Drug-drug interactions and the risk of adverse drug reaction-related hospital admissions in the older population.

AIMS: The aims of this study were to estimate potentially clinically important drug-drug interaction (DDI) prevalence, and the average causal effect of DDI exposure on adverse drug reaction (ADR)-related hospital admission, and to examine differences in health-related quality of life (HRQoL) and length of stay (LOS) per DDI exposure in an older (≥65 years) population acutely hospitalized. METHODS: This was a cross-sectional study conducted among 798 older individuals acutely admitted to hospital in Ireland between 2016 and 2017. Medication (current/recently discontinued/over-the-counter) and clinical data (e.g., creatinine clearance) were available. DDIs were identified using the British National Formulary (BNF) and Stockley's Drug Interactions. Causal inference models for DDI exposure on ADR-related hospital admission were developed using directed acyclic graphs. Multivariable logistic regression was used to estimate the average causal effect. Differences in HRQoL (EQ-5D) and LOS per DDI exposure were examined non-parametrically. DDI prevalence, adjusted odds ratios (aOR), and 95% confidence intervals (CIs) are reported. RESULTS: A total of 782 (98.0%) individuals using two or more drugs were included. Mean age was 80.9 (SD ± 7.5) years (range: 66-105); 52.2% were female; and 45.1% (n = 353) had an ADR-related admission. At admission, 316 (40.4% [95% CI: 37.0-43.9]) patients had at least one DDI. The average causal effect of DDI exposure on ADR-related hospital admission was aOR = 1.21 [95% CI: 0.89-1.64]. This was significantly increased by exposure to: DDIs which increase bleeding risk (aOR = 2.00 [1.26-3.12]); aspirin-warfarin (aOR = 2.78 [1.37-5.65]); and esomeprazole-escitalopram (aOR = 3.22 [1.13-10.25]. DDI-exposed patients had lower HRQoL (mean EQ-5D = 0.49 [±0.39]) compared those non-DDI-exposed (mean EQ-5D = 0.57 [±0.41]), (P = .03); and greater median LOS in hospital (8 [IQR5-16]days) compared those non-DDI-exposed (7 [IQR 4-14] days),(P = .04). CONCLUSIONS: Potentially clinically important DDIs carry an increased average causal effect on ADR-related admission, significantly (two-fold) by exposure to DDIs that increase bleeding risk, which should be targeted for medicine optimization.

Gabapentinoids in Ireland 2010 to 2020: An observational study of trends in gabapentinoid prescribing, law enforcement drug seizures and postmortem toxicology.

AIMS: We explored trends in gabapentinoid prescribing, drug seizures and postmortem toxicology using a national pharmacy claims database, law enforcement drug seizures data and a population-based postmortem toxicology database. METHODS: Gabapentinoid prescribing rates per 100 000 eligible population (2010-2020), annual number of drug seizures involving gabapentinoids (2012-2020) and gabapentinoid detection (positive) rates per 100 postmortem toxicology case (2013-2020) were calculated. Negative binomial regression models were used to evaluate longitudinal trends for gabapentin and pregabalin separately. RESULTS: Gabapentin (adjusted rate ratio [RR] 1.06, 95% confidence interval [CI] 1.05-1.06, P < .001) and pregabalin (adjusted RR 1.08, 95% CI 1.08-1.09, P < .001) prescribing increased annually, with higher rates of pregabalin (vs. gabapentin) observed every year. Drug seizures involving pregabalin also increased over time (RR 1.54 95% CI 1.25-1.90, P < .0001). Of the 26 317 postmortem toxicology cases, 0.92% tested positive for gabapentin, and 6.37% for pregabalin. Detection rates increased for both gabapentin (RR 1.28, 95% CI 1.11-1.48, P < .001) and pregabalin (RR 1.13, 95% CI 1.11-1.48, P < .001) between 2013 and 2020. A total of 1901 cases (7.2%) tested positive for heroin/methadone; this sub-group had a higher detection rate for pregabalin (n = 528, 27.8%) and gabapentin (n = 41, 2.2%) over the study period, with a high burden of codetections for pregabalin with benzodiazepines (peaking at 37.3% in 2018), and pregabalin with prescription opioids (peaking at 28.9% in 2020). CONCLUSION: This study raises concerns regarding the wide availability of pregabalin in Ireland, including a growing illicit supply, and the potential for serious harm arising from poly drug use involving pregabalin among people who use heroin or methadone.

Lessons learned from COVID-19: improving breast cancer care post-pandemic from the patient perspective.

