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Introduction There is concern regarding adverse effects of antihypertensive treatment, including falls and subsequent fractures, especially hip fractures. As frailty is increasingly recognised as an important risk factor for adverse outcomes, we examined its relationship to fracture rates in older patients after starting antihypertensives. Methods Using the Clinical Practice Research Datalink (CPRD), we identified participants over 65-years old starting a first-line antihypertensive medication. Using deficits identified in CPRD we classified patient-level frailty as “Fit”, “Mild”, “Moderate” or “Severe” using the Electronic Frailty Index. We calculated the rate of fractures by frailty level and fracture site, and determined the rate ratio (RR) of first fracture by frailty level, adjusting for confounding, using multivariable poisson regression. We conducted sensitivity analyses to additionally adjust for ethnicity, deprivation, and bisphosphonate use. Results 44% of participants were classified as mildly frail or greater, but frail participants experienced 58% of all fractures, and 63% of hip fractures. The whole cohort showed a crude rate of 14.1 fractures/1000 person-years, with 4.5 hip fractures/1000 person-years. In severe frailty, this rises to 51.0 fractures/1000 person-years, and 17.7 hip fractures/1000 person-years. After adjustment for confounding, increasing frailty was associated with greater rate of any fracture, reaching RR 2.85 (95% confidence interval 2.43–3.33) for severe frailty versus fit. Results were unchanged in sensitivity analyses. Conclusions Frailty and fracture are both common in older participants who start antihypertensive medications. Increasing frailty was positively associated with increased rates of fracture. Clinicians need awareness of this relationship to consider fracture risk assessment and prevention in these patients.

Ireland has the highest rates of overnight hospitalisations for COPD in the OECD, yet lacks estimates of the prevalence of this disease or its pharmacological management. We aimed to estimate the age and sex-specific prevalence of symptomatic COPD and to identify patterns of respiratory medication use to inform interventions to improve pharmacotherapy in this condition. We used the national pharmacy claims database, with data on a publically insured cohort in 2016. We restricted to those aged ≥ 45 years with full eligibility for that year and examined the age and sex distribution of respiratory medications, and patterns of medication use in those suggestive of COPD. In this cohort, 23% filled at least one prescription for a respiratory medication; 14% of males and 16% of females received at least one dispensing of an ICS inhaler. The proportion dispensed a long-acting muscarinic receptor antagonist (LAMA) was considerably lower. Of those newly initiated on a LAMA, 24% did not receive another within 60 days of the last covered day. The prevalence of medication use suggestive of COPD was 15% in males and 16% in females. The prevalence of medication use consistent with the management of symptomatic COPD mirrors international prevalence estimates. Several patterns raise concern: high ICS use in older adults, under use of LAMA therapy and poor persistence of those newly initiated. We recommend the development of an intervention to assist in the implementation of new national prescribing guidelines for the management of COPD.

Background Mandatory co-payments attached to prescription medicines on the Irish public health insurance [General Medical Services (GMS)] scheme have undergone multiple iterations since their introduction in October 2010. To date, whilst patients’ opinions on said co-payments have been evaluated, the perspectives of community pharmacists and general practitioners (GPs) have not. Objective To explore the involvement and perceptions of community pharmacists and GPs on this pharmaceutical policy change. Methods A qualitative study using purposive sampling alongside snowballing recruitment was used. Nineteen interviews were conducted in a Southern region of Ireland. Data were analysed using the Framework Approach. Results Three major themes emerged: 1) the withered tax-collecting pharmacist; 2) concerns and prescribing patterns of physicians; and 3) the co-payment system – impact and sustainability. Both community pharmacists and GPs accepted the theoretical concept of a co-payment on the GMS scheme as it prevents moral hazard. However, there were multiple references to the burden that the current method of co-payment collection places on community pharmacists in terms of direct financial loss and reductions in workplace productivity. GPs independently suggested that a co-payment system may inhibit moral hazard by GMS patients in the utilisation of GP services. It was unclear to participants what evidence is guiding the GMS co-payment fee changes. Conclusion Interviewees accepted the rationale for the co-payment system, but reform is warranted.

Background Two large acute Irish University teaching hospitals changed the manner in which they treated human epidermal growth factor receptor (HER)2-positive breast cancer patients by implementing the administration of trastuzumab via the subcutaneous (SC) route into their clinical practice. The study objective is to compare the trastuzumab SC and trastuzuamb intravenous (IV) treatment pathways in both hospitals and assess which route is more cost-effective and time saving in relation to active health care professional (HCP) time. Materials and Methods A prospective observational study in the form of cost minimization analysis constituted the study design. Active HCP time for trastuzumab SC- and IV-related tasks were recorded. Staff costs were calculated using fully loaded salary costs. Loss of productivity costs for patients were calculated using the human capital method. Results On average, the total HCP time saved per trastuzumab SC treatment cycle relative to trastuzumab IV treatment cycle was 59.21 minutes. Time savings in favor of trastuzumab SC resulted from quicker drug reconstitution, no IV catheter installation/removal, and less HCP monitoring. Over a full treatment course of 17 cycles, average HCP time saved accumulates to 16.78 hours, with an estimated direct cost saving of €1609.99. Loss of productivity for patients receiving trastuzumab IV (2.15 days) was greater than that of trastuzumab SC (0.60 days) for a full treatment course. Conclusion Trastuzumab SC treatment has proven to be a more cost-effective option than trastuzumab IV treatment that generated greater HCP time savings in both study sites. Healthcare policymakers should consider replacing trastuzumab IV with trastuzumab SC treatment in all eligible patients.

