Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis-13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3 months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3 months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay.
Increased susceptibility to co-infection with enteric Gram-negative bacteria, particularly non-typhoidal Salmonella, is reported in malaria and Oroya fever (Bartonella bacilliformis infection), and can lead to increased mortality. Accumulating epidemiological evidence indicates a causal association with risk of bacterial co-infection, rather than just co-incidence of common risk factors. Both malaria and Oroya fever are characterized by hemolysis, and observations in humans and animal models suggest that hemolysis causes the susceptibility to bacterial co-infection. Evidence from animal models implicates hemolysis in the impairment of a variety of host defense mechanisms, including macrophage dysfunction, neutrophil dysfunction, and impairment of adaptive immune responses. One mechanism supported by evidence from animal models and human data, is the induction of heme oxygenase-1 in bone marrow, which impairs the ability of developing neutrophils to mount a competent oxidative burst. As a result, dysfunctional neutrophils become a new niche for replication of intracellular bacteria. Here we critically appraise and summarize the key evidence for mechanisms which may contribute to these very specific combinations of co-infections, and propose interventions to ameliorate this risk.
The COVID‐19 pandemic potentially makes treatment of acute leukaemia more difficult. Most induction chemotherapy regimens for acute leukaemia lead to extended periods of cytopaenia and immunosuppression rendering patients vulnerable to opportunistic infections. As with many aspects of SARS‐CoV‐2, there is no universally accepted way of treating patients who present with acute leukaemia and associated infection.
acute (vaso-occlusive painful crisis, acute chest syndrome, stroke) and chronic (nephropathy, pulmonary hypertension) symptoms, resulting in poor quality of life (QOL) and reduced life expectancy. Access to optimal treatment is a key challenge for many SCD patients. In many cases, patients are treated in acute care centers where knowledge of SCD management may not be optimal. The burden of SCD in patients' daily lives, particularly the psychological impact on the lives of young people, is largely underestimated and can impact successful management of SCD, including vaso-occlusive pain crises. Limited treatment options to manage this complex condition and prevent long-term organ damage may lead to frustration and breakdown of communication between patient and health care provider (HCP). Aims: To conduct a world-wide survey to explore and describe the impact of SCD on patients' QOL (including emotional functioning and fatigue), economic burden, and physician and patient perceptions of overall disease management and treatment approaches. The survey will also describe the interaction between patients and healthcare systems and availability of resources to support disease management in 4 continents. Methods: SWAY is a multi-country cross-sectional survey of SCD patients, caregivers, and treating physicians being conducted in approximately 15 countries across North and South America, Europe, Africa, Asia, and the Middle East. SWAY will consist of 3 separate surveys: patient, proxy (conducted by the parent/guardian/caregiver), and physician. The surveys will be conducted in a variety of formats (online and print) and distribution will be tailored for countries' characteristics and languages. Questions were developed with input from international SCD experts to appropriately address cultural differences and international variations in care. Following a series of screening questions, surveys include 6 categories: demographics, symptoms, impact of disease and use of a caregiver, impact on work and finances, disease management and treatment approaches, and patient-physician relationship. The patient survey includes 2 additional categories: patient education level/engagement and caregiver-/guardian-/parent-specific questions. Patient recruitment will be conducted via treating physicians and engagement with patient association groups. Target enrollment is ~2,000 patients. Results: SWAY began in March 2019 and is currently ongoing. Approximately 50% of target enrollment (1,000 survey responses) will be completed by May 2019, with survey completion and full results available by July 2019. Summary/Conclusion: In times of population movement, disease globalization, and interconnection between health care systems, global analyses of disease burden are necessary to provide meaningful solutions. SWAY aims to elucidate the burden of SCD on patient QOL, as well as the alignment between patient and physician perceptions of SCD treatment, management at a global level. This survey is geared to highlight areas of disconnect and inform fur...