BACKGROUND: Since the onset of the pandemic, breast cancer (BC) services have been disrupted in most countries. The purpose of this qualitative study is to explore the unmet needs, patient-priorities, and recommendations for improving BC healthcare post-pandemic for women with BC and to understand how they may vary based on social determinants of health (SDH), in particular socio-economic status (SES). METHODS: Thirty-seven women, who were purposively sampled based on SDH and previously interviewed about the impact of COVID-19 on BC, were invited to take part in follow-up semi-structured qualitative interviews in early 2023. The interviews explored their perspectives of BC care since the easing of COVID-19 government restrictions, including unmet needs, patient-priorities, and recommendations specific to BC care. Thematic analysis was conducted to synthesize each topic narratively with corresponding sub-themes. Additionally, variation by SDH was analyzed within each sub-theme. RESULTS: Twenty-eight women (mean age = 61.7 years, standard deviation (SD) = 12.3) participated in interviews (response rate = 76%). Thirty-nine percent (n = 11) of women were categorized as high-SES, while 61% (n = 17) of women were categorized as low-SES. Women expressed unmet needs in their BC care including routine care and mental and physical well-being care, as well as a lack of financial support to access BC care. Patient priorities included the following: developing cohesion between different aspects of BC care; communication with and between healthcare professionals; and patient empowerment within BC care. Recommendations moving forward post-pandemic included improving the transition from active to post-treatment, enhancing support resources, and implementing telemedicine where appropriate. Overall, women of low-SES experienced more severe unmet needs, which in turn resulted in varied patient priorities and recommendations. CONCLUSION: As health systems are recovering from the COVID-19 pandemic, the emphasis should be on restoring access to BC care and improving the quality of BC care, with a particular consideration given to those women from low-SES, to reduce health inequalities post-pandemic.

Rethinking Clostridioides difficile infection (CDI) surveillance definitions based on changing healthcare utilisation and a more realistic incubation period: reviewing data from a tertiary-referral hospital, Ireland, 2012 to 2021.

BackgroundCommunity-associated Clostridioides difficile infections (CA-CDI) have increased worldwide. Patients with CDI-related symptoms occurring < 48 hours after hospitalisation and no inpatient stay 12 weeks prior are classified as CA-CDI, regardless of hospital day attendances 3 months before CDI onset. Healthcare-associated (HA) CDIs include those with symptom onset ≥ 48 hours post hospitalisation.AimTo consider an incubation period more reflective of CDI, and changing healthcare utilisation, we measured how varying surveillance specifications to categorise patients according to their CDI origin resulted in changes in patients' distribution among CDI origin categories.MethodsNew CDI cases between 2012-2021 from our hospital were reviewed. For patients with CA-CDI, hospital day attendances in the 3 months prior were recorded. CA-CDI patients with hospital day attendances and recently discharged CDI patients (RD-CDI; CDI onset 4-12 weeks after discharge) were combined into a new 'healthcare-exposure' category (HE-CDI). Time from hospitalisation to disease onset was varied and the midpoint between optimal and balanced cut-offs was used instead of 48 hours to categorise HA-CDI.ResultsOf 1,047 patients, 801 (76%) were HA-CDI, 205 (20%) CA-CDI and 41 (4%) were RD-CDI. Of the CA-CDI cohort, 45 (22%) met recent HE-CDI criteria and, when reassigned, reduced CA-CDI to 15%. Sensitivity analysis indicated a day 4 cut-off for assigning HA-CDI. Applying this led to 46 HA-CDI reassigned as CA-CDI. Applying both HE and day 4 criteria led to 72% HA-CDI, 20% CA-CDI, and 8% HE-CDI (previously RD-CDI).ConclusionCDI surveillance specifications reflecting healthcare exposure and an incubation period more characteristic of C. difficile may improve targeted CDI prevention interventions.

Impact of the COVID-19 pandemic on women living with and beyond breast cancer: a qualitative study of women's experiences and how they varied by social determinants of health.

BACKGROUND: The aim of this study is to explore the general impact of COVID-19 on the access and use of BC services and support and overall well-being in women living with a diagnosis of breast cancer (BC) and to investigate how these experiences varied by the social determinants of health (SDH). METHODS: Semi-structured qualitative interviews were conducted with women selected through stratified purposive sampling to ensure data were available on information-rich cases. Interviews were conducted in early 2021 during government restrictions due to COVID-19. Thematic analysis was conducted to obtain overall experience and variation of experience based on SDH. RESULTS: Thirty seven women participated in interviews. Three major themes, with additional subthemes, emerged from analysis: 1. breast cancer services (screening, active treatment, and routine care); 2. breast cancer support and communication (continuity of care, role of liaison, and support services); and 3. quality of life (QoL) and well-being (emotional well-being; social well-being; and functional well-being). Women's experiences within the themes varied by socio-economic status (SES) and region of residence (urban/rural) specifically for BC services and support. CONCLUSION: The pandemic impacted women living with and beyond BC, but the impact has not been the same for all women. This study highlights areas for improvement in the context of BC care in Ireland and the findings will inform further policy and practice, including standardized BC services, improved communication, and enhancement of cancer support services.

Canadian Blood Services traceback investigation of a suspected case of transfusion-transmitted malaria.

