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1.  Impact analysis studies of clinical prediction rules relevant to primary care: a systematic review 
BMJ Open  2016;6(3):e009957.
Following appropriate validation, clinical prediction rules (CPRs) should undergo impact analysis to evaluate their effect on patient care. The aim of this systematic review is to narratively review and critically appraise CPR impact analysis studies relevant to primary care.
Primary care.
Adults and children.
Studies that implemented the CPR compared to usual care were included.
Study design
Randomised controlled trial (RCT), controlled before–after, and interrupted time series.
Primary outcome
Physician behaviour and/or patient outcomes.
A total of 18 studies, incorporating 14 unique CPRs, were included. The main study design was RCT (n=13). Overall, 10 studies reported an improvement in primary outcome with CPR implementation. Of 6 musculoskeletal studies, 5 were effective in altering targeted physician behaviour in ordering imaging for patients presenting with ankle, knee and neck musculoskeletal injuries. Of 6 cardiovascular studies, 4 implemented cardiovascular risk scores, and 3 reported no impact on physician behaviour outcomes, such as prescribing and referral, or patient outcomes, such as reduction in serum lipid levels. 2 studies examined CPRs in decision-making for patients presenting with chest pain and reduced inappropriate admissions. Of 5 respiratory studies, 2 were effective in reducing antibiotic prescribing for sore throat following CPR implementation. Overall, study methodological quality was often unclear due to incomplete reporting.
Despite increasing interest in developing and validating CPRs relevant to primary care, relatively few have gone through impact analysis. To date, research has focused on a small number of CPRs across few clinical domains only.
PMCID: PMC4800123  PMID: 27008685
risk prediction; clinical prediction rule; impact analysis
3.  Trends and interaction of polypharmacy and potentially inappropriate prescribing in primary care over 15 years in Ireland: a repeated cross-sectional study 
BMJ Open  2015;5(9):e008656.
To examine: (1) changes in polypharmacy in 1997, 2002, 2007 and 2012 and; (2) changes in potentially inappropriate prescribing (PIP) prevalence and the relationship between PIP and polypharmacy in individuals aged ≥65 years over this period in Ireland.
This repeated cross-sectional study using pharmacy claims data included all individuals eligible for the General Medical Services scheme in the former Eastern Health Board region of Ireland in 1997, 2002, 2007 and 2012 (range 338 025–539 752 individuals). Outcomes evaluated were prevalence of polypharmacy (being prescribed ≥5 regular medicines) and excessive polypharmacy (≥10 regular medicines) in all individuals and PIP prevalence in those aged ≥65 years determined by 30 criteria from the Screening Tool for Older Persons’ Prescriptions.
The prevalence of polypharmacy increased from 1997 to 2012, particularly among older individuals (from 17.8% to 60.4% in those aged ≥65 years). The adjusted incident rate ratio for polypharmacy in 2012 compared to 1997 was 4.16 (95% CI 3.23 to 5.36), and for excessive polypharmacy it was 10.53 (8.58 to 12.91). Prevalence of PIP rose from 32.6% in 1997 to 37.3% in 2012. High-dose aspirin and digoxin prescribing decreased over time, but long-term proton pump inhibitors at maximal dose increased substantially (from 0.8% to 23.8%). The odds of having any PIP in 2012 were lower compared to 1997 after controlling for gender and level of polypharmacy, OR 0.39 (95% CI 0.39 to 0.4).
Accounting for the marked increase in polypharmacy, prescribing quality appears to have improved with a reduction in the odds of having PIP from 1997 to 2012. With growing numbers of people taking multiple regular medicines, strategies to address the related challenges of polypharmacy and PIP are needed.
PMCID: PMC4577876  PMID: 26384726
4.  Psychostimulant prescribing trends in a paediatric population in Ireland: a national cohort study 
BMC Pediatrics  2015;15:118.
Psychotropic paediatric prescribing trends are increasing internationally. The aim of this study is to examine the prevalence and secular trends in psychotropic prescribing in Irish children and adolescents between 2002 and 2011.
Data was obtained from the Irish General Medical Services (GMS) scheme pharmacy claims database from the Health Service Executive Primary Care Reimbursement Services (HSE-PCRS). Prescribing rates per 1000 eligible population and associated 95 % confidence intervals (CIs) were calculated across years (2002–2011), age groups (0–4, 5–11, 12–15 years) and gender. Rates of concomitant prescriptions for psycholeptics and antidepressants were also examined. The total expenditure costs were calculated and expressed as a percentage of the cost of all prescriptions for this age group (≤15 years).
In 2002, 3.77/1000 GMS population (95 % CI: 3.53–4.01) received at least one psychostimulant prescription and this rate increased to 8.63/1000 GMS population (95 % CI: 8.34–8.92) in 2011. Methylphenidate was the most frequently prescribed psychostimulant. For both males and females the prevalence of medication use was highest among the 12–15 year old group. On average, a psycholeptic medication was prescribed to 8 % of all psychostimulant users and an antidepressant was concomitantly prescribed on average to 2 %. Total expenditure rose from €89,254 in 2002 to €1,532,016 in 2011.
The rate and cost of psychostimulant prescribing among GMS children and adolescents in Ireland increased significantly between 2002 and 2011. Further research is necessary to assess the safety, efficacy and economic impact of concomitant psychotropic prescribing in this population.
PMCID: PMC4566369  PMID: 26357902
Children; Pharmacoepidemiology; ADHD; Psychostimulant treatment
5.  Statin use in adults at high risk of cardiovascular disease mortality: cross-sectional analysis of baseline data from The Irish Longitudinal Study on Ageing (TILDA) 
BMJ Open  2015;5(7):e008017.
