COVID-19 and pregnancy: A European study on pre- and post-infection medication use.

PURPOSE: The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location. METHODS: We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis. RESULTS: The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1-2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids. CONCLUSION: Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes.

COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort.

AIM: The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. METHODS: Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). FINDINGS: We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. CONCLUSION: Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy.

Effectiveness of an academic detailing intervention in primary care on the prescribing of non-steroidal anti-inflammatory drugs.

PURPOSE: The objective of this study was to examine the impact of an academic detailing programme in primary care in Norway on the prescribing rate of diclofenac, naproxen and non-steroidal anti-inflammatory drugs (NSAIDs) in total. METHODS: An academic detailing programme was delivered to general practitioners (GPs) in two Norwegian cities. The key message was to avoid diclofenac and COX-2 inhibitors and to use naproxen as the NSAID of choice. We analysed prescription data for 12 months before and after the programme to estimate its impact, using interrupted time series to control for underlying trends, and using the rest of Norway as a comparator. The primary outcome was change in the proportion of the population filling a prescription for diclofenac; secondary outcomes were change in naproxen prescribing and change in total NSAID prescribing. RESULTS: Controlling for baseline trends, and relative to changes in the rest of Norway, there was a statistically significant reduction in the prescribing rate of diclofenac in both cities (- 18% and - 16%, respectively) immediately after the intervention. The impact of the programme on prescribing of diclofenac was maintained by the end of the 12 month follow-up period. An increase in the prescribing of naproxen was observed in both cities. The programme had no impact on the overall rate of prescribing of NSAIDs. CONCLUSION: Academic detailing was effective in changing the choice of prescribed NSAID amongst Norwegian GPs. Academic detailing is potentially an important method for providing GPs with independent, evidence-based updates on pharmacotherapy to improve prescribing.

Does a palliative medicine service reduce hospital length of stay and costs in adults with a life-limiting illness?-a difference-in-differences evaluation of service expansion in Ireland.

BACKGROUND: People approaching end of life account disproportionately for health care costs, and the majority of these costs accrue in hospitals. The economic evidence base to improve value of care to this population is thin. Natural experiment methods may be helpful in bridging evidence gaps with credible causal estimates from routine data, but these methods have seldom been applied in this field. This study aimed to evaluate the association between timely palliative care consultation and length of stay for adults with serious illness admitted to acute hospital in Ireland. METHODS: In primary analysis we evaluated if timely palliative care receipt following emergency hospital inpatient admission impacted length of stay (LOS); in secondary analysis we verified if palliative medicine service (PMS) implementation co-occurred with any changes in in-hospital mortality, and we estimated cost differences associated with any change in LOS. This was a secondary analysis on routinely collected data for acute admissions to public hospitals in Ireland. We used difference-in-differences analysis to exploit the staggered implementation of PMS teams at acute public hospitals in Ireland between 2010 and 2015. We identified palliative care receipt following PMS implementation using ICD-10 codes, and we matched admissions involving a palliative care interaction to admissions in years prior to PMS implementation using propensity score weights. RESULTS: Our primary analytic sample included 4,314 observations, of whom 608 (14%) received timely palliative care. We estimated that the intervention reduced LOS by nearly two days, with an estimated associated saving per admission of €1,820. These analyses were robust to multiple sensitivity analyses on regression specification, weighting strategy and site selection. Proportion of admissions ending in death did not change following PMS implementation. CONCLUSIONS: Prompt interaction between suitable patients and palliative care can improve the quality and efficiency of care to this population. Many patients receive palliative care later in the hospital stay, which does not yield cost-savings. Future studies can extend and strengthen our approach with better data, as well as using different methods to understand how to trigger palliative care early in a hospital admission and realise available gains.

Formal health care costs among older people in Ireland: methods and estimates using The Irish Longitudinal Study on Ageing (TILDA).

