The ChAMP App: A Scalable mHealth Technology for Detecting Digital Phenotypes of Early Childhood Mental Health.

Childhood mental health problems are common, impairing, and can become chronic if left untreated. Children are not reliable reporters of their emotional and behavioral health, and caregivers often unintentionally under- or over-report child symptoms, making assessment challenging. Objective physiological and behavioral measures of emotional and behavioral health are emerging. However, these methods typically require specialized equipment and expertise in data and sensor engineering to administer and analyze. To address this challenge, we have developed the ChAMP (Childhood Assessment and Management of digital Phenotypes) System, which includes a mobile application for collecting movement and audio data during a battery of mood induction tasks and an open-source platform for extracting digital biomarkers. As proof of principle, we present ChAMP System data from 101 children 4-8 years old, with and without diagnosed mental health disorders. Machine learning models trained on these data detect the presence of specific disorders with 70-73% balanced accuracy, with similar results to clinical thresholds on established parent-report measures (63-82% balanced accuracy). Features favored in model architectures are described using Shapley Additive Explanations (SHAP). Canonical Correlation Analysis reveals moderate to strong associations between predictors of each disorder and associated symptom severity (r = .51-.83). The open-source ChAMP System provides clinically-relevant digital biomarkers that may later complement parent-report measures of emotional and behavioral health for detecting kids with underlying mental health conditions and lowers the barrier to entry for researchers interested in exploring digital phenotyping of childhood mental health.

Toward Digital Phenotypes of Early Childhood Mental Health via Unsupervised and Supervised Machine Learning.

Childhood mental health disorders such as anxiety, depression, and ADHD are commonly-occurring and often go undetected into adolescence or adulthood. This can lead to detrimental impacts on long-term wellbeing and quality of life. Current parent-report assessments for pre-school aged children are often biased, and thus increase the need for objective mental health screening tools. Leveraging digital tools to identify the behavioral signature of childhood mental disorders may enable increased intervention at the time with the highest chance of long-term impact. We present data from 84 participants (4-8 years old, 50% diagnosed with anxiety, depression, and/or ADHD) collected during a battery of mood induction tasks using the ChAMP System. Unsupervised Kohonen Self-Organizing Maps (SOM) constructed from movement and audio features indicate that age did not tend to explain clusters as consistently as gender within task-specific and cross-task SOMs. Symptom prevalence and diagnostic status also showed some evidence of clustering. Case studies suggest that high impairment (>80th percentile symptom counts) and diagnostic subtypes (ADHD-Combined) may account for most behaviorally distinct children. Based on this same dataset, we also present results from supervised modeling for the binary classification of diagnoses. Our top performing models yield moderate but promising results (ROC AUC .6-.82, TPR .36-.71, Accuracy .62-.86) on par with our previous efforts for isolated behavioral tasks. Enhancing features, tuning model parameters, and incorporating additional wearable sensor data will continue to enable the rapid progression towards the discovery of digital phenotypes of childhood mental health.Clinical Relevance- This work advances the use of wearables for detecting childhood mental health disorders.

Understanding the factors influencing community pharmacist retention - A qualitative study.

Background: Shortages in healthcare workers affects the overall delivery and effectiveness of the provision of healthcare. There are currently insufficient pharmacists working in the community sector in Ireland. While several studies have reported on the factors leading to retention in the medical and nursing profession, there is an absence of robust research examining retention within the pharmacist workforce in Ireland. Objective: To identify and understand the range of factors currently at play in the community pharmacy sector in Ireland which influence the decision-making process for pharmacists deciding whether or not to continue to practice as a community pharmacist. Method: A cross-sectional qualitative descriptive study was used to investigate the factors influencing community pharmacist retention as elicited from the lived experiences of 23 pharmacists. Study recruitment was undertaken using both convenience and purposive sampling. Qualitative content analysis was used to analyze the interview data to identify and explore themes. Results: A broad and diverse range of factors were identified as affecting community pharmacist retention including working conditions, career fulfilment and progression, regulatory and administrative burden, the commercial focus within community practice, lack of representation and their overall health and well-being. Conclusion: The findings show that there are a number of factors which either individually or cumulatively influence a pharmacist's decision to stay in or leave community practice. Various areas for change were identified, which if addressed are considered likely to improve retention in the sector. These include enhanced terms and working conditions, better acknowledgement and resourcing of professional activities, improved opportunities for career progression, reforms to the regulatory model including the personal accountability of a supervising pharmacist for all of the pharmacy's professional activities, a more streamlined model of reimbursement and more effective collective representation.