This study aims to examine the extent to which statins are used by adults at high risk of cardiovascular disease (CVD) compared to European clinical guidelines. The high-risk groups examined are those with (1) known CVD, (2) known diabetes and (3) a high or very high risk (≥5%) of CVD mortality based on Systematic COronary Risk Evaluation (SCORE).
This study is cross-sectional in design using data from the first wave (2009–2011) of The Irish Longitudinal Study on Ageing (TILDA).
Setting and participants
The sample (n=3372) is representative of community living adults aged 50–64 years in Ireland.
Statins were used by 68.6% (95% CI 61.5% to 75.8%) of those with known CVD, 57.4% (95% CI 49.1% to 65.7%) of those with known diabetes and by 19.7% (95% CI 13.0% to 26.3%) of adults with a SCORE risk ≥5%. Over a third (38.5%, 95% CI 31.0% to 46.0%) of those with known CVD, 46.8% (95% CI 38.4% to 55.1%) of those with known diabetes and 85.2% (95% CI 79.3% to 91.1%) of those with a SCORE risk ≥5% were at or above the low-density lipoprotein cholesterol (LDL-C) target of 2.5 mmol/L specified in the 2007 European guidelines.
Despite strong evidence and clinical guidelines recommending the use of statins for secondary prevention, a gap exists between guidelines and practice in this cohort. It is also of concern that a low proportion of adults with a SCORE risk ≥5% were taking statins. A policy response that strengthens secondary prevention, and improves risk assessment and shared decision-making in the primary prevention of CVD is required.
PMCID: PMC4513517  PMID: 26169806
6.  A Multistep Maturity Model for the Implementation of Electronic and Computable Diagnostic Clinical Prediction Rules (eCPRs) 
eGEMs  2015;3(2):1153.
The use of Clinical Prediction Rules (CPRs) has been advocated as one way of implementing actionable evidence-based rules in clinical practice. The current highly manual nature of deriving CPRs makes them difficult to use and maintain. Addressing the known limitations of CPRs requires implementing more flexible and dynamic models of CPR development. We describe the application of Information and Communication Technology (ICT) to provide a platform for the derivation and dissemination of CPRs derived through analysis and continual learning from electronic patient data.
Model Components:
We propose a multistep maturity model for constructing electronic and computable CPRs (eCPRs). The model has six levels – from the lowest level of CPR maturity (literaturebased CPRs) to a fully electronic and computable service-oriented model of CPRs that are sensitive to specific demographic patient populations. We describe examples of implementations of the core model components – focusing on CPR representation, interoperability, electronic dissemination, CPR learning, and user interface requirements.
The traditional focus on derivation and narrow validation of CPRs has severely limited their wider acceptance. The evolution and maturity model described here outlines a progression toward eCPRs consistent with the vision of a learning health system (LHS) – using central repositories of CPR knowledge, accessible open standards, and generalizable models to avoid repetition of previous work. This is useful for developing more ambitious strategies to address limitations of the traditional CPR development life cycle. The model described here is a starting point for promoting discussion about what a more dynamic CPR development process should look like.
PMCID: PMC4537149  PMID: 26290890
Evidence Based Medicine; Health Information Technology; Research Translation; Clinical Prediction Rules; Learning Health System
7.  Prevalence and predictors of initial oral antibiotic treatment failure in adult emergency department patients with cellulitis: a pilot study 
BMJ Open  2015;5(6):e008150.
Assessment of cellulitis severity in the emergency department (ED) setting is problematic. Given the lack of research performed to describe the epidemiology and management of cellulitis, it is unsurprising that heterogeneous antibiotic prescribing and poor adherence to guidelines is common. It has been shown that up to 20.5% of ED patients with cellulitis require either a change in route or dose of the initially prescribed antibiotic regimen. The current treatment failure rate for empirically prescribed oral antibiotic therapy in Irish EDs is unknown. The association of patient risk factors with treatment failure has not been described in our setting. Lower prevalence of community-acquired methicillin-resistant Staphylococcus aureus-associated infection, differing antibiotic prescribing preferences and varying availability of outpatient intravenous therapy programmes may result in different rates of empiric antibiotic treatment failure from those previously described.
Methods and analysis
Consecutive ED patients with cellulitis will be enrolled on a 24/7 basis from 3 Irish EDs. A prespecified set of clinical variables will be measured on each patient discharged on empiric oral antibiotic therapy. A second independent study recruiter will assess at least 10% of cases for each of the predictor variables. Follow-up by telephone call will occur at 14 days for all discharged patients where measurement of the primary outcome will occur. Our primary outcome is treatment failure, defined as a change in route of antibiotic administration from oral to intravenous antibiotic. Our secondary outcome is change in dose or type of prescribed antibiotic. A cohort of approximately 152 patients is required to estimate the proportion of patients failing oral antibiotic treatment with a margin of error of 0.05 around the estimate.
Ethics and dissemination
Full ethics approval has been granted. An integrated dissemination plan, involving diverse clinical specialties and enrolled patients, is described.
Trial registration number
NCT 02230813.
PMCID: PMC4486970  PMID: 26112223
8.  A simplified approach to the pooled analysis of calibration of clinical prediction rules for systematic reviews of validation studies 
Clinical Epidemiology  2015;7:267-280.
Estimating calibration performance of clinical prediction rules (CPRs) in systematic reviews of validation studies is not possible when predicted values are neither published nor accessible or sufficient or no individual participant or patient data are available. Our aims were to describe a simplified approach for outcomes prediction and calibration assessment and evaluate its functionality and validity.
