Impact of the COVID-19 pandemic on cancer care in Ireland - Perspectives from a COVID-19 and Cancer Working Group.

Upon the COVID-19 pandemic onset in Ireland, cancer service disruptions occurred due to prioritisation of COVID-19 related care, redeployment of staff, initial pausing of screening, diagnostic, medical and surgical oncology procedures, staff shortages due to COVID-19 infection and impacts on the physical and mental health of cancer healthcare workers. This was coupled with reluctance among people with symptoms suspicious for cancer to attend for clinical evaluation, due to concerns of contracting the virus. This was further compounded by a cyber-attack on national health service IT systems on May 14th 2021. The Irish Cancer Society, a national cancer charity with a role in advocacy, research and patient supports, convened a multi-disciplinary stakeholder group (COVID-19 and Cancer Working Group) to reflect on and understand the impact of the pandemic on cancer patients and services in Ireland, and discuss potential mitigation strategies. Perspectives on experiences were gathered across domains including timeliness of data acquisition and its conversion into intelligence, and the resourcing of cancer care to address cancer service impacts. The group highlighted aspects for future research to understand the long-term pandemic impact on cancer outcomes, while also highlighting potential strategies to support cancer services, build resilience and address delayed diagnosis. Additional measures include the need for cancer workforce recruitment and retention, increased mental health supports for both patients and oncology professionals, improvements to public health messaging, a near real-time multimodal national cancer database, and robust digital and physical infrastructure to mitigate impacts of the current pandemic and future challenges to cancer care systems.

Potential costs and consequences associated with medication error at hospital discharge: an expert judgement study.

OBJECTIVES: Assessing the cost-effectiveness of complex pharmaceutical care interventions and medication error outcomes is hindered by lack of available data on actual outcomes consequent to errors that were intercepted for patient safety reasons. Expert judgement is an approach to acquire data regarding unknown parameters in an economic model which are otherwise insufficient or not possible to obtain. The aim of this paper is to describe a method to approach this problem using findings from a single intervention study and to calculate the potential costs and consequences associated with discharge medication error. METHODS: Using data from a previous intervention study, the hypothetical consequences of medication error(s) at hospital discharge, in terms of diagnosis, healthcare resource utilisation and impact on health-related quality of life, were identified by expert judgement of anonymised cases. Primary healthcare utilisation costs were derived from published tariffs, inpatient costs were derived by simulation in the hospital discharge activity database test environment and the difference between adjudicated baseline and posterror health state was expressed as quality-adjusted life year (QALY) decrement. RESULTS: Four experts provided judgement on 81 cases. Of these, 75 were judged to have potential clinical consequences. Between 56 and 69 of the 81 cases were variably judged to require remedial healthcare utilisation. The mean calculated cost per case (representing an individual patient), based on all 81 cases, was €1009.58, 95% CI 726.64 to 1585.67. The mean QALY loss was 0.03 (95% CI 0.01 to 0.05). CONCLUSION: An expert judgement process proved feasible and useful to estimate financial cost and QALY loss associated with hospital discharge medication error. These estimates will be employed in model-based economic evaluation. This method could be transferred to other prospective observational patient safety research which seeks to assess value for money of complex interventions.

Protocol for Establishing a Stakeholder Group for Primary Care Research into Cancer Using a Modified 7P Framework and an e-Delphi Process.

Introduction: Currently, no group specifically supports and coordinates primary care focused cancer research in Ireland. The aim of this project is to establish an inclusive stakeholder group for primary care focused cancer research in Ireland, to coordinate research efforts and build capacity in researchers and institutions. Methods: We will convene a stakeholder group, recruiting individuals with personal and professional experience of cancer care in a community setting. "Core stakeholders"-patients, clinicians, researchers, and policymakers-will attend regularly. Additional "specialist stakeholders", such as representatives of secondary care, private healthcare, health insurance, industry, cancer charities, and health research funders, will participate on an ad hoc basis. An e-Delphi consensus process will be used to assess the stakeholders' views on: (1) the relevance and importance of primary care focused cancer research; (2) the potential role and scope of the stakeholder group; (3) how best to engage with lived experience stakeholders and healthcare professionals affected by the research; (4) how to encourage the dissemination of results and the translation of findings into practice. Round 1 will be open-ended and will invite the independent suggestions of stakeholders; in Round 2 and 3, group members will vote on the inclusion of these suggestions in a position statement by the group, with consensus defined as ≥75% agreement. Discussion: The formation of a broad stakeholder group to support primary care focused cancer research will ensure research is relevant, patient centered, and more readily translated into practice. It is also hoped that the group will support capacity building and strategic planning in this important research space.