The Irish Health Service Executive-Primary Care Reimbursement Service (HSE-PCRS) database is a national repository of pharmacy claims data, representing dispensed prescriptions that were wholly or partially funded by public funds. It has been used in pharmacoepidemiology research, drug utilisation research, and health services research. This chapter provides a brief outline of how the Irish health care system operates, a description of the main features of the national dispensing database inclusive of information available and validity, examples of research using these data, and a comment on the future direction of the database.

BackgroundPrevious work has demonstrated that the recording of acute health outcomes, such as myocardial infarction (MI), may be suboptimal in primary healthcare databases.AimTo assess the completeness and accuracy of the recording of stroke in UK primary care.Design & settingA population-based longitudinal cohort study.MethodCases of stroke were identified separately in Clinical Practice Research Datalink (CPRD) primary care records and linked Hospital Episode Statistics (HES). The recording of events in the same patient across the two datasets was compared. The reliability of strategies to identify fatal strokes in primary care and hospital records was also assessed.ResultsOf the 75 674 stroke events that were identified in either CPRD or HES data during the period of the study, 54 929 (72.6%) were recorded in CPRD and 51 013 (67.4%) were recorded in HES. Two-fifths (n = 30 268) of all recorded strokes were found in both datasets (allowing for a time window of 120 days). Among these 'matched' strokes the subtype was recorded accurately in approximately 75% of CPRD records (compared with coding in HES); however, 43.5% of ischaemic strokes in HES were coded as 'non-specific' strokes in CPRD data. Furthermore, 48.2% had same-day recordings, and 56.2% were date-matched within ±1 day.ConclusionThe completeness and accuracy of stroke recording is improved by the use of linked hospital and primary care records. For studies that have a time-sensitive research question, the use of linked, as opposed to stand-alone, CPRD data is strongly recommended.

Objective To study whether treatment recommendations based on age and ethnicity according to United Kingdom (UK) clinical guidelines for hypertension translate to blood pressure reductions in current routine clinical care. Design Observational cohort study. Setting UK primary care, from 1 January 2007 to 31 December 2017. Participants New users of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), calcium channel blockers (CCB), and thiazides. Main outcome measures Change in systolic blood pressure in new users of ACEI/ARB versus CCB, stratified by age (< v ≥55) and ethnicity (black v non-black), from baseline to 12, 26, and 52 week follow-up. Secondary analyses included comparisons of new users of CCB with those of thiazides. A negative outcome (herpes zoster) was used to detect residual confounding and a series of positive outcomes (expected drug effects) was used to determine whether the study design could identify expected associations. Results During one year of follow-up, 87 440 new users of ACEI/ARB, 67 274 new users of CCB, and 22 040 new users of thiazides were included (median 4 (interquartile range 2-6) blood pressure measurements per user). For non-black people who did not have diabetes and who were younger than 55, CCB use was associated with a larger reduction in systolic blood pressure of 1.69 mm Hg (99% confidence interval −2.52 to −0.86) relative to ACEI/ARB use at 12 weeks, and a reduction of 0.40 mm Hg (−0.98 to 0.18) in those aged 55 and older. In subgroup analyses using six finer age categories of non-black people who did not have diabetes, CCB use versus ACEI/ARB use was associated with a larger reduction in systolic blood pressure only in people aged 75 and older. Among people who did not have diabetes, systolic blood pressure decreased more with CCB use than with ACEI/ARB use in black people (reduction difference 2.15 mm Hg (−6.17 to 1.87)); the corresponding reduction difference was 0.98 mm Hg (−1.49 to −0.47) in non-black people. Conclusions Similar reductions in blood pressure were found to be associated with new use of CCB as with new use of ACEI/ARB in non-black people who did not have diabetes, both in those who were aged younger than 55 and those aged 55 and older. For black people without diabetes, CCB new use was associated with numerically greater reductions in blood pressure than ACEI/ARB compared with non-black people without diabetes, but the confidence intervals were overlapping for the two groups. These results suggest that the current UK algorithmic approach to first line antihypertensive treatment might not lead to greater reductions in blood pressure. Specific indications could be considered in treatment recommendations.