BACKGROUND: A 4-month-old infant hospitalized since birth received multiple blood transfusions. In March 2022, Plasmodium falciparum was confirmed with nucleic acid testing. As the mother was assessed as unlikely to be the source of infection, the blood operator initiated a traceback investigation for a potential blood donor source. The patient had received 13 red blood cell (RBC) transfusions (aliquoted from 11 donors), 4 apheresis platelet (PLT) transfusions and 16 buffy coat pooled PLT transfusions. The blood operator medical team developed a supplementary malaria infection risk questionnaire to identify donors at highest risk of life-time malaria infection, based on birthplace, residence, or travel in malaria-endemic regions. RESULTS: With 79 donors initially implicated, initial focus was on donors of RBC components. The 11 RBC donors were contacted and assessed using the supplementary questionnaire. Three donors, all of whom met current malaria-related donor eligibility criteria, were deemed high risk of prior malaria infection. These donors consented to P. falciparum serology and nucleic acid testing (NAT). One donor who was born and had resided in an endemic West African country for 14 years, was positive for P. falciparum by serology (indirect fluorescent antibody test) and NAT-(Ct ≥32). Lookback of this donor's transfused fresh co-components and prior donation identified no other malaria cases. CONCLUSION: This was a probable transfusion-transmitted malaria (TTM) case from an eligible donor who in retrospect was found to have unrecognized, asymptomatic, semi-immune malaria infection, and who was potentially infectious. Blood donor lack of recall of prior malaria infection does not negate the risk of TTM from those who have lived in malaria-endemic countries.

Vitamin D Supplementation: Does It Have a Preventative or Therapeutic Role in Cancer?

Although best known for its role in skeletal health, a deficiency of vitamin D has also been implicated in cancer formation and progression. The aim of this article was to review the relationship between circulating levels of vitamin D {25(OH)D} and both the risk of developing cancer and outcome from cancer. We also reviewed the effects of vitamin D supplementation on cancer risk and outcome. Our primary focus was on patients with colorectal and breast cancer, as these are two of the cancer types best investigated with respect to the effects of vitamin D on cancer risk and outcome. Based on our review of the literature, we conclude that although low circulating levels of 25(OH)D appears to be associated with an increased risk of developing breast and colorectal cancer, the available evidence suggests that supplementation of healthy subjects with vitamin D does not decrease cancer risk. Supplementation may however, improve outcomes in patients who develop cancer, but this finding remains to be confirmed in an appropriately powered randomized clinical trial.

Costs associated with adverse drug reactions in an older population admitted to hospital: a prospective cohort study.

PURPOSE: This study examines healthcare costs associated with adverse drug reactions (ADR) in an older population admitted acutely to an Irish tertiary hospital. METHODS: Prospective cohort study involving older persons admitted to hospital with and without an ADR. Data was collected at baseline, during hospitalisation and post-discharge. Participants provided information on healthcare resource use three months before admission (baseline) and three months after discharge (follow-up). For each healthcare resource, unit costs were derived and applied. The average cost (standard deviation (SD)) associated with the hospital admission for the ADR and non-ADR are presented. In addition, baseline and follow-up care costs were compared using difference-in-difference analysis and presented with 95% confidence intervals (CI). Costs by preventability and severity of ADR are also presented. RESULTS: A total of n = 230 participants were included (n = 93 ADR and n = 137 without ADR). The average cost associated with hospital admission for an ADR was €9538 (SD €10442) and €9828 (SD €11770) for non-ADR. The additional follow-up costs (difference-in-difference) associated with the ADR was estimated at €2047 (95% CI: -€889 to €4983). The mean incremental follow-up cost of definite preventable ADRs was estimated at €1648 (95% CI: -€4310 to €7605), possible preventable ADRs €2259 (95 CI: -€1194 to €5712) and unavoidable ADRs €1757 (95% CI: -€3377 to €6890). The mean incremental follow-up cost associated with moderate severe ADRs was estimated at €1922 (95% CI: -€1088 to €4932) and €3580 (95% CI: -€4898 to €12,058) for severe ADRs.  CONCLUSION: ADRs leading to hospital admission are associated with modest incremental healthcare costs during and three months after admission. Severe and possibly preventable ADRs were associated with higher costs.

Evaluating awareness, knowledge and practice of healthcare professionals following implementation of a revised pregnancy prevention programme for isotretinoin in Ireland: A multi-stakeholder cross-sectional study.

