Possible Sources of Bias in Primary Care Electronic Health Record Data Use and Reuse

Background - Enormous amounts of data are recorded routinely in health care as part of the care process, primarily for managing individual patient care. There are significant opportunities to use this data for other purposes, many of which would contribute to establishing a learning health system. This is particularly true for data recorded in primary care settings, as in many countries, these are the first place patients turn to for most health problems. Objective - In this paper, we discuss whether data that is recorded routinely as part of the health care process in primary care is actually fit to use for these other purposes, how the original purpose may affect the extent to which the data is fit for another purpose and the mechanisms behind these effects. In doing so, we want to identify possible sources of bias that are relevant for the (re-)use of this type of data. Methods –This discussion paper is based on the authors’ experience as users of electronic health records data, as a general practitioner, health informatics experts, and health services researchers. It is a product of the discussions they had during the TRANSFoRm project, which was funded by the EU and sought to develop, pilot and evaluate a core information architecture for the Learning Health System (LHS) in Europe, based on primary care electronic health records. Results – We first describe the different stages in the processing of EHR data, as well as the different purposes for which this data is used. Given the different data processing steps and purposes, we then discuss the possible mechanisms for each individual data processing step, that can generate biased outcomes. We identified thirteen possible sources of bias. Four of them are related to the organization of a health care system, some are of a more technical nature. Conclusions - There are a substantial number of possible sources of bias, and very little is known about the size and direction of their impact. However, any (re-)user of data that was recorded as part of the health care process (such as researchers and clinicians) should be aware of the associated data collection process and environmental influences that can affect the quality of the data. Our stepwise, actor and purpose oriented approach may help to identify these possible sources of bias. Unless data quality issues are better understood and unless adequate controls are embedded throughout the data lifecycle, data-driven healthcare will not live up to its expectations. We need a data quality research agenda to devise the appropriate instruments needed to assess the magnitude of each of the possible sources of bias, and then start measuring their impact. The possible sources of bias described in this paper serve as a starting point for this research agenda

Slower Decline in C-Reactive Protein after an Inflammatory Insult Is Associated with Longer Survival in Older Hospitalised Patients

Background Enhancing biological resilience may offer a novel way to prevent and ameliorate disease in older patients. We investigated whether changes in C-reactive protein (CRP), as a dynamic marker of the acute inflammatory response to diverse stressors, may provide a way to operationalize the concept of resilience in older adults. We tested this hypothesis by examining whether such changes could predict prognosis by identifying which individuals are at greater risk of 6-month mortality. Methods Analysis of prospective, routinely collected datasets containing data on hospitalization, clinical chemistry and rehabilitation outcomes for rehabilitation inpatients between 1999 and 2011. Maximum CRP response during acute illness and CRP recovery indices (time and slope of CRP decay to half maximum, and t

Predicting the Effect of Surface Texture on the Qualitative Form of Prehension

Reach-to-grasp movements change quantitatively in a lawful (i.e. predictable) manner with changes in object properties. We explored whether altering object texture would produce qualitative changes in the form of the precontact movement patterns. Twelve participants reached to lift objects from a tabletop. Nine objects were produced, each with one of three grip surface textures (high-friction, medium-friction and low-friction) and one of three widths (50 mm, 70 mm and 90 mm). Each object was placed at three distances (100 mm, 300 mm and 500 mm), representing a total of 27 trial conditions. We observed two distinct movement patterns across all trials—participants either: (i) brought their arm to a stop, secured the object and lifted it from the tabletop; or (ii) grasped the object ‘on-the-fly’, so it was secured in the hand while the arm was moving. A majority of grasps were on-the-fly when the texture was high-friction and none when the object was low-friction, with medium-friction producing an intermediate proportion. Previous research has shown that the probability of on-the-fly behaviour is a function of grasp surface accuracy constraints. A finger friction rig was used to calculate the coefficients of friction for the objects and these calculations showed that the area available for a stable grasp (the ‘functional grasp surface size’) increased with surface friction coefficient. Thus, knowledge of functional grasp surface size is required to predict the probability of observing a given qualitative form of grasping in human prehensile behaviour

Drug exposure risk windows and unexposed comparator groups for cohort studies in pharmacoepidemiology

Aim: To determine the appropriate size of risk windows in both exposed and unexposed sub-cohorts. Method: Data was taken from a previous study of upper gastrointestinal haemorrhage and perforation. The length of each prescription for NSAIDs was estimated. The risk was calculated for the duration of a prescription plus increments of -30, -25, ..., +115, +120 (i.e. 31 increments). Ten unexposed groups were re-sampled for each increment (stratified for age and sex), using the same lengths of risk window as the exposed group. Mean risks and rate-ratios were calculated (per thousand person-years). Results: The NSAID risk rose from 3·52 at -30 days to a peak of 5·82 at -15 days, and then decreased gradually to 2·83 at +120 days. Unexposed risk was variable for the negative increments, and decreased gradually from 2·16 at +0 days to 1·54 at +120 days. The rate-ratio rose from 1·55 at -30 days to a peak of 2·85 at -5 days, and then decreased to 1·85 at +120 days. Conclusion: Risk windows should be the same as (or slightly less than) the calculated length of a prescription. Lengthy windows should not be used for unexposed comparator groups (the exposed windows may be randomly allocated)