IntroductionAntimicrobial resistance (AMR) is a global health emergency. Acne vulgaris is a highly prevalent condition and the dominant role antibiotics play in its treatment is a major concern. Antibiotics are widely used in the treatment of acne predominantly for their anti-inflammatory effect, hence their use in acne may not be optimal. Tetracyclines and macrolides are the two most common oral antibiotic classes prescribed, and their average use can extend from a few months to several years of intermittent or continuous use. The overall aim of this systematic review is to elucidate what is known about oral antibiotics for acne contributing to antibiotic treatment failure and AMR.Methods and analysisA systematic review will be conducted to address the question: What is the existing evidence that long-term oral antibiotics used to treat acne in those over 8 years of age contribute towards antibiotic treatment failure or other outcomes suggestive of the impact of AMR? We will search the following databases: Embase, MEDLINE, the Cochrane Library and Web of Science. Search terms will be developed in collaboration with a librarian by identifying keywords from relevant articles and by undertaking pilot searches. Randomised controlled trials, cohort and case-controlled studies conducted in any healthcare setting and published in any language will be included. The searches will be re-run prior to final analyses to capture the recent literature. The Cochrane tool for bias assessment in randomised trials and ROBINS-I for the assessment of bias in non-randomised studies will be used to assess the risk of bias of included studies. GRADE will be used to make an overall assessment of the quality of evidence. A meta-analysis will be undertaken of the outcome measures if the individual studies are sufficiently homogeneous. If a meta-analysis is not possible, a qualitative assessment will be presented as a narrative review.Ethics and disseminationEthical approval is not required for this systematic-review. The results will be published in a peer-reviewed journal and any deviations from the protocol will be clearly documented in the published manuscript of the full systematic-review.PROSPERO registration numberCRD42019121738.

ObjectiveUsing US claims data and the most up-to-date pharmacoepidemiological study design tools we aimed to investigate two safety signals for (1) macrolides and heart failure; and (2) non-steroidal anti-inflammatory drugs (NSAIDs) and pneumonia generated from a large-scale screening analysis using a self-controlled sequence symmetry design in Danish data.MethodsWe used IBM Marketscan data to conduct two new-user, active-comparator cohort studies. In the macrolides example, the exposure was clarithromycin or azithromycin and the comparator was amoxicillin/clavulanate, in patients with sinusitis. In the NSAIDs example, the exposure was oral NSAIDs and the comparator was topical diclofenac, in patients with osteoarthritis. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) to adjust for approximately 50 investigator-specified confounders in a propensity score (PS) matched analysis. In a secondary analysis, we used high-dimensional PS (hd-PS) to adjust for 200 additional proxy confounders.ResultsWe had 1,012,364 propensity score matched patients exposed to clarithromycin or azithromycin versus amoxicillin/clavulanate. With 162 outcomes among clarithromycin or azithromycin exposed patients and 134 among amoxicillin/clavulanate, the HR for overall heart failure was 1.14 (95% CI 0.90 – 1.43). In the NSAIDs example, we included 94,490 patients after propensity score matching. With 794 pneumonia outcomes among oral NSAID patients and 700 among topical diclofenac, we found HR 0.98 (95% CI 0.89 – 1.09). Some upward bias was suspected as larger HRs were observed in the days immediately following exposure for both the macrolides and NSAIDs examples. We found similar results in the hd-PS matched analyses for both examples.ConclusionOur findings for NSAIDs and pneumonia suggest the original signal may have been due to protopathic or detection bias. Our analyses for macrolides and heart failure with short-term follow-up also suggest bias, although we encourage further research.

BackgroundAntimicrobial resistance (AMR) is a global health priority. Acne vulgaris is a common skin condition for which antibiotic use ranges from a few months to years of daily exposure.AimTo systemically search for and synthesise evidence on the risk of treatment-resistant infections, and other evidence of AMR, following long-term oral antibiotic use for acne.Design & settingIn this systematic review, a literature search was carried out using the databases Embase, MEDLINE, Cochrane, and Web of Science. They were searched using MeSH, Emtree, or other relevant terms, and followed a pre-registered protocol.MethodSearch strategies were developed with a librarian and undertaken in July 2019. All searches date from database inception. The primary outcome was antibiotic treatment failure or infection caused by a resistant organism. Secondary outcomes included detection of resistant organisms without an infection, rate of infection, or changes to flora.ResultsA total of 6996 records were identified. Seventy-three full-text articles were shortlisted for full review, of which five were included. Two investigated rates of infection, and three resistance or changes to microbial flora. Three studies had 35 or fewer participants (range 20–118 496). Three studies had a serious or high risk of bias, one moderate, and one a low risk of bias. Weak evidence was found for an association between antibiotic use for acne and subsequent increased rates of upper respiratory tract infections and pharyngitis.ConclusionThere is a lack of high quality evidence on the relationship between oral antibiotics for acne treatment and subsequent AMR sequelae. This needs to be urgently addressed with rigorously conducted studies.