PURPOSE: In 2018, following an EU-wide safety review, a revised pregnancy prevention programme (PPP) was introduced for isotretinoin (Roaccutane®). This study aimed to examine awareness, knowledge, and experience implementing the revised isotretinoin PPP in clinical practice across three healthcare professional (HCP) groups in Ireland. METHODS: A cross-sectional study using anonymous online surveys among general practitioners (GPs), community pharmacists, and specialist consultants was undertaken. Descriptive analyses are presented. RESULTS: Across all HCP groups there was high (≥87%) awareness that oral isotretinoin is contraindicated in women of childbearing potential (WCBP) unless the conditions of the PPP are fulfilled, but varying awareness among GPs (54.9%) and community pharmacists (45.9%) that exposure during pregnancy can cause both severe fetal malformations and spontaneous abortions. Implementation of the PPP in clinical practice varied across HCP groups. When initiating isotretinoin in WCBP, 66.7% of specialists and 40.8% of GPs indicated they had considered alternative treatment options, and 71.4% of specialists and 31.6% of GPs reported they first requested a pregnancy test. There was limited provision of the patient reminder card to WCBP, where 26.1% of community pharmacists provide this at each dispensing, while 47.6% of specialists and 11.8% of GPs ensured WCBP had a copy of the card when initiating treatment. Across all HCP groups, there was high (≥81.6%) awareness of the need for urgent consultation and immediate cessation of isotretinoin in the event of an unplanned or suspected pregnancy. CONCLUSIONS: Reinforcement of the provision and utilisation of the isotretinoin patient reminder card may be required, and further targeted education on specific elements of the PPP should be considered for GPs and community pharmacists.

Informing interventions to improve uptake of adjuvant endocrine therapy in women with breast cancer: a theoretical-based examination of modifiable influences on non-adherence.

PURPOSE: To inform intervention development, we measured the modifiable determinants of endocrine therapy (ET) non-adherence in women with breast cancer, using the Theoretical Domains Framework (TDF) and examined inter-relationships between these determinants and non-adherence using the Perceptions and Practicalities Approach (PAPA). METHODS: Women with stages I-III breast cancer prescribed ET were identified from the National Cancer Registry Ireland (N = 2423) and invited to complete a questionnaire. A theoretically based model of non-adherence was developed using PAPA to examine inter-relationships between the 14 TDF domains of behaviour change and self-reported non-adherence. Structural equation modelling (SEM) was used to test the model. RESULTS: A total of 1606 women participated (response rate = 66%) of whom 395 (25%) were non-adherent. The final SEM with three mediating latent variables (LVs) (PAPA Perceptions: TDF domains, Beliefs about Capabilities, Beliefs about Consequences; PAPA Practicalities: TDF domain, Memory, Attention, Decision Processes and Environment) and four independent LVs (PAPA Perceptions: Illness intrusiveness; PAPA Practicalities: TDF domains, Knowledge, Behaviour Regulation; PAPA External Factors: TDF domain, Social Identity) explained 59% of the variance in non-adherence and had an acceptable fit (χ2(334) = 1002, p < 0.001; RMSEA = 0.03; CFI = 0.96 and SRMR = 0.07) Knowledge had a significant mediating effect on non-adherence through Beliefs about Consequences and Beliefs about Capabilities. Illness intrusiveness had a significant mediating effect on non-adherence through Beliefs about Consequences. Beliefs about Consequences had a significant mediating effect on non-adherence through Memory, Attention, Decision Processesg and Environment. CONCLUSIONS: By underpinning future interventions, this model has the potential to improve ET adherence and, hence, reduce recurrence and improve survival in breast cancer.

Prescription drugs with potential for misuse in Irish prisons: analysis of national prison prescribing trends, by gender and history of opioid use disorder, 2012 to 2020.

BACKGROUND: Pharmacotherapy is essential for the delivery of an equivalent standard of care in prison. Prescribing can be challenging due to the complex health needs of prisoners and the risk of misuse of prescription drugs. This study examines prescribing trends for drugs with potential for misuse (opioids, benzodiazepines, Z-drugs, and gabapentinoids) in Irish prisons and whether trends vary by gender and history of opioid use disorder (OUD). METHODS: A repeated cross-sectional study between 2012 and 2020 using electronic prescribing records from the Irish Prison Services, covering all prisons in the Republic of Ireland was carried out. Prescribing rates per 1,000 prison population were calculated. Negative binomial (presenting adjusted rate ratios (ARR) per year and 95% confidence intervals) and joinpoint regressions were used to estimate time trends adjusting for gender, and for gender specific analyses of prescribing trends over time by history of OUD. RESULTS: A total of 10,371 individuals were prescribed opioid agonist treatment (OAT), opioids, benzodiazepines, Z-drugs or gabapentinoids during study period. History of OUD was higher in women, with a median rate of 597 per 1,000 female prisoners, compared to 161 per 1,000 male prisoners. Prescribing time trends, adjusted for gender, showed prescribing rates decreased over time for prescription opioids (ARR 0.82, 95% CI 0.80-0.85), benzodiazepines (ARR 0.99, 95% CI 0.98-0.999), Z-drugs (ARR 0.90, 95% CI 0.88-0.92), but increased for gabapentinoids (ARR 1.07, 95% CI 1.05-1.08). However, prescribing rates declined for each drug class between 2019 and 2020. Women were significantly more likely to be prescribed benzodiazepines, Z-drugs and gabapentinoids relative to men. Gender-specific analyses found that men with OUD, relative to men without, were more likely to be prescribed benzodiazepines (ARR 1.49, 95% CI 1.41-1.58), Z-drugs (ARR 10.09, 95% CI 9.0-11.31), gabapentinoids (ARR 2.81, 95% CI 2.66-2.97). For women, history of OUD was associated with reduced gabapentinoid prescribing (ARR 0.33, 95% CI 0.28-0.39). CONCLUSIONS: While the observed reductions in prescription opioid, benzodiazepine and Z-drug prescribing is consistent with guidance for safe prescribing in prisons, the increase in gabapentinoid (primarily pregabalin) prescribing and the high level of prescribing to women is concerning. Our findings suggest targeted interventions may be needed to address prescribing in women, and men with a history of OUD.

