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Background Adverse drug reactions (ADRs) and adverse drug events (ADEs) in older people contribute to a significant proportion of hospital admissions and are common following discharge. Effective interventions are therefore required to combat the growing burden of preventable ADRs. The Prediction of Hospitalisation due to Adverse Drug Reactions in Elderly Community Dwelling Patients (PADR-EC) score is a validated risk score developed to assess the risk of ADRs in people aged 65 years and older and has the potential to be utilised as part of an intervention to reduce ADRs. Objectives This trial was designed to investigate the effectiveness of an intervention to reduce ADR incidence in older people and to obtain further information about ADRs and ADEs in the 12–24 months following hospital discharge. Methods The study is an open-label randomised-controlled trial to be conducted at the Royal Hobart Hospital, a 500-bed public hospital in Tasmania, Australia. Community-dwelling patients aged 65 years and older with an unplanned overnight admission to a general medical ward will be recruited. Following admission, the PADR-EC ADR score will be calculated by a research pharmacist, with the risk communicated to clinicians and discussed with participants. Following discharge, nominated general practitioners and community pharmacists will receive the risk score and related medication management advice to guide their ongoing care of the patient. Follow-up with participants will occur at 3 and 12 and 18 and 24 months to identify ADRs and ADEs. The primary outcome is moderate-severe ADRs at 12 months post-discharge, and will be analysed using the cumulative incidence proportion, survival analysis and Poisson regression. Summary It is hypothesised that the trial will reduce ADRs and ADEs in the intervention population. The study will also provide valuable data on post-discharge ADRs and ADEs up to 24 months post-discharge.

Medication errors are more prevalent in settings with acutely ill patients and heavy workloads, such as in an emergency department (ED). A pragmatic, controlled study compared partnered pharmacist medication charting (PPMC) (pharmacist-documented best-possible medication history [BPMH] followed by clinical discussion between a pharmacist and medical officer to co-develop a treatment plan and chart medications) with early BPMH (pharmacist-documented BPMH followed by medical officer-led traditional medication charting) and usual care (traditional medication charting approach without a pharmacist-collected BPMH in ED). Medication discrepancies were undocumented differences between medication charts and medication reconciliation. An expert panel assessed the discrepancies’ clinical significance, with ‘unintentional’ discrepancies deemed ‘errors’. Fewer patients in the PPMC group had at least one error (3.5%; 95% confidence interval [CI]: 1.1% to 5.8%) than in the early BPMH (49.4%; 95% CI: 42.5% to 56.3%) and usual care group (61.4%; 95% CI: 56.3% to 66.7%). The number of patients who need to be treated with PPMC to prevent at least one high/extreme error was 4.6 (95% CI: 3.4 to 6.9) and 4.0 (95% CI: 3.1 to 5.3) compared to the early BPMH and usual care group, respectively. PPMC within ED, incorporating interdisciplinary discussion, reduced clinically significant errors compared to early BPMH or usual care.

Background COVID-19 medicines delivery units (CMDU) were established in late December 2021 to deliver early antiviral therapy to patients classified as at risk with the aim of preventing hospitalization. Methods We performed a service evaluation at 4 CMDUs in England. We assessed demographics and triage outcomes of CMDU referral, uptake of antiviral therapy, and the rate of subsequent hospitalizations within 2 weeks of CMDU referral. Results Over a 3-week period, 4788 patients were referred and 3989 were ultimately assessed by a CMDU. Overall, 832 of the patients referred (17%) were judged eligible for treatment and 628 (13%) were ultimately prescribed an antiviral agent. The overall rate of admission within 14 days was 1%. Patients who were admitted were significantly older than those who did not require hospitalization. Of patients prescribed molnupiravir and sotrovimab, 1.8% and 3.2%, respectively, were admitted. Conclusions There was a high volume of referrals to CMDU service during the initial surge of the Omicron wave in the United Kingdom. A minority of patients were judged to be eligible for therapy. In a highly vaccinated population, the overall hospitalization rate was low.

Mouse and human data implicate the NOD1 and NOD2 sensors of the intestinal microbiome and the associated signal transduction via the receptor interacting protein kinase 2 (RIPK2) as a potential key signaling node for the development of inflammatory bowel disease (IBD) and an attractive target for pharmacological intervention. The TRUC mouse model of IBD was strongly indicated for evaluating RIPK2 antagonism for its effect on intestinal inflammation based on previous knockout studies with NOD1, NOD2, and RIPK2. We identified and profiled the BI 706039 molecule as a potent and specific functional inhibitor of both human and mouse RIPK2 and with favorable pharmacokinetic properties. We dosed BI 706039 in the spontaneous TRUC mouse model from age 28 to 56 days. Oral, daily administration of BI 706039 caused dose-responsive and significant improvement in colonic histopathological inflammation, colon weight, and terminal levels of protein-normalized fecal lipocalin (all

Structure activity relationship (SAR) investigation of an oxadiazole based series led to the discovery of several potent FLAP inhibitors. Lead optimization focused on achieving functional activity while improving physiochemical properties and reducing hERG inhibition. Several compounds with favorable in vitro and in vivo properties were identified that were suitable for advanced profiling.

