx.doi.org/10.1093/cid/ciaa132DOI Listing
December 2020

Clinical outcomes of teicoplanin use in the OPAT setting.

Int J Antimicrob Agents 2020 Mar 8;55(3):105888. Epub 2020 Jan 8.

Division of Infection, University College London Hospitals, London, UK; Division of Infection & Immunity, University College London, London, UK. Electronic address:

Teicoplanin possesses several convenient properties for use in the delivery of outpatient parenteral antimicrobial therapy (OPAT) services. However, its use is not widespread and data on its efficacy in the OPAT setting are limited. Here we present a case series of patients undergoing OPAT care being treated by either teicoplanin-based (n = 107) or ceftriaxone-based (n = 191) antibiotic regimens. Clinical failure with teicoplanin occurred in five episodes of care (4.7%) compared with only two episodes of ceftriaxone-based OPAT care (1.0%). Teicoplanin-associated clinical failure was observed in 2 (33.3%) of 6 patients with Enterococcus infections compared with 3 (3.0%) of 101 patients with non-Enterococcus infections. Overall, there were four (2.9%) drug-related adverse events for teicoplanin and four (1.8%) for ceftriaxone, prompting a switch to teicoplanin in three patients. These findings support the continued use of teicoplanin in OPAT as well as its consideration in centres where it is not currently being offered.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.105888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068648PMC
March 2020

Clinical and Economic Impact of Implementing OVIVA Criteria on Patients With Bone and Joint Infections in Outpatient Parenteral Antimicrobial Therapy.

Clin Infect Dis 2020 06;71(1):207-210

Division of Infection, University College London Hospitals, London, United Kingdom.

The OVIVA study demonstrated noninferiority for managing bone and joint infections (BJIs) with oral antibiotics. We report that 79.7% of OPAT patients being treated for BJIs at our center would be eligible for oral antibiotics, saving a median (IQR) 19.5 IV-antibiotic days (8.5-37) and GBP 1234 (569-2594) per patient.
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http://dx.doi.org/10.1093/cid/ciz991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312207PMC
June 2020

Shortening duration of ertapenem in outpatient parenteral antimicrobial therapy for complicated urinary tract infections: A retrospective study.

PLoS One 2019 26;14(9):e0223130. Epub 2019 Sep 26.

Hospital for Tropical Diseases, University College London Hospital, London, United Kingdom.

Background: The incidence of multi-drug resistant ESBL-associated urinary tract infections (UTIs) is increasing globally. Patients with abnormal renal tract anatomy and other co-morbidities are at increased risk of complicated UTI and ESBL-associated infections. The duration and safety of OPAT for this cohort of patients is unknown.

Objectives: This study aims to provide an evidence base to support decision-making regarding duration of antibiotic treatment for complicated UTIs.

Methods: We retrospectively reviewed all patients receiving ertapenem with or without adjunctive fosfomycin for complicated UTIs in the OPAT service of our tertiary infectious diseases hospital. All data had been collected prospectively as part of routine clinical care. Our primary outcomes were microbiological and clinical cure of UTI.

Results: We identified 33 treatment episodes of ertapenem use for UTIs. 76% episodes related to pyelonephritis or urosepsis diagnoses. Renal tract abnormalities or prior urological surgery were present in 45% of patients. The median duration of appropriate parenteral antibiotic therapy in our study was 6 days. Clinical cure was achieved with short-course parenteral treatment alone in 81% of patients and this increased to 96% when adjunctive fosfomycin was used. There was a single treatment failure resulting in hospital admission.

Conclusions: Short duration ertapenem via OPAT with or without adjunctive fosfomycin is safe and effective for the treatment of complicated UTIs. Further studies are required to inform optimal treatment strategies and publication of guidelines in this field.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223130PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762133PMC
April 2020

Managing challenging behaviour in children with possible learning disability-a parent's perspective.

Authors:
Sarah A Logan

BMJ 2019 06 5;365:l2395. Epub 2019 Jun 5.

Hospital for Tropical Diseases-UCLH, London WC1E 6JB, UK.

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http://dx.doi.org/10.1136/bmj.l2395DOI Listing
June 2019

Glucocorticoid induced adrenal insufficiency is common in steroid treated glomerular diseases - proposed strategy for screening and management.