Breast cancer care amidst a pandemic: a scoping review to understand the impact of coronavirus disease 2019 on health services and health outcomes.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, health services for breast cancer (BC) have been disrupted. Our scoping review examines the impact of the COVID-19 pandemic on BC services, health outcomes, and well-being for women. Additionally, this review identifies social inequalities specific to BC during the pandemic. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guidelines, the literature search was conducted using scientific databases starting from March 2020 through November 2021. Studies were identified and selected by two researchers based on inclusion criteria, and the relevant data were extracted and charted to summarize the findings. Ninety-three articles were included in this review. Main themes included are as follows: (i) the impact of COVID-19 on BC services; (ii) the impact of COVID-19 on health outcomes and well-being in women with BC; and (iii) any variation in the impact of COVID-19 on BC by social determinants of health. There were apparent disruptions to BC services across the cancer continuum, especially screening services. Clinical repercussions were a result of such disruptions, and women with BC experienced worsened quality of life and psychosocial well-being. Finally, there were social inequalities dependent on social determinants of health such as age, race, insurance status, and region. Due to the disruption of BC services during the COVID-19 pandemic, women were impacted on their health and overall well-being. The variation in impact demonstrates how health inequities have been exacerbated during the pandemic. This comprehensive review will inform timely health-care changes to minimize long-term impacts of the pandemic and improve evidence-based multidisciplinary needs.

Clostridioides difficile infection in neurosurgical patients in a national centre over 10 years: less common but associated with longer hospital stays.

BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea, contributing to patient morbidity and prolonged length-of-stay (LOS). We retrospectively assessed CDI over a decade in a national neurosurgical centre, with a multi-disciplinary approach to CDI surveillance and antimicrobial stewardship, by comparing CDI patients with other patient groups. METHODS: Data on CDI in neurosurgical inpatients between January 2012 and December 2021 were collated. Disease-specific variables were compared to other inpatients with CDI. Rates per 10,000 bed days used were calculated. Patient-specific differences were compared with neurosurgical patients without CDI. CDI rates by patient group were explored using odds ratio (OR) and χ2 analyses. Negative binomial regression was used to investigate CDI rates over time. RESULTS: Of 50 neurosurgical patients with CDI, all were HA; the average age was 53 years (standard deviation (SD) 16.3 years), 49 were first-episode CDI, and three had severe CDI. The majority (76.7%) had received recent antimicrobials. Compared with non-neurosurgical CDI patients, neurosurgical CDI rates differed significantly (1.9 versus 3.6 per 10,000 bed days used, p < 0.05), neurosurgical patients were younger (p ≤ 0.01), C. difficile testing was more likely to be requested by neurosurgeons (OR 2.4; p ≤ 0.01), and the proportion of severe CDI was higher (6% versus 2%, OR 3.0, p = 0.07, confidence interval (CI) 0.54 to 11.3). Within the neurosurgical cohort, CDI patients had an average LOS four times that of other patients (CI 15.2 to 35.1; p < 0.01) and were older (53.5 versus 47.8 years, CI 0.1 to 11 years; p < 0.05). Only one CDI outbreak was linked to neurosurgical patients. CONCLUSION: CDI in neurosurgery patients differed from the wider hospital, with greater awareness of CDI testing. Longer LOS impacted bed utilisation with limited capacity. Robust surveillance supports proactive antimicrobial stewardship programmes in this vulnerable population.

Valproate utilisation trends among women of childbearing potential in Ireland between 2014 and 2019: A drug utilisation study using interrupted time series.