Cost outcomes of potentially inappropriate prescribing in middle-aged adults: A Delphi consensus and cross-sectional study.

BACKGROUND: Potentially inappropriate prescribing (PIP) is common in older adults and is associated with increased medication costs and costs of associated adverse drug events. PIP also affects almost 1/5 of middle-aged adults (45-64 y), as defined by the PRescribing Optimally in Middle-aged People's Treatments (PROMPT) criteria. However, there has been little research on PIP medication costs within this age group. AIMS: Calculate the medication costs of PIP for middle-aged adults according to the 22 PROMPT criteria and compare with the cost of consensus-validated, evidence-based (adequate) alternative prescribing scenarios. METHODS: Adequate alternatives to the 22 PROMPT criteria were created via literature review. A Delphi consensus panel of experts was recruited (n = 16), supported by a patient and public involvement group, to achieve consensus on the alternatives. A retrospective repeated cross-sectional study from 2014 to 2019 was then conducted utilising pseudonymised primary care data from Lambeth DataNet in South London (41 general practices, n = 1 185 335, using Lambeth DataNet May 2020 extract) to calculate the cost of PIP. RESULTS: The cross-sectional study included 55 880 patients. The total PIP cost was £2.79 million, with adequate alternative prescribing costing £2.74 million (cost savings of £51 278). Duplicate drug classes was the most costly criterion for both PIP and alternative prescribing. CONCLUSION: This study calculated the medication costs of PIP and created alternative prescribing scenarios for the 22 PROMPT criteria. There is no substantial cost difference between adequate prescribing vs. PIP. Future studies should investigate the wider health economic costs of alternative prescribing, such as reducing hospital admissions.

Determinants of long-term opioid prescribing in an urban population: A cross-sectional study.

BACKGROUND: Opioid prescribing has more than doubled in the UK between 1998 and 2016. Potential adverse health implications include dependency, falls and increased health expenditure. AIM: To describe the predictors of long-term opioid prescribing (LTOP) (≥3 opioid prescriptions in a 90-day period). DESIGN AND SETTING: A retrospective cross-sectional study in 41 general practices in South London. METHOD: Multi-level multivariable logistic regression to investigate the determinants of LTOP. RESULTS: Out of 320 639 registered patients ≥18 years, 2679 (0.8%) were identified as having LTOP. Patients were most likely to have LTOP if they had ≥5 long-term conditions (LTCs) (adjusted odds ratio [AOR] 36.5, 95% confidence interval [CI] 30.4-43.8) or 2-4 LTCs (AOR 13.8, CI 11.9-16.1) in comparison to no LTCs, were ≥75 years compared to 18-24 years (AOR 12.31, CI 7.1-21.5), were smokers compared to nonsmokers (AOR 2.2, CI 2.0-2.5), were female rather than male (AOR 1.9, CI 1.7-2.0) and in the most deprived deprivation quintile (AOR 1.6, CI 1.4-1.8) compared to the least deprived. In a separate model examining individual LTCs, the strongest associations for LTOP were noted for sickle cell disease (SCD) (AOR 18.4, CI 12.8-26.4), osteoarthritis (AOR 3.0, CI 2.8-3.3), rheumatoid arthritis (AOR 2.8, CI 2.2-3.4), depression (AOR 2.6, CI 2.3-2.8) and multiple sclerosis (OR 2.5, CI 1.4-4.4). CONCLUSION: LTOP was significantly higher in those aged ≥75 years, with multimorbidity or specific LTCs: SCD, osteoarthritis, rheumatoid arthritis, depression and multiple sclerosis. These characteristics may enable the design of targeted interventions to reduce LTOP.

Is rapid scientific publication also high quality? Bibliometric analysis of highly disseminated COVID-19 research papers.