Background : In developed countries, rates of induction of labour (IOL) have increased and vary between hospitals. We aimed to identify whether national variations could be explained by sociodemographic, clinical and organisational differences. Methods : Two national databases in Ireland that routinely collect clinical and administrative data, the National Perinatal Reporting System and the Hospital Inpatient Enquiry Scheme, were used to analyse data for all women with singleton births weighing ≥500 g in 2009. We used logistic multilevel models to examine variation between hospitals, and to determine how much variation was due to individual level sociodemographic, clinical and organisational variables. Analyses were stratified for nulliparas, multiparas without prior caesarean section (CS) and multiparas with prior CS. Results : Of 69 304 eligible births, the rate of IOL nationally was 25.0% (range 14.5–33.2%).In nulliparas, the mean rate was 30.9% (range 18.6–45.7%). The rate was 24.8% (13.5–33.3%) and 3.8% (0.0–10.2%) for multiparas without and with prior CS, respectively. In nulliparas and multiparas without prior CS IOL was predicted by maternal birth in Ireland, increasing birthweight, antepartum complications, giving birth on a weekday and the model of obstetric care. Even after adjusting for known sociodemographic and clinical variables, variation between hospitals remained. Conclusion : We found that clinical, sociodemographic and organisational factors all contributed to variation. However, unexplained variation persisted possibly due to organisational factors such as hospital-specific policies on IOL. The results indicate that the prevalence of antenatal complications, changing immigration patterns and policies on IOL after previous CS are factors likely to influence future IOL rates.

We assessed the impact of the introduction of a €0.50 prescription copayment, and its increase to €1.50, on adherence to essential and less-essential medicines in a publicly insured population in Ireland. We used a pre-post longitudinal repeated measures design. We included new users of essential medicines: blood pressure lowering, lipid lowering and oral diabetic agents, thyroid hormone, anti-depressants, and less-essential medicines: non-steroidal anti-inflammatory drugs (NSAIDs), Proton Pump Inhibitors/H2 antagonists (PPIs/H2 ), and anxiolytics/hypnotics. The outcome was change in adherence, measured using Proportion of Days Covered. We used segmented regression with generalised estimating equations to allow for repeated measurements. Sample sizes ranged from 7145 (thyroid hormone users) to 136 111 (NSAID users). The €0.50 copayment was associated with reductions in adherence ranging from -2.1%[95% CI, -2.8 to -1.5] (thyroid hormone) to -8.3%[95% CI, -8.7 to -7.9] (anti-depressants) for essential medicines and reductions in adherence of -2%[95% CI, -2.3 to -1.7] (anxiolytics/hypnotics) to -9.5%[95% CI, -9.8 to -9.1] (PPIs/H2 ) for less-essential medicines. The €1.50 copayment generally resulted in smaller reductions in adherence to essential medicines. Anti-depressant medications were the exception with a decrease of -10.0% [95% CI, -10.4 to -9.6] after the copayment increase. Larger decreases in adherence were seen for most less-essential medicines; the largest was for PPIs/H2 at -13.5% [95% CI, -13.9 to -13.2] after the €1.50 copayment. Both copayments had a greater impact on adherence to less-essential medicines than essential medicines. The major exception was for anti-depressant medicines. Further research is required to explore heterogeneity across different socio-economic strata and to elicit the impact on clinical outcomes. Copyright © 2015 John Wiley & Sons, Ltd.

Copayments for prescriptions may increase morbidity and mortality via reductions in adherence to medications. Relevant data can inform policy to minimise such unintended effects. We explored the generalisability of evidence for copayments by comparing two international copayment polices, one in Massachusetts and one in Ireland, to assess whether effects on medication adherence were comparable. We used national prescription data for public health insurance programmes in Ireland and Medicaid data in the U.S. New users of oral anti-hypertensive, anti-hyperlipidaemic and diabetic drugs were included (total n = 14,259 in U.S. and n = 43,843 in Ireland). We examined changes in adherence in intervention and comparator groups in each setting using segmented linear regression with generalised estimating equations. In Massachusetts, a gradual decrease in adherence to anti-hypertensive medications of -1% per month following the policy occurred. In contrast, the response in Ireland was confined to a -2.9% decrease in adherence immediately following the policy, with no further decrease over the 8 month follow-up. Reductions in adherence to oral diabetes drugs were larger in the U.S. group in comparison to the Irish group. No difference in adherence changes between the two settings for anti-hyperlipidaemic drugs occurred. Evidence on cost-sharing for prescription medicines is not 'one size fits all'. Time since policy implementation and structural differences between health systems may influence the differential impact of copayment policies in international settings.