Background: Reliable data on health care costs in Ireland are essential to support planning and evaluation of services. New unit costs and high-quality utilisation data offer the opportunity to estimate individual-level costs for research and policy. Methods: Our main dataset was The Irish Longitudinal Study on Ageing (TILDA). We used participant interviews with those aged 55+ years in Wave 5 (2018) and all end-of-life interviews (EOLI) to February 2020. We weighted observations by age, sex and last year of life at the population level. We estimated total formal health care costs by combining reported usage in TILDA with unit costs (non-acute care) and public payer reimbursement data (acute hospital admissions, medications). All costs were adjusted for inflation to 2022, the year of analysis. We examined distribution of estimates across the population, and the composition of costs across categories of care, using descriptive statistics. We identified factors associated with total costs using generalised linear models. Results: There were 5,105 Wave 5 observations, equivalent at the population level to 1,207,660 people aged 55+ years and not in the last year of life, and 763 EOLI observations, equivalent to 28,466 people aged 55+ years in the last year of life. Mean formal health care costs in the weighted sample were EUR 8,053; EUR 6,624 not in the last year of life and EUR 68,654 in the last year of life. Overall, 90% of health care costs were accounted for by 20% of users. Multiple functional limitations and proximity to death were the largest predictors of costs. Other factors that were associated with outcome included educational attainment, entitlements to subsidised care and serious chronic diseases. Conclusions: Understanding the patterns of costs, and the factors associated with very high costs for some individuals, can inform efforts to improve patient experiences and optimise resource allocation.

Estimating the national carbon footprint of inhalers in healthcare.

BACKGROUND: Metered dose inhalers (MDIs) contain greenhouse gases which have a disproportionate effect on the carbon footprint of healthcare. There are more environmentally friendly alternatives such as dry powder inhalers (DPIs) or soft mist inhalers (SMIs). AIMS: This study aims to approximate the carbon footprint of inhalers dispensed in Irish healthcare. METHODS: Health Market Research data was used to examine the number of inhalers sold in Ireland in 2019 via dispensing data from pharmacy IT systems. The carbon footprint per inhaler data was then used to calculate the total carbon footprint of each drug class, and an estimate for the total carbon footprint of inhalers sold in Ireland was generated. RESULTS: 4,427,287 inhalers were dispensed in Ireland in 2019 of which 2,608,433 (59%) were MDIs and 1,818,854 were DPIs/SMIs (41.1%). The total carbon equivalent of these inhalers was estimated to be 54,765 tCO2. MDIs account for 59% of inhaler units dispensed but account for 97% of inhaler-related carbon emissions. CONCLUSION: Targeting inhaler prescribing offers the potential to significantly improve the carbon footprint of Irish healthcare. Establishing the current carbon footprint of the inhalers that are prescribed, dispensed, and disposed in Ireland is a necessary baseline to inform moving towards a net zero health service.

Evolution of National Guidelines on Medicines Used to Treat COVID-19 in Pregnancy in 2020-2022: A Scoping Review.

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists' societies in thirteen countries in 2020-2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir-ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir-ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19.

Rationalising Antipsychotic Prescribing in Dementia (RAPID) complex intervention: A mixed-methods feasibility intervention study.

