Deriving Novel Quaternary Ammonium Compound Disinfectant Scaffolds from a Natural Product: Mechanistic Insights of the Quaternization of Ianthelliformisamine C.

In the search for novel quaternary ammonium compound (QAC) disinfectants that can evade bacterial resistance, we turned to natural products as a source of inspiration. Herein we used natural product ianthelliformisamine C as a scaffold to design a small library of QACs. We first synthesized ianthelliformisamine C via an amide coupling that allowed for facile purification without the need for protecting groups. We then alkylated and quaternized the internal amines to yield four novel QACs, but all but one demonstrated no antibacterial activity against the tested strains. Using a combination of membrane depolarization and permeabilization assays, we were able to demonstrate that ianthelliformisamine C and the active QAC analog enact cell death via membrane permeabilization, contrary to prior reports on ianthelliformisamine C's mechanism of action.

The Prevalence of Delirium in An Older Acute Surgical Population and Its Effect on Outcome.

BACKGROUND: With an ageing population, an increasing number of older adults are admitted for assessment to acute surgical units. Older adults have specific factors that may influence outcomes, one of which is delirium (acute cognitive impairment). OBJECTIVES: To establish the prevalence of delirium on admission in an older acute surgical population and its effect on mortality. Secondary outcomes investigated include hospital readmission and length of hospital stay. METHOD: This observational multi-centre study investigated consecutive patients, ≥65 years, admitted to the acute surgical units of five UK hospitals during an eight-week period. On admission the Confusion Assessment Method (CAM) score was performed to detect delirium. The effect of delirium on important clinical outcomes was investigated using tests of association and logistic regression models. RESULTS: The cohort consisted of 411 patients with a mean age of 77.3 years (SD 8.1). The prevalence of admission delirium was 8.8% (95% CI 6.2-11.9%) and cognitive impairment was 70.3% (95% CI 65.6-74.7%). The delirious group were not more likely to die at 30 or 90 days (OR 1.1, 95% CI 0.2 to 5.1, p = 0.67; OR 1.4, 95% CI 0.4 to 4.1. p = 0.82) or to be readmitted within 30 days of discharge (OR 0.9, 95% CI 0.4 to 2.2, p = 0.89). Length of hospital stay was significantly longer in the delirious group (median 8 vs. 5 days respectively, p = 0.009). CONCLUSION: Admission delirium occurs in just under 10% of older people admitted to acute surgical units, resulting in significantly longer hospital stays.

Anti-cholinergic burden and patient related clinical outcomes in an emergency general surgical setting.

BACKGROUND/OBJECTIVE: The impact of medications with anti-cholinergic properties on morbidity and mortality of unselected adult patients admitted to the emergency general surgical setting has not been investigated. METHODS: All cases were identified prospectively from unselected adult patients admitted to the emergency general surgical ward between May to July 2016 in a UK centre with a catchment population circa 500,000. Prescribed medication lists were ascertained from case notes and electronic medical records. Anti-Cholinergic Burden (ACB) was calculated from medication lists. Patients were categorised into three groups based on ACB; none (ACB score of 0); moderate (up to ACB score of two); high (ACB score more than two). The effect of increasing ACB on selected outcomes of 30- and 90-day mortality, hospital readmission within 30-days of discharge and increased length of hospital stay were examined using multivariable logistic regression models. RESULTS: The 452 patients had a mean age (SD) of 51.7 (±20.6) years, 273 (60.4%) patients had no ACB burden, 106 (23.5%) had a ACB burden of up to two; and 73 (16.2%) had an ACB burden of > 2. Multivariable analyses showed no association between high ACB burden and 90-day (fully adjusted odds ratio [OR] 0.56 (95%CI 0.12-2.85); P = 0.48) and 30-day mortality (fully adjusted OR = 0.75 (95%CI 0.05-11.04); P = 0.84). A significant association was observed between moderate ACB burden and 30-day hospital readmission (fully adjusted OR = 2.01 (95%CI 1.09-3.71); P = 0.03). CONCLUSIONS: Anti-cholinergic burden may be linked to hospital readmission in adults admitted to an emergency general surgical ward.