The impact of COVID-19 has underlined the need for reliable information to guide clinical practice and policy. This urgency has to be balanced against disruption to journal handling capacity and the continued need to ensure scientific rigour. We examined the reporting quality of highly disseminated COVID-19 research papers using a bibliometric analysis examining reporting quality and risk of bias (RoB) amongst 250 top scoring Altmetric Attention Score (AAS) COVID-19 research papers between January and April 2020. Method-specific RoB tools were used to assess quality. After exclusions, 84 studies from 44 journals were included. Forty-three (51%) were case series/studies, and only one was an randomized controlled trial. Most authors were from institutions based in China (n = 44, 52%). The median AAS and impact factor was 2015 (interquartile range [IQR] 1,105-4,051.5) and 12.8 (IQR 5-44.2) respectively. Nine studies (11%) utilized a formal reporting framework, 62 (74%) included a funding statement, and 41 (49%) were at high RoB. This review of the most widely disseminated COVID-19 studies highlights a preponderance of low-quality case series with few research papers adhering to good standards of reporting. It emphasizes the need for cautious interpretation of research and the increasingly vital responsibility that journals have in ensuring high-quality publications.

Survival and outcomes for stroke survivors living in care homes: a prospective cohort study.

BACKGROUND: Stroke survivors living in care homes require high levels of support with everyday living. The aims of this study were to describe the survival, health status and care received by stroke survivors living in care homes at 1-year post-stroke, compared with those in their own homes. METHODS: A total of 3,548 stroke survivors with a first ever stroke between 1998 and 2017 in the South London Stroke Register were identified for survival analysis. A total of 2,272 were included in the 1-year follow-up analysis. Cox regression and Kaplan-Meier plots were used to describe survival, stratified into four 5-year cohorts. Health status, medications and rehabilitation received at 1-year post-stroke were compared using descriptive statistics. RESULTS: Over the 20-year period, survival improved for stroke survivors discharged to their own home (P < 0.001) but not for those discharged to care homes (P = 0.75). Care home residents were highly disabled (median Barthel index: 6/20, interquartile range: 2-10). Rates of secondary stroke prevention medications at 1-year follow-up increased over time for care home residents, including antiplatelets from 12.3 to 38.1%, although still lower than for those in their own homes (56.3%). Speech and language problems were common in the care home population (40.0%), but only 16% had received speech and language therapy. CONCLUSIONS: Rates of secondary stroke prevention prescribing increased over 20 years but remained lower in care home residents. The lower levels of rehabilitation received by stroke survivors in care homes, despite their higher levels of disability, suggest a gap in care and urgent need for restorative and/or preventative rehabilitation.

Crowdsourcing citation-screening in a mixed-studies systematic review: a feasibility study.

BACKGROUND: Crowdsourcing engages the help of large numbers of people in tasks, activities or projects, usually via the internet. One application of crowdsourcing is the screening of citations for inclusion in a systematic review. There is evidence that a 'Crowd' of non-specialists can reliably identify quantitative studies, such as randomized controlled trials, through the assessment of study titles and abstracts. In this feasibility study, we investigated crowd performance of an online, topic-based citation-screening task, assessing titles and abstracts for inclusion in a single mixed-studies systematic review. METHODS: This study was embedded within a mixed studies systematic review of maternity care, exploring the effects of training healthcare professionals in intrapartum cardiotocography. Citation-screening was undertaken via Cochrane Crowd, an online citizen science platform enabling volunteers to contribute to a range of tasks identifying evidence in health and healthcare. Contributors were recruited from users registered with Cochrane Crowd. Following completion of task-specific online training, the crowd and the review team independently screened 9546 titles and abstracts. The screening task was subsequently repeated with a new crowd following minor changes to the crowd agreement algorithm based on findings from the first screening task. We assessed the crowd decisions against the review team categorizations (the 'gold standard'), measuring sensitivity, specificity, time and task engagement. RESULTS: Seventy-eight crowd contributors completed the first screening task. Sensitivity (the crowd's ability to correctly identify studies included within the review) was 84% (N = 42/50), and specificity (the crowd's ability to correctly identify excluded studies) was 99% (N = 9373/9493). Task completion was 33 h for the crowd and 410 h for the review team; mean time to classify each record was 6.06 s for each crowd participant and 3.96 s for review team members. Replicating this task with 85 new contributors and an altered agreement algorithm found 94% sensitivity (N = 48/50) and 98% specificity (N = 9348/9493). Contributors reported positive experiences of the task. CONCLUSION: It might be feasible to recruit and train a crowd to accurately perform topic-based citation-screening for mixed studies systematic reviews, though resource expended on the necessary customised training required should be factored in. In the face of long review production times, crowd screening may enable a more time-efficient conduct of reviews, with minimal reduction of citation-screening accuracy, but further research is needed.