BMC Nephrol 2019 05 6;20(1):154. Epub 2019 May 6.

Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.

Background: Glucocorticoids (GCs) are frequently used to treat glomerular diseases but are associated with multiple adverse effects including hypothalamic-pituitary-adrenal axis inhibition that can lead to adrenal insufficiency (AI) on withdrawal. There is no agreed GC tapering strategy to minimise this risk.

Methods: This is a single centre retrospective study, between 2013 to 2016, of patients with glomerular disease on GC therapy for more than 3 months screened for GC induced AI with short synacthen stimulation tests (SSTs) done prior to complete GC withdrawal. We investigated the prevalence of AI, predictors, choice of screening tool and recovery.

Results: Biochemical evidence of GC induced AI was found in 57 (46.3%) patients. Total duration of GC did not differ between those with and without AI (p = 0.711). Patients with GC induced AI had a significantly lower pre-synacthen baseline cortisol as compared to patients without AI. A cut off pre-synacthen baseline cortisol of ≥223.5 nmol/l had a specificity of 100% for identifying individuals without biochemical AI. Patients with GC induced AI took a mean of 8.7 ± 4.6 months (mean ± SD) to recover. Patients with persistent AI had a significantly lower index post-synacthen cortisol measurement.

Conclusions: We demonstrate that biochemically proven GC induced AI is common in patients with glomerular diseases, is not predicted by daily dose or duration and takes a considerable time to recover. The study supports the use of morning basal cortisol testing as an appropriate means to avoid the need for SSTs in all patients and should be performed in all patients prior to consideration of GC withdrawal after 3 months duration.
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http://dx.doi.org/10.1186/s12882-019-1354-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503364PMC
May 2019

Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models.

Compr Physiol 2019 03 14;9(2):565-611. Epub 2019 Mar 14.

Medical College of Wisconsin, Department of Cell Biology, Neurobiology & Anatomy, Milwaukee, Wisconsin, USA.

Neurological disorders have emerged as a predominant healthcare concern in recent years due to their severe consequences on quality of life and prevalence throughout the world. Understanding the underlying mechanisms of these diseases and the interactions between different brain cell types is essential for the development of new therapeutics. Induced pluripotent stem cells (iPSCs) are invaluable tools for neurological disease modeling, as they have unlimited self-renewal and differentiation capacity. Mounting evidence shows: (i) various brain cells can be generated from iPSCs in two-dimensional (2D) monolayer cultures; and (ii) further advances in 3D culture systems have led to the differentiation of iPSCs into organoids with multiple brain cell types and specific brain regions. These 3D organoids have gained widespread attention as in vitro tools to recapitulate complex features of the brain, and (iii) complex interactions between iPSC-derived brain cell types can recapitulate physiological and pathological conditions of blood-brain barrier (BBB). As iPSCs can be generated from diverse patient populations, researchers have effectively applied 2D, 3D, and BBB models to recapitulate genetically complex neurological disorders and reveal novel insights into molecular and genetic mechanisms of neurological disorders. In this review, we describe recent progress in the generation of 2D, 3D, and BBB models from iPSCs and further discuss their limitations, advantages, and future ventures. This review also covers the current status of applications of 2D, 3D, and BBB models in drug screening, precision medicine, and modeling a wide range of neurological diseases (e.g., neurodegenerative diseases, neurodevelopmental disorders, brain injury, and neuropsychiatric disorders). © 2019 American Physiological Society. Compr Physiol 9:565-611, 2019.
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http://dx.doi.org/10.1002/cphy.c180025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705133PMC
March 2019

Unusual case of Lemierre's syndrome.

BMJ Case Rep 2018 Nov 28;11(1). Epub 2018 Nov 28.

Infectious diseases, Hospital for Tropical Diseases, London, UK.

A young previously healthy patient presented with sepsis and cavitating pneumonia. was isolated from blood cultures and subsequent CT neck showed an internal jugular vein thrombosis. Treatment was with antibiotics, anticoagulation and supportive management. Lemierre's syndrome is an infectious thrombophlebitis of the internal jugular vein. Although a rare diagnosis since the use of penicillin for treatment of acute pharyngitis, it is being reported with increasing frequency. Usually associated with spp, we believe that this is the first reported case of Lemierre's caused by an anaerobic member of the human oral cavity flora, usually associated with localised periodontal disease. The bacillus was isolated from blood during the acute presentation.
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http://dx.doi.org/10.1136/bcr-2018-226948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301635PMC
November 2018

Intravenous catheter-related adverse events exceed drug-related adverse events in outpatient parenteral antimicrobial therapy.

