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Use of the online poisons information database TOXBASE and admissions rates for poisoned patients from emergency departments in England and Wales during 2008 to 2015

Abstract Background The impact of poison information services on patient care in hospital, particularly decisions on whether to admit patients after initial attendance at an emergency department (ED), is unclear. In the United Kingdom, the vast majority of poisons information is provided by use of the online poisons information database, TOXBASE. We investigated the relationship between rates of hospital access to TOXBASE and rates of poisoning admissions from EDs in England and Wales to begin to address the interactions between use of poisons information and patient management as reflected by hospital activity. Methods Data were obtained on attendances and admissions due to poisoning for individual National Health Service (NHS) Trusts in both England and Wales, together with data on the overall number of accesses to TOXBASE for drugs (pharmaceuticals and drugs of abuse), from 2008 to 2015. Rates of TOXBASE access and admissions per poisoning attendance in London were clearly different to the rest of England and Wales; London was therefore analyzed separately. Negative binomial generalized additive models were fit, incorporating an interaction effect, for accesses, attendances and admissions to check for variability according to hospital size. Additional models were then fit to assess whether there was any variation in association of overall TOXBASE use with rates of admission for 6 key drug subgroups: antidepressants, paracetamol, antipsychotics, opioids (including all medicines, but excluding heroin), heroin and non‐opioid drugs of abuse. Results Rates of TOXBASE use per Trust increased across the study period by 39.3% (95% confidence interval [CI] = 34.1%, 44.8%) in England and 76.9% (24.7%, 151.0%) in Wales, showing an increase in TOXBASE use which was substantially greater than the increase in poisoning attendances. Admission rates exhibited seasonality, with lower rates in January and February, increasing by 2.0% (1.0%, 3.1%) in England and 5.8% (5.5%, 5.9%) in Wales toward the middle of the year. The initial model fit indicated that the average proportion of poisoning patients admitted increased with both increasing attendances and increasing TOXBASE use (England and Wales overall, P < 0.0001; England and Wales excluding London, P < 0.0001; London, P < 0.0001). In England and Wales overall, and in London alone, increased TOXBASE access to non‐opioid drugs of abuse advice was associated with a significant decrease in admissions (England and Wales, −0.15% [−0.29%, −0.01%] [P = 0.032]; London, −1.02% [−1.53%, −0.50%] [P < 0.0001]). In contrast, increased access to heroin advice was associated with a significant increase in admissions in London (+2.03% [+0.11%, +3.99%] [P = 0.034]). Increasing access to TOXBASE for paracetamol advice was associated with lower admissions in England and Wales (England and Wales, −0.11% [−0.23%, −0.01%] [P = 0.036]; England and Wales excluding London, −0.18% [−0.30%, −0.06%] [P = 0.001]) but higher admissions in London (+0.52% [+0.03%, +1.01%] [P = 0.035]). Conclusions We have shown that greater overall use of TOXBASE by hospitals is associated with a higher proportion of poisoning attendances being admitted. Interestingly, looking at particular drug groups, we found significant associations in both directions between overall TOXBASE use and rates of admission for some drug groups. The current methodology is unable to determine whether such decisions might be appropriate or not. Mixed‐methods research is now required to gain a better understanding of how provision of poisons information affects decisions within the ED.

Results: Rates of TOXBASE use per Trust increased across the study period by 39.3% (95% confidence interval [CI] = 34.1%, 44.8%) in England and 76.9% (24.7%, 151.0%) in Wales, showing an increase in TOXBASE use which was substantially greater than the increase in poisoning attendances. Admission rates exhibited seasonality, with lower rates in January and February, increasing by 2.0% (1.0%, 3.1%) in England and 5.8% (5.5%, 5.9%) in Wales toward the middle of the year. The initial model fit indicated that the average proportion of poisoning patients admitted increased with both increasing attendances and increasing TOXBASE use (England and Wales overall, P < 0.0001; England and Wales excluding London, P < 0.0001; London, P < 0.0001). In England and Wales overall, and in London alone, increased TOXBASE access to non-opioid drugs of abuse advice was associated with a significant decrease in admissions (England and

Conclusions:
We have shown that greater overall use of TOXBASE by hospitals is associated with a higher proportion of poisoning attendances being admitted. Interestingly, looking at particular drug groups, we found significant associations in both directions between overall TOXBASE use and rates of admission for some drug groups. The current methodology is unable to determine whether such decisions might be appropriate or not. Mixed-methods research is now required to gain a better understanding of how provision of poisons information affects decisions within the ED.

