COX-2, formally known as prostaglandin endoperoxide H synthase-2 (PGHS-2), catalyzes the committed step in prostaglandin biosynthesis. COX-2 is induced during inflammation and is overexpressed in colon cancer. In vitro, an 18-amino acid segment, residues 595-612, immediately upstream of the C-terminal endoplasmic reticulum targeting sequence is required for N-glycosylation of Asn 594 , which permits COX-2 protein to enter the endoplasmic reticulum-associated protein degradation system. To determine the importance of this COX-2 degradation pathway in vivo, we engineered a del595-612 PGHS-2 (⌬18 COX-2) knock-in mouse lacking this 18-amino acid segment. ⌬18 COX-2 knock-in mice do not exhibit the renal or reproductive abnormalities of COX-2 null mice. ⌬18 COX-2 mice do have elevated urinary prostaglandin E 2 metabolite levels and display a more pronounced and prolonged bacterial endotoxin-induced febrile response than wild type (WT) mice. Normal brain tissue, cultured resident peritoneal macrophages, and cultured skin fibroblasts from ⌬18 COX-2 mice overexpress ⌬18 COX-2 relative to WT COX-2 expression in control mice. These results indicate that COX-2 can be degraded via the endoplasmic reticulum-associated protein degradation pathway in vivo. Treatment of cultured cells from WT or ⌬18 COX-2 mice with flurbiprofen, which blocks substrate-dependent degradation, attenuates COX-2 degradation, and treatment of normal mice with ibuprofen increases the levels of COX-2 in brain tissue. Thus, substrate turnover-dependent COX-2 degradation appears to contribute to COX-2 degradation in vivo. Curiously, WT and ⌬18 COX-2 protein levels are similar in kidneys and spleens from WT and ⌬18 COX-2 mice. There must be compensatory mechanisms to maintain constant COX-2 levels in these tissues.

BackgroundTo compare the clinical and demographic variables of patients who present to the ED at different times of the day in order to determine the nature and extent of potential selection bias inherent in convenience samplingMethodsWe undertook a retrospective, observational study of data routinely collected in five EDs in 2019. Adult patients (aged ≥18 years) who presented with abdominal or chest pain, headache or dyspnoea were enrolled. For each patient group, the discharge diagnoses (primary outcome) of patients who presented during the day (08:00–15:59), evening (16:00-23:59), and night (00:00-07:59) were compared. Demographics, triage category and pain score, and initial vital signs were also compared.Results2500 patients were enrolled in each of the four patient groups. For patients with abdominal pain, the diagnoses differed significantly across the time periods (p<0.001) with greater proportions of unspecified/unknown cause diagnoses in the evening (47.4%) compared with the morning (41.7%). For patients with chest pain, heart rate differed (p<0.001) with a mean rate higher in the evening (80 beats/minute) than at night (76). For patients with headache, mean patient age differed (p=0.004) with a greater age in the daytime (46 years) than the evening (41). For patients with dyspnoea, discharge diagnoses differed (p<0.001). Asthma diagnoses were more common at night (12.6%) than during the daytime (7.5%). For patients with dyspnoea, there were also differences in gender distribution (p=0.003), age (p<0.001) and respiratory rates (p=0.003) across the time periods. For each patient group, the departure status differed across the time periods (p<0.001).ConclusionPatients with abdominal or chest pain, headache or dyspnoea differ in a range of clinical and demographic variables depending upon their time of presentation. These differences may potentially introduce selection bias impacting upon the internal validity of a study if convenience sampling of patients is undertaken.

he quantity of a medication supplied to a hospital ward should closely match the quantity administered to patients. 1 A discrepancy between the amounts supplied and used may reflect medication expiry, wastage, after-hours transfer to other wards, failure to document administration, or theft. 2 In emergency department (EDs), discrepancies have been reported for medications commonly used for self-treatment, and for oral alternatives to parenteral preparations. 1 Unlawful diversion of controlled medications is also a recognised problem. [3][4][5][6][7][8][9] Evaluating medication discrepancies was difficult when records were paper-based, as collating administrative data required a labour-intensive medical record audit. Electronic medication records, including medication supply and administration data, have facilitated the detection of medication discrepancies. 1 In this study, we analysed electronic medication supply and administration data for a variety of inpatient wards and EDs. Our aim was to describe the nature, extent, and cost of medication discrepancies. MethodsWe undertook a multicentre, retrospective observational study in the Austin, Box Hill, Footscray, and Frankston Hospitals in Melbourne, Victoria. The four hospitals are public metropolitan teaching centres with 560, 300, 425, and 401 beds respectively, and their EDs received 90 000, 43 200, 64 604, and 100 616 people in 2019 (according to hospital records).We assessed the quantities of selected medications supplied to two general medical wards, two surgical wards (one general, one orthopaedic) and the ED of each hospital, and the amounts administered to patients during the 2019 calendar year. Medication supply data were extracted from the pharmacy drug management system (MERLIN, PharmHos or iPharmacy, iSoft), and medication administration data from the electronic prescribing system (Millennium, Cerner). Data on doses that were lost, wasted, returned to the pharmacy, or destroyed were not available.For this study, an emergency physician and senior hospital pharmacists purposively sampled medications that are frequently prescribed (eg, for simple analgesia), useful for selftreatment (eg, anti-emetics), are associated with illegal diversion (eg, benzodiazepines), and oral and parenteral preparations of the same or similar medications (eg, oral and parenteral ondansetron). The selection was informed by the results of a pilot study, 1 and was not influenced by medication cost:• Antibiotics ► Phenoxymethylpenicillin (250 mg capsule), benzylpenicillin (1.2 g injection)► Cefalexin (500 mg capsule), ceftriaxone (1 g vial)

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