J Antimicrob Chemother 2019 03;74(3):787-790

The Hospital for Tropical Diseases, Division of Infection, University College London Hospitals NHS Foundation Trust, London, UK.

Background: Drug-related adverse events (AEs) are reported to be common amongst patients receiving outpatient parenteral antimicrobial therapy (OPAT). However, comparative data regarding intravenous (iv) catheter-related AEs are lacking.

Objectives: To compare drug- and iv catheter-related AEs from a large UK OPAT centre.

Patients And Methods: We reviewed 544 OPAT episodes [median (IQR) age: 57 (39-71) years, 60% male, 13% with diabetes] with a median (IQR) duration of 7 (2-18) days. Clinically significant drug- and iv catheter-related AEs were calculated as a percentage of OPAT episodes with an AE and also as AEs per 1000 iv drug/catheter days.

Results: Drug-related AEs complicated 13 (2.4%) OPAT episodes at 1.7 (95% CI 0.9-2.9) per 1000 drug days. Catheter-related AEs occurred more frequently, complicating 32 (5.9%) episodes at 5.7 (95% CI 4.2-7.9) per 1000 iv catheter days (χ2 test for difference in AE rate: P < 0.001). Non-radiologically guided midline catheters were associated with the most frequent AEs (n = 23) at 15.6 (95% CI 10.3-23.4) per 1000 iv catheter days compared with other types of iv catheters (HR 8.4, 95% CI 2.4-51.9, P < 0.004), and self-administration was associated with a higher rate of catheter-related AEs at 12.0 (95% CI 6.0-23.9) per 1000 iv catheter days (HR 4.15, 95% CI 1.7-9.1, P = 0.007).

Conclusions: Clinically significant iv catheter-related AEs occurred more frequently than drug-related AEs, especially when using non-radiologically guided midline catheters. Regular review of the need for iv therapy and switching to oral antimicrobials when appropriate is likely to minimize OPAT-related AEs.
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http://dx.doi.org/10.1093/jac/dky474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376853PMC
March 2019

Propofol Alters Long Non-Coding RNA Profiles in the Neonatal Mouse Hippocampus: Implication of Novel Mechanisms in Anesthetic-Induced Developmental Neurotoxicity.

Cell Physiol Biochem 2018 27;49(6):2496-2510. Epub 2018 Sep 27.

Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Background: Propofol induces acute neurotoxicity (e.g., neuroapoptosis) followed by impairment of long-term memory and learning in animals. However, underlying mechanisms remain largely unknown. Long non-coding RNAs (lncRNAs) are found to participate in various pathological processes. We hypothesized that lncRNA profile and the associated signaling pathways were altered, and these changes might be related to the neurotoxicity observed in the neonatal mouse hippocampus following propofol exposure.

Methods: In this laboratory experiment, 7-day-old mice were exposed to a subanesthetic dose of propofol for 3 hours, with 4 animals per group. Hippocampal tissues were harvested 3 hours after propofol administration. Neuroapoptosis was analyzed based on caspase 3 activity using a colorimetric assay. A microarray was performed to investigate the profiles of 35,923 lncRNAs and 24,881 messenger RNAs (mRNAs). Representative differentially expressed lncRNAs and mRNAs were validated using reverse transcription quantitative polymerase chain reaction. All mRNAs dysregulated by propofol and the 50 top-ranked, significantly dysregulated lncRNAs were subject to bioinformatics analysis for exploring the potential mechanisms and signaling network of propofol-induced neurotoxicity.

Results: Propofol induced neuroapoptosis in the hippocampus, with differential expression of 159 lncRNAs and 100 mRNAs (fold change ± 2.0, P< 0.05). Bioinformatics analysis demonstrated that these lncRNAs and their associated mRNAs might participate in neurodegenerative pathways (e.g., calcium handling, apoptosis, autophagy, and synaptogenesis).