K E Y W O R D S
drugs of abuse, hospital activity analysis, pharmaceuticals, poisons information

Background
Poisons information services aim to improve the care of patients with suspected or confirmed poisoning. They may prevent unnecessary hospital presentations (attendances) and are intended to improve triage (decision whether to admit the patient to hospital or discharge from the emergency department) and care of patients who do present to hospital. When used by the public or primary care services, provision of poisons information reduces attendances at emergency departments and hospital admissions in both North America and the United Kingdom. 1,2 In the United Kingdom, the public is unable to access poisons information directly from poisons information centers. The National Health Service's (NHS) introduction of telephone health information lines for the general public in the early 2000s led to the need for a single authoritative approach to poisons information provision for both pri-mary and secondary care services. 3 The UK National Poisons Information Service had launched its online clinical database TOXBASE in late 1999; it was subsequently adopted as the primary source of poisons information for all healthcare services across the United Kingdom. 4,5 TOXBASE is used routinely in the management of poisoned patients, providing information, not only on the potential toxicity and treatment of compounds, but also the dose thresholds for toxic effects and

Goals
The aim of this project was to evaluate the impact of poisons information services on physician behavior. This is complicated, because hospital activity varies both seasonally and geographically. In addition, use of the TOXBASE database has increased over time. 7 In England and Wales (England and Wales), routine data are available on attendances at emergency departments, with the broad clinical area of reason for attendance described (eg, poisoning), and the proportion of these attendances that are admitted. 8,9 Hospital admissions activity is coded using ICD10, but this coding is not yet applied to attendances. studies. An epidemiological study of this design shows associations, which can then be the focus for further studies; it cannot establish causation. As online information systems are increasingly used in medicine this project may also inform others in the field.

The Bottom Line
Use of poison information services in emergency departments may impact admission decisions. Although greater TOXBASE use in England and Wales was associated with admission for poisoning overall, there was a decrease in admission for non-opioid drugs of abuse and acetaminophen.

Design
Data on the number of admissions and attendances for poisoning in

Setting
This study was conducted using data available from routine NHS data sources on attendance and admissions from hospital emergency departments in the United Kingdom. We also assessed overall usage of TOXBASE pharmaceutical product (agent) entries (including drugs of abuse) as well as 6 common medicines and recreational drug groups: antidepressants, paracetamol, antipsychotics, opioids (including all opioid medicines but excluding heroin), heroin, and non-opioid drugs of abuse. For simplicity, we refer to these together as "Drugs." Heroin was assessed separately from opioids due to the major differences in its supply and usage across the United Kingdom.

Selection
The data set used contained all data available to us for the study period in England and Wales. Because poisoning attendances were not consistently recorded in the early days of these NHS data systems, some data were excluded from these analyses.