PURPOSE: This study aimed to examine trends in valproate use among women of childbearing potential (WCBP) aged 16-44 years in Ireland following two European-directed regulatory interventions in December 2014 and April 2018. METHODS: This was a repeated cross-sectional study using monthly national pharmacy claims data, to examine trend changes in the prevalence of valproate use among WCBP pre and post two separate regulatory events in December 2014 and April 2018. Annual population estimates from the Central Statistics Office were used to calculate the prevalence rate per 1000 eligible women. Segmented regression analysis of interrupted time series with negative binomial regression was used to examine rates for WCBP aged 16-44 years, and by 10-year age groups. Prevalence ratios (PR) are presented with 95% confidence intervals (CIs). RESULTS: Among WCBP aged 16-44 years, there was no statistically significant change in the month-to-month prevalence ratio in the post- compared to pre-December 2014 intervention period. A significant decline was, however, observed in the post-, compared to pre-April 2018 intervention period (PR = 0.998, [95% CIs: 0.996, 1.000]; p = 0.029). Among those aged 16-24 years, a significant decreasing trend in the month-to-month prevalence ratio was found in the post- compared to pre-December 2014 intervention period (PR = 0.991, [95% CIs: 0.984, 0.998];p <0.01). A marginal effect was observed in the post- compared to pre-April 2018 intervention period for those aged 25-34 years (PR = 0.996, [95% CIs: 0.992, 1.000]; p = 0.048). CONCLUSION: Although no evidence of change was observed following the December 2014 intervention period, a significant decline in the prevalence ratio of valproate use was observed after the 2018 intervention, which may reflect the introduction of the most recent contraindication measures.

Comprehensive Geriatric Assessment for community-dwelling, high-risk, frail, older people.

BACKGROUND: Comprehensive Geriatric Assessment (CGA) is a multidimensional interdisciplinary diagnostic process focused on determining an older person's medical, psychological and functional capability in order to develop a co-ordinated and integrated care plan. CGA is not limited simply to assessment, but also directs a holistic management plan for older people, which leads to tangible interventions. While there is established evidence that CGA reduces the likelihood of death and disability in acutely unwell older people, the effectiveness of CGA for community-dwelling, frail, older people at risk of poor health outcomes is less clear. OBJECTIVES: To determine the effectiveness of CGA for community-dwelling, frail, older adults at risk of poor health outcomes in terms of mortality, nursing home admission, hospital admission, emergency department visits, serious adverse events, functional status, quality of life and resource use, when compared to usual care. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, three trials registers (WHO ICTRP, ClinicalTrials.gov and McMaster Aging Portal) and grey literature up to April 2020; we also checked reference lists and contacted study authors. SELECTION CRITERIA: We included randomised trials that compared CGA for community-dwelling, frail, older people at risk of poor healthcare outcomes to usual care in the community. Older people were defined as 'at risk' either by being frail or having another risk factor associated with poor health outcomes. Frailty was defined as a vulnerability to sudden health state changes triggered by relatively minor stressor events, placing the individual at risk of poor health outcomes, and was measured using objective screening tools. Primary outcomes of interest were death, nursing home admission, unplanned hospital admission, emergency department visits and serious adverse events. CGA was delivered by a team with specific gerontological training/expertise in the participant's home (domiciliary Comprehensive Geriatric Assessment (dCGA)) or other sites such as a general practice or community clinic (community Comprehensive Geriatric Assessment (cCGA)). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted study characteristics (methods, participants, intervention, outcomes, notes) using standardised data collection forms adapted from the Cochrane Effective Practice and Organisation of Care (EPOC) data collection form. Two review authors independently assessed the risk of bias for each included study and used the GRADE approach to assess the certainty of evidence for outcomes of interest. MAIN RESULTS: We included 21 studies involving 7893 participants across 10 countries and four continents. Regarding selection bias, 12/21 studies used random sequence generation, while 9/21 used allocation concealment. In terms of performance bias, none of the studies were able to blind participants and personnel due to the nature of the intervention, while 14/21 had a blinded outcome assessment. Eighteen studies were at low risk of attrition bias, and risk of reporting bias was low in 7/21 studies. Fourteen studies were at low risk of bias in terms of differences of baseline characteristics. Three studies were at low risk of bias across all domains (accepting that it was not possible to blind participants and personnel to the intervention). CGA probably leads to little or no difference in mortality during a median follow-up of 12 months (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.76 to 1.02; 18 studies, 7151 participants (adjusted for clustering); moderate-certainty evidence). CGA results in little or no difference in nursing home admissions during a median follow-up of 12 months (RR 0.93, 95% CI 0.76 to 1.14; 13 studies, 4206 participants (adjusted for clustering); high-certainty evidence). CGA may decrease the risk of unplanned hospital admissions during a median follow-up of 14 months (RR 0.83, 95% CI 0.70 to 0.99; 6 studies, 1716 participants (adjusted for clustering); low-certainty evidence). The effect of CGA on emergency department visits is uncertain and evidence was very low certainty (RR 0.65, 95% CI 0.26 to 1.59; 3 studies, 873 participants (adjusted for clustering)). Only two studies (1380 participants; adjusted for clustering) reported serious adverse events (falls) with no impact on the risk; however, evidence was very low certainty (RR 0.82, 95% CI 0.58 to 1.17). AUTHORS' CONCLUSIONS: CGA had no impact on death or nursing home admission. There is low-certainty evidence that community-dwelling, frail, older people who undergo CGA may have a reduced risk of unplanned hospital admission. Further studies examining the effect of CGA on emergency department visits and change in function and quality of life using standardised assessments are required.