Conclusion: This novel report emphasizes that propofol alters profiles of lncRNAs, mRNAs, and their cooperative signaling network, which provides novel insights into molecular mechanisms of anesthetic-induced developmental neurodegeneration and preventive targets against the neurotoxicity.
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http://dx.doi.org/10.1159/000493875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221186PMC
October 2018

Signaling network between the dysregulated expression of microRNAs and mRNAs in propofol-induced developmental neurotoxicity in mice.

Sci Rep 2018 09 21;8(1):14172. Epub 2018 Sep 21.

Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.

Mounting evidence has demonstrated that general anesthetics could induce acute neuroapoptosis in developing animals followed by long-term cognitive dysfunction, with the mechanisms remaining largely unknown. The aim of this study was to investigate the effect of the intravenous anesthetic propofol on the profiles of microRNAs (miRNAs) and messenger RNAs (mRNAs), and their interactive signaling networks in the developing mouse hippocampus. Postnatal day 7 (P7) mice were exposed to propofol for 3 hours. Hippocampi were harvested from both P7 (3 hours after exposure) and P60 mice for the analysis of the expression of 726 miRNAs and 24,881 mRNAs, and apoptosis. Long-term memory ability of P60 mice was analyzed using the Morris Water Maze. Propofol induced acute apoptosis in the hippocampus, and impaired memory function of mice. There were 100 altered mRNAs and 18 dysregulated miRNAs in the propofol-treated hippocampi compared with the intralipid-treated control tissues on P7. Bioinformatics analysis of these abnormally expressed genes on P7 indicated that 34 dysregulated miRNA-mRNA target pairs were related to pathological neurological and developmental disorder processes such as cell viability, cell morphology and migration, neural stem cell proliferation and neurogenesis, oligodendrocyte myelination, reactive oxygen species, and calcium signaling. Neonatal propofol exposure also resulted in the abnormal expression of 49 mRNAs and 4 miRNAs in P60 mouse hippocampi. Specifically, bioinformatics analysis indicates that among these dysregulated mRNAs and miRNAs, there were 2 dysregulated miRNA-mRNA targets pairs (Fam46a/miR-363-3p and Rgs3/miR-363-3p) that might be related to the effect of propofol on long-term cognitive function. Collectively, our novel investigation indicates that acute and long-term dysregulated miRNA-mRNA signaling networks potentially participate in propofol-induced developmental neurotoxicity.
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http://dx.doi.org/10.1038/s41598-018-32474-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155049PMC
September 2018

Factors influencing the smoking status of ex-prisoners reintegrating into the community after release: a pilot study.

N Z Med J 2018 02 23;131(1470):94-96. Epub 2018 Feb 23.

Professor, Public Health Department, University of Otago, Wellington.

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February 2018

Impact of Gastrostomy Feeding Tube Placement on the 1-Year Trajectory of Care in Patients After Stroke.

Nutr Clin Pract 2018 Aug 3;33(4):553-566. Epub 2018 Feb 3.

Department of Health Sciences and Research, College of Health Professions, Medical University of South Carolina, Charleston, South Carolina, USA.

Background: Percutaneous endoscopic gastrostomy (PEG) feeding tubes are commonly placed in acute stroke patients with a need for enteral nutrition. However, PEG tubes are associated with medical complications and a decrease in quality of life. We compared the 1-year care trajectory of stroke patients with and without PEG tube placement to enhance knowledge about the long-term impact of PEG tube placement.

Methods: We conducted a retrospective analysis of commercially insured stroke patients included in the Truven Health MarketScan Research Databases of 2011. We analyzed their index hospital stay and conducted 1-month, 3-months, 6-months, and 1-year follow-ups. We compared admissions to inpatient rehabilitation facilities, acute hospitals, skilled nursing facilities, outpatient hospital visits, and home visits for stroke patients with and without PEG tube placement using unadjusted and adjusted modelling.

Results: Of the 8911 included stroke patients, 148 patients (1.7%) had a PEG tube placed during their index hospital stay. After controlling for age, gender, stroke severity, comorbidities, and stroke type, PEG tube placement was an independent predictor for admissions to inpatient rehabilitation facilities and skilled nursing facilities. Furthermore, PEG tube placement was an independent predictor for all-cause, unplanned hospital readmissions in a multivariable logistic model (area under the receiver operating characteristic curve was .84).

