Systematic review of the diagnosis and management of necrotising otitis externa: Highlighting the need for high-quality research.

OBJECTIVES: To present a systematic review and critical analysis of clinical studies for necrotising otitis externa (NOE), with the aim of informing best practice for diagnosis and management. DESIGN: Medline, Embase, Cochrane Library and Web of Science were searched from database inception until 30 April 2021 for all clinical articles on NOE. The review was registered on PROSPERO (ID: CRD42020128957) and conducted in accordance with PRISMA guidelines. RESULTS: Seventy articles, including 2274 patients were included in the final synthesis. Seventy-three percent were retrospective case series; the remainder were of low methodological quality. Case definitions varied widely. Median patient age was 69.2 years; 68% were male, 84% had diabetes and 10% had no reported immunosuppressive risk factor. Otalgia was almost universal (96%), with granulation (69%) and oedema (76%) the commonest signs reported. Pseudomonas aeruginosa was isolated in 62%, but a range of bacterial and fungal pathogens were reported and 14% grew no organism. Optimal imaging modality for diagnosis or follow-up was unclear. Median antimicrobial therapy duration was 7.2 weeks, with no definitive evidence for optimal regimens. Twenty-one percent had surgery with widely variable timing, indication, or procedure. One-year disease-specific mortality was 2%; treatment failure and relapse rates were 22% and 7%, respectively. CONCLUSION: There is a lack of robust, high-quality data to support best practice for diagnosis and management for this neglected condition. A minimum set of reporting requirements is proposed for future studies. A consensus case definition is urgently needed to facilitate high-quality research.

Mechanical life support algorithm developed by simulation for inpatient emergency management of recipients of implantable left ventricular assist devices.

Background: Published guidance concerning emergency management of left ventricular assist device (LVAD) recipients is both limited and lacking in consensus which increases the risk of delayed and/or inappropriate actions. Methods: In our specialist tertiary referral centre we developed, by iteration, a novel in-hospital resuscitation algorithm for LVAD emergencies which we validated through simulation and assessment of our multi-disciplinary team. A Mechanical Life Support course was established to provide theoretical and practical education combined with simulation to consolidate knowledge and confidence in algorithm use. We assessed these measures using confidence scoring, a key performance indicator (the time taken to restart LVAD function) and a multiple-choice question (MCQ) examination. Results: The mean baseline staff confidence score in management of LVAD emergencies was 2.4 ± 1.2 out of a maximum of 5 (n = 29). After training with simulation, mean confidence score increased to 3.5 ± 0.8 (n = 13).Clinical personnel who were provided with the novel resuscitation algorithm were able to reduce time taken to restart LVAD function from a mean value of 49 ± 8.2 seconds (pre-training) to 20.4 ± 5 seconds (post-training) (n = 42, p < 0.0001).The Mechanical Life Support course increased mean confidence from 2.5 ± 1.2 to 4 ± 0.6 (n = 44, p < 0.0001) and mean MCQ score from 18.7 ± 3.4 to 22.8 ± 2.6, out of a maximum of 28 (n = 44, p < 0.0001). Conclusion: We present a simplified LVAD Advanced Life Support algorithm to aid the crucial first minutes of resuscitation where basic interventions are likely to be critical in assuring good patient outcomes.

Image challenge: A diabetic man with facial swelling following recent Covid-19 infection.

A 68-year-old man with diabetes presented with shortness of breath, left sided facial swelling, and nasal discharge. He had recently returned from India and PCR was positive for SARS-CoV-2 Delta variant. CT head and diffusion-weighted MRI sinuses were performed and the patient underwent endoscopic sinus surgery before being transferred to a specialist skull base centre.

A case report of ChAdOx1 nCoV-19 vaccine-associated encephalitis.

BACKGROUND: Vaccination against COVID-19 continues apace, but side-effects, both common and severe, continue to be reported. We report here the first published case of COVID-19 vaccine-related encephalitis. CASE PRESENTATION: A young woman presented with acute neuropsychiatric symptoms following recent ChAdOx1 nCoV-19 vaccination. Extensive investigation did not identify alternative causes. CONCLUSIONS: This difficult case is here described, including presentation, investigation, and management. Further study on neuropsychiatric side-effects of COVID-19 vaccination, including investigation as to whether there may be a causal link, is required.

14-year trends and resistance patterns of blood and cerebrospinal fluid cultures in children under three years old.