Prevalence and predictors of potentially inappropriate prescribing in middle-aged adults: a repeated cross-sectional study.

BACKGROUND: Potentially inappropriate prescribing (PIP) is common in older adults and known to be associated with polypharmacy and multimorbidity. Less is known about the prevalence and causes of PIP in middle-aged adults. AIM: To determine the prevalence and predictors of PIP in middle-aged adults. DESIGN AND SETTING: A repeated cross-sectional study was conducted using primary care data in London. METHOD: PIP was defined using the PRescribing Optimally in Middle-aged People's Treatments (PROMPT) criteria. Prescribing and demographic data were extracted from Lambeth DataNet (LDN), a pseudonymised database of all patients registered at general practices in Lambeth, for those aged 45-64 years prescribed ≥1 medicines in each year from 2014-2019 (n = 46 633-52 582). Prevalence and trends over 6 years were investigated, including the association of PIP with polypharmacy, multimorbidity, deprivation, sex, and age. RESULTS: The prevalence of PIP decreased from 20% in 2014 to 18% in 2019. The most prevalent PROMPT criteria in 2019 were the use of ≥2 drugs from the same pharmacological class (7.6%), use of non-steroidal anti-inflammatory drugs for >3 months (7.1%) and use of proton pump inhibitors above recommended maintenance dosages for >8 weeks (3.1%). Over the study period, the prevalence of multimorbidity increased (47-52%) and polypharmacy remained stable (27%). Polypharmacy, multimorbidity, deprivation, and age were independently associated with PIP. Sex was the only variable not associated with PIP. CONCLUSION: Almost one-fifth of middle-aged adults prescribed medicines are exposed to PIP, as defined by the PROMPT criteria. This is likely to be linked with exposure to avoidable adverse drug events. The PROMPT criteria may provide a useful aid in interventions to optimise prescribing.

Uncoded chronic kidney disease in primary care: a cross-sectional study of inequalities and cardiovascular disease risk management.

BACKGROUND: Uncoded chronic kidney disease (CKD) is associated with poorer quality of care. AIM: To ascertain the proportion and determinants of CKD, which have not been formally recorded (Read coded), and identify differences in management and quality-of-care measures for patients with coded and uncoded CKD. DESIGN AND SETTING: Cross-sectional survey undertaken in an ethnically diverse adult population using primary care electronic health records (EHRs) from GP clinics in Lambeth, South London, UK. METHOD: Multivariable logistic regression analysis examined the association of demographic factors, selected comorbidities, deprivation, and cardiovascular disease risk management in CKD, with coding status as outcome. RESULTS: In total, the survey involved 286 162 adults, of whom 9325 (3.3%) were identified with CKD stage 3-5 (assigned as CKD based on estimated glomerular filtration rate [eGFR] values). Of those identified with CKD, 4239 (45.5%) were Read coded, and 5086 (54.5%) were uncoded. Of those identified with CKD stage 3-5, individuals aged ≥50 years were more likely to be coded for CKD, compared with those aged <50 years. Lower levels of coding were independently associated with deprivation and black Caribbean, black African, South Asian, and non-stated ethnicities, compared with white ethnicity. Prescribed statin and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker medications were associated with increased odds of coded CKD. CONCLUSION: This study found that >50% of CKD was uncoded and, for those patients, quality of care was lower compared with those with coded CKD. Future research and practices should focus on areas of greater deprivation and targeted initiatives for those aged <50 years and of black African, black Caribbean, South Asian, or non-stated ethnic groups. Possible areas for improvement include diagnostic coding support, automated CKD recording, and clinical decision support (based on adjusted eGFR results) in the GP clinical records.

Barriers and facilitators of medicines reconciliation at transitions of care in Ireland - a qualitative study.