StrokeCog Markov Model: Projected Prevalent and Incident Cases of Stroke and Poststroke Cognitive Impairment to 2035 in Ireland.

BACKGROUND AND PURPOSE: Cognitive impairment no dementia (CIND) and dementia are common stroke outcomes, with significant health and societal implications for aging populations. These outcomes are not included in current epidemiological models. We aimed to develop an epidemiological model to project incidence and prevalence of stroke, poststroke CIND and dementia, and life expectancy, in Ireland to 2035, informing policy and service planning. METHODS: We developed a probabilistic Markov model (the StrokeCog model) applied to the Irish population aged 40 to 89 years to 2035. Data sources included official population and hospital-episode statistics, longitudinal cohort studies, and published estimates. Key assumptions were varied in sensitivity analysis. Results were externally validated against independent sources. The model tracks poststroke progression into health states characterized by no cognitive impairment, CIND, dementia, disability, stroke recurrence, and death. RESULTS: We projected 69 051 people with prevalent stroke in Ireland in 2035 (22.0 per 1000 population [95% CI, 20.8-23.1]), with 25 274 (8.0 per 1000 population [95% CI, 7.1-9.0]) of those projected to have poststroke CIND, and 12 442 having poststroke dementia (4.0 per 1000 population [95% CI, 3.2-4.8]). We projected 8725 annual incident strokes in 2035 (2.8 per 1000 population [95% CI, 2.7-2.9]), with 3832 of these having CIND (1.2 per 1000 population [95% CI, 1.1-1.3]), and 1715 with dementia (0.5 per 1000 population [95% CI, 0.5-0.6]). Life expectancy for stroke survivors at age 50 was 23.4 years (95% CI, 22.3-24.5) for women and 20.7 (95% CI, 19.5-21.9) for men. CONCLUSIONS: This novel epidemiological model of stroke, poststroke CIND, and dementia draws on the best available evidence. Sensitivity analysis indicated that findings were robust to assumptions, and where there was uncertainty a conservative approach was taken. The StrokeCog model is a useful tool for service planning and cost-effectiveness analysis and is available for adaptation to other national contexts.

Rehabilitation interventions to support return to work for women with breast cancer: a systematic review and meta-analysis.

BACKGROUND: Research recommends the development and evaluation of interventions to support women with breast cancer in returning to, or managing, work. Despite this, there has historically been a paucity of rehabilitation interventions to support women with breast cancer to maintain or return to their work role. The aim of this systematic review was to examine key characteristics of rehabilitation interventions, and their effectiveness on work outcomes for women with breast cancer, compared to usual care. METHODS: A systematic review was conducted of controlled studies of rehabilitation interventions with work outcomes for women with breast cancer. Six databases were systematically searched: EMBASE, Web of Science, MEDLINE (OVID), CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL). Results are presented either as pooled odds ratio (OR) or pooled effect size (hedges g) between groups, with 95% confidence intervals (CI). Narrative synthesis was conducted on intervention outcomes not suitable for meta-analysis. RESULTS: Five thousand, five hundred and thirty-five studies were identified. Nine out of 28 abstracts met inclusion criteria. Heterogeneity of interventions and outcomes precluded meta-analysis for most outcomes. Of the interventions included in meta-analysis, no significant differences compared to usual care were found for sick leave (2 studies (12 months); OR 1.11 (95% CI: 0.66 to 1.87), number of sick days taken (2 studies (six months); difference in effect: - 0.08, (95% CI: - 0.48 to 0.38) or working hours (2 studies (12 months); 0.19, (95% CI: - 0.20 to 0.64). Only one study, with a multidisciplinary intervention, showed a significant difference for work outcomes when compared to usual care. Work-specific content featured in three interventions only, none of which provided conclusive evidence for improvement in work outcomes. Enhanced physical and psychological sequalae, and quality of life was observed in some studies. CONCLUSION: There remains a lack of effective and methodologically rigorous rehabilitation intervention studies for breast cancer survivors. The development and evaluation of effective rehabilitation interventions to support return to work is warranted.

Cognitive decline associated with anticholinergics, benzodiazepines and Z-drugs: Findings from The Irish Longitudinal Study on Ageing (TILDA).

