Five years of outpatient parenteral antibiotic therapy with ceftriaxone in the paediatric emergency department: what clinical features are associated with need for admission?

BACKGROUND: More children presenting to Emergency Departments (EDs) with acute infections are now directly referred for outpatient parenteral antibiotic therapy (OPAT). Sparse data exist on what clinical features in these children are associated with OPAT failure. We hypothesised that children who were younger or presented with systemic features of infection would be more likely to need admission. METHODS: We conducted a service evaluation over a 5-year period (12 September 2015-12 September 2020) at a single UK tertiary centre paediatric ED formally known as the Royal Hospital for Sick Children Edinburgh. All children referred from the ED for OPAT with ceftriaxone were included. OPAT failure was defined as a decision by a senior clinician of need for admission. Univariate statistical testing and multivariate logistic regression modelling were performed. RESULTS: 754 children received OPAT in the ED over a 5-year period. 95 children (13%) required admission for inpatient management. Need for admission was independently associated with having a positive blood culture (adjusted OR (aOR) 8.9; 95% CI 1.49 to 47; p=0.01) or an ultrasound performed (aOR 6.8; 95% CI 3.74 to 12.7; p<0.001). We observed no significant association between age and systemic features (fever, white cell count or C reactive protein) with need for admission in our multivariate analysis. CONCLUSION: In children presenting with acute infections to our paediatric ED who were deemed suitable by senior clinicians to be managed using OPAT with ceftriaxone, younger age (above 3 months) and the presence of systemic features were not independently associated with need for admission. Overall, our service was safe and no child came to harm from early ambulation during this evaluation.

Low serum magnesium and 1-year mortality in alcohol withdrawal syndrome.

BACKGROUND: In 2014, the WHO reported that 6% of all deaths were attributable to excess alcohol consumption. The aim of the present study was to examine the relationship between serum magnesium concentrations and mortality in patients with alcohol withdrawal syndrome (AWS). MATERIALS AND METHODS: A retrospective review of 700 patients with documented evidence of previous AWS indicating a requirement for benzodiazepine prophylaxis or evidence of alcohol withdrawal syndrome between November 2014 and March 2015. RESULTS: Of 380 patients included in the sample analysis, 64 (17%) were dead at 1 year following the time of treatment for AWS. The majority of patients had been prescribed thiamine (77%) and a proton pump inhibitor (66%). In contrast, the majority of patients had low circulating magnesium concentrations (<0.75 mmol/L) (64%) and had not been prescribed magnesium (90%). The median age of death at one year was 55 years (P = 0.002). On univariate analysis, age (P < 0.05), GMAWS (P < 0.05), BDZ (P < 0.05), bilirubin (P < 0.001), alkaline phosphatase (P < 0.001), albumin (P < 0.001), CRP (P < 0.05), AST:ALT ratio >2 (P < 0.001), sodium (P < 0.05), magnesium (P < 0.001), platelets (P < 0.05) and the use of proton pump inhibitor medication (P < 0.001) were associated with death at 1 year. On multivariate binary logistic regression analysis, age > 50 years (OR 3.37, 95% CI 1.52-7.48, P < 0.01), AST:ALT ratio >2 (OR 3.10, 95% CI 1.38-6.94, P < 0.01) and magnesium < 0.75 mmol/L (OR 4.11, 95% CI 1.3-12.8, P < 0.05) remained independently associated with death at 1 year. CONCLUSION: Overall, 1-year mortality was significantly higher among those patients who were magnesium deficient (<0.75 mmol/L) when compared to those who were replete (≥0.75 mmol/L; P < 0.001).

Racialized economic segregation and stage at diagnosis of colorectal cancer in the United States.