Study design and methods:
Methodological study of systematic reviews of validation studies of CPRs: a) ABCD2 rule for prediction of 7 day stroke; and b) CRB-65 rule for prediction of 30 day mortality. Predicted outcomes in a sample validation study were computed by CPR distribution patterns (“derivation model”). As confirmation, a logistic regression model (with derivation study coefficients) was applied to CPR-based dummy variables in the validation study. Meta-analysis of validation studies provided pooled estimates of “predicted:observed” risk ratios (RRs), 95% confidence intervals (CIs), and indexes of heterogeneity (I2) on forest plots (fixed and random effects models), with and without adjustment of intercepts. The above approach was also applied to the CRB-65 rule.
Our simplified method, applied to ABCD2 rule in three risk strata (low, 0–3; intermediate, 4–5; high, 6–7 points), indicated that predictions are identical to those computed by univariate, CPR-based logistic regression model. Discrimination was good (c-statistics =0.61–0.82), however, calibration in some studies was low. In such cases with miscalibration, the under-prediction (RRs =0.73–0.91, 95% CIs 0.41–1.48) could be further corrected by intercept adjustment to account for incidence differences. An improvement of both heterogeneities and P-values (Hosmer-Lemeshow goodness-of-fit test) was observed. Better calibration and improved pooled RRs (0.90–1.06), with narrower 95% CIs (0.57–1.41) were achieved.
Our results have an immediate clinical implication in situations when predicted outcomes in CPR validation studies are lacking or deficient by describing how such predictions can be obtained by everyone using the derivation study alone, without any need for highly specialized knowledge or sophisticated statistics.
PMCID: PMC4404967  PMID: 25931829
clinical prediction rules; derivation; validation; meta-analysis; primary care
9.  Clinical prediction rules in practice: review of clinical guidelines and survey of GPs 
The British Journal of General Practice  2014;64(621):e233-e242.
The publication of clinical prediction rules (CPRs) studies has risen significantly. It is unclear if this reflects increasing usage of these tools in clinical practice or how this may vary across clinical areas.
To review clinical guidelines in selected areas and survey GPs in order to explore CPR usefulness in the opinion of experts and use at the point of care.
Design and setting
A review of clinical guidelines and survey of UK GPs.
Clinical guidelines in eight clinical domains with published CPRs were reviewed for recommendations to use CPRs including primary prevention of cardiovascular disease, transient ischaemic attack (TIA) and stroke, diabetes mellitus, fracture risk assessment in osteoporosis, lower limb fractures, breast cancer, depression, and acute infections in childhood. An online survey of 401 UK GPs was also conducted.
Guideline review: Of 7637 records screened by title and/or abstract, 243 clinical guidelines met inclusion criteria. CPRs were most commonly recommended in guidelines regarding primary prevention of cardiovascular disease (67%) and depression (67%). There was little consensus across various clinical guidelines as to which CPR to use preferentially. Survey: Of 401 responders to the GP survey, most were aware of and applied named CPRs in the clinical areas of cardiovascular disease and depression. The commonest reasons for using CPRs were to guide management and conform to local policy requirements.
GPs use CPRs to guide management but also to comply with local policy requirements. Future research could focus on which clinical areas clinicians would most benefit from CPRs and promoting the use of robust, externally validated CPRs.
PMCID: PMC3964449  PMID: 24686888
clinical prediction rules; clinical guidelines; survey
10.  Prevalence of prescribing in pregnancy using the Irish primary care research network: a pilot study 
To establish the prevalence and patterns of prescribing to pregnant women in an Irish primary care setting.
We reviewed electronic healthcare records routinely collected in primary care, of pregnant women attending nine Dublin-based General Practices affiliated to the Irish Primary Care Research Network (IPCRN) for antenatal care between January 2007 and October 2013 (n = 2,361 pregnancies).
Excluding folic acid, 46.8% (n = 1,104) of pregnant women were prescribed at least one medication. Amoxicillin (11.1%, n = 263) and co-amoxiclav (8.0%, n = 190) were the most commonly prescribed medication followed by topical clotrimazole (4.9%, n = 117), salbutamol inhalers (4.1%, n = 96) and paracetamol (4.0%, n = 95). General Medical Services (GMS) patients were more likely to receive a prescription than private patients (OR 2.81; 95%CI (2.28, 3.47)). We applied the US FDA pregnancy-risk categories as a proxy measure of prescribing appropriateness, with FDA Category D and X medications considered inappropriate. FDA Category D drugs were prescribed in 5.9% (n = 140) of pregnancies. FDA Category X drugs were prescribed in 4.9% (n = 116) of pregnancies but after exclusion of oral contraceptives, progestogens, infertility treatments Category X medications were prescribed in 0.6% (n = 13) of pregnancies. After the initial antenatal consultation the prescribing prevalence of FDA Category D medications reduced to 4.7% (n = 110) and Category X to 3.1% (n = 72).
The overall prevalence of prescribing to pregnant women in our cohort is low compared to studies internationally, however similar levels of prescribing for FDA Category D and X were found. Following the initial antenatal consultation levels of prescribing of the FDA Category D and X medications reduced, however there is potential to further reduce their use in early pregnancy. The IPCRN database has provided valuable information on the current practice of antenatal prescribing within this pilot group of practices however it is limited by the absence of morbidity and pregnancy outcome data.
PMCID: PMC4389301  PMID: 25884886
Prescribing; Medication use; Pregnancy; FDA pregnancy-risk categories
11.  Health and use of health services of people who are homeless and at risk of homelessness who receive free primary health care in Dublin 
Homeless populations experience poorer physical and mental health, and more barriers to accessing adequate healthcare. This study investigates the health of this population, following the provision of a free to access primary care service for homeless people in Dublin (Safetynet). The health of this group will be compared to previous studies on homelessness conducted in Dublin prior to the establishment of this service (in 1997 and 2005).