Background: To help address the issue of inappropriate antipsychotic prescribing to nursing home residents with dementia, the 'Rationalising Antipsychotic Prescribing in Dementia' (RAPID) complex intervention was developed, comprising staff education and training, academic detailing and a novel resident assessment tool. Objectives: The primary objective was to assess the feasibility and acceptability of the RAPID complex intervention in a nursing home setting. The secondary objective was to describe associated trends in psychotropic prescribing, falls, and behavioural symptoms. Methods: A mixed-methods feasibility intervention study in one large nursing home in Ireland was undertaken between 07/2017 and 01/2018. Focus groups and semi-structured interviews were conducted with nursing home staff and GPs at the end of the 3-month follow up period to assess participants' experience of the intervention. Quantitative measurements included pre- and post-course evaluation and psychotropic prescribing rates. Results: Sixteen nursing home staff members attended the two education and training days (21% attendance rate), and four GPs participated in the academic detailing sessions (100% attendance rate). Participants of the focus groups and interviews (n = 18) found the education and training beneficial for their work and expressed a desire to continue educating new staff after the study's completion. However, there was limited usage of the resident assessment tool. Participants also offered recommendations to enhance the intervention.The proportion of dementia residents prescribed at least one regular antipsychotic was stable over the 3-months pre-intervention at 45% (n = 18), and at baseline at 44% (n = 19) but decreased slightly to 36% (n = 14) at 3-months post-intervention. At the same time the absolute number of 'PRN' psychotropics administered monthly to dementia residents decreased substantially from 90 at baseline to 69 at 3-months post-intervention. Conclusion: The RAPID complex intervention was broadly feasible to conduct and may be acceptable to stakeholders. However, before it can be evaluated in larger scale studies, certain protocol modifications and further exploratory work are required to improve implementation.

Deciphering patterns of respiratory medication use in Ireland to target interventions appropriately: a focus on COPD.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Developing a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia.

Background: Antipsychotics are commonly prescribed to people living with dementia in nursing home settings, despite strong guideline recommendations against their use except in limited circumstances. We aimed to transparently describe the development process for a complex intervention targeting appropriate requesting and prescribing of antipsychotics to nursing home residents with dementia in Ireland, by nurses and general practitioners (GPs) respectively. Methods: We report the development process for the 'Rationalising Antipsychotic Prescribing in Dementia' (RAPID) complex intervention, in accordance with the 'Guidance for reporting intervention development studies in health research' (GUIDED) checklist.  The UK Medical Research Council framework for developing and evaluating complex interventions guided our overall approach, incorporating evidence and theory into the intervention development process. To unpack the intervention development process in greater detail, we followed the Behaviour Change Wheel approach. Guided by our stakeholders, we conducted three sequential studies (systematic review and qualitative evidence synthesis, primary qualitative study and expert consensus study), to inform the intervention development. Results: The RAPID complex intervention was developed in collaboration with a broad range of stakeholders, including people living with dementia and family carers, between 2015 and 2017. The finalised RAPID complex intervention was comprised of the following three components; 1) Education and training sessions with nursing home staff; 2) Academic detailing with GPs; 3) Introduction of an assessment tool to the nursing home. Conclusions: This paper describes the steps used by the researchers to develop a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia in Ireland, according to the GUIDED checklist. We found that the GUIDED checklist provided a useful way of reporting all elements in a cohesive manner and complemented the other tools and frameworks used. Transparency in the intervention development processes can help in the translation of evidence into practice.

Pharmacist-led academic detailing intervention in primary care: a mixed methods feasibility study.

Background Academic detailing is a form of continuing medical education in which a trained health professional such as a physician or pharmacist visits prescribers in their practice to provide evidence-based information. While academic detailing has been adopted in other countries, this strategy is not routinely used in Ireland. Objective The aim of this study was to assess the feasibility and acceptability to General Practitioners (GPs) of a pharmacist-led academic detailing intervention in Ireland. Setting General Practice in County Cork, Ireland. Method A mixed methods feasibility study comprising a pharmacist-led academic detailing intervention on urinary incontinence in older people, quantitative data from patient medical records, and qualitative data from focus groups with GPs. The medical records for all patients aged ≥ 65 years who were attending a participating GP with a diagnosis of urinary incontinence were analysed using a before-after approach. The measures of prescribing assessed before and after the intervention were: LUTS-FORTA criteria, Drug Burden Index, and the Anticholinergic Cognitive Burden scale. Focus groups were carried out with GPs who participated in the academic detailing intervention. Main outcome measure The quantitative prescribing patterns of the GPs and their qualitative responses from the focus groups. Results Twenty-three GPs participated in the academic detailing intervention from a selection of different types of general practice. The medical records of 154 patients were analysed. There was minimal or no change in any of the prescribing measures used. Fourteen GPs attended focus groups. GPs considered the topic of urinary incontinence as relevant to general practice. Participants appreciated the succinct nature of the information in the educational materials but expressed a preference for a more easily retrievable format, such as an online version rather than paper-based. Conclusion This study demonstrated that a pharmacist-led academic detailing intervention was acceptable to GPs in Ireland. Further research is needed in a larger population evaluating the impact and cost effectiveness of academic detailing to optimise patient care.