Background and aims Sickle cell anaemia (SCA) is an autosomal recessive disorder caused by point mutation of the β-globin gene, resulting in abnormal forms of hemoglobin that cause increased red blood cell rigidity and hemolysis. It is one of the most common hereditary blood conditions, affecting over 14,000 adults in the UK (Dormandy el al, 2017). One of the manifestations of SCA is vaso-occlusive crises. These typically cause severe pain that may require emergency department (ED) attendance for pain management, typically with opioids. Pain relief should be given quickly and response to this assessed on a regular basis to ensure pain management is optimized. Those patients in whom pain relief is not well-controlled are at risk of further complications including acute chest syndrome. The UK National Institute of Clinical Excellence (NICE) published a quality standard in 2014 stating that patients presenting to hospital with an acute painful sickle cell episode should have a pain assessment, a clinical assessment and appropriate analgesia within 30 minutes of presentation (NICE, 2014). This study was performed to assess the Whittington Hospital's compliance to national recommendations and to establish which aspects of care in ED contributed to delays in management. Methods If a Whittington SCA patient attends ED, an automated email is generated that notifies the haematology team of the attendance. This system was used to identify acute sickle cell presentations to ED. Criteria for inclusion in the study was Whittington SCA patients that presented to ED with acute painful sickle cell crises between August 2017 to January 2018. Patients who received analgesia in the ambulance and patients with no documentation available were excluded. The time of presentation, analgesia prescription and administration for each attendance were noted from ED documentation. Results A total of 104 ED SCA attendances were included. 41% of patients presenting with an acute painful sickle cell crisis received analgesia during their first 30 minutes in ED. The average wait for analgesia was 47 minutes, with 75% of SCA patients receiving analgesia within 1 hour of arrival. The time taken to triage SCA patients was on average 8 minutes (range 0 to 29 minutes). Time from arrival to prescription of pain relief was much more variable with an average wait 40 minutes (range 10 minutes to 2 hours 22 minutes). Time from prescription to administration also varied, with 56% administered within 10 minutes of prescription and 87% within 30 minutes Patients who frequently attended Whittington ED (defined as 7 or more attendances within the 6 month period studied) had a shorter average wait for analgesia. Analgesia was given 36 minutes after arrival on average for frequent attenders, whereas patients presenting 6 or fewer times had an average wait of 53 minutes. Conclusions We are not currently meeting our audit standard for provision of analgesia in the emergency department, and performance appears to have worsened progressively since our earliest available date from 2012 (although methodological differences may have contributed to this). In 2015 49% of patients received analgesia within 30 minutes compared to 41% in 2017/18. Most of the delay appears to be due to the time taken for medication to be prescribed, although the time taken to triage the patient and administer the medication was also not insignificant and often amounted to greater than 30 minutes. It is unclear what is contributing to this delay, although it appears that performance is improved when the patient is a repeat attender and therefore known to the department. Educations sessions with the ED department and availability of a SCA specialist nurse may improve management of SCA painful crises in ED. Disclosures Shah: Novartis: Honoraria, Speakers Bureau; Sobi/Apotex: Honoraria; Celgene Corp: Other: Steering committee; Roche: Other: Advisory board meeting.
Activated phosphoinositide 3-kinase (PI3K)δ syndrome (APDS) is a heterogenous primary immunodeficiency caused by autosomal dominant mutations in PIK3CD (APDS1) or P1K3R1 (APDS2), genes that code for the catalytic p110δ and regulatory p85 subunits of PI3Kδ respectively 1,2 . Both forms of APDS result in overactivation of PI3Kδ through gain-of-function mutations in p110δ or loss-of-function mutations in p85 and present with similar immunodeficiency. Over ninety percent of APDS patients present with recurrent ear, nose and throat or respiratory tract infections 1,2 . Both nonneoplastic and neoplastic lymphoproliferation are common, with lymphoma the most frequently experienced malignancy 1,2 . Almost 40% of patients with APDS1 and 20% of patients with APDS2 experience autoimmune or inflammatory disease such as cytopenias, chronic diarrhoea or autoimmune haemolytic anaemia. The majority of patients with APDS are treated supportively with antibiotic prophylaxis. Other therapeutic options include immunoglobulin replacement therapy (IGRT), immunosuppressive therapies and inhibitors of mTOR signalling such as rapamycin 3 . Rapamycin appears to be more effective at controlling non-neoplastic lymphoproliferation but less successful at modulating intestinal disease and cytopenias 3 .
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