Background: Oral cancer is a significant public health problem world-wide and exerts high economic, social, psychological, and physical burdens on patients, their families, and on their primary care providers. We set out to describe the changing trends in incidence and survival rates of oral cancer in Ireland between 1994 and 2009. Methods: National data on incident oral cancers [ICD 10 codes C01-C06] were obtained from the National Cancer Registry Ireland from 1994 to 2009. We estimated annual percentage change (APC) in oral cancer incidence during 1994–2009 using joinpoint regression software (version 4.2.0.2). The lifetime risk of oral cancer to age 79 was estimated using Irish incidence and population data from 2007 to 2009. Survival rates were also examined using Kaplan-Meier curves and Cox proportional hazard models to explore the influence of several demographic/lifestyle covariates with follow-up to end 2012. Results: Data were obtained on 2,147 oral cancer incident cases. Men accounted for two-thirds of oral cancer cases (n = 1,430). Annual rates in men decreased significantly during 1994–2001 (APC = -4.8 %, 95 % CI: −8.7 to −0.7) and then increased moderately (APC = 2.3 %, 95 % CI: −0.9 to 5.6). In contrast, annual incidence increased significantly in women throughout the study period (APC = 3.2 %, 95 % CI: 1.9 to 4.6). There was an elevated risk of death among oral cancer patients who were: older than 60 years of age; smokers; unemployed or retired; those living in the most deprived areas; and those whose tumour was sited in the base of the tongue. Being married and diagnosed in more recent years were associated with reduced risk of death. Conclusion: Oral cancer increased significantly in both sexes between 1999 and 2009 in Ireland. Our analyses demonstrate the influence of measured factors such as smoking, time of diagnosis and age on observed trends. Unmeasured factors such as alcohol use, HPV and dietary factors may also be contributing to increased trends. Several of these are modifiable risk factors which are crucial for informing public health policies, and thus more research is needed.

Aim We assessed the effectiveness of fourth-line mineralocorticoid receptor antagonists in comparison with other fourth-line anti-hypertensive agents in resistant hypertension. Methods and results We systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists with other fourth-line anti-hypertensive agents in patients with resistant hypertension. The outcome was change in systolic blood pressure, measured in the office, at home or by ambulatory blood pressure monitoring. Secondary outcomes were changes in serum potassium and occurrence of hyperkalaemia. We used random effects models and assessed statistical heterogeneity using the I2 test and corresponding 95% confidence intervals. From 2,506 records, 5 studies met our inclusion criteria with 755 included patients. Two studies were randomised and three were non-randomised. Comparative fourth-line agents included bisoprolol, doxazosin, furosemide and additional blockade of the renin angiotensin-aldosterone system. Using data from randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 7.4 mmHg (95%CI 3.2 - 11.6) more than the active comparator. When limited to non-randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 11.9 mmHg (95% CI 9.3 - 14.4) more than the active comparator. Conclusion On the basis of this meta-analysis, mineralocorticoid receptor antagonists reduce blood pressure more effectively than other fourth-line agents in resistant hypertension. Effectiveness stratified by ethnicity and comorbidities, in addition to information on clinical outcomes such as myocardial infarction and stroke, now needs to be determined.

Objectives To determine the concordance between two methods to measure drug exposure duration from pharmacy claim data. Study Design and Setting We conducted a cohort study using 2002–2007 US Medicaid data. Initiators of eight drug groups were identified: statins, metformin, atypical antipsychotics, warfarin, proton pump inhibitors (PPIs), angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (ns-NSAIDs), and coxibs. For each patient, we calculated two measures of exposure duration using (1) observed days' supply available in US pharmacy claims and (2) the World Health Organisation's Defined Daily Dose (DDD) methodology. We used Wilcoxon signed rank tests to compare medians and Spearman correlations to assess correlation between the two measures. Results Cohort sizes ranged from 143,885 warfarin users to >3,000,000 ns-NSAID users. Similar median exposure durations were observed for ACE inhibitors (70 days vs.75 days), PPIs (44 days vs. 45 days), and coxibs (44 days vs. 45 days). The DDD method overestimated exposure duration for ns-NSAIDs and underestimated for the remaining drug groups, relative to days' supply. Spearman correlation coefficients ranged from 0.2 to 0.8. Conclusion Using DDDs to estimate drug exposure duration can result in misclassification. The magnitude of this misclassification might depend on doses used which can vary according to factors such as local prescribing practices, renal function, and age.

Recent evidence points to the effectiveness of spironolactone vs placebo in the treatment of resistant hypertension (RH). However, placebo is rarely a realistic treatment choice in uncontrolled hypertension. Using meta-analysis, we assessed the effectiveness of alternative 4 line anti-hypertensive agents in comparison to 4 line spironolactone/eplenerone in RH. Pubmed, EMBASE and the Cochrane library were systematically searched for randomised and non-randomised studies that compared any 4 line anti-hypertensive agent to spironolactone/eplenerone in RH. Data extraction and quality appraisal were carried out in duplicate. The outcome was change in systolic BP, measured in the office, at home or by ambulatory blood pressure monitoring (AMBP). A random effects model was used to pool the data. Statistical heterogeneity was assessed using the I test. Sensitivity analyses were carried out according to study design and method of BP measurement. From 2,506 records, we identified 1 RCT and 5 observational studies according to our inclusion criteria with 877 included patients (Table 1). The mean age was 57.3yrs, 29.5% female, 41.4% diabetic, mean eGFR of 83.7 ml/min and mean BMI of 29.8 kg/m. The baseline systolic BP was 143.1 mmHg. Other 4 line agents included bisoprolol, doxazosin and furosemide. When all the data was pooled, spironolactone reduced systolic BP by -10.19mmHg (95% CI 6.76 - 13.62) (Figure 1) more than the active comparator. When limited to studies that measured 24hr AMBP, spironolactone reduced BP by 9.99mmHg (95% CI 7.14 - 12.84) relative to the comparator. Analysing observational studies only, spironolactone reduced systolic BP by 11.24mmHg (95% CI 8.04 - 14.43). On the basis of this meta-analysis, spironolactone reduces systolic BP more effectively than other potential 4 line treatment options in RH. The comparative effectiveness of 4 line agents with regard to clinical outcomes such as myocardial infarction and stroke now needs to be determined.