A cohort study (with re-sampled comparator groups) to measure the association between new NSAID prescribing and upper gastrointestinal hemorrhage and perforation

This cohort study examined the relationship between newly prescribed NSAIDs (none in the previous six months) and upper gastrointestinal hemorrhage and perforation in Tayside, Scotland. Exposure was classified by prescription duration. The study population consisted of the population of Tayside. A Comparator Group was chosen at random (within age and sex strata). Two hundred re-sampled comparator groups were created. Statistical analyses were carried out by Poisson regression (repeated for each of the re-samples). The analyses controlled for age, sex, prior hospitalization for upper gastrointestinal events, prior endoscopy, and the use of ulcer healing drugs. There were 78,191 subjects in the NSAID group, and 78,207 in each of the comparator groups. The increased risk with NSAIDs was only apparent for subjects without a history of upper gastrointestinal events; univariate rate ratio = 2.76 (1.90, 4.01). The final, re-sampled estimate of NSAID risk was rate ratio = 2.48 (1.87, 3.29)

Serum Sodium Level Variability As A Prognosticator In Older Adults

Our aim was to explore biological variation of serum sodium levels as a method of quantifying health risk in older adults. We investigated whether dynamic changes in serum sodium levels could provide additional prognostic information to standard predictors of mortality in older people. Analysis of routinely collected clinical datasets containing information on demographics, hospitalisation, biochemistry, haematology and physical function for Dundee in-patient rehabilitation services, between 1999 and 2011. Older people admitted to inpatient rehabilitation following an acute medical or surgical hospitalisation. Five dynamic measures of sodium levels homeostasis – minimum, maximum, standard deviation, and minimum and maximum deviation from mean – were derived for each individual, using biochemistry data from the year preceding their rehabilitation discharge. Cox regression models tested for associations with time to death. Covariates included age, sex, discharge Barthel score, co-morbid diagnoses, haemoglobin, albumin and eGFR. 3021 patients were included (mean age 84 years, 1776 (58.8%) females). 1651 (54.7%) patients experienced hyponatraemia and 446 (14.8%) became hypernatraemic. Mean sodium was correlated with all mean, minimum and SD of sodium. Kaplan–Meier survival curves showed that those without sodium perturbations had the best mortality outcomes, whilst those with both hyponatremia and hypernatremia had the worst. Multivariate Cox regression showed that standard deviation and hypernatraemia were significant predictors of death in non-adjusted models, but not fully adjusted models. All dynamic measures of dysnatraemia were associated with increased mortality risk, but failed to add predictive value to established static measures after adjusting for covariates

Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure

Non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in the aetiology of acute renal failure (ARF), but epidemiological studies examining this association have produced disparate results. We conducted a case-control study using a purposebuilt record-linkage database for a population of 420 600 patients, resident in Tayside since May 1990. Patients (n = 207) hospitalized with a diagnostic code for ARF between 1990 and 1992 had their diagnosis validated by a renal physician. Six community controls and two hospital controls, matched for age and sex, were generated for each of these cases. Exposure to dispensed oral NSAIDs, topical NSAIDs and aspirin during the 90 days prior to the index date were investigated (recent exposure), as was exposure at any time since January 1989 (previous exposure). The most significant associations were modelled using conditional logistic regression. When community controls were used, recent exposure to NSAIDs and previous exposure to aspirin were independently associated with hospitalization for ARF, with adjusted odds ratios of 2.20 (1.49-3.25) and 2.19 (1.46-3.30), respectively. Only recent exposure to oral NSAIDs was associated when hospital controls were used: 1.84 (1.14-2.93). No significant interactions were present with previous chronic renal failure, other possible causes of ARF or whether the diagnosis was primary or secondary. There is an approximate doubling of the risk of hospitalization for ARF with use of oral NSAIDs

Association Between Kidney Function, Rehabilitation Outcome, and Survival in Older Patients Discharged From Inpatient Rehabilitation

BackgroundChronic kidney disease (CKD) is common in older people, but it is unclear if it affects survival and rehabilitation outcomes independent of comorbid conditions and physical function in this population.Study DesignCohort analysis of prospective, routinely collected, linked clinical data sets.Setting & ParticipantsPatients discharged from a single inpatient geriatric rehabilitation center over a 12-year period.PredictorsAdmission estimated glomerular filtration rate (eGFR) category as a predictor of improvement in the 20-point Barthel score (activities of daily living measure) during rehabilitation; discharge eGFR category and Barthel score as predictors of survival postdischarge.OutcomesSurvival postdischarge was modeled using Cox regression analyses, unadjusted and adjusted for age, sex, morbidities (ischemic heart disease, chronic obstructive pulmonary disease, stroke, diabetes, and heart failure), Barthel score and eGFR category on discharge, and serum calcium, hemoglobin, and albumin levels. The effect of admission eGFR category on change in Barthel score during admission was modeled using analysis of covariance, adjusted for admission, Barthel score, and comorbid conditions.Results3,012 patients were included; mean age, 84 years. 2,394 patients died during a mean follow-up of 8.3 years. Compared with patients with eGFR of 60 to 89 mL/min/1.73 m2, adjusted HRs for death were 1.26 (95% CI, 1.13-1.40), 1.45 (95% CI, 1.29-1.63), and 1.68 (95% CI, 1.42-1.99) for eGFR categories of 45 to 59, 30 to 44, an