AIMS: To estimate the association between patterns of anticholinergic, benzodiazepine and Z-drug medication use and change in cognitive function in middle-aged and older adults. METHODS: This prospective cohort study used data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA), including community-dwelling adults aged ≥50 years followed for up to 4 years (n = 7027). Cognitive function was assessed using the Mini Mental State Examination, animal naming test and word recall tests. Regular medication use was self-reported at baseline and follow-up interviews at 2 and 4 years. Pharmacy dispensing claims for a subset (n = 2905) allowed assessment of medication use between interviews and cumulative dosage. Medication use at consecutive waves of TILDA was analysed in relation to change in cognitive function between waves. RESULTS: Strongly anticholinergic medications (Anticholinergic Cognitive Burden scale 3), benzodiazepines and Z-drugs were reported by 7.3%, 5.8% and 5.1% of participants, respectively, at any time during the study. Adjusting for potential confounders, new anticholinergic use between interviews was associated with change in recall score (-1.09, 95% confidence interval -1.64, -0.53) over 2 years compared to non-use, but not with MMSE (0.07; 95% CI -0.21, 0.34) or animal naming (-0.70; 95% CI -1.43, 0.03). The pharmacy claims analysis was consistent with this finding. Other hypothesised associations were not supported. CONCLUSIONS: Except for new use of anticholinergic medications, no other findings supported a risk of cognitive decline over 2-year periods in this middle-aged and older cohort. Patients and prescribers should weigh this potential risk against potential benefits of commencing anticholinergic medications.

Longitudinal Medication Adherence in Older Adults With Multimorbidity and Association With Health Care Utilization: Results From the Irish Longitudinal Study on Ageing.

BACKGROUND: The association between objectively measured nonadherence and health care utilization in multimorbid older people is unclear. OBJECTIVE: To measure medication adherence across multiple chronic conditions, identify adherence patterns, and estimate the association between adherence and self-reported health care utilization. METHODS: This is a retrospective cohort study of multimorbid participants aged ≥70 years in the Irish LongituDinal Study on Ageing (TILDA). Eligible participants had linked pharmacy claims data and completed TILDA wave 2 (2 years after wave 1). The RxRisk-V tool was used to identify multimorbidity. Average adherence (AA) across RxRisk-V conditions was estimated using the CMA7 function (AdhereR). Group-based trajectory models (GBTMs) identified adherence patterns in the 12 months following wave 1. Negative binomial regression was used to estimate the association between adherence and the rate of subsequent self-reported general practitioner [GP] visits, emergency department (ED) visits, outpatient visits, and hospitalizations in the 12 months following adherence measurement (reported at wave 2). Adjusted Incident Rate Ratios (aIRR) and 95% CIs are presented. RESULTS: Higher AA (CMA7) was associated with a small significant decrease in GP visit rate (aIRR = 0.70; CI = 0.53-0.94) and outpatient visit rate (aIRR = 0.44; CI = 0.23-0.81). GBTM identified 6 adherence groups (n = 1050). Compared with high adherers, group 1 (rapid decline, modest increase) membership (aIRR = 1.72; CI = 1.09-2.73) and group 4 (high adherence, delayed decline) membership (aIRR = 1.92; CI = 1.19-3.05) significantly increased ED visit rate. CONCLUSION AND RELEVANCE: Suboptimal medication adherence in multimorbid older adults is associated with increased health care utilization. Identification of suboptimal adherence groups for medication management interventions may help decrease the health system burden and health care costs.

Impact of changes in controlled drugs legislation on benzodiazepine receptor agonist prescribing in Ireland: a repeated cross-sectional study.

PURPOSE: To examine the impact of new controlled drugs legislation introduced in May 2017 on benzodiazepine receptor agonist (BZRA) prescribing in Ireland. METHODS: A repeated cross-sectional analysis was conducted using publically available monthly pharmacy claims data from the General Medical Services (GMS) database. The study population comprised all GMS-eligible individuals aged ≥ 16 years from January 2016 to September 2019. Monthly prevalence rates of individuals receiving BZRA prescriptions per 10,000 eligible population were calculated and trends examined over time. Segmented linear regression of prevalence rates was used to examine changes before and after introduction of the legislation stratified by gender and age groups. Regression coefficients (ß) and 95% confidence intervals (CIs) for monthly change were calculated. RESULTS: Pre-legislation (January 2016 to April 2017), there was a significant monthly decline in benzodiazepine prevalence rate (ß = - 1.18; 95% CI - 1.84, - 0.51; p < 0.001) but no significant change in Z-drug prescribing. Post-legislation (May 2017 to September 2019), increases in prevalence rates were observed for benzodiazepines (ß = 1.04; 95% CI 0.17, 1.92; p = 0.021) and Z-drugs (ß = 1.04; 95% CI 0.26, 1.83; p = 0.010). Post-legislation trends showed increases in BZRA prevalence rates among the youngest subgroup (16-44 years), with variable changes in the middle-aged subgroup (45-64 years) and no changes in the oldest subgroup (≥ 65 years). CONCLUSIONS: This study indicates that introduction of new legislation had limited impact on BZRA prescribing on the main public health scheme in Ireland. Interventions targeting specific population subgroups may be required to achieve sustained reductions in prescribing.