Utilization Patterns of Oral Disease-Modifying Drugs in Commercially Insured Patients with Multiple Sclerosis.

BACKGROUND: The approval of new oral disease-modifying drugs (DMDs), such as fingolimod, dimethyl fumarate (DMF), and teriflunamide, has considerably expanded treatment options for relapsing forms of multiple sclerosis (MS). However, data describing the use of these agents in routine clinical practice are limited. OBJECTIVE: To describe time trends and identify factors associated with oral DMD treatment initiation and switching among individuals with MS. METHODS: Using data from a large sample of commercially insured patients, we evaluated changes over time in the proportion of MS patients who initiated treatment with an oral DMD and who switched from an injectable DMD to an oral DMD between 2009 and 2014 in the United States. We evaluated predictors of oral DMD use using conditional logistic regression in 2 groups matched on calendar time: oral DMD initiators matched to injectable DMDs initiators and oral DMD switchers matched to those who switched to a second injectable DMD. RESULTS: Our cohort included 7,576 individuals who initiated a DMD and 1,342 who switched DMDs, of which oral DMDs accounted for 6% and 39%, respectively. Oral DMD initiation and switching steadily increased from 5% to 16% and 35% to 84%, respectively, between 2011 and 2014, with DMF being the most commonly used agent. Of the potential predictors with clinical significance, a recent neurologist consultation (OR = 1.60; 95% CI = 1.20-2.15) and emergency department visit (OR = 1.43; 95% CI = 1.01-2.01) were significantly associated with oral DMD initiation. History of depression was noted to be a potential predictor of oral DMD initiation; however, the estimate for this predictor did not reach statistical significance (OR = 1.35; 95% CI = 0.99-1.84). No clinically relevant factors measured in our data were associated with switching to an oral DMD. CONCLUSIONS: Oral DMDs were found to be routinely used as second-line treatment. However, we identified few factors predictive of oral DMD initiation or switching, which implies that their selection is driven by patient and/or physician preferences. DISCLOSURES: This study was funded by CVS Caremark through an unrestricted research grant to Brigham and Women's Hospital. Shrank and Matlin were employees of, and shareholders in, CVS Health at the time of the study; they report no financial interests in products or services that are related to the subject of this study. Spettell is an employee of, and shareholder in, Aetna. Chitnis serves on clinical trial advisory boards for Novartis and Genzyme-Sanofi; has consulted for Bayer, Biogen Idec, Celgene, Novartis, Merck-Serono, and Genentech-Roche; and has received research support from NIH, National Multiple Sclerosis Society, Peabody Foundation, Consortium for MS Centers, Guthy Jackson Charitable Foundation, EMD-Serono, Novartis Biogen, and Verily. Desai reports receiving a research grant from Merck for unrelated work. Gagne is principal investigator of a research grant from Novartis Pharmaceuticals Corporation to the Brigham and Women's Hospital and has received grant support from Eli Lilly, all for unrelated work. He is also a consultant to Aetion and Optum. Minden reports grants from Biogen and other fees from Genentech, EMD Serano, Avanir, and Novartis, unrelated to this study. The other authors have no conflicts to report. This study was presented as a poster at the International Society for Pharmacoepidemiology 32nd Annual Meeting; August 25-28, 2016; Dublin, Ireland.