Economic evaluation of a collaborative model of pharmaceutical care in an Irish hospital: cost-utility analysis.

Background: A complex, collaborative pharmaceutical care intervention including medication review and reconciliation demonstrated a statistically significant reduction in the prevalence of discharge medication error and improved quality of prescribing for hospitalised adults.  This study sought to assess the cost-effectiveness of this intervention. Methods: A cost-utility analysis was undertaken using a decision-analytic framework. The evaluation was undertaken from the Health Service Executive's perspective, the payer for primary and secondary care settings. Direct costs associated with managing hypothetical harm consequent to intercepted discharge medication error and consequences in terms of quality-adjusted life years loss were key input parameters. Analysis was structured within a decision tree model in Microsoft Excel® populated with consequences as utilities, estimated costs using macro- and micro-costing approaches, and event probabilities generated from the original study. Incremental analysis, one-way and probabilistic sensitivity analyses were performed. Results: The results of analysis for the base-care demonstrated that the intervention dominated standard care with an incremental cost-effectiveness ratio of -€36,537.24/quality-adjusted life year, indicating that the intervention is less costly and more effective. The one-way and probabilistic sensitivity analyses both demonstrated that the intervention dominated standard care. The model was relatively robust to variation in input parameters through one-way sensitivity analysis. The cost of discharge medication error and effect parameters relating to standard care were most sensitive to change. Discussion: The analysis demonstrated the cost-effectiveness of a complex pharmaceutical intervention which will support decision-making regarding implementation. This is the first cost-utility analysis of a complex, collaborative pharmaceutical care intervention, adding to the scant evidence-base in the field.

Chest-Based Wearables and Individualized Distributions for Assessing Postural Sway in Persons With Multiple Sclerosis.

Typical assessments of balance impairment are subjective or require data from cumbersome and expensive force platforms. Researchers have utilized lower back (sacrum) accelerometers to enable more accessible, objective measurement of postural sway for use in balance assessment. However, new sensor patches are broadly being deployed on the chest for cardiac monitoring, opening a need to determine if measurements from these devices can similarly inform balance assessment. Our aim in this work is to validate postural sway measurements from a chest accelerometer. To establish concurrent validity, we considered data from 16 persons with multiple sclerosis (PwMS) asked to stand on a force platform while also wearing sensor patches on the sacrum and chest. We found five of 15 postural sway features derived from the chest and sacrum were significantly correlated with force platform-derived features, which is in line with prior sacrum-derived findings. Clinical significance was established using a sample of 39 PwMS who performed eyes-open, eyes-closed, and tandem standing tasks. This cohort was stratified by fall status and completed several patient-reported measures (PRM) of balance and mobility impairment. We also compared sway features derived from a single 30-second period to those derived from a one-minute period with a sliding window to create individualized distributions of each postural sway feature (ID method). We find traditional computation of sway features from the chest is sensitive to changes in PRMs and task differences. Distribution characteristics from the ID method establish additional relationships with PRMs, detect differences in more tasks, and distinguish between fall status groups. Overall, the chest was found to be a valid location to monitor postural sway and we recommend utilizing the ID method over single-observation analyses.

Digital Phenotypes of Instability and Fatigue Derived From Daily Standing Transitions in Persons With Multiple Sclerosis.

Impairment in persons with multiple sclerosis (PwMS) can often be attributed to symptoms of motor instability and fatigue. Symptom monitoring and queued interventions often target these symptoms. Clinical metrics are currently limited to objective physician assessments or subjective patient reported measures. Recent research has turned to wearables for improving the objectivity and temporal resolution of assessment. Our group has previously observed wearable assessment of supervised and unsupervised standing transitions to be predictive of fall-risk in PwMS. Here we extend the application of standing transition quantification to longitudinal home monitoring of symptoms. Subjects (N=23) with varying degrees of MS impairment were recruited and monitored with accelerometry for a total of  âˆ¼  6 weeks each. These data were processed using a preexisting framework, applying a deep learning activity classifier to isolate periods of standing transition from which descriptive features were extracted for analysis. Participants completed daily and biweekly assessments describing their symptoms. From these data, Canonical Correlation Analysis was used to derive digital phenotypes of MS instability and fatigue. We find these phenotypes capable of distinguishing fallers from non-fallers, and further that they demonstrate a capacity to characterize symptoms at both daily and sub-daily resolutions. These results represent promising support for future applications of wearables, which may soon augment or replace current metrics in longitudinal monitoring of PwMS.