Analysis
The seasonal and long-term trends in the rate of poisoning admissions and the rate of TOXBASE accesses were explored using generalized additive models, which allow for smoothly varying relationships through time. The smooth terms and parameters in these models were estimated via an iterative process. At each step, the terms were estimated based on the response values minus the current estimates of each other term in the model, so that the values being used to estimate the components were overall centered around zero but still retained some pattern that is to be estimated, herein referred to as the centered response. It is the final values of this iterative process that will be presented and interpreted as the trends in the model.
The first model in this article examined the appropriateness of an interaction term in examining the effect of TOXBASE use on admissions. The model fit was of the form shown below: In this model, E(log (y i )) is the expected log number of admissions, and log (a i ) is the log number of poisoning attendances. The result of this is that this model provides insight into the rate of poisoning admissions per poisoning attendance, rather than the number of admissions due to poisoning. We wanted to incorporate some measure of hospital size in the model, hence the total number of attendances is represented by x 1i . The rate of TOXBASE access per attendance is represented in the model using x 2i , and x 1i x 2i denotes an interaction between hospital size and TOXBASE accesses, which will account for differences in the effect of TOXBASE access by hospital size. The final 2 terms represent the overall (f(t i )) and seasonal (g(m i )) patterns in the rate of admissions per attendance. Positive values of β 1 or β 2 indicated that admissions grow with attendances or accesses, whereas negative values indicated a decrease in admissions with attendances or accesses respectively. The coefficient β 3 of the interaction term indicated how admissions change with attendances for different levels of TOXBASE usage.
The above model was used as a starting point for the analysis and was simplified where appropriate. These data exhibited overdispersion, a common artefact in count data, where the variance is larger than the mean. This does not hold with the assumption of equal mean and variance distribution made by use of the Poisson distribution.
In order to account for this over-dispersion, a negative binomial model was used.
Similar models were then used to summarize how the rate of admission varied in an average trust, with respect to the proportion of accesses to the 6 aforementioned drug sub-groups. These models took a simpler form as outlined in the following equation: Here, y i is the proportion of attendances due to poisoning that resulted in admission within each Trust, whereas x i is the proportion of accesses made to the relevant drug group. Each drug group was assessed independently, but the results will be presented as a whole. In this analysis, we expect the coefficient β 1 to be negative when increasing proportions of accesses are associated with a decreasing proportion of admissions.
Temporal changes were explored by fitting models for rates of TOXBASE access and rates of admission by trust, through time. The models were of the form: where y represents either the rate of access to TOXBASE or the rate

RESULTS
During the period studied, after accounting for issues with data record-

Long-term and seasonal trends
The seasonal and long-term trends in the rate of admissions due to drugs poisoning and the rate of TOXBASE accesses/month are shown in Figure 1

Regional variability
We then investigated regional variability in the proportion of poisoning attendances admitted and in the rate of TOXBASE accesses per poisoning attendance across England and Wales. This was done by examining NHS Regional level maps of the data. These NHS Regions were changed during the period covered by the study to a much larger number of smaller areas run by NHS Clinical Commissioning Groups. For simplicity, we have used the older regional classification.
Overall rates of admission and TOXBASE access per attendance were calculated as the total number of admissions or accesses in that region, over the entire period, divided by the total number of attendances due to poisoning in that region over the entire period.
We found there to be little variability in the proportion of poisoning

Interaction models
We then assessed the relationship between rate of TOXBASE use per poisoning attendance and the rate of admissions due to drugs poisoning per poisoning attendance. This was initially done using the interaction model outlined in Equation 1, which took account of the effect of overall attendances on the rate of admissions, to investigate whether the effect of TOXBASE use varied depending on hospital size.
We found that the interaction term in the model was 4.073 × 10 −6 (standard error (se) 4.515 × 10 −7 ), P < 0.001. This implies that were large hospitals to increase their rate of accesses to TOXBASE the predicted increase in the admission rate is proportionately higher than in a smaller hospital which increases its access rate. However, the magnitude of this effect is minor as evidenced by the estimated coefficient, given the magnitude of the coefficient of the main effect of the TOXBASE access rate ( Table 2).
For the data overall, the model including the interaction term resulted in 75.4% of the variance in the observed data being explained-this was only a marginal improvement over the model excluding the interaction term, which had 75.2% variance explained.
These results were similar for the data excluding London and for London individually. This indicates that the interaction effect does not contribute a great deal to the fit of the model, and for simplicity, the model excluding this interaction will be presented here.
We found that the rate of admissions due to poisoning (per poisoning attendance) tended to decrease as hospital size increased, as indicated by the negative estimate of the coefficient in the first row of  Table S1).
The positive association between TOXBASE use and admissions described by the model coefficients seems counterintuitive, given the opposing trends in the rate of admission and the rate of TOXBASE use seen in Figure 1. Further exploration of this is shown in Figure 3, which plots the rate of admissions per poisoning attendance against the rate of TOXBASE access per poisoning attendance. The data have been aggregated over trusts, so that each point in the plot corresponds to a month of data. The points are colored based on which year the data were observed in, and it can be seen that points observed in earlier years tend to be on the left-hand side of the plot, with later years sitting on the right-hand side of the plot. There is, overall, a decreasing trend in these observations, which is due to the overall temporal pattern, where the average rate of admission has decreased over time.
Examining individual groups of points, it can be seen that, particularly in recent years, there is positive correlation between the rate of admission and the rate of TOXBASE access per poisoning attendance.
It is this which is driving the positive coefficient for TOXBASE use in the models above (Tables 2 and 3).