In the 3rd paragraph and 2nd line of the Conclusion section the correct sentence should be: It is now important to encourage policy and decision makers to facilitate and accommodate future linkage of data.

Background A 50 cent prescription levy was introduced in 2010 on the General Medical Services (GMS) scheme (Irish public health insurance). This study sought to examine patient attitudes and opinions surrounding the 50 cent copayment. Given the small momentary value of the prescription fee, these results are of interest to policymakers internationally who wish to reduce copayments rather than abolish them. Methods A qualitative research design was used; semi structured interviews were carried out. Twenty four GMS eligible participants were interviewed in 23 interviews. Fifteen females and 9 males took part. Ages varied from 31- >70 years. Patients were invited to be interviewed in both independent and chain community pharmacies in three types of setting; 1) a socially deprived urban area, 2) a suburban affluent area and 3) a rural area. The Framework method was used for data management and analysis using QSR International’s NVivo 9.2 qualitative data analysis software. The “Francis method” was used to test for data saturation. Results Results are of interest to the Irish context and also at a broader international level. Patients were mostly accepting of the prescription levy with some reservations concerning an increased price and the way in which generated revenue would be used by government. Participants identified waste of prescription drugs at the hand of patients (moral hazard), but there was discordant opinion on whether the 50 cent copayment would halt this moral hazard. Interviewees felt the levy was affordable, albeit some may suffer a financial impact more than others. Conclusions This qualitative study gives important insights into the experiences of GMS patients with regard to the prescription levy. Information regarding the appropriateness of a 50 cent copayment as a symbolic copayment needs to be confirmed by quantitative analysis. Further insight is required from a younger population.

Objective: Internationally, caesarean section (CS) rates are rising. However, mean rates of CS across providers obscure extremes of CS provision. We aimed to quantify variation between all maternity units in Ireland. Methods: Two national databases, the National Perinatal Reporting System and the Hospital Inpatient Enquiry Scheme, were used to analyse data for all women delivering singleton births weighing ≥500g. We used multilevel models to examine variation between hospitals in Ireland for elective and emergency CS, adjusted for individual level sociodemographic, clinical and organisational variables. Analyses were subsequently stratified for nullipara and multipara with and without prior CS. Results: The national CS rate was 25.6% (range 18.2% ─ 35.1%). This was highest in multipara with prior CS at 86.1% (range 6.9% ─ 100%). The proportion of variation in CS that was attributable to the hospital of birth was 11.1% (95% CI, 6.0 ─ 19.4) for elective CS and 2.9% (95% CI, 1.4 ─ 5.6) for emergency CS, after adjustment. Stratifying across parity group, variation between hospitals was greatest for multipara with prior CS. Both types of CS were predicted by increasing age, prior history of miscarriage or stillbirth, prior CS, antenatal complications and private model of care. Conclusion: The proportion of variation attributable to the hospital was higher for elective CS than emergency CS suggesting that variation is more likely influenced by antenatal decision making than intrapartum decision making. Multipara with prior CS were particularly subject to variability, highlighting a need for consensus on appropriate care in this group. Health Research Board

Background Pharmacy claims data have been demonstrated to be specific and sensitive in identifying patients with diabetes. This study generates new up to date estimates of the prevalence and incidence of type 1 (T1DM) and type 2 diabetes mellitus (T2DM) in Ireland using the national pharmacy claims database. In the absence of a national diabetes register, this augments existing estimates based on survey data or modelling. Methods The Primary Care Reimbursement Services database houses data on all prescriptions filled in the Republic of Ireland on the main national health insurance programme, referred to as the General Medical Services (GMS) scheme. This scheme covers approximately 40% of the population on a means tested basis, with almost 100% of the over 70s represented due to different income thresholds. We used data from July 2011–December 2012. T1DM was classified as any individual under 45 years who used an insulin product (ATC A10A) and who had never used an oral/injectable hypo-glycaemic agent. T2DM was classified as any user of an oral/injectable anti-diabetic agent (ATC A10B), irrespective of insulin use and with no age restriction. Incidence of T1DM and T2DM was calculated by estimating the number of new users of A10A or A10B respectively, precluding prior use in a 6 month look back period. Prevalence was calculated using number of prevalent users divided by the age specific GMS eligible population. Results We used data from 1,799,285 individuals to calculate an incidence rate of 0.14% (95% CI 0.13–0.14) and a prevalence rate of 0.42% (95% CI 0.41–0.43) for T1DM. In the general GMS population, the incidence rate of T2DM was 0.90% (95% CI 0.88–0.91), while prevalence was estimated at 4.38% (95% CI 4.35–4.41). When stratified across 8 age groups ranging from Conclusion Our estimates are similar to prior estimates but provide a more up to date reference and are derived from a larger sample population, including almost all the over 70s population in Ireland. A limitation is that undiagnosed diabetes cannot be estimated. Further analyses will include sensitivity analyses for the length of look back period in estimating new users and age used to define TIDM. Indirect age standardisation will be used to calculate prevalence and incidence in the entire Irish population.

