John Busby

Patient flow within UK emergency departments: a systematic review of the use of computer simulation modelling methods

Objectives Overcrowding in the emergency department (ED) is common in the UK as in other countries worldwide. Computer simulation is one approach used for understanding the causes of ED overcrowding and assessing the likely impact of changes to the delivery of emergency care. However, little is known about the usefulness of computer simulation for analysis of ED patient flow. We undertook a systematic review to investigate the different computer simulation methods and their contribution for analysis of patient flow within EDs in the UK. Methods We searched eight bibliographic databases (MEDLINE, EMBASE, COCHRANE, WEB OF SCIENCE, CINAHL, INSPEC, MATHSCINET and ACM DIGITAL LIBRARY) from date of inception until 31 March 2016. Studies were included if they used a computer simulation method to capture patient progression within the ED of an established UK National Health Service hospital. Studies were summarised in terms of simulation method, key assumptions, input and output data, conclusions drawn and implementation of results. Results Twenty-one studies met the inclusion criteria. Of these, 19 used discrete event simulation and 2 used system dynamics models. The purpose of many of these studies (n=16; 76%) centred on service redesign. Seven studies (33%) provided no details about the ED being investigated. Most studies (n=18; 86%) used specific hospital models of ED patient flow. Overall, the reporting of underlying modelling assumptions was poor. Nineteen studies (90%) considered patient waiting or throughput times as the key outcome measure. Twelve studies (57%) reported some involvement of stakeholders in the simulation study. However, only three studies (14%) reported on the implementation of changes supported by the simulation. Conclusions We found that computer simulation can provide a means to pretest changes to ED care delivery before implementation in a safe and efficient manner. However, the evidence base is small and poorly developed. There are some methodological, data, stakeholder, implementation and reporting issues, which must be addressed by future studies.

Low-dose Aspirin Use Does Not Increase Survival in 2 Independent Population-based Cohorts of Patients With Esophageal or Gastric Cancer

BACKGROUND & AIMSnPreclinical studies have shown aspirin to have anticancer properties and epidemiologic studies have associated aspirin use with longer survival times of patients with cancer. We studied 2 large cohorts to determine the association between aspirin use and cancer-specific mortality in patients with esophageal or gastric cancer.nnnMETHODSnWe performed a population-based study using cohorts of patients newly diagnosed with esophageal or gastric cancer, identified from cancer registries in England from 1998 through 2012 and the Scottish Cancer Registry from 2009 through 2012. Low-dose aspirin prescriptions were identified from linkages to the United Kingdom Clinical Research Practice Datalink in England and the Prescribing Information System in Scotland. Deaths were identified from linkage to national mortality records, with follow-up until September 2015 in England and January 2015 in Scotland. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by low-dose aspirin use after adjusting for potential confounders. Meta-analysis was used to pool results across the 2 cohorts.nnnRESULTSnThe combined English and Scottish cohorts contained 4654 patients with esophageal cancer and 3833 patients with gastric cancer, including 3240 and 2392 cancer-specific deaths, respectively. The proportions surviving 1 year, based on cancer-specific mortality, were similar in aspirin users vs non-users after diagnosis with esophageal cancer (48% vs 50% in England and 49% vs 46% in Scotland, respectively) or gastric cancer (58% vs 57% in England and 59% vs 55% in Scotland, respectively). There was no association between postdiagnosis use of low-dose aspirin and cancer-specific mortality among patients with esophageal cancer (pooled adjusted HR, 0.98; 95% CI, 0.89-1.09) or gastric cancer (pooled adjusted HR, 0.96; 95% CI, 0.85-1.08). Long-term aspirin use was not associated with cancer-specific mortality after diagnosis of esophageal cancer (pooled adjusted HR, 1.03; 95% CI, 0.85-1.25) or gastric cancer (pooled adjusted HR, 1.06; 95% CI, 0.85-1.32).nnnCONCLUSIONSnIn analyses of 2 large independent cohorts in the United Kingdom, low-dose aspirin usage was not associated with increased survival of patients diagnosed with esophageal or gastric cancer.