OBJECTIVES: Bacterial infections are a major cause of UK paediatric hospitalisations, yet longitudinal data on causative organisms or antimicrobial resistance are scarce. This retrospective analysis describes trends in blood and cerebrospinal fluid (CSF) cultures and resistance patterns in children under three years old from a large UK centre. METHODS: All culture results, and resistance data for Gram-negative rods (GNR) in blood cultures, collected between January 2005 and December 2018 were extracted from Oxford University Hospitals NHS Foundation Trust microbiology database. RESULTS: Of 49,298 samples, 6.7% of blood and 3.1% of CSF cultures were positive for bacterial growth; 2.3% and 1.1%, respectively grew pathogens. Number of cultures taken increased over time; the proportion growing pathogens declined. Resistance of GNR to first-line antimicrobials was 9.3% to gentamicin (neonatal units), and 17.1% and 25.8% to ceftriaxone (paediatric ED and wards respectively). Resistance to any two of ceftriaxone, ciprofloxacin, gentamicin, or meropenem was ≤ 6% in both areas. CONCLUSIONS: The proportion of positive cultures declined over time. Resistance of GNR to empirical antimicrobials were observed, but resistance to a second agent were lower. Our study informs clinician decisions on when, and to which antimicrobials, to escalate if a child is not improving on empirical therapy.

False-negative RT-PCR for COVID-19 and a diagnostic risk score: a retrospective cohort study among patients admitted to hospital.

OBJECTIVE: To describe the characteristics and outcomes of patients with a clinical diagnosis of COVID-19 and false-negative SARS-CoV-2 reverse transcription-PCR (RT-PCR), and develop and internally validate a diagnostic risk score to predict risk of COVID-19 (including RT-PCR-negative COVID-19) among medical admissions. DESIGN: Retrospective cohort study. SETTING: Two hospitals within an acute NHS Trust in London, UK. PARTICIPANTS: All patients admitted to medical wards between 2 March and 3 May 2020. OUTCOMES: Main outcomes were diagnosis of COVID-19, SARS-CoV-2 RT-PCR results, sensitivity of SARS-CoV-2 RT-PCR and mortality during hospital admission. For the diagnostic risk score, we report discrimination, calibration and diagnostic accuracy of the model and simplified risk score and internal validation. RESULTS: 4008 patients were admitted between 2 March and 3 May 2020. 1792 patients (44.8%) were diagnosed with COVID-19, of whom 1391 were SARS-CoV-2 RT-PCR positive and 283 had only negative RT-PCRs. Compared with a clinical reference standard, sensitivity of RT-PCR in hospital patients was 83.1% (95% CI 81.2%-84.8%). Broadly, patients with false-negative RT-PCR COVID-19 and those confirmed by positive PCR had similar demographic and clinical characteristics but lower risk of intensive care unit admission and lower in-hospital mortality (adjusted OR 0.41, 95% CI 0.27-0.61). A simple diagnostic risk score comprising of age, sex, ethnicity, cough, fever or shortness of breath, National Early Warning Score 2, C reactive protein and chest radiograph appearance had moderate discrimination (area under the receiver-operator curve 0.83, 95% CI 0.82 to 0.85), good calibration and was internally validated. CONCLUSION: RT-PCR-negative COVID-19 is common and is associated with lower mortality despite similar presentation. Diagnostic risk scores could potentially help triage patients requiring admission but need external validation.

The WorldWide Antimalarial Resistance Network Clinical Trials Publication Library: A Live, Open-Access Database of Plasmodium Treatment Efficacy Trials.

Parasite resistance to antimalarial drugs poses a serious threat to malaria control. The WorldWide Antimalarial Resistance Network (WWARN) aims to provide a collaborative platform to support the global malaria research effort. Here, we describe the "WWARN clinical trials publication library," an open-access, up-to-date resource to streamline the synthesis of antimalarial safety and efficacy data. A series of iteratively refined database searches were conducted to identify prospective clinical trials assessing antimalarial drug efficacy with at least 28 days of follow-up. Of approximately 45,000 articles screened, 1,221 trials published between 1946 and 2018 were identified, representing 2,339 treatment arms and 323,819 patients. In trials from endemic locations, 75.7% (787/1,040) recruited patients with Plasmodium falciparum, 17.0% (177/1,040) Plasmodium vivax, 6.9% (72/1,040) both, and 0.4% (4/1,040) other Plasmodium species; 57.2% (585/1,022) of trials included under-fives and 5.3% (55/1,036) included pregnant women. In Africa, there has been a marked increase in both P. falciparum and P. vivax studies over the last two decades. The WHO-recommended artemisinin-based combination therapies alone or with a gametocidal drug were assessed in 39.5% (705/1,783) of P. falciparum treatment arms and 10.5% (45/429) of P. vivax arms, increasing to 78.0% (266/341) and 22.9% (27/118), respectively, in the last five years. The library is a comprehensive, open-access tool that can be used by the malaria community to explore the collective knowledge on antimalarial efficacy (available at https://www.wwarn.org/tools-resources/literature-reviews/wwarn-clinical-trials-publication-library). It is the first of its kind in the field of global infectious diseases, and lessons learnt in its creation can be adapted to other infectious diseases.

Serotonin syndrome triggered by postoperative administration of serotonin noradrenaline reuptake inhibitor (SNRI).