Background Current evidence points to a difference in the rate of caesarean section depending on whether the delivery is funded privately or publicly in Ireland. This paper evaluates the extent of the difference in elective and emergency caesarean delivery rates between public and private women in public maternity hospitals, in addition to quantifying the contribution of different maternal and clinical characteristics in explaining the difference in the rates. Methods Cross-sectional analysis using a combination of two routinely collected administrative databases was performed. Data were for 19 public hospital maternity units in the Republic of Ireland. A non-linear extension of the Oaxaca-Blinder method was used to decompose the difference between public and private elective/emergency caesarean delivery rates into the proportion explained by the differences in observable maternal and clinical characteristics and the proportion that remains unexplained. Nulliparous women with a singleton delivery (live or stillborn) in hospital who were discharged between January 1st and December 31st 2009 were included. We stratified across elective CS (ELCS) and emergency CS (EMCS). Results Of 29,870 births, 7,792 were delivered via CS (26.1%), 79.6% of which were coded as EMCS deliveries. Higher prevalence of ELCS was associated with having had a CS previously (69.2%), breech presentation (64.5%), and other malpresentation (53.5%). Higher prevalence of EMCS was associated with placenta praevia or placental abruption (55.3%), prematurity (44.6%), dystocia in labour (40.6%), and fetal distress (31.0%). Slightly more than half of the variation in ELCS rates between public and private patients was explained by our models (55.9%). All of the variation for EMCS could be explained. Conclusion Controlling for clinical and maternal risk factors explained approximately half of the variation in ELCS rates across publicly and privately funded deliveries. This raises a question of what other factors may be explanatory. Given the globally increasing CS rates and both the benefits and harms this is associated with, further research is required to identify such factors.

Background Generalisability has been reported as a barrier to using evidence in policy making. Little data are available on whether US and Canadian based evidence on cost-sharing and medication adherence is generalizable to international populations. To explore external validity, we compared the impact of two similar cost sharing policies, one in the US and one in Ireland, on medication adherence. Methods A repeated measures longitudinal study design was employed to measure individual drug adherence before and after the introduction of drug cost-sharing policies. The Irish policy introduced a 50 cent copayment/prescription item in a publicly insured population in 2010. A similar policy occurred in the Massachusetts Medicaid population in 2003. Prescription data were obtained from centrally held pharmacy claims databases; HSE-PCRS, in Ireland and Medicaid Analytical Extract in the US New users of anti-hypertensive, anti-hyperlipidaemic and anti-diabetes drugs entered the cohort 6 months prior to initiation of cost-sharing polices and were followed for 12 months post-policy change. Segmented regression with generalised estimating equations and an autoregressive correlation structure was used. Results The Irish policy change resulted in a 3.9% (95% CI, 2.91%-5.02%) immediate drop in adherence to anti-hypertensive drugs in Ireland, whereas the US policy did not affect anti-hypertensive adherence. Relative to the US, the Irish population had a 5.3% (95% CI, 3.68% - 6.92%) additional decrease in adherence to anti-hypertensive drugs immediately after the policy change. Adherence to anti-hyperlipidaemic drugs was insignificantly reduced (-0.6235%, 95% CI, - 2.41%-1.16%) immediately post-policy change in the U. S. However, adherence to anti-hyperlipidaemics was reduced in Ireland by 3.4% (95% CI, 2.25%-4.62%). Compared to the US, Irish patients decreased their adherence to anti-hyperlipidaemics by 2.8% (95% CI, 0.673%-4.945%). Adherence to anti-diabetic drugs did not differ internationally post-policy change. There was no evidence for international differences in the long-term impact (12 months) of policy changes. Conclusion Irish and US populations had different changes in adherence to anti-hypertensive and anti-hyperlipidaemic drugs directly after implementation of cost-sharing policies, with greater reductions in adherence in the Irish population. However, changes in adherence to anti-diabetic drugs were similar between the populations. This study suggests that North American and Canadian evidence may not be automatically internationally generalizable. Rather, the specific attributes of a setting should always be considered before applying evidence to policy. This novel study will be of interest to global policymakers as they seek to develop evidence based cost-sharing policies.