Drug group specific modelling
We did not have access to diagnostic coding for attendances or admissions, preventing us from relating drug-specific TOXBASE accesses to attendances and admissions for that same drug. However, we obtained drug group TOXBASE access data for 6 important drug groups (antidepressants, paracetamol, antipsychotics, opioid medicines [excluding heroin], heroin, and non-opioid drugs of abuse, Table 4) and compared it with the overall proportion of poisoning admissions per Trust. Across groups, we noted regional variation in TOXBASE accesses, with London often being high or low for the proportion  of accesses to each drug group (Table 4, Supporting Information   Table S1).
Models were fit to assess the effect of TOXBASE access rates on admissions for these drug groups. The effects of the drugs categories on admission were in some cases quite different between London and elsewhere in England and Wales (Table 5

DISCUSSION
In this paper, we examined the interaction between hospital activityspecifically the decision to admit a poisoned patient attending the emergency department-and the level of use of the online poison information service TOXBASE. We used statistical models for this analy-   10 and in particular use of local management protocols, such as we have previously described. 11 The patterns of attendances and TOXBASE use are different in London compared to the rest of England and Wales. These findings are in line with the regional differences we have previously found in paracetamol poisoning admissions 12  Going forward, we believe these data have the potential to be used for audit of performance of individual units as a tool for public health, and to do that, optimally, we would need data on presentation ingestions to be included, which is not presently the case. This has also prevented analysis of admissions as a proportion of presentations for specific drugs. This is one reason we are unable to assess the reasons for different patterns in London and the rest of the United Kingdom.
Such information would also better support policy in managing poisoning in the United Kingdom.

LIMITATIONS
The paper is limited by our inability to show causality. However, because we show that the rates of admission are related to TOXBASE use at Trust level, and these effects are significant at the national level, the association has face validity.
Data had to be excluded from the analysis due to incompleteness or to inconsistency in the way attendance reasons were recorded. We are dependent on hospital coding for our analyses, with discharge coding being used in the case of admission. A proportion of coding errors are likely to have occurred in all hospitals but are unlikely to have affected our conclusions; furthermore, detailed analysis of discharge coding has suggested these are generally >95% accurate. 14 We have not considered the effect of National Poisons Information Service's telephone information services, which are available 24/7 to support clinicians managing more complex poisoning. However, because at least 97% of poison information enquiries from EDs come via the internet and TOXBASE, differences in telephone call numbers cannot explain the significant differences we have observed. It is also likely that most triage decisions occur after review of TOXBASE advice and not after a phone call, because these tend to deal with specific treatment advice. 6 The hospital attendance and admission data did not contain information on the agents involved, which may have confounded the analysis, particularly for smaller hospitals that receive fewer cases and do not tend to handle complex cases poisoning. However, as the data in England pertain to trusts, differences in case mix should have been averaged out. The imputation of small numbers could potentially add error, but this is minimized due to the inclusion of many of these smaller hospitals within the larger Trusts used in our analysis.
Finally, in the drug group-level analysis, access to specific drug groups on TOXBASE was used to describe the trend in drugs poisoning overall. A better comparison could be made if data were available on admissions and attendances due to poisoning by each specific drug group. However, even if the data were available, the number of admissions and attendances would be small, requiring a large amount of data suppression to maintain patient confidentiality, markedly reducing usability.

CONCLUSIONS
In summary, we have shown that increased hospital use of an internetbased poisons information database, TOXBASE, is associated with an increase in overall admission rates overall, but rates of access to particular drug groups differ in their relationships with admission rates.
These findings suggest a possible direct effect of TOXBASE on clinician behavior and patient management decisions and highlight the potential use of point-of-care internet poisons information systems.
Further mixed-methods research is required to obtain better evidence on how TOXBASE is used in EDs and how it might affect clinical practice.

AUTHOR CONTRIBUTIONS
KP and CR formulated and carried out the analysis presented. ME and ES contributed data and advice relating to TOXBASE. DNB and KP drafted the manuscript and all authors contributed to its revision.