Selective serotonin reuptake inhibitor use and breast cancer survival: a population-based cohort study

BackgroundNearly 50% of breast cancer patients suffer from depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for depression, have been implicated in breast cancer development through increased prolactin levels and tamoxifen metabolism inhibition. Previous studies of breast cancer progression have focused on tamoxifen users, or have been limited by their small sample size and methodology. Therefore, we used UK population-based data to more robustly investigate the association between SSRI use and cancer-specific mortality.MethodsA cohort of patients with newly-diagnosed breast cancer between 1998 and 2012 was selected from English cancer registries and linked to prescription records from the Clinical Practice Research Datalink, andxa0to death records from the Office for National Statistics. We used Cox regression models to calculate hazard ratios (HRs) comparing mortality between post-diagnostic SSRI users and non-users (using time-dependant covariates), after adjusting for demographics, comorbidities and pre-diagnosis use of hormone replacement therapy or oral contraceptives. We conducted several additional analyses to assess causality.ResultsOur cohort included 23,669 breast cancer patients, of which 2672 used SSRIs and 3053 died due to their breast cancer during follow-up. After adjustment, SSRI users had higher breast cancer-specific mortality than non-users (HRu2009=u20091.27; 95% confidence interval (CI) 1.16, 1.40). However, this association was attenuated when restricting to patients with a prior history of depression (HRu2009=u20091.14; 95% CI 0.98, 1.33), and when comparing to users of other antidepressant medications (HRu2009=u20091.06; 95% CI 0.93, 1.20). There was some evidence of higher mortality among long-term SSRI users, even when restricting to patients with prior depression (HRu2009=u20091.54; 95% CI 1.03, 2.29).ConclusionsIn this large breast cancer cohort, SSRI use was associated with a 27% increase in breast cancer mortality. The cause of this is unknown; however, confounding by indication seems likely as it was largely attenuated when restricting to patients with prior depression, or when comparing SSRIs to other antidepressant medications. Clinicians should not be unduly concerned when prescribing SSRIs to breast cancer patients, but the increase in mortality among long-term SSRI users warrants further investigation.

Angiotensin receptor blocker use and gastro-oesophageal cancer survival: a population-based cohort study

Angiotensin receptor blockers (ARBs; including candesartan, losartan, olmesartan and valsartan) are widely used to treat hypertension, heart failure and diabetic neuropathy. There is considerable pre‐clinical evidence that ARBs can reduce cancer progression, particularly for gastric cancer. Despite this, epidemiological studies have yet to assess the impact of ARB use on gastro‐oesophageal cancer survival.

How do population, general practice and hospital factors influence ambulatory care sensitive admissions: a cross sectional study

BackgroundReducing unplanned hospital admissions is a key priority within the UK and other healthcare systems, however it remains uncertain how this can be achieved. This paper explores the relationship between unplanned ambulatory care sensitive condition (ACSC) admission rates and population, general practice and hospital characteristics. Additionally, we investigated if these factors had a differential impact across 28 conditions.MethodsWe used the English Hospital Episode Statistics to calculate the number of unplanned ACSC hospital admissions for 28 conditions at 8,029 general practices during 2011/12. We used multilevel negative binomial regression to estimate the influence of population (deprivation), general practice (size, access, continuity, quality, A&E proximity) and hospital (bed availability, % day cases) characteristics on unplanned admission rates after adjusting for age, sex and chronic disease prevalence.ResultsPractices in deprived areas (at the 90th centile) had 16% (95% confidence interval: 14 to 18) higher admission rates than those in affluent areas (10th centile). Practices with poorer care continuity (9%; 8 to 11), located closest to A&E (8%; 6 to 9), situated in areas with high inpatient bed availability (14%; 10 to 18) or in areas with a larger proportion of day case admissions (17%; 12 to 21) had more admissions. There were smaller associations for primary care access, clinical quality, and practice size. The strength of associations varied by ACSC. For example, deprivation was most strongly associated with alcohol related diseases and COPD admission rates, while continuity of primary care was most strongly associated with admission rates for chronic diseases such as hypertension and iron-deficiency anaemia.ConclusionsThe drivers of unplanned ACSC admission rates are complex and include population, practice and hospital factors. The importance of these varies markedly across conditions suggesting that multifaceted interventions are required to avoid hospital admissions and reduce costs. Several of the most important drivers of admissions are largely beyond the control of GPs. However, strategies to improve primary care continuity and avoid unnecessary short-stay admissions could lead to improved efficiency.