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.

Beyond consumption: a qualitative investigation of hospital clinician attitudes to receiving feedback on antimicrobial prescribing quality.

Background: Feedback on optimal antimicrobial prescribing to clinicians is an important strategy to ensure antimicrobial stewardship (AMS) in the hospital setting. Objective: To explore the perceptions of antimicrobial prescribing feedback among clinicians in acute care. Study design: Prospective qualitative design. Setting: A large inner-city tertiary referral center in Dublin, Ireland. Participants: Clinicians were recruited from the hospital clinician population. Methods: A qualitative study was conducted with a purposive sample of multidisciplinary clinicians. Focus groups and semistructured interviews were used to collect data that were analyzed inductively to identify themes. Results: In total, 30 clinicians from medical, surgical, nursing and pharmacy professions participated in the study. We identified 5 themes: (1) antimicrobial consumption perceived as a proxy measure for prescribing quality; (2) lack of connection between antimicrobial prescribing and patient outcomes; (3) relevance and impact of antimicrobial prescribing feedback associated with professional role; (4) attitudes regarding feedback as an AMS strategy; and (5) knowledge regarding AMS, including antimicrobial prescribing quality measures. Conclusions: Focused feedback on antimicrobial prescribing, with clear goals for improvement, could serve as a useful AMS strategy among clinicians in the acute-care setting. The need for further education and training in AMS was also identified.

Bridging the gap between healthcare professions' regulation and practice: the "lived experience" of community pharmacists in Ireland following regulatory change.

BACKGROUND: Reforms to models of health and care regulation internationally have adapted to address the challenges associated with regulating healthcare professionals. Pharmacists in Ireland entered a new era of regulation with the enactment of the Pharmacy Act in 2007 which significantly updated the law regulating pharmacy in Ireland and expanded the regulatory scope considerably. An earlier study in 2017 examined the experiences of 20 community pharmacists of the Act. This follow-up study aimed to expand the scope of the original study to all community pharmacists in Ireland, to report their "lived experience" of the regulatory model introduced by the Act, assessing its impact on their professional practice using the principles of "better regulation". METHODS: Survey methodology was used to assess the perception of all community pharmacists registered with the Pharmaceutical Society of Ireland of the Act, as implemented, on their practice using an experimental design based on the seven principles of "Better Regulation". Descriptive statistics analyzed quantitative responses while answers from open-ended questions were analyzed using a combination of a modified framework analysis and a qualitative content analysis. RESULTS: Respondents agreed that the Act was necessary, although its implementation by the regulator was largely not viewed as fulfilling the remaining "Better Regulation" principles of being effective, proportional, consistent, agile, accountable and transparent. In particular, its proportionality was questioned. This resulted in pharmacists perceiving that their professional competency to act in the best interests of their patients was not appropriately acknowledged by the regulator, which in turn compromised their ability to provide optimal care for their patients. CONCLUSION: While healthcare professional regulation must primarily be concerned with public protection, it must also have regard to its impact on those delivering healthcare services. The findings highlight the challenge internationally of balancing rigidity and flexibility in professional health and care regulation, and the importance of a regulatory conversation occurring between those regulating and those regulated. This would serve to promote mutual learning and understanding to create a responsive approach to regulation, underpinned by mutual trust, effective risk assessment and adherence to the principles of "Better Regulation".

UVM KID Study: Identifying Multimodal Features and Optimizing Wearable Instrumentation to Detect Child Anxiety.

