The effects of copayment policies on adherence to prescription medicines in publicly insured populations

Introduction: Copayments for prescriptions are associated with decreased adherence to medicines resulting in increased health service utilisation, morbidity and mortality. In October 2010 a 50c copayment per prescription item was introduced on the General Medical Services (GMS) scheme in Ireland, the national public health insurance programme for low-income and older people. The copayment was increased to €1.50 per prescription item in January 2013. To date, the impact of these copayments on adherence to prescription medicines on the GMS scheme has not been assessed. Given that the GMS population comprises more than 40% of the Irish population, this presents an important public health problem. The aim of this thesis was to assess the impact of two prescription copayments, 50c and €1.50, on adherence to medicines.Methods: In Chapter 2 the published literature was systematically reviewed with meta-analysis to a) develop evidence on cost-sharing for prescriptions and adherence to medicines and b) develop evidence for an alternative policy option; removal of copayments. The core research question of this thesis was addressed by a large before and after longitudinal study, with comparator group, using the national pharmacy claims database. New users of essential and less-essential medicines were included in the study with sample sizes ranging from 7,007 to 136,111 individuals in different medication groups. Segmented regression was used with generalised estimating equations to allow for correlations between repeated monthly measurements of adherence. A qualitative study involving 24 individuals was conducted to assess patient attitudes towards the 50c copayment policy. The qualitative and quantitative findings were integrated in the discussion chapter of the thesis. The vast majority of the literature on this topic area is generated in North America, therefore a test of generalisability was carried out in Chapter 5 by comparing the impact of two similar copayment interventions on adherence, one in the U.S. and one in Ireland. The method used to measure adherence in Chapters 3 and 5 was validated in Chapter 6. Results: The systematic review with meta-analysis demonstrated an 11% (95% CI 1.09 to 1.14) increased odds of non-adherence when publicly insured populations were exposed to copayments. The second systematic review found moderate but variable improvements in adherence after removal/reduction of copayments in a general population. The core paper of this thesis found that both the 50c and €1.50 copayments on the GMS scheme were associated with larger reductions in adherence to less-essential medicines than essential medicines directly after the implementation of policies. An important exception to this pattern was observed; adherence to anti-depressant medications declined by a larger extent than adherence to other essential medicines after both copayments. The cross country comparison indicated that North American evidence on cost-sharing for prescriptions is not automatically generalisable to the Irish setting. Irish patients had greater immediate decreases of -5.3% (95% CI -6.9 to -3.7) and -2.8% (95% CI -4.9 to -0.7) in adherence to anti-hypertensives and anti-hyperlipidaemic medicines, respectively, directly after the policy changes, relative to their U.S. counterparts. In the long term, however, the U.S. and Irish populations had similar behaviours. The concordance study highlighted the possibility of a measurement bias occurring for the measurement of adherence to non-steroidal anti-inflammatory drugs in Chapter 3. Conclusions: This thesis has presented two reviews of international cost-sharing policies, an assessment of the generalisability of international evidence and both qualitative and quantitative examinations of cost-sharing policies for prescription medicines on the GMS scheme in Ireland. It was found that the introduction of a 50c copayment and its subsequent increase to €1.50 on the GMS scheme had a larger impact on adherence to less-essential medicines relative to essential medicines, with the exception of anti-depressant medications. This is in line with policy objectives to reduce moral hazard and is therefore demonstrative of the value of such policies. There are however some caveats. The copayment now stands at €2.50 per prescription item. The impact of this increase in copayment has yet to be assessed which is an obvious point for future research. Careful monitoring for adverse effects in socio-economically disadvantaged groups within the GMS population is also warranted. International evidence can be applied to the Irish setting to aid in future decision making in this area, but not without placing it in the local context first. Patients accepted the introduction of the 50c charge, however did voice concerns over a rising price. The challenge for policymakers is to find the ‘optimal copayment’ – whereby moral hazard is decreased, but access to essential chronic disease medicines that provide advantages at the population level is not deterred. This evidence presented in this thesis will be utilisable for future policy-making in Ireland.