PURPOSE: In order to improve colorectal cancer outcomes in the United States, there is an urgent need for research on the drivers of geographic disparities in stage at diagnosis. Our objective was to determine the effects of racialized economic segregation on the odds of late diagnosis. METHODS: Among 187,843 adults (≥ 18 years old) with new diagnoses of colorectal cancer reported to the Surveillance, Epidemiology and End-Results program between 1st January 2009 and 31st December 2013, exposure to racialized economic segregation was measured at the county-level using Index of Concentration at the Extremes metrics. Multilevel logistic regression models including registry and county random effects were fit to examine the association between racialized economic segregation and odds of metastatic disease at time of diagnosis. RESULTS: Odds of late diagnosis were greatest in counties with the lowest compared to highest quintile for racial and economic privilege (OR 1.14; 95% CI 1.09-1.20). In multilevel models adjusting for individual-level covariates, odds of late diagnosis were greater for all patients except those living in counties with the highest concentration of white high-income individuals. There was significant effect modification of this relationship by age, with greater adverse effects for younger adults (OR 1.16; 95% CI 1.02-1.32) than older adults (OR 1.06; 95% CI 1.00-1.11). Racialized economic segregation was strongly associated with access to affordable healthcare. CONCLUSIONS: Spatial social polarization, quantified in relation to racialized economic segregation, increases the odds of late diagnosis of colorectal cancer for persons residing in the least compared to most privileged counties.

Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials.

BACKGROUND: Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the effects of gastroprotectants in different clinical settings are scarce. We aimed to examine the effects of proton-pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs) in different clinical circumstances by doing meta-analyses of tabular data from all relevant unconfounded randomised trials of gastroprotectant drugs. METHODS: We searched MEDLINE and Embase from Jan 1, 1950, to Dec 31, 2015, to identify unconfounded, randomised trials of a gastroprotectant drug (defined as a PPI, prostaglandin analogue, or H2RA) versus control, or versus another gastroprotectant. Two independent researchers reviewed the search results and extracted the prespecified outcomes and key characteristics for each trial. We did meta-analyses of the effects of gastroprotectant drugs on ulcer development, bleeding, and mortality overall, according to the class of gastroprotectant, and according to the individual drug within a gastroprotectant class. FINDINGS: We identified comparisons of gastroprotectant versus control in 849 trials (142 485 participants): 580 prevention trials (110 626 participants), 233 healing trials (24 033 participants), and 36 trials for the treatment of acute upper gastrointestinal bleeding (7826 participants). Comparisons of one gastroprotectant drug versus another were available in 345 trials (64 905 participants), comprising 160 prevention trials (32 959 participants), 167 healing trials (28 306 participants), and 18 trials for treatment of acute upper gastrointestinal bleeding (3640 participants). The median number of patients in each trial was 78 (IQR 44·0-210·5) and the median duration was 1·4 months (0·9-2·8). In prevention trials, gastroprotectant drugs reduced development of endoscopic ulcers (odds ratio [OR] 0·27, 95% CI 0·25-0·29; p<0·0001), symptomatic ulcers (0·25, 0·22-0·29; p<0·0001), and upper gastrointestinal bleeding (0·40, 0·32-0·50; p<0·0001), but did not significantly reduce mortality (0·85, 0·69-1·04; p=0·11). Larger proportional reductions in upper gastrointestinal bleeding were observed for PPIs than for other gastroprotectant drugs (PPIs 0·21, 99% CI 0·12-0·36; prostaglandin analogues 0·63, 0·35-1·12; H2RAs 0·49, 0·30-0·80; phet=0·0005). Gastroprotectant drugs were effective in preventing bleeding irrespective of the use of non-steroidal anti-inflammatory drugs (phet=0·56). In healing trials, gastroprotectants increased endoscopic ulcer healing (3·49, 95% CI 3·28-3·72; p<0·0001), with PPIs more effective (5·22, 99% CI 4·00-6·80) than prostaglandin analogues (2·27, 1·91-2·70) and H2RAs (3·80, 3·44-4·20; phet<0·0001). In trials among patients with acute bleeding, gastroprotectants reduced further bleeding (OR 0·68, 95% CI 0·60-0·78; p<0·0001), blood transfusion (0·75, 0·65-0·88; p=0·0003), further endoscopic intervention (0·56, 0·45-0·70; p<0·0001), and surgery (0·72, 0·61-0·84; p<0·0001), but did not significantly reduce mortality (OR 0·90, 0·72-1·11; p=0·31). PPIs had larger protective effects than did H2RAs for further bleeding (phet=0·0107) and blood transfusion (phet=0·0130). INTERPRETATION: Gastroprotectants, in particular PPIs, reduce the risk of peptic ulcer disease and its complications and promote healing of peptic ulcers in a wide range of clinical circumstances. However, this meta-analysis might have overestimated the benefits owing to small study bias. FUNDING: UK Medical Research Council and the British Heart Foundation.