Anxiety and depression, collectively known as internalizing disorders, begin as early as the preschool years and impact nearly 1 out of every 5 children. Left undiagnosed and untreated, childhood internalizing disorders predict later health problems including substance abuse, development of comorbid psychopathology, increased risk for suicide, and substantial functional impairment. Current diagnostic procedures require access to clinical experts, take considerable time to complete, and inherently assume that child symptoms are observable by caregivers. Multi-modal wearable sensors may enable development of rapid point-of-care diagnostics that address these challenges. Building on our prior work, here we present an assessment battery for the development of a digital phenotype for internalizing disorders in young children and an early feasibility case study of multi-modal wearable sensor data from two participants, one of whom has been clinically diagnosed with an internalizing disorder. Results lend support that sacral movement responses and R-R interval during a short stress-induction task may facilitate child diagnosis. Multi-modal sensors measuring movement and surface biopotentials of the chest and trapezius are also shown to have significant redundancy, introducing the potential for sensor optimization moving forward. Future work aims to further optimize sensor placement, signals, features, and assessments to enable deployment in clinical practice. Clinical Relevance- This work considers the development and optimization of technologies for improving the identification of children with internalizing disorders.

How Much Data Is Enough? A Reliable Methodology to Examine Long-Term Wearable Data Acquisition in Gait and Postural Sway.

Wearable sensors facilitate the evaluation of gait and balance impairment in the free-living environment, often with observation periods spanning weeks, months, and even years. Data supporting the minimal duration of sensor wear, which is necessary to capture representative variability in impairment measures, are needed to balance patient burden, data quality, and study cost. Prior investigations have examined the duration required for resolving a variety of movement variables (e.g., gait speed, sit-to-stand tests), but these studies use differing methodologies and have only examined a small subset of potential measures of gait and balance impairment. Notably, postural sway measures have not yet been considered in these analyses. Here, we propose a three-level framework for examining this problem. Difference testing and intra-class correlations (ICC) are used to examine the agreement in features computed from potential wear durations (levels one and two). The association between features and established patient reported outcomes at each wear duration is also considered (level three) for determining the necessary wear duration. Utilizing wearable accelerometer data continuously collected from 22 persons with multiple sclerosis (PwMS) for 6 weeks, this framework suggests that 2 to 3 days of monitoring may be sufficient to capture most of the variability in gait and sway; however, longer periods (e.g., 3 to 6 days) may be needed to establish strong correlations to patient-reported clinical measures. Regression analysis indicates that the required wear duration depends on both the observation frequency and variability of the measure being considered. This approach provides a framework for evaluating wear duration as one aspect of the comprehensive assessment, which is necessary to ensure that wearable sensor-based methods for capturing gait and balance impairment in the free-living environment are fit for purpose.

A Digital Therapeutic Intervention Delivering Biofeedback for Panic Attacks (PanicMechanic): Feasibility and Usability Study.

BACKGROUND: Panic attacks (PAs) are an impairing mental health problem that affects >11% of adults every year. PAs are episodic, and it is difficult to predict when or where they may occur; thus, they are challenging to study and treat. OBJECTIVE: The aim of this study is to present PanicMechanic, a novel mobile health app that captures heart rate-based data and delivers biofeedback during PAs. METHODS: In our first analysis, we leveraged this tool to capture profiles of real-world PAs in the largest sample to date (148 attacks from 50 users). In our second analysis, we present the results from a pilot study to assess the usefulness of PanicMechanic as a PA intervention (N=18). RESULTS: The results demonstrate that heart rate fluctuates by about 15 beats per minute during a PA and takes approximately 30 seconds to return to baseline from peak, cycling approximately 4 times during each attack despite the consistently decreasing anxiety ratings. Thoughts about health were the most common trigger and potential lifestyle contributors include slightly worse stress, sleep, and eating habits and slightly less exercise and drug or alcohol consumption than typical. CONCLUSIONS: The pilot study revealed that PanicMechanic is largely feasible to use but would be made more so with modifications to the app and the integration of consumer wearables. Similarly, participants found PanicMechanic useful, with 94% (15/16) indicating that they would recommend PanicMechanic to others who have PAs. These results highlight the need for future development and a controlled trial to establish the effectiveness of this digital therapeutic for preventing PAs.

Implementing Outcomes-Based Managed Entry Agreements for Rare Disease Treatments: Nusinersen and Tisagenlecleucel.