The prediction of the outcome from coma is of considerable importance to the patients, their relatives and attendant medical staff, and yet current clinical methods lack sensitivity and specificity. Objective investigations can enhance the accuracy of such predictions and are an important adjuvant when reaching decisions to continue or terminate life support. Of the neurophysiological methods available, electroencephalography and short-latency somatosensory evoked potentials have proved the most useful in the clinical setting. These tests are good predictors of an adverse outcome; however, they tell us only about the ongoing cerebral activity and integrity of the primary somatosensory pathways, respectively. The presence of long-latency event-related potentials has been shown to be a useful predictor of a favourable neurological outcome, and thus their use complements other neurophysiological techniques. Their potential application in clinical practice is reviewed.

n Context: Topical corticosteroids are the recommended first-line treatment for all severities of persistent asthma and moderate to severe allergic rhinitis. Potential adrenal suppression resulting from corticosteroid administration necessitates monitoring of children participating in clinical studies. Measurement of pretreatment cortisol concentrations is necessary to assess effects on adrenal function. Objective: Plasma cortisol concentrations are assay dependent; normal reference range values must be obtained for each assay. Our objective is to provide these values for children as determined by HPLC. Design and Patients: Two multicenter, randomized, double-blind, placebo-controlled studies evaluating basal and cosyntropin-stimulated morning plasma cortisol concentrations for patients aged 5 to younger than 12 months with asthma and patients aged 2 to younger than 6 yr with allergic rhinitis using HPLC were conducted. Main Outcome Measures: Main planned outcomes of these studies are reported elsewhere. This manuscript reports plasma cortisol concentration reference range values. Results: In general, mean basal plasma cortisol concentrations (n = 177) (mean +/- SD, nmol/liter) were similar among the 5 to younger than 9 months, 9 to younger than 12 months, 2 to younger than 3 yr, 3 to younger than 4 yr, 4 to younger than 5 yr, and 5 to younger than 6 yr age groups (218 +/- 149, 281 +/- 144, 257 +/- 105, 231 +/- 83, 298 +/- 118, and 237 +/- 65, respectively) and increased to comparable levels 60 min after cosyntropin stimulation (n +/- 178; 622 +/- 176, 638 +/- 176, 697 +/- 99, 655 +/- 103, 662 +/- 113, and 610 +/- 68, respectively). However, patients younger than 12 months had wider ranges of basal and stimulated values. Conclusions: Basal and cosyntropin-stimulated morning plasma cortisol concentrations of children aged 5 to younger than 12 months and 2 to younger than 6 yr were consistently measurable, with the large majority similar among the age groups examined, and comparable with those reported elsewhere for adults.

This chapter sketches the outlines of what a reasonable form of nativism might look like. The neuroconstructivists' challenge indicates that some misunderstanding continues to exist among certain self-titled nonnativists over what it is that practicing nativists actually claim, together with a mistaken belief that current neurodevelopmental data is not or cannot be compatible with the nativist program. Both these issues are addressed by first providing further explication of the claims of practicing nativists, and then showing how these claims provide the basis for a reasonable nativism that is fully cognizant of and consistent with empirical data from all the developmental sciences, neuroconstructivism included.

The PA xpress phayngeal airway (PA x ) is a new single use airway device that might be used for airway maintenance during anaesthesia or cardiopulmonary resuscitation. We evaluated the performance of the PA x in 103 anaesthetised non-paralysed patients undergoing non-emergency anaesthesia. We recorded success of insertion, quality of airway achieved and complications of its use. We were successful in establishing a clear airway on the first attempt on 68 (67%) occasions. We were unable to establish a patent airway in nine (9%) patients. Partial or intermittent airway obstruction occurred during maintenance of anaesthesia in ten (11%) cases but none required removal of the device. Jaw thrust was used to assist insertion in all cases. A mean of 1.37 further manipulations per patient were required to establish an airway and 0.60 per patient were required during maintenance of anaesthesia. In the 94 patients in whom an airway was established, assisted ventilation was excellent in 77 (82%). Leak pressure was 20 cmH 2 O or above in 58% cases. Intracuff pressure was measured in 55 patients: mean pressure was 68 cmH 2 O and was above 100 cmH 2 O in ten (18%) cases. Complications occurred in 38 (37%) patients during insertion, in a further 12 (13%) during maintenance and in eight (9%) during emergence. The device was difficult to insert and associated with a high incidence of trauma: blood was visible on the device after removal in 56 (55%) cases. We conclude that the PA x is associated with too high a failure rate and too high an incidence of minor complications for routine airway maintenance.