Participants were recruited through Safetynet clinics. A 133-item questionnaire was administered to determine participants’ physical and mental well-being, use of health services and healthcare needs. Prescription data was extracted from participants’ electronic health records.
A total of 105 participants were recruited. The majority were < 45 years of age (69%), male (75%), single (52%), Irish (74%) and had children (52%). Multimorbidity was common; with 5.3 ± 2.7 (mean ± SD) physical conditions reported per person. A large proportion of participants had at some point received a formal diagnosis of a mental health condition (70%; 73/105), including depression (50%; 52/105), addiction disorder (39%), anxiety (36%; 38/105), schizophrenia (13%; 14/105) and bipolar disorder (6%; 6/105). With regards to illicit drug use, 60% (63/105) of participants reported ever using drugs, while 33% (35/105) reported being active drug users. Based on AUDIT C criteria, 53% had an alcohol problem. Compared to previous studies, participants reported more positive ratings of health (70% vs. 57% in 1997 and 46% in 2005). The proportion of participants on one or more prescription medication was higher than in previous studies (81% vs. 32% in 1997 and 49% in 2005) and there was a decrease in attendance at outpatients departments (17% vs. 27% in 2005) and a trend towards a decrease in attendance at Accident and Emergency departments (A & E) (29% vs. 37% in 2005).
This vulnerable population has many physical and mental health problems. Use of drugs, alcohol and smoking is common. Following the establishment of Safetynet, self-reported health was rated more positively, there was also a decrease in the use of A & E and outpatient services and an increase in prescription medicines.
Electronic supplementary material
The online version of this article (doi:10.1186/s12913-015-0716-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4343065  PMID: 25884629
12.  Longitudinal prevalence of potentially inappropriate medicines and potential prescribing omissions in a cohort of community-dwelling older people 
This study aims to compare the prevalence of potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs) using several screening tools in an Irish community-dwelling older cohort, to assess if the prevalence changes over time and to determine factors associated with any change.
This is a prospective cohort study of participants aged ≥65 years in The Irish Longitudinal Study on Ageing (TILDA) with linked pharmacy claims data (n = 2051). PIM and PPO prevalence was measured in the year preceding participants’ TILDA baseline interviews and in the year preceding their follow-up interviews using the Screening Tool for Older Persons’ Prescriptions (STOPP), Beers criteria (2012), Assessing Care of Vulnerable Elders (ACOVE) indicators and the Screening Tool to Alert doctors to Right Treatment (START). Generalised estimating equations were used to determine factors associated with change in prevalence over time.
Depending on the screening tool used, between 19.8 % (ACOVE indicators) and 52.7 % (STOPP) of participants received a PIM at baseline, and PPO prevalence ranged from 38.2 % (START) to 44.8 % (ACOVE indicators), while 36.7 % of participants had both a PIM and PPO. Common criteria were aspirin for primary prevention (19.6 %) and omission of calcium/vitamin D in osteoporosis (14.7 %). Prevalence of PIMs and PPOs increased at follow-up (PIMs range 22–56.1 %, PPOs range 40.5–49.3 %), and this was associated with patient age, female sex, and numbers of medicines and chronic conditions.
Sub-optimal prescribing is common in older patients. Ongoing prescribing review to optimise care is important, particularly as patients get older, receive more medicines or develop more illnesses.
Electronic supplementary material
The online version of this article (doi:10.1007/s00228-015-1815-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4356885  PMID: 25666030
STOPP; START; Beers criteria; ACOVE indicators; Cohort; Potentially inappropriate prescribing
13.  TElehealth in CHronic disease: mixed-methods study to develop the TECH conceptual model for intervention design and evaluation 
BMJ Open  2015;5(2):e006448.
To develop a conceptual model for effective use of telehealth in the management of chronic health conditions, and to use this to develop and evaluate an intervention for people with two exemplar conditions: raised cardiovascular disease risk and depression.
The model was based on several strands of evidence: a metareview and realist synthesis of quantitative and qualitative evidence on telehealth for chronic conditions; a qualitative study of patients’ and health professionals’ experience of telehealth; a quantitative survey of patients’ interest in using telehealth; and review of existing models of chronic condition management and evidence-based treatment guidelines. Based on these evidence strands, a model was developed and then refined at a stakeholder workshop. Then a telehealth intervention (‘Healthlines’) was designed by incorporating strategies to address each of the model components. The model also provided a framework for evaluation of this intervention within parallel randomised controlled trials in the two exemplar conditions, and the accompanying process evaluations and economic evaluations.
Primary care.
The TElehealth in CHronic Disease (TECH) model proposes that attention to four components will offer interventions the best chance of success: (1) engagement of patients and health professionals, (2) effective chronic disease management (including subcomponents of self-management, optimisation of treatment, care coordination), (3) partnership between providers and (4) patient, social and health system context. Key intended outcomes are improved health, access to care, patient experience and cost-effective care.
A conceptual model has been developed based on multiple sources of evidence which articulates how telehealth may best provide benefits for patients with chronic health conditions. It can be used to structure the design and evaluation of telehealth programmes which aim to be acceptable to patients and providers, and cost-effective.
PMCID: PMC4322202  PMID: 25659890
14.  Potentially inappropriate prescribing and adverse health outcomes in community dwelling older patients 
This study aimed to determine the association between potentially inappropriate prescribing (PIP) and health related outcomes [adverse drug events (ADEs), health related quality of life (HRQOL) and hospital accident and emergency (A&E) visits] in older community dwelling patients.