BACKGROUND AND OBJECTIVE: Enthusiasm for the use of outcomes-based managed entry agreements (OBMEAs) to manage uncertainties apparent at the time of appraisal/pricing and reimbursement of new medicines has waned over the past decade, as challenges in establishment, implementation and re-appraisal have been identified. With the recent advent of innovative treatments for rare diseases that have uncertainties in the clinical evidence base, but which could meet a high unmet need, there has been renewed interest in the potential of OBMEAs. The objective of this research was to review the implementation of OBMEAs for two case studies across countries in the European Union, Australia and Canada, to identify good practices that could inform development of tools to support implementation of OBMEAs. METHODS: To investigate how OBMEAs are being implemented with rare disease treatments, we collected information from health technology assessment/payer experts in countries that had implemented OBMEAs for either nusinersen in spinal muscular atrophy or tisagenlecleucel in two cancer indications. Operational characteristics of the OBMEAs that were publicly available were documented. Then, the experts discussed issues in implementing these OBMEAs and specific approaches taken to overcome challenges. RESULTS: The OBMEAs identified were based on individual outcomes to ensure appropriate use, manage continuation of treatment and in two cases linked to payment schedules, or they were population based, coverage with evidence development. For nusinersen, population-based OBMEAs are documented in Belgium, England and the Netherlands and individual-based schemes in Bulgaria, Ireland, Italy and Lithuania. For tisagenlecleucel, there were population-based schemes in Australia, Belgium, England and France and individual-based schemes in Italy and Spain. Comparison of the OBMEA constructs showed some clear published frameworks and clarity of the uncertainties to be addressed that were similar across countries. Agreements were generally made between the marketing authorisation holder and the payer with involvement of expert physicians. Only England and the Netherlands involved patients. Italy used its long-established, national, web-based, treatment-specific data collection system linked to reimbursement and Spain has just developed such a national treatment registry system. Other countries relied on a variety of data collection systems (including clinical registries) and administrative data. Durations of agreements varied for these treatments as did processes for interim reporting. The processes to ensure data quality, completeness and sufficiency for re-analysis after coverage with evidence development were not always clear, neither were analysis plans. CONCLUSIONS: These case studies have shown that important information about the constructs of OBMEAs for rare disease treatments are publicly available, and for some jurisdictions, interim reports of progress. Outcomes-based managed entry agreements can play an important role not only in reimbursement, but also in treatment optimisation. However, they are complex to implement and should be the exception and not the rule. More recent OBMEAs have developed document covenants among stakeholders or electronic systems to provide assurances about data sufficiency. For coverage with evidence development, there is an opportunity for greater collaboration among jurisdictions to share processes, develop common data collection agreements, and share interim and final reports. The establishment of an international public portal to host such reports would be particularly valuable for rare disease treatments.

COVID-19 related regulatory change for pharmacists - The case for its retention post the pandemic.

The delivery of healthcare including the provision of pharmacy services globally is highly regulated internationally in order to protect public health and welfare. However, the onset of the COVID-19 pandemic has precipitated the need internationally to amend the model of regulation in order to ensure that people were able to continue to access a range of healthcare services in a timely and effective manner. Many of the changes introduced to the regulation of pharmacy services in Ireland have been replicated in other countries. These include the introduction of electronic means to transmit prescriptions and other orders for medications, relaxing the legal restrictions in place controlling the emergency supply of prescription only medicines and more fully utilizing the professional competency of pharmacists by empowering them to use their expertise and judgment to support their patients accessing the healthcare services that they need. Many of the regulatory changes that have been introduced to support the COVID-19 public health emergency effort are ones that pharmacists have previously sought to enable them provide a more effective and expanded model of pharmaceutical care to their patients. Accordingly, many pharmacists will want these regulatory changes to be retained and further expanded in the aftermath of the COVID-19 public health emergency in order to extend their scope of practice and support them in the care of their patients.

Evaluating patient attitudes to increased patient engagement with antimicrobial stewardship: a quantitative survey.