BACKGROUND: Medication error at transitions of care is common. The implementation of medicines reconciliation processes to improve this issue has been recommended by many regulatory and safety organisations. The aim of this study was to gain insight from healthcare professionals on the barriers and facilitators to the medicines reconciliation implementation process. METHODS: Semi-structured interviews were conducted in Ireland with a wide range of healthcare professionals (HCPs) involved with medicines reconciliation at transitions of care. Thematic analysis was undertaken using an adaptation of a combined theoretical framework of Grol, Cabana and Sluisveld to classify the barriers and facilitators to implementation of medicines reconciliation. RESULTS: Thirty-five participants were interviewed, including eleven community pharmacists (CPs), eight hospital pharmacists (HPs), nine hospital consultants (HCs), five general practitioners (GPs), and two non-consultant hospital doctors (NCHDs). Themes were categorized into barriers and facilitators. Barriers included resistance from existing professional cultures, staff interest and training, poor communication and minimal information and communications technology (ICT) support. Solutions (facilitators) suggested included supporting effective multidisciplinary teams, greater involvement of pharmacists in medicines reconciliation, ICT solutions (linked prescribing databases, decision support systems) and increased funding to provide additional (e.g. admission and discharge reconciliation) and more advanced services (e.g. community pharmacist delivered medicines use review). CONCLUSIONS: Medicines reconciliation is advocated as a solution to the known problem of medication error at transitions of care. This study identifies the key challenges and potential solutions that policy makers, managers and HCPs should consider when reviewing the practices and processes of medicines reconciliation in their own organisations.

Unintended discontinuation of medication following hospitalisation: a retrospective cohort study.

OBJECTIVES: Whether unintended discontinuation of common, evidence-based, long-term medication occurs after hospitalisation; what factors are associated with unintended discontinuation; and whether the presence of documentation of medication at hospital discharge is associated with continuity of medication in general practice. DESIGN: Retrospective cohort study between 2012 and 2015. SETTING: Electronic records and hospital supplied discharge notifications in 44 Irish general practices. PARTICIPANTS: 20 488 patients aged 65 years or more prescribed long-term medication for chronic conditions. PRIMARY AND SECONDARY OUTCOMES: Discontinuity of four evidence-based medication drug classes: antithrombotic, lipid-lowering, thyroid replacement drugs and respiratory inhalers in hospitalised versus non-hospitalised patients; patient and health system factors associated with discontinuity; impact of the presence of medication in the hospital discharge summary on continuity of medication in a patient's general practitioner (GP) prescribing record at 6 months follow-up. RESULTS: In patients admitted to hospital, medication discontinuity ranged from 6%-11% in the 6 months posthospitalisation. Discontinuity of medication is significantly lower for hospitalised patients taking respiratory inhalers (adjusted OR (AOR) 0.63, 95% CI (0.49 to 0.80), p<0.001) and thyroid medications (AOR 0.62, 95% CI (0.40 to 0.96), p=0.03). There is no association between discontinuity of medication and hospitalisation for antithrombotics (AOR 0.95, 95% CI (0.81 to 1.11), p=0.49) or lipid lowering medications (AOR 0.92, 95% CI (0.78 to 1.08), p=0.29). Older patients and those who paid to see their GP were more likely to experience increased odds of discontinuity in all four medicine groups. Less than half (39% to 47.4%) of patients had medication listed on their hospital discharge summary. Presence of medication on hospital discharge summary is significantly associated with continuity of medication in the GP prescribing record for lipid lowering medications (AOR 1.64, 95% CI (1.15 to 2.36), p=0.01) and respiratory inhalers (AOR 2.97, 95% CI (1.68 to 5.25), p<0.01). CONCLUSION: Discontinuity of evidence-based long-term medication is common. Increasing age and private medical care are independently associated with a higher risk of medication discontinuity. Hospitalisation is not associated with discontinuity but less than half of hospitalised patients have medication recorded on their hospital discharge summary.

Prevalence of potentially inappropriate prescribing in older people in primary care and its association with hospital admission: longitudinal study.