A retrospective cohort study of 931 community dwelling patients aged ≥70 years in 15 general practices in Ireland in 2010. PIP was defined by the Screening Tool of Older Person's Prescriptions (STOPP). ADEs were measured by patient self-report and medical record for the previous 6 months and reviewed by two independent clinicians. HRQOL was measured by the EQ-5D. A&E visits were measured by patients’ medical records and self-report. Multilevel logistic, linear and Poisson regression examined how ADEs, HRQOL and A&E visits varied by PIP after adjusting for patient and practice level covariates: socioeconomic status, co-morbidity, number of drug classes and adherence.
The overall prevalence of PIP was 42% (n = 377). Patients with ≥2 PIP indicators were twice as likely to have an ADE (adjusted OR 2.21; 95% CI 1.02, 4.83, P < 0.05), have a significantly lower mean HRQOL utility (adjusted coefficient −0.09, SE 0.02, P < 0.001) and nearly a two-fold increased risk in the expected rate of A&E visits (adjusted IRR 1.85; 95% CI 1.32, 2.58, P < 0.001). The number of drug classes and adherence were also significantly associated with these same adverse health outcomes.
Reducing PIP in primary care may help lower the burden of ADEs, its associated health care use and costs and enhance quality of life in older patients.
PMCID: PMC3895361  PMID: 23711082
adverse drug events; health care use; HRQOL; older populations; potentially inappropriate prescribing; STOPP
15.  Risk Prediction Models to Predict Emergency Hospital Admission in Community-dwelling Adults 
Medical Care  2014;52(8):751-765.
Supplemental Digital Content is available in the text.
Risk prediction models have been developed to identify those at increased risk for emergency admissions, which could facilitate targeted interventions in primary care to prevent these events.
Systematic review of validated risk prediction models for predicting emergency hospital admissions in community-dwelling adults.
A systematic literature review and narrative analysis was conducted. Inclusion criteria were as follows; Population: community-dwelling adults (aged 18 years and above); Risk: risk prediction models, not contingent on an index hospital admission, with a derivation and ≥1 validation cohort; Primary outcome: emergency hospital admission (defined as unplanned overnight stay in hospital); Study design: retrospective or prospective cohort studies.
Of 18,983 records reviewed, 27 unique risk prediction models met the inclusion criteria. Eleven were developed in the United States, 11 in the United Kingdom, 3 in Italy, 1 in Spain, and 1 in Canada. Nine models were derived using self-report data, and the remainder (n=18) used routine administrative or clinical record data. Total study sample sizes ranged from 96 to 4.7 million participants. Predictor variables most frequently included in models were: (1) named medical diagnoses (n=23); (2) age (n=23); (3) prior emergency admission (n=22); and (4) sex (n=18). Eleven models included nonmedical factors, such as functional status and social supports. Regarding predictive accuracy, models developed using administrative or clinical record data tended to perform better than those developed using self-report data (c statistics 0.63–0.83 vs. 0.61–0.74, respectively). Six models reported c statistics of >0.8, indicating good performance. All 6 included variables for prior health care utilization, multimorbidity or polypharmacy, and named medical diagnoses or prescribed medications. Three predicted admissions regarded as being ambulatory care sensitive.
This study suggests that risk models developed using administrative or clinical record data tend to perform better. In applying a risk prediction model to a new population, careful consideration needs to be given to the purpose of its use and local factors.
PMCID: PMC4219489  PMID: 25023919
risk prediction model; emergency hospital admission; community-dwelling adults
16.  The development of the PROMPT (PRescribing Optimally in Middle-aged People’s Treatments) criteria 
Whilst multimorbidity is more prevalent with increasing age, approximately 30% of middle-aged adults (45–64 years) are also affected. Several prescribing criteria have been developed to optimise medication use in older people (≥65 years) with little focus on potentially inappropriate prescribing (PIP) in middle-aged adults. We have developed a set of explicit prescribing criteria called PROMPT (PRescribing Optimally in Middle-aged People’s Treatments) which may be applied to prescribing datasets to determine the prevalence of PIP in this age-group.
A literature search was conducted to identify published prescribing criteria for all age groups, with the Project Steering Group (convened for this study) adding further criteria for consideration, all of which were reviewed for relevance to middle-aged adults. These criteria underwent a two-round Delphi process, using an expert panel consisting of general practitioners, pharmacists and clinical pharmacologists from the United Kingdom and Republic of Ireland. Using web-based questionnaires, 17 panellists were asked to indicate their level of agreement with each criterion via a 5-point Likert scale (1 = Strongly Disagree, 5 = Strongly Agree) to assess the applicability to middle-aged adults in the absence of clinical information. Criteria were accepted/rejected/revised dependent on the panel’s level of agreement using the median response/interquartile range and additional comments.
Thirty-four criteria were rated in the first round of this exercise and consensus was achieved on 17 criteria which were accepted into the PROMPT criteria. Consensus was not reached on the remaining 17, and six criteria were removed following a review of the additional comments. The second round of this exercise focused on the remaining 11 criteria, some of which were revised following the first exercise. Five criteria were accepted from the second round, providing a final list of 22 criteria [gastro-intestinal system (n = 3), cardiovascular system (n = 4), respiratory system (n = 4), central nervous system (n = 6), infections (n = 1), endocrine system (n = 1), musculoskeletal system (n = 2), duplicates (n = 1)].
PROMPT is the first set of prescribing criteria developed for use in middle-aged adults. The utility of these criteria will be tested in future studies using prescribing datasets.
PMCID: PMC4229620  PMID: 25410615
Potentially inappropriate prescribing; Explicit criteria; Delphi technique; Middle-age; Polypharmacy; Multimorbidity
17.  Development and validation of a clinical prediction rule to identify suspected breast cancer: a prospective cohort study 
BMC Cancer  2014;14:743.