BACKGROUND: Antimicrobial stewardship (AMS) describes interventions designed to optimize antimicrobial therapy, minimize adverse treatment consequences and reduce the spread of antimicrobial resistance (AMR). Previous research has investigated the patient's role in healthcare infection prevention but the patient's role in AMS has not been extensively explored. OBJECTIVES: To investigate the willingness of hospital inpatients to question staff about prudent antimicrobial use in an Irish hospital and evaluate the impact of patient and public involvement in research (PPI) on this study. METHODS: A survey was co-designed with the hospital Patient Representative Group (PRG) to evaluate patient willingness to engage with prudent antimicrobial treatment. A random sample of 200 inpatients was selected to self-complete the survey using pen and paper. PRG members provided feedback on their involvement. RESULTS: Of the 200 inpatients randomly selected to participate, 120 did not fulfil the inclusion criteria. Of the remaining 80, 67 participated (response 84%). Median respondent age was 58 years, 30% were employed and 30% had a third-level education degree. Over 90% had not heard of AMS while just over 50% had not heard of AMR. Patients preferred asking factual questions rather than challenging ones but did not have a preference in asking questions of doctors compared with nurses. Older patients were less likely to ask questions. PRG members reported an overall positive experience as research collaborators. CONCLUSIONS: Future patient-centred AMS interventions should empower patients to ask about antimicrobial treatment, in particular the older patient cohort. PPI is a valuable component of patient-centred research.

Pharmacist-led pre-treatment assessment, management and outcomes in a Hepatitis C treatment patient cohort.

Background Medication reconciliation and drug-drug interaction management represent important patient safety processes completed by pharmacists as part of Hepatitis C patient care. Objectives To describe the pharmacist-led interventions of medication reconciliation and drug-drug interaction assessment, grading and management in a real-world Hepatitis C treatment cohort and to assesses the impact on patient outcomes. Setting Two Hepatitis C hospital outpatient clinics at St. James's Hospital, Dublin. Method Patients treated with Hepatitis C direct acting anti-viral agents between December 2014 and February 2017 were included in this retrospective cohort study. The study employed a standardised medication reconciliation proforma and drug-drug interaction reference list. Main outcome measures Analyse medication variances identified during pharmacist-led medication reconciliation. Assess the prevalence, type and severity of drug-drug interactions between direct acting anti-virals and co-medications. Assess the rate of prescriber acceptance of the pharmacist-developed drug-drug interaction management strategies. Results Among the 300 patients in this study, medication reconciliation identified 1543 co-medications, with 71% of patients prescribed co-medications which were subject to a potential drug-drug interaction. Drug-drug interaction assessments assigned a rating of severe to 68 interaction episodes. At least one co-medication was stopped during treatment in 25% of patients to facilitate drug-drug interaction management. Pharmacist proposed management recommendations were accepted by prescribers in 96.9% of cases. The sustained virological response rate among the cohort was 92.7%. Conclusions In this Hepatitis C pre-treatment pharmacist assessment analysis, a significant number of medication reconciliation variances and clinically significant drug-drug interactions were identified which present unique and important patient safety risks. Pharmacist-led management strategies aided the achievement of optimum treatment response while promoting patient safety and antiviral stewardship.

Design and Evaluation of a New National Pharmacy Internship Program in Ireland.

Objective. To design, deliver, and evaluate a National Pharmacy Internship Program that met the educational requirements of pharmacy graduates to register as competent pharmacists and earned graduates a master's level degree. Methods. The National Pharmacy Internship Program was designed as a 12-month, full-time, blended-learning, competency-based program leading to a master's degree. Intern performance was assessed academically and by pharmacy preceptor (tutor) appraisals. Interns who demonstrated competency were invited to sit for the Professional Registration Examination (PRE). Feasibility and performance were evaluated and a longitudinal approach allowed intern and preceptor views to be compared to the former preregistration year. Results. Overall performance in the PRE was good and relatively consistent with almost all interns proceeding to register as pharmacists. Interns believed that the program had enabled them to develop the knowledge, skills, and overall competencies required for future independent practice as a pharmacist. Preceptors considered the program to have built on prior learning and provided a sufficiently rounded experience for professional practice. Preceptors also stated that the program was an improved educational experience over the former, less structured, preregistration training. Conclusion. The National Pharmacy Internship Program was perceived to be an improvement on the previous preregistration year. The program quality assured pharmacy education outcomes at the entry-to-practice level on a national basis, and uniquely recognized the students' accomplishment by awarding them a master's degree.