OBJECTIVE: To determine whether hospital admission is associated with potentially inappropriate prescribing among older primary care patients (aged ≥65 years) and whether such prescribing was more likely after hospital admission than before. DESIGN: Longitudinal study of retrospectively extracted data from general practice records. SETTING: 44 general practices in Ireland in 2012-15. PARTICIPANTS: Adults aged 65 years or over attending participating practices. EXPOSURE: Admission to hospital (any hospital admission versus none, and post-admission versus pre-admission). MAIN OUTCOME MEASURES: Prevalence of potentially inappropriate prescribing assessed using 45 criteria from the Screening Tool for Older Persons' Prescription (STOPP) version 2, analysed both as rate of distinct potentially inappropriate prescribing criteria met (stratified Cox regression) and binary presence of potentially inappropriate prescribing (logistic regression) and adjusted for patients' characteristics. A sensitivity analysis used matching with propensity scores based on patients' characteristics and diagnoses. RESULTS: Overall 38 229 patients were included, and during 2012 the mean age was 76.8 (SD 8.2) years and 43% (13 212) were male. Each year, 10.4-15.0% (3015/29 077 in 2015 to 4537/30 231 in 2014) of patients had at least one hospital admission. The overall prevalence of potentially inappropriate prescribing ranged from 45.3% (13 940/30 789) of patients in 2012 to 51.0% (14 823/29 077) in 2015. Independently of age, sex, number of prescription items, comorbidity, and health cover, hospital admission was associated with a higher rate of distinct potentially inappropriate prescribing criteria met; the adjusted hazard ratio for hospital admission was 1.24 (95% confidence interval 1.20 to 1.28). Among participants who were admitted to hospital, the likelihood of potentially inappropriate prescribing after admission was higher than before admission, independent of patients' characteristics; the adjusted odds ratio for after hospital admission was 1.72 (1.63 to 1.84). Analysis of propensity score matched pairs showed a slight reduction in the hazard ratio for hospital admission to 1.22 (1.18 to 1.25). CONCLUSION: Hospital admission was independently associated with potentially inappropriate prescribing. It is important to determine how hospital admission may affect appropriateness of prescribing for older people and how potential adverse consequences of admission can be minimised.

Impact of medication reconciliation for improving transitions of care.

BACKGROUND: Transitional care provides for the continuity of care as patients move between different stages and settings of care. Medication discrepancies arising at care transitions have been reported as prevalent and are linked with adverse drug events (ADEs) (e.g. rehospitalisation).Medication reconciliation is a process to prevent medication errors at transitions. Reconciliation involves building a complete list of a person's medications, checking them for accuracy, reconciling and documenting any changes. Despite reconciliation being recognised as a key aspect of patient safety, there remains a lack of consensus and evidence about the most effective methods of implementing reconciliation and calls have been made to strengthen the evidence base prior to widespread adoption. OBJECTIVES: To assess the effect of medication reconciliation on medication discrepancies, patient-related outcomes and healthcare utilisation in people receiving this intervention during care transitions compared to people not receiving medication reconciliation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, seven other databases and two trials registers on 18 January 2018 together with reference checking, citation searching, grey literature searches and contact with study authors to identify additional studies. SELECTION CRITERIA: We included only randomised trials. Eligible studies described interventions fulfilling the Institute for Healthcare Improvement definition of medication reconciliation aimed at all patients experiencing a transition of care as compared to standard care in that institution. Included studies had to report on medication discrepancies as an outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts, assessed studies for eligibility, assessed risk of bias and extracted data. Study-specific estimates were pooled, using a random-effects model to yield summary estimates of effect and 95% confidence intervals (CI). We used the GRADE approach to assess the overall certainty of evidence for each pooled outcome. MAIN RESULTS: We identified 25 randomised trials involving 6995 participants. All studies were conducted in hospital or immediately related settings in eight countries. Twenty-three studies were provider orientated (pharmacist mediated) and two were structural (an electronic reconciliation tool and medical record changes). A pooled result of 20 studies comparing medication reconciliation interventions to standard care of participants with at least one medication discrepancy showed a risk ratio (RR) of 0.53 (95% CI 0.42 to 0.67; 4629 participants). The certainty of the evidence on this outcome was very low and therefore the effect of medication reconciliation to reduce discrepancies was uncertain. Similarly, reconciliation's effect on the number of reported discrepancies per participant was also uncertain (mean difference (MD) -1.18, 95% CI -2.58 to 0.23; 4 studies; 1963 participants), as well as its effect on the number of medication discrepancies per participant medication (RR 0.13, 95% CI 0.01 to 1.29; 2 studies; 3595 participants) as the certainty of the evidence for both outcomes was very low.Reconciliation may also have had little or no effect on preventable adverse drug events (PADEs) due to the very low certainty of the available evidence (RR 0.37. 95% CI 0.09 to 1.57; 3 studies; 1253 participants), with again uncertainty on its effect on ADE (RR 1.09, 95% CI 0.91 to 1.30; 4 studies; 1363 participants; low-certainty evidence). Evidence of the effect of the interventions on healthcare utilisation was conflicting; it probably made little or no difference on unplanned rehospitalisation when reported alone (RR 0.72, 95% CI 0.44 to 1.18; 5 studies; 1206 participants; moderate-certainty evidence), and had an uncertain effect on a composite measure of hospital utilisation (emergency department, rehospitalisation RR 0.78, 95% CI 0.50 to 1.22; 4 studies; 597 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The impact of medication reconciliation interventions, in particular pharmacist-mediated interventions, on medication discrepancies is uncertain due to the certainty of the evidence being very low. There was also no certainty of the effect of the interventions on the secondary clinical outcomes of ADEs, PADEs and healthcare utilisation.

