Extended spectrum β-lactamases (ESBLs) are enzymes produced by a variety of Gram negative bacteria which confer an increased resistance to commonly used antibiotics. They are a worrying global public health issue as infections caused by such enzyme-producing organisms are associated with a higher morbidity and mortality and greater fiscal burden. Coupled with increasing prevalence rates worldwide and an ever diminishing supply in the antibiotic armamentarium, these enzymes represent a clear and present danger to public health. This article aims to give an overview of the current situation regarding ESBLs, with a focus on the epidemiology and management of such infections.
Aims-To describe characteristics of a series of people accidentally and deliberately killed by air powered weapons. Methods-Five cases of fatal airgun injury were identified by forensic pathologists and histopathologists. The circumstances surrounding the case, radiological examination, and pathological findings are described. The weapon characteristics are also reported. Results-Three of the victims were adult men, one was a 16 year old boy, and one an eight year old child. Four of the airguns were .22 air rifles, the other a .177 air rifle. Two committed suicide, one person shooting himself in the head, the other in the chest. In both cases the guns were fired at contact range. Three of the cases were classified as accidents: in two the pellet penetrated into the head and in one the chest. Conclusions-One person each year dies from an air powered weapon injury in the United Kingdom. In addition there is considerable morbidity from airgun injuries. Fatalities and injuries are most commonly accidents, but deliberately inflicted injuries occur. Airguns are dangerous weapons when inappropriately handled and should not be considered as toys. Children should not play with airguns unsupervised. (J Clin Pathol 1998;51:525-529)
We report the case of a 39-year-old man with severe pain due to unresectable squamous-cell carcinoma of the maxillary sinus that had invaded cranial bone and had metastasized to the cervical spine. Tolerance to opioids had developed, and high doses of transdermal, continuous intravenous, and epidural opioids did not control his pain. An acute episode of extremely severe head pain was immediately controlled with a subanesthetic dose of ketamine after failure of a stress dose of corticosteroid and intravenous lidocaine. Because the patient was terminally ill and invasive procedures were not options, we controlled his pain using a low-dose ketamine infusion until his death 13 days later. Ketamine may be a good co-analgesic for breakthrough pain and for severe pain caused by terminal cancer when invasive techniques are inappropriate. Its mechanism of action may include reversal of opioid tolerance in addition to an inherent analgesic effect.
Summary Transmission of Coronavirus Disease 2019 (COVID-19) in healthcare settings has significant implications for patients and healthcare workers, can amplify local outbreaks, and place additional burden on already stretched resources. Risk of missed or late diagnosis of COVID-19 was high during the United Kingdom’s initial ‘containment phase’, because of strict criteria for testing. The risk remains due to asymptomatic/pre-symptomatic transmission, complicated by challenges faced with laboratory testing. We present a case study of potential nosocomial transmission associated with the first case of COVID-19 at a large acute NHS Trust in South-West London and describe the prevailing burden of nosocomial infections.
3509 Background: PF-02341066 (PF) is a selective, ATP-competitive, small molecule oral inhibitor of the c-Met/HGFR and ALK receptor tyrosine kinases that has not previously been tested in humans. A Phase 1 dose-escalation trial evaluating PF as an oral single agent was conducted to investigate safety, PK and PD in patients (pts) with advanced cancer (excluding leukemias). Methods: PF was administered under fasting conditions QD or BID on a continuous schedule to pts in successive dose-escalating cohorts at doses ranging from 50 mg QD to 300 mg BID. Pts with advanced cancer were enrolled in the study. Results: Thirty-seven pts were enrolled into the dose escalation part of the study. Tumor types included colorectal, pancreatic, sarcoma, ALCL and NSCLC. The MTD was 250 mg BID. Three DLTs were observed: grade 3 increase in ALT (1 pt at 200 mg QD) and grade 3 fatigue (2 pts at 300 mg BID). The most common AEs were nausea, emesis, fatigue and diarrhea. Nausea and emesis were independent of dose or duration of treatment. Mean AUC (30–57% CV) and Cmax (36–69% CV) increased proportionally with dose from 100 mg QD to 300 mg BID. The median terminal half-life was 46 hours. A 2- to 4-fold increase in the oral midazolam (MDZ) AUC was observed following 28-days of PF dosing at 100 mg QD (n = 3) and 300 mg BID (n = 2), respectively, suggesting PF to be an inhibitor of CYP3A. Ten pts have entered an enriched RP2D cohort of pts with tumors harboring c-Met amplification/gene mutation or ALK fusion genes. There has been 1 confirmed PR in a sarcoma pt with ALK rearrangement (inflammatory myofibroblastic tumor). Among 10 NSCLC pts whose tumors harbor EML4-ALK rearrangement, 1 pt has had a PR, 2 pts have achieved unconfirmed PR and 4 pts have had SD (3 have experienced reduction in tumor burden by ∼20% in measurable lesions and 1 has been treated for 28 weeks). Conclusions: The MTD of PF is 250 mg BID. The major AEs were fatigue or GI-related, and all AEs were manageable and reversible. There was no evidence of non-linear PK at PF doses >100 QD. Treatment with PF-02341066 resulted in promising clinical activity against tumors carrying activating ALK gene rearrangements. Further study of PF in pts with ALK-dependent tumors is warranted. [Table: see text]
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