Prevalence of multimorbidity and its association with outcomes in older emergency general surgical patients: an observational study.

OBJECTIVES: Multimorbidity is the presence of 2 or more medical conditions. This increasingly used assessment has not been assessed in a surgical population. The objectives of this study were to assess the prevalence of multimorbidity and its association with common outcome measures. DESIGN: A cross-sectional observational study. SETTING: A UK-based multicentre study, included participants between July and October 2014. PARTICIPANTS: Consecutive emergency (non-elective) general surgical patients admitted to hospital, aged over 65 years. OUTCOME MEASURES: The outcome measures were (1) the prevalence of multimorbidity and (2) the association between multimorbidity and frailty; the rate and severity of surgery; length of hospital stay; readmission to hospital within 30 days of discharge; and death at 30 and 90 days. RESULTS: Data were collected on 413 participants aged 65-98 years (median 77 years, (IQR (70-84)). 51.6% (212/413) participants were women. Multimorbidity was present in 74% (95% CI 69.7% to 78.2%) of the population and increased with age (p<0.0001). Multimorbidity was associated with increasing frailty (p for trend <0.0001). People with multimorbidity underwent surgery as often as those without multimorbidity, including major surgery (p=0.03). When comparing multimorbid people with those without multimorbidity, we found no association between length of hospital stay (median 5 days, IQR (1-54), vs 6 days (1-47), (p=0.66)), readmission to hospital (64 (21.1%) vs 18 (16.8%) (p=0.35)), death at 30 days (14 (4.6%) vs 6 (5.6%) (p=0.68)) or 90-day mortality (28 (9.2%) vs 8 (7.6%) (p=0.60)). CONCLUSIONS AND IMPLICATIONS: Multimorbidity is common. Nearly three-quarters of this older emergency general surgical population had 2 or more chronic medical conditions. It was strongly associated with age and frailty, and was not a barrier to surgical intervention. Multimorbidity showed no associations across a range of outcome measures, as it is currently defined. Multimorbidity should not be relied on as a useful clinical tool in guidelines or policies for older emergency surgical patients.

The prevalence of hyperglycaemia and its relationship with mortality, readmissions and length of stay in an older acute surgical population: a multicentre study.

BACKGROUND: The purpose of the study is to examine the prevalence of hyperglycaemia in an older acute surgical population and its effect on clinically relevant outcomes in this setting. METHODS: Using Older Persons Surgical Outcomes Collaboration (OPSOC) multicentre audit data 2014, we examined the prevalence of admission hyperglycaemia, and its effect on 30-day and 90-day mortality, readmission within 30 days and length of acute hospital stay using logistic regression models in consecutive patients, ≥65 years, admitted to five acute surgical units in the UK hospitals in England, Scotland and Wales. Patients were categorised in three groups based on their admission random blood glucose: <7.1, between 7.1 and 11.1 and ≥11.1 mmol/L. RESULTS: A total of 411 patients (77.25±8.14 years) admitted during May and June 2014 were studied. Only 293 patients (71.3%) had glucose levels recorded on admission. The number (%) of patients with a blood glucose <7.1, 7.1-11.1 and ≥11.1 mmol/L were 171 (58.4), 99 (33.8) and 23 (7.8), respectively. On univariate analysis, admission hyperglycaemia was not predictive of any of the outcomes investigated. Although the characteristics of those with no glucose level were not different from the included sample, 30-day mortality was significantly higher in those who had not had their admission glucose level checked (10.2% vs 2.7%), suggesting a potential type II error. CONCLUSION: Despite current guidelines, nearly a third of older people with surgical diagnoses did not have their glucose checked on admission highlighting the challenges in prognostication and evaluation research to improve care of older frail surgical patients.