The number of primary care referrals of women with breast symptoms to symptomatic breast units (SBUs) has increased exponentially in the past decade in Ireland. The aim of this study is to develop and validate a clinical prediction rule (CPR) to identify women with breast cancer so that a more evidence based approach to referral from primary care to these SBUs can be developed.
We analysed routine data from a prospective cohort of consecutive women reviewed at a SBU with breast symptoms. The dataset was split into a derivation and validation cohort. Regression analysis was used to derive a CPR from the patient’s history and clinical findings. Validation of the CPR consisted of estimating the number of breast cancers predicted to occur compared with the actual number of observed breast cancers across deciles of risk.
A total of 6,590 patients were included in the derivation study and 4.9% were diagnosed with breast cancer. Independent clinical predictors for breast cancer were: increasing age by year (adjusted odds ratio 1.08, 95% CI 1.07-1.09); presence of a lump (5.63, 95% CI 4.2-7.56); nipple change (2.77, 95% CI 1.68-4.58) and nipple discharge (2.09, 95% CI 1.1-3.97). Validation of the rule (n = 911) demonstrated that the probability of breast cancer was higher with an increasing number of these independent variables. The Hosmer-Lemeshow goodness of fit showed no overall significant difference between the expected and the observed numbers of breast cancer (χ2HL: 6.74, p-value: 0.56).
This study derived and validated a CPR for breast cancer in women attending an Irish national SBU. We found that increasing age, presence of a lump, nipple discharge and nipple change are all associated with increased risk of breast cancer. Further validation of the rule is necessary as well as an assessment of its impact on referral practice.
PMCID: PMC4197234  PMID: 25277332
Breast cancer; Diagnosis; Primary care
18.  Interventions to improve adherence to lipid lowering medication 
Lipid lowering drugs are still widely underused, despite compelling evidence about their effectiveness in the treatment and prevention of cardiovascular disease. Poor patient adherence to medication regimen is a major factor in the lack of success in treating hyperlipidaemia. In this review we focus on interventions, which encourage patients at risk of heart disease or stroke to take lipid lowering medication regularly.
To assess the effect of interventions aiming at improved adherence to lipid lowering drugs, focusing on measures of adherence and clinical outcomes.
Search strategy
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycInfo and CINAHL. Date of most recent search was in February 2003. No language restrictions were applied.
Selection criteria
Randomised controlled trials of adherence-enhancing interventions to lipid lowering medication in adults for both primary and secondary prevention of cardiovascular disease in an ambulatory setting.
Data collection and analysis
Two reviewers extracted data independently and assessed studies according to criteria outlined by the Cochrane Reviewers’ Handbook.
Main results
The eight studies found contained data on 5943 patients. Interventions could be stratified into four categories: 1. simplification of drug regimen, 2. patient information/education, 3. intensified patient care such as reminding and 4. complex behavioural interventions such as group sessions. Change in adherence ranged from −3% to 25% (decrease in adherence by 3% to increase in adherence by 25%). Three studies reported significantly improved adherence through simplification of drug regimen (category 1), improved patient information/education (category 2) and reminding (category 3). The fact that the successful interventions were evenly spread across the categories, does not suggest any advantage of one particular type of intervention. The methodological and analytical quality was generally low and results have to be considered with caution. Combining data was not appropriate due to the substantial heterogeneity between included randomised controlled trials (RCTs).
Authors’ conclusions
At this stage, no specific intervention aimed at improving adherence to lipid lowering drugs can be recommended. The lack of a gold standard method of measuring adherence is one major barrier in adherence research. More reliable data might be achieved by newer methods of measurement, more consistency in adherence assessment and longer duration of follow-up. Increased patient-centredness with emphasis on the patient’s perspective and shared-decision-making might lead to more conclusive answers when searching for tools to encourage patients to take lipid lowering medication.
PMCID: PMC4163627  PMID: 15495105
*Patient Compliance; Antilipemic Agents [*therapeutic use]; Cardiovascular Diseases [prevention & control]; Randomized Controlled Trials as Topic; Humans
19.  Potentially inappropriate prescribing among older people in the United Kingdom 
BMC Geriatrics  2014;14:72.
Potentially inappropriate prescribing (PIP) in older people is associated with increases in morbidity, hospitalisation and mortality. The objective of this study was to estimate the prevalence of and factors associated with PIP, among those aged ≥70 years, in the United Kingdom, using a comprehensive set of prescribing indicators and comparing these to estimates obtained from a truncated set of the same indicators.
A retrospective cross-sectional study was carried out in the UK Clinical Practice Research Datalink (CPRD), in 2007. Participants included those aged ≥ 70 years, in CPRD. Fifty-two PIP indicators from the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria were applied to data on prescribed drugs and clinical diagnoses. Overall prevalence of PIP and prevalence according to individual STOPP criteria were estimated. The relationship between PIP and polypharmacy (≥4 medications), comorbidity, age, and gender was examined. A truncated, subset of 28 STOPP criteria that were used in two previous studies, were further applied to the data to facilitate comparison.
Using 52 indicators, the overall prevalence of PIP in the study population (n = 1,019,491) was 29%. The most common examples of PIP were therapeutic duplication (11.9%), followed by use of aspirin with no indication (11.3%) and inappropriate use of proton pump inhibitors (PPIs) (3.7%). PIP was strongly associated with polypharmacy (Odds Ratio 18.2, 95% Confidence Intervals, 18.0-18.4, P < 0.05). PIP was more common in those aged 70–74 years vs. 85 years or more and in males. Application of the smaller subset of the STOPP criteria resulted in a lower PIP prevalence at 14.9% (95% CIs 14.8-14.9%) (n = 151,598). The most common PIP issues identified with this subset were use of PPIs at maximum dose for > 8 weeks, NSAIDs for > 3 months, and use of long-term neuroleptics.