A combined connectivity mapping and pharmacoepidemiology approach to identify existing medications with breast cancer causing or preventing properties

We applied a novel combined connectivity mapping and pharmacoepidemiological approach to identify medications that alter breast cancer risk.

Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: an analysis of two independent population-based databases

Excessive lower oesophageal sphincter relaxation increases gastro‐oesophageal acid reflux, an oesophageal adenocarcinoma risk factor. Medications that relax this sphincter (benzodiazepines, calcium channel blockers, nitrates, β2 agonists and xanthines) could promote cancer. These medications were investigated in two independent datasets. In the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case–control study of oesophageal cancer was performed using GP prescription records. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for medication use and oesophageal cancer. In UK Biobank, a cohort study was conducted using self‐reported medication use. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs for medication use and oesophageal cancer, and by tumour subtype. Overall, 1,979 oesophageal cancer patients were matched to 9,543 controls in PCCIU, and 355 of 475,768 participants developed oesophageal cancer in UK Biobank. None of the medications investigated were significantly associated with oesophageal cancer risk apart from β2 agonists, which were associated with increased oesophageal cancer risk in PCCIU (adjusted OR 1.38, 95% CI 1.12, 1.70) but not in UK Biobank (adjusted HR 1.21, 95% CI 0.70, 2.08). Medications that relax the lower oesophageal sphincter were not associated with oesophageal cancer, apart from β2 agonists. This increased cancer risk in β2 agonist users merits further investigation.

Post-diagnostic calcium channel blocker use and breast cancer mortality: a population-based cohort study: a population-based cohort study

Background: There have long been concerns that calcium channel blockers (CCBs), widely used to treat hypertension, may contribute to malignant growth through the evasion of apoptosis and proliferation of cancer cells. Worryingly, a recent cohort study found breast cancer patients who used CCBs had higher death rates, but interpreting these results was difficult as they were based on all-cause mortality and medication use before cancer diagnosis. We used UK population-based data to more robustly investigate the association between CCB use and cancer-specific mortality. Methods: We selected a cohort of patients with breast cancer diagnosed between 1998 and 2012 from English cancer registries. We linked to prescription and clinical records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used adjusted, time-dependent Cox regression models to calculate hazard ratios (HRs) comparing breast cancer–specific and all-cause mortality between postdiagnostic CCB users and nonusers. Results: Our cohort included 23,669 breast cancer patients, of whom 5,141 used CCBs and 3,053 died due to their breast cancer during follow-up. After adjustment, CCB users had similar breast cancer–specific mortality to nonusers (HR = 0.98, 95% confidence interval [CI] = 0.88, 1.08). There was no evidence of a dose–response relationship. We found similar associations for specific CCBs, and for all-cause mortality. Conclusions: In this large population-based breast cancer cohort, we did not find any evidence that CCB use is associated with increased mortality.BACKGROUNDnThere have long been concerns that calcium channel blockers (CCBs), widely used to treat hypertension, may contribute to malignant growth through the evasion of apoptosis and proliferation of cancer cells. Worryingly, a recent cohort study found breast cancer patients who used CCBs had higher death rates, but interpreting these results was difficult as they were based on all-cause mortality and medication use before cancer diagnosis. We used UK population-based data to more robustly investigate the association between CCB use and cancer-specific mortality.nnnMETHODSnWe selected a cohort of patients with breast cancer diagnosed between 1998 and 2012 from English cancer registries. We linked to prescription and clinical records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used adjusted, time-dependent Cox regression models to calculate hazard ratios (HRs) comparing breast cancer-specific and all-cause mortality between postdiagnostic CCB users and nonusers.nnnRESULTSnOur cohort included 23,669 breast cancer patients, of whom 5,141 used CCBs and 3,053 died due to their breast cancer during follow-up. After adjustment, CCB users had similar breast cancer-specific mortality to nonusers (HR = 0.98, 95% confidence interval [CI] = 0.88, 1.08). There was no evidence of a dose-response relationship. We found similar associations for specific CCBs, and for all-cause mortality.nnnCONCLUSIONSnIn this large population-based breast cancer cohort, we did not find any evidence that CCB use is associated with increased mortality.