BACKGROUND: Serotonin syndrome is a rare but potentially severe disease, which is caused by hyperstimulation of serotonin receptors in the central nervous system. Several antidepressants exert their effect by modulating intrasynaptic serotonin concentration and anesthetics may affect the metabolism of serotonin, implicating to induce serotonin syndrome in patients taking those antidepressants. We present a case which provoked serotonin syndrome immediately after taking serotonin noradrenaline reuptake inhibitor (SNRI) in the postoperative period. CASE PRESENTATION: A 31-year-old female underwent laparoscopic ovarian cystectomy under general anesthesia with propofol, fentanyl, and remifentanil. She has been taking duloxetine, a SNRI for depression. She developed myoclonus seizure with an increase of blood pressure and heart rate after taking duloxetine on the day after the surgery, which was subsided by a non-selective serotonin receptor antagonist. CONCLUSIONS: Anesthesiologists should be aware of the risk of perioperative serotonin syndrome in patients taking antidepressants affecting serotonin metabolism.

Antimicrobial Resistance in Invasive Bacterial Infections in Hospitalized Children, Cambodia, 2007-2016.

To determine trends, mortality rates, and costs of antimicrobial resistance in invasive bacterial infections in hospitalized children, we analyzed data from Angkor Hospital for Children, Siem Reap, Cambodia, for 2007-2016. A total of 39,050 cultures yielded 1,341 target pathogens. Resistance rates were high; 82% each of Escherichia coli and Klebsiella pneumoniae isolates were multidrug resistant. Hospital-acquired isolates were more often resistant than community-acquired isolates; resistance trends over time were heterogeneous. K. pneumoniae isolates from neonates were more likely than those from nonneonates to be resistant to ampicillin-gentamicin and third-generation cephalosporins. In patients with community-acquired gram-negative bacteremia, third-generation cephalosporin resistance was associated with increased mortality rates, increased intensive care unit admissions, and 2.26-fold increased healthcare costs among survivors. High antimicrobial resistance in this setting is a threat to human life and the economy. In similar low-resource settings, our methods could be reproduced as a robust surveillance model for antimicrobial resistance.

Neuropeptide glutamic acid-isoleucine (NEI)-induced paradoxical sleep in rats.

Neuropeptideglutamic acid-isoleucine (NEI) as well as melanin concentrating hormone (MCH) is cleaved from the 165 amino acid protein, prepro-melanin concentrating hormone (prepro-MCH). Among many physiological roles of MCH, we demonstrated that intracerebroventricular (icv) injection of MCH induced increases in REM sleep episodes as well as in non REM sleep episodes. However, there are no studies on the effect of NEI on the sleep-wake cycle. As for the sites of action of MCH for induction of REM sleep, the ventrolateral periaqueductal gray (vlPAG) has been reported to be one of its site of action. Although MCH neurons contain NEI, GABA, MCH, and other neuropeptides, we do not know which transmitter(s) might induce REM sleep by acting on the vlPAG. Thus, we first examined the effect of icv injection of NEI on the sleep-wake cycle, and investigated how microinjection of either NEI, MCH, or GABA into the vlPAG affected REM sleep in rats. Icv injection of NEI (0.61µg/5µl: n=7) significantly increased the time spent in REM episodes compared to control (saline: 5µl; n=6). Microinjection of either NEI (61ng/0.2µl: n=7), MCH (100ng/0.2µl: n=6) or GABA (250mM/0.2µl: n=7) into the vlPAG significantly increased the time spent in REM episodes and the AUC. Precise hourly analysis of REM sleep also revealed that after those microinjections, NEI and MCH increased REM episodes at the latter phase, compared to GABA which increased REM episodes at the earlier phase. This result suggests that NEI and MCH may induce sustained REM sleep, while GABA may initiate REM sleep. In conclusion, our findings demonstrate that NEI, a cleaved peptide from the same precursor, prepro-MCH, as MCH, induce REM sleep at least in part through acting on the vlPAG.

Alteration of fatal 1:1 conducted atrial flutter to less conducted ratio by landiolol infusion.

An 84-year-old male patient with a past history of atrial-flutter-fibrillation and dementia underwent an urgent femoral neck fracture surgery. Preoperative electrocardiography demonstrated atrial flutter (AFL) with ventricular conduction at a ratio of 2:1-4:1, and transthoracic echocardiography showed severe left ventricular dysfunction with Ejection Fraction of 14.6 %. Femoral nerve block and Lateral femoral cutaneous nerve block with sedation was planned for the surgery. Upon entry to the operating room, ECG showed 2:1 conducted AFL at the rate of 128 beats min(-1). Due to the stimulation of urethral catheter insertion, it has altered to 1:1 conducted AFL. Loading dose of landiolol hydrochloride 7.5 mg followed by 1.5-3 µg/kg/min continuous administration was given, which had decreased the conduction ratio to 2:1 without causing hypotension. A further episode of 1:1 conducted AFL occurred when the pin was inserted to the thighbone, which caused circulatory collapse. Additional bolus dose of landiolol immediately altered it to 2:1 before operating cardioversion and stabilized the hemodynamics. He maintained AFL with 2:1 conduction thereafter, and 1:1 conduction was never seen postoperatively even after discontinuation of landiolol.