PIP was prevalent in the UK and increased with polypharmacy. Application of the comprehensive set of STOPP criteria allowed more accurate estimation of PIP compared to the subset of criteria used in previous studies. These findings may provide a focus for targeted interventions to reduce PIP.
PMCID: PMC4091750  PMID: 24919523
Potentially inappropriate prescribing; Older people; Screening tool of older persons potentially inappropriate Prescriptions (STOPP); CPRD
20.  Long-term risk of stroke after transient ischaemic attack: a hospital-based validation of the ABCD2 rule 
BMC Research Notes  2014;7:281.
The ABCD2 clinical prediction rule is a seven point summation of clinical factors independently predictive of stroke risk. The purpose of this cohort study is to validate the ABCD2 rule in a Bulgarian hospital up to three years after TIA.
All consecutive admissions to an emergency department with symptoms of a first TIA were included. Baseline data and clinical examinations including the ABCD2 scores were documented by neurologists. Discrimination and calibration performance was examined using ABCD2 cut-off scores of ≥3, ≥4 and ≥5 points, consistent with the international guidelines. The Hosmer-Lemeshow test was used to examine calibration between the observed and expected outcomes as predicted by ABCD2 score within the logistic regression analysis.
Eighty-nine patients were enrolled to the study with a mean age of 63 years (+/- 12 years). Fifty-nine percent (n = 53) of the study population was male. Seven strokes (7 · 8%) occurred within the first year and six further strokes within the three-year follow-up period. There was no incident of stroke within the first 90 days after TIA. The rule demonstrated good predictive (OR = 1 · 58, 95% CI 1 · 09-2 · 29) and discriminative performance (AUCROC = 0 · 72, 95% CI 0 · 58-0 · 86), as well as a moderate calibration performance at three years.
This validation of the ABCD2 rule in a Bulgarian hospital demonstrates that the rule has good predictive and discriminative performance at three years. The ABCD2 is quick to administer and may serve as a useful tool to assist clinicians in the long-term management of individuals with TIA.
PMCID: PMC4013429  PMID: 24886654
Stroke; Transient ischaemic attack; Risk prediction; ABCD2 rule; Bulgaria
21.  Potential for alcohol and drug interactions in older adults: evidence from the Irish longitudinal study on ageing 
BMC Geriatrics  2014;14:57.
Older adults are susceptible to adverse effects from the concomitant use of prescription medications and alcohol. This study estimates the prevalence of exposure to alcohol interactive (AI) medications and concomitant alcohol use by therapeutic class in a large, nationally representative sample of older adults.
Cross-sectional analysis of a population based sample of older Irish adults aged ≥60 years using data from The Irish Longitudinal Study on Ageing (TILDA) (N = 3,815). AI medications were identified using Stockley’s Drug Interactions, the British National Formulary and the Irish Medicines Formulary. An in-home inventory of medications was used to characterise AI drug exposure by therapeutic class. Self-reported alcohol use was classified as non-drinker, light/moderate and heavy drinking. Comorbidities known to be exacerbated by alcohol were also recorded (diabetes mellitus, hypertension, peptic ulcer disease, liver disease, depression, gout or breast cancer), as well as sociodemographic and health factors.
Seventy-two per cent of participants were exposed to AI medications, with greatest exposure to cardiovascular and CNS agents. Overall, 60% of participants exposed to AI medications reported concomitant alcohol use, compared with 69.5% of non-AI exposed people (p < 0.001). Almost 28% of those reporting anti-histamine use were identified as heavy drinkers. Similarly almost one in five, combined heavy drinking with anti-coagulants/anti-platelets and cardiovascular agents, with 16% combining heavy drinking with CNS agents. Multinomial logistic regression showed that being male, younger, urban dwelling, with higher levels of education and a history of smoking, were associated with an increased risk for concomitant exposure to alcohol consumption (both light/moderate and heavier) and AI medications. Current smokers and people with increasing co-morbidities were also at greatest risk for heavy drinking in combination with AI medications.
The concurrent use of alcohol with AI medications, or with conditions known to be exacerbated by alcohol, is common among older Irish adults. Prescribers should be aware of potential interactions, and screen patients for alcohol use and provide warnings to minimize patient risk.
PMCID: PMC4008399  PMID: 24766969
Drug interactions; Alcohol interactive medications; Alcohol drinking/epidemiology; Aged
22.  Prescriber variation in potentially inappropriate prescribing in older populations in Ireland 
BMC Family Practice  2014;15:59.
Health care policy-makers look for prescribing indicators at the population level to evaluate the performance of prescribers, improve quality and control drug costs. The aim of this research was to; (i) estimate the level of variation in potentially inappropriate prescribing (PIP) across prescribers in the national Irish older population using the STOPP criteria; (ii) estimate how reliably the criteria could distinguish between prescribers in terms of their proportion of PIP and; (iii) examine how PIP varies between prescribers and by patient and prescriber characteristics in a multilevel regression model.
1,938 general practitioners (GPs) with 338,375 registered patients’ ≥70 years were extracted from the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. HSE-PCRS prescriptions are WHO ATC coded. Demographic data for claimants’ and prescribers’ are available. Thirty STOPP indicators were applied to prescription claims in 2007. Multilevel logistic regression examined how PIP varied between prescribers and by individual patient and prescriber level variables.
The unadjusted variation in PIP between prescribers was considerable (median 35%, IQR 30-40%). The STOPP criteria were reliable measures of PIP (average >0.8 reliability). The multilevel regression models found that only the patient level variable, number of different repeat drug classes was strongly associated with PIP (>2 drugs v none; adjusted OR, 4.0; 95% CI 3.7, 4.3). After adjustment for patient level variables the proportion of PIP varied fourfold (0.5 to 2 times the expected proportion) between prescribers but the majority of this variation was not significant.