Hyperactive locomotion in a Drosophila model is a functional readout for the synaptic abnormalities underlying fragile X syndrome.

Fragile X syndrome (FXS) is the most common cause of heritable intellectual disability and autism and affects ~1 in 4000 males and 1 in 8000 females. The discovery of effective treatments for FXS has been hampered by the lack of effective animal models and phenotypic readouts for drug screening. FXS ensues from the epigenetic silencing or loss-of-function mutation of the fragile X mental retardation 1 (FMR1) gene, which encodes an RNA binding protein that associates with and represses the translation of target mRNAs. We previously found that the activation of LIM kinase 1 (LIMK1) downstream of augmented synthesis of bone morphogenetic protein (BMP) type 2 receptor (BMPR2) promotes aberrant synaptic development in mouse and Drosophila models of FXS and that these molecular and cellular markers were correlated in patients with FXS. We report that larval locomotion is augmented in a Drosophila FXS model. Genetic or pharmacological intervention on the BMPR2-LIMK pathway ameliorated the synaptic abnormality and locomotion phenotypes of FXS larvae, as well as hyperactivity in an FXS mouse model. Our study demonstrates that (i) the BMPR2-LIMK pathway is a promising therapeutic target for FXS and (ii) the locomotion phenotype of FXS larvae is a quantitative functional readout for the neuromorphological phenotype associated with FXS and is amenable to the screening novel FXS therapeutics.

PIPc study: development of indicators of potentially inappropriate prescribing in children (PIPc) in primary care using a modified Delphi technique.

OBJECTIVE: There is limited evidence regarding the quality of prescribing for children in primary care. Several prescribing criteria (indicators) have been developed to assess the appropriateness of prescribing in older and middle-aged adults but few are relevant to children. The objective of this study was to develop a set of prescribing indicators that can be applied to prescribing or dispensing data sets to determine the prevalence of potentially inappropriate prescribing in children (PIPc) in primary care settings. DESIGN: Two-round modified Delphi consensus method. SETTING: Irish and UK general practice. PARTICIPANTS: A project steering group consisting of academic and clinical general practitioners (GPs) and pharmacists was formed to develop a list of indicators from literature review and clinical expertise. 15 experts consisting of GPs, pharmacists and paediatricians from the Republic of Ireland and the UK formed the Delphi panel. RESULTS: 47 indicators were reviewed by the project steering group and 16 were presented to the Delphi panel. In the first round of this exercise, consensus was achieved on nine of these indicators. Of the remaining seven indicators, two were removed following review of expert panel comments and discussion of the project steering group. The second round of the Delphi process focused on the remaining five indicators, which were amended based on first round feedback. Three indicators were accepted following the second round of the Delphi process and the remaining two indicators were removed. The final list consisted of 12 indicators categorised by respiratory system (n=6), gastrointestinal system (n=2), neurological system (n=2) and dermatological system (n=2). CONCLUSIONS: The PIPc indicators are a set of prescribing criteria developed for use in children in primary care in the absence of clinical information. The utility of these criteria will be tested in further studies using prescribing databases.