Conclusion: Stroke patients who receive a PEG tube can expect a significantly different care trajectory after being discharged from the acute hospital. Our findings can aide in predicting recovery and planning resources and identifying gaps and points for improvement in stroke care for patients with PEG tube placement.
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http://dx.doi.org/10.1002/ncp.10015DOI Listing
August 2018

Effectiveness of the GoCheck Kids Vision Screener in Detecting Amblyopia Risk Factors.

Am J Ophthalmol 2018 03 2;187:87-91. Epub 2018 Jan 2.

Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina.

Purpose: The GoCheck Kids smartphone photoscreening app (Gobiquity Mobile Health, Scottsdale, Arizona, USA), introduced in 2014, is marketed to pediatricians with little published validation. We wished to evaluate the GoCheck Kids Screener for accuracy in detecting amblyopia risk factors (ARF) using 2013 American Association for Pediatric Ophthalmology and Strabismus guidelines.

Design: Validity assessment.

Methods: Children 6 months to 6 years of age presenting from October 2016 to August 2017 were included. Children were screened with the GoCheck preloaded Nokia Lumia 1020, software version 4.6 with image processing version R4d, prior to undergoing a comprehensive eye examination by a pediatric ophthalmologist masked to the screener results. Determination of the presence of age-specific ARF was made based upon the examination and compared with the GoCheck recommendation.

Results: A total of 206 children were included (average age 43 months). When compared to examination, GoCheck had a sensitivity of 76.0% and specificity of 67.2% in detecting ARF. Positive predictive value was 57.0% and negative predictive value 83.0%. The screener results of 13 children were changed from "no risk factors" to "risk factors identified" based on the GoCheck remote review process. Four images remained "not gradable" and screening was unsuccessful in 3 children.

Conclusion: In our high-risk population, this version of the Gocheck Kids smartphone app was useful in identifying ARF in children who are often not able to cooperate with visual acuity testing. This study informs pediatricians about the efficacy of this new screener as they make decisions about how to best detect vision problems in young children.
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http://dx.doi.org/10.1016/j.ajo.2017.12.020DOI Listing
March 2018

Wyburn-Mason Incidentally Diagnosed on Evaluation of Eye Redness.

Ophthalmology 2017 12;124(12):1763

Baylor College of Medicine, Department of Ophthalmology-Cullen Eye Institute, Houston, Texas; Texas Children's Hospital, Houston, Texas.

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http://dx.doi.org/10.1016/j.ophtha.2017.08.010DOI Listing
December 2017

Schistosomiasis-A Disobedient Ureter, a Disobedient Diagnosis.

J Endourol Case Rep 2017 1;3(1):114-118. Epub 2017 Aug 1.

Department of Infectious Diseases, University College London Hospitals NHS Foundation Trust, London, United Kingdom.

Schistosomiasis is rare in western countries, but remains a potentially serious disease. It is known to result in severe urogenital complications; prompt diagnosis can therefore significantly affect outcomes. We report the case of a 41-year-old male with pleuritic chest pain and visible hematuria who had emigrated from Zimbabwe to the United Kingdom 20 years previously. CT imaging revealed a hydronephrotic right pelvicaliceal system, with a dilated ureter to its distal portion. Preliminary tests for schistosomiasis, including terminal urine microscopy and serology, were negative. An initial ureteroscopy was challenging owing to a tight ureteral stricture such that a retrograde stent insertion and not ureteroscopic visualization or biopsy was carried out. A relook ureteroscopy after 6 weeks revealed a dense distal ureteral stricture, biopsies were taken, the stricture was ablated with LASER, and a retrograde stent was placed. Microscopic examination of the biopsies confirmed . Treatment consisted of a divided dose of praziquantel and a reducing dose of steroids. At a third look ureteroscopy the stricture was ablated with LASER again, and the stent was removed. Subsequent renograms indicated recurrent obstruction despite LASER treatment and a retrograde ureteral stent was replaced. The patient ultimately had a Boari flap ureteral reimplant with good results. This case illustrates the clinical challenges of diagnosing and treating ureteral schistosomiasis. It shows that all the initial tests can be negative, but where the clinical picture points toward schistosomiasis it is worth persevering and a good tissue biopsy may be the only way to verify an otherwise elusive diagnosis.
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http://dx.doi.org/10.1089/cren.2017.0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628567PMC
August 2017
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