PIP is of concern for all prescribers. Interventions aimed at enhancing appropriateness of prescribing should target patients taking multiple medications.
PMCID: PMC4021047  PMID: 24690127
Potentially inappropriate prescribing; General practice; Prescriber variation; STOPP; Older populations
23.  Prevalence of potentially inappropriate prescribing and prescribing omissions in older Irish adults: findings from The Irish LongituDinal Study on Ageing study (TILDA) 
We sought to estimate the prevalence of potentially inappropriate prescriptions (PIP) and potential prescribing omissions (PPOs) using a subset of the STOPP/START criteria in a population based sample of Irish adults aged ≥65 years using data from The Irish LongituDinal Study on Ageing (TILDA).
A subset of 26 PIP indicators and 10 PPO indicators from the STOPP/START criteria were applied to the TILDA dataset. PIP/PPO prevalence according to individual STOPP/START criteria and the overall prevalence of PIP/PPO were estimated. The relationship between PIP and PPOs and polypharmacy, age, gender and multimorbidity was examined using logistic regression.
The overall prevalence of PIP in the study population (n = 3,454) was 14.6 %. The most common examples of PIP identified were NSAID with moderate-severe hypertension (200 participants; 5.8 %) and aspirin with no history of coronary, cerebral, or peripheral vascular symptoms or occlusive event (112 participants; 3.2 %). The overall prevalence of PPOs was 30 % (n = 1,035). The most frequent PPO was antihypertensive therapy where systolic blood pressure consistently >160 mmHg (n = 341, 9.9 %), There was a significant association between PIP and PPO and polypharmacy when adjusting for age, sex and multimorbidity (adjusted OR 2.62, 95 % CI 2.05–3.33 for PIP and adjusted OR 1.46, 95 % CI 1.23–1.75 for prescribing omissions).
Our findings indicate prescribing omissions are twice as prevalent as PIP in the elderly using a subset of the STOPP/START criteria as an explicit process measure of potentially inappropriate prescribing and prescribing omissions. Polypharmacy was independently associated with both PPO and PIP. Application of such screening tools to prescribing decisions may reduce unnecessary medication, related adverse events, healthcare utilisation and cost.
Electronic supplementary material
The online version of this article (doi:10.1007/s00228-014-1651-8) contains supplementary material, which is available to authorized users.
PMCID: PMC3978378  PMID: 24493365
Potentially inappropriate prescribing; Potential prescribing omissions; STOPP; START; Older people
24.  Is the Timed Up and Go test a useful predictor of risk of falls in community dwelling older adults: a systematic review and meta- analysis 
BMC Geriatrics  2014;14:14.
The Timed Up and Go test (TUG) is a commonly used screening tool to assist clinicians to identify patients at risk of falling. The purpose of this systematic review and meta-analysis is to determine the overall predictive value of the TUG in community-dwelling older adults.
A literature search was performed to identify all studies that validated the TUG test. The methodological quality of the selected studies was assessed using the QUADAS-2 tool, a validated tool for the quality assessment of diagnostic accuracy studies. A TUG score of ≥13.5 seconds was used to identify individuals at higher risk of falling. All included studies were combined using a bivariate random effects model to generate pooled estimates of sensitivity and specificity at ≥13.5 seconds. Heterogeneity was assessed using the variance of logit transformed sensitivity and specificity.
Twenty-five studies were included in the systematic review and 10 studies were included in meta-analysis. The TUG test was found to be more useful at ruling in rather than ruling out falls in individuals classified as high risk (>13.5 sec), with a higher pooled specificity (0.74, 95% CI 0.52-0.88) than sensitivity (0.31, 95% CI 0.13-0.57). Logistic regression analysis indicated that the TUG score is not a significant predictor of falls (OR = 1.01, 95% CI 1.00-1.02, p = 0.05).
The Timed Up and Go test has limited ability to predict falls in community dwelling elderly and should not be used in isolation to identify individuals at high risk of falls in this setting.
PMCID: PMC3924230  PMID: 24484314
25.  A Prospective Cohort Study of Alcohol Exposure in Early and Late Pregnancy within an Urban Population in Ireland 
Most studies of alcohol consumption in pregnancy have looked at one time point only, often relying on recall. The aim of this longitudinal study was to determine whether alcohol consumption changes in early and late pregnancy and whether this affects perinatal outcomes. We performed a prospective cohort study, conducted from November 2010 to December 2011 at a teaching hospital in the Republic of Ireland. Of the 907 women with a singleton pregnancy who booked for antenatal care and delivered at the hospital, 185 (20%) abstained from alcohol in the first trimester but drank in the third trimester, 105 (12%) consumed alcohol in the first and third trimesters, and the remaining 617 (68%) consumed no alcohol in pregnancy. Factors associated with continuing to drink in pregnancy included older maternal age (30–39 years), Irish nationality, private healthcare, smoking, and a history of illicit drug use. Compared to pre-pregnancy, alcohol consumption in pregnancy was markedly reduced, with the majority of drinkers consuming ≤ 5 units per week (92% in first trimester, 72–75% in third trimester). Perhaps because of this, perinatal outcomes were similar for non-drinkers, women who abstained from alcohol in the first trimester, and women who drank in the first and third trimester of pregnancy. Most women moderate their alcohol consumption in pregnancy, especially in the first trimester, and have perinatal outcomes similar to those who abstain.
PMCID: PMC3945584  PMID: 24549147
alcohol exposure; prospective cohort study; pregnancy; perinatal outcomes

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