Novel coatings for hard tissue implants

A novel deposition process named CoBlastTM, based on grit blasting technology, has been used to deposit hydroxyapatite (HA) onto titanium (Ti) metal using a dopant/abrasive regime. The various powders (HA powder, apatitic abrasives) and the treated substrates were characterised for chemical composition, coating coverage, crystallinity and topography including surface roughness. The surface roughness of the HA surfaces could be altered using apatitic abrasives of different particle sizes. Compared to the standard plasma spraying process, the CoBlast surface produced excellent coating adhesion, lower dissolution, higher levels of mechanical and chemical stability in stimulated body fluid (SBF). Enhanced viability of osteoblastic cells was also observed on the CoBlast HA surfaces compared to the microblast and untreated Ti as well as the plasma HA coating. CoBlast offers an alternative to the traditional methods of coating HA implants with added versatility. Apatites substituted with antimicrobial metals can also be deposited to add functionality to HA coatings without cytotoxicty. The potential use of these coatings as an infection preventing strategy for application on hard tissue implants was assessed in vitro and also in vivo. Surface physicochemical properties and morphology were determined in addition to surface cytocompatibility assessments using a MG-63 osteoblast cell line. The antibacterial potential of the immobilised metal ion on the surface and the eluted ion to a lesser extent, contributed to the anticolonising behaviour of the surfaces against a standard bacteria strain (S. aureus) as well as a number of clinically relevant strains (MRSA, MSSA and S. epidermis). The results revealed that the surfaces coated with silver substituted apatites (AgA) outperformed the other apatites examined (apatites loaded with Zn, Sr and both Ag and Sr ions). Assessment of bacterial adherence on coated K-wires following subcutaneous implantation in a nude mouse infection model (S. aureus) for two days demonstrated that the 12% wt surface outperformed the 5% wt AgA coating. Lower inflammatory responses were activated with the insertion of the Ag loaded K-wires with a localised infection at the implantation site noted over the two day study period. These results indicated that the AgA coating on the surface of orthopaedic implants demonstrate good biocompatibility whilst inhibiting bacterial adhesion and colonising of the implant surface.

Monitoring behaviours and experiences before, during and after pregnancy in Ireland