Incorporating single-arm evidence into a network meta-analysis using aggregate level matching: Assessing the impact.

Increasingly, single-armed evidence is included in health technology assessment submissions when companies are seeking reimbursement for new drugs. While it is recognized that randomized controlled trials provide a higher standard of evidence, these are not available for many new agents that have been granted licenses in recent years. Therefore, it is important to examine whether alternative strategies for assessing this evidence may be used. In this work, we examine approaches to incorporating single-armed evidence formally in the evaluation process. We consider matching aggregate level covariates to comparator arms or trials and including this evidence in a network meta-analysis. We consider two methods of matching: (i) we include the chosen matched arm in the data set itself as a comparator for the single-arm trial; (ii) we use the baseline odds of an event in a chosen matched trial to use as a plug-in estimator for the single-arm trial. We illustrate that the synthesis of evidence resulting from such a setup is sensitive to the between-study variability, formulation of the prior for the between-design effect, weight given to the single-arm evidence, and extent of the bias in single-armed evidence. We provide a flowchart for the process involved in such a synthesis and highlight additional sensitivity analyses that should be carried out. This work was motivated by a hepatitis C data set, where many agents have only been examined in single-arm studies. We present the results of our methods applied to this data set.

Health-related quality of life in hepatitis C patients who achieve sustained virological response to direct-acting antivirals: a comparison with the general population.

PURPOSE: To compare health-related quality of life (HRQoL) between hepatitis C patients who achieve sustained virological response (SVR) to direct-acting antivirals and a sex- and age-paired sample of the general population. METHODS: HRQoL was evaluated in patients recruited in Navarre, Spain, from May 2016 to April 2017 at baseline and after SVR, using the EQ-5D-5L questionnaire. Both results were compared to those of general population of the same sex and age obtained from the 2011/12 National Health Survey in Spain. Observed/expected (O/E) ratios for health dimensions and differences between O-E in EQ-5D utility and visual analogical scale (VAS) scores were calculated. RESULTS: 206 patients were studied. Before treatment, patients had more problems than the general population in every domain of EQ-5D-5L, except in self-care dimension (O/E = 1.1). After SVR, patients continued having more limitation, especially for usual activities (O/E = 3.1), anxiety/depression (O/E = 2.8) and EQ-5D utility (- 0.086, p < 0.001); however, differences in VAS score between patients and general population disappeared (74.8 vs 76.5, p = 0.210). F0-F1 patients with SVR had minor differences with the general population in EQ-5D-5L dimensions, utility and VAS score. Although cirrhotic patients also reduced that difference, they still had worse HRQoL, especially in usual activities, self-care, EQ-5D utility (- 0.152, p < 0.001) and VAS score (- 8.5, p = 0.005). CONCLUSIONS: HRQoL of chronic hepatitis C patients remains lower than that of the general population despite viral clearance, with primary problems in usual activities and anxiety/depression. Knowledge of these on-going problems despite cure serves to guide healthcare interventions and patient's follow-up.

Survival and clinical events related to end-stage liver disease associated with HCV prior to the era of all oral direct-acting antiviral treatments.

Background: The aim of this study was to describe the natural long-term course of end-stage liver disease associated with chronic hepatitis C (HCV) infection by measuring survival and complication rates in the era prior to the arrival of new direct-acting antiviral (DAA) drugs. Methods: A retrospective population-based cohort study was designed to establish the follow-up of patients hospitalized for a decompensated cirrhotic event or hepatocellular carcinoma using electronic records from hospital discharge databases from 2009 to 2015. Their survival was compared with a sex, age and non-liver mortality excess matched simulation of the general Spanish population. Results: A total of 253 patients were included in the study. Among those with decompensated cirrhosis (n = 151) the hospital admission rate was 1.88 per patient-year with a mortality rate of 0.16 per patient-year. Mean survival was 4.10 years for patients with decompensated cirrhosis, and 1.75 for non-transplanted hepatocellular carcinoma, compared to 18.39 years for the general population. Conclusion: Our results show the complexity and rapid progression of end-stage liver disease associated with HCV infection. The considerable loss of life expectancy associated with the development of decompensated cirrhosis in patients with chronic HCV infection in the absence of viral clearance through treatment is acutely evident.