Background The General Medical Services (GMS) scheme, a means tested public health insurance covering approximately 40% of the population, has traditionally provided prescription medicines without charge. In 2010, a 50c/item charge was introduced, which was increased to €1.50/item in 2013. The international literature points to an association between prescription charges and decreased adherence with consequential increases in morbidity and mortality. However, to date, there are no data on the impact of prescription charges on the GMS scheme on adherence. The aim was to assess the impact of two charges on adherence to prescription medicines. Methods A longitudinal repeated measures design was used to measure individual adherence to medicines before and after the introduction of charges. Pharmacy claims data from the national database (HSE-PCRS) were used for intervention and comparator groups. Two consecutive cohorts, including new users of anti-hypertensive, anti-hyperlipidaemic and oral anti-diabetic medicines, were established to analyse the effect of both charges. Follow up was 12 and 8 months. Segmented regression with generalised estimating equations was used. Sensitivity analyses according to age, sex and essential/non-essential drug status were conducted. All anlayses were carried in out in R version 2.15.2. Results Immediately after the introduction of the 50c charge, adherence to anti-hyperlipidaemic medicines was reduced by 2.2% (95% CI 1.24–3.12, p Conclusion The introduction of the 50c charge had a greater immediate effect on adherence to anti-hyperlipidaemic and anti-diabetes medicines than the €1.50 charge, suggesting reducing price elasticity of demand. This is the first analysis of the impact of prescription charges on adherence on the GMS. Further changes to cost-sharing policies in Ireland should be informed by national and international evidence.

Background The General Medical Services (GMS) scheme is a means tested public health insurance, covering approximately 40% of the Irish population. Eligibility for this scheme depends largely on income; however it is unknown how other demographic and socio-economic factors influence eligibility. We aimed to evaluate how demographic and socio-economic factors predicted GMS coverage from years 2006 (economic boom) to 2008 (start of recession) and 2010 (impact of austerity). Methods Cross-sectional data from the nationally representative EU Survey of Income and Living Conditions (EU-SILC) were used, n = 12,140 for 2006, n = 10,315 for 2008 and n = 8968 for 2010. Response rates were >77% for each year; missing data were generated by children. Variables are available on income, education, employment status, health status, private health insurance status, and multiple demographic factors (age, sex, marital status and nationality). The outcome variable was having GMS coverage or not. Logistic regression models were used to examine how the strength of predictors varied from year to year using R version 2.15.2. Results In univariate models, younger age (15–24 years and 25–49 years) and educational attainment predicted GMS status to a greater extent in 2010 than in 2006. The strength of unemployment as a predictor decreased over the study period, but this reduction was not significant (change in OR 1.210, 95% CI -3.411–2.940). Retired people were less likely to qualify for a medical card in 2010 than in 2006 (change in OR 12.260, 95% CI, 9.440–12.790). In multivariate models, only age and income remained predictive across the study period. For 15–24 years age category the OR increased each year, 2006 OR=0.021 (95% CI, 0.016–0.028), 2008 OR = 0.036 (95% CI, 0.019–0.070) and 2010 OR = 0.062 (95% CI, 0.032–0.120). For the 24–49 years age category in 2006 OR = 0.036 (95% CI, 0.028–0.045), in 2008 OR = 0.040 (95% CI, 0.023–0.070) and in 2010 OR = 0.078(95% CI, 0.045–0.135). While income was strongly predictive in each year, no yearly change in OR was observed. Conclusion Younger age categories increasingly predicted GMS status from 2006 through to 2010. This may be indicative of unemployment and falling income resulting from economic recession, however, unemployment did not appear as a significant predictor. Income was a consistent predictor each year. This is the first study to characterise population characteristics associated with GMS coverage. The results are timely given on-going and planned revisions to eligibility criteria as part of the phased introduction of universal health insurance.

INTRODUCTION: Copayments are intended to decrease third party expenditure on pharmaceuticals, particularly those regarded as less essential. However, copayments are associated with decreased use of all medicines. Publicly insured populations encompass some vulnerable patient groups such as older individuals and low income groups, who may be especially susceptible to medication non-adherence when required to pay. Non-adherence has potential consequences of increased morbidity and costs elsewhere in the system. OBJECTIVE: To quantify the risk of non-adherence to prescribed medicines in publicly insured populations exposed to copayments. METHODS: The population of interest consisted of cohorts who received public health insurance. The intervention was the introduction of, or an increase, in copayment. The outcome was non-adherence to medications, evaluated using objective measures. Eight electronic databases and the grey literature were systematically searched for relevant articles, along with hand searches of references in review articles and the included studies. Studies were quality appraised using modified EPOC and EHPPH checklists. A random effects model was used to generate the meta-analysis in RevMan v5.1. Statistical heterogeneity was assessed using the I(2) test; p>0.1 indicated a lack of heterogeneity. RESULTS: Seven out of 41 studies met the inclusion criteria. Five studies contributed more than 1 result to the meta-analysis. The meta-analysis included 199,996 people overall; 74,236 people in the copayment group and 125,760 people in the non-copayment group. Average age was 71.75 years. In the copayment group, (verses the non-copayment group), the odds ratio for non-adherence was 1.11 (95% CI 1.09-1.14; P =