Background: On-going surveillance of behaviours during pregnancy is an important but overlooked population health activity that is particularly lacking in Ireland. Few, if any, nationally representative estimates of most maternal behaviours and experiences are available. While on-going surveillance of maternal behaviours has not been a priority thus far in European countries including Ireland, on-going surveillance was identified as a key priority in the United States (US) during the 1980’s when the Pregnancy Risk Assessment Monitoring System (PRAMS), was established. Today, PRAMS is the only surveillance programme of maternal behaviours and experiences world-wide. Although on-going prevalence estimates are required in Ireland, studies which examine the offspring health effects of maternal behaviours are also required, since various questions regarding maternal exposures and their offspring health effects remain unanswered. Gestational alcohol consumption is one such important maternal exposure which is common in pregnancy, though its offspring health effects are unclear, particularly at lower or moderate levels. Thus, guidelines internationally have not reached consensus on safe alcohol recommendations for pregnant women. The aims of this thesis are to implement the PRAMS in Ireland (PRAMS Ireland), to describe the prevalence of health behaviours around the time of pregnancy in Ireland and to examine the effect of health behaviours on pregnancy and child outcomes (specifically the relationship between alcohol use during pregnancy and infant and child growth). Structure: In Chapter 1, a brief background and rationale for the work, as well as the thesis aims and objective is provided. A detailed description of the design and implementation of PRAMS Ireland is described in Chapter 2. Chapter 3 and Chapter 4 describe the methodological results of the implementation of the PRAMS Ireland pilot study and PRAMS Ireland main study. In Chapter 5, a comparison of alcohol prevalence in two Irish studies (PRAMS Ireland and Growing up in Ireland (GUI)) and one multi-centre prospective cohort study, Screening for Pregnancy Endpoints (SCOPE) Study is detailed. Chapter 6 describes findings on adherence to National Clinical Guidelines on health behaviours and nutrition around the time of pregnancy in PRAMS Ireland. Findings on exposure to alcohol use in pregnancy and infant growth outcomes are described in Chapter 7 and Chapter 8. The results of analysis conducted to examine the impact of gestational alcohol use on offspring growth trajectories to age ten are described in Chapter 9. Finally, a discussion of the findings, strengths and limitations of the thesis, direction for future research, policy, practice and public health implications are discussed in Chapter 10.Results: Implementation of PRAMS: PRAMS may be an effective system for the surveillance of health behaviours around the time of pregnancy in the Irish context. PRAMS Ireland had high response rates (67% and 61% response rates in the pilot and main study respectively), high item completion rates and valid prevalence estimates for many health behaviours. Examining prevalence of health behaviours: We found high levels of alcohol consumption before and during pregnancy, poor adherence to healthy diets and high levels of smoking before and during pregnancy among women in Ireland. Socially disadvantaged women had higher rates of deleterious health behaviours before pregnancy, although women with the most deleterious behaviour profiles before pregnancy appeared to experience the greatest gain in protective health behaviours during pregnancy. The impact of alcohol use on infant and offspring growth: We found that low and moderate levels of alcohol use did not impact on birth outcomes or offspring growth whereas heavy alcohol consumption resulted in reduced birth length and birth weight; however, this finding was not consistently observed across all studies. Selection, reporting and confounding biases which are common in observational research could be masking harmful effects. Conclusion: PRAMS is a valid and feasible method of surveillance of health behaviours around the time of pregnancy in Ireland. A surveillance program of maternal behaviours and experiences is immediately warranted due to high levels of deleterious health behaviours around the time of pregnancy in Ireland. Although our results do not indicate any evidence of harm, given the quality of evidence available, abstinence and advice of abstinence from alcohol may be the most prudent choice for patients and healthcare professionals respectively. Further studies of the effects of gestational alcohol use are required; particularly those which can reduce selection bias, reporting bias and confounding.

The effect of positive psychological interventions on psychological and physical well-being during pregnancy

Prenatal well-being can have significant effects on the mother and developing foetus. Positive psychological interventions, including gratitude and mindfulness, consistently demonstrate benefits for well-being in diverse populations. No research has been conducted on gratitude during pregnancy; the few studies of prenatal mindfulness interventions have demonstrated well-being benefits. The current study examined the effects of gratitude and mindfulness interventions on prenatal maternal well-being, cortisol and birth outcomes. Five studies were conducted. Study 1 was a systematic review of mindfulness intervention effects on cortisol; this highlighted potential benefits of mindfulness but the need for rigorous protocols in future research. In Study 2 a gratitude and a mindfulness intervention were developed and evaluated; findings indicate usefulness of two 3 week interventions. Study 3 examined the effects of these interventions in a randomised controlled trial (RCT) of non-pregnant women, before examining a pregnant group. No significant intervention effects were found in this study, potentially due to insufficient power and poor protocol adherence. Changes in expected directions were observed for most outcomes and the potential utility of a combined gratitude and mindfulness intervention was noted. In Study 4 a gratitude during pregnancy (GDP) scale was developed and the reliability of an existing mindfulness measure (MAAS) was examined in a pregnant group. Both scales were found to be suitable and reliable measures in pregnancy. Study 5 incorporated the findings of the previous four studies to examine of the effect of a combined mindfulness and gratitude intervention with a group of pregnant women. Forty-six participants took part in a 5-week RCT that examined intervention effects on prenatal gratitude, mindfulness, happiness, satisfaction with life, social support, prenatal stress, depression and sleep. Findings indicated that the intervention improved sleep quality and that effects for prenatal distress were approaching significance. Issues of attrition and non-compliance to study protocols were problematic and are discussed. In summary, the current thesis highlights the need for robust measurement, and intervention and cortisol sampling protocols in future research, particularly with pregnant groups. Findings also demonstrate tentative benefits of a gratitude and mindfulness intervention during pregnancy.