Model for Identifying Individuals at Risk for Esophageal Adenocarcinoma

BACKGROUND & AIMS The prognosis for most patients with esophageal adenocarcinoma (EAC) is poor because they present with advanced disease. Models developed to identify patients at risk for EAC and increase early detection have been developed based on data from case–control studies. We analyzed data from a prospective study to identify factors available to clinicians that identify individuals with a high absolute risk of EAC. METHODS We collected data from 355,034 individuals (all older than 50 years) without a prior history of cancer enrolled in the UK Biobank prospective cohort study from 2006 through 2010; clinical data were collected through September 2014. We identified demographic, lifestyle, and medical factors, measured at baseline, that associated with development of EAC within 5 years using logistic regression analysis. We used these data to create a model to identify individuals at risk for EAC. Model performance was assessed using area under the receiver operating characteristics curve (AUROC), sensitivity, and specificity analyses. RESULTS Within up to 5 years of follow up, 220 individuals developed EAC. Age, sex, smoking, body mass index, and history of esophageal conditions or treatments identified individuals who developed EAC (AUROC, 0.80; 95% CI, 0.77–0.82). We used these factors to develop a scoring system and identified a point cut off that 104,723 individuals (29.5%), including 170 of the 220 cases with EAC, were above. The scoring system identified individuals who developed EAC with 77.4% sensitivity and 70.5% specificity. The 5‐year risk of EAC was 0.16% for individuals with scores above the threshold and 0.02% for individuals with scores below the threshold. CONCLUSION We combined data on several well‐established risk factors that are available to clinicians to develop a system to identify individuals with a higher absolute risk of EAC within 5 years. Studies are needed to evaluate the utility of these factors in a multi‐stage, triaged, screening program.

The effect of medications which cause inflammation of the gastro-oesophageal tract on cancer risk : a nested case–control study of routine Scottish data

Bisphosphonate, tetracycline and spironolactone use has been shown to increase gastro‐oesophageal inflammation, an accepted risk factor for cancer. However, evidence of the effect of these medications on gastro‐oesophageal cancer risk are mixed or missing entirely. Therefore, we conducted a nested case–control study using the Primary Care Clinical Information Unit Research (PCCIUR) database from Scotland. Cases with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five controls based on age, gender, year of diagnosis and general practice. Medication use was ascertained using electronic prescribing records. Conditional logistic regression was used to calculate odds ratios (ORs) for the association between medication use and cancer risk after adjustment for comorbidities and other medication use. A similar proportion of gastro‐oesophageal cancer cases received bisphosphonates (3.9% vs. 3.5%), tetracycline (6.0% vs. 6.0%) and spironolactone (1.4% vs. 1.1%) compared with the controls. The adjusted ORs for the association between gastro‐oesophageal cancer and bisphosphonates, tetracycline and spironolactone were 1.05 (95% CI: 0.85, 1.31), 0.99 (95% CI: 0.84, 1.17) and 1.04 (95% CI: 0.73, 1.49). Further analysis revealed bisphosphonates were associated with increased oesophageal cancer risk (1.34, 95% CI: 1.03, 1.74) but reduced gastric cancer risk (0.71, 95% CI: 0.49, 1.03), although there was no obvious dose–response relationship. Overall, there is little evidence that the use of bisphosphonate, tetracycline or spironolactone is associated with increased risk of gastro‐oesophageal cancer. Our findings should reassure GPs and patients that these widely‐used medications are safe with respect to gastro‐oesophageal cancer risk.